Writing in plain English
Zoonoses
Second edition
Zoonoses
SECOND EDITION
Martin Shakespeare
RD, BPharm, MRPharmS, DipAgVet, DipCP(DES), RNR
Pharmacist, UK
London
•
Chicago
Published by the Pharmaceutical Press
An imprint of RPS Publishing
1 Lambeth High Street, London SE1 7JN, UK
100 South Atkinson Road, Suite 200, Grayslake, IL 60030–7820, USA
© Pharmaceutical Press 2009
is a trade mark of RPS Publishing
RPS Publishing is the publishing organisation of the Royal Pharmaceutical Society
of Great Britain
First edition published in 2002
Second edition published in 2009
Typeset by J&L Composition, Scarborough, North Yorkshire
Printed in Great Britain by TJ International, Padstow, Cornwall
ISBN 978 0 85369 753 4
All rights reserved. No part of this publication may be reproduced, stored in a
retrieval system, or transmitted in any form or by any means, without the prior
written permission of the copyright holder.
The publisher makes no representation, express or implied, with regard to the accuracy
of the information contained in this book and cannot accept any legal responsibility or
liability for any errors or omissions that may be made.
The right of Martin Shakespeare to be identified as the author of this work has been
asserted by him in accordance with the Copyright, Designs and Patents Act, 1988.
A catalogue record for this book is available from the British Library
Contents
Preface
Acknowledgements
About the author
xii
xiii
xiv
1
Introduction to zoonoses
A basic definition
Causative pathogens
Emerging zoonoses
Routes of transmission
Ingestion
Direct contact
Fomite spread
Vectors
Importance of zoonoses
Risk groups
Implications for industry
Produce loss
Personnel loss
Public impact
References
1
1
1
4
7
9
11
12
12
14
18
20
20
20
21
24
2
Zoonoses of companion animals
Birds
Introduction
Cryptococcosis
Mycobacterium avium complex
Psittacosis (ornithosis)
Cats and dogs
Introduction
26
27
27
28
29
31
33
33
vi | Contents
Dogs
Cat Scratch Disease
Echinococcosis
Hookworm
Ancylostomiasis
Cutaneous larva migrans or creeping eruption
Ringworm
Scabies
Toxocariasis (visceral larva migrans and optical larva migrans)
Toxoplasmosis
Horses
Introduction
Glanders, farcy
Leptospirosis
Miscellaneous zoonoses of companion animals
References
3
Zoonoses of agricultural animals
Birds
Newcastle disease
Influenza
The current HP H5N1 outbreak
Vaccine development
Cattle
Brucellosis
Foot-and-mouth disease
Pseudo-cowpox
Q fever
Tapeworm
Bovine tuberculosis
Sheep
Chlamydiosis (gestational psittacosis)
Giardiasis
Orf
Pigs
Introduction
Ascariasis
Pasteurella
Streptococcus suis
Trichinosis or trichinellosis
References
34
35
36
40
40
41
42
44
45
48
53
53
54
56
58
59
61
62
63
65
70
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75
75
78
80
81
84
87
91
92
94
96
98
98
98
100
102
104
107
Contents | vii
4
Food-borne zoonoses
Typical transmission pathway
Food-borne zoonoses associated with fish
Ciguetera
Shellfish poisoning
Food-borne zoonoses associated with meat
Escherichia coli
Listeriosis
Salmonella
Milk-borne diseases
The usual suspects
Clostridium spp. perfringens and C. botulinum
Botulism
Yersinia enterocolitica
Cryptosporidiosis
Campylobacter spp.
Campylobacter and Guillain–Barré syndrome
Food Standards Agency inspection and enforcement
Reducing zoonotic risks in food
HACCP (Hazard Analysis Critical Control Points)
Stepwise prevention strategies
General food hygiene recommendations
Miscellaneous items
References
110
111
111
111
112
113
113
118
122
126
126
126
127
131
132
133
134
135
135
136
136
138
139
140
5
Prion diseases
Animal TSEs and BSE
The significance of scrapie
Variant CJD and human TSEs
Variant Creutzfeldt–Jakob disease
Chronic wasting disease
Useful addresses
References
143
144
145
146
147
158
158
158
6
Pandora’s box
Introduction
Anthrax
Disease in animals
Transmission
Disease in humans
Diagnosis
160
160
162
163
164
164
165
viii | Contents
Treatment
Cutaneous anthrax
Prophylaxis
Prevention
Cases associated with drum makers
Potential as a biological warfare agent
Ebola
Transmission
Disease in humans
Outbreak statistics
Treatment
Prevention
Plague
The disease
Wild foci
The world picture
Epidemiology
Climate change
Disease in animals
Transmission
Disease in humans
Diagnosis
Treatment
Prophylaxis
Prevention
Rabies (hydrophobia)
The UK and Europe
Rabies in North America
Rabies elsewhere in the world
Disease in animals
Transmission
Disease in humans
Diagnosis
Treatment
Prophylaxis
Vaccination regimens
Other related viruses
Case histories
Prevention
165
167
167
169
169
170
172
173
173
174
175
175
176
177
177
178
179
180
181
182
182
184
185
186
187
188
188
189
190
191
191
191
192
192
193
194
196
197
199
Contents | ix
7
Deliberate release – bioterrorism
Initial definitions
Public health dimension
Preparedness
References
202
202
205
206
206
Viral zoonotic diseases
Notes on arrangements of monographs
Alphaviruses
Chikungunya
Eastern equine encephalomyelitis
Mayaro virus
Arenaviruses
Zoonotic arenaviruses
Bunyaviruses
Crimean–Congo haemorrhagic fever
Hantaviruses
Human disease
HFRS
HPS
Transmission
Diagnosis
Treatment
Prevention
Cache Valley virus
La Crosse virus
Oropouche virus
Rift Valley fever
Coronaviruses
SARS
Filoviruses
Marburg virus
Paramyxoviruses – henipaviruses
Hendra virus
Nipah virus
Other unusual paramyxoviruses in fruit bats
Flaviviruses
West Nile virus/Kunjin virus
Japanese encephalitis
209
209
209
209
210
211
211
211
214
214
215
215
215
216
217
217
217
217
218
218
218
219
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219
220
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221
221
222
226
226
226
231
x | Contents
St Louis encephalitis
Other flaviviruses
Borna disease
Closing comments
References
232
233
233
235
235
8
Zoonoses of exotic, feral and wild animals
Transmission pathways
Bushmeat and the live animal trade
Escapees and releases
Zoological parks, circuses and city farms
Exotic pets
Examples of diseases associated with wildlife
Raccoon roundworm
Rat-bite fever (Haverhill fever, Soduku)
Typhus fever
Zoonoses of deer
Lyme disease
Tularaemia
Viruses associated with primates
Herpes B virus
Monkeypox
Simian foamy virus
Simian immunodeficiency viruses
Prevention of spread of wildlife diseases
Surveillance
References
238
240
241
243
243
244
244
245
245
246
246
247
251
256
257
257
259
259
260
261
262
9
Implications for healthcare
Significance of zoonotic disease
Disease prevention strategies
Benefits of companion animal ownership
Benefits from domesticated animals
Risk assessment
Harm reduction and prevention
Constituent measures for prevention strategies
Health promotion and education
Treatment
Antimicrobial resistance
Direct impact of antibiotic resistance on healthcare
265
265
266
266
267
268
270
272
274
275
277
280
Contents | xi
UK Legislation
The Health and Safety at Work etc. Act 1974
Management of Health and Safety at Work Regulations
1992
Control of Substances Hazardous to Health Regulations
1999
Notifiable disease legislation
Statutory notification of infectious diseases (human)
Notifiable disease in animals
Notifiable diseases in the USA
Other US legislation
Points to ponder
Choice of companion animal
Xenotransplantation and transgenic animals
References
280
281
281
282
282
282
284
285
286
286
287
287
288
Appendix 1 Web resources
European
International
The UK
The USA
Canada
290
290
291
291
293
294
Appendix 2 Useful addresses
Creutzfeldt–Jakob disease and variant Creutzfeldt–Jakob
disease
295
Index
297
296
Preface
Like the first edition of Zoonoses, the second edition is aimed at trained and
trainee healthcare professionals. It seeks to provide, in a compact format, an
introduction and easily accessible reference for the more commonly encountered zoonotic diseases and some discussion of the issues surrounding
zoonoses, and their societal and economic impact. This volume discusses
zoonoses not only within the context of domestic disease, but also in the
wider world. Healthcare and healthcare problems become more international
every day, with the massive increase in numbers of people travelling from
place to place for business or pleasure. This makes it increasingly necessary
for us, as healthcare professionals, to widen our horizons, so that we can
respond appropriately to patient needs.
Zoonoses pose a constant challenge to healthcare and our society, and
I hope that even dipping into the volume will give readers some awareness
of the ways in which these conditions are so important in our history,
infrastructure and lives.
There is an emphasis on those zoonoses that are considered to be significant, established or emerging in the UK or the USA, and that are likely to
present in domestic healthcare settings in the sections on companion and
domestic animals. However, for some sections of the volume, conditions or
disease states have been included that have a worldwide significance, not
only for completeness, but also for information and educational purposes.
Since the first edition, several changes in disease patterns around the
world have occurred in the world. The section on bird flu has been revised
and expanded, and some other sections have been reduced to reflect diminishing interest. This volume still includes a chapter, designated Pandora’s box
(Chapter 6), that aims to dispel some of the mythology surrounding the more
emotive and dramatic zoonoses found elsewhere in the world, especially
those where media reporting may be too dramatic for more scientific tastes.
This also now includes a section on bioterrorism, including the Amerithrax
incident in September 2001.
I hope that readers will find this second edition as rewarding to read as
I found it challenging and interesting to write.
Martin Shakespeare
January 2009
Acknowledgements
I would like to dedicate this edition to my mother and father, both of whom
have died since the first edition was published. My thanks go to my wife,
Josephine Sheppard, who has supported and encouraged me to continue to
pursue my interest in this area of study. Without her, none of this would
have happened. My thanks also go to the members and Committee of the
Veterinary Group of the Royal Pharmaceutical Society of Great Britain and
the staff of the Pharmaceutical Press.
About the author
Martin Shakespeare graduated in 1980 with a Bachelor of Pharmacy degree
from the London School of Pharmacy, University of London, and went on
to undertake his preregistration year at St Bartholomew’s Hospital, London.
After registration, he continued his studies by undertaking the Diploma in
Crop Protection at Harper Adams Agricultural College, Shropshire.
While working in community pharmacy, he completed the Diploma in
Agricultural and Veterinary Pharmacy in 1986. His subsequent career has
been varied. A long-standing interest in zoonoses led to Martin being invited
to make a presentation at the British Pharmaceutical Conference in 1999.
The writing of an education package for the Scottish Centre for Post
Qualification Pharmaceutical Education on zoonoses for pharmacists
followed in early 2000, with the material being developed and expanded to
produce the first edition of Zoonoses. Martin currently works for the Royal
Navy.
1
Introduction to zoonoses
A basic definition
In the study of any scientific subject it is important that the terms used are
understood from the outset. So, what is a zoonosis? The best scientifically
agreed definition is that developed and used by the World Health Organization
(WHO), which defines a zoonosis as:
Those diseases and infections which are naturally transmitted
between vertebrate animals and man.
As with many definitions, some of the conditions that are generally classified as zoonoses may lie outside the strict definition, e.g. ciguatera and the
related complex of shellfish poisonings are the result of ingested toxins, not
an infective agent, and shellfish are invertebrates; however, as this condition
is not easily placed into any other disease classification, and can be caused
by eating fish, it is generally accepted as being zoonotic.
Other afflictions, such as malaria, that most people assume to be
zoonoses are not. The malarial mosquitoes are only a vector for the disease,
with the reservoir of infection being infected humans, rather than animals.
In this particular case, the confusion arises because some animals can be a
temporary alternative food supply for the mature mosquito, but do not
show clinical signs of suffering from the disease in significant numbers. A
comparison of malaria with other mosquito-borne infections, such as West
Nile virus (WNV), where the infective reservoir may be one of many animal
species, and particularly birds, highlights the difference.
Causative pathogens
The causative organisms responsible for zoonoses are very diverse and
representative of a wide range of pathogens, or parasites (Table 1.1).
2 | Zoonoses
Table 1.1 Types of causative agent
Types of causative agent
Examples
Arthropods
Scabies (also as vectors)
Bacteria
Brucellosis, tuberculosis
Fungi
Cryptococcus, ringworm
Helminths
Ascariasis, Toxocara
Prions
BSE/vCJD
Protozoa
Toxoplasmosis, cryptosporidia
Rickettsia
Q fever
Viruses
Ebola, rabies
BSE, bovine spongiform encephalopathy; vCJD, variant Creutzfeldt–Jakob disease.
The range of symptoms and effects that this extensive range of causative
organisms produce in both their animal hosts and humans is just as diverse,
from the asymptomatic, through the slightly inconvenient, to some associated cases with fatalities in excess of 50% of infected individuals. This can
reach more than 90% in an outbreak of Ebola virus. An outbreak of Ebola
in the Republic of The Democratic Republic of the Congo in May 2005
killed 9 of the 11 confirmed human cases; previous outbreaks in the Sudan,
in 2004, killed 7 of 17 confirmed cases, and in a major outbreak in Gulu
district, northern Uganda, during the autumn of 2000, over 150 died,
including many healthcare workers. Fortunately it is not native to Europe or
the Americas, and rare in its normal range of sub-Saharan Africa.1
It can be seen that the causative pathogen of a zoonosis usually comes
from a class of organism already capable of causing disease in single-species
groups. The important difference between those pathogens responsible for
zoonotic disease and other members of the same group or family of
pathogens lies in their ability to cause disease across at least two groups of
species, of which human beings, implicitly by the definition of a zoonosis,
must be one. The process of the spread of the disease or pathogen into
another species is known as ‘crossing or jumping the species gap’.
This ability is the one common factor in all pathogens responsible for
zoonotic infections. Regardless of type, they must have the ability to cross
between an animal and a human host under suitable circumstances or conditions. Any disease that can cross the species gap is described as having a
zoonotic potential. Although this is essential, the importance of the pathogen
in epidemiological or healthcare terms rests on the ease with which it makes
this transfer. A highly virulent pathogen that requires extreme circumstances
Introduction to zoonoses | 3
for cross-species transfer poses little or no general threat, although significant
for the individual infected. An organism capable of transferring easily from
the animal source with occasional serious sequelae in infected human
patients will in practice be more significant.
Foot-and-mouth disease, although of undoubted virulence in cattle, is so
difficult for a human to contract, and the necessary circumstances so extreme
for transfer to occur, that the disease is almost not classed as zoonotic, with
only 40 confirmed cases being reported to the WHO in the last century. On
the other side of the coin, if an extensive survey of blood donations is
accurate, more than 40% of the residents of the UK have at one time or
another been infected with Toxoplasma gondii. In the USA, it is estimated
that 60 million people (22% of the population) are infected, although few
have symptoms.2
It is essential to recognise that only some animal diseases have a zoonotic
potential, but all zoonoses have to, by definition, have an animal host. Some
other diseases, although classed or viewed as zoonoses, are actually environmental pathogens, capable of affecting both animals and humans. The
reasoning behind classifying these pathogens as zoonotic lies in the animal
forming an additional and perhaps more efficient transmitter of the disease
to humans than solely environmental exposure. In these and other zoonoses,
the animal host not only can act just as a reservoir of infection, but is also
often capable of amplifying the infection by allowing the organism to
multiply, sometimes with the host remaining asymptomatic.
Some organisms with a zoonotic potential do not cause currently recognised disease states; however, the more investigations undertaken, the greater
our knowledge and the more complex our outfit of investigative tools, the
more zoonoses are identified. Changes in farming practice, dietary preference
or other factors, may also allow previously unknown organisms to move into
a position where they can begin to pose a threat to human health.
An example of a zoonotic pathogen under intensive investigation is
Mycobacterium avium var. paratuberculosis, the causative organism of
Johne’s disease in cattle worldwide. Infection in humans with this
bacterium, and the subsequent development of Crohn’s disease, has been
anecdotally linked for many years. Transmission of the pathogen from cattle
to humans by ingestion of infected dairy products has been demonstrated.
Arguments between experts in the field continue over the evidence relating
to the clinical role of the bacterium, with no firm conclusion as to a causal
linkage. The organism is difficult to culture in the laboratory because, as
with many species of mycobacteria, it is notoriously slow growing and
requires specific and optimal conditions. This may partly explain why it has
been isolated from only some samples obtained from Crohn’s disease
sufferers, and not all. Much research is being undertaken to determine or
disprove any linkage between the affliction and the organism.3
4 | Zoonoses
Linking cause and effect can be difficult because of the long incubation
or pre-patent period associated with some zoonotic diseases. Infection with
Lyme disease, a tick-borne zoonosis of deer, may become evident in humans
only when the serious sequelae of cardiac damage, neuropathies or arthritis
appear many years afterwards.
Many cases of zoonoses go undetected or resolve spontaneously, often as
a result of antibiotic use for another condition destroying the zoonotic
pathogen before either the end of the pre-patent period or the appearance of
clinical signs. With blind usage of broad-spectrum antibiotics becoming less
common as part of antimicrobial resistance strategies, the use of specific
agents against cultures of sensitive organisms may well emerge as the norm.
It is possible that this will lead to more cases of long pre-patent zoonotic
disease and an increase in clinical significance, because there will be a failure
to eradicate the pathogen before it can pose a risk to susceptible infected
individuals.4
There is a need, which has been addressed in some cases, for the significance and scale of infection with some zoonotic pathogens to be evaluated.
Until screening for Chlamydia spp. and Toxoplasma spp. was developed it
was impossible to determine the incidence of these infections in pregnant
women. Many cases of spontaneous abortion attributable to these pathogens
had been blamed on a wide range of other causes. It was only with retrospective investigations of serological markers that the true incidence of infection
and causal attribution could be made. These investigations have allowed the
development of harm-reduction and prevention strategies which, coupled
with health information campaigns, have reduced the significance of these
diseases for human morbidity and mortality.2
Emerging zoonoses
Healthcare is constantly changing, with new products and techniques
affecting practice. There is a continual challenge from newly identified
pathogens and diseases often identified and differentially diagnosed only by
the improvement in or development of testing technologies.
About 80% of these new diseases and pathogens are zoonotic. The emergence of a new zoonosis may not be linked just to the ability of the causative
agent to cross the species barrier, although this is a significant factor. The
pathogen must have the opportunity to cross that barrier, always including
interspecies contact, which is often related to a variety of other external
factors. A change in the ecosystem, the meteorological pattern, global
warming, farming practice or food handling can significantly alter the
potential that a known or unknown pathogen has to cause disease in
humans, with humans coming into closer or more prolonged contact with
carrier species. After this contact there needs to be pathogen transmission,
Introduction to zoonoses | 5
either directly or via a vector, such as a biting insect, and this transmission
must be sustainable, with the pathogen in some cases colonising the vector
if there is one. Once these condition have been met, the pathogen may also
adapt to human physiology and immunology.5
The disease states discussed in this volume to date are mostly well known,
recognised, detectable and classifiable. Their clinical course, the likely infective pathway and any treatment are well documented. For emerging diseases,
some or all of these parameters are either less well known or remain subjects
for speculation. The conclusion that the disease identified is zoonotic may be
made from detecting, culturing and typing the causative organism in affected
humans and animals; however, the linkage between the two, i.e. the transmission pathway and infective route, is sometimes neither well defined nor
practically demonstrable. Treatment regimens may not be defined due to a
lack of success with empirical treatment or the inability to identify a useful
drug or treatment regimen before either death or recovery intervenes.
Another factor that often characterises an emergent pathogen is its
ability to undergo gradual genetic modification, in a manner reminiscent of
Darwin’s finches, so that it reinvents itself as better adapted to exist in a
particular population. This change can enable an organism, which is benign
in other species, to become an efficient pathogen in humans or animals.
Another factor is exposure: in many parts of the world forest clearance or
the pressure on other habitats brings humans and animals into close proximity. Sometimes these will be species or populations that have previously
remained apart. As we know from the introduction of smallpox into the
Americas by the Spanish, the result of the exposure of previously unexposed
groups to a novel pathogen can produce devastating effects.
It is not only pathogens that can migrate: the trade in used tyres has
successfully spread malarial mosquitoes from one country to another in the
stagnant water held in these unusual receptacles. Non-degradable plastic
containers, abandoned in large numbers across the world, are capable of
trapping rainwater and make viable alternatives to traditional wetland habitats for mosquitoes to maintain breeding populations. A rise in the density
of a vector population can allow a previously species-discrete pathogen with
a zoonotic potential to break out of its normal niche.6
In the UK, most of the landscape and its fauna have been shaped by
humans, so that all major predator species have been eradicated and other
wild species have become extinct. Thus the opportunity to encounter an
isolated population of another species with an associated reservoir of a
major zoonotic pathogen is minimal, although the arrival of migratory birds
and the existence of vector populations, such as mosquitoes capable of
spreading a disease organism, continue to be a cause for concern.
This is not the only route for emergence; the unexpected can still happen
when the safeguards of good practice or common sense are ignored. In
6 | Zoonoses
terms of common sense, feeding dead sheep to cattle defies belief, and has
led to unforeseen but nevertheless dramatic consequences.
The USA has seen a number of emerging pathogens, of which West Nile
virus (WNV) has in recent years been the most spectacular. Changes in
migratory bird patterns and the increase in suitable mosquito vector populations within the areas now under the birds’ flight paths have led to the
infection spreading first into the eastern seaboard, and now across virtually
all of mainland USA. It is of note that this particular disease requires both
of these factors to be present in the same geographical location for it to
become a threat. The presence of infected birds or suitable mosquitoes alone
is not enough to precipitate an outbreak, thus providing an opportunity to
control the disease.
Many emerging pathogens are seen in tropical and subtropical areas,
because either the relationship of humans with animals is closer or environmental factors such as extreme heat encourage workers to be less careful with
their use of protective clothing. High levels of ambient environmental heat
and humidity allow pathogens to survive in the environment for longer and
multiply faster on a susceptible host. The presence of humans in previously
undisturbed rain forest or other ecosystems can lead to circumstances in
which exposure to novel pathogens occurs.
The careful study of the associated epidemiology of emerging diseases,
and their routes of infection and natural reservoirs, is the only way to gain
the insights necessary to put in place the measures needed to prevent
epidemic zoonose outbreaks. This is true for several of the zoonoses
mentioned in this chapter; scientists and health professionals involved in the
control of the outbreaks had to make informed assumptions from the case
profiles or epidemiological pattern. It is only on subsequent investigation that
their assumptions can be proved. Wherever the assumptions or deductions
made are of importance they are included in the text, as examples of the
processes essential to disease management.
A factor that needs to be considered in relation to all the diseases
explored in this section is that emerging infections or diseases may actually
be re-emerging. Systems break down, and the reasons for public or
personal health measures may become forgotten or lost in the mists of time.
Several pathogens that were scourges of past ages are showing a resurgence, with outbreaks highlighting ageing or decaying infrastructure
systems, such as sewage or water treatment, and the failure of consumers
to know, understand or heed common-sense warnings related to animal
handling or food preparation.7
It also worthy of note that the knowledge base of most healthcare practitioners does not extend beyond their years; we are all children of our
times. Symptoms and signs that would historically have sent alarm messages
are ignored, or pass unseen. The lesson from the current outbreaks of
Introduction to zoonoses | 7
human tuberculosis in the UK is that pathogens can only rarely be designated
as eradicated; they are more likely to be in a state of abeyance, awaiting the
chance to go on a rampage of infection.
The price of our continued safety in western Europe and the USA, behind
the ramparts of our healthcare and social systems, is constant vigilance.
Worldwide this role is borne by public organisations charged with the monitoring of public, human and animal health. In addition, the WHO and other
organisations, such as the Institut Pasteur, have networks of laboratories
worldwide that undertake surveillance on a spectrum of diseases, some of
zoonotic origin.
Detection and identification are assisted by continual testing of indicator
populations for susceptible species. In the USA the presence of WNV is monitored by just such a programme, using regularly inspected captive domesticated birds to determine ambient levels of the causative organism. Similar to
the canary in a cage in a submarine or mine, these precautions are designed
to alert the experts and the populations for which they are responsible to the
likelihood of an outbreak.
In the event of an outbreak of a zoonotic disease, there is a requirement
for the lead organisation to be identified quickly and for it to take charge of
all aspects of the outbreak. On occasions this is a difficult process, because
rivalry and maintenance of jurisdiction often become more of an issue than
the disease itself. It behoves anybody involved with an outbreak to remember
that all other issues are peripheral to controlling the disease and preventing
human casualties and fatalities.
Routes of transmission
A potential zoonosis may not necessarily cause detectable symptomatic
disease in the animal host, nor is transmission to humans certain from every
exposure to the pathogen. As with any other infection, the size of inoculum
necessary to initiate progress to clinical disease varies from causative organism
to causative organism, and also depends on the route of transmission. The
level of inoculum necessary in an infection of a human by Yersinia pestis
(the causative pathogen of the plague) is believed to be a single bacterium
delivered by a bite from an infected flea. Bacillus anthracis (anthrax) is also
claimed to be capable of causing the cutaneous form of the disease from the
infection of an existing skin abrasion by a single viable spore.
These two cases are exceptional and stem from infection occurring by
direct injection of the organisms into the bloodstream, or infection of an
existing wound or laceration; they are also coupled to the aggressiveness
and pathogenicity of the organism concerned. Moderate-sized inocula or
repeated infection with small cumulative amounts of pathogen are considered
to be more the norm.
8 | Zoonoses
An exceptionally large inoculum may be necessary, e.g. in certain types of
food poisoning. Necrotic enteritis or pigbel is caused by the ingestion of large
quantities of the exotoxin from Clostridium perfringens, with or without the
living organism being present. In most recorded cases the infective dose of the
toxin is estimated to be produced by ⬎ 108 cells of the pathogen. The ensuing
intestinal damage caused by the toxin, with overwhelming colonisation of the
gut by either the associated pathogen or other opportunistic bacteria, leads to
septicaemia which may be rapidly overwhelming, with fatal outcome.8
The mode of transmission varies from zoonosis to zoonosis, and can also
vary for the same causative organism from host species to host species
(Table 1.2). Transmission from animal to human can be not only by direct,
but also by indirect contact. Indirect spread by physical contact with a
previously infected object or surface is known as fomite spread.
Direct transmission may be by contact with infected body fluids such as
fresh blood, saliva, urine or faeces, especially into open wounds, inhalation
of infected aerosols or accidental ingestion of infected material.
Indirect spread may also involve animal-associated organic residues, such
as urine, faecal matter or tears, and nasal secretions. Chlamydophila psittaci
can be spread by inhalation of dried bird faeces and causes psittacosis (also
known as ornithosis) in humans – the parrot’s disease of comedy. A serious
clinical case is no laughing matter for a human victim, because it can lead
to serious sequelae including death in rare cases. The same pathogen is also
endemic in sheep, but the route of transmission is very different as the
organism is transferred to humans by contact with contaminated fluids or
tissues.
The disease presentation and the clinical course associated with a particular pathogen may also vary depending on the route and mode of infection.
Table 1.2 Mode of transmission
Aerosol inhalation
Blood, saliva
Faeces, urine
Fomite contact
Food and water
Oral or physical contact
Parasitic vectors (fleas, mosquitoes, lice, ticks)
Scratches, bites or wounds
Skin, hair or wool
Introduction to zoonoses | 9
C. psittaci also affords an excellent, and dramatic example of how dissimilar the pattern of disease can be depending on the route of infection. The
form of the illness associated with infection acquired from avian sources
usually presents as a flu-like illness with fever and chills, followed by pneumonia and associated dry cough. It seldom causes systemic disease; however,
in rare cases it can progress to a septic form with hepatitis, endocarditis and
ultimately death.
By contrast, infections of sheep origin can demonstrate rapid progression
to systemic disease with serious consequences, especially in pregnant
women. Colonisation of the placenta occurs and can be fatal for both
mother and baby, with late term abortion and neonate death. This particular pathogen is virulent enough for even the most indirect contact to be
sufficient to spread the disease. Following investigations of reported cases,
pregnant women whose partners work in close contact with sheep are
advised not even to handle unwashed overalls which may be contaminated
with blood or secretions from ewes or lambs, and wherever possible to
avoid contact with pre-, peri- or postpartum ewes or young lambs.
In most diseases infection is by more obvious routes. The transfer of
whole blood or exuding plasma from an infected individual forms a very
effective and direct transmission route for many pathogens. Farcy or glanders caused by Burkholderia mallei is seen in humans after contamination
of cuts and grazes by exudate from wounds on horses and other equids.
Jockeys or stable hands in countries where the disease is endemic are especially at risk. Although the last case was seen in the UK in 1928, and in the
USA in 1945, the disease is still seen in many other countries. Horse racing
and other equine pursuits are international, and horses transferred into and
out of the UK to other race venues are carefully monitored for this and other
diseases; however this only protects the equids, not the rider. There is a
potential risk to the growing number of leisure horse owners and riders who
may not be aware of the significance or risk that this infection may pose,
and may choose to ride while abroad, where the disease may be endemic.
Ingestion
Ingestion of contaminated foodstuffs or water also offers an effective route
for a zoonotic pathogen to cross the species barrier. Unpasteurised milk has
historically been recognised as a source of several important zoonoses, and is
becoming increasingly important in the USA because raw milk consumption
has increased in the last decade. Classic tuberculosis (TB) (Mycobacterium
bovis) of animal origin was spread widely in the past by infected dairy
produce. The introduction and refinement of a system of milking, storage,
treatment and distribution with strict temperature and bacterial monitoring,
coupled with establishment of a comprehensive herd-screening programme,
10 | Zoonoses
have virtually eliminated the bovine-derived infection from the human
population. In the 1830s, when the first Euston station in London was built
on a site previously occupied by a particularly infected and disreputable
urban dairy, several medical authorities of the day claimed the demolition of
the dairy to be one of the most significant factors in an observed reduction
of infections linked to the consumption of milk by young children in the city.
It was not until 1882 that Koch identified the causative organism in milk
and that any major advances were made in prevention strategies. Most cases
of TB in the UK are now considered to be of human origin and are caused
by Mycobacterium tuberculosis hominis which is non-zoonotic.9
TB is not the only disease that can spread by ingestion of dairy produce.
Milk can also carry the causative organism of Q fever (Coxiella burnetii),
which usually causes a mild illness similar to flu, but in rare cases can cause
pneumonia, hepatic and cardiac damage, and death. The use of effective
pasteurisation is still tremendously important in preventing this and other
diseases spreading from this source, and has been refined and improved over
time as research has identified the optimal temperature and time necessary
to produce effective disinfection. That said, on occasions systems fail and
this can allow pathogens to survive and cause infection.
Contamination of water or food by faecal matter or urine causes many
infections. Direct ingestion of faecal matter, especially by children, can also
occur. This process, known as pica, is especially significant in infection with
Toxocara spp. and Toxoplasma gondii. Weil’s disease, caused by Leptospira
spp., follows consumption of water contaminated with infected bovine,
equine or rodent urine. Such consumption may be unwitting or accidental,
and is most common among devotees of water sports and other outdoor
pursuits. Many cases of Q fever are related to the occupational exposure of
stock workers to the infected urine of cattle in their charge, rather than to
ingestion of contaminated dairy produce.
Meat, especially poorly cooked or incorrectly stored comminuted meat
products such as beef burgers or sausages, can carry a wide variety of organisms, some responsible for potentially harmful zoonotic infections. The
pathogens usually cause self-limiting diarrhoea and other gastrointestinal
disturbances in otherwise healthy individuals, but can be fatal for already
debilitated individuals. There is believed to be dramatic under-reporting of
food poisoning, with an estimated 10 cases for every one of the approximately
71 000 reported to the Health Protection Agency (HPA) in England and Wales
in 2006.10
From the early 1990s, in the UK, the zoonotic disease that exercised the
imagination of the British public and healthcare professionals was the
dietary and societal impact of bovine spongiform encephalopathy/variant
Creutzfeldt–Jakob disease (BSE/vCJD) linked to the consumption of beef
derived from infected cattle. The theory that this disease is caused by a prion
Introduction to zoonoses | 11
is now fairly widely accepted as the most likely explanation for the pattern
of infection and disease. A prion is defined as a polypeptide entity with no
nucleic acid, consisting solely of a sequence of amino acids. Once inside the
body of the host it is capable of replicating intracellularly, especially in
nervous tissue. After migration of the prion, it leads to the development of
a spongiform encephalopathy, where the brain and central nervous system
are affected.
At postmortem examination, the appearance of areas of the brain is
similar to a sponge. Proteinaceous sheets are found in the remaining cell
structure, and large vacuoles or spaces in between the sheets give confirmation of the diagnosis. The emergence of this disease has had a profound effect
on the meat and livestock trade, from farmer to retailer. The final death toll
is hard to predict; however, the rate of infection/fatality has reduced dramatically since the outbreak was identified, and both husbandry and slaughter
techniques have been modified to reduce infectious risk over the period since
the first identification and characterisation of the infection.11
Other organisms associated with the ingestion of infected meat and meat
products have also hit the headlines. Salmonella infection originating from
a chain of Chinese takeaways in Lanarkshire was a 9-day wonder and
caused several people to receive hospital treatment. The most significant and
deadly outbreak of Escherichia coli (enterohaemorrhagic E. coli or EHEC)
O157 in the UK remains the one linked to J Barr, butchers and bakers, of
Wishaw, Scotland in 1996. The total fatalities associated with the outbreak
reached 21 following the consumption of contaminated meat products. A
recent outbreak in Leeds during July 2006 was also associated with a
butcher with multiple outlets across the city.
This outbreak and others demonstrate the continuing lack of knowledge
displayed by the general public relating to the safe storage and preparation
of food. Following the establishment of the Food Standards Agency (FSA) in
the wake of the Wishaw outbreak, it has been given the role of watchdog and
educator. It is also responsible for making policy and enforcing standards
across the food industry in production, distribution and retailing.12
Under government sponsorship, lessons on food safety have now been
introduced into the curriculum in secondary schools in an attempt to
address the lack of understanding and knowledge. Until the level of education of the public at large relating to the handling, storage and cooking of
food improves, it is likely that further high-profile cases of infection related
to food-borne zoonoses will occur.
Direct contact
Physical damage of the skin or body tissue can lead to open wounds
capable of acting as a window for opportunistic pathogen transfer. The
12 | Zoonoses
obvious individuals likely to fall victim to infections from this route of
infection are people who handle animals in the course of their work, be they
agricultural workers, abbatoir workers, veterinary surgeons or animal
rescue workers. A less obvious group at risk from this mode of transmission
is any pet owner, especially those foolish enough to allow their animal to
kiss or lick them. Anybody who is bitten or scratched by an animal is placed
at an increased risk of contracting zoonotic diseases.
Rabies, fortunately currently not present in the UK but widely distributed in continental Europe, the Americas and most of the rest of the world,
can be transferred by the bite of an infected animal. Scratches inflicted by
an infected cat can transfer Bartonella henselae, the causative organism of
Cat Scratch Disease, to humans; however, there have also been reported cases
where owners have been infected after being foolish enough to allow cats to
lick their open wounds.13
Physical contact does not pose a risk just from the living animal. Animal
skins, hair or wool can act as a physical reservoir, particularly in anthrax.
Once known in its pulmonary form as Woolsorter’s Disease, infection can
occur following inhalation of spores from infected fleeces or hides during
processing. An isolated case in August 2000 in Bradford in a textile worker
is a striking example of re-emergence of a supposedly eradicated condition.
In 2006, two drummers, in unrelated incidents – one in the USA and one in
Scotland – both contracted inhalational anthrax, with a further case occurring in a drum maker in the USA in October 2008. In the past, customs officials in the USA and the UK impounded goatskin bags brought from Haiti
by tourists because these were found to be heavily contaminated with
anthrax spores.
Fomite spread
Touching an object or surface that has been in physical contact with an
infected animal can also lead to infection. This is known as fomite spread, and
is significant in ringworm and anthrax in its cutaneous form. The inoculum
on the fomites may consist of active organism, spores or encysted forms. After
infection, surface colonisation may occur or disease progression may occur
after the introduction of the initial inoculum into wounds, inhalation or
ingestion.
Vectors
Transmission of zoonotic pathogens may also be caused by the involvement
of vector species, particularly fleas, mosquitoes, lice and ticks. Physical
contact with animals can lead to transfer of arthropod vectors; however,
these vectors can also be encountered in the wider environment. Once
Introduction to zoonoses | 13
infected, arthropods may act not only as an infective vector, but also as a
persistent or temporary reservoir of infection with vertical transmission
from generation to generation via an infected mother to her eggs (transovarian transfer). Interestingly, controlling the arthropod vector is usually
the mainstay of prevention in many of these infections, because, without the
vector, humans and infected animals may occupy the same geographical
area without disease transfer taking place. The absence or control of the
vector may not arrest the disease in the animal host; however, it can prevent
or reduce the spread into the human population.
The spread of Lyme disease from deer to humans occurs mainly through
being bitten by a tick such as Ixodes dammini. In areas where it is endemic,
clearance of low vegetation in woods and around footpaths where the tick
loiters awaiting its next host reduces infection rates.4
Flea control by the use of insecticides or development-arresting agents,
in both domestic and commercial settings, is not only effective at
preventing the irritation associated with the mental and physical effects of
the bite, but also important in the control of possible zoonoses. Fleas are
usually host specific, especially as adults, when the female will try to obtain
a blood meal only from a preferred host; if the preferred host is not available, it will prey on any warm-blooded host. It is therefore not sufficient
to control fleas but also the normally associated host must be controlled.
This is particularly important in arresting the spread of Yersinia pestis, the
causative organism of plague, where both rats and their fleas require
control and eradication.
Mosquitoes can also be vectors in the spread of specific zoonoses. The
first outbreak of WNV in New York in 2000 was initially believed to be
St Louis Encephalitis. Carried by migratory birds, transmission to humans
follows the bite of infected culicoides mosquitoes, which have previously
obtained a blood meal from a diseased bird. An increase in the number of
mosquitoes in the urban New York area had followed discontinuation of
pesticide spraying on areas of standing fresh water, including Central Park,
where mosquito larvae develop. Coupled to a change in weather conditions,
which altered patterns of migration for infected birds, host, pathogen and
suitable vector were all co-located, leading to the outbreak. The disease has
subsequently spread widely across the USA and Canada.14
Humans preyed on by a vector are infected only if the vector has previously bitten an infected host. In most cases the vector is essential for the
pathogen to cross the species barrier. Controlling the vector can therefore
stop or slow transmission and spread of the pathogen, and its associated
disease. Once across the species barrier, infection spreads within the human
population, following similar pathways to any other diseases if the pathogen
has the potential for human-to-human transmission. These can include
physical and sexual contact, inhalation and ingestion.
14 | Zoonoses
Importance of zoonoses
The importance of zoonoses in terms of human health and well-being cannot
be underestimated. They affect how we live our lives, not only in a narrow
health-related sense but also in a much wider cultural context. The threat
that zoonotic diseases pose has shaped human history and many aspects of
the infrastructure of our physical and social environment, including animal
welfare – both domesticated and wild – food safety, and public health and
hygiene.
The emphasis on the importance placed on zoonoses is reflected in the
UK by the establishment of the joint Human Animal Infections and Risk
Surveillance (HAIRS) group. This is a multi-agency, cross-disciplinary group
with members from the HPA, the Department for Environment, Food and
Rural Affairs (DEFRA), the Veterinary Laboratories Agency (VLA) and the
Department of Health (DH); it is chaired by the HPA’s Department of
Emerging Infections and Zoonoses (EIZ) at the Centre for Infections (CFI).
The group meets monthly to identify and discuss infections with potential
for interspecies transfer (particularly zoonotic infections) which may pose a
threat to public health in the UK.
The HAIRS group undertakes systematic examination of formal and
informal reports on infectious incidents in animal and human populations
globally. A wide range of sources of information is scanned, including
informal news reports and bulletins, early warning communications, surveillance data and peer-reviewed scientific literature. The multidisciplinary
nature of the HAIRS group enables it to assess these reports in an objective
and scientific manner.
If infections are thought to be of potential significance, they are included
in the Infectious Disease Surveillance and Monitoring System for Animal
and Human Health: Summary of notable events/incidents of public health
significance which is produced monthly and circulated to a wide audience
within health (both human and animal) bodies and government.
The Centers for Disease Control and Prevention (CDC) undertakes a
similar role in the USA, monitoring emerging diseases, and advising federally
on countermeasures, treatment and epidemiology.
The earliest encounters of humans and zoonosis will have occurred
before the start of written history. Handing on to the next generation the
knowledge necessary to avoid illness or death from such diseases, in association with measures necessary to control other illnesses, has become part of
certain religious conventions and proscriptions. This is particularly true
when we consider food-borne zoonoses. The rules relating to food preparation and consumption within halal or kosher disciplines and secular folk
tradition encompass measures that can be linked to prevention or limitation
of the spread of diseases, including certain zoonotic infections.
Introduction to zoonoses | 15
Any infection stemming from an organism occurring in a foodstuff of
wholly animal origin, present in the animal or its products at the time that
it is ‘harvested’, is considered to be a food-borne zoonosis. In the past the
risks associated with consumption of food were an accepted part of day-today living and dying. Today, with greater life expectancy, and the desire for
and reality of a cleaner and safer environment, mortality associated with
such diseases has become unacceptable.
In modern western society much traditional knowledge has been lost with
social changes and fragmentation of family and social structures. A lack of
knowledge among most of the population about basic food hygiene, coupled
with our more extensive diet and demand for cheap and fast food, has led to
the situation where the safety and availability of our food supply is not so
much dependent on the turn of the seasons, as on specialised transportation,
storage and the application of modern farming methods. Supply of foodstuffs
is globalised, with fresh produce being air freighted and shipped by sea as
well as by land. The supply chain for some products has lengthened dramatically, and the need for clean ‘harvesting’ and appropriately monitored transportation has never been greater. Storage of produce, as either raw material
or processed product, at correctly maintained temperatures, has become
essential in protecting the public from a whole range of pathogens, including
some zoonoses.15
The changes in agricultural practice are particularly significant in relation
to the re-emergence of certain zoonoses, because many modern animal
varieties are bred to suit mass-marketing conditions and mechanisation of
processing. The development of these breeds and the methods of feed and
housing to optimise production often give rise to individuals with a decreased
immunity, or a higher population of pathogens. The increased risk that such
individuals pose to the wider animal population was addressed by the widespread use of antibiotics as growth promoters; however, after these products
were banned across the European Union (EU), producers have had to review
production methods and husbandry practice. Concern continues that the use
of antibiotics in agricultural production, especially those moieties related to
those used in human medicine, is leading to the emergence of resistant
pathogens, although studies suggest that the major driver behind the
development of resistance stems from antibiotic use/misuse in humans.16
Some of the more significant of these pathogens have a zoonotic potential, or are existing recognised causative agents of zoonoses. The organism
with probably the most developed resistance to antimicrobials is Salmonella
typhimurium DT104 R serotype. This had been found to be resistant to
ampicillin, chloramphenicol, streptomycin, sulphonamides, tetracyclines,
trimethoprim and the quinolones. A systematic review of the use of such
agents was undertaken by DEFRA. This triggered changes in agricultural
industry practice in the UK; however, it is unlikely to affect many other
16 | Zoonoses
countries’ use of these substances in agriculture. The previously mentioned
globalisation of the food market may become increasingly significant in our
attempts to manage antibiotic-resistant strains of bacterial pathogens.17
Much of the legislation in agriculture, and the food-handling industry,
stems from the need to deliver a safe product to the consumer. Failures in
systems or inspection procedures can lead to contamination of the production and supply chain. This in turn can lead to spectacular outbreaks, sometimes associated with fatalities, which serve as timely reminders of the need
for care in handling and storing food. The Wishaw outbreak in November
1996 of E. coli O157 killed 18 people initially, and was the second most
fatal incident ever recorded from this pathogen anywhere in the world. If we
include the three people who died afterwards from complications caused by
the infection, it becomes the most fatal. In the aftermath, the ensuing investigation into the outbreak and the subsequent report by Sir Hugh
Pennington formed one of the political catalysts that motivated the UK
government to establish the FSA. The report also highlighted the ignorance
in a large proportion of the public of basic hygiene precautions relating to
food storage and preparation, as have subsequent surveys.12,17
It is important to remember that, in agriculture, domesticated animals
are tended for gain; they can contract zoonotic disease by its transfer from
wild animal populations although sometimes links are difficult to prove, as
in the possible transfer of TB from badgers to cattle. Farmers will often
view zoonoses in solely monetary terms, which can have beneficial and
detrimental implications for any control programmes, depending on the
financial provisions of any compensation package. When contamination
with a zoonotic organism downgrades a product in quality and associated
value, the agricultural industry will spend much time and money in
attempting to control not only the initial infection, but also the associated
disease.
Present and past eradication campaigns, by either compulsory slaughter or
vaccination, have massively reduced the incidence of brucellosis, TB, anthrax
and tetanus, which were major causes of morbidity and mortality in previous
decades. The massive slaughter of cattle carried out after the outbreak of BSE
reduced the possibility of contaminated meat entering the food chain, and
probably reduced the spread and incidence of vCJD in the human population.
It also reduced the likelihood of breeding stock carrying the disease, so
preventing possible recurrence.
In a wider context, most of the population in the UK now lives and
works in urban areas, thus having no link with the countryside or its associated industries. Therefore most people’s closest encounters with animals
are with those species kept as companion or leisure species, in the domestic
setting. The idea of our pets being a potential source of disease has also
become more recognised.
Introduction to zoonoses | 17
Recommendations for pet owners on handling and caring for their animals
stem from the need to control potential zoonoses and reduce infection rates.
The appointment and use of dog wardens in urban areas, and campaigns by
the Royal Society for the Prevention of Cruelty to Animals (RSPCA) in the UK
and the Society for Prevention of Cruelty to Animals (SPCA) in the USA have
reduced the number of stray dogs and cats, diminishing the possible reservoir
for many animal diseases, including some zoonotic conditions.
Expanding interest in exotic animals as pets has generated its own problems. Snakes and reptiles are recognised as being the biggest population
reservoir for certain unusual Salmonella spp. As a general rule, the more
exotic the pet the more likely it is to carry unusual pathogens. Although
there have been no proven clinical cases arising from a zoonotic source, it is
known that armadillos are the only other species except humans that can
suffer from leprosy.18
Responsible pet owners usually safeguard their pets through veterinary
surgeon-led programmes to ensure comprehensive vaccination, worming
and pest control of companion animals. Public awareness of animal welfare
and the related animal health issues seems to increase with every episode of
the currently popular television series involving real-life ‘fly-on-the-wall’
animal hospital documentaries.
Geographically, the UK is very fortunate. The temperate climate and
physical isolation from continental Europe, coupled with the absence of large
native predators and non-human primates, make many of the physical and
legislational controls very effective and reduce the possibility of outbreaks of
certain zoonoses. The current quarantine regulations for the movement of
animals in and out of the UK prevent rabies in companion and other animals.
The introduction of ‘pet passports’ linked to an effective vaccination
programme, and the electronic tagging of vaccinated animals has proved very
successful for both owners and their animals in disease prevention.
The continental USA is very different; it has a wide range of ecological
and environmental parameters across a vast geographical area. Although it
has no native primates, there are vast wild animal populations, including
wild species closely related to domesticated animals, i.e. bison, mustang,
and wild rodent and bird populations that provide a reservoir for many
significant zoonotic diseases, including rabies and plague.
In both the UK and the USA, the social infrastructure offers protection
from zoonoses and other diseases in many ways that are taken for granted
or not recognised. The provision of high-quality, fresh, clean drinking water
confers protection against disease, including some zoonoses. Current levels
of public health and hygiene, with provision of safe sewage disposal and
processing, reduce the risks from water-borne organisms and environmental
contamination, reducing or preventing the spread of disease. The collection
and safe disposal of domestic and industrial organic waste also offers a high
18 | Zoonoses
degree of protection. All these measures form part of a protective umbrella
that shields the populations from spectacular outbreaks of diseases such as
cholera and typhoid – diseases that were endemic in the UK and the USA in
the nineteenth century, and are still seen routinely in other places around the
world.
Local authority responsibility for pest control forms an important part
of public health protection, preventing rats, mice and other alternative hosts
and their associated vectors from reaching sufficient numbers to precipitate
a zoonotic epidemic.
Historically this was not always the case. The Black Death and the
Plague of London were two memorable examples of epidemic zoonotic
infection affecting the UK. The causative organism Y. pestis, still kills
people every year in the south-western USA, Africa and Asia. We associate
the spread of plague with rats; however, they are not the only associated
host. Chipmunks, squirrels, dogs, cats, camels and rabbits can all act as
alternative hosts, and their associated fleas as disease vectors.19
The understanding of causative organisms, their detection, classification
and control have taken place only in the last century and a half. The
emergence of BSE, a prion disease, is an object lesson that should teach us
that, although our knowledge has advanced, we still have much to learn.
It is in the nature of human affairs that the response to control the
spread, or threat of spread, of disease normally follows rather than preempts an epidemic or well-publicised outbreak. It is important that healthcare professionals and society in general never forget that our infrastructure
and legislation, although sometimes cumbersome, shield us from much
morbidity and mortality associated with zoonoses and other diseases.20
Risk groups
Having discussed the threat that zoonoses pose, and the potential sources of
infection, let us now turn to identifying those individuals most likely to
contract disease on exposure to the pathogen. Most healthy adults with a
competent immune system are unlikely to acquire a zoonotic infection at
every exposure to the pathogen, even if an inoculum of potentially infective
magnitude is present. Against an infective challenge, they are also likely to
display better developed resistance to a range of possible causative organisms. This does not indicate that infection does not occur in this group – only
that it is less likely than in the groups shown in Table 1.3, who are identified
by the WHO as primarily ‘at risk’.
In general, those most at risk are those individuals who come into daily
contact with animals, are less resistant to infection or have less regard than
normal for hygiene routines. Children and elderly people have traditionally
been seen as more susceptible to certain of these infections. In addition,
Introduction to zoonoses | 19
Table 1.3 Main risk groups for zoonotic infection
Animal handlers
Neonates and children
Elderly and infirm people
Agricultural and food industry workers
Immunosuppressed or compromised individuals
Pregnant women
those individuals with a suppressed or damaged immune system stemming
from whatever cause, be it infectious disease, chemotherapy or organ
failure, are also at an enhanced level of risk. The realisation that animal
handlers and food-industry operatives have an enhanced risk of infection or
transmitting these diseases has led to health and safety legislation and
recommendations on working practices to reduce risk.
Pregnant women are at risk from particular zoonoses. Information about
Listeria, Toxocara felis, toxoplasmosis and chlamydial infection is now widely
available from maternity services and special-interest groups such as the
Toxoplasmosis Trust. Testing is not routinely carried out; however, individuals
with particular additional risk factors, such as employment in agriculture or
animal welfare, cat owners or food-industry operatives, would normally be
screened for any infections likely to pose a threat to mother or baby.
Since the emergence of human immunodeficiency virus/acquired immune
deficiency syndrome (HIV/AIDS), research has shown that individuals who
are immunocompromised or immunosuppressed, for whatever reason, are
more at risk from a range of pathogens, including some zoonoses. Patients
who have had a total or partial splenectomy, are on high or prolonged doses
of steroids, and patients undergoing chemotherapy or radiotherapy for treatment of cancer, also fall within this risk group. The diagnosis and recognition of the risk that cryptosporidial diarrhoea, psittacosis, toxoplasmosis
and TB (whether avine, bovine or human) poses for immunocompromised
patients have led to a process of risk reduction, and an extensive programme
of education for patients and healthcare professionals.21
Risk factors appear to be additive in terms of associated risk from
zoonoses. Any individual who falls within several of the identified risk
groups has an increased risk of infection. An immunosuppressed agricultural worker, who keeps pet cats, and eats unpasteurised dairy products,
while being licked by a pet dog, would be considered to be at a greatly
enhanced level of risk.
Genetic susceptibility may also be an additional risk factor. The pattern
of transmission demonstrated by the prion responsible for scrapie in sheep
20 | Zoonoses
appears, on the best available evidence, to be a good model for the behaviour of BSE in cattle and vCJD in humans. It has been established that a
sheep must have a certain amino acid sequence on its genes to be susceptible
to acquiring a primary case of scrapie from environmental sources. The identification of clusters of human cases of vCJD in Leicestershire and Doncaster
demonstrated the similarity in genetic make-up of the victims and offers a
vital clue to unravelling the mystery of susceptibility and risk associated with
exposure to the causative agent.
Implications for industry
In the UK and the USA, a developed system of legislation and mandatory
inspection safeguards us from many zoonotic infections linked to animals
and processes within our system of food production. To be effective these
controls have to be enforced rigorously at all levels within the chain from
the animal, through processing and distribution to the arrival at the
consumer. At harvesting, routine inspection of meat, livestock slaughterhouse controls and the advisory work of DEFRA and the US Department
of Agriculture (USDA) reduce transmission rates of many potentially
dangerous pathogens. Further down the process of field to food, enforced
regulation of food suppliers and vendors, sell-by dates, refrigeration and
education of consumers all lead to lower levels of infection and associated
illness or mortality.
Produce loss
Uncontrolled zoonotic disease can lead to produce loss caused by poor
appearance or product contamination by pathogens. In the event of contamination or loss of quality, there will be an associated monetary loss, with
destruction or downgrading of produce. Controlling the risk of zoonoses
often requires increased inputs to achieve a higher quality in the finished
product, so as to reach the standard required by processors, suppliers and
consumers. Charging a higher price for the produce can often offset these
costs; however, food pricing is a sensitive issue. In the quest for food cheap
enough to compete in the global market, it may be very tempting for a
producer to cut corners, and this can lead to outbreaks of disease stemming
from inadequate or inconsistent standards of treatment or implementation.
Personnel loss
When zoonoses are present, personnel within the industry can suffer from
anxiety, which may be as debilitating as the possible infection. Frank illness
will often lead individual workers to change career path or employment.
Introduction to zoonoses | 21
Long-term effects due to prolonged exposure of pathogens may lead to
disability and ultimately increased likelihood of morbidity and mortality,
where appropriate measures to control spread of disease are not in place.
This places additional health and safety requirements on employers to protect
their workers from these risks.
The associated issues of compensation to individuals contracting
zoonoses in the work place and the issues of recruitment and retention have
encouraged producers and processors to put good working practices in
place.
Public impact
The impact of zoonoses on the public (Table 1.4) can be profound, especially
when the knowledge and understanding are mainly fuelled by adverse and
dramatic media hype. Food scares are probably the most memorable of these
manifestations. Eggs, beef, milk, cheese and pork have all suffered a bad
press in their turn. In many of the cases reported by the media the causative
agents of the outbreak were already well known, and the problem was
already being addressed before the media chose to sensationalise it. In a
population dominated by an appetite for sound bites, profound fear and
anxiety can rapidly be generated by such reports. The only solution to the
problem is education relating to the true likelihood of infection and its
associated risks.
Media misreporting of zoonoses can be dramatic and misleading. During
the recent outbreak of foot-and-mouth disease in the UK, there was an
isolated news report stating that during the 1968 epidemic a man had died
of the disease. An extensive search of reference books, archival material and
other sources revealed no confirmation that there was any evidence of footand-mouth disease being a fatal zoonotic disease. Only two confirmed cases
had been recorded in humans: one in the 2001 outbreak and one in 1967.
There was overwhelming evidence that, although a wide range of animals
were either susceptible to the disease or capable of acting as carriers, under
normal circumstances humans were not liable to contract the affliction. No
Table 1.4 Public impact of zoonoses
Food scares with boycotts and dietary change
Increased legislation and consumer/producer costs
Public and private fear and anxiety
Morbidity and mortality
Political fallout
22 | Zoonoses
trace could be found of any report either in the UK or anywhere else in the
world linking human fatalities with the disease.22
In desperation, a phone call was made to a friend and colleague who is
a consultant epidemiologist. After he had finished laughing, he told me the
following story:
During the 1967–1968 outbreak, the British Army was employed to go
on to some farms to kill and destroy the livestock. On one farm, night
was falling as the troops carried on the work of building and lighting
the funeral pyres. The farmer and his family had vacated the farmhouse
and it stood empty with all the family’s possessions inside. Some of the
soldiers saw a man sneaking around the buildings and then break a
window and enter the house. When he re-emerged clutching items he
had looted from the house they were waiting for him. When called
upon to stop by the now armed soldiers, the looter decided to try and
run away and make his escape, so the troops shot him. He died, not of
foot-and-mouth but of high-velocity lead poisoning. His death did
much at the time to dissuade other opportunist criminals from looting
deserted farmhouses.
The moral of this story appears to be that, when reading reports of
zoonoses in the media, it is essential to remember the old adage ‘Don’t
believe everything you read in the newspapers’. It could be argued that,
although not directly responsible for the fatality, the infection was, at one
remove, associated with the death, if somewhat apocryphally.
Long-term effects of food zoonoses on the public are usually confined
to consumer avoidance of products perceived as suspect. Food retailers
usually respond to such crises by demanding or imposing higher standards
on their suppliers, which in their turn force producers to increase their
inputs. Confidence in foodstuffs is easily lost, and takes a long time to be
regained.
Morbidity and mortality arising from zoonoses are of particular public
concern. The implications for the food industry of such events were
explored earlier in this chapter; however, the public impact is not confined
to those who work within the various stages of the food production and
food-retailing chain. Individuals may become convinced that they are going
to die, regardless of the true risk, from zoonotic infections; in the last few
years in the UK, several individuals have committed suicide fearing that they
were going to die of vCJD.
Reports of children dying from E. coli infection, following an educational visit to a farm, fuels and highlights the hysteria such cases are capable
of generating. Many parents are extremely chary of allowing their children
to go on organised agricultural visits or camping holidays. Although the
statistical risk of infection is low, and the risk of mortality almost negligible,
Introduction to zoonoses | 23
one of the less attractive facets of our society is a very obvious driver of
political policy in this context. There appears to be a concerted desire within
certain groups for risk reduction in normal everyday affairs to the point of
absurdity. The complete absence of risk is unachievable, and would require
restrictions to be placed on every aspect of human endeavour. This fallacy
of a completely risk-free existence is an ever-present and all-pervading urban
myth, which needs to be arrested.23
The realisation that education in both cerebral and physical skills is the
most important factor in protecting individuals and society from the risks
that these diseases pose needs emphasising by all involved in the day-to-day
health of the nation. There is no substitute for knowledge, the provision
and application of which could safeguard people far more effectively than
legislation, and which would also ensure that future generations lead
healthy, full lives.
In general, consumer pressure groups serve a useful purpose in encouraging government and others to be responsible when crises arise. In contrast,
they can also increase public aversion or panic by unrestrained and illinformed lobbying. This is especially significant where their agenda does not
coincide with, or is diametrically opposed to, any of the other parties affected
by the issue. The understandable aversion response of many members of the
general public to the BSE/vCJD outbreak resulted in many people in the UK
choosing to eschew meat, and become vegetarians. As a considered decision,
based upon the known facts, this was a reasonable conclusion for people to
reach. The less considered and sinister aspect was the declarations made by
the more extreme groups and individual activists involved in the animal
rights and extreme vegetarian movements, who informed the world that this
was a judgement, or punishment, visited upon wicked people for their
consumption of meat.
The more dramatic incidents associated with zoonoses can – especially if
morbidity or mortality occurs – lead to significant political repercussions not
only for entire governments and their departments, but also for individual
politicians. Resignations over unwise utterances are not unknown. DEFRA or
its various previous incarnations and USDA have been the graveyard for many
an aspiring politician. Quick-fire legislation has peppered UK parliamentary
proceedings over many decades and is often a knee-jerk response to zoonotic
problems. As with many measures introduced rapidly, it can often be
poor-quality law, being too draconian, too complex or unenforceable.
Much of the increase in regulations associated with animal husbandry
has been the result of the perceived need to introduce new systems, rather
than ensuring that existing schemes were made to work efficiently and
comprehensively. Often the need to be seen to be doing something
outweighs the more pragmatic approach, especially where this could lead to
loss of votes or position.
24 | Zoonoses
This chapter has attempted to introduce zoonoses and place them in a
wider societal context, and sets the scene for the more detailed examination
in the remainder of the book. The following chapters aim to examine the
more significant conditions in greater detail.
Once an awareness of these diseases is gained, it is remarkable how
many chance conversations with patients, relatives or friends, snippets from
radio or television, or newspaper and magazine stories become associated
with these conditions. This disparate group of diseases and pathogens is of
major significance in our day-to-day living and its associated processes, and
it is not a matter that we should ever forget or ignore.
References
1. World Health Organization. Ebola Haemorrhagic Fever in the Republic of Congo. May
2005 and updates May and June 2005. Geneva: WHO, 2005.
2. Department of the Environment, Food and Rural Affairs. Zoonoses Report UK 2006.
London: Defra, 2007.
3. Sechi LA, Mura M, Tanda E, Lissia A, Fadda G, Zanetti S. Mycobacterium avium sub.
paratuberculosis in tissue samples of Crohn’s disease patients. New Microbiol 2004; 27:
75–7.
4. Hayes EB, Piesman J. How can we prevent Lyme disease? N Engl J Med 2003; 348:
2424–30.
5. Palmer S, Brown D, Morgan D. Early qualitative risk assessment of the emerging
zoonotic potential of animal diseases. BMJ 2005; 331: 1256–60
6. Reiter P, Sprenger D. The used tire trade: a mechanism for the worldwide dispersal of
container breeding mosquitoes. J Am Mosq Ctrl Assoc 1987; 3: 494–501.
7. Taylor LH, Latham SM, Woolhouse ME. Risk factors for human disease emergence.
Philos Trans R Soc Lond B Biol Sci 2001; 356: 983–9
8. Clostridium perfringens gastroenteritis associated with corned beef served at St Patrick’s
day meals – Ohio and Virginia, 1993. MMWR 1994; 43: 137–8, 143–4.
9. Geiter L, ed. Ending Neglect: The elimination of tuberculosis in the United States.
Washington DC: National Academies Press, 2000.
10. Health Protection Agency. Statutory Notifications of Infectious Diseases in England and
Wales: MIDI Report for 2006. London: HPA. 2007.
11. Prusiner SB. Prions. Proc Natl Acad Sci USA 1998; 95: 13363–83.
12. The Pennington Group. Report on the Circumstances Leading to the 1996 Outbreak of
Infection with E. coli O157 in Central Scotland, the Implications for Food Safety and the
Lessons to be Learned. Edinburgh: The Scottish Office, 1998.
13. Chomel BB, Belotto A, Meslin FX. Wildlife, exotic pets and emerging zoonoses. Emerg
Infect Dis 2007; 13(1): E-edn.
14. Watson JT, Gerber SI. West Nile Virus: A brief review. Pediatr Infect Dis J 2004; 23:
357–8.
15. World Health Organization. WHO Global Strategy: Safer food for better health. Geneva:
WHO, 2002.
16. Teale CJ, Martin PK, Watkins GH et al. VLA Antimicrobial Sensitivity Report. Norwich:
HMSO, 2004.
17. Advisory Committee on the Microbiological Safety of Food. Report from the DEFRA
Antimicrobial Resistance Co-ordination Group (DARC). London: Defra Secretariat,
2005.
18. Public Health Laboratory Service. Salmonella infection and reptiles. PHLS press release.
London: Public Health Laboratory Service, 2000.
Introduction to zoonoses | 25
19. Laudisoit A, Leirs H, Makundi RH et al. Plague and the human flea, Tanzania. Emerg
Infect Dis 2007; 13: 687–93.
20. Gratz NG. Emerging and resurging vector-borne diseases. Annu Rev Entomol 1999; 44:
51–75.
21. O’Rourke K. Veterinarians’ role in the AIDS crisis. JAVMA 2002; 221: 764–5.
22. World Health Organization. Foot and Mouth Disease: Consequences for public health.
Geneva: WHO (CSR), 2001.
23. Stirling J, Griffith M, Dooley JS et al. Zoonoses associated with petting farms and open
zoos. Vector Borne Zoonotic Dis 2008; 8(1): 85–92.
2
Zoonoses of companion
animals
With a population, at the last recorded census in 2004, of 6.8 million dogs
and 9.58 million cats, the UK deserves its reputation as a nation of animal
lovers. Of the 25 million households in the UK approximately half own a
Table 2.1 Companion animal populations in the UK and the USA
Percentage of
households
Pet type
No. of households
Pet nos
In the UK
24.6
Cats
6.1 million
9.58 million
21.1
Dogs
5.2 million
6.8 million
4.6
Rabbits
2.5
Hamsters
7.2
Birds (including parrots, finches, etc.)
1.39 million
0.9
Horses/Ponies
975 000
In the USA
31.6
Cats
33.2 million
70.8 million
36.1
Dogs
37.9 million
61.6 million
4.6
Birds
4.8 million
10.1 million
1.7
Horses
1.75 million
5.1 million
Sources:
Pet Food Manufacturers’ Association. UK Pet Population Statistics, London: PMFA 2004.
The Henley Centre. A report on research on the Horse Industry in Great Britain. London: Defra and British
Horse Industry Confederation, 2004.
Wise JK, Heathcott BL, Gonzalez ML. Results of the AVMA survey on companion animal ownership in US
pet-owning households. JAVMA 2002;221:1572–3.
Zoonoses of companion animals | 27
pet of some description. In the USA only about 34% of all households had
pets of any description. These figures include only the accepted classes of
companion animals. People also keep pets as diverse as bats, tarantulas,
reptiles and sharks.
As the population of the UK has become increasingly urban, and families have become more fragmented, companion animals have gained importance. Studies show that there is a range of benefits in terms not only of
health, but also in general well-being for individuals who keep pets. People
who are bereaved, drug addicts, mentally ill or in long-term care settings
have all been shown to benefit from animal contact.1,2
Under a scheme run by Pets as Therapy (PAT), part of the Pro Dogs
Charity (PRO), there are over 10 000 dogs and their owners who visit
hospitals, hospices and residential homes regularly as therapeutic support
for patients. An equivalent scheme runs in Scotland called Therapet.
The benefits of pet ownership, or contact, do come at a price, in terms of
healthcare, especially in people who have certain medical conditions. This
chapter explores the more significant zoonoses associated with the main
companion animal groups. Horses are also included in this chapter, as most
of the 975 000 horses in the UK are not working animals in the accepted
sense, being mostly kept for leisure purposes. This is not so true in the USA,
although at least 6.6 million of the 9.2 million horses are designated in the
American Horse Association survey as being kept solely for leisure.
Birds
Introduction
The species of birds kept as companion animals are extremely varied. Caged
birds are often kept as pets, with budgerigars and canaries still being
popular choices. There are many other species of bird as companion animals
with everything from parrots, parakeets, cockatoos or cockatiels, to racing
and fancy pigeons, rare poultry, hawks and owls. Most species have at least
one breed society or a network of fanciers.
The main zoonotic diseases that birds can harbour are normally spread
by inhalation of dried faecal material, often during cleaning out of cages or
housing. Most infected people show no signs of disease; however, elderly,
young and immunocompromised individuals are particularly at risk.
Mycobacterium avium complex, Cryptococcus neoformans and psittacosis
are particularly important in human immunodeficiency virus/acquired
immune deficiency syndrome (HIV/AIDS) patients, where development of
any of these diseases can be rapidly fatal. Recently, with the emergence of a
strain of highly pathogenic avian influenza, H5N1, which has the potential
to become a pandemic strain in humans, there has been an increased interest
28 | Zoonoses
and awareness of the risks that avian zoonotic pathogens pose. The
pathogens covered in this chapter are not the only zoonoses of birds; others
can be found in the section on birds in Chapter 3, especially avian flu, and
also in Chapter 7.
Cryptococcosis
This is an uncommon infection except in immunocompromised patients,
especially those with HIV/AIDS. The causative organism is Cryptococcus
neoformans, a yeast-like fungal agent that occurs worldwide. The organism
is naturally found in birds, cats and dogs, cattle, sheep, horses, plants and
soil. It is an uncommon pathogen and appears to have a predilection for
pigeons because it is found most commonly in these birds or in their faecal
matter. It has also been found in other birds, but less frequently.3
Disease in animals
Although it is rare in cats and dogs, it usually presents as systemic disease
affecting the respiratory tract and central nervous system (CNS), and often
animals present with enlarged lymph nodes. Occasionally distinctive skin
lesions appear. It is seen as an opportunistic pathogen in cats that are
immunosuppressed, particularly together with feline leukaemia virus (FLV).
This is a disease that progresses in cats in a similar manner to HIV in
humans.
Transmission
Transmission to humans is usually by inhaled dusts and aerosols; however,
there is some evidence that inoculation of wounds can also initiate infection.
Healthy individuals show no clinical signs of disease, although the organism
can be grown from mouth swabs, skin scrapings and gut contents. Patients
who are immunosuppressed as a result of organic disease, e.g. HIV/AIDS or
leukaemia, or long-term steroid therapy are at a small but significant risk of
catching the disease.4
Disease in humans
The disease usually presents as meningitis in immunosuppressed patients. As
with animals, skin papules, usually with a necrosed centre, may be seen;
however, this is rare. The disease may also be systemic, affecting the gut,
lungs and nervous system.5
Treatment
Treatment for cryptococcosis is usually initiated in specialist units, using a
variety of systemic antifungals. Therapy has to be closely monitored due to
potential drug interactions and potentially life-threatening side effects,
Zoonoses of companion animals | 29
especially in immunocompromised patients. Women being treated for this
condition are usually advised to use effective contraception due to the
potential teratogenicity of the drug therapy.
Prevention
As the condition is rare, blanket prophylaxis to pre-empt infection is not
recommended, especially as interactions with retrovirals can complicate
therapy regimens. Widespread use of antifungal drugs could also lead to the
development of resistant strains.
Complete protection from the organism is not possible due to the wide
range of possible animal hosts and environmental sources. Immunosuppressed
patients should avoid exposure to pigeons and their faeces, especially coops or
roof spaces where birds roost.
Mycobacterium avium complex
Tuberculosis or TB is classically caused by Mycobacterium tuberculosis
(hominis), although M. bovis, a zoonotic pathogen, is responsible for a
small percentage of cases. The term is often loosely used to describe a complex
of infection states caused by a variety of aerobic bacteria of the genus
Mycobacterium.
Several sections in this book deal with various members of this genus,
some of which are associated with various diseases states that are often classified under this umbrella term. As the first section dealing with this family
of microbes, there are some general remarks relating to these infections
below.
General remarks
Mycobacteria are aerobic bacilli found widely in a variety of animal species,
including humans, and also free living within the environment. They are
intracellular dwelling and particularly capable of developing resistance to a
variety of antimicrobial agents. The most significant members of the genera
in terms of possible zoonotic infections are M. bovis (found in cattle, dogs
and pigs), M. avium (found in birds, pigs and sheep) and M. marinum
(found in seals, sea lions and fish).
M. tuberculosis is mainly found in humans and the infection circulates
within that population. For this reason it is not seen as a zoonotic disease,
although it has been isolated from primates, cattle, dogs, pigs and parrots.
In general, mycobacteria are transmitted from infected individuals, be
they humans or animals, primarily by the aerosol route. Infection is also
possible via contact with, or ingestion of, infected tissue, bodily secretions,
or body fluids such as blood or plasma. Cutaneous inoculation is also possible
via cuts or lacerations.
30 | Zoonoses
After infection there can be a short or long pre-patent period depending
on the health of the individual and the strain and virulence of the organism.
The disease progresses with the organism becoming disseminated throughout
the body. Major sites of colonisation are usually the lungs, lymph nodes,
circulatory system, liver, spleen and other major organs. Signs and symptoms
vary depending on the main sites of infection. The classic tubercular lung
disease usually presents as a persistent cough that does not resolve. As the
condition worsens, quantities of mucus are produced which may contain
traces of blood. As pulmonary damage worsens, coughing up of overt blood
(haemoptysis) is seen. Other symptoms include loss of appetite and anorexia,
fever that may be episodic, weariness and extreme fatigue. It is thought that
the ‘consumption’ of the last centuries, immortalised in romantic fiction and
drama by leaving the hero or heroine of the piece dying dramatically, was
probably pulmonary TB. The disease can also manifest in a cutaneous form
with ulcers and lesions progressing to persistent suppurative sores.
M. avium is endemic in wild and caged birds and, coupled with M. intracellulare, it can cause a form of TB with both pulmonary and systemic forms
in susceptible humans. This is known as Mycobacterium avium complex or
MAC. It is a major clinical problem in immunocompromised patients and is
one of the marker infections in the progression of HIV infection to AIDSrelated complex (ARC). There is some debate as to whether MAC is a
zoonotic infection because the pathogen is widespread in the environment
and some isolates display different serological profiles to classic bird-borne
types. However, there is some evidence that infection may spread from birds
in occupational and domestic settings. In addition to the well-documented
manifestation of MAC in HIV/AIDS, there is continuing discussion about the
possible involvement of M. avium in Crohn’s disease. Any clinical links are
as yet unproven.
Transmission
Transmission of M. avium usually occurs by inhalation of infected aerosols
or dusts. Sneezing or coughing birds with subclinical cases can be prolific
excreters of viable organisms. Ingestion or cutaneous contact has been
postulated as an alternative route of infection; opinion is divided on the
importance of this particular mode of infection.
Disease in humans
Infection usually starts with the development of foci in either the lungs or
the gastrointestinal tract. Disseminated infection may develop from these
foci, with an associated morbidity and mortality, especially in cases of
advanced HIV.
Zoonoses of companion animals | 31
Diagnosis
Diagnosis is often presumptive because M. avium can cross-react to skin
testing for other mycobacterial conditions. Isolation and culture are difficult
due to the intracellular nature of the bacterium; however, this does produce
a definitive diagnosis and also allows drug-sensitivity testing.
Treatment and drug prophylaxis
There are specific problems with antimicrobial-resistant serotypes in this
infection, which is especially important in immunodeficient patients. There
are also additional complications relating to dose adjustments of other
concomitant drug therapies when treatment or prophylaxis for MAC is
necessary. For this reason patients with MAC are not normally initiated on
drug therapy in primary care. Specialist secondary care practitioners initiate
treatment.
Rifamycin has been used in the UK; however the adverse effects of the
drug may mimic MAC infection and so the progress of treatment has to be
monitored by culture and on serological findings.
By contrast, in the USA an alternative regimen is used with a macrolide
antibiotic, either clarithromycin or azithromycin, being considered suitable
alone or in combination with rifabutin. The premise for the use of this
combination therapy is that it reduces the risk of producing drug resistance
and also of secondary infections.6
Prophylaxis aimed at preventing the development of disseminated MAC
is recommended for patients with a CD4 cell count ⬍ 50 cells/lL. There is
some evidence that prophylaxis can be discontinued when the CD4 cell count
tops 100 cells/lL. This is a decision that must be made carefully by secondary
care agencies. The use of highly active antiretroviral treatment (HAART)
has altered the prevalence and treatment of MAC and its prophylaxis in
HIV/AIDS patients, and the latest recommendations should always be
followed.
Psittacosis (ornithosis)
Psittacosis is the classic ‘parrot’s disease’ of comedy, although clinical cases
will not have patients splitting their sides with laughter. The disease is also
referred to as avian chlamydiosis (AC). The causative agent is Chlamydophila
psittaci (formerly known as Chlamydia psittaci) which typically, like all other
Chlamydophila spp., is an intracellular parasite. It has a biphasic reproductive
cycle, with only one phase being infectious. A closely related organism is an
important zoonosis of sheep, although the pattern of disease and the
transmission pathway are very different (see p. 91).
32 | Zoonoses
Disease in animals
C. psittaci is widespread in both wild and domestic birds. Parrots are the most
frequently encountered hosts in a companion animal setting, and 1% of the
population are estimated to have active disease at any time. Other potential
hosts as zoonotic reservoirs include turkeys, ducks, geese, pigeons, starlings,
pheasants and birds kept for competitive showing. Estimates have been made
of the prevalence of infection in wild pigeon populations in the USA. These
range from 50% to 100% of all feral pigeons within a population sample.
The number of birds infected within a population increases where overcrowding or stress occurs. The associated levels of inadequate ventilation and
cleanliness in poor and overcrowded commercial housing also promote the
rate of infection with the disease in commercial flocks. Infection in birds is
usually subclinical and may remain latent for a period of months or years.
Apparently healthy birds can shed viable organisms and cause infection in
others during the latent period. The pathogen can survive in the environment
for extended periods following contamination with infected droppings or
aerosols originating from the nasal discharge of infected birds. The organism
is resistant to drying, and can be found in dust in hen houses, pigeon lofts
and other roosting sites. Bird cages, pet shops, lofts or roof spaces inhabited
by wild and feral species must be treated as possibly contaminated.
Transmission
Transmission to humans follows inhalation of dried bird faeces or nasal
discharge from infected birds, direct contact with birds or their feathers and
by bird bite (a rare but possible occurrence, especially in aggressive nondomesticated parrots). Once across the species barrier, human-to-human
transmission may occur by the aerosol route. Poultry workers in the turkey
industry, in either rearing or processing birds, show an increased incidence of
the disease. Individuals who handle wild, pet or domesticated birds in any
setting are at increased risk. However, obvious risk is not reliable as a diagnostic yardstick, because 20% of cases reviewed in the USA could remember
no overt contact with birds. Verification of the presence of C. psittaci may be
difficult; as yet there is no rapid test available to differentiate serologically
between this and other Chlamydophila spp.
Disease in humans
The infection may be subclinical, leading to under-diagnosis. Onset of the
disease is gradual; an incubation period of 1–2 weeks is followed by a series
of symptoms similar to influenza or a respiratory infection. Symptoms include
malaise, fever, chills and headache, and associated photophobia and nonproductive cough. An unusual feature is that, although the temperature is
elevated, the pulse rate does not undergo an associated rise. Joint and muscle
Zoonoses of companion animals | 33
pain with weight loss and loss of appetite may also be seen. Occasionally a
full-blown acute pneumonia may occur.7
Rarely seen in children, the infection is most severe in elderly and immunocompromised individuals. In severe cases, liver and splenic enlargement with
gastrointestinal symptoms, including vomiting, diarrhoea and constipation,
may occur. Cardiac involvement with valve failure and endocarditis is
possible. Spread into the CNS may follow with disorientation, depression or
delirium followed by meningitis or encephalitis. Severe breathing difficulties
can follow exacerbation of pulmonary symptoms. Death can follow
pulmonary insufficiency and toxaemia. In clinical cases fatality occurs in
approximately 1%.
Treatment
Treatment consists of tetracyclines as the antibiotic of choice, with supportive
measures. Tetracycline is given at a dose of 250–500 mg three to four times
daily for at least 7 days, with the treatment period extended as needed.
Doxycycline has also been used at a dose of 200 mg/day, as has azithromycin
and erythromycin, although their use is normally associated with
Chlamydophila spp. which cause urinogenital infection or endocarditis. Early
diagnosis is very important to reduce complications, and prolonged treatment
may be required to prevent reinfection or relapse in some cases. It is
recommended as good practice to inform a consultant in communicable
diseases of cases of psittacosis where there could be a public health risk.
Prevention
Prevention depends on education of individuals in high-risk groups. Early
detection of cases in birds is an important part of any prevention strategy.
Reduction in stress and overcrowding is recommended to control infective
spread. Placing birds suspected of having psittacosis in isolation until they
can be tested, and subsequently treated or slaughtered in confirmed cases, is
also recommended as good working practice. Treatment of imported
companion birds with prophylactic antibiotics is important, especially
before their sale as pets. Good flock management at agricultural sites can
reduce infection, and feral birds should be excluded from feed mills and
rearing sheds. No vaccines are available for either humans or birds.
Cats and dogs
Introduction
The population of cats in the UK was estimated as 9.58 million in 2004 (the
latest survey). This figure shows a marked increase in the number over the
34 | Zoonoses
previous decade, and has now outstripped the dog population. This is associated with changes in lifestyle: urban living, employment patterns and the
number of single-person households have all altered the balance of ownership towards animals that require less care. The Pet Food Manufacturers’
Association (PFMA: http://www.pfma.com) has estimated that 34% of
households in the UK own at least one cat, with the greatest density in
south-east England. A similar pattern is seen in the populations associated
with Europe and the USA, with 47 and 75 million cats, respectively.
The reasons most frequently given for cat ownership are companionship
and love, with many cat owners allowing their pets the run of their houses.
Cats are capable of carrying a wide range of zoonoses and, as the pattern
of behaviour of certain owners falls outside the normal realms of good
hygienic practice, there are many opportunities for the transfer of infection
to occur. As the companion animal of choice for large numbers of the
population, the control and prevention of cat-associated zoonoses are
particularly important.
Cats are especially significant in two well-recognised conditions – toxocariasis and toxoplasmosis – both of which pose a well-publicised risk to
children and pregnant women. Cat Scratch Disease (CSD) is now recognised
as a serious condition in immunocompromised individuals, and the effective
treatment or prophylactic therapy of cat owners with HIV/AIDS has begun
to reflect the importance of this and other potentially serious zoonotic
conditions.
Dogs
The PFMA survey for 2004 shows an estimated 6.8 million dogs in 5.2 million
households across the UK. However, dogs are not just kept as companions;
working dogs are still part of farming and sheepdogs are still invaluable for
managing sheep, especially on extensive upland farms. Dogs are also used
by the police, and as drug and explosive detectors, not forgetting hearing
dogs for the deaf and guide dogs for the blind.
Many of the zoonoses associated with cats may also be acquired from
canines; however, there are pathogens that may have a species-specific
subtype; although differentiation may be possible it is not necessarily useful
in clinical terms.
The following zoonoses are associated with either cats or dogs or with
both, and are particularly important because they affect the urban population, who are often more in need of education and assistance in understanding
that their companion animals, however cute, may be the source of serious
disease.
Zoonoses of companion animals | 35
Cat Scratch Disease
Cat Scratch Disease is caused by a rickettsia, Bartonella henselae (formerly
known as Rochalimaea henselae). Little recognised in the UK, it is widely
documented in the USA and shows a worldwide distribution. Other
Bartonella spp. cause a number of diseases in humans, including trench
fever (B. quintana), which occurs worldwide. B. quintana is transmitted to
humans via bites from lice or fleas associated with rats.
Transmission
Although CSD was recognised previously as a distinct infection and illness,
it was not until 1992 that the causative organism was identified because of
difficulties in culturing the slow-growing bacterium. Infected cats carry the
pathogen and show no ill effects; however, they can shed viable organisms,
especially in their urine, for prolonged periods. In-species transmission
between cats occurs usually through physical damage sustained in fighting,
i.e. bites and scratches. Recent research has indicated that a flea that sucks
blood from an infected cat becomes infected. B. henselae replicates and
colonises the flea’s digestive tract; subsequently viable organisms are passed
in the faeces. Cats may be infected by bacteria in flea faeces introduced into
a flea-bite wound or other cuts and abrasions by either scratching or
grooming. This mode of transmission, of the introduction of contaminated
arthropod faeces into wounds, occurs in other diseases caused by Bartonella
spp. and is especially important in the rodent reservoir for trench fever.8
Human infection follows either a scratch or a bite from an infected
animal. Saliva contaminated with flea faeces from the cat grooming itself or
nibbling at the site of flea bites is presumed to be one source of the infective
inoculum. The role of fleas in the direct transmission of B. henselae from
cats to humans has not been characterised yet. Humans may also be able to
contract the infection in a similar manner to cats by introducing flea faeces
into a wound; this hypothesis is currently under investigation.
Disease in humans
A primary lesion appears at the injury site, usually forming a single, circular,
pink, flat lesion or plaque or series of plaques along the length of the scratch.
The initial primary lesion appears in 50% of cases after 10 days. Transient
lymph node tenderness and swelling with some discomfort may develop and
then regress. In about 15% of cases progression to more serious disease
occurs with serious sequelae, which may include CNS damage, osteomyelitis
and involvement of the lungs and respiratory tract. Immunocompromised
patients may develop liver damage and hepatic lesions.9
36 | Zoonoses
CSD can also cause bacillary angiomatosis, a vascular proliferative
disease seen in individuals with established HIV or those who are immunocompromised for a variety of reasons. It can be fatal, progressing from skin
lesions, which are the most common symptom, to lesions in the bones and
bone marrow, gastrointestinal and respiratory tracts, lymph nodes and CNS.
Fever, weight loss, and associated swelling and tenderness of various internal
organs are commonly seen. It is also suspected of causing bacillary peliosis,
a condition associated with relapsing bacteraemia and endocarditis. Cystic,
blood-filled spaces develop in the liver, spleen or lymph nodes. Fever,
abdominal pain and weight loss follow gastrointestinal disturbance. A febrile
bacteraemic syndrome associated with B. henselae is also seen in immunocompromised patients. Symptoms include chronic or cyclical fever, joint and
muscle pain, and severe headache. Patients with long-term asymptomatic
infections may shed viable organisms in their urine.
Treatment
Treatments recommended in the US literature are reserved for complicated
cases. Simple cases are not usually considered for therapeutic intervention.
In cases with complications, azithromycin 500 mg daily for 1 week followed
by 250 mg for 4 weeks is recommended. In bacillary angiomatosis erythromycin 500 mg once daily for 3 months or doxycycline 100 mg twice daily
for 3 months may be required to prevent relapse and effect a full cure. In
peliosis hepatitis the same drugs may be used for 4 months.
Prevention
Owners are advised to avoid rough play with cats to reduce the risks of
scratches and bites. Any wounds inflicted by the cat should be washed and
disinfected immediately. The common-sense precautions of preventing a cat
licking any human wound and washing any exposed areas after petting or
stroking the cat are strongly recommended. Children and adults, especially
those who are immunosuppressed, should avoid stroking or touching stray
or feral cats. Immunocompromised patients, especially those with advanced
HIV (or ARC), may need to consider keeping their cat indoors at all times
to prevent it associating with other cats that may be infected.
Echinococcosis
Hydatid disease or hydatidosis
Worldwide, echinococcosis is caused by a number of species of Echinococcus
that belong to a subgroup of tapeworms known as tissue cestodes, because
for part of their larval life cycle they encyst in body tissues. Echinococcus
granulosus causes cystic echinococcosis, the most commonly seen form of
the disease. Another species, E. multilocularis, causes alveolar echinococ-
Zoonoses of companion animals | 37
cosis. In the UK only E. granulosus has been found and is usually confined
to areas where there is intensive sheep farming. E. multilocularis has been seen
in other countries in western Europe, but as yet no clinical cases have been
seen in the UK, although there is a theoretical risk that tourists or travellers
could pick up E. multilocularis while abroad.
The disease state caused by E. granulosus is sometimes known as unilocular hydatid, because only a single site is initially colonised, whereas
E. multilocularis colonises multiple sites simultaneously and therefore leads
to more serious clinical disease. In humans these tapeworms cause a condition
known as hydatid disease where cysts of great size may develop over long
periods post-infection.
Luckily, human infections in the UK with the tapeworm larvae responsible for the condition are rare. Over the last decade there has been
reporting of between 5 and 26 cases annually, although it would appear that
reporting is incomplete. In 2005 there were 11 reported human cases in
England and Wales, and none in Scotland.
In the continental USA the disease is considered to be rare at less than
one case per million inhabitants a year. As the disease has a long pre-patent
period of between 10 and 20 years before cysts become palpable, the
numbers of people with the disease may be higher because many subclinical
cases may go undetected where there is no postmortem examination after
death from other causes.
Disease in animals
These species of tapeworm require dogs (or foxes) and sheep to be present
in the same environment for their complete normal life cycle to take place.
Humans, although they can suffer the unpleasant effects of infection by
these organisms, are a dead-end host in which the tapeworm cannot
complete its life cycle (Figure 2.1). In the UK, sheep are the most important
intermediate host, although cattle, horses and pigs can also carry the
encysted larval stage.
The normal life cycle of the tapeworm consists of the following phases:
• A sheep grazing on contaminated pastures ingests eggs in faecal matter
from dogs or foxes.
• The sheep acts as the intermediate host and after ingestion the eggs
hatch into larvae, which migrate through the intestinal wall and then
encyst in the organs and tissues, where they can multiply.
• After death, dogs eat tissue from the sheep contaminated with cysts;
after ingestion the encysted larvae emerge and progress to adult
tapeworms in the intestine of the dog.
• Eggs are then produced and pass out with the faecal matter, and so the
cycle starts once more.
38 | Zoonoses
Figure 2.1 Hydatidosis in humans and the life cycle of Echinococcus granulosus in dogs and
sheep. Open circles show probable sites for hydatid cyst formation.
In animals infection is often asymptomatic, although a heavy burden of
developing larvae or adult worms may lead to diarrhoea. In dogs, segments
of the adult worm or even the worm may become apparent either in the
stools or in some cases protruding from the anus. Inspection of meat from
infected sheep after slaughter can detect the cysts. Such carcasses will be
condemned for human or animal consumption.
Transmission
Human infection follows consumption of food or water contaminated with
viable eggs from dog faeces. In the USA, there is some evidence that infection
may also occur by a hand-to-mouth route after stroking a dog with faecal
contamination, or by handling objects contaminated with faecal matter.
Disease in humans
Following infection, the eggs hatch and the resulting larvae migrate and then
encyst. The encysted larvae will then start a slow growth and multiplication
process to form multiple hydatids, an infective larval form. Known as
hydatid sand, this may consist of thousands of particles in a large cyst. Due
to the slow growth, physical detection of the cyst may follow only after more
than a decade. The most common site where the cyst forms is in the liver,
with the mass restricted by a thickened membrane. Clinical signs and detection follow abdominal swelling and pressure on other internal organs or bile
duct obstruction with associated nausea and pain. The retaining membrane
may rupture into the abdomen, pericardium or pleural cavity with the possibility of anaphylactic shock, or severe allergic response to the fluid contained
Zoonoses of companion animals | 39
within the cyst or the hydatid particles. Death may follow, as can the
formation of new cysts in other locations by the released hydatids.
Primary cysts may also form in other sites, with the lungs, kidneys, CNS
and bone marrow being, in decreasing order, the most likely sites. Lung
cysts are usually asymptomatic until they become large enough to block
airways or they rupture. Persistent dry cough, pain or coughing of blood
may occur.10 Cysts in the CNS cause symptoms earlier than those in other
locations, with epileptiform fits or paraesthesia. Spontaneous fracture and
bone pain can be a result of cysts in the bone marrow, with the most
common sites being the vertebrae. Compression of the spinal cord or
dependent nerves may follow, with associated paralysis or weakness.
Diagnosis
Diagnosis is usually made by ultrasonography or serology testing.
Exploratory or investigative surgery can be risky unless precautions are
taken to avoid membrane rupture.
Treatment
Treatment traditionally was surgical to remove the cyst or cysts and the
contents. After surgery washing out of the affected body cavity with ethanol,
formaldehyde solution, hypertonic saline, iodine solution, hydrogen peroxide
or silver nitrate solution has been recommended to destroy any hydatids that
have escaped the cyst membrane and could start new cysts. Although surgery
is still seen as the main option, prophylactic medication may be necessary to
keep the cyst from recurring and drug treatment may be the only choice
where cysts are in inoperable locations.11
Albendazole has been recommended for E. granulosis echinococcosis, with
albendazole or mebendazole being used in cases of E. multilocularis.12,13
The World Health Organization (WHO) recommends albendazole 800 mg/
day in divided doses for 28 days, followed by 14 drug-free days as a treatment
cycle. Where surgery is impossible, the WHO suggests repeat treatments for
up to three full cycles. As an adjunct in surgical treatment of hydatid cysts,
before and/or after surgery, one cycle is suggested.
Prevention
Prevention strategies include the regular worming of dogs, especially
working sheepdogs, with praziquantel. Stray dogs should be controlled by
the usual methods of impounding or culling. Feeding dogs with sheep offal
or infected meat should be avoided, with rigorous abattoir checks to prevent
infected meat entering the food chain. Preventing human infection, as with
other parasitic diseases such as toxoplasmosis, relates to implementation of
strict hygiene measures and education. The condition is considered to be an
occupational hazard for shepherds and others who work with sheep.
40 | Zoonoses
Although cases of echinococcosis associated with E. multilocularis have
never been confirmed in the UK, a few notes are appended for the sake of
completeness. Infection with E. multilocularis, also known as alveolar disease,
follows the same pattern, with ingestion of eggs associated with faecal
contamination from dogs, cats or foxes. The normal intermediate hosts are
rodents rather than sheep. The cycle is completed when dogs, cats or foxes eat
mice or other infected rodents. Unlike cysts associated with E. granulosus the
cysts of E. multilocularis have no membrane and can therefore spread from
the original foci more rapidly. Primary foci are usually in the liver or lungs and
occasionally in other tissue sites. The associated hydatids are invasive and the
condition can be rapidly fatal, with an estimated 90% of untreated cases
dying within 10 years.
Hookworm
Ancylostomiasis; cutaneous larva migrans; creeping eruption
The hookworms Ancylostoma duodenale, A. braziliense, A. caninum and
Necator americanus are associated with two clinical conditions affecting
human beings: ancylostomiasis and cutaneous larva migrans. The adult worms
are found in the gut of cats and dogs and the eggs are passed in the faeces to
the soil. Under suitable soil conditions the eggs remain viable for considerable
periods. Once hatched the eggs produce larvae that undergo two larval moults
in the soil. On attaining the third larval stage they become infective. They
can penetrate intact human skin, usually at the base of a hair follicle, or are
ingested by consumption of contaminated food or water. The larvae then
subsequently begin to migrate. The type of migration following infection is
determined by the species involved and is classified by the clinical signs seen.
Ancylostomiasis
In ancylostomiasis, the larvae begin to migrate by deep tissue penetration,
and by transit via blood vessels to the lungs. They then penetrate the
alveolar sacs and migrate via the bronchi and trachea, where they are
swallowed into the gut lumen.
The hookworm is named for the shape and structure of its mouth parts,
which aid its attachment to the blood vessels in the gut of the host, from which
they feed copiously. Once in the gut they grow to between 5 and 100 mm in
length and in heavy infestations can cause anaemia. The worms produce and
secrete hyaluronidase so that at their site of attachment they can continue
to feed freely. Even after they lose their hold or are killed by use of an
anthelmintic, continued blood loss can occur due to the presence of residual
hyaluronidase and its anticoagulant effect. The worm matures in the gut and
then produces eggs, which are passed in the stools. It is unclear if some
Zoonoses of companion animals | 41
species can or cannot complete their life cycle in humans, or if they can
reach maturity only in other species.14
Disease in humans
Symptoms of infection in humans can include pneumonia related to damage
caused by the migrating worms, anaemia, nausea, vomiting, abdominal
pain, bloody diarrhoea or blood in the stools, and generalised weakness
usually associated with anaemia.15 Some larvae may penetrate other organs
or structures than the lungs. Larvae have been found in the cornea, liver and
spleen. In dogs maternal transfer to puppies is seen via the milk or through
the placenta; this has never been documented in humans.
Treatment
As the anaemia produced by a hookworm infection is probably the most
serious effect in humans there may be a requirement for iron therapy simultaneous with anthelmintic treatment. The British National Formulary
(BNF) recommends the use of mebendazole at a dose of 100 mg twice daily
for 3 days. In refractive cases, where a large population of worms across
larval and adult stages is present, a repeat regimen may be needed to resolve
the infestation.
Cutaneous larva migrans or creeping eruption
This condition is caused by the cat or dog hookworm A. braziliense and
also, more rarely, by A. caninum. It is normally seen in tropical and subtropical areas; because of the nature of the infection and its aetiology it is
often seen in travellers returning from beach holidays. Many of the public
beaches in the West Indies, India and Sri Lanka are known to be sources of
this infection. The presentation is very distinctive and diagnosis is based on
the unusual appearance of the lesions.16
Disease in humans
The condition is most often seen in children, because their skins are softer,
especially on their feet.17 Clinical signs commence after penetration of the
skin by the infective third-stage larvae, usually as a result of walking on
contaminated sand or soil in bare feet. At the site of entry itchy reddened
spots appear. After 2–3 days the larvae then start to migrate through the
germinative layer of the skin, leaving a raised red and itchy track with
localised swelling. The track extends by several millimetres daily. Although
distressing, the condition is usually self-limiting because the larvae soon die.
Although only one track is usually seen, multiple tracks are also possible. In
the case of multiple tracks, or where the lesion continues to advance, and
in cases where a secondary infection results from scratching, therapeutic
interventions may be necessary.18
42 | Zoonoses
Treatment
Treatment uses anthelmintic preparations, with the use of ivermectin,
albendazole or tiabendazole by mouth, all of which are available on a
named-patient basis from IDIS Ltd (see Appendix 2).
Use of any of the broad-spectrum antihistamines by mouth or as a local
application will help control itching. The choice of antibiotic in secondary
infection follows the usual protocol for cutaneous or subcutaneous infection. Flucloxacillin has been used successfully with its ability to produce
adequate therapeutic levels in deep tissue. Topical antibiotics such as fusidic
acid have also been used.
Prevention strategies for both conditions
As physical contact with contaminated material is necessary for infection,
wearing shoes on ground that could be contaminated with dog or cat faeces
is recommended. If dogs are kept in closed areas the run should be disinfected with a chlorinated or phenolic disinfectant to ensure full decontamination and destruction of any egg cysts. In the UK the passing of bylaws and
associated fines encourages dog owners to clean up after their pets when
they foul in public places, thus reducing contamination of the environment.
The exclusion of dogs from recreation areas frequented by children and the
use of dog wardens to impound stray and feral dogs are useful measures to
prevent this and other zoonoses arising from canine sources. Education of
children in basic hygiene procedures helps prevent infection after exposure
to the causative organism. In a holiday environment, wearing beach shoes
and using beaches where dogs are excluded, and the sand is regularly raked
and cleaned, reduce the chance of exposure. Dogs and cats should be
regularly wormed to eliminate the adult parasite. The emphasis is on a
programme of treatment, because one animal will often have not only adult
worms present in the gut but migrating larval stages as well.
Vaccines to prevent hookworm infections are under development and may
be of future importance for the health of animals and humans in developing
countries, where the disease is more prevalent.19,20
Ringworm
Ringworm is a common dermatological affliction of cats, dogs, cattle and
horses caused by the fungi Trichophyton spp. and Microsporum spp. The
causative organisms of ringworm are so widespread in the environment that
it is often impossible to determine the source of infection. Ringworm is also
known as zoonotic dermatophytosis (or dermatomycosis). The lesions are
commonly circular in form, and historically were believed to be caused by a
worm, hence its common name. Defining the causative organism is very
Zoonoses of companion animals | 43
difficult even for expert mycologists, because there are at least four fungal
species capable of affecting dogs that may cause clinical disease in canines
and humans. Other carrier animals have as many or more species of
causative organism, which may be host specific or shared between many
species of mammalian host.21
The most commonly identified zoonotic organisms causing ringworm in
humans are Microsporum canis, carried by dogs and cats, and Trichophyton
verrucosum, carried by cattle. It is possible for pet animals to contract the
disease from humans.
The picture of ringworm infection in humans is further complicated by
a spectrum of organisms belonging to the genus Tinea. These are sufficiently
ubiquitous for them to be classed as environmental pathogens. Differential
diagnosis is often unnecessary before treatment begins, so it is sometimes
difficult to determine whether or not infections are zoonotic.
Transmission
Fungal spores are shed by the animal host and then passed to humans either
by direct contact with an infected animal, or by indirect contact with animal
housing, fences and other contaminated fomites. Spores can remain viable
for long periods of time, especially in unclean conditions. After infection the
spores have an incubation period of approximately 10–12 days. After this
time lesions may appear, with isolated plaques gradually forming the characteristic weals as the infection establishes. The circular appearance is caused
by the healing of the central area, while the organism proliferates outward.
The fungus establishes in the hair follicles and may cause the hair shaft to
fracture at skin level. This leads to hair loss, which may be permanent in
some cases.
Established infections gradually lose the circular appearance as they
progress away from the initial site of infection. The lesions are red, scaly,
itchy and inflamed, oozing and crusted, especially where secondary infection after scratching occurs. Autoinfection may also result from spores
trapped beneath the fingernails. Ringworm can be serious in very young
children, who are specifically at risk of scalp infection, which can lead to
extensive and rapid hair loss.
Elderly patients and immunocompromised individuals are also at risk:
dermatomycosis causes further complications in individuals who already
have a spectrum of infections and afflictions.21
Incidence
M. canis can be carried by up to 89% of asymptomatic cats. Up to 50% of
people exposed to infected cats, both symptomatic and asymptomatic, have
serological markers for past or present infection. Infection is more likely
from animals displaying overt signs of infection.
44 | Zoonoses
Diagnosis
Diagnosis in animals and humans may be assisted by the use of an ultraviolet light, because the lesions will often fluoresce. Definitive diagnosis
requires culture of the organism; however, this is normally unnecessary or
not undertaken.
Treatment
The condition is usually self-limiting, although use of topical and/or systemic
antifungals may be required. Topical imidazole antifungal agents such as
miconazole and clotrimazole are probably the most frequently used topical
creams in mild cases. Terbinafine cream is usually reserved for more serious
or resistant fungal manifestations. Ketoconazole shampoo may be used in
scalp infections.
In persistent systemic infections, griseofulvin, terbinafine or fluconazole
may be necessary. Therapy usually needs to be prolonged so that the
therapeutic agent can penetrate to the dermis surface in the skin cells.
Therapy in immunocompromised patients is further complicated by
significant drug interactions between imidazole and triazole agents and a
spectrum of drugs including antiretrovirals, rifamycins, tacrolimus and
certain cytotoxics. Expert advice and monitoring are essential with dose
adjustments.
Prevention
Infected animals should be treated when clinical signs develop, and prophylactically where deemed necessary. Individuals identified as being particularly
at risk should be encouraged to handle animals as little as possible, particularly where animals are wild or feral in habit. As the disease can arise from
fomite transfer, animal pens, blankets, bedding, etc. should be disinfected and
cleaned to prevent initial infection or reinfection.
Scabies
Scabies is caused by a burrowing arachnid mite, Sarcoptes scabiei, in
humans. Recent work has demonstrated that each mammalian species has a
specific species of the parasite. Zoonotic infection by mites other than of the
human-specific species can be extremely irritant; however the organisms do
not demonstrate the ability to complete their life cycle on a human host.22
Disease in animals
Sources of zoonotic scabies include dogs, foxes, cats, horses and, on occasion, pigs. Infection results from close direct physical contact and also fomite
spread. After zoonotic infection the mite does not burrow under the skin
surface and is believed to cause itching and an associated rash solely by
causing a contact dermatitis.
Zoonoses of companion animals | 45
Feline scabies caused by Notedres cati, also known as notoedric mange,
causes intense itching on the face, ears and neck of the cat.
Disease in humans
Feline scabies is transmissible to humans. It presents with blisters, red papules
and crusting. It appears rapidly, is intensely itchy, and when the lesions have
been scratched, crusting may be seen. Lesions appear on the areas of the body
in contact with the cat and are especially common on the arms, chest, legs and
abdomen. Canine scabies shows a similar pattern in human infection.
Diagnosis
Diagnosis may be difficult, as in zoonotically acquired disease the distinctive burrows are absent. The usual techniques of the burrow ink test or skinscraping examination will therefore not produce definitive results. The
condition is usually of short duration, and it may be necessary to treat
blindly and symptomatically. A more serious problem may be the secondary
infection of the lesions by other opportunistic infections, especially in
immunocompromised patients.
Treatment
Insecticides are the usual therapeutic choice for treatment, with both
malathion and permethrin normally being effective; however, permethrin is
preferred on safety grounds. When hyperkeratotic lesions are present repeat
applications may be required. The itching and irritation normally associated
with the condition can be treated with topical or oral antihistamine
preparations. Oral ivermectin has also been used, but is not licensed in the
UK.23
Toxocariasis (visceral larva migrans and optical larva migrans)
Disease in animals
Toxocara canis and T. cati are roundworms of the dog and cat, respectively,
and are found in animals worldwide. The main zoonotic reservoir is latent
infections in female dogs and cats that are reactivated during pregnancy.
Transmission
T. canis is mainly transmitted from dog to dog and from dog to human by
the ingestion of material infected with encysted eggs. Indirect transmission
via an intermediate host is also possible. Unusually in dogs, transmission
from bitch to puppies is possible via the placenta and milk. The life cycle of
T. cati is similar, although transmission across the placenta has not been
demonstrated and is believed not to occur.24 Toxocara spp. demonstrate
both direct and indirect life cycles in dogs, whereas in cats only the indirect
46 | Zoonoses
cycle is seen. In the direct cycle the eggs are passed with the dog’s faeces;
these eggs have a variable latent period before they become infective. Eggs
of Toxocara spp. are extremely resistant to damage and desiccation and can
remain viable and infectious in the soil for many years. The eggs may also
develop into infective larvae under suitable conditions. Eggs are spherical
and 75–90 lm in size.
Once mature eggs or young larvae are ingested on faecally contaminated
matter, they hatch or mature through the first larval stage in the small intestine. The second larval stage (L2) penetrates the wall of the intestine into the
lymphatic system and thence into the bloodstream. Migration continues
through the heart and lungs. In the lungs the larvae moult to the third larval
stage (L3). The L3 larvae migrate up the trachea and are ingested for a
second time. Returning to the small intestine, the final moult occurs and the
adult worms mate and produce eggs, and the cycle begins again.
In contrast, in the indirect life cycle there is a requirement for an intermediate host, which is normally small rodents in the case of Toxocara spp.
These ingest viable oocysts that subsequently hatch in the small intestine.
Once the larvae reach L2 they migrate and penetrate muscle tissue. A dog
or cat that subsequently eats the infected rodent will become infected with
the encysted larvae. Once in the gut the larvae will then migrate into the
tissues of the dog or cat. They soon go back to a state of dormancy. In a
bitch or queen, the dormant larvae become active during late pregnancy.
Subsequently some larvae migrate to the small intestine and others migrate
to the unborn pups in dogs. The cycle then starts over again, in either direct
or indirect modes in the dog and in indirect mode in cats (Figure 2.2).
There has been some evidence in cats that reinfection may result from the
cats grooming either themselves or their kittens.
Disease in humans
Infection is acquired by ingesting encysted eggs (oocysts) in soil contaminated with cat or dog faeces. The eggs hatch, and larvae penetrate the
intestinal wall and migrate through body tissues. In most cases, toxocara
infections are not serious and many people, especially adults infected by a
small number of larvae, may not notice any symptoms. Annually approximately 20 cases a year in the UK are reported to the Health Protection
Agency (HPA). In the USA, there are an estimated 10 000 cases of infection
with Toxocara spp. in humans annually (approximately one case/27 000
people). Due to the nature of the disease and the lack of clinical signs, this
figure does not represent a true picture of the number of people infected at
any time. The most severe cases are rare, but are more likely to occur in
young children who often play in dirt or eat soil. Humans are a dead-end
host for Toxocara spp. in that the larvae that hatch from any ingested eggs
cannot progress to full maturity.25
Zoonoses of companion animals | 47
Ingestion of faecal
contamination
Maternal
transfer
and
grooming
Ingestion of faecal
contamination
Hunting and
consumption
of rodents or
scavenging
Maternal
transfer
and
grooming
Figure 2.2 Toxocara transmission cycle with direct and indirect pathways from animal to animal
and animal to human.
There are two conditions that are recognised as affecting human hosts:
visceral larva migrans and ocular larva migrans.
Visceral larva migrans
Visceral larva migrans occurs when hatched larvae migrate through the
body of the affected individual. The larvae may continue to migrate for up
to 6 months. They finally lodge in various organs, particularly the lungs and
liver and less often the brain, eyes and other tissues, where they produce
eosinophilic granulomas up to 1 cm in diameter. Migration can result in
multiple abscesses, hepatomegaly and pneumonitis. Symptoms include
coughing, nausea, vomiting and fever, wheezing, splenomegaly and
lymphadenopathy. The acute phase may last 2–3 weeks, but resolution of all
physical and laboratory findings may take up to 18 months.
Ocular larva migrans
Ocular larva migrans is a rare form of visceral larva migrans that can cause
blindness. The migrating larva enters the eye, encapsulates and causes a
localised inflammatory reaction with the production of scar tissue (granuloma) on the retina, which may be confused with retinoblastoma. In some
cases the larva can re-emerge and move within the eye structure later in life.
48 | Zoonoses
Sufferers can experience permanent or partial loss of vision. Variable degrees
of ocular inflammation occur, and more severe manifestations of ocular larva
migrans may require aggressive therapy to avoid serious sequelae such as
glaucoma and blindness.
Treatment
Treatment relies on anthelmintic therapy with tiabendazole, mebendazole and
ivermectin at normal clinical doses for both adults and children. Corticosteroids,
antibiotics, antihistamines and analgesics can be used concomitantly for
symptomatic relief. The ocular form may require vitrectomy with adjunctive
laser treatment if drug therapies are not effective.
The current BNF carries no recommendations, and treatment is usually
initiated by secondary care specialists.
Prevention
Prevention of larva migrans in humans involves a combination of human
hygiene and vigilance, stray dog and cat control (where possible), and
parasite control in pets. The following hygiene measures should be adopted:
• Children and adults should always wash hands well with soap and
water after playing with pets and after outdoor activities, especially
before eating.
• Children should be taught not to eat soil or sand.
• Regular periodic worming treatment of puppies, kittens, and pregnant
and nursing dogs and cats will prevent acquisition and shedding of the
parasite.
• Play areas and sandpits used by children should be protected to reduce
contamination from animal faeces.
• Areas that are believed to be contaminated with eggs may be
disinfected using ultraviolet light or by scorching.
Toxoplasmosis
Toxoplasmosis is caused by an intracellular protozoan parasite, Toxoplasma
gondii, which can infect any mammal and is found worldwide. It poses a
well-publicised threat to human health, especially to pregnant women, and
is also a significant pathogen in immunocompromised individuals. The
causative organism is transmitted by contact with, and ingestion of, material
contaminated with cysts or oocysts, especially food or water (Figure 2.3).
The disease is notifiable in Scotland, but not in the rest of the UK. In 2005
there were 102 cases reported to the HPA in England and 11 in Scotland.
There is believed to be a significant underreporting of cases because, in an
extensive survey of blood donations, more than 40% of the residents of the
Zoonoses of companion animals | 49
Direct transmission by faecal contamination
Transplacental
transfer
to neonate
Uncooked meat or ofal
Inadequately
cooked meat
Maternal
transfer
and
grooming
Reactivation of quiescent infection in elderly,
immunocompromised or pregnant individuals
Faecal
contamination
of pasture
Figure 2.3 Toxoplasmosis transmission pathways.
UK had serological markers for having been at one time or another infected
with Toxoplasma gondii. In the USA, it is estimated that 60 million people
(22% of the population) are infected; however, few have symptoms.
Disease in animals
The major source of infection is cat faeces or food and water contaminated
with faecal matter. The definitive hosts for T. gondii in which it can
complete its life cycle and produce sexual oocysts are cats, either wild or
domesticated. Feral cats are recognised as a significant reservoir because
they hunt and consume rodents carrying the disease. Cats pass oocysts in the
faeces; these become infective after a period of 24 hours, and can remain
infective under suitable environmental conditions for more than a year.
Sheep and goats are the main non-feline reservoir, especially pregnant or
perinatal ewes, and their unpasteurised milk or cheese derived from the milk
can be contaminated with the organism. Infection in sheep arises from
grazing on pasture contaminated with cat faeces. Any other animal then
infected acts as an intermediate host.
50 | Zoonoses
Transmission
In an intermediate host the organism will hatch from ingested oocysts, and
the invasive form or tachyzoite will actively spread into cell structures,
where it proliferates and invades the body via the blood supply. Cysts are
then formed in tissues and organs, especially muscle, heart and brain. The
cysts are filled with bradyzoites, a slowly maturing form, which if subsequently ingested by another susceptible animal can progress to disease.
Dogs, cattle, pigs and rodents have been demonstrated to suffer from the
condition and act as a reservoir. Meat from an infected animal may contain
viable cysts; handling or consuming raw or undercooked meat may lead to
infection. Thorough cooking is necessary to kill cysts before consumption of
infected meat to prevent infection. Infection by fomite transfer has been
demonstrated, and pregnant women should not handle overalls of people
involved in lambing, nor should they handle perinatal ewes or neonate
lambs. A live vaccine is available for sheep, and pregnant women are
advised to avoid handling the vaccine or any recently vaccinated sheep.
Contaminated material containing viable oocysts introduced into open cuts
or wounds can also act as an inoculum.
Disease in humans
Although infection is common in humans (some surveys report that more
than 50% of adults in the UK and 22.5% of the population in the USA over
the age of 12 show immunological markers) serious disease is fortunately
less common. Children or adults infected for the first time may well present
with a generalised lymphadenopathy which is self-limiting, and resolves after
a few weeks, leaving the individual resistant to infection, with possibly low
numbers of encysted organisms in tissue or organs and persistent serological
markers. Once infected, an individual can carry the cysts asymptomatically
until reactivation occurs, especially in immunosuppressed patients. As with
animals, the cysts are usually located in skeletal muscle, heart or brain
tissue.26,27
If a woman has been infected previously (usually during childhood) with
Toxoplasma spp., when she becomes pregnant, the fetus will be protected
by the mother’s immunity. However, if a pregnant women contracts toxoplasmosis shortly before or after conception, the unborn child runs a far
greater risk of congenital infection following transplacental spread. In
general, the earlier in pregnancy the disease occurs, the worse the outcome,
with miscarriage, stillbirth, or visual and CNS damage, which becomes
apparent after delivery, or later. The neonate may present with hydrocephalus or retinochondritis, which is an inflammatory condition of the
retina and choroid in the eye. Nystagmus or squint may also be present, as
may brain calcifications that can precipitate seizures and epilepsy.
Zoonoses of companion animals | 51
Pregnant women in the UK are not routinely tested for toxoplasmosis.
Testing is encouraged if they belong to a high-risk group such as cat rescue
workers, those employed in agriculture, or those who have cats as pets. A
concerned pregnant woman can also request a test, although the risks and
limitations of the test should be explained. Testing can demonstrate whether
infection is recent or historical, and may lead in some cases to either treatment
of mother and unborn child, or termination of the pregnancy.
In immunosuppressed patients, toxoplasmosis can cause prolonged
illness with acute episodes following either reactivation of an old infection
or a new infection. Initially similar to glandular fever, symptoms include
sore throat, swollen glands in the neck, armpits and groin, headache, fever,
night sweats, and generalised skeletal and muscular aches. In HIV patients
the development of clinical toxoplasmosis is one of the markers for transition to ARC. Reactivation can cause inflammatory lesions in the brain,
leading to headache, impaired coordination, seizures, sensory loss, tremor,
loss of vision, personality changes, disorientation and coma. Abscesses may
also be present in the CNS. In a new infection, the disease is rapid and
severe, requiring prompt and thorough therapeutic intervention.28
The pathogen may also cause severe pneumonitis, and can affect the
retina with consequent loss of vision, and ultimately blindness.
Diagnosis
Diagnosis in pregnant women is usually made using pathogen-specific antibody testing of blood samples. Any positive findings are confirmed by a
toxoplasma reference unit.
Polymerase chain reaction (PCR) tests on tissue and fluid samples have
also been used. In AIDS/HIV patients antibody testing is not considered
useful, because it only confirms that exposure has occurred and, as many
cases are the results of reactivation of dormant cysts, other methods are
needed to determine the status of the individual in relation to infection or
active disease. Biopsy specimens of brain tissue can detect cysts, and the
presence of tachyzoites is a sign of active disease.
Computerised tomography, magnetic resonance and radiographic
imaging can also be used to detect cysts in the CNS, and monitor the
effectiveness of therapeutic interventions.
Treatment
For most cases of toxoplasmosis, no therapeutic intervention is required.
For pregnant women, HIV/AIDS sufferers and any individual with optical
involvement, intervention is necessary. Treatment is particularly essential
where evidence of encephalitis is seen.
The BNF recommends a combination of pyrimethamine and sulfamethoxasole given for a period of weeks, with addition of folinic acid if
52 | Zoonoses
required; however, it is not the treatment of choice in pregnancy (see below).
Combinations of pyrimethamine and clindamycin, azithromycin or clarithromycin have also been used. Expert advice is essential when drug therapy
is initiated, and, with the toxicity of the agents used, constant monitoring is
required, because pyrimethamine is a folate antagonist. Spiramycin, widely
used in continental Europe for toxoplasmosis treatment, is available in the
UK on a named-patient basis from IDIS Ltd (see in Appendix 2), and may
reduce the risk of transmission of maternal infection to the foetus. Steroids
are used as an adjunctive therapy to reduce intracranial pressure.
It must be borne in mind that, although the condition will respond to
treatment, long-term therapy is necessary to prevent recurrence, and monitoring is essential. Individuals who have survived toxoplasmosis encephalitis
(TE) should have lifelong prophylaxis. In some studies into the effectiveness
of post-TE prophylaxis, relapse rates of between 20% and 30% have been
seen. Non-compliance is a major problem, and relates to the complexity of
dosing needed, as is the spectrum of adverse events associated with long-term
use of these therapeutic moieties.
Dosage regimens vary depending upon complicating factors – including
pregnancy – and adverse reactions, response to therapy, and age or weight
of the person. Specialist units or consultants should make decisions about
when to start therapy, monitoring and duration of therapy. Specific dosages
are not given, because regimens change and alter rapidly with new research
and trials being carried out.
Prevention
It is recommended that all individuals in high-risk groups eat only meat that
has been thoroughly cooked, and avoid consuming raw cured meats such as
Parma ham or cured venison. Unpasteurised goats’ or ewes’ milk and cheese
should not be eaten. Good food hygiene should be routine: all fruit and
vegetables should be washed before being eaten and all utensils should be
washed well after raw meat has been processed. Personal hygiene routines
and hand washing should be as frequent as necessary to prevent infection.
Gloves should be worn when cleaning cat litter trays. This should be undertaken daily to remove the infective focus before any oocysts shed in the
faecal matter can mature to an infectious stage. In HIV/AIDS patients it may
be preferable for another person, who is not in a high-risk group, to carry
out tray cleaning.29
Children should be encouraged in good personal hygiene habits, and
wherever possible sandpits and other areas should be covered when not in
use and cleaned to remove feline faecal material promptly. Patients in at-risk
groups should wear gloves when gardening and clean both hands and gloves
after use.
Pet cats belonging to people in at-risk groups should be kept inside and fed
Zoonoses of companion animals | 53
canned or dry foods to prevent infection from wild rodents or undercooked
meat. Provided that adequate precautions are undertaken, there is no need to
remove the cat from the domestic scene permanently.
Sheep may be inoculated against toxoplasmosis. This carries some risk
to the operatives involved, and they should rapidly seek medical advice if
accidental inoculation occurs. Swill fed to pigs should be heat treated to
prevent infection.
Horses
Introduction
According to a survey carried out by Henley Research for the Department
for Environment, Food and Rural Affairs (DEFRA) in 2004 endorsed by the
British Horse Society, in the UK, approximately 2.4 million people ride,
some occasionally, but many routinely as part of their lifestyle or work. In
a horse population survey carried out in 1999 there were 900 000 horses in
the UK, from shetlands to shires, via hunters, to cobs and racehorses.
In the USA, the American Horse Council, in a survey conducted in 2005,
found that there were an estimated total of 9.2 million horses, with nearly
4 million being kept or ridden for recreation.
Horses and their riders participate in many events, from the Horse of the
Year show, to the local gymkhana, and keeping horses as a leisure activity
is becoming ever more popular. With this amount of human–animal contact,
there is always some risk of medical problems. Luckily there are few
zoonoses solely carried by equines; the likelihood of injury from other
horse-associated activities is greater, with falls, kicks and occasional bites
requiring the most acute medical care.
The diseases discussed in this section are, or have been, of major significance. Glanders was feared until the beginning of the last century, and has
re-emerged as a significant zoonosis in other areas of the world. With the
flooding that much of the country has experienced in recent years, the
incidence of leptospirosis is increasing, and is likely to become more significant
in future if the changes in weather patterns are sustained.
Tetanus is still a major issue in terms of public health measures, and the
control of the disease requires constant application of a comprehensive
vaccination programme.
Horses can transmit or carry other zoonotic diseases that are normally
primarily associated with other animals. This is mentioned in other sections
under the primary host animal. References to these conditions will be found
in the index.
54 | Zoonoses
Glanders, farcy
Glanders or farcy is caused by the bacterium Burkholderia (formerly
Pseudomonas) mallei. It is a notifiable disease of, in particular, horses but
also donkeys and mules. Goats, cats and dogs have also been known to
acquire the disease. Import of susceptible animals from countries where the
disease has been reported is forbidden. In 2004, DEFRA issued a control
notice that required increased control of horses imported from the United
Arab Emirates (UAE) after the identification of clinical cases in native
horses. It was deemed unlikely that bloodstock that enters the UK for racing
or breeding purposes would have been infected; however, extra checks and
procedures were put in place. Geographically, the disease is endemic in
Africa, Asia, the Middle East, and Central and South America.30
The last recorded case in the UK occurred in 1928, but it is possible that
many subclinical cases are not identified due to blind antibiotic use without
sample culture. It is a notifiable disease under the Notification of Infectious
Diseases System (NOIDS) regulations.
Historically it was very significant because it caused rapid fatality in
horses and humans – this was a disaster in a society that was reliant on true
horsepower for its transport of both people and goods. In 1902 many
London boroughs closed their public animal water troughs because of an
outbreak of the disease. In human patients, in the era before antimicrobial
agents were available, 95% of victims with clinical signs would die. The use
of antibiotics has reduced this toll dramatically.
Human infection is luckily now rare; however, it has been seen in
pulmonary (glanders) and cutaneous (farcy) forms. It can affect stable
personnel or people in close physical contact with horses in the course of their
work. Infection in laboratory workers has also been seen. The inoculum
necessary to cause infection is small, and the organism has been considered as
a potential agent for biological warfare or terrorism.31
Transmission
The organism is spread by discharge from wounds and aerosols. Ingestion,
inhalation or physical contact with the inoculum allows the bacterium to
colonise the next victim. In several cases the initial inoculum has also
occurred through the eye or nasal mucosa. Physical inoculation of wounds or
abrasions with infected material has been shown to occur. In melioidosis,
caused by a closely related bacterium, sexual transfer has been demonstrated
and there is a single report of this also occurring in farcy, where human-tohuman spread occurred. Once across the species barrier, patients’ carers,
especially where there is close physical contact, are at risk.
Zoonoses of companion animals | 55
Disease in humans
Following inoculation, the incubation period usually ranges from 1–14 days.
Symptoms in humans depend on the route of transmission. The cutaneous
form is characterised by skin pustules that suppurate; localised lymph node
swelling may then occur. Non-specific symptoms can include headache, with
raised temperature, and aching muscles. If mucosal membranes are involved,
excessive tear production or nasal discharge may be seen. The disease can
then become systemic with an undulant fever, enlargement of the liver and
spleen, an overwhelming septicaemia and a high associated mortality rate if
left untreated.
The pulmonary form follows the same pattern in terms of early nonspecific symptoms; subsequently pneumonia develops with copious mucus
production. Abscess formation in the lung may occur with pleurisy and lung
collapse. The bacteria may be shed in urine, blood, mucosal secretions and
pus from skin lesions, leading to a risk of further infection.
Treatment
Human cases of glanders are rare so limited information is available about
antibiotic treatment of the organism in humans. This also leads to problems
with diagnosis, because serological assays are not reliable or readily available.
Culturing the organism is time-consuming and, as the disease can be rapidly
fatal, treatment usually starts on the presumption of illness. Sulfadiazine at an
intravenous dose of 25 mg/kg four times a day has been found to be effective
in experimental animals and in humans.
B. mallei is also usually sensitive to some or all of the following: penicillins
(particularly amoxicillin either alone or in combination as co-amoxiclav),
tetracyclines (especially doxycycline), ciprofloxacin, streptomycin, gentamicin,
ticarcillin, azlocillin, imipenem, aztreonam, ceftazidime and ceftriaxone.
Resistance to chloramphenicol has been reported. Streptomycin in combination with tetracyclines or chloramphenicol has been used historically in
the USA but has been replaced by other agents. Where systemic infection
with deep-tissue abscesses is present, therapy may have to be prolonged
to resolve the infection; durations of more than 14 days have been
reported.32
Prevention
No vaccine is available to prevent infection with B. mallei. Where the infection is endemic, prevention strategies consist of controlling and eliminating
the disease in the animal reservoir. Any patient suspected of being infected
must be carefully nursed to avoid infection, with appropriate measures
including gloves, masks and gowns.
56 | Zoonoses
Leptospirosis
Weil’s disease, haemorrhagic jaundice (Leptospira icterohaemorrhagiae),
canicola fever (L. canicola), dairy-worker fever (L. hardjo)
Leptospirosis is caused by motile spirochaetes of the genus Leptospira.
These organisms occur worldwide and are most common in temperate or
tropical climates. They may be found associated with animals and humans,
or free-living in water or soil. The most important zoonotic leptospires are
L. icterohaemorrhagiae, found in rodents and dogs (specifically the organism
responsible for Weil’s disease), L. hardjo, associated with cattle and horses,
L. canicola in dogs, and L. pomona in pigs and cattle, although there are
other species that are occasionally seen, especially in cases affecting
returning travellers. Incidence of the disease ranges from endemic in some
areas to sporadic in others. More cases are seen in areas that have been
flooded, because soil-living pathogens are released into the surface water
and cause wider contamination of potable water sources.33
The disease is notifiable to the HPA in England and Wales and Health
Protection Scotland in Scotland. It is considered by the Health and Safety
Executive (HSE) to be a hazard at work and is subject to the Control of
Substances Hazardous to Health (COSHH) Regulations 1994 in terms of
provision of protective clothing and prevention measures for people at risk
of occupational exposure. The disease is also covered by the Reporting
of Injuries, Diseases, and Dangerous Occurrences Regulations 1995
(RIDDOR 95).
Disease in animals
The pattern of clinical signs in infected animals varies from species to
species. Cattle often present with weight loss and a high fever, with mastitis
in ‘in-milk’ heifers and declining milk yields. This disease is the most
frequently diagnosed cause of bovine abortion in the UK: abortion occurs
spontaneously in ‘in-calf’ heifers with afterbirth retention. Hepatic enlargement, anaemia and jaundice may also be seen. In dogs, acute haemorrhage,
jaundice and hepatitis are seen with infection with L. canicola, and kidney
damage in infection with L. icterohaemorrhagiae. Diarrhoea and gastritis
may also be seen. Rodents are the only order of mammals that can show no
sign of disease, yet are able to shed viable organisms throughout their lives,
and are considered to be not only a reservoir for the disease, but also a
vector. Organisms are shed in the urine of infected animals and contaminate
soil or water.
Transmission
Transmission to humans usually follows either ingestion of water contaminated with infected animal urine, and particularly that of rodents, or contact
Zoonoses of companion animals | 57
with contaminated soil or food. The organism can also enter the body by
skin abrasions or cuts, and also via the mucosal membranes of the nose,
mouth or eyes. Bathing or swimming in infected waters appears to be a
major route.34 The disease is an occupational hazard for sewage, water and
canal workers. Vets, aid workers and water-sport enthusiasts are also at a
higher than average risk of contracting the disease. There are rare incidents
of human-to-human transfer.
There were 3 confirmed reports of leptospirosis in humans during 2006
in Scotland, 3 in Northern Ireland and 44 in England and Wales, of which
34 were contracted in the UK, and 2 fatalities occurred. Of the 34, 18 were
confirmed as L. icterohaemorrhagiae, 3 as L. hardjo, 1 as L. saxkoebing, 1 as
L. australis, 1 as L. autumnalis and 1 as L. javanica, the other 9 not being
serotyped. There is believed to be massive under-reporting of cases.
Disease in humans
After infection, there is a pre-patent period ranging from a few days to
several weeks. Clinical signs vary from unapparent to severe acute manifestations with associated mortality. The onset may be sudden with high fever,
headaches, aching muscles and fatigue. Vomiting may also occur.
Depending upon the causative organism and the severity of the disease
there may be a second phase of the disease. After an apparent recovery the
patient becomes ill again with declining kidney and liver function, mental
confusion and delusion, meningitis, breathing difficulties and catastrophic
hypotension. In the second phase, symptoms are continuous and do not
regress until recovery or death occurs. This biphasic form is usually caused
by L. icterohaemorrhagiae and is known as Weil’s disease or icteric
leptospirosis. The disease may last for days or weeks and untreated it can be
fatal. Recovery can be prolonged, with an extended convalescence of months
after clinical illness ends.
Diagnosis
Early in the disease, the organism may be identified by dark-field
microscopy of a blood film or by culture. The organism is difficult to grow
on conventional media and may require a period of weeks to establish identifiable colonies. More rapid diagnosis can be made using a dot enzymelinked immunosorbent assay (DOT-ELISA) test. Recently a dipstick test has
been developed using an immunoglobulin agglutination method and is now
marketed under a number of trade names. This has allowed rapid diagnosis
and enables early therapeutic intervention.
Treatment
Treatment is normally with penicillin at normal therapeutic doses or, in the
case of penicillin allergy, tetracyclines at normal doses as alternative drugs
58 | Zoonoses
of choice. Therapy should be initiated early in the course of disease and
intravenous antibiotics should be used for people with severe manifestations.
Studies suggest that prophylaxis using oral doxycycline at a dose of
200 mg/week is effective in reducing infection in groups at high risk, due
to either their occupational or their recreational pursuits.35
Prevention
Dogs, pigs and cattle may be vaccinated against the disease, reducing the
infective reservoir. The vaccination is not necessarily routine in cattle because
vaccinated cattle may be unacceptable for export to certain countries.
Wherever possible, individuals should avoid swimming in or drinking
from potentially contaminated water. Workers likely to suffer occupational
exposure should be supplied with adequate protective clothing. Rodent populations must be controlled wherever possible and prophylaxis with antibiotics
should be considered for workers, especially where cases have been reported.
Rodent carcasses should not be handled and cuts and abrasions should be
covered with plasters or dressings.
Miscellaneous zoonoses of companion animals
All animals have diseases specific to species or genera. It is inevitable that
some of the causative organisms of these diseases will be potential zoonoses.
In general, the more unusual the animal, the more outrageous the possible
zoonoses.
The fashion for keeping primates as pets has luckily almost disappeared
because our closest cousins carry some very unpleasant pathogens. These
may not cause clinical signs in the ape, but they are potentially fatal in
humans. Apart from atypical mycobacteria and Salmonella spp., including
S. typhi, simians can also harbour hepatitis A, herpes B virus (fatal in all
recorded human cases), and other hazardous viruses such as Marburg (Green
monkey). Primates can also become aggressive as they mature. Bites or
wounds inflicted on owners or keepers can rapidly become seriously
infected and pose a serious hazard.36
Reptiles such as turtles or terrapins, snakes and lizards have been identified
as harbouring a variety of Salmonella spp. and are probably inappropriate
as pets for owners who are not willing to become experts in their care and
to devote sufficient time to appropriate hygiene routines.
Some of these diseases and conditions are covered in Chapter 8; however,
there are many more zoonoses than it is possible to cover in a book of this
size, and a decision has been made to exclude those that are not of major
significance. To highlight the variety of pathogens that are potential
zoonoses, it is enough to consider that armadillos are the only other known
species in the world that can suffer from leprosy, apart from humans.37 No
Zoonoses of companion animals | 59
cases have ever been attributed to zoonotic spread, and nobody in the UK
keeps armadillos as pets because their importation is prohibited under the
Convention on International Trade in Endangered Species (CITES) treaty.
Other exotic species probably harbour novel pathogens that might also be
zoonotic, and are probably best avoided as pets.
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5. Kim JH, Shin DH, Oh MD et al. A case of disseminated cryptococcosis with skin
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6. Benson CA, William PL, Cohn DL et al. Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients
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7. Eidson M. Zoonosis update. Psittacosis/avian chlamydiosis. JAVMA 2002; 221:
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8. Chomel BB, Boulouis HJ, Maruyama S, Breitschwerdt EB. Bartonella spp. in pets and
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9. Chomel BB, Boulouis HJ, Breitschwerdt EB. Cat scratch disease and other zoonotic
Bartonella infections. JAVMA 2004; 224: 1270–9.
10. Yilmaz A, Tuncer LY, Damadoglu E, Sulu E, Takir HB, Selvi UB. Pulmonary hydatid
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11. Papathanassiou M, Petrou P, Zampeli E, Vergados I, Paikos P. Disseminated hydatid
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1034–6
12. Adas G, Arikan S, Kemik O, Oner A, Sahip N, Karatepe O. Use of albendazole sulfoxide,
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13. Arif SH, Shams-Ul-Bari, Wani NA et al. Albendazole as an adjuvant to the standard
surgical management of hydatid cyst liver. Int J Surg 2008; 6: 448–51.
14. Tu CH, Liao WC, Chiang TH, Wang HP. Pet parasites infesting the human colon.
Gastrointest Endosc 2008; 67: 159–60.
15. Budhathoki S, Shah D, Bhurtyal KK, Amatya R, Dutta AK. Hookworm causing melaena
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16. Heukelbach J, Feldmeier H. Epidemiological and clinical characteristics of hookwormrelated cutaneous larva migrans. Lancet Infect Dis 2008; 8: 302–9.
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migrans (Ancylostoma braziliense). Cutis 2008; 82: 239–40.
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21. Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide.
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molecular aspects. Clin Microb Rev 2003; 16: 265–72.
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3
Zoonoses of agricultural
animals
There is a large and active indigenous farming and livestock operation in the
British Isles and the USA. Eggs, milk and meat are currently produced in
quantity for human consumption by domestic flocks and herds.
In June 2006, the Department for Environment, Food and Rural Affairs
(Defra) estimated that there were 149 million poultry (hens, chickens,
pheasants, ducks, etc.), 10.2 million cattle (dairy or beef), 34.7 million sheep
Table 3.1 Provisional figures for number of livestock for each country in UK,
June 2006a
England
Wales
Scotland
N. Ireland
UK
Cattle
5 378 028
1 326 300
1 929 990
1 635 700
10 270 000
Sheep
15 673 409
9 350 700
7 608 100
2 070 500
34 722 000
4 057 433
b
463 330
386 600
4 933 000
114 905 849
b
12 119 320
16 297 900
148 929 000
Goats
82 774
b
4 130
3 400c
98 000
Deer
21 000d
b
6 380
3 397e
36 000
b
30 220
Pig
Poultry
Horses
a
2 578 000
10 300
Notef
Figures do not total due to rounding and data from different time period.
Results for 2006 not available.
c
2001.
d
2002.
e
2004 data.
f
Equine database should give more accurate figures in future: figures relate generally to horses on
agricultural land.
Figures courtesy of DEFRA.
b
62 | Zoonoses
and 4.9 million pigs in the UK. This probably represents a fairly accurate
estimate of the numbers today (Table 3.1) broken down by region.
The Health and Safety Executive (HSE) estimate that there are more than
20 000 cases of zoonoses in agricultural and other associated workers annually. Many of these cases have been reported under the Control of Substances
Hazardous to Health (COSHH) regulations, because the causative pathogens
fall under the terms of reference for those regulations. Much has been done
to reduce the risks associated with zoonotic infection while caring for domesticated animals or processing animals and their products from farm to table,
but much remains to be done. The provision of protective clothing and
equipment, the adoption of safe working practices and other safeguards
protect not only workers but also the public at large.
Many of the diseases in this chapter have a long historical association with
animal husbandry, probably dating from the first domestication of wild
species. Many of the pathogens are almost household names and certainly
maintain a hold on our collective consciousness, sometimes out of proportion
to their current significance. Others are less familiar; nevertheless, they may
still pose a risk.
One of the recent developments in agricultural enterprise has been the
extended range of animal species kept for commercial purposes, as farms
have responded to the changing market by diversifying. These changes in the
spectrum of species, with which those employed in the industry come into
close contact, can lead to different zoonotic pathogens becoming more
important. The last section of this chapter deals with some examples of such
diseases.
Birds
Birds currently kept for commercial purposes in agriculture come from a
variety of species across the avian genera. It is hard to come to terms with
an industry where not only do traditional poultry have a place, as providers
of meat and eggs, but also other non-traditional species such as the ostrich
and the Gressingham duck (a cross between traditional domesticated ducks
and the mallard).
In recent years, while there has been a diversification within the poultry
farm and other bird-based enterprises, the pattern of farming has also
changed. Eggs produced by battery hens can still be seen on supermarket
shelves, but in response to consumer pressure the free-range hen and its eggs
are making a dramatic comeback on the basis of better animal welfare and
improved flavour. Chickens and capons are again being reared solely for the
table, rather than as a sideline to the industrial broiler unit.
These changes come at a price to healthcare. The implications for food
and its consumption are discussed in Chapter 4; the importance for zoonotic
Zoonoses of agricultural animals | 63
disease in poultry workers is slightly different. Any of the zoonotic conditions discussed in Chapter 2, which are capable of affecting companion bird
species, may also strike domesticated fowl. In addition there are a variety of
other conditions that tend to be seen only in commercial bird flocks.
The change in husbandry practice carries with it the exposure of the birds
to a wider environment and, with it, wild bird species. With the current risk
of pandemic bird flu, this has had some repercussions for commercial flocks.
In Northern America, the West Nile virus (WNV) is known to be established
in wild birds across the continent in endemic areas, acting as a reservoir for
the pathogen that may then infect domestic flocks, which do not act as a
reservoir for the virus, but are victims of it.
In the past, wild species were excluded from poultry housing by never
allowing birds out, and by controlling feral pigeons and other birds from
gaining access to feed mills and storage. This probably slowed the spread of
possible pathogens, be they zoonotic or not. There is a growing realisation
that new patterns of operation may require heightened vigilance and
monitoring.
Newcastle disease (UK)
Exotic Newcastle disease (USA) (pseudo-fowl pest)
Newcastle disease is caused by avian paramyxovirus type 1 (APMV-1), and
similar disease can be caused by eight other serotypes (APMV-2–APMV-9).
It is a notifiable disease in poultry and routine vaccination prevents major
outbreaks, which historically rapidly wiped out whole flocks. The organism
is classified under the Advisory Council on Dangerous Pathogens as a
Group 2 Hazard. It is also controlled under Part 7 of the Anti-Terrorism,
Crime and Security Act 2001 (Extension to Animal Pathogen Order 2005).
It is notifiable under the Animal Health Act 1981, the Diseases of Poultry
(England) Order 2003, and also the Animal Health Act 2002 and the Avian
Influenza and Newcastle Disease (England & Wales) Order 2003.
It was named for Newcastle upon Tyne in England, where the first cases
of clinical disease were seen following the feeding of dead chickens from a
ship that had arrived from the Far East to local poultry.
The last recorded outbreak in the UK was in 2006, in East Lothian. To
control the disease 14 000 birds, principally grey partridge, had to be culled.
In the previous year there was also an outbreak in pheasants near Guildford,
Surrey, which was controlled after the slaughter of approximately 10 000
birds. The natural reservoir for the disease is in wild birds, and the severity
of the infection varies from species to species, to such a degree that in some
species the disease can be unapparent.
This is insignificant in economic and casualty terms compared with
an outbreak of exotic Newcastle disease (END) that started in southern
64 | Zoonoses
California in October 2002. It spread from small non-commercial flocks
into commercial flocks by mid-December 2002. By mid-January 2003,
despite efforts to control the outbreak by culling, the disease had spread
into Nevada. The resulting ban on exports of poultry and poultry products
from California caused considerable economic loss.
The previous major outbreak of END virus in commercial poultry in the
USA occurred in southern California during 1971–3. A total of 1341
infected poultry flocks were identified, and about 12 million birds were
destroyed at a cost of $US56 million. Imported pet birds were the source of
infection. There have been several other recorded small-scale outbreaks that
were rapidly brought under control by the US Department of Agriculture
(USDA).
Disease in animals
The clinical course of the disease is brief; following infection there is a brief
incubation period averaging 5 days, but ranging between 2 and 15 days.
Birds then often have catastrophic diarrhoea, breathing difficulties and
copious mucus discharge from nostrils and mouth. The birds may become
comatose and die, although in the most virulent form death is so rapid that
few other symptoms are seen.
Transmission
Transmission occurs after inhalation of infected material, such as faecal
matter, or direct contact with infected birds or their carcasses or live vaccine.
Contamination of the conjunctiva can also occur via bird and plumage dusts.
Fomite contact in intensive housing with high levels of infection can also lead
to transmission.
Disease in humans
Individuals employed within the poultry industry are most at risk. Accidental
infection during vaccination occurs occasionally. Slaughterhouse operatives
and laboratory workers are also considered to be at risk if they are handling
infected birds or clinical samples.1
The first clinical symptom of infection in humans is usually a painful
self-limiting conjunctivitis. On occasions a debilitating low fever of up to
3 weeks’ duration with spontaneous rapid recovery has been reported.
Treatment
Treatment is usually symptomatic. It may include antiviral or antibacterial
eye preparations to treat either primary or secondary infection. Aciclovir eye
ointment has proved effective in early primary infection, with either
chloramphenicol or fusidic acid preparations for controlling any secondary
pathogens.
Zoonoses of agricultural animals | 65
Prevention
Prevention strategies involve thorough and comprehensive vaccinations of
all poultry to prevent disease. Poultry workers should wear respirators and
facemasks when working with flocks and in housing. Precautions should be
adopted to prevent accidental inhalation of vaccine droplets during air-carried
vaccination procedures, and all housing should be thoroughly cleaned when
not in use.
Influenza
Flu, avian, swine and equine influenza, fowl plague
Influenza or ‘the flu’ is a familiar disease to most healthcare professionals and
the public at large. Recently there has not been a pandemic outbreak associated with mass fatalities; however, the emergence over the last decade of a
highly pathogenic avian strain of the virus brings the possibility of a pandemic,
similar in nature to the one that occurred at the end of World War I, closer.
That outbreak is estimated to have killed approximately 20 million people
worldwide – more than the armed conflict itself. Subsequent pandemics in
1957 and 1968 led to many deaths. The causative agent, an orthomyxovirus,
is categorised in three types – A, B and C – of which the A and B types cause
the most serious disease. The virus is further characterised into subtypes
according to the characteristics and proportions of the two main viral proteins
– haemagglutinin (H) and neuraminidase (N), hence H5N5, H5N1.2
Influenza viruses are famous for their ability to mutate. In both types an
antigenic drift following minor changes in the amino acid sequencing in the
haemagglutinin portion can be observed, resulting in the structure of the
virus altering gradually over a series of generations, either by endogenous
re-sequencing or by exchanging blocks of amino acids with other influenza
viral strains. This allows the virus to continue to be infective and avoid the
development of an immune response and host immunity.
Type A viruses can additionally undergo dramatic sudden changes in
structure called antigenic shift. The impact of this ability is the emergence of
new strains overnight with an associated possible increase in virulence or
pathogenicity. All the major pandemics are believed to have been caused by
type A viruses capable of circulating within and between animal and human
populations, that had undergone antigenic shift (Figure 3.1).
Viral subtypes are classified not only according to protein make-up but
also by their place of origin and the year in which they were isolated. The
1918 virus, commonly known as Spanish flu, is believed to have arisen from
an unholy union between bird and pig strains, with a few characteristics
derived from human viral types completing the mix.3 Until recently no
animal reservoir of type B viruses was believed to exist; however, this type
of influenza virus has now been found in harp seals.4
66 | Zoonoses
Antigenic drift
Antigenic drift
Antigenic shift
Antigenic drift
Figure 3.1 Antigenic shift and drift and the infection cycle in influenza.
Birds, pigs, humans and horses have been identified as reservoirs for the
influenza viruses, most of which are species specific. The organisms cycle
within the susceptible species, and remain within that population. Wild
populations of these creatures can also maintain the virus, with wild boar
carrying different viral types to the domestic swine in the same locality.
Occasionally an outbreak of pure strain virus associated with another
species, such as birds or pigs, has caused human disease.
It is more usual that infection in another species other than the normal
host follows a mutation of the causative virus. Flocks of birds and herds of
pigs can be decimated by outbreaks, which are seasonal, from viral subtypes
particularly pathogenic to that species.
As stated above, in general, pure avian or swine-derived subtypes have a
low potential to cause human disease and, although most workers in these
industries can be demonstrated to have the antibodies to these families of
viruses, clinical disease is rare. There are notable exceptions. In 1976, a type
A virus arising from pigs caused anxiety when it was identified in army
recruits at Fort Dix in the USA. Antigenically similar to 1918 Spanish flu,
fears arose that a pandemic might occur. However, the outbreak was
confined to the camp and did not cause any fatalities, although it was
capable of transmission from person to person and caused severe symptoms.
Zoonoses of agricultural animals | 67
The World Health Organization (WHO) states that a prompt response
to the emergence of new strains is essential, especially where they have high
toxicity potential. The pathogenicity of any subtype not only stems from its
ability to cause severe symptoms but is also related to the potential for
person-to-person spread. The identification of a new pathogenic viral
subtype, now known as H5N1, led to a widespread cull of pigs in Hong
Kong during October 1999.
The three conditions for a pandemic are that a new influenza subtype has
to emerge, it must be able to infect humans causing serious illness, and it
spreads easily and sustainably among humans. Currently the H5N1 virus
does not spread easily from birds to humans and also person-to-person
spread has been very rare (and as yet not fully substantiated) and seen only
where continued close contact between victims has occurred, which could
also be the result of a common source of exposure.
The first two conditions for a pandemic have been met. It awaits the last
condition being met to see whether the current avian epidemic will escalate
to a full human pandemic. Of concern is that there is no pre-existing immunity in humans to H5N1 and there is currently no vaccine, although many
of the leading health organisations in the world are cooperating over vaccine
research and development programmes together with vaccine manufacturers.5
As a result of concerns over a pandemic, most of the current focus on
influenza centres on H5N1; however, there are a number of other pathogenic
subtypes currently circulating. Serious clinical disease in humans in the
Netherlands was caused by H7N7 in 2004.
Mexican Swine Flu (H1N1) – May 2009
As if to prove that with the influenza virus it is mandatory to expect the
unexpected, in late April 2009, a new strain virus, now characterised as
H1N1, emerged in Mexico, as this volume was going to press. Dubbed
‘swine flu’ by the media, as most initial cases had contact with pigs, it is an
influenza A virus, with a mixture of elements of avian, swine and humanderived viruses. It has shown the ability to transfer from human to human,
and this has led to the WHO Pandemic Index for this outbreak being raised
to 6, following sustained human-to-human spread in more than two countries worldwide. This means that a worldwide pandemic is now in progress.
The virus is currently susceptible to oseltamivir and zanamivir in most countries, but is resistant to amantidine. Some isolates in Denmark and Japan are
now showing resistance to oseltamivir.
Initially blamed for over 100 deaths in Mexico, this has been revised
downward reflecting only those cases confirmed by tissue sample (74 at 20
May 2009). Many (over 70) of the dead could not be tested. The picture
68 | Zoonoses
may also be complicated by a possible concurrent outbreak of H3N2 in
North America (USA, Canada, Mexico).
Carried by returning tourists and other air travellers, the virus had
spread worldwide by mid-May, with the majority of the cases being in
Mexico, the USA and Canada. The majority of the deaths outside of Mexico
have been seen in patients who had other underlying health problems. The
USA has declared a public health emergency, with cases reported across 48
states. In the UK, the approach to the outbreak switched in early July from
a prevention to a treatment strategy, with prescribing of antivirals being
restricted to serious cases.
Transmission
Infection in animals follows the inhalation of infected aerosols. There is often
a fever of rapid onset, followed by cough and breathing difficulties. Copious
quantities of mucus and nasal discharge are produced which, associated with
the cough, produce further infected aerosols capable of continuing the
infection in other individuals. Recovery is usually speedy, as is the only other
possible outcome – death.
Disease in humans
The clinical pattern and treatment of H5N1 differ to other viral subtypes so
the following section refers only to non-highly pathogenic (HP) H5N1 disease
in animals and humans; for information on HP H5N1 see ‘The current
outbreak of HP H5N1’.
In humans infection similarly follows the inhalation of infected aerosols
derived from infected individuals coughing or sneezing in the immediate
vicinity. There are particular groups who are potentially more likely to catch
the disease; the ‘at-risk’ groups are very young children because they have an
immature immune response, elderly people, and those people with asthma,
diabetes, kidney or heart disease. Individuals who are immunocompromised
for whatever reason are also at higher risk of complications following infection. The incubation period is usually no longer than 2–3 days. Clinical onset
is characterised by fever, with temperatures as high as 40°C that may last for
up to 5 days. Associated with the fever are loss of appetite, headaches,
lethargy, cough, generalised joint pain, sore throat and nasal discharge.
Gastrointestinal disturbance may also be seen in children. Patients are probably infective from the time that symptoms appear up to about 5 days later.
As the fever starts to subside nasal congestion sets in. Convalescence
normally does not extend beyond a period of 2 weeks once the major symptoms resolve; however, in elderly people and other major at-risk groups
bacterial or viral pneumonia may follow, with risks of mortality. Bronchitis
can also arise in individuals with previous lung damage.
Zoonoses of agricultural animals | 69
Diagnosis
Diagnosis is usually symptomatic, although for monitoring purposes swabs
will be cultured to ascertain prevalent subtypes.
Treatment
Treatment in non-H5N1 cases in humans usually consists of simple symptomatic control. Patients are advised to rest and use suitable minor analgesics
and anti-inflammatory drugs, preferably paracetamol or ibuprofen. Cough
suppressants or mucolytics may also be useful. Dehydration is also a risk, so
patients should be encouraged to drink copious quantities of fluids.
Amantadine is licensed in the UK as an antiviral for use against type A
viral subtypes as an acute treatment or a prophylactic measure; however, it
is currently not recommended by the National Institute for Health and
Clinical Excellence (NICE). For acute cases in adults and children aged over
10 years a dose of 100 mg/day for 4–5 days is considered suitable. The same
dose may also be used as prophylaxis in people identified as at risk but is
not suitable for vaccination and healthcare workers. Prophylaxis may be
extended, usually to 6 weeks or the end of an outbreak. Individuals who
have been vaccinated can receive amantadine for 2–3 weeks until immunity
develops. There are issues relating to the drug’s use for treatment and
prevention within the same household, arising from concerns over the
possibility of viral subtypes developing resistance.
A therapeutic advance in the treatment of influenza (both types A and B)
was the development of the neuraminidase inhibitors, zanamivir and
oseltamivir. They are licensed for therapeutic use in the UK. Therapy has to
be initiated as soon as possible after exposure and no later than 48 hours
after the onset of clinical symptoms. The data available suggest that the duration of the infection can then be reduced by a day or several days, depending
on how quickly it is used. The neuraminidase, an enzyme, prevents the virus
from migrating from infected cells to the rest of the respiratory tract.
Zanamivir is available as a dry powder inhaler with 5-mg blisters; the
recommended adult dose is 10 mg twice a day for 5 days.
NICE currently recommends that they not be used for seasonal or postexposure prophylaxis. They are also NOT to be used for the treatment of
otherwise healthy individuals with influenza. NICE does recommend their
use for post-exposure prophylaxis in at-risk adults, residents in care establishments and adolescents who are not effectively protected by vaccination;
prophylaxis should commence within 48 hours of possible exposure. At-risk
adults who show symptoms of influenza should be treated with these agents
if they display symptoms of influenza, with treatment commencing within
48 hours of onset of clinical signs.
70 | Zoonoses
The current HP H5N1 outbreak
In 1997, a type A virus classified as H5N1 of avian origin with a high
lethality was detected in Hong Kong. A comprehensive cull of all poultry
(chicken, ducks and geese) was carried out in the region following the death
of many chickens and several people. Of the 20 human cases recorded in
this first outbreak, 6 died, and the 14 survivors were seriously affected and
their convalescence was protracted. A subsequent outbreak in 2001 led to
another cull. The source of this secondary outbreak is believed to have been
the local wild bird population, because the primary cull of domesticated
fowl was very complete.6
Since these first outbreaks, two forms of the virus have been identified:
a low pathogenic type that causes only mild symptoms in birds, and a highly
pathogenic type that causes dramatic rapidly and massively fatal outbreaks
in wild bird and poultry flocks, with death following multiple organ failure,
often within 48 hours of first infection.
The virus has spread rapidly across continents and is now viewed as
being endemic in certain areas, with sporadic outbreaks with associated
mortality in bird flocks. Its geographical spread has been unprecedented.
The virus is now established in the wild bird populations and can move
freely along migration routes.
H5N1 has also been seen in pigs, cats, dogs, civets and weasels. Some of
the most dramatic cases were those in tigers in Bangkok Zoo where 141
animals out of a population of 447 died after ingesting infected raw chicken
meat.7,8 The virus is heat sensitive and can be destroyed by thorough
cooking. This applies not only to meat but also to eggs.
UK animal cases to date
The only avian case of H5N1 at the time of writing in the UK associated
with a wild bird was a case in Scotland. On 29 March 2006, a dead
Whooper swan (Cygnus cygnus) was found at Cellardyke in Fife. In early
April 2006, the swan was confirmed to have died from HP H5N1. There
have been no further cases since identified in the wild bird population.
In February 2007, vets were called to the Bernard Matthews farm in
Holton, Suffolk. Bernard Matthews is the largest provider to UK supermarkets of turkey products, and has extensive managed flocks of turkeys.
Initial tests showed that 2600 of the birds had died of HP H5N1. A 3-km
protection zone was established in a radius around the affected farm with a
surveillance zone out to 10 km. Subsequently the rest of the flock were
culled with 159 000 birds being gassed on site. The outbreak was linked
back to imports of processed turkey meat from Hungary. No further
outbreaks have occurred since.
Zoonoses of agricultural animals | 71
The Department of the Environment, Food and Rural Affairs (DEFRA)
have set up a series of protocols to control this and any future outbreaks. At
the site of the outbreak all poultry have to be culled, visitors have to be disinfected and access is restricted. Within the 3-km zone all poultry have to be
kept indoors and tested. Within the 10-km surveillance zone, there can be no
movement of poultry to or from the area except for slaughter. No trains
carrying live poultry can stop anywhere in the protection zone; all bird fairs
and markets are banned. There is increased surveillance of wetlands for dead
birds. Measures have to be made to isolate domestic from wild birds and
prevent them sharing water – both for drinking and for swimming.
To prevent any risk of spread of H5N1, DEFRA introduced a ban on
pigeon racing in July 2007. This followed the detection of the virus in wild
birds in France.
So far in the USA only low pathogenic (LP) H5N1 has been isolated from
wild birds in Michigan, Pennsylvania and Maryland, with no mass die-offs.
The USA has imposed a comprehensive import ban on birds and bird
products from all infected areas.
International surveillance and collaboration is happening on both a
European and a global basis. Notification of outbreaks and statistics are
shared as widely as possible, with human and animal case data being
shared with organisations as diverse as the Organisation for Animal Health
(OIE), the European Commission, WHO and many bodies involved in civil
contingency planning.
Transmission of H5N1
The disease remains rare in humans; luckily, HP H5N1 has a low transmission potential, keeping the total number of cases and deaths relatively
low. The virus seems to prefer to colonise the lower lung, hence the clinical
symptoms and the current low transmissibility because infection requires a
very narrow particle size, which does not cause deposition in the higher
airways but is sufficiently large to give an infective inoculum.9
As of January 2009, there had been nearly 400 clinical cases of H5N1
in humans with an associated mortality rate of approximately 60% across
the Near East, Middle East, Africa and south-east Asia. Unlike classic
influenza, most cases have been in children and young adults younger than
40. Morbidity has been highest in 10–19 year olds. The most significant
factor in contracting the disease is contact with sick or dead poultry (or wild
birds) or their faeces, visiting a poultry market, or consumption of blood or
meat from infected birds. Many of the cases in south-east Asia appear to
relate to the close proximity of the population and their poultry in that area.
Slaughtering, plucking, butchering and preparing birds for cooking have
also led to infection.
72 | Zoonoses
The largest numbers of clinical cases of HP H5N1 to date in humans
have been seen in Indonesia and Vietnam. There has been some evidence of
human-to-human transmission with probable child-to-mother transfer in a
Thai hospital. There have also been a numbers of clusters of cases seen in
humans, mostly in blood-related family members living in the same household. It is not yet known if this reflects genetic susceptibility or is purely a
common route of exposure to the pathogen.10
In human cases the incubation period is 3–4 days post-exposure with a
range of 2–8 days. Initial symptoms include fever, sore throat, muscular
aches, headache, lethargy and conjunctivitis. The H5N1 virus shows clinical
symptoms similar to the 1918 Spanish flu of avian origin. Difficulty
breathing with chest pains may rapidly progress to acute respiratory distress
syndrome (ARDS) and multiorgan failure. Diarrhoea is often seen as a
symptom, unlike in classic influenza.
Treatment of HP H5N1
In H5N1 cases the treatment regimen is very different. In Vietnam, Thailand
and Indonesia resistance to amantadine has been seen in H5N1 cases.11 This
leaves the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir
(Relenza) as treatment options. The efficacy of these agents depends upon
their early administration within 48 hours of symptom onset. The WHO
recommends the choice of oseltamivir over zanamivir. Zanamivir has been
effective against a small number of oseltamivir-resistant cases seen to date.
There is also some evidence for the use of a neuraminidase inhibitor and
amantadine in synergistic combination.12
In Vietnam, some cases of H5N1 demonstrate a rapid elevation of
cytokine levels, which are associated with fatality. The rapid initiation of
antiviral therapy can reduce this risk. Lymphopenia and thrombocytopenia
have been seen in patients and have been linked to cytokine release, with
increased fatality associated with the development of septic shock. This is
the only reason for using corticosteroids in the treatment of influenza, and
is not desirable but may be necessary as a life-saving measure.
Associated pneumonia should be treated with antibiotics only if necessary, and usually empirically with a b-lactam (cefotaxime, etc.) plus
azithromycin or fluoroquinolones. Adjunctive therapy with oxygen may also
be necessary.
Prevention of influenza (both classic and H5N1)
Due to the potential seriousness of an epidemic/pandemic, a new major
public health monitoring scheme for influenza in the UK was introduced in
late September 2006. A similar scheme is run in Scotland, called GP Flu
Spotter, along with another scheme, the Scottish Enhanced Respiratory
Virus Infection Surveillance (SERVIS). NHS Direct also has an analysed call
Zoonoses of agricultural animals | 73
data scheme that would allow epidemic monitoring, and is believed to offer
an opportunity to monitor geographical spread. Given the name QFLU
(QResearch Centre for Influenza), it monitors daily numbers of people being
seen by general practitioners (GPs) with influenza and influenza-like illnesses,
those suffering from respiratory infections, such as pneumonia, and the
numbers being given antivirals. The Royal College of General Practitioners
also collects data from GP practices. The Health Protection Agency (HPA)
and Health Protection Scotland (HPS) have surveillance schemes monitoring
types and subtypes currently circulating in the human population. This
information, when collated for pathogenicity, case incidence and subtype, is
passed to the Chief Medical Officer (CMO) and is used to drive campaigns
aimed at increasing the uptake of vaccination in at-risk groups. Data is
also fed into the WHO monitoring scheme.
The Medical Officers of Schools Association (MOSA) monitors infection
in approximately 9000 children at 35 boarding schools. The Office of
National Statistics also monitors deaths from respiratory illnesses such as
bronchitis, pneumonia and influenza. All of these data are coordinated by
the HPA Communicable Disease Surveillance Centres (CDSCs) in England
and Wales, and Northern Ireland, and by the HPS.
The strategy for prevention is geared to the production and comprehensive uptake of an effective vaccine. The uptake of the vaccine is monitored
by the HPA Centre for Infections (CPI), Colindale in England and HPS in
Scotland.
In the UK and the USA, there is a major pandemic prevention and planning process being undertaken, involving an integrated approach across a
large number of government departments. There is a programme of assistance for both domestic and international surveillance in both bird and
human populations, and also support for clinical research into treatment
and diagnosis. Stockpiles of vaccine and antiviral are being prepared for
emergency use.13
As the circulating subtypes of influenza have the potential to mutate
rapidly, preparation has to be predicted on emerging and current subtypes.
The WHO makes the decision twice a year as to which subtypes should be
used as the basis for the vaccine. This decision is based on the data that it
derives from its monitoring laboratories in London, UK (the National
Institute for Medical Research [NIMR]), Atlanta, USA, Tokyo, Japan and
Melbourne, Australia, which are fed by a worldwide network of National
Influenza Centres (NICs).
Following the decision, vaccine manufacture begins immediately, and is
released as rapidly as possible. The effectiveness of the vaccine hinges on the
sophistication and accuracy of the prediction and monitoring system. During
the 2007–8 season, the UK Department of Health (DH) ordered 15 million
doses of vaccine for administration in the UK.
74 | Zoonoses
In classic influenza, those individuals considered to be suitable and most
likely to benefit from vaccination are elderly people, workers in social care
and healthcare services, and those who are immunosuppressed. It is particularly important that elderly people in long-stay residential accommodation
are vaccinated because a localised outbreak has the ability to spread rapidly.
Physically fit adults under 65 years of age and children are not considered
to need immunisation unless they are healthcare workers or carers, or they
have chronic respiratory, renal, heart or liver disease.
In addition it was recommended for the first time by the HPA in 2007,
for the 2007–8 season, for patients who have had a stroke or a transient
ischaemic attack (TIA), have multiple sclerosis (MS) or a chronic degenerative neurological disease (i.e. Parkinson’s disease), and all patients with
diabetes. Individuals identified as at risk should be encouraged to stay at
home rather than frequent public places during epidemics to avoid infection.
The decisions on classes of people requiring immunisation in the event of
an H5N1 epidemic will be different, with essential workers across society
being a major priority. This reflects anticipated mortality rates and the
different pattern of infection that it displays.
Normally animals are not vaccinated against influenza; however, English
zoos have been permitted to vaccinate their birds against avian influenza
because of their vital role in global conservation. English zoos wishing to
vaccinate their birds can now apply for permission, subject to meeting the
eligibility criteria. During 2006–7, four zoos took advantage of the permission
to vaccinate and proceeded to vaccinate their birds.
Vaccine development
A novel influenza vaccine is being developed by Immune Targeting Systems
(ITS) in the UK. Their aim is to produce a ‘universal vaccine’ that provides
protection against an emerging influenza subtype, including H5N1. ITS is
not alone in trying to develop this type of vaccine, with companies across the
world also attempting to develop a product that can be used against antigen
families present across a spectrum of influenza A viruses. The resulting
vaccine could be manufactured in advance of any pandemic and, although it
would not offer complete strain specificity, it could give some protection until
a strain-specific product could be manufactured.14
The vaccine contains immune response-stimulating complexes linked to
antigenic proteins, giving a vaccine that is also capable of conferring immunity in the face of viral mutation. The technology may also be applicable to
other rapidly mutating viral diseases such as HIV or hepatitis C.
In the USA, the government has set a challenge to the Defense Advanced
Research Project Agency (DARPA) to develop new technologies for
influenza vaccine technology and production.
Zoonoses of agricultural animals | 75
Industry measures
In agriculture, importing poultry from areas where avian influenza is
endemic is prohibited under the Animals and Animal Products (Import and
Export) (England and Wales) Regulations 2000 and the Products of Animal
Origin (Import and Export) Regulations 1996. All poultry, hatching eggs
and poultry meat must be declared free of avian influenza and other notifiable
diseases by the producer and the importer.
When the Ministry of Agriculture is informed of an outbreak, a declaration may be made by the Minister making it an offence to import specified
animals and/or animal products from the affected country or region. This
led to the banning of eggs and poultry from some regions of Italy during
2000.
Defra and the HSE’s advice to poultry workers is that they should wear
protective clothing, including respirators, wherever and whenever fowl
plague is present in flocks. This is good practice at any time.
Cattle
Cattle are kept around the world for the production of meat, milk and
cheese, and hides for leather. The zoonotic infections that cattle suffer are
particularly important, not only because they are emotive (such as bovine
spongiform encephalopathy/variant Creutzfeldt–Jakob disease [BSE/vCJD]),
but also because of the widespread consumption of cattle products.
Concerted efforts have been made over past decades to reduce the risks of
particularly important zoonoses, such as brucellosis and bovine tuberculosis,
and the success of the measures taken is demonstrated by the current low
incidence of these diseases.
Prion disease is discussed further in Chapter 5, because its emergence is
considered to be one of the most significant events of zoonotic transfer that
has occurred recently in the UK. In the following section the diseases discussed
are those that have either currently or historically been of significant
healthcare importance.
Brucellosis
Mediterranean fever, undulant fever, Malta fever
Brucellosis was named after Bruce who, in 1887, identified the bacterium
that caused Malta dog, a disease familiar to many generations of seafarers.
He named this pathogen, which he isolated from goats’ milk, Brucella
melitensis. This is only one of the causatives of the group of diseases that are
aggregated under the general name of brucellosis. They are caused by various
species of Brucella, depending on source of infection and the associated
animal host. As our knowledge and exploration of the bacterial fauna of
76 | Zoonoses
other species have become more extensive, there has been the identification
of varieties of Brucella associated with species as diverse as dolphins, seals
and rats. Other species such as hares have been identified as carriers, capable
of infecting other animals, particularly pigs, over wide geographical areas.15
The species responsible for most human infections are B. abortus from
cattle, B. melitensis from sheep and goats, B. canis from dogs and B. suis
from pigs. The diseases are distributed worldwide and are particularly
prevalent in South America, Africa, the Mediterranean, Asia and eastern
Europe, where large flocks of animals are tended, and eradication
programmes are impracticable or unenforceable. The WHO has an ongoing
programme of eradication by slaughter and vaccination aimed at controlling
the disease in countries around the Mediterranean basin. A significant
numbers of cases were seen in Malta during 1995, which led to cases in the
UK in returning travellers. In England and Wales all cases seen in humans
are known to have been acquired abroad, with 19 cases in 2004 and 8 in
2005. Some cases of Brucella abortus are seen in Northern Ireland; however,
the rest of the UK declared eradication in 1993, and the use of pasteurisation, vaccination and slaughter inspection has been successful so far in
preventing recurrence. B. melitensis has never been isolated from animals in
the UK and is therefore not considered to pose a threat. Only a small
proportion of dairy produce is derived from goats and sheep in the UK and
there is a testing and screening programme in place, which constantly
monitors for this pathogen.16
Disease in animals
In animals the main symptoms in all breeds suffering from the four main
zoonotic strains previously mentioned are focal necrosis of the placenta,
abortion and future infertility. The birth fluids and afterbirth are highly
infective, and grazing cattle are infected by ingesting contaminated material from pasture. The disease is not apparent before the heifer aborts.
Bulls may also be infected and can sexually transmit the pathogen, until
ultimately becoming sterile. Cattle may be infected with any of the
zoonotic strains, whereas horses appear to be resistant to all of the known
zoonotic strains.
A new species of Brucella (tentatively named Brucella maris) has been
identified in seals, cetaceans (whales, dolphins and porpoises) off the
northern coast of England, in an otter from the south-western coasts of
England, and in a bottle-nosed dolphin from California. It is unknown yet
if this strain is zoonotic.16
Disease in humans
Disease in humans usually follows the ingestion of unpasteurised milk or
milk products, contaminated with either B. abortus or B. melitensis. An
Zoonoses of agricultural animals | 77
alternative route for infection is by contact with contaminated bodily fluids,
membranes or aborted young. In some countries where the disease is
endemic, it may be spread at slaughter in abattoirs by direct contact with
infected blood or meat. There is some evidence for aerosol spread by
infected droplets or dusts. There have been isolated reports of human-tohuman transmission by sexual contact, and also from mother to child by
infected breast milk.17,18
Human disease presents with lymph node swelling, enlargement of the
spleen, fever, testicular swelling, influenza-like symptoms, and lethargy,
nausea and weight loss. Endocarditis or meningitis may follow, sometimes
with fatal results.19
There is also a chronic undulant form that was often seen in people who
work with cows and veterinary surgeons. Periodic bouts of high fever and
clinical symptoms are interspersed with periods of remission with no clinical
signs. This can persist for years or decades. The use of antibiotics quickly
resolves most clinical cases; however, prolonged therapy may be necessary in
refractory cases.
A septicaemic form is also occasionally seen. There is evidence that this
is caused by the inhalation of infected aerosols in abattoirs and meatprocessing plants where infected animals or their tissues are processed. It is
characterised by an acute systemic disease with high fever.
Diagnosis
Diagnosis follows blood culture or using polymerase chain reaction (PCR)
testing. The bacteria are relatively slow growing and successful culture in
laboratories can prove difficult. Complement fixation is also now used in
diagnosis.
Treatment
Treatment relies on the use of antimicrobials, usually in combination to
prevent resistance. The British National Formulary (BNF) and the WHO
recommend the use of doxycycline plus rifampicin or streptomycin. In the
past co-trimoxazole was often used; associated toxicity has led to its
replacement by more suitable agents. Therapy is usually prolonged; the
WHO recommends 6 weeks as a minimum duration. The BNF recommends
rifampicin 600 mg to 1.2 g daily in two to four divided doses with doxycycline 100–200 mg/day; the WHO recommendation is similar: rifampicin
600–900 mg/day plus doxycycline 200 mg. In severe cases streptomycin
may be used in place of or in addition to rifampicin. Longer-term therapy
may be required in the undulant form of the disease.
Quinolones in combination with rifampicin have undergone trials and
been demonstrated to be as effective. Currently no effective vaccine for
human brucellosis is available.
78 | Zoonoses
Prevention
Suitable protective clothing will reduce the risk from occupational exposure.
The use of disinfectants, especially chlorinated or iodine- or ammonia-based
products, can prevent environmental hazards. The mainstay of prevention is
eradication by animal vaccination or slaughter programmes. On a personal
basis, travellers to areas where the disease is endemic should be encouraged
to avoid unpasteurised dairy products and undercooked meat.
Following the discovery of sea mammals infected with a variety of
Brucella, which is not currently known to be zoonotic, the following advice
had been offered by the HPA in the UK:
People who handle or work with seals or small cetaceans are advised to take
suitable precautions to avoid any risk of infection although the new species
of Brucella is not known to present any risk to human or animal health.
In domesticated animals, once Brucella is detected, often during routine
testing and carcass screening, any infected beasts will be culled, and herds
will be subject to a strict testing regime. Wild animals, such as deer that may
be infected in the local area, will also be monitored post mortem.
Foot-and-mouth disease
It is questionable whether foot-and-mouth disease (FMD) is a zoonosis,
although as a disease it has a huge economic impact for livestock farmers.20
It does have a zoonotic potential, as a single case in the 1967 UK outbreak
and one confirmed case in the 2001 UK outbreak demonstrated. However,
the circumstances leading to human infection are usually extreme.21
The disease is found worldwide and all cloven-hoofed animals are
affected. Caused by an aphthovirus, there are several different serotypes, of
which the most virulent is serotype O (pan-Asiatic), which was responsible
for the last UK epidemic.
Transmission
The virus can be transmitted by a number of routes, which include contact
with already infected animals, infected aerosols (which can carry long
distances downwind), fomites, and also uncooked or insufficiently cooked
meat that is contaminated, especially where this is incorporated into animal
feed.
Disease in animals
The first symptom of infection in animals is a high fever; blisters and ulceration develop on the mouth and the feet, leading to lameness and poor
feeding ability. The disease spreads rapidly within herds, as infected animals
are actively infectious and large amounts of live virus are produced before
Zoonoses of agricultural animals | 79
and after clinical symptoms start. Piglets are the worst affected, and the
disease can cause high mortality.
Spread to other sites is believed to occur on the wind or by physical
means, including vehicular, livestock or human movement. The virus can
also infect wild deer which can then become a reservoir for infection.
Disease in humans
The WHO has recorded only about 40 confirmed cases of FMD in humans
worldwide in the twentieth century, of which most were related to the O
serotype. Transmission was first documented following deliberate ingestion
of unpasteurised milk from infected cows by three German veterinary
surgeons in 1834. In brief, very close contact with infected cattle or their
products seems to be necessary for infection to occur.
Following an incubation period of between 2 and 6 days, clinical signs
of infection commence. Blisters appear on the hands and sometimes on the
feet and in the mouth and/or the tongue. Symptoms normally resolve
spontaneously, usually within a week of the last appearance of blistering.22
Media misconceptions have much to do with the publicity that this condition has received. There is another, non-zoonotic, virus of the Coxsackie
family that produces similar symptoms in children, called hand, foot and
mouth disease, which leads to confusion, as may infection with other viral
pathogens.
Diagnosis
Confirmation of the diagnosis is made by serology testing on clinical
samples.
Treatment
There is no treatment except symptomatic support. Prevention of disease in
humans is normally managed by protective clothing for personnel handling
or culling infected animals, and the pasteurisation of dairy products. A
vaccine is available for animal use; however, there is no provision or clinical
need for its use in humans.
Prevention
Prevention of FMD in animals relies upon a host of organisations. Importation
of infected foodstuffs, which then entered the animal food chain after inadequate heat treatment of swill, was probably the source of the latest UK
outbreak. Customs services have the task of controlling this trade, but individual travellers may illegally import meat, meat products or contaminated
dairy products into the UK in their luggage, making the task of control
impossible. Importation of contaminated livestock has also been suggested
80 | Zoonoses
as a means of spread, and outbreaks in continental Europe have been linked
to infected livestock exported from the UK.
Locally, disinfectant in foot and vehicular baths helps prevent physical
transfer. In the UK, DEFRA provides a list of disinfectants that are approved
under the Diseases of Animals (Approved Disinfectants) 1978 as amended
for use against FMD and/or in respect of General Orders (25 April 2001).
Case histories
The two confirmed human cases in the UK – the first in the 1966 outbreak
and the other in 2001 – bear examination, if only to emphasise how difficult
it is to catch the disease.
In 1966, a 35-year-old agricultural machinery salesman, Bobby Brewis,
lived on a farm at Yetlington, Northumberland, with his brother. The cattle
on the farm were slaughtered, having developed FMD. Mr Brewis took no
part in the slaughter, but watched from some distance. Later he developed
the symptoms of the disease. On being diagnosed he fainted, believing that
he would be shot, like the infected cattle.
It is unclear how he became infected, but it is believed that he may have
consumed milk deriving from the infected herd. As a result he was
ostracised by the local community, lost his job and was last heard of as a
fish-and-chip shop proprietor in Sunderland.
Details of the 2001 case are sketchier, with a confirmed case in a contract
worker employed to cull cattle in Cumbria. From the details released, it
would appear that the man was contaminated while dealing with a carcass.
Material from the dead or dying animal sprayed the man copiously, and he
later developed symptoms of the disease. As a spokesman for the then Public
Health Laboratory Service (PHLS – now part of the HPA) so neatly put it:
‘If you place a human being in contact with that size of inoculum, there is
always a chance they will develop the disease.’
Pseudo-cowpox
Milkers’ nodules, milkers’ wart, paravaccinia, false cowpox
This is caused by a parapoxvirus, known as paravaccinia virus or milkers’
nodule virus (MNV). It is endemic in cattle worldwide. The virus is closely
related to orf and bovine papular stomatitis virus, both of which are capable
of causing zoonotic infection.23
In cattle, horseshoe-shaped crusted lesions or erosions are seen around
the mouth and nose, with papules or other lesions on the teats and udder.
Considered to be an occupational disease, human infection follows
contact with infected cattle, especially the teats of infected cows; however,
infection can also be via fomites because the causative agent is resistant to
desiccation.
Zoonoses of agricultural animals | 81
As it is usually self-limiting, most people involved in the cattle industry
accept that they will be infected and, as immunity follows infection, most
cases are not seen by, or notified to, healthcare workers.
Disease in humans
Following infection, there is a pre-patent period of between 4 and 21 days.
The clinical presentation is usually a single painful or itchy nodule on the
digits, hands or lower arms. This develops into a reddened, weeping and
then crusted lesion, which heals, usually with little or no scarring.24 In rare
cases, where systemic infection occurs, there may be fever, lymph node
swelling, skin rashes and secondary infection. Sometimes gastrointestinal
disturbance may occur.
Diagnosis
Differential diagnosis may be difficult and is often based on patient history.
Culture of the causative virus usually takes longer than the course of the
disease. Differentiation between milkers’ nodules and orf is impossible in
most settings.
Treatment
There is no treatment, although use of antibiotics and local antiviral cream
prevents secondary infection and may accelerate healing. Symptomatic
treatment may also be useful in reducing fever and other symptoms.
Prevention
Gloves should be worn when handling animals suspected of being infected;
however, due to the self-limiting nature of the disease, and its ability to
survive on fomites, this may just defer rather than prevent infection and
associated immunity.
Q fever
Query fever, Balkan influenza, abattoir fever
Q fever, first described in Australia in the 1950s, is a disease that stems from
cattle, although it usually causes no symptoms in the host animal. It is
caused by a rickettsia, Coxiella burnetii, an obligate intracellular bacterium.
The causative organism has a global distribution and it is possible for many
species, including ticks, fleas and lice, as well as many vertebrates, to carry
the disease. The main significant zoonotic reservoir is considered to be
bovines and also sheep. Once infected, the organism colonises and
produces infective foci in the mammary glands and the placenta of pregnant animals. During birth large quantities of the organism can be found
in the amniotic fluid and on the placenta. The organism is capable of
82 | Zoonoses
forming an environmentally resistant spore form capable of forming the
inoculum for delayed outbreaks. Surveys carried out on dairy herds in
England and Wales suggest that up to 20% of all stock may be infected.25
The presence of the organism in milk results from the colonisation of the
mammary system, and host animals can carry the disease for prolonged
periods, with shedding occurring sporadically or constantly during lactation. The organism is resistant to heat but ideal pasteurisation conditions
will remove it from milk; however, there is a risk from unpasteurised or
incompletely pasteurised milk or milk products. It has been postulated that
urine or faeces from infected animals may also be a carrier medium for the
organism.
Seventeen cases of Q fever were reported in England during 2005, and
six in Northern Ireland. Most cases were in male agricultural workers who
were probably exposed to the pathogen in the course of their work.
Transmission
Transmission to humans usually follows exposure to infected material and
DEFRA considers it to be an occupational zoonosis of agricultural and other
workers closely involved with cattle and sheep. The people at highest risk are
veterinary surgeons and stock people who assist at births, although the
organism is highly resistant to desiccation and therefore can infect individuals
working with hides, fleece or bones of infected animals. Transmission is by
direct contact with contaminated materials, especially the afterbirth or material contaminated with amniotic fluid. There is some evidence that inhalation
of dust from infected straw or bedding and even soil may also cause infection.
Further down the food-processing chain, transport drivers and abattoir
workers may also be at risk. Drinking milk or consuming contaminated milk
products is also a possible route of infection, and transmission via ticks, lice
or fleas has been demonstrated.26
Disease in humans
Most exposed individuals display no signs of clinical disease. Infection rates
and recording of clinical cases correspond to lambing and calving cycles,
allowing for the time lag associated with the organism’s incubation period.
After infection there is an incubation period of between 2 and 4 weeks
followed by an acute onset with high fever, associated chills, profuse
sweating and severe headache. Unlike other rickettsial diseases, in humans
there is no skin rash. The patient may also present with anorexia, sickness
and lethargy. The fever may last anything from 9–14 days and can recur at
intervals, with a total duration of up to 3 months. A dry cough may be
present, with pain in the chest cavity similar to pleuritic pain. ‘Cracking’ in
the chest may also be heard during respiration. Lesions in the lungs may be
Zoonoses of agricultural animals | 83
apparent on radiographic examination. Liver enlargement or tenderness
with associated hepatitis-type symptoms can be seen.
Untreated cases can resolve within 5–14 days, although symptoms may
not regress for more than 7–8 weeks and relapses may occur. The untreated
fatality rate is estimated at 1% of cases. Following severe infection there
may be a need for prolonged convalescence. Elderly patients are particularly badly affected by this disease and may require prolonged supportive
measures.
A chronic form also exists that causes a prolonged endocarditis leading
to valvular damage, especially of the aortic valve. Recent figures show that
damage is more common in patients with pre-existing valve damage.
Symptoms can appear long after the disease has run its clinical course and
may require replacement of damaged valves. The fatality associated with
this form is estimated to be as high as 60% of cases unless corrective surgery
is undertaken. Chronic hepatitis also develops in a small number of cases.
Diagnosis
Diagnosis follows serological testing, because the organism is slow growing
and almost impossible to culture from clinical specimens. There are several
techniques, of which the most reliable are indirect immunofluorescence,
complement fixation, enzyme-linked immunosorbent assay (ELISA) and
microagglutination.
Treatment
C. burnetii can be difficult to treat because it can show a lack of response,
rather than true resistance to antibiotics. The BNF recommends the use of
tetracyclines at usual clinical doses, and historically chloramphenicol has
been used, although it is reserved for recalcitrant infections due to the incidence of major side effects. The length of the course may require adjustment
so that therapy is extended for a period of days after the fever regresses to
prevent relapse. Patients with endocarditis and valvular damage will need
prolonged prophylaxis up to and beyond surgery, with valve replacement or
repair. Studies have shown that the organism has a heightened susceptibility
to combinations of drugs, which results in acidification of the intracellular
vacuole. Chloroquine in combination with doxycycline has been used with
some notable success, although there is a need for continued patient
observation to prevent build-up of chloroquine in the eye. A minimum of
3 years’ therapy prevents relapse.
Prevention
As with many other zoonoses, prevention strategies revolve around good
personal and environmental hygiene. Bedding contaminated by postpartum
84 | Zoonoses
material and the material itself should be carefully handled, with collection
and subsequent burying or incineration. Disinfection of housing and other
areas should be carried out with DEFRA- or USDA-approved products.
Protective clothing, including respirators, overalls and gloves, must be worn
wherever feasible. In the USA a vaccine for cattle has been developed; it is
not licensed for use in the UK. Carrier animals have been subject to eradication by slaughter policy. Nevertheless, the organism is considered to be
widespread in the environment and preventing animals from becoming
infected is deemed to be practically impossible. All milk and milk products
should be pasteurised, and monitoring of the process should be maintained
in the normal manner to ensure that optimal temperatures and duration
standards are met.
Tapeworm
The beef tapeworm (Taenia saginata, also known as Cysticercus bovis) and
the pork tapeworm (T. solium), which is found in pigs and wild boar, are very
similar in both overall appearance and life cycle. They are both members of
the cestode worm family, and the definitive host for both worms is humans:
the tapeworm reaches maturity only in the lumen of the human gut. The
associated animal is an intermediate host, necessary for the larvae to infect
humans after ingesting infected, inadequately cooked meat from a suspect
carcass. Comparison with Echinococcus granulosus is of interest (see
p. 36); this is also a cestode, but humans are blind intermediate hosts, and
the usual cycle uses dogs as a host and sheep as a full intermediate host – the
exact reverse of Taenia spp.27
In 2005 there were 72 reports in England and Wales made to the HPA of
human infection with Taenia spp. Of the patients, three were travellers and
were considered to have become infected while abroad. There have been no
reported cases of T. solium in the UK since 1994. In the USA, most cases are
seen in recent migrants, usually from Latin America, and specifically Mexico.
General parasitology and disease in humans
The adult worm is flat in cross-section and widens gradually from the head
or scolex, through the proglottids or body segments. The scolex attaches to
the gut wall of the host by means of suckers and/or hooks, depending on the
species involved.
The body segments or proglottids are produced from just behind the
scolex, and the oldest and most mature are at the opposite end of the worm.
As the segments mature they develop both male and female reproductive
organs, self-fertilise and produce eggs that are contained within the
proglottid wall. The mature proglottids break away from the body (or
Zoonoses of agricultural animals | 85
strobila, consisting of all the proglottids and the scolex) and pass out of the
gut via the anus. The secondary or intermediate host, in which the larvae
can develop, is then infected by ingestion of either the eggs or embryos
present in faecal matter.
The tapeworm absorbs nutrients from the gut of the host over its whole
body surface, and has a rudimentary nervous and digestive system. The
worms are host specific and exist as an adult solely in the gut of their
preferred host. When eggs hatch in the gut of a host, either primary or intermediate, larvae penetrate the wall of the gut, and then migrate to a preferred
site, usually in muscle tissue or other organs. In either pigs or cattle these
normally migrate and encyst again in muscle tissue, where the cyst may
develop daughter cysts with multiple internal scolices.
Alternatively they may migrate to other organs and cause a condition
known as cysticercosis. The beef tapeworm rarely causes cysticercosis;
however, the pork tapeworm can cause this condition in humans. In
cysticercosis the migrating larvae encyst in sites as diverse as the brain or
other areas of the central nervous system (CNS), eyelid and conjunctiva. The
condition is seen mainly in intermediate hosts, but may also be seen in
humans, where either eggs or larvae are ingested, or where the gravid
proglottid (a mature proglottid full of eggs or embryos) ruptures in the gut
before it can be expelled.
In cysticercosis, the cysts may be quiescent or active. Where active cysts
are present they undergo a budding and proliferation process, called
racemose cysticercosis, leading to a series of connected cysts with multiple
scolices in the vacuole. When the cysts are sited in the brain, complications,
including neurological disturbances, follow.28 The intensity and type of
symptoms seen in cases of neurocysticercosis depend upon the number of
lesions present and their location, size and status. Live foci are usually
asymptomatic; as the cysts degenerate and die there is a progressive inflammatory response causing encephalitis and swelling. Epileptic seizures are
the most frequent symptom. Meningitis, raised intracranial pressure and
paraesthesia may also occur.
Adult beef tapeworms can reach a size of between 12.5 and 25 m in length;
the pork tapeworm is much smaller, only reaching between 2 and 7 m. They
are usually solitary occupants of any infested gut as multiple worms can cause
intestinal obstruction. The beef tapeworm differs from the pork tapeworm in
having no hooks on the scolex. Both species are capable of producing a
strobila of 1000–2000 proglottids, and can live for up to 25 years. There are few
symptoms associated with the adult worm, except slight irritation of the site
of attachment or vague abdominal symptoms with hunger pangs, loss of
weight and general condition, indigestion, diarrhoea and/or constipation.
Discomfort and embarrassment may be caused by migrating proglottids
86 | Zoonoses
when they reach the anus. The proglottids may be seen with the naked eye,
either grouped or as single segments in the stool. The proglottids may be
mobile when moist, becoming quiescent as they become desiccated.
Diagnosis
Definite diagnosis of infestation either follows isolation of eggs or proglottids
from the stool or protrusion of a portion of the strobila through the anal
sphincter.
Serological testing using ELISA methods confirms diagnosis, and in cases
of cysticercosis imaging by computerised tomography, radiology or magnetic
resonance is usually necessary. Biopsy of subcutaneous cysticerci will also
confirm other findings.
Treatment
For adult tapeworms treatment is undertaken using either niclosamide or
praziquantel. The BNF states that niclosamide is available from IDIS Ltd
(see Appendix 2) on a named-patient basis. It is solely active against adult
worms and does not kill larval stages. Side effects are usually limited to
gastrointestinal disturbances and itching with occasional rash. To prevent
any risk of cysticercosis by autoinfection following emesis, an antiemetic
should be given at the same time as the niclosamide, on wakening.
Praziquantel is available from Merck on a named-patient basis. It is
deemed to be as effective as niclosamide, and should be given at a single
dose of 10–20 mg/kg body weight after a light breakfast.
There is some controversy surrounding treatment of cysticercosis. Usually
surgical removal of the cysts is advocated in humans before damage ensues,
with concomitant administration of anthelmintics. This is very important in
infection associated with the eyes.29
In CNS involvement, symptom control of associated epilepsy is achieved
using the usual anticonvulsants. The BNF does not make any recommendations on the use of anthelmintics (or cestocides) in neurocysticercosis;
however, elsewhere in the world praziquantel or albendazole has been
routinely used. Albendazole is a benzimidazole anthelmintic and is
approved for treatment of only hydatid disease and neurocysticercosis in the
USA. It is teratogenic in animals, so a careful risk–benefit analysis must be
carried out before it is used in women who are pregnant or of child-bearing
years. It is hepatotoxic, and can also destroy bone marrow, so complete
blood chemistry analyses and liver function tests should be routinely carried
out before and during therapy. There are risks associated with the use of
anthelmintics in neurocysticercosis, because they can cause serious adverse
effects, so a risk–benefit analysis always has to be undertaken.30
To obtain a cestocidal effect praziquantel at an oral dose of 50–100
mg/kg per day three times daily for 30 days or albendazole at 15 mg/kg
Zoonoses of agricultural animals | 87
orally two to three times a day for 8–15 days, depending on radiological
findings, has been shown to destroy viable cysts. Symptomatic treatment is
also necessary to ensure good clinical outcome.
Prevention
Tapeworm infection is not common in the UK or the USA due to a strict
system of meat inspection. This is not true of the rest of western Europe.
Germany and France report significant numbers of cases annually, associated with the consumption of infected meat in national delicacies. In nonMuslim developing countries there is a high incidence of the disease, causing
more than a third of all cases of adult-onset epilepsy. Due to the longevity
of the parasite, immigrants from these countries could present with symptoms of the disease long after their arrival in the UK. In the USA there have
been sufficient cases among migrant workers for the condition of cysticercosis to be routinely tested in cases of epilepsy among this sociological
group. The numbers of tourists travelling to areas of risk, such as south-east
Asia, the Indian subcontinent and Africa, have increased dramatically in the
past decade, so tapeworm infestation should be excluded in any diagnostic
path relating to persistent abdominal symptoms or seizures following such
trips.
Suspect meat or meat products should be thoroughly cooked, avoiding
wherever possible eating meat from dubious sources that is either raw or
under-cooked. Suspect carcasses or meat should be frozen for at least 3 weeks
to kill any larvae. Viable eggs or embryos may also be present in water
contaminated by faecal matter; the usual precautions when drinking water
of unknown quality should be applied.
Separation of human sewage and intermediate host animals is important
in breaking the infective cycle. Sewage sludge should not be used to dress
pasture where animals destined for human consumption are actively grazing
or housed. Care should be taken after flooding where there is a possible risk
of human sewage contaminating pasture.
Recent work on a vaccine to prevent animals from becoming infected has
shown promise.31
Bovine tuberculosis
Although the prime cause of tuberculosis (TB) in humans is Mycobacterium
tuberculosis (var. hominis), there are still some cases recorded annually of the
condition being caused by the closely related zoonotic organism M. bovis. In
England and Wales fewer than 1% of cases of TB are caused by M. bovis.
Clinical signs and symptoms seen in the infection are identical regardless of
which of the two mycobacteria is present. The disease can also infect a large
number of other mammal species, and has become a source of bitterly
88 | Zoonoses
contested debate between cattle farmers and wildlife groups in the UK over
the role of badgers as a reservoir of infection. In the USA, the case rate of
M. bovis is also approximately 1% of all TB cases. There is a connection to
the consumption of dairy products sourced in Mexico; however, there are
some cases linked to domestic cattle, with wild deer acting as a wildlife
reservoir.
Disease in animals
The primary reservoir of M. bovis was historically cattle. Early control
measures were focused on improving herd hygiene, culling infected beasts
and preventing spread within herds. The most effective control measure was
the development of reliable pasteurisation of milk, the primary source of
transfer of infection from cattle to humans.
Within cattle herds the disease is transferred by aerosol inhalation with
subsequent pulmonary infection, in addition, infection from cow to calf has
been well documented, as has reinfection of TB-free herds by infected
humans. Badgers suffering from the disease have long been suspected of
infecting cattle. The hard scientific evidence is sketchy, and the mechanism
of transmission is as yet unproven. The bacterium has also been found in
many other species of animal, both in the UK and elsewhere in the world,
with pigs, sheep, goats, horses, cats, dogs and foxes all being capable of
carrying infection in endemic areas. In the USA, there is a monitoring
programme in place to ensure that cattle herds are disease free and, except
for some licensed producers, all dairy products are pasteurised. Deer and
other wild animals act as a reservoir, so continual review of disease status in
domesticated cattle is required.
In the UK, cattle have been compulsorily and routinely tested using the
tuberculin skin test since the 1950s. Beasts with a positive test are slaughtered as a mandatory requirement under the Tuberculosis Orders (1984)
and related Orders made under the Animal Health Act 1981. The provision
within the legislation for agreed valuation and compensation payments to
farmers has been a major asset in achieving farmers’ agreement to the
measures. Investigation of herds may also stem from veterinary slaughterhouse
inspection of cattle and carcasses.
Testing frequency depends upon known regional prevalence, and has led
to the UK achieving disease-free status. Devon, Cornwall, the West Midlands,
South Wales and Northern Ireland have the highest current incidence of the
disease in cattle; the level has risen since an all-time low in the 1980s. In
2006, a total of 50 327 tests were carried out across the UK. A total of just
over 22 000 cattle were slaughtered as test reactors, contacts or inconclusive
test reactors. The disease is only controlled, not eradicated, and could
re-emerge if vigilance is not maintained.
Zoonoses of agricultural animals | 89
Clinical signs in cattle are variable. Some animals rapidly lose condition
and cough, and there may be udder involvement in dairy cattle. Other cattle
may remain sleek and healthy; it was not unknown in the past for the bestlooking beast in a herd to be the most infective. Ulcers may be seen in a
cutaneous form of the disease that can affect some animals, usually with
advanced disease. Generalised symptoms may be seen, with diarrhoea and
enlargement of the liver and spleen. Pulmonary disease normally develops
from a soft cough to haemoptysis. Physical examination of the walls of stalls
for blood-stained mucus was a very primitive method of determining infection in animals, and fortunately this has now been superseded. Any of the
other major organs can become affected, and persistent, extensive lymph
node swelling may be present. Skeletal involvement can also occur. Paralysis
of the hindquarters may occur in some cases.
Transmission
Transmission normally follows the ingestion of inadequately or nonpasteurised infected milk or dairy produce. Stock handlers are also at significantly elevated risk if their charges are infected. Transmission may follow
inhalation of infected aerosols, or skin contact with cutaneous lesions on
infected animals. In the UK only 34 cases of confirmed human infection
were reported in 2006; in two of the cases multi-drug-resistant M. bovis was
responsible. There was nothing to link any of the cases with diseased cattle,
so these may represent reactivated disease contracted at an earlier date.
Elsewhere in the world control programmes have not been as effective in
cattle, so there is a risk of infection following ingestion of dairy produce,
especially in developing countries.
Disease in humans
Clinical symptoms vary depending on the source of contamination or route
of infection, although this is not always associated. General symptoms
include weight loss, pronounced fatigue and fever, all of which may gradually worsen. The classic pulmonary pattern of the disease may be seen with
cough and haemoptysis. Ulcers or other lesions may be present in cutaneous
disease. As with cattle, the organism can colonise any or all of the major
organs or the skeleton, producing symptoms related to site and severity of
infected foci. In the USA it has been found that TB patients infected with
M. bovis are more likely to have extrapulmonary disease with organ or
tissue involvement than those with M. tuberculosis.
Patients may be asymptomatic for long periods after infection. Activation
and progression of disease may then occur when disease or age affects the
immune system. Many of the current cases are among elderly people who
were infected in their youth. The disease poses a considerable risk, along
90 | Zoonoses
with other mycobacterial infection, to patients suffering from human
immunodeficiency virus (HIV)/Acquired Immune Deficiency Syndrome
(AIDS). Other people at an enhanced risk of contracting the disease are
veterinary and animal workers. Migrant workers and members of other
immigrant groups may also have the disease; however, as treatment of
M. bovis and M. tuberculosis is similar, drug therapy of one will normally
eradicate the other.32
In England and Wales, 25 cases of TB were caused by M. bovis in 2006,
down from 28 cases in 2005. There were three cases in Northern Ireland, and
six in Scotland in 2006. A cluster of six cases was seen between 2004 and
2006, in a socially closely linked group, with possible person-to-person transmission, because not all the cases, including one that was fatal as a result of
M. bovis meningitis, could be linked to the consumption of unpasteurised
dairy products.33
In the USA, there have been several studies into M. bovis infection. In New
York City a cluster of cases was studied. Approximately 1% of all cases of TB
seen were associated with M. bovis and the patients were mostly Mexican or
Latino, either by ethnicity or by descent. The same pattern had previously
been noted in a monitoring exercise undertaken in San Diego, California.
Most infections were related to the ingestion of imported, unpasteurised,
Mexican cheese. Studies have shown that 20% of milk produced in Mexico
and 17% of meat are infected with M. bovis.
Diagnosis
Diagnosis follows positive skin reaction to tuberculin purified protein derivative (PPD). Bacille Calmette–Guérin (BCG) inoculation produces a positive
test, so this must be excluded. Radiographic imaging, sputum testing or
ELISA of samples supports the findings from skin testing. Differentiation of
the causative Mycobacterium sp. usually follows growth of the organism;
however, this can be difficult. PCR assay has been used to this end, with
considerable success.
Treatment
The treatment of infection with M. bovis is identical to that for M. tuberculosis, and should be carried out by specialist centres. The regimens suggested
by the Joint Tuberculosis Committee of the British Thoracic Society are
normally used in the UK, and are regularly updated as data relating to
prevalence of resistant serotypes are forthcoming. It is not appropriate for
the regimens to be discussed in detail because these change rapidly.
In the USA, a standard four-drug regimen is used for the treatment of
TB, consisting of isoniazid, rifampicin, pyrazinamide and ethambutol.
Pyrazinamide-resistant isolates of M. bovis have been found. Since 2003,
Zoonoses of agricultural animals | 91
streptomycin is no longer routinely used in the treatment regimen due to
both the emergence of resistant strains and safety concerns.34
Prevention
Prevention in animals revolves around the cattle scheme, as outlined above.
Other animals may contract the disease and are usually destroyed if found
to be positive for the disease.
Personnel at particular risk should wear protective clothing when
handling suspect animals, and must be immunised whenever possible. BCG
vaccine is made from a live attenuated strain of M. bovis, and is used to
immunise people against contracting TB from both animal and human
sources. In response to the reduction in the number of cases of TB seen in
the UK, the immunisation programme has changed. Up to 2005, all children
were routinely inoculated with BCG vaccine when they reached the age of
13. Since then, immunisation against TB has become targeted with vaccination being offered to babies living in areas of the UK where there is a high incidence of TB (i.e. 40 cases per 100 000 people per year, or more), or babies
whose parents or grandparents lived in a country with a high incidence of TB.
Children (⬍ 16 years) who have come to live in the UK from countries
where TB is common (i.e. at least 40 cases per 100 000 people per year) who
have not previously been immunised, and adults ⬍ 35 years who have come
to live in UK from countries where there is a high rate of TB (⬎ 500 cases
per 100 000 people per year), or unimmunised contacts of patients with TB
are also offered the vaccination.
In addition those people who are at a high occupational risk such as
health workers, emergency service workers, prison staff and some public
transport employees are routinely inoculated.
The vaccine should not be used in HIV-positive patients because it has
been reported as causing cases of clinical disease. HIV-positive patients who
travel to countries where M. bovis is endemic should be advised to boil all
milk and abstain from any dairy produce that has not been pasteurised or
cooked.
Sheep
Historically, the UK has always been a prolific producer of wool. In the
seventeenth century, sheep were known as ‘God’s own animal’, not only
because of associated Christian symbolism but also because the sheep gave
wool for textiles, meat for the table and milk or cheese. There are many
varieties of sheep, and many have been specially bred for fleece or meat
quality. Other breeds have been developed for hardiness in large areas of
the UK, especially in upland areas in the North or in Wales where no other
92 | Zoonoses
agricultural enterprise is possible due to the poor quality of the land and
its pasture.
As a result of the numbers of animals involved, and the amount of
human contact sheep receive, especially when lambing, there are a number
of zoonotic conditions that are particularly important. It will come as no
surprise that most cases of these diseases are reported from rural areas, and
knowledge of these conditions is especially important in these regions.
Chlamydiosis (gestational psittacosis)
Infection with Chlamydophila psittaci has already been discussed in
Chapter 2. Chlamydophilae are all intracellular dwelling parasites and have
a strange biphasic reproductive cycle, in which only one phase is infective.
Previously, it was not possible to determine if the Chlamydophila spp.
responsible for infection in birds was the same as that seen in sheep and
other species, because the serological and PCR tests used for diagnosis were
not sensitive enough to produce species differentiation. Recently, the species
have been differentiated and reclassified, and it is now known that the
species of Chlamydophila responsible for infection in sheep and goats is a
separate species, C. pecorum, and has been found in cattle, goats, sheep,
swine and koalas, although it is not implicated in causing abortion. The
species found specifically associated with cases of abortion in cattle, sheep
and occasionally humans is identified as C. abortus. As it is difficult to
determine the species present in animals from the clinical signs, the notes
below provide general information. In addition to the main species mentioned
above, there is another, C. felis, found in cats, which is also zoonotic, that
is responsible for rare cases of conjunctivitis (see below).
Disease in animals
The species found in sheep, goats and occasionally cattle can cause a chronic
infection, particularly in female animals. The disease in sheep is known as
enzootic abortion, and in flocks with high incidence of infection is a major
cause of economic losses due to low numbers of live-birthed lambs. It is
usually isolated from the uterus and reproductive organs. In pregnant
animals it causes placental insufficiency and abortion. The infection appears
to be transmitted between animals by either the sexual or the faecal–oral
route. Infected animals pass live organisms in the faeces, and after abortion
or birth the organism is found plentifully in the uterus, vagina and placental
material. Lambs may also be contaminated, especially while still wet and
before maternal cleaning has occurred. The incidence rate in sheep is not
known; however, in 2005, out of 1272 diagnoses of sheep abortion in the
UK, this organism was implicated in 464 ewes. Numbers of cases of abortion in sheep related to Chlamydophila spp. in the last decade have ranged
Zoonoses of agricultural animals | 93
between 1000 and 1700 annually. No human abortions were attributed to
C. abortus in 2005, although nine infected women were identified; luckily
none was pregnant.
Transmission
Transmission to humans follows inhalation of dried faecal matter, direct
contact with faeces, or contact with pregnant or postpartum ewes, lambs,
birth fluids or placental tissue. The organism is capable of surviving
desiccation and survives in dung or soil for several months.
Disease in humans
Following infection there is normally a 1- to 2-week pre-patent period. The
disease usually then presents as an influenza-like illness with cough and
congestion followed by high fever, aching muscles, and occasional back
and abdominal pain. Respiratory symptoms are common, with dry cough
and pneumonia. Anaemia and liver dysfunction with hepatic and splenic
enlargement may also be present.
In pregnant women the disease may be life threatening. This form was
first identified and reported in the UK in 1967, and is luckily rare. The
disease can progress to give placental insufficiency, neonatal distress, and late
term miscarriage or premature birth. In some cases, emergency termination
may be necessary to save the mother’s life. Disseminated clotting may occur
in all major blood vessels.35,36
Diagnosis
Diagnosis is usually made using immunofluorescence techniques, ELISA or
PCR tests.
Treatment
Tetracyclines or erythromycin is the drug of choice. Erythromycin is preferable in pregnant women because tetracyclines are contraindicated in pregnancy, although in resistant cases they may need to be used where the
benefits of treatment outweigh the risks. Caesarean section at early term
may also be necessary.
Prevention
Sheep may be vaccinated to reduce the incidence of enzootic abortion and
shedding of organisms. Suitable protective clothing should be worn,
including face protection, when handling pregnant ewes. Ewes that have
aborted should be isolated until any vaginal discharge ceases.
Pregnant women should, wherever possible, avoid contact with pre-,
peri- or postpartum ewes or goats, and kids or lambs. Contact with
placental material or aborted lambs must be avoided. They should not
94 | Zoonoses
handle unwashed overalls that may be contaminated with blood or secretions from ewes or lambs, or milk ewes. Any pregnant woman who has been
in contact with sheep should seek medical advice if she has an onset of
influenza-like symptoms or fever.
Additional notes
There is another species of Chlamydophila, C. felis (feline keratoconjunctivitis agent), which typically causes rhinitis, pneumonia or conjunctivitis in
cats. This strain can also be transmitted to humans, but it is extremely rare.
The resulting conjunctivitis responds to the use of antibiotic eyedrops or eye
ointment, particularly chlortetracycline or fusidic acid.37
Giardiasis
Giardiasis is caused by the flagellate protozoan Giardia lamblia. It has a
worldwide distribution and, although humans are one of the main reservoirs
for the disease, it is considered to be zoonotic because sheep, cattle, pigs, dogs,
birds such as budgerigars and parrots, and other species are known to
harbour the parasite. It is a biphasic protozoan, having an encysted and a freeliving or trophozoite form. The trophozoite is killed by gastric acid so only the
encysted form poses a risk of infection to humans. The disease is endemic in
developing countries where it is prevalent in most animals and children.
Giardiasis is recognised not only as an issue for public health, but also as a
traveller’s zoonosis and as an infection of other risk groups domestically.38
Disease in animals
Infected animals may be asymptomatic; alternatively they may have weight
loss with chronic diarrhoea and partially formed fatty stools. The parasite
matures and reproduces in the host’s intestine and is then passed with the
stool. Once expelled, the cysts can survive adverse environmental conditions
for prolonged periods.
Transmission
Faecal contamination of water or food and its subsequent consumption by
humans is the most common route of infection. Water from wells or other
ground systems can be contaminated with faecal matter, and when either
unfiltered, or inadequately filtered, before consumption poses a significant
risk. Tap water in countries with poor infrastructure support can also be a
source of infection.39
The oral–faecal route of infection is also common, especially in children.
The cysts are infectious virtually immediately they are passed in the stool, so
person-to-person spread can occur as a result of poor personal hygiene. This
can be of particular importance in care settings, such as day care, nurseries
Zoonoses of agricultural animals | 95
and other premises. Fomite spread by faecal contamination of surfaces or
objects is well documented.
In addition to young children and elderly people living in communal
settings, the other risk groups are travellers (especially those on a budget using
poor-quality accommodation or eating in substandard venues), outdoor
enthusiasts, sexually active homosexual males and immunocompromised
individuals. Patients with HIV will often present with giardial infection;
untreated this appears to adversely affect clinical outcomes and survival
times.40
Disease in humans
The inoculum necessary to produce clinical disease has been estimated at as
low as a single viable cyst, making it extremely infective. Following ingestion the cysts hatch in the small intestine. They can live free in the gut lumen
or attach to the gut wall. The parasite reproduces rapidly and encysts as it
progresses towards the large intestine. Infection may be asymptomatic; in
other patients clinical signs appear after a pre-patent period of between 1
and 4 weeks.
The disease may present as diarrhoea of either chronic or acute nature,
and of either mild or severe character. Unlike other organisms, the stools
are associated with considerable gas and are usually fatty, frothy and foul
smelling. They are usually free from blood or mucus. There is associated
bloating, gastrointestinal spasm and abdominal pain. The patient may feel
weary and nauseous, and report loss of weight and appetite. Dehydration
may occur.
Untreated, the condition normally lasts for 1–2 weeks. Some individuals
can develop a chronic form of the disease that may last for months or years,
which leads to chronic malabsorption states with associated anorexia.
Disaccharide intolerance may develop in almost 40% of any giardial sufferers
during and for up to 6 months after infection. Once resolved, infection seems
to confer some immunity against reinfection.
Diagnosis
Diagnosis has traditionally been by isolating viable cysts from faecal material
of suspected sufferers. An ELISA test is now available, as is a fluorescent
antibody test, which simplifies rapid confirmation of clinical findings.
Treatment
Metronidazole is the treatment of choice for giardiasis – either 2 g/day for
3 days or 400 mg three times a day for 5 days. Alternatively, tinidazole as a
single dose of 2 g or mepacrine hydrochloride 100 mg every 8 hours for 5–7
days can be used. Mepacrine is unlicensed in the UK for this condition;
however, it is available on a named-patient basis or as a special item from
96 | Zoonoses
BCM (see Appendix 2). As previously mentioned, rehydration therapy may
be necessary as an adjunct to other therapy.
Chronic cases are often refractory, requiring repeated treatment courses
to achieve elimination of the protozoan.
Prevention
The following general advice is applicable to many faecal-borne pathogens,
and also forms a backbone of good practice for travellers. In countries
where the disease is endemic or suspected, drink only bottled water and
avoid drinking water or consuming foods that have not been washed in
bottled water. Hot drinks, prepacked carbonated drinks and pasteurised
items are usually safe. Ice in drinks made from local water should be
avoided. Only fruit or vegetables that have a peel or can be peeled and then
washed should be consumed. Any vegetables should be washed in bottled or
boiled water and adequately cooked.
When consuming water from a suspect source is the only alternative,
water purification tablets should be used or the water should be boiled
before consumption.
Domestically, normal hygiene routines of washing hands after defecating
and before handling food prevent spread. For care workers and others
working where faecal contamination of patients or objects is commonplace,
wearing gloves and ensuring that personal hygiene is observed aid prevention
of infection and also spread.
Individuals with HIV should be encouraged to have their companion
animals tested for giardiasis regularly and treated to eliminate the organism if
present. Objects, areas and materials contaminated with animal faeces should
be disinfected and cleaned. In severely immunocompromised individuals, pets
may need to be housed permanently indoors to prevent reinfection.
Orf
Contagious pustular dermatitis
Orf is caused by a parapoxvirus of the Poxviridae family. It is endemic in
sheep and goats and occurs globally; some herds are completely free of the
organism. At present there is considerable discussion as to whether the
incidence of the disease has been increased by the vaccination of herds
where there was previously no history of cases.
Disease in animals
In sheep or goats, crusty lesions on or around the muzzle, eyelids, mouth,
feet or external genitalia may be laden with virus. Necrosis of the skin of
the gastrointestinal and urogenital tract can occur. The virus is shed by
Zoonoses of agricultural animals | 97
infected animals in secretions from lesions and also in faeces and urine.
The virus is persistent in the environment and may survive for many years.
The disease is under-reported because most farmers and veterinary
surgeons recognise the condition and do not need to submit samples to
confirm the diagnosis. In 2005, 27 incidents in sheep were recorded in the
UK at government-associated laboratories. Since 1991 the number of
recorded diagnoses of the condition in sheep has varied between 24 and
58 (average 40 per year).
Transmission
Orf is an uncommon disease in humans; however, it is easily transmitted by
contact with lesions on animals or infected wool. Accidental infection with
live vaccine during vaccination of sheep also poses a risk.
Disease in humans
After infection, ulcerative suppurating lesions on face, hands and arms
appear. Shepherds, sheep shearers and others who handle live sheep, warm
carcasses or unprocessed fleeces or wool are at risk.23
The low number of cases reported by laboratories is likely to represent a
small proportion of the total number of cases seen by GPs in rural areas as
diagnosis of human orf infection is often made on the basis of clinical
presentation and history.
Cases of infection with parapoxviruses are generally under-reported. In
2005, one human case was reported in Scotland, and one in England and
Wales occurred in an abattoir worker. There were no human cases reported
in Northern Ireland in 2005. An annual average of 8 (range 1–25) cases of
orf virus infection were identified between 1991 and 2005.
Treatment
Treatment is purely supportive, because no therapy is recommended.
Lesions usually regress within 6–8 weeks with minimal scarring. Secondary
infection of sores may occur and management using antiseptics or antibiotics
may be required.
Prevention
Good hygiene practices and wearing rubber gloves when handling infected
sheep helps to prevent infection in individuals at risk due to their occupation. Fomite contact may also be responsible for spread, and prevention
strategies centre around good disinfection procedures. Care when using the
live attenuated vaccine to vaccinate flocks is essential.41
98 | Zoonoses
Pigs
Introduction
Although the domestic pig industry has gone through a difficult period in
the last decade, there are still approximately 4.94 million pigs in the UK, of
which approximately 82% are in England. Much of the industry still focuses
on the intensive pig unit, using selectively bred animals geared to the
requirements of producers for rapid growth and of consumers for lean
bacon and pork.
With the current increase in grain prices, and the programme of set-aside
land coming to an end, it is unclear what acreage in the UK will be available
for outside pig enterprises; however, there is an increasing demand by
consumers for better welfare, and thus retailers are moving to require this
from producers. This has the added advantage for producers that they are
able to gain higher returns on their products while satisfying the demands
for high welfare products by consumer lobby groups. It has also enabled
producers to return to using older breeds of pig, with a reduction in the
therapeutic interventions and medicated foodstuffs associated with intensive
enterprises. It should also not be forgotten that some producers have
switched to wild boar or boar/pig hybrids in an attempt to develop new
products and tastes for the public palate.
The pig has always been considered to be the best and easiest option for
xenotransplantation, and is considered to be closest of all our domesticated
animals in biochemical terms to humans. Therefore it can be readily seen
that diseases of pigs are likely to have a significant potential as zoonoses.
Ascariasis
Large roundworm
Infection with roundworm is estimated to affect at least 1 billion people
worldwide. The intestinal nematodes of the genus Ascaris are common
culprits. A. lumbricoides is usually deemed to be a human-to-human parasite
transmitted by the faecal–oral route. The related worm A. suum is normally
found in pigs; zoonotic cases have been seen. The infection is more common
in areas where sanitation or hygiene routines are inadequate. Travellers to
developing countries can return having been infected, as may immigrants or
refugees. A previous infestation does not prevent reinfection, so patients who
have been successfully treated can present with the same condition after
subsequent exposure.42
Disease in animals
Parallel symptoms and signs are seen to human infection (see below).
Migrating larvae can cause pulmonary symptoms. Symptoms of abdominal
Zoonoses of agricultural animals | 99
pain with diarrhoea or enteritis may be present. It is usually suckling pigs or
weaners that show the worst effects. The condition is rarely fatal; however,
larvae that migrate to sites other than the gut can produce unusual and
severe symptoms. The cycle time from egg to adult is believed to be quicker
in pigs infected with A. suum than it is in humans.
Transmission
Infection can be by one of two routes, either directly from ingestion of soil
contaminated with eggs, or after the ingestion of vegetables or salad
containing viable eggs adhering to it. The eggs hatch in the duodenum and
migrate through the gut wall and then via the bloodstream to the lungs.
Disease in humans
The condition may be asymptomatic or initially there may be generalised
symptoms of fever and headache. Symptoms derive initially from the immune
response to the infestation from either the organism itself or its metabolic
products. Larvae can cause pulmonary symptoms, with asthma, pneumonia,
cough and wheeze. The larvae are usually coughed up or migrate up the
bronchi and are then swallowed again.
Once they return to the gut the larvae will pass through their remaining
larval stages. Adults will breed in the gut; the female worm is larger than
the male. Females may reach up to 35 cm in length and 4 cm in diameter.
They may migrate into the biliary or pancreatic ducts. Symptoms may
include gastric cramps, vomiting and diarrhoea. Pancreatitis can occur, as
may intestinal obstruction and malnutrition with weight loss. Jaundice may
be seen if the common bile duct is obstructed.43,44
The whole cycle from egg to adult takes about 2 months. Eggs passed in
the faeces become infective after 2 weeks. Some larvae may not migrate
directly to the lungs and can cause complications arising from their travels
or residence in the brain, eyes, liver or kidneys. The worm and its larva
cause sensitisation. In some patients allergic reactions, some of which are
severe, can be seen when reinfection occurs.
Diagnosis
Eggs may be identified in the stool; larvae or adults may be seen in faeces or
recovered from the throat, mouth or nose. Larvae may also be present in
sputum. Ultrasonography, computed tomography or endoscopy may assist
the diagnostic process.
Treatment
The condition is usually treated with anthelmintics. The BNF states that
levamisole (available from IDIS Ltd – see Appendix 2) is very effective against
A. lumbricoides and is considered to be the drug of choice. Well tolerated,
100 | Zoonoses
it can cause nausea and vomiting in approximately 1% of patients. A single
dose of 120–150 mg in adults is normally sufficient to resolve the condition.
Mebendazole may be used at a dose of 100 mg twice daily for 3 days.
Piperazine has also been used but is considered to be less suitable due to the
incidence of side effects. When used it should be given as a single dose of
4–4.5 g for adults as piperazine hydrate. Albendazole, metronidazole and
pyrantel have all been used for human treatment in the USA.
Physical removal may be possible during endoscopic investigations.
Larvae that migrate to sites other than the lungs during the invasive phase
of development may require surgical removal. The use of anthelmintics may
be associated with this migration, because it can cause larvae to flee the gut
into other body organs in a random manner, leading to further complications. Early treatment of Ascaris-related pancreatitis usually results in complete
recovery, although untreated cases can lead to a fatality rate of 3% in endemic
areas.
Prevention
Vegetables and salads should be thoroughly washed before consumption to
reduce or remove any contamination. Pig manure should not be used as a
fertiliser or slurry on field, where produce is being actively grown.
Pasteurella
Shipping fever, fowl cholera
Pasteurella spp. form a group of well-recognised pathogens that are responsible for species-specific diseases. There are currently moves to rename at
least some of this group of bacteria as Mannheimia spp. One member of the
group, P. multocida, has particular zoonotic potential.
Disease in animals
The organism can cause pneumonia with concurrent pleurisy in pigs, often
in a mixed infection with other Pasteurella spp. or mycobacteria. Infected
pigs are feverish and display pulmonary insufficiency, with exaggerated
gasping and panting. There will often be production of blood-flecked foam
from the lungs, which can be seen in the mouth. Untreated cases can be
fatal. A septicaemic form of the disease has also been seen in pigs and
other mammals. Transmission between animals is usually by aerosol
transfer.
In poultry the course of infection is very different. Turkeys, hens and other
birds exhibit overwhelming diarrhoea, which is rapidly fatal in unvaccinated
birds. This is normally due to P. multocida, although other Pasteurella spp.
may be present and synergistic in the disease.
Zoonoses of agricultural animals | 101
Transmission
In addition to pigs and birds, many dogs, cats and horses carry P. multocida
as part of their oral flora, and can transmit it to other animals and humans
via aerosols or saliva. These animals are often asymptomatic. Direct
inoculation can occur through animal-inflicted bites or wounds. Ingestion
of contaminated food or water can also lead to development of the
disease.45
Disease in humans
Following transmission to humans there is usually localised inflammation
around the infected bite or wound, followed by abscess formation and
septicaemia. Pneumonia and meningitis may also occur, depending on the
route of infection.
Infection by this organism is a serious risk, particularly to children, who
tend to receive more bites from companion animals in rough play, to elderly
people and immunocompromised individuals, in whom infection can be
rapidly progressive and fatal. Septicaemic forms have been seen in patients
with HIV/AIDS or liver cirrhosis, or who are on chemotherapy regimens.46
The disease is notifiable, and the HPA receives on average notification of
approximately 200 cases annually, usually following bite injuries.
Treatment
Antibiotic therapy at standard therapeutic doses is normally sufficient to
cure the condition, although in more serious cases supportive treatment may
also be required. The drugs of choice are the tetracyclines, penicillins or
cephalosporins; length of course and dosages are linked to age, weight, drug
allergies and clinical response in the normal manner.
Prevention
Wounds, especially those inflicted by animals, must be thoroughly and
rapidly cleansed and disinfected. Companion animals should not be allowed
to lick patients’ faces or wounds. Encouraging children to wash their hands
and, if necessary, faces after playing with or touching animals is an important preventive measure. Vaccination is available and widely used in pigs and
poultry to lower the incidence of the disease. Those involved in equestrian
pursuits should recognise that bites from horses pose a particular threat from
this organism.
Case study
In August 2006, a farmer’s son in Suffolk died after catching Pasteurella
multocida from dead rabbits. The 29 year old is believed to have been infected
through a raw blister on his hand which became contaminated by infected
body fluids from the rabbits. He contracted the bacterium on 1 August and
102 | Zoonoses
died in Ipswich Hospital 4 days later. He initially displayed symptoms of flu,
and then died from overwhelming septicaemia.
Streptococcus suis
Disease in animals
Streptococcus suis is a pathogenic streptococcus endemic in most countries
that have domestic or wild swine. There are at least 35 different serotypes
recorded, and of these the type 2 serotype is classically responsible for severe
disease in swine, and also for the occasional cases seen in other animals
including cattle, sheep, dogs, cats and birds. This serotype is also responsible
for most cases in humans, although recently serotype 14 has been recognised
as having the capability to be a human pathogen. The disease is prevalent in
China, possibly due to the high density of pig farms and the number of
swine processed annually.
Infection is often not apparent, with the pathogen being carried in the
tonsils and nasal cavities; however, in clinical cases it can cause pneumonia,
septicaemia, septic arthritis, endocarditis and meningitis, with behavioural
changes, fever and ultimately paralysis. It may also cause abortion in pregnant
sows. Infections in herds of swine can result in high rates of mortality and are
often the result of poor husbandry or housing conditions.47
Transmission
Transmission to humans follows the handling of infected meat or carcasses,
and it is therefore no surprise that most cases occur in abattoir workers,
meat handlers, farm workers or veterinary surgeons where the disease is an
occupational hazard. The annual case rate in humans is usually in low single
figures, which suggests that the risk is low. In the UK, the disease is notifiable under the Statutory Notifiable Disease 1998 Notification of Infectious
Diseases System (NOIDS) regulations, the Reporting of Injuries, Diseases,
and Dangerous Occurrences Regulations 1995 (RIDDOR 95) and animal
health legislation. It is also a prescribed industrial disease and reportable to
the HSE if acquired occupationally.
Disease in humans
Following infection, usually through cuts or skin abrasions, the pathogen
can cause severe infection in humans, with fever, septicaemia and, very
occasionally, meningitis or endocarditis. Infection can lead to toxic shock
syndrome, which may in turn lead to multiple-organ failure. Residual deafness and balance disturbances have been reported in patients after the infection has resolved. Asplenic or immunosuppressed patients are at a greater
risk. S. suis infection is rare among humans in England and Wales: an
average of two human cases are reported each year. In 2005, two cases were
Zoonoses of agricultural animals | 103
reported in England and Wales. There were no cases in Scotland and
Northern Ireland. The last fatal case in the UK occurred in a farm worker
in 1999, due to S. suis type 14. During 2004 a total of 112 isolates were
found in pigs in England and Wales, of which 46% (51) were S. suis type 2.
Diagnosis
Diagnosis is confirmed by culturing the organism or using PCR assay.
Treatment is usually initiated before identification.
Treatment
Treatment is usually oral penicillins or erythromycin with monitoring as to
efficacy, because resistant serotypes have been identified in mainland Europe.
Prevention
Prevention revolves around good hygiene procedures and the use of protective clothing. All wounds should be covered and any occurring during
handling of meat or carcasses should be disinfected thoroughly and dressed
swiftly. An experimental vaccine has been developed for animals but the
clinical efficacy has not yet been fully established.
Case History – S. suis type 2 outbreak in China
In south-west China’s Sichuan Province, 215 people became ill, of whom 39
died between June and mid-August 2005. All the initial victims were from
villages and towns across Yanjiang and Jianyang districts, and were farmers
or butchers or had had contact with sick and dead pigs or sheep before
becoming ill. Some also ate meat originating from the same beasts.48
Later cases were reported with a wider distribution across the region,
including cases in Chengdu, Hong Kong and Guangdong. Media reporting
of the outbreak was allegedly controlled, and the WHO did not gain access
to the area. The WHO noted the ‘disconcertingly high mortality rate’ and
said that it was monitoring the situation closely. Raw pork was impounded
by officials in Nanshan, Shenzhen and Guangdong, and movement of live
pigs was halted. People who had consumed cooked pork were monitored.
Other provinces of China, Macau and Hong Kong halted sales of frozen
pork from Sichuan, Shenzhen and Henan. Vietnam banned imports of all
live pigs and pork products. Taiwan requested residents to refrain from
travelling to Sichuan and its neighbouring areas following the outbreak.
These precautions, which were endorsed by the WHO, prevented further
spread.49 Initially there was also concern that the cases could have resulted
from infection with a Nipah-like virus, or by a porcine influenza; both of
these possibilities were excluded through sample testing.
The disease onset was rapid, associated with high fever, fatigue, nausea
and vomiting, followed by meningitis, the appearance of bruising, toxic
104 | Zoonoses
shock, coma and then death. Initial cases were suspected of having haemorrhagic fever with renal syndrome, but laboratory testing excluded this. The
course of the disease and its high fatality rate have been linked to its short
latent period and ability to cause multiorgan failure. The head of an expert
panel set up by the Chinese Ministry of Health stated that some patients
died within 10 hours of infection, and in one case a man died 2 hours after
slaughtering a sick pig.50
Laboratory tests confirmed infection by S. suis serotype 2 of a particularly
virulent and aggressive strain that produced a potent exotoxin. The
pathogen was also isolated from pigs in the region. An emergency team
from Beijing was deployed to Sichuan to assist in treating patients.
A complicating factor in this particular outbreak may also have been the
presence of a tranche of population in rural areas in China who have been
infected with HIV due to trading in human blood. Any aggressive toxin or
infective agent could rapidly kill individuals with this underlying condition.
There was no reporting of person-to-person spread.
Trichinosis or trichinellosis
This condition is caused by a tissue nematode of the genus Trichinella. In
the past most cases were associated with T. spiralis, but recently there have
been cases of other Trichinella spp., such as pseudospiralis, britovi or
nativa, causing human disease.51
The parasite is normally associated with pigs (T. spiralis, T. pseudospiralis) and dogs (T. nativa). Rats, cats and certain wild carnivores or omnivores are also capable of acting as zoonotic reservoirs. It is an affliction that
is worldwide in its distribution, but is luckily rare in the UK and the USA,
often being associated with imported meat, or affecting returning travellers.
The FSA carried out a survey on foxes in the UK for the presence of
Trichinella spp. between September 2004 and March 2005. All tests were
negative; however, since then, T. spiralis has been detected in a fox in
Northern Ireland.52 All carcasses of pigs and horses slaughtered in the UK
are routinely tested for Trichinella spp. and no positive results have been
found.
Disease in animals
Pigs fed on offal or swill containing meat (especially pork) that has not been
sufficiently heat treated are at the greatest risk of contracting the disease,
although there have been cases recorded after pigs have eaten the corpses of
rats. The number of human cases seen in western countries has been
dramatically reduced by changes in feeding practice for pigs and by meat
inspection. A group of cases of T. pseudospiralis in 1999 was related to the
ingestion of wild boar meat in the Camargue area of France,53 and a further
Zoonoses of agricultural animals | 105
group outbreak was seen in October 2003, in southern France, related to
the consumption of frozen wild boar meat, although the causative organism
was characterised as T. britovi, which is not normally associated with
swine.54 Some of the largest outbreaks have been seen in Thai migrant
workers in Israel who ate uninspected meat from wild boar killed in the
Upper Galilee valley. In a large outbreak in 2005, 18 of 47 workers who had
consumed boar meat presented with symptoms and needed treatment.55 The
organism was characterised as T. spiralis. Turkey holds the record for the
largest outbreak yet. In Izmir between January and March 2004, beef meatballs adulterated with pork infected with T. britovi were sold; 1089 patients
presented to local medical services with symptoms, of whom 418 were
diagnosed with acute trichinellosis.56 In France there have also been sporadic
human cases linked to the consumption of infected horse meat.57
Encysted larval stages are ingested in animal tissue and then hatch in the
gut of the host; these then develop into adults in the surface layers of the
intestine. Eggs are produced by the female worms, and these hatch to
produce larvae. The larvae pass through the intestinal wall and penetrate
into the associated lymphatic or venous blood vessels. They can then be
distributed around the rest of the host’s body and will normally encyst in
muscle tissue as a result of the host’s immune response. The cysts may
become calcified over time and can be detected in the muscle. The fibres of
the muscle may be torn or damaged by the invasion of the parasite. The
affected animal normally displays no clinical signs of infection. Infection
with T. pseudospiralis does not evoke the same immune response and the
cyst wall is normally not present.
Transmission
As with other mammals, infection in humans follows the ingestion of
infected animal tissue.
Disease in humans
The severity of symptoms displayed is proportional to the number of viable
encysted larvae ingested. The mildest cases are usually subclinical, with
perhaps a small amount of muscle soreness being present. In heavy infestations there may be an abrupt onset of muscle pain, fever and swelling of the
eyelids, followed by haemorrhages in the retina, conjunctiva and mouth with
associated pain. An aversion to bright light (photophobia) may also occur.
The most commonly seen sites for larvae to encyst are the diaphragm, ribs,
biceps, larynx, tongue and jaw, or neck muscles. This may lead to difficulties
in chewing and swallowing.
As the infection progresses, patients may display a profound thirst, with
profuse sweating. There may be gastrointestinal disturbance with diarrhoea, stomach cramps and nausea. In 10–20% of patients showing severe
106 | Zoonoses
2
5
3
4
Ingestion of
undercooked meat
(esp. pork)
Ingestion of
meat scraps
or animals
i
1
d
1
Pigs
2
5
d
i
Encysted larva in
striated muscle
3
4
1
Carnivorism
i
Carnivorism
Larva released in
small intestine
2
2
5
3
4
d
Rodents
Encysted larva in
striated muscle
i
d
3
5
Circulation
i
⫽ Infective stage
d
⫽ Diagnostic stage
4
Adults in
small intestine
Larva deposited
in mucosa
Figure 3.2 Trichinella life cycle.
symptoms there may be progression to cardiac, renal or CNS involvement.
Fatalities due to myocardial failure have been recorded. Provided that
patients do not succumb to the condition, it is normal for a complete
recovery to be made over a period of months, although there may be
residual damage with sequelae.
Between 1975 and 2005, 39 laboratory-confirmed cases of human
trichinellosis occurred in the UK. All cases were believed to have contracted
the disease abroad or from consumption of infected meat imported into the
UK. The last recorded outbreak in UK was eight cases, reported in 2000.
This also followed ingestion of infected meat or meat products imported
into the UK. There were no human cases reported in England and Wales,
Northern Ireland and Scotland in 2005.
Diagnosis
Diagnosis is made using serological testing or muscle biopsy. ELISA and
PCR methods can be used successfully.
Zoonoses of agricultural animals | 107
Treatment
Most cases resolve spontaneously, so purely symptomatic treatment and
support are necessary. The BNF makes no recommendations, and specialist
advice would be necessary in treating clinical cases of the disease. In the USA,
tiabendazole anthelmintics such as mebendazole, tiabendazole or albendazole have been used to treat the condition. There is evidence, however, that
once an infection is established these drugs only eliminate the adults and
larvae in the gut, and prevent further egg and larval production, leaving any
migrating or tissue-dwelling larvae intact.
Corticosteroids have been used to control the systemic inflammation
caused by migrating larvae. The patients in the 1993 French case cluster of
T. pseudospiralis were treated with albendazole at a rate of 800 mg/day for
10 days combined with prednisolone at a dosage of 30 mg/kg per day for
the first 3 days. The outbreak among Thai migrant workers in Israel was
treated with 5 mg/kg of mebendazole twice a day for 5 days.
Prevention
Ensuring that all swill or offal fed to pigs has been thoroughly heated at
greater than 77°C prevents infection by ingestion of any infected animal
tissue. Rats should be controlled in pig units and general hygiene measures,
including the isolation and removal of sick individuals, should be enforced.
There may be an issue relating to organic methods of pig rearing, and the
possibility of infection being acquired from wild sources. This is also true of
herds of domesticated or semi-domesticated boar, now extensively bred for
meat in outdoor conditions. As T. pseudospiralis has now been identified as
a possible human pathogen, there are some concerns that current meat
inspection methods, which are geared to the detection of encysted forms,
may not be sufficient, because this species does not evoke cyst formation
response from the afflicted host. If more cases arise, there may be a need for
alternative methods of detection.
Meat should be carefully inspected, and pork should be thoroughly
cooked so as to reach more than 77°C in the centre. Suspect meat can also
be rendered safe by prolonged freezing for more than 3 weeks.
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4
Food-borne zoonoses
Food-borne zoonoses are defined as ‘those diseases contracted from eating
foods of animal origin’. This is a broad definition and covers a wide spectrum
of pathogens, although the most important on a day-to-day basis are mainly
bacteria.
The importance to our society of food-borne zoonoses must not be underestimated. In 2000, the Health Protection Agency (HPA) in the UK estimated
that there were 1.4 million cases of food poisoning, not all of which had a
zoonotic source, which led to approximately 21 000 hospital admissions and
480 deaths. It is considered by some healthcare organisations, that due to the
likelihood of under-reporting the actual case figures are much higher.
Our domestic system of agricultural production is regulated to reduce
transmission of disease into the food chain, and considerable sums of money
are expended annually to make our food safe. Retailers have a statutory
responsibility to handle food correctly and inspections should be carried out
regularly by local and national enforcement bodies, to ensure compliance
with the provisions of a wide range of regulations.
In the event of a profound failure in the system, by either an unforeseen
emerging infection or a system or regulatory failure, the effects can be
profound, e.g. bovine spongiform encephalopathy (BSE) or mass outbreaks
of Escherichia coli. It can be very difficult after such occurrences to deal
with ensuing public fear or panic, whether or not justifiable. The media
have often been vilified, with some justification, for escalating some dramas
into crises.
That said, food safety, the protection of the public, and addressing the
concerns of consumers and their organisations are of paramount importance. The prevention of unnecessary disease, whether mildly inconvenient
or fatal, has to be the concern of all individuals and organisations involved
in food supply and public health and safety. Within the realm of healthcare
professionals, those patients seen with infections acquired from food may
Food-borne zoonoses | 111
have already been failed by some of the safety measures normally in place,
although inability to store, handle or cook food correctly can also be a
potential source of such infections.
Typical transmission pathway
An animal suffering from a disease, which may not be apparent, creates a
product of either milk or body tissue in which the causative organism is
entrained. This product is either further processed or directly passed to a final
consumer who then either with or without cooking eats the contaminated
item, and in susceptible cases develops the disease after a variable incubation
period.
Food-borne zoonoses associated with fish
The most significant disease sometimes associated with fish is cholera,
although as humans are one of the main reservoirs for the disease there is a
continuing debate as to its status as a zoonosis.
Of more potential significance is a complex of diseases associated with
certain types of planktonic algae called dinoflagellates. These produce toxins
that accumulate in shellfish and certain other fish at a primary level, then
moving up the food chain into carnivorous and predatory species of fish, and
into the human food chain. Sporadic outbreaks may relate to weather, tidal,
current and ambient temperature/sunlight, often with associated algal
blooms, providing some predictive data for prevention schemes.
Ciguatera
This disease is associated with the consumption of farmed salmon, and also
carnivorous species such as shark, barracuda, grouper and snapper, especially those found in tropical and subtropical regions between 35°N and
35°S. This disease now occurs worldwide due to transportation of fish to
geographically distant regions for the gourmet restaurant trade.1
The toxin occurs in a dinoflagellate – Gambierdiscus toxicus – and then
spreads into a variety of fish species. Transmission to humans occurs when
contaminated fish is consumed, especially when it has been undercooked.
Symptoms start with perioral numbness and tingling, which may become
generalised. Tooth pain, nausea, vomiting and diarrhoea may follow as the
condition progresses. Neurological symptoms include paraesthesia, arthralgia,
myalgia, headache and acute temperature sensitivity. Vertigo and muscular
weakness may also be seen. Cardiovascular involvement with bradycardia,
tachycardia and hypotension can occur.
112 | Zoonoses
The condition is usually self-limiting, and symptoms regress within
several hours or days. In isolated cases neurological symptoms can persist,
although normally there is no permanent damage.
In the UK cases are normally seen on a sporadic basis, with farmed
salmon or imported exotic fish being the source. In the USA, there were two
recorded cases in Texas in 1998, and South Carolina in 2004; however, it is
known to be massively unreported, with many fishermen aware of the
symptoms, and prepared to accept them as part of their diet and way of life.
Contaminated fish are particularly prevalent in the Caribbean and
Florida (on both coasts and in the Gulf of Mexico). Other areas where the
problem occurs include Hawaii, Puerto Rico, Guam, the US Virgin Islands,
Tahiti and the South Pacific generally.
There have been recent reports of cases in the Canary Islands, indicating
that fish from West African waters may be contaminated.
Shellfish poisoning
In cases of poisoning following ingestion of shellfish a complex of afflictions is seen depending on the variety of toxins ingested. These vary
depending on the different groups of dinoflagellates responsible. In general,
saxitoxin derivatives cause paralytic shellfish poisoning (PSP), okadaic acid
and yessotoxin cause diarrhoeic shellfish poisoning (DSP), brevetoxins cause
neurotoxic shellfish poisoning (NSP) and domoic acid causes amnesic
shellfish poisoning (ASP).2
In serious cases, if the individuals were to get all of the poisoning symptoms
together, they would not be able to speak, they would be numb all over, the
bottom would be dropping out of their world and they would not know why.
The last publicised case of DSP in the UK occurred in June 1997.
Forty-nine people ate mussels or mussel-containing soups at two London
restaurants. These mussels originated in UK waters. It was the first incident
in 30 years attributable to domestic shellfish. DSP toxins were first detected
in shellfish from the Thames estuary in 1991; no previous outbreak had
occurred in the UK. No cases have ever been seen in the USA; however, the
causative diatom is known to be prevalent in US coastal waters.
ASP can be a life-threatening syndrome, causing both gastrointestinal
and neurological symptoms. Nausea, diarrhoea and cramps occur within
24 hours of the consumption of contaminated shellfish, with neurological
symptoms appearing later (up to 48 hours). In 1987, four people died after
consuming contaminated mussels from Prince Edward Island, Canada.
Canadian waters are now monitored to prevent a reoccurrence. No cases of
ASP have been reported in the UK. Where the disease does occur it is
believed to be worst in elderly patients, and fatalities have occurred.
Food-borne zoonoses | 113
The last case report of PSP in the UK was in 1968. This condition is
particularly dramatic as the toxins can cause respiratory paralysis within
24 hours and, unless supportive therapy is given, death follows rapidly.
The Department for Environment, Food and Rural Affairs (DEFRA) has
a system of location warnings geared towards preventing dinoflagellatecontaminated crustacea and fish being harvested from affected sea and tidal
areas. The warnings are generated by analysis of shellfish harvested from
monitoring sites at a number of indicator sites around estuaries and coastal
waters. Food protection legislation invoking emergency prohibitions are used
to ban fishing in affected waters. Similar measures are in place around the USA,
with the Food and Drug Administration (FDA), US Department of Agriculture
(USDA) and local state authorities carrying out monitoring and enforcement.
Elsewhere in the world, especially in tropical waters where conditions are
suitable for the causative dinoflagellates to multiply rapidly, these diseases
are significant. Most international fish-trading nations have established
similar monitoring and enforcement systems.
Food-borne zoonoses associated with meat
Most of the UK and US population still eat meat, although vegetarianism is
on the increase. Meat may be consumed as discrete cuts, comminuted meat
products, i.e. beefburgers or sausages, processed items such as spam or
corned beef, and cured, smoked or salted products. The exact source of any
outbreak can be linked to dietary preference which is usually set by cultural
factors and prevailing religious belief. This can protect or expose populations to a variable spectrum of pathogens. The bacteria within this next
section, however, form a universal threat to human health. The following
section deals with probably the most serious pathogen of this group.
Escherichia coli
E. coli forms a part of most mammalian bacterial gut flora. It has a vast array
of serotypes: some are benign, whereas others are dramatically pathogenic.
This can vary from species to species; a benign form in one animal may be a
deadly organism in another.3
The particular serotype of major concern is O157:H7, which was first
identified as a major cause of serious outbreaks of food poisoning in the
USA and Canada during the 1980s. This serotype is variously known as
enterohaemorrhagic E. coli (EHEC), shiga toxin-producing E. coli (STEC)
or verocytotoxin-producing E. coli (VTEC) O157. There are other serotypes
that can produce similar clinical disease; however, this is both the most
commonly seen in clinical cases and also the most severe. The Health
Protection Agency (HPA) record approximately 1200 cases of E. coli O157
114 | Zoonoses
infection annually, of which approximately 50% are food borne. In 2006,
minor UK outbreaks were linked to restaurants, schools, nursing homes, an
open farm and a paddling pool. In the USA, there are an estimated 70 000
human cases of E. coli O157 per annum.4
Transmission
Disease in humans follows the consumption of food, usually meat or meat
products, milk or water, that has become contaminated with faecal material.
Direct contact with infected animal faeces has also been shown to be an efficient means of transmission. The organism is particularly associated with
ruminant animals, especially cattle, sheep and goats, which remain healthy
and asymptomatic, despite carrying the organism in significant numbers. It
is also carried by horses, pigs, dogs, geese and wild rabbits, with viable
organisms being shed in the faeces.
Contamination of carcasses with faeces at slaughter has also been
demonstrated. Meat from such carcasses poses a considerable risk if jointed,
sold and subsequently consumed undercooked. To prevent or reduce infection from this source, recommendations have been made that vets at abattoirs assess the faecal load of the animal’s body surface before slaughter. Any
animals likely to produce carcasses with high levels of possible contamination should be rejected, further cleaned and resubmitted, or processed with
particular attention to hygiene procedures and additional precautions, as
deemed necessary. Contamination may also occur following contact between
cooked products and raw meat, or the instruments or surfaces used while
processing raw meat. The inoculum necessary to initiate progression to
clinical disease has been estimated at fewer then 100 viable organisms.
Outbreaks may be sporadic, and may affect only single individuals; these
are often associated with animal faecal contamination of water or milk.
Collective outbreaks with large numbers of cases usually stem from breakdowns in controls within catering establishments. During a widespread
outbreak, there may be secondary spread from patient to carer, or other
person-to-person transmission.
Disease in humans
Once in the gastrointestinal tract the organism adheres to the gut wall where
it proliferates and produces a toxin that is capable of damaging the gut
lining to a variable degree. Only 30% of those who become infected show
symptoms. The effect of the toxin may cause solely fluid loss and diarrhoea;
in more severe cases there is also haemorrhage into the gut lumen and this
is known as haemorrhagic colitis (HC). The condition can progress to
haemolytic–uraemic syndrome (HUS), especially in children, with kidney
damage that may progress to full renal failure with associated haemolytic
anaemia and occasionally death. HUS occurs in roughly 5–10% of clinical
Food-borne zoonoses | 115
cases. The organism is now recognised as the main cause of HUS in children.
Recently there has been some evidence5 that the development of HUS may
be linked to the use of antibiotics in patients, with the drugs rapidly killing
the bacteria, and producing massive toxin release. In adults (especially
elderly people), but also occasionally infants, the course may be slightly
different. Neurological disturbances may develop in addition to the HUS
symptoms; this complex is known as thrombocytopenic purpura, and
fatalities follow its development.5
Treatment
Treatment is supportive, because there is no specific treatment that shortens
or ameliorates the course of the disease. Rehydration is essential; dialysis
may be necessary, especially where there is significant kidney involvement.
If kidney failure occurs, short-term dialysis followed by later kidney
transplantation is the only option. As previously mentioned, the use of
antibiotics is considered to be inappropriate.
Incidence
The incidence of infection is currently decreasing, with 1002 cases in the UK
in 2006, compared with 1429 in 1999. The major risk groups affected are
infants, children, and elderly or immunocompromised individuals. There
appears to be a seasonal pattern of infection – statistics show an increase in
reporting during August and September. Within the UK there is also a
characteristic geographical spread, with more cases being reported in
Scotland and northern England.
Analysis of an outbreak
The largest outbreak of E. coli O157 in the UK occurred in November 1996,
in Wishaw, Scotland (Table 4.1). The source of the outbreak was crosscontamination in the premises of a butcher, J. Barr, who also ran a bakery
and catering business. There was an extensive supply and distribution
network from his premises, with meat and meat products being supplied to
85 outlets in central Scotland. The outbreak was finally declared over in
January 1997, but not before 969 associated incidents of food poisoning
were reported, with 496 viewed as suspected cases, 272 confirmed, 60
probably and 164 possibly linked to consumption of contaminated food
from the single source.6
A total of 127 people were admitted to hospital: 13 required dialysis and
18 died. Three further patients died later from complications associated with
infection, giving a final figure of 21 fatalities for the outbreak. Of the dead,
eight had attended a church luncheon, and six were residents of a local
nursing home, to which cooked meats had been supplied. The 18 people who
died in the initial phase of the outbreak were all over 69 years of age.
116 | Zoonoses
Table 4.1 Wishaw outbreak timeline
17 November 1996
A pensioners’ lunch is held at Wishaw Parish Church; the buffet is provided by
J. Barr and Son, Butchers of Wishaw (initial infection)
22 November 1996
The possibility of outbreak of Escherichia coli O157 is identified after a history is
taken from 9 of 15 confirmed or suspected cases. Eight of the nine consumed food
directly or indirectly from J. Barr of Wishaw
23 November 1996
A birthday party is held at the Cascade Public House in Wishaw, with J. Barr as
caterer. Outbreak control team established
24 November 1996
Barr’s product chain is properly identified and its full extent mapped. There was an
extensive supply and distribution network with meat and meat products being
supplied to 85 outlets in central Scotland
26 November 1996
The first food hazard warning is issued
27 November 1996
The Wishaw premises of J. Barr are closed down
15 December 1996
The last case of infection linked to products from this source is reported
20 January 1997
The outbreak is declared over
Mr Barr was tried for recklessly supplying contaminated meat but
acquitted and has since been privately sued for damages by about 120
people.
The significance of this outbreak cannot be underestimated. At the time
this was the second-highest number of deaths associated with an E. coli O157
outbreak anywhere in the world. It was only surpassed by an outbreak in
Japan in 1996 where nearly 10 000 people were infected, with an associated
mortality in excess of 30 individuals.
Outbreak procedures
In any outbreak, it can be difficult to identify the focus. In the Wishaw case,
as in many epidemics, it was difficult to identify the problem until people
became ill. History taking becomes very important, because it is often the
only key to identifying the source of the infection.
Once there is a presumption that an outbreak is occurring, an outbreak
control team must be formed that meets daily during the outbreak until it is
controlled. This allows successful coordination of health service matters
with local and regional government environmental health agencies. It also
forms a forum for epidemiology and other specialist support to be discussed
and implemented in forming policy and strategy to control the outbreak.
In this outbreak it was of great significance that J. Barr was not solely a
butcher. His premises also had a bakery and purveyed raw meat, cooked
meat products and bakery items, which were sold from the premises, and
also distributed as wholesale goods over a wide geographical area.
Food-borne zoonoses | 117
The records of the transactions involving sale and supply of products
from the Wishaw premises were complex, and sometimes vague. It took a
considerable amount of time and effort for health officials to ascertain their
full extent. This allowed contaminated products to remain on sale for longer
than was desirable. J. Barr and Son had more than 400 employees, including
part-time workers, who lived in the local area, all of whom had to be tested,
taking time and effort away from other areas.
For all of these reasons, this outbreak was serious and extensive. The
lessons learned from this outbreak have informed later legislation and
practice, with enhanced requirements for record-keeping and food hygiene.
Other outbreaks
In the USA, there have been several recent E. coli O157 outbreaks. Two of
these were related to contaminated vegetable matter (spinach and lettuce),
and two to meat products (beef patties and pepperoni). The lettuce outbreak
in October 2006 was the worst, with 199 cases across 26 states; 102
patients were hospitalised, with 31 developing HUS and 3 deaths – 2 elderly
women and 1 baby. The beef pattie-related outbreak between July and
September 2007 resulted in 111 cases across 8 states, of which 21 were
hospitalised; 2 developed HUS, but there were no deaths; 21.7 million
pounds (approximately 10 million kg/10 000 tonnes) of frozen beef patties
had to be recalled and destroyed.
In the UK, since the Wishaw outbreak, there have been a number of
small outbreaks, usually associated with care settings such as schools,
nursing homes and pre-school nurseries. Other outbreaks are associated
with failures of food or environmental hygiene mechanisms, such as faulty
pasteurisation, contact with raw sewage or consumption of contaminated
water.
The Pennington report
Following the outbreak at Wishaw, Professor Sir Hugh Pennington was
commissioned to investigate and make recommendations for future control
of the disease. The group that he chaired produced a report that made 32
recommendations. The main points were that there should be enforced
separation of cooked and raw meat at catering premises, a programme of
lessons on food handling for children and an E. coli awareness programme
for farm workers. In addition it was recommended that all butchers should
be licensed, with one of the conditions of gaining and maintaining
accreditation being mandatory staff training.6
The report’s recommendations led to a media furore and, together with
fears over Listeria and Salmonella and the onset of BSE/vCJD, formed part
of the demand for the establishment of a Food Standards Agency (FSA) in
the UK.7
118 | Zoonoses
Listeriosis
Listeriosis is an often serious infection, caused by eating food contaminated
with the bacterium Listeria monocytogenes. In the UK during 2006 there
were 210 clinically proven cases reported to the HPA; this was lower than
the number of cases reported in the previous 3 years, which all showed a
marked increase over case levels in the 1990s. In the USA, despite health
warnings from various responsible government agencies, an estimated
average of 2500 people become seriously ill with this disease annually, of
whom in excess of 20% die. Refrigerated products can spread the disease,
because L. monocytogenes is capable of slow growth at low temperatures.
Transmission
L. monocytogenes is found in soil and water. Vegetables can become
contaminated from the soil or from manure used as fertiliser. Animals can
carry the bacterium without appearing ill and can contaminate foods of
animal origin, such as meats and dairy products. The bacterium has been
found in a variety of raw foods, such as uncooked meats and vegetables, as
well as in processed foods that become contaminated after processing, such
as soft cheeses and cold cuts at the deli counter.
Unpasteurised (raw) milk or milk products made from unpasteurised
milk may contain the bacterium. Humans and animals may also contract the
disease by direct contact with infected faecal matter. A cutaneous form of
the disease can occur from such contact. Transfer of the pathogen from
mother to fetus or neonate has been well documented, as has infection
following inhalation of infected aerosols, again in both humans and other
animals. Venereal spread has been documented in cattle. It is estimated that
5% of the human population carries the bacterium asymptomatically in the
gut.8
Risk groups
The main significant risk group is pregnant women. The disease can affect
both mother and baby, and fetal or neonate death may follow maternal
consumption of contaminated products. In an outbreak in north Carolina,
USA, between late 2000 and early 2001, following the ingestion of infected
Mexican-style soft cheese, of 11 women presenting with clinical signs, 10
were pregnant. As a result there were five stillbirths, three premature births
and two infected neonates required treatment.9
Immunocompromised patients, from whatever cause, are also likely to
suffer serious illness, with fatalities in serious cases. This is also true for
elderly people or infirm patients. In otherwise healthy individuals, infection
is possible; however, they are less prone to display serious or fatal sequelae.
A study in the USA has also established that patients who use quantities of
Food-borne zoonoses | 119
antacids or who take cimetidine may be at increased risk of contracting
disease, due to the inhibition of gastric acid. It is not known whether this
also applies to patients receiving proton pump inhibitors.
Disease in humans
In most cases, infection occurs following ingestion of contaminated foodstuffs. There is a pre-patent period of up to 10 weeks after infection. Clinical
onset usually follows fever, headache, nausea and vomiting, and symptoms
similar to a severe chill. Abdominal cramps, stiffness of the neck and photophobia may also be present. The condition may progress with organ involvement, including endocarditis, internal lesions, metritis, septicaemia and
meningitis. As central nervous system involvement becomes more widespread,
there may be convulsions, confusion and vertigo.10
Focal necrosis in the placenta may occur with spontaneous abortion,
premature birth or infective transfer to the baby at birth. Babies may display
a septicaemic infection within the first week after birth, or a septicaemic
form with associated pneumonia within the first month of life.
A fatality rate of higher than 20% of clinical cases has been seen when
treatment is not made, or is not started quickly.
Treatment
There is no vaccine available to prevent listeriosis in humans or animals.
Treatment options are limited to the use of supportive measures and
antibiotics.
Oral penicillins, especially amoxicillin at high doses by mouth, i.e.
500 mg three times daily for 5–7 days, have been shown to be effective.
Erythromycin can be substituted in patients who are allergic to penicillin, at
a dose of 500 mg four times daily for 1 week. In serious cases, penicillin or
amoxicillin has been used successfully either intravenously or by mouth at
high doses. Ampicillin plus gentamicin, or trimethoprim/sulfamethoxazole
has also been used; however, this is normally reserved for secondary care
usage under the control of expert opinion and monitoring. Even with
prompt treatment some infections result in death. Use of recombinant DNA
tests has undergone trials to speed diagnosis and treatment.
Prevention
Listeria spp. are killed by pasteurisation, and heating procedures used to
prepare ready-to-eat processed meats should be sufficient to kill the
bacterium; however, unless good manufacturing practices are followed,
contamination can occur after processing.
The general guidelines recommended for the prevention of listeriosis are
similar to those used to help prevent other food-borne illnesses, such as
salmonellosis. Food from animal sources should be thoroughly cooked,
120 | Zoonoses
especially beef, pork and poultry. Raw vegetables must be washed
thoroughly in clean water before eating. Uncooked meats, vegetables and
cooked or ready-to-eat foods should be stored separately or segregated.
Unpasteurised milk or milk products should be avoided. General food
hygiene precautions apply – knives, cutting boards and hands should be
washed after each occasion of handling uncooked foods.
Recommendations for people at high risk, such as pregnant women
and people with weakened immune systems are in addition to the
recommendations listed above. In 1988 the following advice was issued by
the Chief Medical Officer (CMO) in the UK:
The CMO has established that the incidence of listeriosis in pregnancy stands at 1 in 30 000 live and stillbirths. Pregnant women
should avoid certain ripened soft cheese, feta, Brie, Camembert, blueveined cheeses such as Danish Blue, Stilton and Gorgonzola, and
Mexican-style cheeses. Additionally they should not consume meatbased pâté. Cheddar and Cheshire-type cheeses, or soft fresh cheeses
such as cottage cheese or fromage frais, do not pose a threat as they
rarely contain Listeria or, if contaminated, carry insufficient organisms to cause infection. The same is true of processed cheeses, which
have often undergone pasteurisation. Pregnant women should reheat
chilled meals and ready-to-eat poultry thoroughly until piping hot.
They should not assist with lambing, milk recently lambed ewes,
touch the afterbirth or come into contact with newborn lambs. These
recommendations also apply to immunodeficient individuals. Healthy
children more than 4 weeks old are not at risk.
This advice is still current and valid.
In the USA similar advice has been issued by the Centers for Disease
Control and Prevention (CDC), with general recommendations that reduce
the risk not only from Listeria, but also from other food-borne pathogens:
• Thoroughly cook raw food from animal sources, such as beef, pork
and poultry.
• Wash raw vegetables thoroughly before eating.
• Keep uncooked meats separate from vegetables and from cooked foods
and ready-to-eat foods.
• Avoid unpasteurised (raw) milk or foods made from unpasteurised
milk.
• Wash hands, knives and cutting boards after handling uncooked foods.
• Consume perishable and ready-to-eat foods as soon as possible.
The CDC makes further recommendations for people at high risk, such
as pregnant women and those with weakened immune systems, in addition
to the general recommendations listed above:
Food-borne zoonoses | 121
• Do not eat hot dogs, luncheon meats or deli meats, unless they are
reheated until steaming hot.
• Avoid getting fluid from hot dog packages on other foods, utensils and
food preparation surfaces, and wash hands after handling hot dogs,
luncheon meats and deli meats.
• Do not eat soft cheeses such as feta, Brie and Camembert, blue-veined
cheeses, or Mexican-style cheeses such as queso blanco, queso fresco
and Panela, unless they have labels that clearly state that they are made
from pasteurised milk.
• Do not eat refrigerated pâtés or meat spreads. Canned or shelf-stable
pâtés and meat spreads may be eaten.
• Do not eat refrigerated smoked seafood, unless it is contained in a
cooked dish, such as a casserole. Refrigerated smoked seafood, such as
salmon, trout, whitefish, cod, tuna or mackerel is most often labelled
as ‘nova-style’, ‘lox’, ‘kippered’, ‘smoked’ or ‘jerky’. The fish is found
in the refrigerator section or sold at deli counters of grocery stores and
delicatessens. Canned or shelf-stable smoked seafood may be eaten.
Listeria outbreaks
Europe
During January 2000, after two deaths in France, Coudray, producer of a
variety of meat products, was forced to disinfect its factory completely. In
1992 the same factory was the source of a listeria outbreak in which, of 279
cases, 63 people died and 20 women aborted their babies.11
In February 2000, the deaths of a 75-year-old man and a baby less than
a month old followed consumption of pork-based coarse pâté by the
pensioner and the mother of the baby. These deaths were followed by seven
more, including two other infants.
Coudray exported widely within and outside Europe, so an extensive
product recall and publicity campaign was mounted to stimulate consumer
awareness. In France, health authorities were unable to identify the source
of infection that left another 23 people ill across 19 regions of the country.
In August 2000, analysis of ice cream produced at a North Wales creamery
was found to contain Listeria. Production was halted, and on investigation
faulty processing was found to be to blame.
A cluster of five cases of listeriosis in pregnant women in Swindon, UK,
was traced back to pre-packed sandwiches supplied at a hospital in Autumn
2003. There were no fatalities.12
The USA
A multi-state outbreak of listeria infection in the north-eastern USA was
linked to pre-cooked turkey meat. Of 50 infected people, most were hospitalised, with 7 deaths, and stillbirth or miscarriage in 3 pregnant women. Six
122 | Zoonoses
of the dead were immunocompromised. A widespread recall was instituted,
with 27 million pounds (12.5 million kg/12 500 tonnes) of product having to
be recalled.
A group of four cases of listeriosis, with two fatalities, in Massachusetts
was traced back to contaminated dairy products supplied from a single
dairy in summer 2007.
Salmonella
Famously, in 1988, in a statement made to the House of Commons, Edwina
Currie (a then junior Health Minister) stated that ‘most egg production in
the UK is contaminated with Salmonella’. The resulting media frenzy and
reaction from the public forced her to resign from her post. An investigation
was launched in response to her statement and, in 1989, a cull policy was
introduced to try to control the incidence of the disease. Two million
chickens were slaughtered – with no detectable effect on disease incidence.
The monitoring and testing for Salmonella spp. and other food-borne
pathogens in the UK were tightened after this debacle.
On the basis of the outbreak data available from the HPA it is believed
that the majority of all Salmonella infections affecting humans in the UK are
derived from food, with 14 000 laboratory-confirmed cases of salmonellosis
in 2006, half the incidence in 1997 (30 000 cases). It is believed that only one
in four cases is confirmed, giving a true figure of 56 000 cases per annum. In
the USA, there are believed to be approximately 1.4 million cases a year, with
15 000 hospital admissions and 400 deaths.13
Salmonella enteritidis is the main culprit in eggs and poultry, with 12 800
of the total cases (84%) in the UK in 2006 being this serotype, of which
almost half were phage type 4 (PT4). In the USA, since the identification of
epidemic S. enteritidis in eggs between 1978 and 1996, the introduction of egg
quality assurance programmes (EQAPs) has led to significant reductions in
infection rates, with current estimates that only 1 in 20 000 eggs is infected
with S. enteritidis.
S. typhimurium is primarily associated with cattle but has also spread to
pigs, sheep and poultry, and represented 12.5% of the total cases in the UK
during 2006. Other Salmonella spp. are also clinically significant, with
certain of the approximately 2300 serotypes so far identified being particularly invasive, specifically S. virchow and S. paratyphi var. Java. Reported
cases of salmonella poisoning show a distinct consistent seasonal pattern,
with a peak of infection observed in late summer and autumn, although
with modern agricultural practice, and food supply patterns, cases may
occur at any time.14
Comminuted meat products and eggs have been identified as a major
source of infection, especially sausages and burgers, although the microbes
Food-borne zoonoses | 123
have also been found in beef, pork, chicken and other meats. Contamination
of other foodstuffs by faecal matter can result in some Salmonella spp. being
isolated from foodstuffs as diverse as cereals, spices, vegetables, peanut
butter and fruit.
Disease in animals
Animals may be asymptomatic carriers of Salmonella spp. They may also
suffer clinical disease with intestinal disturbance, septicaemia and death.
Spread within herds or flocks can be rapid, with disastrous results. Salmonella
spp. are also an issue in companion animals: dogs, cats and particularly
reptiles can act as carriers.
Transmission
Transmission usually follows ingestion of infected food, or direct or indirect
contact with animal faecal material.
Disease in humans
Symptoms include sickness, diarrhoea, abdominal pain and fever. The infection can also not be apparent and present as unexpected overwhelming
septicaemia. Susceptible groups include the usual individuals, with elderly,
very young, infirm and immunocompromised individuals being at most risk.
In the USA, recurrent salmonella septicaemia is used as a marker for
progress from human immunodeficiency virus (HIV)-positive status to
acquired immune deficiency syndrome (AIDS).
The most significant serotype in terms of mortality is S. typhimurium
DT104, which shows a 3% mortality rate. It is especially dangerous in elderly
people. There is also a threat from resistant serotypes, with more than half the
isolates of Salmonella DT104 being multi-drug resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides and tetracyclines. The R-serotype
of this pathogen is, in addition, resistant to trimethoprim and quinolones. In
the USA there has been increasing resistance to fluoroquinolones and
cephalosporins in a number of Salmonella spp.15
Treatment
Treatment is usually symptomatic, using rehydration or antimotility agents
such as loperamide. In severe or invasive cases, ciprofloxacin or trimethoprim
is used at doses related to the age and weight of the patient and the severity
of disease.
Prevention
There is now statutory surveillance for all breeding flocks of poultry, and
voluntary monitoring for all other flocks in the UK. Under the Zoonoses
Order 1989, Salmonella spp. isolated from animals must be reported to the
124 | Zoonoses
Minister responsible for DEFRA. In breeding flocks, under the provisions of
the European Directive 92/117/EEC, any confirmed Salmonella enteritidis
or typhimurium infection results in comprehensive slaughter to protect the
food chain, with two flocks having to be culled in 2007. This ensures that
chickens used for egg production start their working lives free of Salmonella
spp. Industry codes of practice have also been established to complement the
statutory Salmonella control programme. There is a vaccine available that
can be used in laying flocks, and is used by many suppliers to the supermarket trade to ensure clean egg supply. These measures have resulted in a
reduction in the number of human cases associated with poultry and eggs.
In the USA, EQAPs have had a similar impact.
Animal feed and its ingredients are routinely tested for Salmonella spp.
and contaminated batches are rejected. Domestic precautions should be
based on good hygiene practice in the kitchen, and ensuring that food is
adequately cleaned and cooked.
The British Egg Information Service has issued the following guidelines
for consumers relating to the consumption of eggs:
Consumers should avoid eating raw eggs; refrigerate unused or left-over
egg-containing foods; discard cracked or dirty eggs; avoid cross-contamination
of food by washing hands, cutting surfaces and plates after contact with
uncooked eggs; and look for the lion logo and best-before date stamped on
eggs. (The lion logo indicates that the eggs have been produced according to
guidelines laid down by the Egg Marketing Inspectorate, a department of
Defra with inspection and enforcement powers.)
Case histories
UK
Eggs
In 2007 there were two outbreaks of salmonellosis in the UK and Channel
Islands, probably linked to pasteurised egg products imported from France.
The UK outbreak in October 2007 followed a formal dinner with 7 of 59
guests becoming ill, and S. enteritidis was isolated from pasteurised egg yolks
and whites used in preparing the dessert.
Another outbreak, in which 10 of 83 diners became ill in the Channel
Islands after a dinner also in October 2007, was linked to the same products.
These products had been supplied across most of the UK, and there was
a possibly related cluster of cases in the East Midlands. The distributor
recalled the product and the producer was informed and has taken measures
to prevent future contamination.
Lettuce
In 2001 across the UK, and in 2004 solely in Northern Ireland, there were
outbreaks of S. newport related to contaminated lettuces.
Food-borne zoonoses | 125
Chocolate
Cadbury, a major manufacturer of chocolate bars in the UK, had to recall
more than 1 million chocolate bars after Salmonella was detected in some
products between January and March 2006. Forty-two people became ill
after eating the bars, with three requiring hospital treatment. The firm was
fined £1 million.
USA
Outbreaks related to eggs
South Carolina, February–March 2001: 688 of 2317 inmates in 4 prisons in
South Carolina were infected with Salmonella enteritidis by eggs obtained
from a single source. Discontinuing supply resolved the outbreak.15
North Carolina, June–August 2001: 82 people became ill after consuming
eggs from an unidentified source or sources, with the pathogen being identified
as S. enteritidis.
Oregon, September 2003: 18 people were diagnosed with S. typhimurium
infection following consumption of egg salad kits that were prepared using
inadequately cooked processed eggs.
Tennessee outbreak from raw milk, 2002–3
Unpasteurised (raw) milk from a single dairy in Tennessee led to the infection
of 62 people with S. typhimurium. The dairy stopped supplying raw milk
and switched to pasteurising all of its product.
Multistate outbreak related to pet rodents December 2003–4
This was an outbreak of multidrug-resistant S. typhimurium associated with
pet rodents (including rats, hamsters and mice) obtained from pet shops.
Multistate outbreaks related to reptiles
Between 1998 and 2002, there were a number of cases of salmonellosis
linked to a variety of lizards (iguanas, bearded dragons, frogs, toads and
skinks) kept as pets across the USA.16
Thirty cases of S. kingabwa, which rarely causes human disease and is
normally confined to the area of Africa previously known as the Belgian
Congo, were detected between 1995 and 2004 across the USA. All patients
had had contact with lizards or other reptiles.
In 2006–7 a multistate outbreak of S. pomona related to reptiles led to
19 confirmed case and 1 fatality. A year later there was another multistate
outbreak of 103 cases with 56% of patients being below 10 years of age of
S. paratyphi var. Java (a particularly invasive species of Salmonella) related
to small turtles (defined as turtles less than 4 inches in length). Although
sales of small turtles have been prohibited since 1975, they are still available
in some pet shops, flea markets and street stalls. There were no fatalities in
the latter outbreak. It would appear that the turtles had become infected
from a common source, probably at a wholesale market.17
126 | Zoonoses
Outbreaks linked to contaminated foodstuffs
There have been several large outbreaks of Salmonella spp. related to a
variety of contaminated foodstuffs in the USA – fresh fruit salad (especially
cantaloupe and honeydew melons) in 2006 (41 cases across 10 states), raw
tomatoes between 2005 and 2006 (459 people across 21 states), and peanut
butter in 2006–7 (628 people in 47 states). Each of the incidents stemmed
from different routes of contamination, and illustrates the need for control,
quality and tracking systems to be thorough and maintained to prevent
recurrence.
Milk-borne diseases
Some of the zoonotic diseases that may be acquired from drinking infected
milk will already be familiar from other chapters of this book. Brucellosis
was discussed in Chapter 3. There are still occasional cases of infection
caused by Brucella abortus, but B. melitensis has not been responsible for
any cases of disease in the UK since case recording began. Surveillance for
this organism is continually carried out by Defra.
Tuberculosis caused by Mycobacterium bovis needs no introduction.
Human-to-human spread of resistant serotypes of M. tuberculosis is now
more significant than the bovine form acquired from dairy products.
Q fever can also be spread by milk, and is deemed to be a serious
zoonotic infection (see Chapter 3).
The usual suspects
In addition to the previously mentioned organisms, cases of food poisoning
may relate to a selection of the ‘usual suspects’. They are all guilty as
charged, and constitute a threat to consumers of badly or inadequately
prepared food.
Clostridium spp. perfringens and C. botulinum
Clostridium perfringens, the causative anaerobic bacterium of many cases of
gas gangrene, may also cause a food-borne disease. Widespread in the environment, and an inhabitant of the gastrointestinal tracts of humans and
animals, it is often found in foodstuffs as a result of faecal contamination.
As with other forms of clostridial disease, it is the production of
exotoxins by the pathogen that causes the main damage, especially where
the ingested food carries a large inoculum, or heavy toxin load. The usual
pattern of disease is linked to the ingestion of a number of viable C. perfringens organisms that may produce clinical symptoms of abdominal cramps,
diarrhoea and fever. The symptoms begin within 24 hours of ingestion and
Food-borne zoonoses | 127
the clinical course is usually of short duration. Elderly patients and young
children are most affected by this pathogen.
The more serious form, known as enteritis necroticans or pigbel, is
linked to ingestion of a massive inoculum of C. perfringens type C. This
form of the disease can be fatal, and is usually a result of inadequate
cooking or slow cooling of cooked meats or meat products, with inadequate
reheating, allowing the bacteria to multiply and produce quantities of
exotoxin.
The clinical signs are linked to the effect of the exotoxin on the gut wall.
Cell death and invasive necrosis lead to overwhelming septicaemia and
circulating toxin levels that are toxic to major organs, including the heart,
liver and kidneys (compare gas gangrene). Diagnosis is often presumptive,
confirmed by isolation of the organism or the exotoxin from a stool sample.
Treatment is usually solely supportive.
Large outbreaks are usually associated with communal events or places
and mass catering, from either professional or domestic sources, especially
where food prepared in advance is not correctly stored. One of the largest
thoroughly documented outbreaks occurred at a factory in Connecticut, USA
in 1985. An employee banquet prepared for over 1300 people resulted in 600
cases, linked to previously prepared gravy, which had been incorrectly stored
and inadequately reheated.18
Nothing as dramatic has been seen since, although there is a continued
sporadic number of cases in both the UK and the USA every year.
Botulism
Botulism as a complex of disease state arises from contact with C. botulinum
or its associated neurotoxin. As with other species of Clostridia, it is an
anaerobe that forms spores, which can survive desiccation and heat until
conditions alter to those allowing their growth. There are seven types of
botulism toxin associated with the bacteria, designated by the letters A–G.
Only the A, B, E and F toxins are known to cause illness in humans.
Often associated with ducks, geese and some other types of poultry, it
can also be found in cattle and horses, which can act as hosts and amplifiers
for some strains. The organism is found in the environment, and also in the
gastrointestinal tract of infected mammals that may be asymptomatic
carriers and amplifiers, although certain strains of botulism can affect them
also. In the UK, during August 2006, there were concerns that a prolonged
drought and the stagnation of lakes and ponds could encourage C. botulinum
to grow, with water birds becoming infected.
There are no specific risk groups for botulism. It can affect anybody,
anywhere, at any time under the right circumstances. There are several
distinct recognised types of botulism. These are food borne, infant and
128 | Zoonoses
wound associated. Luckily there is a very low incidence of all three forms in
the UK and the USA.19
In the UK, there have only been two cases of infant botulism and four
cases of food-borne botulism in the last decade, with the food-borne cases
being predominantly from home-preserved meat brought in from outside
the UK. There has been a large increase in the number of wound botulism
cases associated with injecting or intravenous drug users (IDUs).
In the USA an average of 110 cases of botulism are reported each year.
Of these, approximately 25% are food borne, 72% are infant botulism and
the rest are wound botulism. Annually there are incidents of food-borne
botulism often caused by eating contaminated home-preserved foods. The
number of cases of food-borne and infant botulism has changed little in
recent years, but, similar to the picture in the UK, wound botulism has
increased because of the use of black-tar heroin, especially in California.
There are two other forms of botulism, but one is extremely rare and the
other has never been detected in practice. Inhalation botulism has occurred
in laboratory workers after inhalation of the toxin, with symptoms similar
to those of the food-borne form. In theory, the toxin could also be water
borne; however, as western water treatment processes inactivate the toxin,
the risk is considered to be negligible.
Food borne
The food-borne disease has to be differentiated from other types of botulism
because it is not caused by an infective form, but solely by ingestion of botulinum toxin, and is normally associated with products such as duck pâté,
sausages and seafood, including smoked fish, that have been inadequately
heat treated, sufficient to kill the organism but not enough to destroy the
neurotoxin which is destroyed at high temperatures. The amount of toxin
necessary to cause clinical signs is measured in nanograms, so, although
foods ingested may contain no active bacteria, the residual toxin content can
be sufficient to produce symptoms.20
The disease usually begins 18–36 hours after the ingestion of the toxin.
Early signs include gait difficulties, dysphagia and impaired vision. Respiratory
distress, muscle weakness, and abdominal distension and constipation may
appear progressively. In severe cases assistance to maintain breathing by
mechanical ventilation is required to prevent death.
Many cases of food-borne botulism are believed to go undiagnosed,
because the symptoms may be transient and clinical signs may be confused
with Guillain–Barré syndrome (see p. 134).
In the USA, between 1990 and 2000, there were 97 cases of food-borne
botulism, of which 91 (over 90%) occurred in Alaska. Alaska has the
highest incidence of food-borne botulism due to the native foods consumed
by native Alaskans, with most being prepared from marine mammals, such
Food-borne zoonoses | 129
as whales or seals, by processes that do not kill the causative organism, i.e.
dessication or fermentation. In July 2002, a cluster of 12 cases occurred
after Alaskan Eskimos consumed meat and blubber from a beached beluga
whale, which had died some time previously. All the victims tested positive
for type E toxin, and were treated accordingly. There were no fatalities.21
Case number and fatality rate reduction in Alaska have been reduced since
by the implementation of an education programme, which has also meant that
patients or their families can rapidly access evacuation services, bringing
sufferers to hospital rapidly. All local hospitals hold stocks of antitoxin,
which, administered rapidly, can limit the consequences of the infection or
intoxication.
Botulinum antitoxin is used to treat the condition and, provided that
respiratory support is maintained, most cases will make a full recovery. The
antitoxin may be obtained from locally designated centres throughout the
UK, and in emergencies through the Department of Health Duty Officer on
telephone number ⫹44 (0)20 7210 3000. There are cautions related to its
use, because hypersensitivity reactions are not uncommon. Therapy should
start only after specialist advice has been obtained.
In the USA, it is illegal to use any drug product that is not licensed by
the FDA; however, the FDA can approve drugs or biological products as
investigational new drugs (INDs) and will permit treatment for a serious or
immediately life-threatening condition, where no comparable or satisfactory
alternative drug or therapy is available. IND status is maintained by the
CDC Drug Service for certain products; most are manufactured by foreign
drug companies and are commercially available in countries outside the
USA, and the demand for them in the USA is so limited that commercial
licensure is not practical or profitable, so these products are available in the
USA if needed.
In the case of botulinum antitoxin, there are two products available
through the CDC, the first being for toxin A and B, which has a full licence,
and the second being an IND product solely for toxin E. The latter is only
for concomitant administration with the anti-A and -B toxin product where
contaminated fish or marine mammal material has been consumed. The
CDC will release the products only for suspected or clinically confirmed
cases of botulism, and where requests are made through state or local health
departments, allowing the CDC to maintain effective surveillance and
rapidly detect any outbreaks. It is stored around the USA at CDC quarantine stations within airports, so that it can be delivered wherever it is
required rapidly. Requests should be made to the CDC on ⫹1 (0)770 488
7100.
As a final note on the food-borne form of the disease, it should be noted
that it has also been associated with non-animal-derived foodstuffs. In two
outbreaks in the USA, one in 1985 and the other in 1989, chopped garlic in
130 | Zoonoses
olive oil was the source of the toxin. This has been resolved since by the
FDA insisting that such products be acidified using phosphoric or citric acid,
thus destroying the toxin. There was also a case with two victims who ate
home-prepared soya bean tofu, which had become contaminated.
Infant botulism
The disease stems from contamination of food with spores of C. botulinum,
usually from environmental sources. In September 2007, an 8-month-old
infant was admitted to a London hospital and later diagnosed with botulism
(type A toxin). The source of the infection was never determined.
In the UK, there have only been six other cases since 1978, and the last
case before 2007 was recorded in 2001 in a child aged 6 months during July
2001 which resulted in a recall of batches of formula baby milk. Confined
to children aged under 1 year, the disease follows ingestion of viable spores.
These become active, and over a period of days to weeks colonise the gut,
producing the neurotoxin. This causes constipation and muscular weakness;
the inability to control head movement is a particularly marked symptom, as
well as a weak cry. There is marked lethargy and a disinclination to feed.22
As the loss of muscle tone and coordination progresses, the child may
become floppy, with respiratory distress. Diagnosis is made by isolating the
organism from stool samples or by toxin testing of faecal matter.
Treatment with the adult antitoxin is not suitable and antibiotic therapy
has to be carefully initiated, because this can cause massive death of the
organism with subsequent overwhelming toxin release. Respiratory support
may be necessary. Over time, even in severe cases, the paralysis lessens and
there is usually a full recovery with no major sequelae.
A human-derived botulinum antitoxin (Baby BIG) has been available for
the treatment of infant botulism since October 2003 from the Californian
Department of Health Services Infant Botulism Treatment and Prevention
Program, and was used for the first time in the UK on the child in the 2007
case. The infant recovered fully.23 The Californian Department of Health
Services Infant Botulism Treatment and Prevention Program can be contacted
on ⫹1 (0)510 231 7600 (24 hours a day, 7 days a week, including public
holidays). More information can be found at http://www.infantbotulism.org.
One of the major food sources of C. botulinum is honey, and fears
relating to infant botulism have led to advice that children under 1 year of
age should not be fed honey. The gastrointestinal tracts of older children
and adults have sufficiently robust bacterial flora to prevent the colonisation,
even if active bacteria are ingested.
In September 2006 the Advisory Committee on the Microbiological
Safety of Food (ACMSF), a statutory committee set up in 1990, providing
expert advice to the government on questions relating to microbiological
issues and food, published a report on chilled and frozen baby foods, and
Food-borne zoonoses | 131
concluded that there was no evidence to suggest that these foods had caused
any cases of infant botulism, and that jarred or tinned baby food also
carried a low risk.
The study had been prompted by concerns that the cooking processes used
in chilled or frozen products might not be adequate to prevent C. botulinum
growth. The manufacturing and process controls used in the production of
chilled and frozen baby foods were examined and found to be safe.
Wound associated
Wound-associated botulism follows the inoculation of an open wound with
material containing either viable spores or active bacteria. The progressive
production of toxins causes systemic paralysis radiating from the inoculation site. Treatment is usually with antibiotics and antitoxin as necessary.
Previously seen as a rare disease, the incidence has increased recently, associated with IDUs, especially where they use the intramuscular or intradermal administration route. The contamination seems to stem from the
material used to ‘cut’ (adulterate) the drugs. First seen in New York City in
1982, it was not reported in the UK until 2000. There have been a total of
134 cases with 8 fatalities up to the end of 2007, and it is now the most
common clinical presentation of botulism in the UK. It has also been seen in
Europe, with 12 cases in Cologne, Germany during October and November
2005.24
Most cases have been associated with type A toxin, some with type B and
in a few cases both type A and type B. A laboratory confirmation should not
be awaited. If clinical symptoms indicate botulism, antitoxin therapy should
be initiated as soon as possible to gain the greatest clinical advantage, once
consideration has been given to possible adverse reactions. C. botulinum is
sensitive to benzylpenicillin and metronidazole. It may also be possible to
undertake surgical debridement of wounds to reduce organism load.
Clinical uses of botulinum toxin
Purified botulinum A toxin continues to be used in spasticity. In an
extremely diluted form, it is also currently used for cosmetic use to reduce
facial wrinkles. Although well tolerated on the whole, there have been
incidents where side effects and toxicity have been seen.
Yersinia enterocolitica
Of the same bacterial genus as plague, it is transmitted to humans by ingestion of foods as diverse as meat (pork, beef and lamb), oysters, fish and raw
milk. It causes an acute-onset gastroenteritis with diarrhoea and vomiting,
marked fever and abdominal pain. The pain can be so severe that it mimics
appendicitis and has also led to misdiagnosis of Crohn’s disease. It is capable
132 | Zoonoses
of producing clinical complications which include septic arthritis, colonisation of existing wounds, bacteraemia and urinary tract infections. Luckily it
is rarely fatal. The inoculum is usually traced to environmental sources,
including soil and water; however squirrels, pigs and rodents form an
animal reservoir.25
Cryptosporidiosis
Cryptosporidium spp. are spore-forming parasitic protozoans found widely
in the environment in an extensive variety of foodstuffs, including salad and
vegetables, raw meat and meat products, offal and milk, usually associated
with contamination arising from animal faecal matter. Cryptosporidium
parvum is considered to be a particularly significant pathogen. Calves, lambs
and deer have been identified as asymptomatic animal reservoirs, capable of
shedding viable organisms in their faeces.26
Transmission
Human infection follows either direct contact with animal faeces or
consumption of inadequately cleaned or cooked products. There have also
been recorded incidents of individuals contracting the disease after swimming
or otherwise undertaking water-based recreational activities in contaminated
water, often where disinfection routines have become compromised. Personto-person spread has been recorded, and is a particular risk in care settings.
Disease in humans
An inoculum of fewer than 100 encysted organisms can cause clinical
disease. Following a pre-patent period of between 2 and 14 days, and in
individuals with no underlying risk factors, there is profuse self-limiting
watery diarrhoea, with abdominal pain and cramps, and a low fever that
may last up to 7 days. Loss of appetite and anorexia can follow with severe
weight loss, especially in immunocompromised patients. There is also a high
probability of relapse, with many patients having another bout of diarrhoea
within 14 days of apparent cure.
In patients with HIV/AIDS the disease may progress chronically,
spreading to the bile duct, central nervous system and lungs. Unless treated
swiftly, death will follow.
Treatment
In low-risk patients, treatment is purely supportive. Severe cases may need
intensive care; however, treatment is difficult and as yet there is no specific
therapy for conquering the pathogen. The strategy employed in HIV/AIDS
patients centres on boosting the already damaged immune system with
optimal retroviral therapy. There are some indications that those patients
Food-borne zoonoses | 133
receiving clarithromycin or azithromycin, with or without rifabutin for
prophylaxis against Mycobacterium avium complex, show less incidence of
this disease.
Prevention
The pathogen can be destroyed by freezing, drying, heating materials to
greater than 65°C and irradiation. It is resistant to many disinfectants in
common use.
Campylobacter spp.
Campylobacter spp. is a much under-rated cause of food poisoning. The
pattern of infection in the UK is very different to that in the USA for this
pathogen. In the UK, 80% of clinical cases are linked to contaminated food,
whereas in the USA most cases are water borne, although there have been
clusters of cases associated with the consumption of unpasteurised milk.27
This particular pathogen is widespread and present in many farm
animals. In particular, poultry are very susceptible to heavy bacterial loading.
Under normal circumstances, the animals show no sign of disease, although
there have been cases of abortion in sheep being linked to C. jejuni. The
bacterium has been isolated from pigs, birds, cattle, dogs, cats, unpasteurised
milk and water supplies. The measures in place to control Salmonella spp.
have had little or no impact on the prevalence of Campylobacter spp. The
two species considered significant in human disease are C. jejuni and C. coli,
with the infective dose considered to be fewer than 100 viable organisms.
In 2003, a survey of animals at slaughter point across the UK indicated that
54.6% of cattle, 43.8% of sheep and 69.3% of pigs carried Campylobacter
spp. This has led to the FSA initiating a control strategy (see Prevention below)
Transmission
The main route of infection is faecal contamination of carcasses ante or post
mortem, or of milk.21
The organism is capable of surviving freezing and has been shown to
survive for several months in frozen poultry, minced meat and certain
chilled foods. Thus cross-contamination could be a factor in infectious
spread.
Disease in humans
The most immediate symptom of campylobacter infection is a self-limiting
diarrhoea of 2–10 days’ duration, sometimes with bloody stools.
Campylobacter mainly affects babies and young children, and immunocompromised and debilitated individuals. Other symptoms include fever, nausea
and abdominal cramps which may vary from mild to severe, with occasional
134 | Zoonoses
misdiagnosis as appendicitis, similar to Yersinia enterocolitica. Symptoms
may regress and reappear over a period of weeks. A septicaemic form has
been seen in HIV/AIDS patients. Clinical cases of Campylobacter infection
are associated with 20–40% of cases of Guillain–Barré syndrome. The triggering of reactive arthritis has also been associated with the disease. After
infection it is estimated that less than 1% of the population may become
asymptomatic carriers.28
In 2006, 463 339 cases of Campylobacter infection were reported in
England and Wales to the HPA (up over 2005 by 4.5%). During the Infectious
Intestinal Disease (IID) study29 in England during 1993–6 it was estimated
that there were 870 cases per 100 000 head of population annually, with only
1 in 8 cases being reported, which has been confirmed in other epidemiological
studies. This would give a total of 370 000 cases in 2006.
Treatment
In most cases the disease is controlled without resort to antibiotics. However,
as it may be life threatening in immunocompromised patients, antibiotics may
have to be used.
Campylobacter spp. display high levels of resistance to fluoroquinolones,
so any of the macrolide antibiotics are preferable; there are now some
isolates that are dually resistant to both antimicrobial groups, which is a
cause for some concern. In acute cases where resistance is suspected, tetracyclines, chloramphenicol and gentamicin have all been used. This is usually
only initiated in secondary care settings after sensitivity testing has been
done.
Prevention
The main control measure is the reduction of faecal contamination of
carcasses at and after slaughter. Hazard analysis critical control point
(HACCP) measures (see below), including keeping raw and cooked meats
separate and ensuring that temperature-controlled processing of products is
correctly undertaken, are effective in controlling spread through the food
industry. In the home, using pasteurised milk and thoroughly cooking meat
and poultry are recommended for everybody and especially for members of
high-risk groups. Pets can carry and spread the organism and should be
excluded from kitchens. The organism is sensitive to heat and drying, so
thorough cooking acts as an effective control measure.
Campylobacter and Guillain–Barré syndrome
Guillain–Barré syndrome can affect any individual, and is often associated
with diarrhoea. It is an acute inflammatory episode in which demyelination
of multiple neurons occurs. This can affect large portions of the peripheral
Food-borne zoonoses | 135
neural network, and muscle weakness and paralysis may affect motor function, including breathing. Patients often require intensive care, especially if
lung function is significantly impaired. Most patients recover, although
convalescence may be prolonged. Luckily, fewer than 5% of cases are fatal.
Some theories suggest that this may be an autoimmune disease triggered by
bacterial or viral pathogens, of which Campylobacter spp. is only one of
several possible culprits. As yet there is no clear scientific evidence, although
research is currently being undertaken.30
Food Standards Agency inspection and enforcement
In the UK, the FSA was established in response to the Pennington report. It is
responsible for monitoring safety and standards of all food for human
consumption, advising on diet and nutrition, and enforcing the law pertaining
to food. It is also tasked with commissioning research into food safety. The
FSA is directed by an executive board, appointed to act in the public interest,
and is established so as not to represent particular sectors of industry or
government. Its members come from a wide and varied background, and
bring to their work a range of relevant skills and experience.
The stated aim of the agency is to ‘protect public health from risks which
may arise in connection with the consumption of food, and otherwise to
protect the interests of consumers in relation to food’.
The FSA has initiated a campaign called ‘from farm to fork’, aimed at
making food less contaminated and safer for the ultimate consumer. Initiatives
have also been launched for clearer labelling, and to educate the public on
food safety, nutrition and diet.
The FSA is accountable to Parliament through the Minister of Health. As
a safeguard for its independence, it has the unique distinction of being given
by statute the legal power to publish the advice that it gives to the government.
The Meat Hygiene Service is now accountable to the FSA.
At a local level, environmental health inspectors from local and county
councils conduct inspection visits, and enforce standards at producer,
supplier and retail levels.
In the USA, the Food Safety Inspection Service of the USDA acts in a
similar role, in consort with the FDA, and public/environmental health
departments across counties and states.
Reducing zoonotic risks in food
Reducing the risks of zoonotic disease from foodstuffs is not just a process
that begins and ends with the final consumer. Legislation and other physical
measures to reduce or exclude pathogens from food are applicable to every
step of the food chain, from field to table. Examining the process step by
136 | Zoonoses
step gives some knowledge of the systems in place and, when considered
against the information given in this chapter, allows some insight into the
system failures that enable outbreaks to occur.
HACCP (Hazard Analysis Critical Control Points)
One of the major food industry schemes for recognising and identifying risk
and its remedies is the HACCP process, derived from an engineering quality
control and production model, with wide application in other industries. This
is now internationally accepted as the preferred system for the management of
food safety in food businesses, and is used in the UK, the USA and Europe.
HACCP analysis identifies hazards and allows risk reduction and mitigation at all stages of production, distribution and retailing. It has seven
principles that provide a structured format for food safety by controlling
hazards inherent in the food handling and production process:31
1.
2.
3.
4.
5.
6.
7.
Conduct a hazard analysis
Determine the critical control points (CCPs)
Establish critical limits
Establish monitoring procedures
Establish corrective actions
Establish verification procedures
Establish record keeping and documentation procedures.
Food producers as well as government bodies, such as the Advisory
Committee on the Microbiological Safety of Food, have endorsed it as the
gold standard. The HACCP also applies to retailing and catering premises
through current legal measures. From 1 January 2006, Regulation 852/2004
of the European Parliament came into force, making HACCP mandatory for
all food producers and associated industries.
This reinforces the stepwise approach to infection control that previously
existed and was used by the most conscientious.
Stepwise prevention strategies
Knowledge of zoonotic infections is the key to producing an effective stepwise programme that informs the HACCP process. Understanding the likely
routes of infection and the life cycle of the pathogen allows selective measures to be applied in a focused way, breaking the transmission route at its
weakest point. The following generic points are used as an illustration only;
a full case-by-case examination of all possible pathogens and their control
is outside the scope of a book of this size. The references at the end of this
chapter offer scope for deeper exploration of any or all of the topics raised.
Food-borne zoonoses | 137
Some of these measures may not be familiar or fully comprehensible to
healthcare professionals as they relate to industrial processes. However, they
do form a non-medical system for prevention of disease, and are no less
valid than more therapeutically oriented methods.
Step 1: control the disease in the animal
The incidence of zoonotic disease in animals may be reduced by the use of
vaccination, clean foodstuffs and water, and good housing and husbandry.
Overcrowded or unsanitary conditions can often lead to overt disease or
unthrifty animals, requiring more therapeutic support for them to maintain
sufficient health to attain slaughter weight or to continue to be productive.
A reduction in infection rates has a dramatic effect on the incidence of infection further down the food or product chain. The associated lower levels of
inoculum produce a lower likelihood of illness. The difficulties in implementing strategies at this point in the system are often economic; although
the measures may be available, there may be little or no economic benefit to
using them. Good housing and intensive staffing of livestock units are expensive, not only in capital outlay, but also in continuing infrastructure costs. In
some cases those costs can become offset by higher prices for produce, but
that is not always the case. The lobby for animal welfare and organic
produce has improved the willingness of producers and consumers to follow
this route, and it has been proven that there is a portion of the public who
will willingly pay more for their food if it is of better quality. The converse is
that there is also a need for food at the lowest price, and a bulk producer for
a large supply contract may need to cut corners to stay in business, increasing
perceived, if not actual, risks.
Step 2: reduce contamination at harvesting
When eggs are picked out, or cows milked, the application of sensible
hygiene precautions is essential. Eggs should be free of droppings and
cleaned and date marked. In dairies, the udder of the cow and the milking
machinery should be as clean and hygienic as possible, with subsequent
disinfection after each milking. Pipework and items such as clusters should
be maintained and replaced as necessary to maintain adequate operating
parameters. Milk should pass to a bulk tank and be subsequently chilled
rapidly for later transport and pasteurisation.
At abattoirs, tight veterinary inspection both pre- and post-slaughter
must be practised. Animals that display heavy faecal contamination should
be cleaned or rejected. Slaughterhouse controls should prevent or reduce
onward transmission into the food chain, with rejection of suspect
carcasses. Prompt refrigeration of meat and careful cleaning of the carcass
can reduce bacterial contamination drastically.
138 | Zoonoses
Step 3: retailing controls
Disinfection of working tools and areas, along with personal and premises
hygiene procedures, protect consumers and workers from zoonotic infection.
Sourcing products from assured suppliers, temperature and environmental
monitoring, and the separation of cooked and raw products reduce the possibility of amplification and transmission of infection. The tight control of
‘use-by’ and ‘sell-by’ dates is mandatory, as is periodic inspection by public
health officials, and the implementation of monitoring of refrigeration and
freezer plants.
Step 4: domestic precautions
In the home, consumers should use common-sense measures, including
disinfection of surfaces and equipment, personal hygiene procedures and
thorough appropriate cooking techniques. Using a refrigerator correctly and
observing sell-by dates would prevent many cases of food poisoning.
It is perceived that the public in general has an acute need for education
related to such matters, and the Health Education Authority and the FSA
are to start a campaign aimed at addressing this problem.
General food hygiene recommendations
In the UK, the FSA, the Food and Drinks Association and other public
bodies have made various recommendations regarding food handling. These
measures are designed to prevent cross-contamination of raw and cooked
foods, and also to reduce the risk of consumers eating products that are raw
or undercooked. Similarly in the USA, the CDC, Food Safety and Inspection
Service (FSIS) and other public bodies run education campaigns, and issue
guidelines in an attempt to cut infection rates. In the UK, the advice is that
people should clean surfaces, equipment and containers that have come into
contact with raw meat. They must wash their hands after handling raw
meat and before handling other utensils. The same plate should not be used
for cooked and raw meat without washing the plate in between. Meat
should be cooked until the juices run clear; this especially applies to burgers.
Barbecues are considered to be particularly risky as meat may not be fully
cooked and, if previously chilled or frozen, may be raw or undercooked in
the middle.
These recommendations were made after surveys had shown that public
awareness of food hygiene was lamentable. Figures obtained from the Food
and Drink Federation survey in 2002 indicated that:
• 23% had never been taught to cook or prepare food
• 50% do not follow cooking instructions
Food-borne zoonoses | 139
•
•
•
•
15% admit not cooking meat fully or properly
25% do not always wash hands before cooking
10% do not separate raw meat from other foods
8% do not keep perishable items in a refrigerator.
It appears from these figures that the general public has a profound need
for education and information related to basic food safety and hygiene.
In 2006, when the latest survey was carried out by the same organisation,
things had not improved. Of 1000 people questioned:
• nearly 50% did not cook burgers and sausages thoroughly
• 33% admitted to eating food past its use-by date
• of those with pets, 14% said that they washed their pet’s bowl with
their own washing up; food storage was also found to be a big area of
confusion
• nearly 50% did not know that they needed to keep their fridge at
0–5°C to store food safely
• 16% store raw meat on the top shelf of the fridge and a further 8%
would store it anywhere – risking the chance that juices could drip
onto ready-to-eat foods below.
Miscellaneous items
Food sterilisation
Provision of appropriate information and an understanding of likely infections
in risk groups form part of the support role of many hospital pharmacists.
Knowledge of prevention strategies and animal handling guidelines is a
valuable tool in the non-drug management of many patients.
Among the measures that may be needed in secondary care to manage the
seriously ill patient is the non-technical issue of food provision. Sterilisation
of foodstuffs, the education of food handlers and their screening as carriers
of resistant organism serotypes may be necessary in certain care contexts,
especially where immunocompromised patients are routinely treated.
Lower-input animals and higher-priced food
The continued debate over price as the sole arbiter of food supply, and the
use of organic and high-welfare systems in agriculture, has a direct impact
on zoonotic disease and antibiotic resistance. The use of older breeds of
animal with lower input requirements in terms of therapeutic intervention
and their higher innate resistance to infections, including zoonoses, is
becoming increasingly important in agriculture.
140 | Zoonoses
This option for control of all zoonoses, and in particular those that are
food borne, will impact on the consumer. It will require considerable political
will and willingness on the part of consumers to reach deeper into their
pockets to make such initiatives commonplace.
The globalisation of food production and trading also has the potential
to affect any country’s domestic situation, and pathogens previously
unknown in a country may easily be introduced on foodstuffs. There is still
a debate raging over whether or not the epidemic of foot and mouth in the
UK in 2000–1 followed the importation of infected meat, which was fed in
inadequately treated swill to pigs.
Farm visits
Over the past decade, there has been considerable adverse publicity
surrounding cases of illness following farm visits, especially as there have
been some fatalities in young children. In the UK, Professor Sir Hugh
Pennington, the eminent microbiologist who carried out the Wishaw enquiry
and who has since advised government on zoonotic infection risks, has
suggested that very young children should not visit farm premises because of
the risk of infection.
The Health and Safety Executive has issued guidance to farmers under
the Control of Substances Hazardous to Health (COSHH) provisions and
there is a useful information sheet.32 The CDC issues similar guidance in the
USA.33
Farmers must consider that visitors may be exposed to contaminated
faeces and other materials. Any farm open to the public should ensure that
there are adequate washing facilities for visitors, with warm running water,
soap and clean towels adjacent to all areas where the visitors may contact
animals. Signs should be erected advising visitors to wash before eating,
drinking or smoking, and also advising parents to check that their children do
not put dirty hands or fingers in their mouths. Provision should be made for
separate eating areas, close to washing facilities. After the visit, teachers and
parents should notify health authorities or their GP of any illness, especially
gastrointestinal.
References
1. Lewis RJ. The changing face of ciguatera. Toxicon 2001; 39: 97–106.
2. Todd ECD. Domic acid and amnesic shellfish poisoning: a review. J Food Protn 1993; 56:
69–83.
3. Tarr PI, Gordon CA, Chandler WL. Shiga toxin-producing Escherichia coli and
haemolytic uraemic syndrome. Lancet 2005; 365: 1073–86.
4. Rangel JM, Sparling PH, Crowe C, Griffin PM, Swerdlow DL. Epidemiology of
Escherichia coli O157:H7 outbreaks, United States, 1982–2002. Emerg Infect Dis 2005;
11: 603–9.
Food-borne zoonoses | 141
5. Wong CS, Jelacic S, Habeeb RL et al. The risk of the haemolytic–uremic syndrome after
antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 2000; 342:
1930–6.
6. The Pennington Group. Report on the Circumstances Leading to the 1996 Outbreak of
Infection with E. coli O157 in Central Scotland, the Implications for Food Safety and the
Lessons to be Learned. Edinburgh: Scottish Office, 1998.
7. Advisory Committee on the Microbiological Safety of Food. Report on VerocytotoxinProducing Escherichia coli. London: HMSO, 1995.
8. Lorber B. Listeriosis. Clin Infect Dis 1997; 24: 1–11.
9. Anonymous. Outbreak of listeriosis associated with homemade Mexican style cheese.
North Carolina October 2000. MMWR 2001; 50: 560–2.
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Listeria monocytogenes infection: a FoodNet case-control study: United States, 2000–2003.
International Conference on Emerging Infectious Diseases, 29 February–3 March 2004,
Atlanta, USA.
11. Dorozynski A. Seven die in French listeria outbreak. BMJ 2000; 320: 601.
12. Health Protection Agency. Cluster of pregnancy associated Listeria cases in the Swindon
area. Communicable Disease Report 50. London: HPA, 2003.
13. Schroeder CM, Naugle AL. Estimate of illnesses from Salmonella enteritidis in eggs,
United States, 2000. Emerg Infect Dis 2005; 11: 113–15.
14. DEFRA. Zoonoses Report. London: DEFRA, 2006.
15. Voetsch AC, Van Gilder TJ, Angulo FJ et al. FoodNet estimate of the burden of illness
caused by nontyphoidal Salmonella infections in the United States. Clin Infect Dis 2004;
38: S127–34.
16. Mermin J, Hutwagner L, Vugia D et al. Reptiles, amphibians, and human Salmonella
infection: a population-based, case-control study. Clin Infect Dis 2004; 38(suppl 3):
S253–61.
17. CDC. Turtle-associated salmonellosis in humans – United States, 2006–2007. MMWR
2007; 56: 649–52.
18. Anonymous. Clostridium perfringens gastroenteritis associated with corned beef served
at St Patrick’s day meals – Ohio and Virginia, 1993. MMWR 1994; 43: 137–8, 143–4.
19. Cherington M. Clinical spectrum of botulism. Muscle Nerve 1998; 21: 701–10.
20. Sobel J, Tucker N, Sulka A, McLaughlin J, Maslanka S. Foodborne botulism in the
United States, 1990–2000. Emerg Infect Dis 2004; 10: 1606–11.
21. McLaughlin JB, Sobel J, Lynn T, Funk E, Middaugh JP. Botulism type E outbreak associated
with eating a beached whale, Alaska. Emerg Infect Dis 2004; 10: 1685–7.
22. Brett MM, McLauchlin J, Harris A et al. A case of infant botulism with a possible link
to infant formula milk powder: evidence for the presence of more than one strain of
Clostridium botulinum in clinical specimens and food. J Med Microbiol 2005; 54:
769–76.
23. Arnon SS, Schechter R, Maslanka SE, Jewell NP, Hatheway CL. Human botulism
immune globulin for the treatment of infant botulism. N Engl J Med 2006; 354: 462–71.
24. Brett MM, Hallas G, Mpamugo O. Wound botulism in the UK and Ireland. J Med
Microbiol 2004; 53: 555–61.
25. Lindsay J. Chronic sequelae of foodborne disease. Emerg Infect Dis 1997; 3: 443–52.
26. Dillingham RA, Lima AA, Guerrant RL. Cryptosporidiosis: epidemiology and impact.
Microbes Infect 2002; 4: 1059–66.
27. Allos BM. Campylobacter jejuni infections: update on emerging issues and trends. Clin
Infect Dis 2001; 32: 1201–6.
28. Lee W, Mijch A. Campylobacter jejuni bacteremia in human immunodeficiency virus
(HIV)-infected and non-HIV-infected patients: comparison of clinical features and review.
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30. Schmidt-Ott R, Schmidt H, Feldmann S, Brass F, Krone B, Gross U. Improved serological
diagnosis stresses the major role of Campylobacter jejuni in triggering Guillain–Barré
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of criteria using quantitative risk assessment. Food Microbiol 1995; 12: 81–90.
32. Health and Safety Executive. Avoiding Ill Health at Open Farms: Advice to Farmers
(with Teachers’ Supplement). AIS 23. Sudbury, Suffolk: HSE, 2002.
33. CDC. Compendium of measures to prevent disease associated with animals in public
settings, 2005: National Association of State Public Health Veterinarians, Inc.
(NASPHV). MMWR 2005; 54(RR-4): 1–12.
5
Prion diseases
For centuries sheep and goats have suffered from a condition of until recently
unknown aetiology called scrapie, which is not zoonotic. All attempts to
identify or classify the causative agent had failed, although infectivity had
been demonstrated by using an inoculum of brain tissue from sheep to sheep
in the late 1930s. Until the last decade of the twentieth century a ‘slow virus’
was suggested as the most likely cause, although no viral particle was ever
isolated. The causative agent was known to be resistant to almost all
methods and materials known to destroy or inactivate viral particles.
Research workers in the 1990s identified a protein fragment apparently
responsible for the affliction. These fragments were designated prions, and
defined as ‘small proteinaceous infectious particles which resist inactivation
by procedures that modify nucleic acids’. In 1997 Professor Stanley Prusiner
won the Nobel Prize for Medicine for his discovery of prions (proteinaceous
infectious particles), which contain no DNA or RNA. He postulated that
prions may play a part in Alzheimer’s disease, Parkinson’s disease and other
degenerative neural diseases. Most scientists now believe prions to be the
causative agent of scrapie, bovine spongiform encephalopathy or variant
Creutzfeldt–Jakob disease (vCJD) and a variety of other transmissible
spongiform encephalopathies (TSEs), which affect most mammalian species,
although other factors, such as manganese deficiency and bacterial infections,
may be moderators in the rate of disease progression.1
Prions are unconventional as an infectious agent. Consisting of protein
alone, with no nucleic acid, the diseases that they cause are also different to
any other infection or disease, because both infective material and hereditary factors that give genetic susceptibility have to be present for disease to
occur. It is now believed that, after infection by a sufficient inoculum of
aggressive prions, genetically susceptible individuals can develop the clinical
signs of TSEs. Their name reflects the finding post mortem of brain and
central nervous tissue riddled with holes like a sponge.
144 | Zoonoses
The prion theory suggests that the responsible agent affects proteasesensitive protein production, so that, after a spontaneous or acquired
genetic modification, the protein (a normal constituent of cell walls) changes
conformation to become protease resistant. This change triggers a chain
reaction: the rate of protein conformation change becomes exponential so
that there is a rapid laying down of the mutated form of protein (designated
PrPsc – the sc for scrapie, the oldest known prion disease).
The physical symptoms of the disease spectrum caused by prion agents
arise from the alteration of cell-wall proteins into insoluble forms after
exposure to and incorporation of prion proteins. The process then becomes
a self-sustaining chain reaction, which produces sheets of insoluble protein
in neural tissue and particularly in the central nervous system, with
inevitably fatal results following segmentation and gradual, progressive
destruction.
Animal TSEs and BSE
The best-known animal TSEs are bovine spongiform encephalopathy (BSE)
affecting cattle, chronic wasting disease (CWD), which affects elk in Northern
America, scrapie affecting sheep worldwide with the exception of the
Antipodes, and transmissible mink encephalopathy (TME) which affects
mink, polecats and ferrets. There are also related feline/canine diseases and
certain rodent diseases. It is difficult to substantiate some of these diseases in
other species because they tend to appear slowly and are usually seen in the
mature animal. For some species, attaining sufficient age to display the disease
may not be achievable, as death from other causes intervenes before clinical
signs are seen, and postmortem examination will not be possible or routine.
The two most significant TSEs in the UK at present are BSE and scrapie,
which have an associated link to vCJD in humans. Prion strain typing has
shown scrapie to be closely related to the prion responsible for BSE in cattle,
and that the causative agent of vCJD in humans is very close to BSE in its
characteristics. In the USA, CWD is significant in deer and elk and, although
as yet there is no definitive link to human illness, monitoring is ongoing.
BSE is a fatal neurological disease of cattle that was first identified in the
UK in November 1986. The feeding of meat and bone meal (MBM) to cattle
and changes to the method of rendering animal carcasses before incorporating them into MBM appears to have enabled the prion agent to survive
and led to the outbreak. Feeding as little as 1 g infected material from the
brain or spinal cord of a sheep has been shown to be sufficient to cause BSE
in 70% of those animals genetically susceptible to the disease. After clinical
onset is observed the disease is rapidly fatal, within either weeks or months.
A ban was put in place in July 1988 by the UK to prevent the inclusion of
ruminant-derived protein in cattle feed. In November 1989 a voluntary ban
Prion diseases | 145
40 000
35 000
Number of confirmed cases annually
30 000
25 000
20 000
15 000
10 000
2007
2005
2003
2001
1999
1997
1995
1993
1991
0
1989
5000
Figure 5.1 Confirmed cases of BSE.
supported by animal feed manufacturers stopped the inclusion of MBM in
ruminant feeds. Since then various legislational measures have been taken to
prevent a reoccurrence.2
By October 1996, BSE had been reported from 10 countries outside the
UK, some arising from the importation of contaminated feed, and others
linked to the importation of livestock from the UK for breed improvement
or other purposes. As it is now known, once in the cattle herd, BSE can
spread by maternal transfer; other cases arose in herds by this method.
After the first appearance and identification of BSE in cattle, a dramatic
rise in incidence was seen, some of which could have been solely attributable to better surveillance. All cattle identified as suffering from the disease
are slaughtered. The numbers have declined dramatically from a peak in the
12 months 1992–3 of 36 680 cases to 104 confirmed cases in 2006–7
(Figure 5.1).3
Measures at slaughter include a rigid adherence to non-invasive stunning,
and the removal of all specified bovine material (SBM) from cattle carcasses,
along with stringent inspection of meat at abattoirs, prevents contaminated
material from entering the food chain. SBM includes the head, spinal cord,
tonsils, spleen, intestines and thymus gland. All SBM must be rendered
(temperature treated by boiling or steam heating), and then destroyed. The
material must not under any circumstances be included in material for
human consumption.
The significance of scrapie
Scrapie infection is important in our understanding of TSEs and is seen as
the original source of BSE, and thus vCJD in humans. Research undertaken
146 | Zoonoses
on scrapie has shown that susceptible animals need to be genetically predisposed to develop the disease, and for the infective agent to be present. It is
now known from research carried out in the 1950s that, in sheep, inoculation stems from grazing on pasture contaminated with placental matter or
other bodily material. Once in a susceptible animal population, further
spread can occur by maternal transfer, so that it becomes a genetic inherited
disorder in future generations. An infected animal can remain asymptomatic
for a variable period of time. There is no evidence of the prion responsible
for scrapie being able to cross the species barrier directly into humans.
Variant CJD and human TSEs
HG Creutzfeldt first described the disease now known as sporadic or classic
Creutzfeldt–Jakob disease (CJD) in 1920. In 1921 another German neurologist, Jakob, described four more cases. CJD appears to occur as a sporadic
disorder in 90% of known cases. Most of the remaining 10% show a strong
relationship to a dominant inherited genetic trait. This was unexplained
until the mapping of the human genome discovered that a mutation of
chromosome 20 could lead to the damage necessary to initiate CJD. It
appears that the genetic mutation, in association with ageing, produces a
disease clinically indistinguishable from prion-mediated disease.
Several cases of CJD were related to the use of either brain tissue grafts
originating from sufferers, or human growth hormone originating from the
pituitary glands of cadavers. A case arose in 1974 after a corneal graft, and
contaminated neurosurgical instruments have been implicated in several other
cases. Following these cases a policy on destruction of surgical instruments
and the use of synthetic hormones has prevented recurrence.4
The disease is invariably fatal and patients usually display a rapidly
progressive state of dementia, with muscle spasm and tremor and a characteristic electroencephalogram (EEG) pattern. On postmortem examination,
spongiform changes are found in the central nervous system.
The affliction occurs worldwide at a rate of about one case per million
per year. There are higher rates in Slovakia and in a discrete group of Israelis
who are all Libyan born. In these groups one case per year per 10 000 is
seen. A blanket study of cell samples from postmortem examination of large
cohorts of cadavers has shown that as many as 1 in 10 000 show signs of
the mutation that can lead to CJD. It has also been suggested that, due to
the limitations of the technique and the survey, this could be a substantial
underestimate of the true incidence. Epidemiological surveillance of CJD
was reinstated in the UK in 1990 to identify any changes in the occurrence
of this disease after the epidemic of BSE in cattle.
There are three other human conditions that appear to be caused by
similar but different modification of chromosome 20, each of which have
Prion diseases | 147
slightly different clinical signs: Gerstmann–Sträussler–Schenker (GSS)
syndrome (first described in 1928–36), fatal familial insomnia (FFI) (first
described in 1986) and kuru. GSS and FFI are both related to an inherited
genetic modification. Kuru may also be similar, but it exists solely in a single
tribe from Papua New Guinea, the Fore Highlanders. A degenerative neural
disorder, it was first described in 1957 by an Australian anthropologist. The
disease was linked to the cannibalistic practice of eating deceased relatives’
brains as part of an animistic religious rite. Since this practice has been
discontinued the disease has virtually disappeared. Yet again the disease was
characterised by gradual loss of neural capability. Postmortem findings of
spongiform changes in the brain were also characteristic. Our knowledge
of kuru and scrapie, the identification of their method of spread and how
the disease progresses have been extremely important in gaining some
understanding of the mechanism of spread of BSE and vCJD.
Variant Creutzfeldt–Jakob disease
Dr Robert Will first described vCJD in a 1996 paper in The Lancet. He stated:
In the past few weeks we believe we may have identified a new
clinico-pathological phenotype of CJD which may be unique to the
UK. This raises the possibility of a causative link between BSE and
CJD. The identification of a form of CJD that might be causally
linked to BSE will result in widespread anxiety and concern.
This was an amazingly studied understatement.5
Initially known as new variant CJD, the ‘new’ designation for the disease
was dropped by the Spongiform Encephalopathy Advisory Committee
(SEAC) in March 1999, leaving the disease to be designated variant CJD. The
identification of this variant arose from a series of deaths and postmortem
findings which, although having many of the characteristics of classic CJD,
did not fit the accepted case profiles. When compared with classic CJD cases,
they were found to have an earlier age of onset, with a much longer period
from clinical manifestation to death. The patients also did not have the characteristic EEG findings of sporadic CJD. At the time of the article in The
Lancet, no similar cases had been seen in any other European country, thus
triggering the possible link with BSE.
Patients suffering from vCJD have an average duration of illness of 2 years
rather than the classic CJD pattern where it was unusual for a patient to
survive for longer than 12 months. Classic (or sporadic) CJD affected
patients aged 50–75, whereas vCJD affects a much younger group, with
victims so far aged between 18 and 41 years.
Initially the hypothesis that vCJD and BSE were linked emerged from the
association of two diseases of similar aetiology and clinical progress
148 | Zoonoses
occupying the same location and time frame. It is now widely accepted that
this disease is linked to BSE and that consumption of infected meat or other
bovine material provides the inoculum (Figure 5.2). The evidence from
studies in mice and monkeys supports the hypothesis.
It is still unclear how the prion invades the body after ingestion of
infected material; however, a theory relating to Peyer’s patches in the
gastrointestinal tract of children and young adults is currently under development. Peyer’s patches allow pathogens to be presented to the immune
system in a controlled manner so that immunity can be developed. They
recede in size and number as the child matures into adulthood. The theory
proposes that the prion is absorbed from the gut, ingested by mobile
lymphoid cells and then travels to other parts of the lymph node system,
where it is subsequently able to develop in susceptible individuals. Neural
pathways from the nodes can lead directly to the central nervous system, so
the prion gains access by this route.6
The cumulative number of definite and probable cases to January 2008
totalled 166, including 46 where no diagnostic confirmation will ever be
possible because the bodies were cremated, or the relatives refused permission for exhumation and postmortem examination (Figure 5.3). A particular
genetic variation has been found in all of the cases tested to date with a
modification of gene 20. This has been found to occur in approximately
vCJD
Consumption of
contaminated
meat
Meat and
bone meal
Maternal
spread
Maternal spread
and contaminated
pasture
Maternal
spread
BSE
Scrapie
Figure 5.2 Diagrammatic representation of the most likely scenario for the emergence of
variant Creutzfeldt–Jakob disease (vCJD). BSE, bovine spongiform encephalopathy.
Prion diseases | 149
30
28
Confirmed cases
Numbers include
11 probable deaths
where diagnosis was
not confirmed by
neuropathological
findings.
25
20
20
18
15
10
10
5
17
18
15
10
9
5
5
5
3
1
0
1995
1997
1999
2001
2003
2005
2007
Figure 5.3 Number of deaths from variant Creutzfeldt–Jakob disease (vCJD) reported by year.
(Figures courtesy of vCJD Surveillance Unit.)
40% of the population of the UK. This does not exclude the possibility of
people without this genotype becoming victims of the disease.
In September 2000, the first report of possible maternal transmission of
vCJD appeared. A baby born to a mother who subsequently died of vCJD
was suspected of having the disease. The baby showed signs of brain
damage with fits and convulsions, and was not developing normally.
Confirmation of the diagnosis was not possible; however, the possibility of
such an event is consistent with the findings in both BSE and scrapie.
Disease symptoms
Victims initially present with non-specific psychiatric symptoms. The clinical
disease presentation shows progression from anxiety, depression, to gradually worsening changes in behaviour. Altered perception and painful sensory
distortion are also seen in approximately 50% of patients.7 There is a gradual
loss of neuron density and function. After weeks, or months, the disease
affects coordination and patients may have difficulty walking and picking
things up; involuntary movements and convulsions occur. Memory problems
develop and patients have reality perception difficulties, loss of motor
control, dementia, paralysis and wasting. Patients deteriorate rapidly and
require intensive nursing, as in the final phase of the disease total immobility
occurs and the patient becomes mute. Death following overwhelming
pneumonia is not uncommon.8
Diagnosis
Diagnosis in the initial stages of clinical onset is made difficult by the
resemblance between this and other neurological and psychiatric disorders.
150 | Zoonoses
Differential diagnosis relies on the use of magnetic resonance imaging
(MRI), computerised tomography (CT) and EEG. MRI has shown abnormal
features in areas at the base of the brain in some vCJD patients, but the significance of these findings is not yet known. CT excludes other conditions, but
does not definitively support the diagnosis. The use of lumbar puncture has
proved of no benefit.9
The EEG findings in vCJD are consistently abnormal and do not show
the distinctive changes associated with classic CJD. A mild elevation of
hepatic enzyme levels has been seen, but is believed to be transient.
Confirmation of diagnosis is usually obtained only post mortem, where
the characteristic spongiform changes with microscopic findings of
abnormal protein clusters encircled by holes are seen, resulting in a daisylike appearance described as ‘florid plaques’. A biopsy specimen has been
obtained in some cases before death, which can confirm the diagnosis, but
the process may distress both the patient and relatives so it is unlikely to be
used routinely in the future. There are some indications that testing tissue
from the tonsils may allow definitive diagnosis to be made without the need
for invasive techniques.
Treatment for vCJD patients and the BSE enquiry
As has been previously stated, many patients with vCJD are never properly
diagnosed until after their demise. The disease is invariably fatal, and it is
likely that, by the time signs and symptoms are seen, and a presumptive
diagnosis made, the disease will be well advanced and death will follow
swiftly. As the disease presents in a dramatic way, with mental illness,
anorexia and loss of motor function, there is considerable distress for both
patient and relatives.
In the interests of scientific research and public health, all patients
suspected of suffering from a TSE are reported to the national Creutzfeldt–
Jakob Disease Surveillance Unit (CJDSU), based in Edinburgh. Doctors
from the unit visit all people with the disease and attempts are made to take
a detailed history from the patient and relatives. The diagnosis of the case
will also be reviewed at the same time. The CJDSU has produced a set of
diagnostic guidelines that help place patients within classification groups of
TSEs. Patients may be reclassified as their clinical symptoms and test results
develop. Case notes are closed only after the death of the patient and when
no further data is likely to be forthcoming.2
The task of the CJDSU is to identify and investigate all cases of CJD and
other TSEs in humans occurring in the UK. The unit is also responsible for
a comprehensive national surveillance programme. The programme aims to
track case trends over time, and to detect case clusters. Research is also
being undertaken to detect risk factors and mechanisms of transmission.
This work is aimed at determining the magnitude of the public health
Prion diseases | 151
problem, and to produce informed prevention strategies and valid diagnostic
tests.
The annual report of the CJDSU and its database of cases have identified
two clusters; these are examined later in this chapter.
Treatment
There have been a number of experimental drug therapies tried in an effort
to slow the progression of the disease. Amantadine and amphotericin,
although effective at slowing or arresting the condition in vitro, have little
or no effect on the disease in sufferers. Aciclovir, interferon, antibiotics,
steroids and other antiviral agents have also been tried and have failed to
alter the outcome significantly.
Current trials centre on a number of agents. The first, pentosan polysulphate (PPS), which has been used with some limited success in several cases,
is currently not licensed for human use, and each case has to be evaluated
on an individual case basis before legal permission is given for it to be
used.10 It has to be directly infused into the brain. The second moiety is
quinacrine, an antimalarial; a trial in CJD patients had been undertaken in
the USA.11 In the USA, three phenothiazines – chlorpromazine, promazine
and acepromazine – are also under consideration, because they have
displayed the ability in vitro to inhabit prion formation. In Germany,
flupirtine has been undergoing trials in classic CJD patients.12
A decision is awaited on a clinical trial agreement for these drugs, but
due to the nature of the disease there will be no placebo-controlled trials.
As patients deteriorate, rehydration and liquid feeds need to be used. Pain
control may also be necessary. Clonazepam or sodium valproate can be given
to control spasm and spasticity at normal doses, with titration to response.
Future hopes for therapies centre around protein stabilisers to prevent
conversion of normal protein into prion protein. Anti-gene therapies are also
proposed: such agents would destroy the gene responsible for producing
the prion protein; however, it is unclear if this modification would carry
with it a risk that the responsible gene has other metabolic functions, which
may be currently unknown, within normal healthy body systems. Even these
therapies may only slow progression, and are not seen as effecting a cure.
As the average age of the victims so far has been low in comparison to
classic CJD, specialist strategies were not previously in place for dealing with
young victims of degenerative disorders. Beds are now available in hospices
or other facilities for the terminal care of these patients. Much of the healthcare professional input in the care of victims of vCJD is palliative and relies
heavily on good nursing practice. The Department of Health now provides a
key coordinating worker to be appointed as soon as possible after diagnosis
for every patient. The key worker ensures that there is an adequate care
package in place, not only for the sufferer but also for relatives.
152 | Zoonoses
The BSE inquiry
A government-led enquiry into BSE commenced in December 1997 with it
finally making its report in October 2000. The enquiry found that standards
of care and support for families varied widely and suggested that improvements were needed, including speedy diagnosis with informed, sympathetic
advice to relatives about the future course of the disease and the needs of the
patient. It is now recognised that there is a requirement for rapid assistance
for families to allow victims to be cared for in their own homes and access to
hospice or similar care settings in the final phases of the disease’s progress.
The necessary measures include many of the items of care normally seen in
association with care for elderly or disabled people, or those with cancer.
They include home adaptations, respite care and, especially if the victim is
the main breadwinner, financial support.
Epidemiological clusters
Clusters of cases form a very important part of the tools available to
epidemiologists to identify not only past exposure and infection pathways,
but also future trends. Through the work of the CJDSU, two clusters of
cases have been identified. A cluster of cases of vCJD was first identified in
the Leicestershire village of Queniborough in November 1998. In July 2000,
when the investigation began, the number of possibly linked cases had risen
to five. Between August 1996 and January 1999 five people developed the
disease and subsequently died. All the victims lived in the area between
1980 and 1991, and this was the only time that a common exposure could
have occurred.
An investigation was also undertaken into three deaths, in Armthorpe,
near Doncaster. Two of the victims came from the same street, and the third
visited the area frequently.
The expert findings into these two clusters excluded a number of factors
that linked the victims including surgery and blood transfusions, dental
surgery, occupational exposure, immunisations, injections, body piercing,
cuts and animal bites, baby foods, school meals, drinking water and high
manganese levels. All of these factors had been postulated as causing or
contributing to the development of vCJD, but the links were unproven.
In each cluster the source appears to have been contaminated beef from
cattle with BSE derived from animals that were Friesian–Hereford crosses
born of dairy cattle and fattened on for slaughter. Such animals are slow to
fatten and were therefore slaughtered at 30–36 months of age, rather than
at the younger age normally associated with beef breeds. Being older, and
given their feeding pattern, it was more likely that these animals could have
had subclinical BSE at slaughter. This was compounded by slaughtering
practice in local abattoirs. Cattle were slaughtered using a captive bolt as
usual; however, in some local abattoirs and butchers, a pithing rod was also
Prion diseases | 153
used to prevent the beast kicking after slaughter. The use of a pithing rod
ruptures the brain structure and is more likely to release infective material
into the work area, or onto the carcass, especially as the prion is most
concentrated in brain material. Some local butchers also removed the brain
from the head of the beast for further processing, increasing the chance of
contaminating the meat.
Small abattoirs also often used a cloth to wipe down the beast after
slaughter to remove any unwanted tissue, rather than hosing the carcass
down as was usual practice in larger slaughterhouses. This practice
increased the likelihood of contaminating the meat with infective material.
At the time there was no legislation to define best practice.
The initial work of the enquiry team found that there was an association
between the vCJD cases and the consumption of beef purchased from
butchers where meat could have been contaminated with bovine brain. All
the possible sources of meat were investigated to try to identify the butchery
and slaughter methods used. The result showed that the victims were 15
times more likely to have purchased and consumed beef from a butcher who
removed the brain from a beast compared with control groups who
purchased meat from outlets where cross-contamination with brain material
was not a risk.
The careful and exhaustive investigation of these clusters identified the
likely timeframe for infection and has allowed the incubation period in
humans of vCJD to be estimated as within the range of 10–16 years from
infection.
Prevention of vCJD and BSE
The BSE enquiry2 stated that government policy was ‘All pathways by which
vCJD may be transmitted between humans must be identified and all
reasonably practicable measures taken to block them’.
The prevention of the passage of vCJD from sufferers to other humans
is addressed in several ways: the World Health Organization (WHO)
became involved soon after it became apparent that there might be a link
between BSE and the emergence of vCJD. A series of consultations was
undertaken with a variety of governmental bodies and eminent scientists. As
a result, the WHO made a series of recommendations relating to foodstuffs
and products derived from cattle. Milk was considered to be safe; however,
tallow and gelatin were considered to be safe only if, during manufacturing,
the process involved could inactivate or destroy any prion present. They also
recommended that it is important that the pharmaceutical industry obtain
bovine materials for use in parenteral, oral or other products from countries
that have a surveillance system for BSE in place and that report either no or
only sporadic cases of BSE. In addition, they encouraged the development
of diagnostic methods and surveillance to ascertain the spread of vCJD.
154 | Zoonoses
In the UK regulations have been introduced covering the use of bovine
materials in medicines and vaccines. The law came into effect on 1 March
2001 for human medicines, and from 1 June 2001 for veterinary medicines.
All manufacturers of licensed medicinal products are affected and the
Medicines Control Agency (MCA) and Veterinary Medicines Directorate
(VMD) ensure compliance.13
All gelatin, collagen, tallow derivatives, amino acids and peptides made
from bovine material and used in the pharmaceutical industry are derived
from material obtained from animals slaughtered outside the UK.
Classic CJD has occurred by the transplantation of brain tissue or the use
of brain-derived extracts. As a result, surgeons, especially neurosurgeons who
treat CJD patients, are advised to destroy all surgical instruments after use.
Disposable single-use instruments for tonsillectomies were introduced in 2001,
although delays in their introduction led to a backlog of cases awaiting surgery.
Blood and blood products have been identified as carrying a particular
risk of transmitting vCJD, with four cases being reported by the Health
Protection Agency (HPA) to date. Measures have been taken to treat blood
used in the UK by leukodepletion to reduce any transmission risk. Fresh
frozen human plasma has been imported to produce certain blood products
from countries where BSE/vCJD is unknown.14
The UK blood transfusion services are informed every 6 months of all
definite and probable cases of sporadic and familial CJD who were reported
as blood donors and blood product recipients. Whenever a suspected case
of vCJD is confirmed as a ‘probable’ case, comprehensive information is
passed to the transfusion service so that any donated blood can be withdrawn, and any blood donors whose blood has been given to the patient
traced. Canada and the USA have banned blood donations from people who
have spent long periods in the UK, and other countries are considering
introducing similar measures.
Prevention strategies
Prevention of a recurrence of the BSE/vCJD outbreak is of paramount
importance to the government of the UK, and its subordinate departments.
As a result there are a series of measures in place to reduce the risks of
BSE-infected meat entering the human food chain.13
Primary prevention focuses on preventing a resurgence of BSE in the UK
cattle herd, and the presence of the disease in cattle at slaughter. Additional
precautions are aimed at implementing and ensuring good butchery practice.
Any cattle suspected of having BSE are compulsorily slaughtered and
their bodies destroyed. Milk produced by cows that are suspected of having
BSE may not be used for any purpose other than feeding the cow’s own calf.
In addition to this very obvious measure there are several other measures in
place to protect animal and, by implication, human health.
Prion diseases | 155
All cattle reared for beef destined for human consumption are ideally to
be slaughtered at an age of less than 30 months. The requirement for
removing the bones from meat before retail sale has now been lifted.
The Over Thirty Months Slaughter (OTMS) scheme banned the sale of
meat derived from cattle aged over 30 months at the point of slaughter for
human consumption and was introduced by the Spongiform Encephalopathy
Advisory Committee (SEAC) in 1996. On 7 November 2005, following extensive consultation and risk assessments, a system of BSE testing was introduced
for slaughtered cattle aged over 30 months (OTM) intended for human
consumption. This system replaced the OTMS rule prohibiting the sale of
beef for human consumption from OTM cattle. This scheme deals with
dairy cattle that have reached the end of their productive lactations, old
bulls, herd casualties and any other beasts.
Cattle identification and tracing
All cattle born or imported into the UK after September 1998 are registered
on a national cattle tracing system managed and operated by the Department
for Environment, Food and Rural Affairs (DEFRA). All movements of any
particular beast are documented from birth until death. Each individual
beast has a full passport on which the data are entered. All cattle are also
numerically ear tagged to comply with European Commission regulations,
making tracing easier.
Feed controls
Mammalian-derived meat and bone meal (MMBM) is outlawed from inclusion in ruminant feeds, and all feed mills and farms have had to be cleaned
to remove any previous contamination from feed in which MMBM might
have been present. A continuing inspection programme is coordinated by
DEFRA. Feed is regularly inspected and sampled to ensure compliance.
Bull semen
The use of semen from infected bulls was identified as a possible method for
introducing BSE into a country or herd of cattle previously certified as
disease free. Following measures instituted by DEFRA to ensure that only
disease-free semen was available, the export ban of this material was lifted to
the European Union in 1996, and to other countries as bilateral agreements
were reached based on guarantees of disease-free status. These are now in
place in the USA, Canada, South Africa, Australia and New Zealand. The
continuance of all these agreements hinges on no cases arising in cattle sired
by exported semen.
Exported and imported meat
Regulations are now in place that prohibit the export or import of beef, or
beef products, which are not certified free of BSE. The penalties and fines
156 | Zoonoses
applicable to persons or organisations that break the rules are heavy,
including fines of up to £5000 and up to 2 years’ imprisonment. Any products detected as breaching the regulations are destroyed. Secondary prosecutions in the EU and other states are also possible. Meat for export must
be accompanied by a valid Export Health Certificate, issued in accordance
with the provisions of the Products of Animal Origin (Import and Export)
Regulations 1992. Heavy fines are imposed for breaches of the regulations
in conjunction with destruction of the produce. All exports of beef are
deboned before dispatch under the provisions of the Date Based Export
Scheme (DBES). The EU ban on exports of cattle and bovine products from
the UK was lifted on 2 May 2006 and the UK BSE controls are now identical
to those in other EU member states.
Offspring cull
To arrest the arrival in the adult cattle herd of calves born from cattle diagnosed with BSE, all suspect offspring have to be slaughtered. This eradication
and slaughter programme was a prerequisite for the resumption of beef
exports from the UK.
Specified risk material
Specified risk material (SRM) is controlled both by law in the UK and under
a decision of the European Commission in Europe. Pithing is also to be
outlawed both within the European Community and by import control in
all countries wishing to export to the European Community. The measures
aim to prevent material entering not only the human food chain but also
animal feed, fertiliser or other cattle-derived materials. SRM may not be fed
to any animal, nor may MMBM be incorporated in agricultural fertiliser.
Controls on SRM prohibit the use of certain specified animal products that
are known to harbour, or might theoretically harbour, the causative prion.
The future for vCJD
It is still uncertain what the future will hold in terms of case numbers;
however, it is now seen as unlikely that there will be mass fatalities, although
a few confirmed cases are expected annually.15
Situation in the USA
In December 2003, a single cow was diagnosed with BSE in Washington
State. Precautions were taken to prevent meat derived from the carcass
entering the food chain. The cow was traced back to a Canadian herd.
Following this case, the US Department of Agriculture (USDA) announced
a number of measures to further minimise the possibility of contaminated
meat entering the food chain, including banning the use of ‘downer’ cattle
(i.e. cattle found that are unable to rise) from being slaughtered for meat. In
Prion diseases | 157
addition the Food Safety and Inspection Service (FSIS) requires SRM to be
removed from all cattle aged over 30 months at slaughter.16
BSE surveillance was initiated in the USA in 1990, but this was the first
case identified in the USA. The feeding of rendered cattle products to other
cattle has been prohibited since 1997, and the importation of cattle and
cattle products from countries with BSE or considered to be at high risk for
BSE has been prohibited since 1989; these measures have minimised the
potential exposure of animals and humans to the BSE agent.
In June 2005, the USDA confirmed BSE in an approximately 12-year-old
cow born and raised in Texas. This was the first indigenous BSE case in the
USA.
Imported human case
In October 2002, a clinical case of vCJD was seen in a Florida resident, who
had been born and lived in the UK before emigrating to the USA; she died
in 2004. It is assessed that the patient had been infected while in the UK. As
the patient had not donated blood in the USA, or had any major surgery, it
was considered that there were no medical risks that others had been
infected from this case. This case and the proven blood-borne transmission
of vCJD reinforces the necessity for continued surveillance.17
Monitoring
Since 1996, the Centers for Disease Control and Prevention (CDC) have
used several mechanisms to conduct surveillance for classic CJD and vCJD
in the USA. The CDC reviews data relating to cause of death to monitor the
epidemiology of CJD in the USA. The CDC, in collaboration with state and
local health departments, investigates CJD cases in persons aged ⬍55 years
to identify cases of possible vCJD. It routinely provides assistance in the
investigation of suspected cases of vCJD spontaneously reported by healthcare providers. The CDC, in collaboration with the American Association
of Neuropathologists, established the National Prion Disease Pathology
Surveillance Center (NPDPSC). These surveillance efforts have not detected
any cases of indigenous vCJD in the USA.18
In the USA, the risk of blood-borne transmission of vCJD is low because
of the absence of indigenous vCJD and a donor policy instituted by the FDA
in 1999. This policy excludes from donating blood in the USA people who
resided in or had extended visits to the UK or other European countries
during periods of greatest concern for BSE exposure. In 2001, this policy
was expanded to exclude donors who have travelled to other European
countries for an extended period of time since 1980.
Suspected vCJD cases should be reported to local and state health
departments. As the clinical manifestations and age distribution of vCJD
patients can overlap with those of classic CJD patients, a brain postmortem
158 | Zoonoses
examination should be conducted in all such cases to distinguish suspected
or diagnosed vCJD from classic CJD.
Chronic wasting disease
CWD was first described in the USA in the 1960s and classified as a TSE in
1978. Previously localised to a contiguous endemic area in north-eastern
Colorado and south-east Wyoming, since 2000, CWD has been found in
free-ranging deer or elk in Illinois, Nebraska, New Mexico, South Dakota,
Wisconsin, and outside the previously known endemic areas of Colorado and
Wyoming. CWD has also been identified in captive deer or elk in Colorado,
Kansas, Minnesota, Montana, Nebraska, Oklahoma, South Dakota and
Wisconsin. Concern has been raised about the possibility that the prion
associated with CWD might be transmitted to humans in a similar way.19
In February 2003, a retrospective study identified that there was a possibility that three individuals who had died of degenerative neurological
disease had also participated in wild game feasts. Although two of the
patients were found to have died of CJD, no evidence was found that this
was associated with the consumption of meat contaminated with CWD. A
previous investigation of unusually young CJD patients in whom the transmission of CWD was suspected also did not provide convincing evidence for
a causal relationship between CWD and CJD. Subsequent investigations
have not identified links between other cases of CJD-type illness and the
consumption of venison; however, there is a need for continued surveillance.
It is recommended that venison derived from animals with evidence of CWD
is not consumed by humans, or animals.20
Useful addresses
There are a large number of organisations that now monitor CJD and vCJD
across the world. The addresses given in Appendix 2 are solely as examples.
References
1. Zerr I, Brandel JP, Masullo C et al. European surveillance on Creutzfeldt–Jakob disease:
a case–control study for medical risk factors. J Clin Epidemiol 2000; 53: 747–54.
2. Anonymous. Report of the BSE Inquiry. London: The Stationery Office, 2000.
3. Andrew NJ. Incidence of vCJD disease diagnoses and deaths in the UK January
1994–December 2007. Statistics Unit, Centre for Infections, HPA January 2008
4. Garske T, Ward HJT, Clarke P, Will RG, Ghani AC. Factors determining the potential for
onward transmission of variant Creutzfeldt–Jakob disease via surgical instruments. J R Soc
Interface 2006; 3: 757–66.
5. Will RG, Ironside JW, Zeidler M et al. A new variant of Creutzfeldt–Jakob disease in the
UK. Lancet 1996; 347: 921–5.
Prion diseases | 159
6. St Rose SG, Hunter N, Matthews L et al. Comparative evidence for a link between Peyer’s
patch development and susceptibility to transmissible spongiform encephalopathies.
BMC Infect Dis 2006; 6: 5.
7. MacLeod MA, Knight R, Stewart G, et al. Sensory features of variant Creutzfeldt–Jakob
disease. J Neurol Neurosurg Psychiatry 2000; 69: 413–14.
8. Collins SJ, Lawson VA, Masters CL. Transmissible spongiform encephalopathies. Lancet
2004; 363: 51–61.
9. Will RG, Zeidler M, Stewart GE et al. Diagnosis of new variant Creutzfeldt–Jakob
disease. Ann Neurol 2000; 47: 575–82.
10. Todd NV, Morrow J, Doh-ura K et al. Cerebroventricular infusion of pentosan
polysulphate in human variant Creutzfeldt–Jakob disease. J Infect 2005; 50: 394–6.
11. Barret A, Tagliavini F, Forloni G et al. Evaluation of quinacrine treatment for prion
diseases. J Virol 2003; 77: 8462–9.
12. Otto M, Cepek L, Ratzka P et al. Efficacy of flupirtine on cognitive function in patients
with CJD: a double-blind study. Neurology 2004; 62: 714–18.
13. Minor PD, Will RG, Salisbury D. Vaccines and variant CJD. Vaccine 2000; 19: 409–10.
14. Llewelyn CA, Hewitt PE, Knight RS et al. Possible transmission of variant
Creutzfeldt–Jakob disease by blood transfusion. Lancet 2004; 363: 417–21.
15. Ghani AC, Donnelly CA, Ferguson NM, Anderson RM. Updated projections of future
vCJD deaths in the UK. BMC Infect Dis 2003; 3: 4.
16. Centers for Disease Control and Prevention. Bovine spongiform encephalopathy in a
dairy cow – Washington state, 2003. MMWR 2003; 52: 1280–5.
17. Belay ED, Sejvar JJ, Shieh W-J et al. Variant Creutzfeldt–Jakob disease death, United
States. Emerg Infect Dis 2005: 11; 1351–4.
18. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of
emerging forms of Creutzfeldt–Jakob disease in the United States. Neurology 2003; 60:
176–81.
19. Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic
wasting disease and potential transmission to humans. Emerg Infect Dis 2004; 10:
977–84.
20. MacWhinney S, Pape WJ, Forster JE, Anderson CA, Bosque P, Miller MW. Human prion
disease and relative risk associated with chronic wasting disease. Emerg Infect Dis 2006;
12: 1527–35.
6
Pandora’s box
Pandora was the first woman to be created, fashioned from clay by
Hephaestus at the request of Zeus. She was given every advantage by
the gods that they were able to grant. Zeus then gave her a box to
present to the man who married her. He planned to destroy man, who
had been created by Prometheus, by giving a man Pandora as a wife.
Knowing that Prometheus would be too wise to accept the gift, Zeus
persuaded his less cautious brother Epimetheus to marry her. Later
Pandora, against the instructions of the gods, opened the box and let
loose upon the world all evils and diseases. In the bottom of the box
only Hope remained.
Ancient Greek myth
Introduction
Most of the zoonoses already discussed in this volume lead to death only in
an infected human after a prolonged untreated infection. The zoonoses
discussed in this chapter are less benign. Their very names – anthrax, Ebola,
plague and rabies – carry an echo of evil. This may be only a fantasy or a
folk memory, yet the facts speak for themselves. Once infected, and they
tend to be highly infective and pathogenic, the levels of associated mortality
are higher than with other zoonoses, especially if treatment is delayed once
symptoms appear.
Their impact having been dramatised in a variety of media, this chapter
aims to realistically answer some of the questions relating to how dangerous
these infections are, what their mortality statistics are and what treatments
are available.
Although not endemic in the UK, all of these diseases could appear here
carried by fomites, animals or humans, depending on their mechanism of
spread. If robust measures were not put in place rapidly on the appearance
of an initial case, a pestilence of biblical proportions could ensue. It is not
Pandora’s box | 161
for nothing that one of the horsemen of the apocalypse is named as pestilence
or plague.
In the USA, rabies, although rare in humans, is widespread, and plague
is found in natural reservoirs in some states. Anthrax is endemic in both the
UK and the USA, although, due to industrial and domestic precautions, few
clinical cases occur.
The UK is afforded some degree of protection by its temperate climate,
geographical isolation and quarantine system. The system of quarantine has
afforded comprehensive protection against rabies for many years, and the
advent of a well-regulated system of pet passports has not compromised that
system. The system cannot, however, quarantine human beings except in rare
and exceptional circumstances, nor do all arrivals to our country – be they
animal or human – stop at the immigration office on the way in, nor is it
possible to tell if they are infected if they do. Migrating birds are believed to
have been responsible for the outbreak of West Nile virus in New York,
which killed eight people between September 2000 and September 2001, and
has now spread across virtually the whole of the North American continent.
Similarly, the current pathogenic strain of avian influenza – H5N1 – which
has already killed millions of birds and some humans, and could under suitable circumstances cause a human pandemic, may be triggered by similar
events. The case of the swan that died in March 2006 in Scotland emphasises
well that wild birds do not stop at borders for a health check.
In the past, bubonic plague was introduced into the UK by rats from
ships, and the outbreak known as the Black Death began with the first cases
being seen at Melcombe in Dorset. The likelihood of a recurrence of plague
from such a source is reduced by inspections and mandatory fumigation of
vessels as well as the system of public health measures aimed at controlling
rodent populations. Nevertheless there still remains a risk, and the price of
safety is constant vigilance. Part of any system of vigilance has to be the
education of healthcare professionals in the signs and symptoms associated
with these diseases and this chapter aims to forward that objective.
It is not only animals and humans that travel today; goods are transported from far and near to fuel the appetite of our domestic market.
Fomites transfer or objects contaminated with spores are particularly
important in the transmission of anthrax. Recently the importation by both
tourists and commercial companies of items made from goatskins in Haiti
and the Dominican Republic has been banned because these items have been
shown to be contaminated with anthrax spores. It is believed that the illegal
import of infected skins, which he later turned into drum skins, led to
serious illness in a drummer, Vado Diomande, in New York in February
2006, and may have been related to the death of another man who was also
a drum maker in Scotland in a separate incident in October 2006.
162 | Zoonoses
There is another dimension to several of the diseases examined in this
section. Biological warfare and bioterrorism have been the subject of a wide
debate in modern society. The use of infectious disease in warfare, in either
conventional or asymmetrical conflicts, has a long and less than glorious
history, ranging from the catapulting of dead animals and humans into
besieged strongholds by our ancestors, to the possibility of missiles loaded
with anthrax being fired in recent, or future, conflicts. Biological warfare is
banned by international treaty, and enforced by United Nation’s inspection.
However, as the anthrax attacks of 2001 in the USA have shown, this is not
sufficient to prevent individuals or states pursuing this route in the hope of
causing casualties to their adversaries. Some of the organisms discussed in
this chapter have the potential to be biological agents for weapons of mass
destruction and also to be used by terrorists. The aim of this chapter is to
be realistic in the assessment of their potential, to dispel some of the wilder
journalistic assertions and to give some understanding of the healthcare
implications.1
Anthrax
Malignant pustule, woolsorter’s disease, charbon, malignant oedema,
splenic fever
Anthrax is an acute bacterial disease of animals and humans which can
cause rapid fatality (hence the old English name of ‘struck’ for the disease in
cattle). It is caused by Bacillus anthracis, a Gram-positive, encapsulated,
spore-forming bacterium that spores rapidly on contact with oxygen. When
cultured it produces dense colonies on agar with long chains of bacteria
forming so-called ‘medusa-head colonies’ from their shape and appearance.
This disease occurs worldwide and is an occupational hazard for those
involved in processing the wool, hide, hair or bones of animals, such as
farmers, slaughterers, skinners, hideworkers, tanners and woolworkers.
Most mammals are susceptible to the disease. It is most commonly seen in
cattle; goats, sheep, horses and pigs can also contract the disease.
Anthrax is a notifiable disease in the UK and the USA. Notification also
applies to animals suspected of having died of the disease. Carcasses must
be disposed of by burning or by liming followed by deep burial. Definitive
diagnosis is not always possible because opening or moving suspect
carcasses is also prohibited.
In the UK, the disease is rare. The last case before that of an amateur
drum maker in Scotland in July 2006 (see case studies) occurred in
November 2001 after a man involved in the animal hide trade was diagnosed as having the cutaneous form. After treatment he survived. There
were a total of 14 cases of cutaneous anthrax confirmed in the UK between
1981 and 2000. Many of those affected were involved in the handling of
Pandora’s box | 163
dead animals, such as abattoir workers, or those whose work involved
handling animal hides, bonemeal or wool.2
In the USA, before the cluster of cases associated with malicious contamination of mail in 2001 (see below), industrial processing of animal hair or
hides was associated with 153 (65%) of 236 anthrax cases reported to the
Centers for Disease Control and Prevention (CDC) in the period between
1955 and 1999. Of the remainder, products made from animal hair or hides
accounted for an additional five (2%) cases. Of the total of 158 cases, the
majority presented with the cutaneous form of the disease, with only 10 being
inhalational anthrax. Many of the non-fatal cases in the USA associated with
the handling of contaminated mail have also been of the cutaneous form (see
Case history below).
An outbreak in 1979 at Sverdlosk, Russia, was later admitted by the
Russian Government in November 2001 to have been related to an accidental release from a biological weapons research facility. Sixty-eight people
died, although the authorities claimed at the time that the cases resulted
from the ingestion of poorly cooked infected meat.3
A large outbreak in Zimbabwe from October 1979 to March 1980
caused more than 6000 (mostly cutaneous) cases. In Paraguay, 25 cutaneous
cases were seen in 1987 after the slaughter of an infected cow. Currently the
Department of Health (DH) considers South and Central America, southern
and eastern Europe, Asia, Africa, the Caribbean and the Middle East as areas
where the disease may occur in significant amounts.
There are sporadic occasional cases, in isolation or in clusters across
eastern Europe, the Balkans and Turkey, usually associated with consumption
of meat harvested from infected carcasses.
Disease in animals
Anthrax in animals often follows the grazing of pasture infected with viable
spores. Symptoms in animals are usually acute, with high fever of sudden
onset, localised swellings and profuse bleeding from orifices. Death usually
occurs 24–72 hours after onset. Animals may be found dead or moribund.
In the USA, anthrax is endemic, with cases being reported on a regular
basis, e.g. in September 2005, the Journal of the American Veterinary
Medical Association reported that anthrax had been found in the states of
South and North Dakota and Texas in the preceding months.4 In South
Dakota Animal Industry Board a group of almost 300 unvaccinated buffalo
and rodeo bulls were believed to have been exposed to anthrax after grazing
on contaminated pasture, with approximately 40 of the animals being found
dead. The remainder of the herd were treated with antimicrobials, vaccinated
and the carcasses safely disposed of.
164 | Zoonoses
Concurrently in the south-east of North Dakota, anthrax was detected
at in excess of 20 locations, with confirmed cases in cattle, horses, bison and
farmed elk. All surviving animals in the herds containing infected animals
were quarantined and vaccinated.
The spores are resistant to a wide range of climatic conditions and can
remain in contaminated ground for many years. In one reported incident
from Hawaii, a cow died after grazing a pasture where the carcass of a cow
suspected of having died of the disease 20 years previously was buried.
Animals may also demonstrate in-species spread from infected meat or by
close contact with an infected beast.
In April 2006, two cattle were confirmed as having died of anthrax on a
farm in Rhonda Cynon Taff, South Wales, where there had been a previous
outbreak 35 years before. Five cattle had also died in the previous month;
however, the last two carcasses were the first to test positive for anthrax. No
cattle from the farm had been sent for slaughter into the food chain for the
previous 12 months. The source was identified as a pool on the farm, which
is believed to have become contaminated.
Transmission
The spores present in the animal’s blood or secretions, infected pastures,
hides and bone or meat. Transmission to humans follows contact with these
spores.
Disease in humans
The disease presents in distinct forms in humans depending on the route of
infection. These are:
• Cutaneous, following physical contact with spores and their
subsequent inoculation into wounds or abrasions
• Pulmonary, following inhalation of spores from infected hides
• Intestinal, following ingestion of spores or organism in undercooked
meat from infected carcasses.
Infected individuals display the disease after a variable incubation period
depending on route of infection. The cutaneous form develops after 2–10 days,
the pulmonary after 1–5 days and the intestinal after 2–5 days.
The cutaneous form, once known as malignant pustule, is responsible for
98% of cases worldwide. After the incubation period, a papular spot
develops on the skin. This papule becomes vesicular and turns black in the
centre. This forms an eschar (a plug of dead tissue, skin and blood) which
causes necrosis of the underlying tissue and then sloughs off. There is very
little pain or tenderness associated with the condition, although local lymph
Pandora’s box | 165
nodes usually swell. Extensive oedema affecting the whole limb or upper
body is often seen and is important in differentiating the disease from tickborne disease where an eschar may also be present. Some patients will
display fever, lethargy, sickness and severe headache. The skin lesion will
often heal without treatment, but there is a 5–20% risk of untreated cases
progressing to septicaemia or meningitis with fatal consequences after the
eschar sloughs. Cutaneous spread to other people is possible.
In December 2004, a 31-year-old female Belgian traveller developed a
cutaneous anthrax lesion on one finger following contact with dead antelope
and a hippopotamus while touring South Africa.5
Pulmonary anthrax, known as woolsorter’s disease, follows inhalation of
spores from infected hides or wool. It presents as a flu-like illness after the
incubation period, followed by cough and severe shortness of breath. This
develops into respiratory failure and can be fatal within 24 hours, usually
following septicaemic spread.
All of the fatal cases seen in the US terrorist attacks during 2001 were
from the pulmonary form. Before the extensive number of cases seen in this
incident, this form of the disease was believed to be fatal in all cases regardless of the rapidity with which treatment was commenced. This has proved
erroneous, with death occurring in only 40% of cases.6 There are still no
known cases stemming from pulmonary spread from existing patients to
other individuals, although precautions have been taken to prevent such an
eventuality.
Intestinal anthrax follows ingestion of infected meat. The rarity of the
condition is related to the low incidence of the disease in meat in developed
countries, and the unlikely nature of ingesting enough viable spores or
organisms to cause disease.
Severe copious diarrhoea occurs after the incubation period. Half of
untreated cases will die.
Diagnosis
Identifying the causative organism in blood smears is diagnostic. Growing
samples on standard culture media leads to the development of characteristic colonies, with the bacterium showing centrally placed spores.
Immunofluorescent and enzyme-linked immunosorbent assay (ELISA)
techniques can also be used.
Treatment
In the UK, the Health Protection Agency (HPA) makes the following recommendations for the treatment of anthrax. The antibiotics of choice are
ciprofloxacin and doxycycline. Later therapy may be switched to amoxicillin
166 | Zoonoses
if the infective strain is susceptible. Cephalosporins must not be used because
they are ineffective.
As with any other therapy, the latest recommendations from the DH or
HPA should be checked before initiating therapy. It should be noted that
ciprofloxacin is not licensed for use in children or pregnant women, but
may be indicated in life-threatening illness, and also that doxycycline is
not recommended in childhood or pregnancy; however, its use would be
considered in a serious infection such as anthrax.
Where a diagnosis of infection by anthrax is suspected due to clinical
signs or patient history, an early initiation of therapy before laboratory
confirmation may be required to reduce fatalities. Usually a short course
(3 days) of ciprofloxacin is used until blood culture results become available.
It should be noted that, in this case, other likely causes of acute respiratory
illness need to be investigated and treated concurrently.
In cases of inhalational and ingestional anthrax, ideally drug therapy
should be administered intravenously initially. As the patient improves and
once the drug sensitivity of the bacterium is identified, treatment can be
continued using oral antibiotics.7
In addition to ciprofloxacin, there is some evidence that additional antibiotics or vaccination may be incorporated into a multidrug antibiotic regimen
and that this can reduce mortality in inhalational anthrax.8 In anthrax
meningitis, moieties with good central nervous system (CNS) penetration
are essential additions, with penicillin, ampicillin, meropenem, vancomycin
and rifampin being proposed as suitable. Corticosteroids have been used
concomitantly to reduce cerebral oedema in some cases.9
The detailed HPA recommendations as of December 2008 are as follows.
Inhalational/ingestional anthrax
• Adults (including pregnant women):
– ciprofloxacin 750 mg i.v. every 12 h (750 mg twice daily by mouth
when appropriate)
– or doxycycline 100 mg i.v. every 12 h (100 mg twice daily by
mouth when appropriate)
– plus one or two additional antibiotics (agents with in vitro activity
include rifampicin, vancomycin, gentamicin, chloramphenicol,
penicillin, amoxicillin, imipenem, meropenem and clindomycin).
• Children:
– ciprofloxacin 10 mg/kg i.v. every 12 h, with the total dose not to
exceed the adult dose of 1500 mg/day (when changing to oral
therapy if appropriate, dosage is to be altered to 15 mg/kg by
mouth, not to exceed the adult dosage of 1500 mg/day)
– or doxycycline initiated intravenously and then changed to oral
therapy when appropriate dosages are
Pandora’s box | 167
orally – older than 8 years and weighing more than 45 kg: 100 mg
every 12 h
intravenously – older than 8 years: 2.2 mg/kg every 12 h
– plus one or two additional antibiotics (agents with in vitro activity
include rifampicin, vancomycin, gentamicin, chloramphenicol,
penicillin, amoxicillin, imipenem, meropenem and clindamycin).
• In all cases, both adults and children, therapy should be continued for
60 days.
Cutaneous anthrax
Treatment as in inhalational anthrax is normally using ciprofloxacin or
doxycycline as first-line therapy. Unlike inhalational anthrax, treatment can
be initiated in adults with oral ciprofloxacin 750 mg or doxycycline 100 mg
twice daily for 7 days. If later the organism is found to be susceptible, or the
patient cannot tolerate fluoroquinolones or tetracyclines, this can be changed
to oral amoxicillin 500 mg three times a day.
For children, the doses of ciprofloxacin or doxycycline follow the same
oral regimen as that already detailed for inhalational anthrax. If using
amoxicillin, a total daily dose of 80 mg/kg divided into three equal portions
and given every 8 hours is an option for completion of therapy after clinical
improvement. The oral amoxicillin dose needs to be sufficient to achieve
minimum inhibitory concentration levels.
Where cases of cutaneous anthrax show signs of systemic disease, with
extensive oedema, or lesions on the head or neck, intravenous therapy may
be required, with multidrug therapy being recommended.
If a deliberate release is suspected, treatment may need to be continued
for up to 60 days, so as to provide cover for inhalational anthrax, which
may have been acquired concurrently.
Prophylaxis
In people known to have been exposed to anthrax, and where no clinical
disease is currently present, prophylaxis using antibiotics must be initiated
as soon as possible.
Ciprofloxacin is the current drug of choice for all patients. Ciprofloxacin
is also the drug of choice in prophylaxis against two other biological agents
that could be deliberately released, plague and tularaemia, so its use covers
the risk in advance of laboratory testing and identification. The risk of
adverse effects associated with administration of antibiotic prophylaxis has
to be weighed against the risk of developing a life-threatening infection. The
prophylaxis should continue for 60 days to cover the prolonged latency
period possible before germination of inhaled spores.
168 | Zoonoses
In the UK, usually only 5 days’ supply of ciprofloxacin is initially made
to individuals, especially in an incident believed to be a deliberate release, in
accordance with DH guidelines, and the emergency drug ‘pods’ deployed by
the HPA. After the initial treatment with ciprofloxacin, doxycycline may be
substituted to complete the 60-day prophylaxis, this needs to be supplied
through local prescribing or dispensing systems. There are patient group
directions (PGDs) in place for the initial and further supply of ciprofloxacin
and the further supply of doxycycline in the event of exposure to a suspect
biological agent (details may be found on the DH/HPA websites).
Made under Article 7 of the Prescription Only Medicines (Human Use)
Order 1997 (the POM Order) PGDs make it legal for medicines to be given
to groups of patients, e.g. in a mass casualty situation, without individual
prescriptions having to be written for each patient. This empowers staff other
than doctors (e.g. paramedics, pharmacists and nurses) to legally give the
medicine, but only in accordance with the detailed provisions of the PGD.
If anthrax exposure is confirmed, and the organism is identified as being
susceptible to penicillin, prophylaxis may be continued using oral amoxicillin
as an alternative to ciprofloxacin or doxycycline.
The detailed HPA recommendations as of December 2008 are:
• Adults (including pregnant women), initial (5-day) therapy:
– ciprofloxacin 500 mg orally twice a day followed by a further
(55-day) therapy of either ciprofloxacin 500 mg or doxycycline
100 mg orally twice daily
– if the strain is found to be susceptible, amoxicillin 500 mg orally
three times a day may be substituted.
• Children, initial (5-day) therapy:
– the dose of ciprofloxacin is age and weight dependent, with the
recommendation being that newborn babies up to the age of 6
months receive 100 mg/day in divided doses, and older children
receive 15 mg/kg orally twice a day (dose not to exceed 1 g/day,
i.e. adult dosage) followed by a further (55-day) therapy of either
ciprofloxacin at the same dosage or doxycycline
– only if older than 8 years and weighing more than 45 kg, at a dose
of 100 mg orally every 12 h
– if the strain is susceptible, amoxicillin may be substituted at a rate
of 80 mg/kg per day, in three divided doses (not to exceed 500 mg/
dose).
In the USA, ciprofloxacin was the primary antibiotic used during the
outbreak in 2001 in the USA, with doxycycline and amoxicillin being used
only if a contraindication to fluoroquinolones existed. Combination therapy
was also used.
Pandora’s box | 169
The current CDC recommendations are similar to those of the HPA, with
in addition, levofloxacin now being approved by the US Food and Drug
Administration (FDA) for prophylactic therapy for B. anthracis exposure.10,11
In Europe, BICHAT (Task Force on Biological and Chemical Agent
Threats) have made similar recommendations.12
Prevention
A vaccine derived from a cell-free filtrate of killed bacteria is available and
licensed for human use in the UK. Supplies are kept by the HPA and usually
issued for use in workers considered to be at a high occupational risk. The
vaccination regimen consists of three doses given over a period of 6 weeks
with a booster dose given after 6 months. An annual booster is necessary to
maintain immunity. A vaccine is also available for animals, but it is only for
emergency use and is obtained through the Department for Environment,
Food and Rural Affairs (DEFRA).
Physical prevention methods are based on preventing or limiting contact
with infected animals or their hides, hair or meat. All surface wounds
should be disinfected and covered. Physical disinfection of hides and hair is
considered to be good practice in the tanning and wool industry. The use of
formaldehyde as a disinfectant is carried out by specialist companies for
imports of hide, bones and bonemeal (much reduced in volume since the
advent of bovine spongiform encephalopathy (BSE)) and wool. Heat treatment is also used. Animals suspected of having died of the disease are to
be handled in accordance with biohazard procedures. Suitable protective
clothing and filtered ventilation helmets should be worn.
Spores may be killed by heat with autoclaving or boiling infected materials
or instruments where appropriate. In areas where anthrax is endemic, meat
should be thoroughly cooked or avoided.
Formaldehyde and glutaraldehyde are effective disinfectants for dealing
with local contamination and spillages, although it is recommended that
clothing and other articles of victims should be incinerated carefully.
Cases associated with drum makers
Vado Diomande, a dancer and drum maker, domiciled in New York, but
originally from the Ivory Coast, was hospitalised and then diagnosed with
inhalational anthrax in February 2006. He appears to have become infected
from spores present on hides that he had imported into the USA from West
Africa to make his own drumskins. Diomande may have inhaled the spores
when, after soaking and stretching them, he scraped the hair off the hides.
He was also working untreated hides purchased from US suppliers at the
same time, so the source cannot be accurately determined. After extensive
170 | Zoonoses
antibiotic therapy he survived. Most of the contents of his workshop and
apartment were removed and destroyed by public health officials in the
ensuing decontamination operation. Close associates were tested for the
disease and given antibiotic prophylaxis.13
In July 2006, a Scottish artist who lived in Hawick, Scottish Borders,
died of anthrax. This was the first fatal case of anthrax in the UK for 30
years, with the previous fatality occurring in 1971. The victim, Christopher
‘Pascal’ Norris, apparently became infected after he used infected, imported,
untreated animal hides to make drum skins. The hides were scraped and
worked in a manner that could produce aerosols of infected matter. He
developed a rapidly progressive septicaemia and subsequently died. He had
previously been treated for cancer, and it is possible that the progress of the
disease was increased due to his impaired immune system. It was only
retrospective testing of postmortem samples that identified the causative
agent as anthrax, and by then his body had been cremated.
His house was quarantined, and had to be systematically decontaminated. Most of his close friends and relatives had to be screened for infection,
as a wake was held in the house after the funeral, with guests being
encouraged to take away items as keepsakes.
Another case in late 2008 led to the death of another drum maker/
drummer in the East End of London.
These were not the first cases associated with the conversion of untreated
animal hides into drum skins, with a similar case being recorded in Florida
in 1974.
In 2001, a woman was hospitalised in Vancouver, British Columbia,
Canada, with cutaneous anthrax on the palm of her hand, which she
contracted while handling animal hides during a drum-making class.
Potential as a biological warfare agent
Anthrax can be cultured successfully and its spores harvested. The spores can
then be turned into a dry powder. During World War I, the Germans
produced sugar lumps inoculated with anthrax for feeding to allied draught
horses. There were also incidents of bags of powder containing anthrax
spores being dropped from German aircraft. In 1942–3, the British
conducted trials on Gruignard Island off the north-west coast of Scotland to
investigate the feasibility of biological warfare using anthrax. (The island was
finally declared safe in 1990.) In an associated programme, Britain developed
cattle cakes inoculated with anthrax for retaliatory strikes against Germany.
These were to have been dropped from bomber aircraft in the event of a
German strike. In Germany warheads containing anthrax were developed for
attachment to V1 and V2 weapons. The escalation of hostilities that such
weapons would have caused led to neither side employing them offensively.
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In Japan, during the 1990s, the Aum Shinrikyo cult released anthrax
spores in Tokyo. Luckily there were no fatalities. Following the Iran–Iraq
war and the Gulf War, Iraq was shown to have produced shells and missile
warheads packed with spores.
Many authorities view anthrax as the greatest threat for use in biological
warfare or terrorism. With the cases caused by contaminated mail in the
USA in the aftermath of the events of 11 September, it has become apparent
that as a terrorist weapon it has a tremendous potential to cause widespread
concern with some fatalities, even when the potency has not been enhanced
by finely grinding the powder containing the spores.
Amerithrax: the 2001 cases in the USA
In September and October 2001, there were a cluster of cases of cutaneous
and inhalational anthrax, after maliciously contaminated mail was sent
through the US Postal Service to addressees in the US Congress, US government departments, prominent journalists and other media figures across the
USA (Florida, New York, Washington, New Jersey).14
Initial diagnosis of patients was slow; however, once it was recognised
that a bioterrorism attack using anthrax spores had occurred, tracing and
screening were initiated.15 There were 22 cases, of whom 19 were confirmed
and 3 classed as probable, with 5 being fatal. Cases were seen in people
directly exposed to the contaminated letters, and indirectly by secondary
spread from sorting machines, or other post that was passing through the
mail facilities at the same time as the contaminated letters.
All the contaminated mail contained powder containing anthrax spores
The four letters that were recovered during the investigation also contained
notes, purporting to be from Islamic extremists, although this was later
dismissed as misdirection by the perpetrator. It is believed that seven letters
were sent in total; however, the other three have never been found.
Following detection of cases, work places where the letters had been
handled were screened for contamination, and then decontaminated. All
workers were tested for exposure, and given antibiotics (ciprofloxacin,
doxycycline or amoxicillin) as either treatment or prophylaxis; however, in
the cases of some postal workers and other victims this was not initiated
rapidly enough to prevent fatalities. Some suspected cases were never
confirmed as the bacterium could not be isolated from initial samples and,
as antibiotics were given on a precautionary basis, re-testing was negative.
Some of the fatal cases were sporadic (i.e. not linked to direct exposure
to the contaminated letters), with one in a healthcare worker apparently
after secondary exposure to infected clothing in a hospital emergency room,
and another (an elderly woman in Connecticut) being notionally linked to
mail contaminated by passing through a sorting machine at the same time
as one of the deliberately contaminated letters.16
172 | Zoonoses
A criminal investigation was launched by the FBI; however, it was
initially hampered by the need to focus on the events following the 9/11
attack on the World Trade Centre and the Pentagon. With the strain
identified as one normally associated with scientific establishments, the FBI
focused on using profiling to try to identify suspects. To date nobody has
been charged in relation to the attack.
Facilities contaminated included mail offices, sorting offices and other
premises. The clean-up to date has cost many millions of dollars, and it has
been difficult to agree the level of decontamination required by workers’
unions to allow premises to re-open.
Before and since the Amerithrax incident, there have been a number of
hoax letters containing powder across the world, notably in Canberra in
2005 and again in 2008, against the Church of Scientology in the USA
in 2006 and 2008, and by anti-abortionists in the USA and Canada, a
campaign that pre-dated the Amerithrax incident; there has been a total of
655 letters to date, including 554 mailed by one US activist in November
2001. The aim in all these incidents, none of which to date has contained
anthrax, seems to be to cause the maximum amount of disruption while
making a political or ethical point. The costs of dealing with such incidents
are high, requiring specialist staff and equipment to contain, identify and
control possible contamination.
Ebola
African haemorrhagic fever; Ebola haemorrhagic fever
Ebola is probably one of the most dramatic zoonotic infections. It is caused
by a virus similar in form to Marburg virus but distinguished by differences
in antigen testing profile. The virus is named after a river in The Democratic
Republic of the Congo (DRC; formerly Zaire). Classified as an RNA
filovirus, it shows strange branching and filamentous forms displayed by no
other viral group. There are four subtypes of the virus. The three demonstrated to be pathogenic in humans are Ebola–Ivory Coast, Ebola–Sudan
and Ebola–Zaire. The fourth, Ebola–Reston, has been shown to be pathogenic in apes but not for infected humans. This last type was identified in
monkeys imported from the Philippines into Italy and North America for
laboratory use. Several research workers became infected with the virus,
although none became ill.17
Ebola haemorrhagic fever was first recognised in 1976, when large
outbreaks occurred in southern Sudan and neighbouring northern Zaire.
Since then it has appeared sporadically in these and other areas of Africa.
There has been only one case recorded outside Africa with a single non-fatal
case in a laboratory in the UK after a needlestick injury. The pathogenic
forms of the virus are not known to be native to other continents.
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Transmission
The natural reservoir of Ebola virus is not proven fully; however, it has been
detected in three species of fruit bats. Scientists from the Institut Pasteur,
Paris, have also detected it in small rodents in the Central African Republic.
There is still work to be done to discover how the virus is transmitted to
apes and monkeys, which have previously been identified as the link to human
infection. The handling of ill or dead infected chimpanzees was shown to be
the source of human infection in outbreaks in the Ivory Coast, Gabon and
the DRC.18,19
The main concern for countries outside Africa stems from the latent
period of the infection. In theory it would be possible for an infected
individual to carry the disease into a city or country where, unrecognised,
the disease could rapidly spread. Mortality rates have been as high as 90%
in some outbreaks so the fear is not unfounded.
Disease in humans
The virus has an incubation period of between 2 and 21 days after exposure and infection in humans before clinical signs are seen. Weakness and
lethargy follow a sudden onset of fever with a temperature as high as 39ºC.
Muscle and joint pain are seen in most cases, with sore throat, headache
and occasionally hiccups. More severe symptoms follow with anorexia,
nausea, vomiting and diarrhoea. The development of a severe skin rash and
mental confusion is concurrent with the progression of the illness. Kidney
and liver damage occurs and catastrophic internal and external haemorrhage leads to death towards the beginning of the second week. The virus
is present in high concentrations in the blood, tissue fluids and most organs
of the body. Patients lucky enough to survive require extended periods of
care.
Human-to-human transmission occurs after direct contact with the blood,
secretions or semen of infected patients. Following the first confirmed or
index case, transmission occurs to those in closest contact with the victim.
These can be friends, family or healthcare workers. Nosocomial spread or
spread from a clinic or hospital to staff or other patients has occurred
several times in major outbreaks, leading to high mortality rates. In Africa
limitations on availability of disposable equipment and protective clothing
have also led to transmission. The disease can also be sexually transmitted
through semen up to 7 weeks after clinical recovery. All Ebola virus
subtypes have displayed the ability to be spread through aerosols under
research conditions, although aerosol spread has not been demonstrated
during outbreaks.
174 | Zoonoses
Outbreak statistics
In the first recorded outbreak, between June and November 1976, the
Ebola virus infected 284 people in Sudan, with 117 deaths. During the
outbreaks 76 of the 230 staff at Maridi Hospital contracted Ebola fever,
with 41 subsequently dying. In Zaire (now the DRC) there were 318 cases
and 280 deaths in September and October 1976.
There was an isolated case in the DRC in 1977 and a second outbreak
in Sudan in 1979. One human case of Ebola haemorrhagic fever and several
cases in chimpanzees were confirmed in the Ivory Coast in 1994 when a
scientist contracted the disease after conducting a postmortem examination
on a wild chimpanzee found dead with signs of haemorrhagic disease.
Fortune favours the foolish and the brave and he spontaneously recovered.
A large epidemic occurred in Kikwit, DRC in 1995 with 315 cases, 244
of whom died. This outbreak was thought to have occurred after the index
case handled a monkey and smoked its flesh.
Ebola virus infections were not reported again until the autumn of 2000
when an outbreak occurred in the Gulu district of northern Uganda. This
was the first outbreak ever documented in Uganda and, by the time that
it was declared over in February 2001, there had been 425 cases, including
224 deaths. Spread had been dramatic both in the community and in
hospitals, with healthcare workers among the dead.
In Gabon, Ebola haemorrhagic fever was first documented in 1994 and
two outbreaks occurred in February 1996 and July 1996, with 37 cases and
21 deaths in Mayibout related to cooking a chimpanzee, and 61 cases and 45
deaths in Booue. Another outbreak occurred in Gabon, and the neighbouring
area of the DRC, between October 2001 and March 2002 with 122 cases, of
whom 96 died.
Since then there have been series of outbreaks in the DRC, between
December 2002 and April 2003, November and December 2003, and May
and June 2005. All of these outbreaks were in the Cuvette Ouest Region of
the DRC. In the 2005 outbreak, only one case was laboratory confirmed
and 11 others epidemiologically linked; of these 12, 9 subsequently died.
Other contacts were monitored for 21 days after the last reported death, but
none was infected.
In 2004, a small outbreak occurred in Sudan with a concurrent measles
epidemic. This confused the differential diagnosis, with the final number of
cases actually attributable to Ebola being revised to 17 cases and 7 deaths.
The latest outbreaks were in 2007 and 2008, in the DRC and Uganda.
The 2007 outbreak in the DRC started in August, and finished in October
with 249 suspected cases and 183 deaths; another outbreak began in
December 2008. The last outbreak in Uganda was between November 2007
and February 2008. There were 149 cases with 37 deaths. Characterisation
Pandora’s box | 175
of the virus in the Uganda outbreak has led to the conclusion that this may
be a new species of Ebola virus, which as yet remains unnamed.
Treatment
There is no therapeutic treatment for the disease. Supportive measures, such
as rehydration by intravenous fluids, blood transfusion, use of nutritional
supplements (again by intravenous route) and management of kidney failure,
can improve the outcome of the disease. Rapid treatment of secondary infections is also very important, especially in the convalescent patient. During the
Kikwit outbreak in 1995, eight patients were given blood donated by
survivors. Seven of the eight patients recovered, probably as a result of the
conferred immunity, although this treatment has not been properly clinically
evaluated.20 Research continues to try to develop a vaccine, and some
progress has been made with experimental protection using a live-attenuated,
recombinant, vesicular, stomatitis virus vector expressing the Ebola virus
glycoprotein.21 This product has been experimentally shown to completely
protect rodents and non-human primates from lethal Ebola virus challenge.22
Prevention
Since 1989, there have been a number of cases of Ebola–Reston, fatal to
monkeys, but so far harmless in humans in quarantine facilities in the USA,
Philippines and Italy, all linked to primates sourced from the facility in the
Philippines where fresh-caught and captive-bred apes were mixed. The
recommendations from the CDC and other responsible bodies are that any
imported apes that have not been bred in captivity must be strictly quarantined. For best practice this should be extended to all primates. Strict
hygiene measures should be employed. Appropriate protective clothing
should be worn at all times.
Suspected Ebola haemorrhagic fever is a notifiable disease in the UK and
the USA, both domestically and to the World Health Organization (WHO).
For healthcare workers strict barrier nursing and the use and careful disposal
of gloves, syringes, needles and dressings are essential. All clinical specimens
have to be handled according to guidelines for extremely hazardous
substances. Immediate disposal of bodies in secure body bags with prompt
burial or cremation is necessary during an outbreak.
Case contacts or individuals exposed in laboratories must be placed
under health surveillance for 3 weeks after their last possible exposure to
infection. If there is the onset of febrile symptoms they must be placed in
strict isolation until diagnostic test results have been obtained.
In Africa, as the infection route is still incompletely understood, prevention of Ebola poses a major problem. Educating healthcare workers and
176 | Zoonoses
others to identify a suspected case early and be able to isolate the patient
with appropriate barrier nursing techniques is seen as the main thrust of
current limitation strategies. The main obstacle to the success of such a
strategy is the availability of sterile materials, protective clothing and
appropriate facilities. Usually once a case has been confirmed by diagnostic
tests an outbreak is already under way.
Plague
The Black Death, Bubonic and Pneumonic plague
Any book about zoonoses would not be complete without a section on
plague, and any section on plague must detail the historical importance of the
ravages associated with the disease. Even today, it is not unusual to see children in the playground singing and acting out ‘Ring-a-ring o’roses, a pocket
full of posies, a-tishoo, a-tishoo, we all fall down’. This anonymous nursery
rhyme, originating in the middle of the seventeenth century, is a graphic and
simple representation of the effects of an outbreak of pneumonic plague. The
importance of rat control is emphasised in the same way, with the telling of
the tale of the Pied Piper of Hamelin.
Historians differ in their view of the worst results of epidemic plague,
and the numbers of casualties quoted for pandemics are probably in legal
terms ‘unsafe’. The widest geographical epidemics are usually known as
pandemics and the consensus of opinion is that in recorded history there
have been three outbreaks that could be thus classified.
The first to spread across Europe started in the sixth century, and was
known as the Plague of Justinian. There were widespread fatalities. This
outbreak was seen as a visitation by God on a sinful people; however, the
religiosity that it engendered was no protection against flea bites and disease.
The outbreak now termed the Second Pandemic, or the Black Death, started
from a natural focus somewhere in Mesopotamia in western Turkey during
the eleventh century. Plague-infected rats and their associated fleas, carried
aboard trading ships, spread the Black Death from Tana in the Crimea,
Ukraine, to Messina in Sicily in 1347. In the ensuing European plague, which
endured up to the end of the seventeenth century, it is variously estimated that
a quarter to a half of the population died as a result of this disease alone. At
the height of the epidemic in the fourteenth century, the effect upon all aspects
of social and international development was profound: large swathes of land
in Europe became uninhabited. The epidemic in the UK in the 1660s, which
caused the Plague of London and other local outbreaks, stemmed from this
pandemic. Although important in British history, it was insignificant in world
terms, with only 70 000 fatalities.
The third and last pandemic occurred during the late nineteenth century.
It owed its rapid spread to commercial shipping, with infected rats
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becoming stowaways on fast steam packets leaving Hong Kong and Canton
in 1894 for many other ports the world over. Within a decade it had spread
to over 70 ports on 5 continents. Coming as it did at a time when scientific
endeavour and disciplines were developing, the bacterium, its association
with rats and the rat flea as a vector were soon identified, allowing prevention
strategies to be put in place.
The disease
The pathogen responsible for plague is Yersinia pestis, a Gram-negative
coccobacillus. A facultative anaerobe, the bacterium is capable of forming
an encapsulated spore swiftly when exposed to the air. The risk of infection
from the spores, which are able to survive under suitable conditions for
prolonged periods of time, is considered to be significant in archaeological
excavations of burial sites.
During World War II, part of the Blitz upon London was aimed at
disturbing the plague pits used for burials during the Plague of London three
centuries previously, in the hope of releasing viable spores into the environment. Had this succeeded, the death toll from this disease, let loose in a city
with increasing rodent numbers, poor sanitation and a displaced human
population, would arguably have been high.
This was not the first use of the disease as a weapon of war. Corpses of
humans and animals that had died of this and other diseases have in the past
been hurled into besieged cities using catapults. This stratagem was used in
the hope and certainty of infecting the garrison from the earliest recorded
incidents of siege warfare until modern times. In 1346 a Tartar army
besieging the city of Kaffa, in what is now Turkey, suffered from plague.
They threw their dead into the city over the walls, and the resulting
epidemic forced the defenders to surrender.
Plague has been identified as a pathogen at the centre of several countries’ programmes of biological warfare development. Russia is known to
have designed for use a genetically manipulated strain. Both North Korea
and Israel are known to have studied the use of this pathogen extensively in
an offensive military role. If employed, the pathogen would be delivered
using an air-borne route, so giving pneumonic plague to victims.
Wild foci
Wild plague foci, where suitable rodent populations and habitat conditions
exist, are found in the western USA, some countries in South America,
extensive areas of north-central, eastern and southern Africa, Madagascar,
Iran, and also along the frontier between Yemen and Saudi Arabia, central
and south-east Asia, and portions of the former Soviet Union23 (Figure 6.1).
178 | Zoonoses
Figure 6.1 Sylvatic (wild) plague foci across the world.
These foci are associated with dry areas, usually where desert or prairietype landscapes form. Foci are normally away from urban areas because of
their inaccessibility, or their inhospitable nature. It is therefore unusual to find
human cases emanating from wild foci sources; however, in the USA where
there has been rapid expansion of urban areas and isolated condominium
building, an increasing number of human cases come from this source.
Rodents in a natural plague focus become immune to the disease.
However, if they spread from the focus into another distinct rodent population, especially one linked to an urbanised site, infection of a susceptible
population of rodents may produce massive fatalities. This can lead to the
phenomenon known as rat-fall, where a large number of rodent corpses are
seen in open areas. Associated with this event are usually reports of fleas
biting humans: the rat fleas leave the corpses in search of new hosts, and this
results in disease transfer.
The world picture
The WHO and the CDC have formed the World Health Organization
Colloborating Center or WHOCC for Plague at the CDC, Fort Collins,
Colorado, USA. The centre provides epidemiological assistance, with
advice on prevention strategies, diagnostic support (including a reference
collection of strains), and in-country training. It also supports research
into all aspects of plague. Plague is one of only three infectious diseases
Pandora’s box | 179
subject to international health regulations. All confirmed cases should be
reported to the WHO.23
The last worldwide study of plague was completed by the WHO in 1997,
and the overall world picture remains consistent with that study; however, this
may change in the future as alterations in climate may alter the epidemiology
(see below).
In 2003, when the CDC conducted a survey, there were 2118 recorded
cases of plague worldwide with 1882 fatalities. Over 98% of the cases and
98% of the fatalities occurred in various plague foci in Africa.
In Africa, Madagascar reports the highest number of cases in most years,
probably due to the large numbers of rodents in its unique ecosystem. The
disease has also been reported in Algeria, the DRC, Malawi, Tanzania and
Uganda.24
In the USA, there are two main regions where natural plague foci are
found: northern New Mexico, northern Arizona, southern Colorado and
California, southern Oregon and far western Nevada.
Plague also occurs across South America with cases being reported
recently from Bolivia, Brazil, Ecuador and Peru.
In Asia, cases have been recorded in China, India, Indonesia, Kazakhstan,
Mongolia, Myanmar and Vietnam. Although cases are reported it is
possible that reporting may be incomplete.
Epidemiology
In terms of the development of an epidemic, the re-emergence of plague in
India in 1994 after a gap of reported cases of almost 30 years was dramatic. In
1993 a severe earthquake hit areas previously identified as having wild
plague foci. The resulting devastation allowed the rat population to increase
dramatically, with a corresponding increase in the population of their associated fleas. In August 1994 a village in the Beed district reported rat-fall
and subsequent flea nuisance. An outbreak of bubonic plague followed,
with 596 cases but no fatalities.
A separate outbreak in Gujarat followed flooding associated with a
record monsoon rainfall. During the clean-up operation, workers came into
contact with infected animal corpses. The initial cases turned into secondary
pneumonic plague, and subsequently, during an influx of people into Surat
City for a religious festival, an outbreak of pneumonic plague ensued. Of
151 cases, 52 died.
Only sporadic cases were seen in India from 1994 until 2002, when a
cluster of cases was seen in Himachal Pradesh. The index case had killed a
sick wild cat, and then skinned it; he subsequently developed pneumonic
plague, infecting 13 of his relatives (probably due to close contact and
180 | Zoonoses
poorly ventilated living accommodation) and 2 other people who acquired
the disease while in the same hospital as other victims.
In the USA, there were 107 cases and 11 deaths from human plague
between 1990 and 2005; of these cases 81 were bubonic, 19 septicaemic, 5
pneumonic and 2 unclassified. In 2006 there were thirteen cases, of which
two were fatal, in four US states: seven in New Mexico, three in Colorado,
two in California and one in Texas; five were septicaemic and eight bubonic.
The most dramatic cases in the USA, and the ones that caused a major
public health response, were a married couple from Santa Fe, New Mexico
who travelled to New York City in November 2002. After arriving in New
York they both became ill, and were diagnosed with plague. An alert emergency doctor who carried out the initial case assessment became aware that
the couple might have the disease, and a comprehensive health response led
to a number of healthcare workers and other contacts receiving antibiotic
prophylaxis. No further cases resulted. This case highlighted the risk that
infected people might travel to different areas, where the disease might not
be recognised during the pre-patent period.
There have been a number of outbreaks in Africa: Malawi (2002),
Uganda (2004) and the DRC (2005). The DRC outbreak in Oriental
province was unusual in that there were 130 suspected cases of pneumonic
plague, of whom 57 died. Thousands of people fled the region to avoid the
infection.25
An outbreak in Oran, Algeria in 2003 was not linked to a previously
identified focus; however, it may have been triggered by the building of a
new flour mill with subsequent rodent colonisation. Oran had historically
had a number of outbreaks, notably in the last two pandemics.26
In Tanzania, a natural focus has been identified in Lushoto province.
This focus is believed to have led to 7600 cases of plague in the period
1980–2004.
The area of most concern in plague infection in Africa is currently
Madagascar. A strain of Y. pestis showing multiple antibiotic resistance
has emerged there.24 The island has an unusual animal population: rodent
species are widespread, leading to an atypical pattern of foci with a higher
risk to the human population. The majority of cases are bubonic, due to the
virtually universal source of infection being primary contact with rodent
fleas.
Climate change
The current changes in world climate with warmer springs and wetter
summers might increase the incidence of plague. This could stem from a
number of factors, such as increases in the numbers of rodents and more fleas
Pandora’s box | 181
(which because of the higher temperatures are more active and breed faster).
A 1°C increase in temperature in Kazakhstan over spring and summer has led
to a 59% increase in the number of reported cases of plague. Increased
temperatures were also associated historically with the previous pandemics.
A similar pattern has been seen in the USA around foci, with high rainfall in spring, and cool summers increase the numbers of rodents and fleas,
leading to pressure on rodents to move outward from the foci, thus
contacting susceptible rodents or humans.
Disease in animals
The primary wildlife reservoirs of plague are rodent species. The rat, either the
domestic black rat (Rattus rattus) or the urban brown rat (R. norvegicus), was
the most important reservoir and rodent vector in terms of previous
pandemics. Other species may be involved depending on the site and situation of the natural foci involved. In the USA, ground squirrels, rabbits and
chipmunks have been identified as important maintenance hosts. Under
the normal circumstances in a natural wild focus, the disease cycles within
the rodent population and is transferred by fleas, which are often specific
to the rodent species involved27 (Figure 6.2).
Urban
focus
Sylvatic
focus
Pneumonic
spread
Figure 6.2 Plague cycle from sylvatic (wild) focus to urban rodent focus and humans.
182 | Zoonoses
Other animal species capable of carrying, amplifying or transmitting
plague include goats, dogs, cats, squirrels, camels and rabbits. Dogs usually
have a brief illness and often recover; cats are not so fortunate. They will
often have severe fatal infection with high fever, swollen lymph nodes,
pneumonic symptoms and encephalitis. Cats have caused human infection,
usually after bites or scratches or inhalation by the human of aerosolised cat
secretions. Other non-rodent species are also theoretically able to infect
humans via similar routes.
Transmission
The infection of the first, and sometimes only, victim in an outbreak can
almost be classed as accidental, following bites from rodent fleas, either in
a natural focus or after a rat-fall. The infection may also follow direct
contact with rodents or other infected animals, especially if they are
butchered or skinned. The route of infection under these circumstances can
be by direct transfer of blood, ingestion of infected tissue, or inhalation of
infected aerosols of blood or mucus. There is some evidence that fomite
spread by knives or other instruments used to slaughter or butcher rodents
is also possible.
Once an infected host has been bitten, the bacterium is ingested and
multiplies in the flea’s gut. The bacterium secretes a coagulase, causing an
occlusive clot to form in the mid-gut of the flea. This causes blood from a
previous bite to be regurgitated during the next bite, due to the obstruction
and the structure of the flea’s mouth parts. Inevitably this leads to transfer
of the bacteria in the most efficient manner possible.
Once infected, fleas can remain infective for a period of weeks or
months. The coagulated mass can also ultimately kill the flea. The inoculum
necessary to initiate clinical disease, if delivered by the bite of a flea, is
believed to be a single viable organism.
The usual route of infection for humans is by rat flea bite. There have
also been cases of plague being transmitted from human to human via the
bite of a human flea. This is believed to be extremely rare.
Disease in humans
The course that the disease then takes depends upon the route of infection
and the symptoms displayed. Cases are classified as bubonic, septicaemic,
meningeal, pharyngeal or pneumonic plague.
Bubonic plague
This is the classic pattern of infection following the bites of infected fleas or
inoculation of a wound with contaminated material. After infection, an
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incubation period of 2–6 days is normally seen. As with many other
diseases, the initial signs and symptoms after inoculation can be very generalised and non-specific, but with an acute onset. A fever with headache,
chills, fatigue, sickness, joint pain and sore throat are the first clinical signs,
indistinguishable from infection with other pathogens.
Following these initial symptoms, and the development of a persistent
fever that may increase, there is a progressive swelling of the lymph nodes.
This usually commences with the node nearest the site of inoculation. The
nodes become tender and are known as buboes, hence the condition’s name.
Vomiting and muscle pain with delirium usually follow. The swollen nodes
fill with pus and the disease spreads, through both the lymphatic system and
the bloodstream. The skin over the node becomes reddened, shiny and
swollen.
On treatment the reddening starts to resolve. However, the buboes, especially the first, subside only over a period of time. The initial site can remain
swollen for weeks and may require surgical removal for full recovery to take
place. In untreated cases, more than half of patients will die.
Septicaemic plague
Primary septicaemic plague does not present with a bubo. There is a high
fever, with gastrointestinal disturbance. Symptoms may be confused with
urinary tract or chest infections, appendicitis or a viral infection. Pneumonic
plague may develop. The disease is progressive, and mediated by an endotoxin
secreted by the pathogen. There is an overwhelming immunological response,
resulting in a syndrome similar to anaphylactic shock. Intravascular coagulation may occur with multiple-organ failure and respiratory distress, thrombosis and subdermal haemorrhage leading to the blackening and focal
necrosis (the symptom from which the soubriquet ‘Black Death’ comes) of the
skin. Meningeal plague can be present, as can ophthalmic involvement and
hepatic or splenic abscesses.
Meningeal plague
Usually seen as a complication of bubonic or septicaemic plague, it can also
be a primary infection. Fever, headache and stiffness of the neck, with
increasing delirium and confusion followed by coma, are normally seen. The
pathogen can be isolated from the cerebrospinal fluid. Most cases follow
delayed, inappropriate or bacteriostatic antibiotic therapy. The use of any
antibiotic incapable of crossing the blood–brain barrier carries with it the
risk of developing this form of disease.
Pharyngeal plague
Pharyngeal plague follows inhalation and deposition in the nose, mouth or
throat of large droplets of infected pulmonary exudate or ingestion of
184 | Zoonoses
infected raw or undercooked meat. Clinical signs mimic bacterial or viral
pharyngitis, with severe lymph node swellings. The only way of characterising the infection and the responsible pathogen is by identification from a
throat swab and subsequent culture. The course of the disease is variable;
however, it normally progresses to a bubonic infection if the patient survives
that long.
In 1994 (finally reported in 2005), there was a cluster of cases of pharyngeal plague associated with eating raw camel liver from an infected animal.
The index case slaughtered the camel, and presented with the bubonic form,
although he also did not eat any meat from the animal. People who ate raw
liver contracted pharyngeal plague, and a large number of other people who
ate the cooked meat or liver remained disease free.28
Pneumonic plague
Patients suffering from bubonic or septicaemic plague may have a dissemination of infection to form a focus in the lungs, known as secondary
pneumonic infection. Although their infection remains mainly bubonic, and
the clinical course is relatively unaltered, they can develop cough with
production of aerosolised infected pulmonary exudate. This can transfer
infections to other individuals who then develop a primary pneumonic form
of the disease. Once individuals display pneumonic symptoms, they are
extremely contagious and the spread of the disease within human outbreaks
is usually by this rapid route, without the further involvement of rodents or
fleas. For the infection to spread, other individuals need to usually be within
2 m of an actively coughing patient. Humid overcrowded living areas
encourage and promote human-to-human spread by this transmission
route.29
Pneumonic plague is the form of the disease associated with the highest
rate of fatality. The pre-patent period is very short: 24–72 hours after exposure. The initial symptoms are similar to other forms of the disease but there
is marked physical weakness and respiratory difficulty. A productive cough
with copious thin sputum, gradually increasing chest pain, breathing difficulties and the coughing of blood are progressive signs as the condition
worsens. Deterioration is very rapid and death occurs within 3 days in
almost all untreated patients.
To avert this outcome, antibiotic therapy must be commenced within
18–24 hours of clinical onset. Development of concurrent septicaemic plague
and associated complications make supportive therapy and nursing difficult.
Diagnosis
The WHOCC recommends that, immediately a diagnosis of human plague
is suspected on clinical and epidemiological grounds, appropriate specimens
Pandora’s box | 185
for diagnosis should be obtained and the patient should be started on specific
antimicrobial therapy without waiting for laboratory results. Victims
suspected of having the pneumonic form should be placed in isolation wards
and barrier nursed.
Confirmation of the diagnosis follows isolation, culture and identification of Y. pestis from specimens. Staining with Wayson or Giemsa stain
leaves the pathogen showing a distinctive bipolar appearance. On microscopic examination they have a distinctive ‘safety-pin’ shape. Serological
testing, ELISA and antibody testing can also be used if available. In some
cases, diagnosis is only confirmed retrospectively post mortem.
Treatment
The first response to plague infection is antibiotics. The following notes
come from the WHO, CDC and HPA; however, not all drugs are licensed in
every country for use in plague. Any cases seen in the UK or the USA would
be treated by specialists.
Streptomycin, tetracyclines and chloramphenicol have been traditionally used to treat plague, with streptomycin being the treatment of choice,
especially in severe infections, in particular the pneumonic form. However,
the HPA now recommends gentamicin instead. Two pieces of research
suggest that gentamicin (either alone or in combination with a tetracycline
– doxycycline) was as effective as streptomycin and that doxycycline can be
used on its own as a monotherapy.30,31
Chloramphenicol
Chloramphenicol is a suitable alternative to aminoglycosides in the
treatment of bubonic or septicaemic plague and is the drug of choice for
treatment of patients with meningeal, ophthalmic or pleural complications.
Chloramphenicol may be used together with either streptomycin or
gentamicin.
Tetracyclines
The tetracyclines are bacteriostatic, and their use can lead to the development
of complications. However, they are deemed suitable for use in uncomplicated
cases. Tetracyclines can be used in addition to other agents.32
Other antibiotics
Fluoroquinolones such as ciprofloxacin and levofloxacin have been shown to
be effective against Y. pestis in laboratory and animal studies.33 Penicillins,
cephalosporins and macrolides have been shown to be ineffective or of
variable effect in the treatment of plague and they should not be used for
this purpose.
186 | Zoonoses
In the UK the current HPA recommendations are:
• Adults:
– gentamicin (first choice in pregnancy) 5 mg/kg i.m. or i.v. once a
day or 2 mg/kg loading dose followed by 1.7 mg/kg i.m. or i.v.
three times daily (renal function should be monitored and blood
taken for gentamicin or streptomycin levels)
– if aminoglycosides are unsuitable ciprofloxacin 400 mg i.v. twice
daily may be used (in milder cases only, 500 mg orally twice daily
may be used), or doxycycline 100 mg orally twice daily (for
ciprofloxacin, other fluoroquinolones with proven activity, e.g.
ofloxacin, levofloxacin, may be substituted, at equivalent doses)
– if plague meningitis is suspected chloramphenicol 25 mg/kg i.v.
four times daily may be given.
• Children:
– ciprofloxacin 10 mg/kg i.v. twice daily (max. 400 mg) not to
exceed 800 mg/day (in milder cases only, 15 mg/kg orally twice
daily may be given with total dose not to exceed 1 g/day)
– or doxycycline 100 mg orally twice daily in children ⬎ 8 years and
who weigh ⬎ 45 kg; in children ⬎ 8 years but weighing ⬍ 45 kg
the dosage of doxycycline should be 2.2 mg/kg every 12 h
– in cases of suspected meningeal plague, chloramphenicol 25 mg/kg
(max. 500 mg) orally or i.v. four times daily can be used.
• In both adults and children therapy should be continued for 14 days.
Prophylaxis
Healthcare workers or others who come into close contact with infected
patients should receive prophylactic treatment. It may also be suitable for
scientific fieldworkers investigating plague foci. Tetracycline, doxycycline or
co-trimoxazole is currently used. Chloramphenicol has fallen from favour,
due to the incidence of severe side effects.
In the event of exposure to a deliberate release, or contact with a case of
pneumonic disease, prophylactic antibiotic therapy should be initiated immediately. Contacts of cases of bubonic plague should be assessed for the need
for prophylaxis. For adults, children and pregnant women, ciprofloxacin is
the drug of choice.
The risk of adverse effects from antibiotic prophylaxis must be weighed
against the risk of developing clinical disease in both adults and children.
Other antibiotics, such as chloramphenicol or co-trimoxazole, could be
used in individuals who cannot tolerate the antibiotic, or where the risk is
considered to be too great.
Pandora’s box | 187
After initial treatment with ciprofloxacin, doxycycline may be substituted
to complete the 7-day prophylaxis. People who come into contact (⬍ 2 m)
with patients with pneumonic plague should receive antibiotic prophylaxis
for 7 days. In healthcare and laboratory staff with continuing exposure,
prophylaxis should be extended to 7 days after the last contact with a patient
or sample considered to be infectious. Prophylaxis should continue until
exposure has been excluded.
As with anthrax, in the UK, the duration of initial course of antibiotic
treatment is currently 5 days from the HPA emergency system, and a PGD has
been developed to provide the necessary continuation course. Details may be
found on the DH website. In the UK the current HPA recommendations are:
• Adults (including pregnant women), initial (5-day) therapy:
– ciprofloxacin 500 mg orally twice a day followed by a further
(2-day) therapy of either ciprofloxacin 500 mg or doxycycline
100 mg orally twice daily.
• Children, initial (5-day) therapy:
– the dose of ciprofloxacin is age and weight dependent, with the
recommendation being that newborn babies up to the age of
6 months receive 100 mg/day in divided doses, and older children
receive 15 mg/kg orally twice a day (dose not to exceed 1 g/day,
i.e. adult dosage) with a further (2-day) treatment of ciprofloxacin
at the same dose
– doxycycline may also be used at the following dosages: if the child
is ⬎ 8 years and weighs ⬎ 45 kg at a dose of 100 mg orally every
12 h; in children ⬎ 8 years but weighing ⬍ 45 kg the dosage of
doxycycline should be 2.2 mg/kg every 12 h.
Prevention
Vaccination is available; however, the likelihood of travellers contracting
plague is very low. People going to work or live in areas where there is a
known wild focus may be vaccinated. Laboratory workers who could be
exposed to plague through clinical samples should be vaccinated in endemic
areas, especially if investigating the focus. Development of immunity takes
at least 1 month after immunisation. Immunisation with the vaccine does
not protect against developing primary pneumonic plague, so workers in
risk areas, especially if geographically isolated, should be educated about
signs and symptoms and encouraged to carry suitable antibiotics for immediate use if required. The vaccine is available in the UK through specialised
centres, such as the Hospital for Tropical Diseases and the DH, and in the
USA through the CDC. It is unlicensed in the UK, although if needed this is
188 | Zoonoses
probably not significant. The vaccine does not offer immediate protection
and should be used only for prophylaxis.
Avoiding exposure to rodents and their fleas, and controlling rodents
and their fleas, remain the best methods of prevention. Domestic and
companion animals in endemic areas should be treated for fleas, and bites
and scratches avoided wherever possible.21
Rabies (hydrophobia)
Classic rabies is caused by a genus Lyssavirus, family Rhabdoviridae virus,
sometimes known as genotype 1 virus, to distinguish it from other closely
related viruses that have been identified as causing similar illnesses (see
below). It is a continual challenge to public health systems worldwide,
especially in developing countries, with an estimated 55 000 deaths, and
approximately 10 million people receiving post-exposure prophylaxis
(PEP) annually worldwide, mainly in Africa and Asia.34
The expense of vaccine as PEP for patients exposed to animals suffering
from the disease or potentially rabid animals is a significant cost for the
public health purse in countries or areas where the disease is endemic.
The UK and Europe
The UK benefits from a geographical advantage when it comes to rabies.
As an island it has been possible to eradicate the disease in the past and
prevent its re-introduction. The last indigenous case of rabies was in 1902,
and after a nationwide campaign and enforcement of a system of strict
quarantine the country was declared disease free. The continued enforcement of these regulations and the strict rules relating to the issuing of pet
passports has maintained the UK in this status; however, this is not true of
continental Europe.
Rabies is believed to have crossed the Polish border into Europe in the
late 1930s. At this point, the virus transferred from dogs (its previous reservoir) into its main reservoir species in western Europe, the red fox (Vulpes
vulpes); however, it is now believed that it also spread into the raccoon dog
(Nycterentes procyonides). This has led to the current pattern of dogmediated rabies in eastern Europe, fox-mediated rabies in east and central
Europe, and raccoon dog rabies in north-eastern Europe. Currently, only
Turkey has ‘dog-mediated rabies’, where wild and feral dogs form the main
disease reservoir. The southern portion of the former Soviet Union is unique
in having a mixed pattern of dog- and fox-mediated infection.35
The area where the disease was considered to be endemic advanced
towards the English Channel at approximately 20–60 km (12–36 miles) each
year, and had engulfed Paris by the late 1970s. A concerted effort by European
Pandora’s box | 189
governments over a number of years to vaccinate domesticated animals and
wildlife (by using baits loaded with an oral vaccine) has led to many states
being declared ‘rabies free’. The effectiveness of such schemes can be gauged
from the reduction seen in Germany, from 10 000 animal cases per year in
the late 1970s, to 56 cases in 1999, to 6 bat-linked cases in 2007.
During 2007, the WHO European rabies monitoring centre reported a
total of 9563 cases. Of these, 54% occurred in wild animals and 45% in
domestic animals. There were only nine human cases, with six in the Russian
Federation, two in the Ukraine and one in Romania.
Cases in domestic animals totalled 4329, of which cats and dogs were
the most significant species. Cattle, horses, sheep and other farm animals
can also contract the disease, but onward transmission is unlikely. Rodents
and other small mammals may also carry and suffer from the disease. The
WHO programme also records and includes the detection of bats with
lyssavirus; however, although in 2007 26 bats were found with the disease,
reporting is probably incomplete.
Many European countries are now considered to be rabies free, but this
status can be lost due to unforeseen circumstances, e.g. in September 2004,
France notified the WHO of a recent case of rabies in a dog illegally
imported from Morocco into France, which could have transmitted rabies
to humans and other dogs during August 2004; 187 people were given PEP,
no secondary cases were detected in animals during this period and the area
was declared rabies free again in March 2005.
In March 2008, France lost its rabies-free status after the illegal importation of an infected dog, which subsequently infected two other dogs. A low
but increased risk of rabies was declared in three areas of France (Gers,
Grandpuits and Calvados). If no cases had been detected following this case,
the ‘rabies-free’ status should have been reinstated later in 2008.36 However,
after another case of rabies in an infected dog in October 2008, France is still
not considered to be rabies free. Similar incidents have occurred elsewhere in
Europe, notably in Switzerland in 2003.
Rabies in North America
Historically, rabies was endemic across the USA. The pattern of rabies infection in the USA has altered dramatically since the early twentieth century
when canine rabies predominated. Following extensive vaccination
programmes and a culling policy from the 1850s, domesticated animals, and
particularly dogs, as a source of rabies declined from 82.6% of reported cases
in 1950 to 7.9% in 2006. The total number of rabies cases in animals – both
wild and domesticated – across the USA in 2006 was 6490, of which 318
(4.6%) were in cats. Cases of canine rabies have been seen stemming from
imported animals posing the risk of accidental reintroduction.37
190 | Zoonoses
New reservoirs of infection have now been identified in wild animal
populations, with raccoons, skunks, ferrets, beavers and bats forming disease
reservoirs. Raccoon rabies has spread across the eastern USA since 1981, and
has also spread into skunks. It is possible that, in a similar manner to the
change seen in western Europe in the 1940s, a new genotype will emerge.
This would have implications for control measures which centre around
oral inoculation using baits, as the vaccine used is efficient in raccoons, but
less so in skunks. The first known human death occurred in Virginia in 2003
with a man aged 25 becoming ill after being bitten by a rabid animal.38
In Canada, efforts have been made to eliminate the disease. A comprehensive vaccination by bait programme in Toronto, Canada has virtually
eliminated fox-mediated Arctic variant rabies with over 300 000 baits being
distributed between 1989 and 1999. Only 5 cases of rabid foxes were seen
between 1990 and 2006 compared with 19 cases between 1972 and 1989,
with the last rabid fox in the greater Toronto area being reported in 1996.
Rabid bats have been detected in every US state except Hawaii since the
1950s, and have also been detected in Canada. Approximately three-quarters
of rabies deaths in the USA are now associated with bat rabies. Between
1990 and 2000, of 32 human cases of rabies, 24 were linked to bats, and
only 2 cases reported being bitten. Bats are difficult to control; they are
nocturnal, capable of living in large colonies in urban areas and often
protected by wildlife preservation statutes.
Bat bites can be unrecognisable, or easily overlooked, and transmission
may have followed inoculation of wounds, mucous membranes or abrasions
with infected saliva. In many cases victims could not identify having been
bitten or exposed to contact with a bat, although they or their families
recalled bats being present in the patient’s work place or home. This has led
the CDC to issue guidance to clinicians that aggressive use of post-exposure
vaccination in individuals suspected of possible exposures to bats should be
considered.
Rabies elsewhere in the world
In Asia and Africa, canine rabies predominates and is considered to be the
most significant animal reservoir worldwide, and control of rabies in canids
is seen as a high priority for preventing human infection. Rabies control
measures have improved in many South American countries, and the pattern
of infection has changed with canine rabies becoming less prevalent;
however there is another transmission path that has become more important
– transmission of the disease by vampire or haematophagous bats. Outbreaks
of bat-transmitted rabies have occurred in several remote areas in Brazil,
Peru and Venezuela, with sporadic cases occurring in Mexico, Chile and
Colombia.
Pandora’s box | 191
The increase in vampire bat attacks and the transmission of rabies
appear to be linked to deforestation, and the change of roost from forest to
caves and disused mines.
During 2006, there were two rabies outbreaks in Portel and Viseu
municipalities in Para State, northern Brazil associated with vampire bats. A
total of 21 human deaths occurred. There had also been a outbreak in
Turiacu, northern Brazil in October 2005 which killed 12 people, and
another outbreak in Para in 2004.39
Disease in animals
The causative rhabdovirus is shed in large numbers into the saliva of infected
mammals. Transmission follows inoculation of a bite wound or abrasion
with infected saliva. Any animal suffering from rabies will display symptoms
of CNS disturbance. After the incubation period and before the ‘mad’ or
excitative phase, the animal may display certain prodromal symptoms.
Behaviour will start to change: animals may display antisocial behaviour,
becoming solitary and sexually aroused, and having increased urinary
frequency.
The animal shows a lack of appetite for food and will not drink. After a
few days the animal may become very excitable and vicious, biting or
attacking anything or anybody in close proximity. This phase may be
prolonged or short, and in some species is totally absent. The third or paralytic stage of the disease follows. As paralysis sets in, the animal becomes
progressively more docile and death follows rapidly, usually within 10 days of
the start of clinical signs.
Transmission
Humans contract the disease from bites of rabid animals, or by inoculation
of wounds with virus-containing saliva. The possibility of air-borne droplet
transmission has been demonstrated in caves where there are large populations of bats. The possibility of contracting the disease by organ or corneal
transplantation from patients dying of undiagnosed disease has also been
documented (see below). There is a theoretical risk of transmission of rabies
from the consumption of milk or meat from an infected animal, although
pasteurisation or thorough cooking is known to inactivate the virus.
Disease in humans
The virus is localised for a period post-exposure in the immediate vicinity of
the wound. The area around the site of entry may be painful or itch.
Localised numbness, especially of the limb nearest the site, may be reported.
192 | Zoonoses
There is a pre-patent period following infection: this period seems to vary
according to where the wound is in relation to the CNS – the closer the
wound, the shorter the period. However, it is usually between 3 and 12 weeks,
with variations linked to amount of inoculum and age of the patient; higher
inocula and younger patients show more rapid onset of disease. Incubation
periods of more than a year have occasionally been reported, with the
longest being 19 years and the shortest 4 days. Of infected people 93%
show symptoms earlier than 12 months after exposure.
The virus migrates from the point of inoculation during this period, and
enters the CNS. Early symptoms are very generalised, consisting of fever,
headache and lassitude. As the CNS involvement begins, more serious clinical signs occur, often with acute onset. Symptoms progress as the neurological involvement increases. These can include insomnia, confusional states,
anxiety, paralysis, hypersalivation, with swallowing difficulties caused by
spasm of the oesophageal and laryngeal muscles (leading to the classic
symptom of foaming at the mouth), altered perception and aggression. The
patient may be extremely excited and often has convulsions. Disturbances
of normal breathing and cardiac function are also seen. In the final stages of
the disease, most victims pass through phases of delirium, convulsions to the
almost invariable outcome of death.
The synonym hydrophobia for the disease relates to the physical difficulties of drinking experienced by humans and animals, which are probably
exacerbated by the abnormal mental state that occurs. The duration of the
disease is short: death follows within a few days of the start of clinical signs.
Person-to-person transmission is extremely rare; however, precautions
should be taken to prevent exposure to the saliva of the diseased person.
Diagnosis
Diagnosis is often presumptive from the patient’s history or presence of bite
wounds. The virus can be isolated from bodily fluids or tissue samples and
identified by microscopy, after treatment with fluorescent antibody-staining
techniques. Rabies nucleic acid can also be detected using polymerase chain
reaction tests. Isolating and identifying the virus from brain tissue or saliva
post mortem often confirms diagnosis.
Treatment
Vigorous cleansing of bites or wounds with copious amounts of surfactant
disinfectants or soap and water is a vital measure to reduce the risk of infection. This must be carried out immediately or as soon after the event as is
practicable. In children, any bites are usually on the limbs, head, face or
neck, and they must be cleaned very thoroughly. Rapid use of post-exposure
Pandora’s box | 193
vaccination is recommended. Suturing should not take place because this
can spread the virus more rapidly.
Post-exposure treatment also uses human rabies immunoglobulin (HRIG)
(also known as antirabies immunoglobulin) locally infiltrated around the
wound site with concurrent administration intramuscularly. The dose used
is calculated on a weight basis at a rate of 20 units/kg; if all of the dose
cannot be infiltrated locally, or the wound has healed or is not visible, the
remainder may be given intramuscularly in the thigh, but not the buttocks.
HRIG is manufactured by Bio Products Laboratory and is available in the
UK from HPA laboratories and regional blood transfusion centres in England
and Wales. It is also available to the Scottish National Blood Transfusion
Service (see Appendix 2).
In patients with overt clinical signs intensive care is required to maintain
respiration. If convulsions and seizures are controlled using anticonvulsants,
there is a small chance of survival.
In 2004, a 15-year-old girl who had contracted rabies after a bat bite in
Wisconsin, USA, was placed in a drug-induced coma and treated with intravenous ribarvin. She was kept in the coma for 7 days, and her antirabies IgG
titre rose steadily. On day 33 of her illness she was taken off a ventilator and
3 days later transferred to a rehabilitation unit.40
This case was the sixth known human recovery from rabies; however, the
case was unique because the patient received no rabies prophylaxis either
before or after symptoms were seen. Previously no unvaccinated patients
had survived. All other survivors were either previously vaccinated or
received some PEP before symptom onset.
The treatment method has been used in several cases since, with some
clinical variations; however, no other patient has survived.
Prophylaxis
Vaccination programmes in domestic animals, with rigid guidelines on the
control of stray or feral dogs, cats and other mammals, are important in
reducing risks and exposure in countries where the disease is present. The
vaccination of wild animal populations using inoculated baits has become
very important in reducing levels of disease in the wild animal reservoir
within endemic areas. Rigid control of animal imports, and the use of pet
passport schemes or quarantine facilities, allow risks to be reduced and
disease-free status to be maintained.
Travellers to rabies-endemic countries should be warned about the risk
of acquiring rabies, although rabies vaccination is not a requirement for
entry into any country. The avoidance of bites and scratches from stray dogs
or companion animals in countries where rabies is endemic is the most
important part of any prevention strategy.
194 | Zoonoses
Pre-exposure rabies vaccination should be considered for patients who
will be staying a month or more in countries where dog rabies is endemic.
The necessity of post-exposure rabies prophylaxis after an animal bite
should be discussed with patients planning to travel to a non-industrialised
country. They should be made aware that vaccination within a few days
after a bite is capable of preventing the disease developing. Prophylaxis is
recommended for travellers going to countries where there is a risk that
post-exposure therapy may be unavailable, or available only using products
of dubious quality.
All travellers to such countries may wish to ensure that they carry sterile
packs containing needles and syringes. In the event of the need for vaccination, clean equipment is then available. Travellers should be encouraged to
avoid handling, feeding or caressing wild and feral animals unless wearing
appropriate protective clothing.
Individuals at risk of occupational exposure, such as workers in laboratories, quarantine facilities, port officials, customs officers, animal and bat
handlers, and veterinary surgeons, whose employment is likely to carry a
higher risk of exposure, should be considered for routine immunisation.
Healthcare workers likely to be exposed to patients with the disease must be
immunised wherever possible.
Vaccination regimens
There are wide regional variations in the types of rabies vaccines available.
In the UK a human diploid cell rabies vaccine (HDCV: Pasteur Mérieux)
is available, as is a purified chick embryo cell (PCEC) vaccine (Rabipur:
Novartis, MASTA); both are inactivated, containing no live virus, and may
be used interchangeably in the event of supply disruption.
In other countries, especially developing nations, other products may be
in use. These include neural tissue vaccines prepared from sheep or mouse
tissue. These vaccines have a high incidence of associated neurological
complications; however, they may be the only product available. Some
countries also use more modern vaccines prepared on different substrates
to those in common use in western Europe or the USA. These include
purified Vero cell rabies vaccine (PVRV) and purified duck embryo vaccine
(PDEV).
The UK DH recommends that for prophylactic use HDCV vaccine should
be given in a three-dose schedule on days 0, 7 and 28, with booster doses
every 2–3 years if the individual is at continued risk. The last dose may be
given from day 21 if insufficient time is available before the individual
travels to an endemic area. A booster dose should be given 12 months after
the first dose for those at regular or continuous risk, with further doses at
3- to 5-year intervals thereafter. For people at intermittent risk, or where
Pandora’s box | 195
they are returning to risk areas, and where no ready access to safe medical
care is available, a subsequent dose after every 2 years is required.
Although pre-exposure vaccination does not eliminate the need for additional therapy after an incident, it does simplify post-exposure treatment by
removing the need for rabies immunoglobulin and by decreasing the number
of doses of vaccine required.
Where it is not known what regimen (if any) a patient has been given as
prophylaxis, a full post-exposure regimen must be adopted unless there is
serological evidence of antibody response following a risk assessment.
Recommended post-exposure regimens differ according to the previous
vaccinations given. Fully immunised patients exposed to whatever level of
risk should be given two booster doses on days 0 and 3. Individuals who
have not been previously immunised, or who may have inadequate or outof-date prophylaxis, should receive a course of injections starting as soon as
practicable after exposure on days 0, 3, 7, 14 and 30, with a dose of HRIG
on day 0 if considered to be at high risk.
Concomitant treatment with antimalarials, such as chloroquine and
mefloquine, interferes with the antibody response to HDCV. For patients
taking these medicines, intradermal vaccination is not recommended. The
intramuscular route must always be used.
As with other immunisations, there may be a reaction to the injection.
Pain can occur at the injection site, with reddening, swelling or itching.
Headaches, nausea, gastrointestinal disturbance, generalised aching and
dizziness have been reported. Due to the serious nature of the disease, postexposure programmes must be continued despite mild localised or systemic
symptoms, or other factors such as pregnancy. The gluteal muscle must not
be used as an administration site, because past experience has shown that
there is a poor response to vaccine administered here.
WHO recommendations
The WHO endorses the use of the Essen or five-dose regimen in postexposure vaccination. This consists of five injections of one dose of vaccine
intramuscularly on days 0, 3, 7, 14 and 28. Day 0 is considered to be either
the day of the injury or the date at which treatment begins. In theory both
should coincide; however, in practice this may not always be the case.41
There is also a four-dose regimen with two doses of vaccine being given
on day 0, one in each deltoid/thigh, followed by one dose on days 7 and 21.
In addition to these vaccination schemes, there are other regimens that have
been developed to reduce the cost but not the effectiveness of post-exposure
treatment.
Both of the following regimens use intradermal inoculation, reducing the
amount of vaccine required to produce a sufficient immune response. The
eight-site scheme requires injection of 0.1 mL at eight sites (one in each
196 | Zoonoses
upper arm, one in each lateral thigh, one on each side of the suprascapular
region, and one on each side of the lower quadrant of the abdomen) on day
0, one injection in each upper arm and each lateral thigh on day 7, and one
dose in each upper arm on days 30 and 90.
The two-site scheme requires one injection of 0.1 mL at two sites on days
0, 3, 7 and 28.
Other related viruses
There are a number of related lyssaviruses often referred to by genotype that
can cause a disease which in general terms is clinically similar to rabies.
They are closely related to the classic virus (genotype 1), and rabies vaccine
cross-reacts with these viruses, giving prophylaxis and treatment in human
cases. There are a number of other lyssaviruses identified in Russia that have
not yet been fully genotyped but are also capable of causing rabies-like
disease. These are known as Aravan, Khajard, Yuli, Irkut and West
Caucasian bat virus (Table 6.1).42
Lagos bat virus is carried by bats and has never been associated with
known human disease to date; it has recently been detected in bats in South
Africa, and appears to be sporadic, possibly reflecting bat migrational
patterns.43
Mokala virus is unusual in that it is carried by shrews, rodents, cats and
dogs. Mokala virus is believed to have caused disease in humans in Nigeria
during the 1970s shortly after its discovery, but no recent human cases have
been identified, although it has been identified in cats and dogs in South
Africa.
Duvenhage virus is also carried by bats, with the last recorded clinical
human case being recorded in 2006, when after a bat scratch a 77-year-old
South African man died; this was only the second human case ever attributed
Table 6.1 Other lyssaviruses capable of causing rabies-like disease
Genotype
Name
2
Lagos bat virus
3
Mokala virus
4
Duvenhage virus
5
European bat lyssavirus 1
6
European bat lyssavirus 2
7
Australian bat lyssavirus
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to the virus, with the previous case occurring in 1970, when the virus was
first identified.44
European bat lyssavirus (bat rabies)
The risk of European bat lyssavirus (EBLV) is thought to be low; however,
much emphasis is placed on it in British public health circles. Since 1977
there have been five human deaths in Europe (three confirmed, two
possible) from EBLVs, all in cases where the human had been bitten or
scratched by bats and had not received rabies vaccination either before or
after the incident. Many other people have been bitten or scratched by bats;
however, they all received PEP.45
EBLV is split into two distinct genotypes: EBLV-1 is the predominant
genotype across Europe, but has been identified only in one (of 273 examined) serotine bat (Eptesicus serotinus) in southern England. EBLV-2 has
been detected in the UK with seven Daubenton’s bats (Myotis daubentonii)
testing positive: a pregnant female in 1996 in Sussex, a juvenile female in
2002 and an adult male in 2002 in Lancashire, a juvenile female in 2004 in
Surrey, an adult female in Oxfordshire in 2006, an adult female in Shropshire
in 2007 and another in Shropshire in 2008. In November 2002 in Scotland,
a bat handler became the first victim of EBLV-2 in the UK, after a bite from
an infected bat. Healthy bats often show lyssavirus antigens, although they
are not clinically ill, and are therefore believed to be capable of surviving
rabies-like disease.
All bats in Britain are protected species and should not be handled,
particularly if sick or injured, except by professional bat handlers. In the
USA the situation is similar, and bats should not be handled by the general
public, if at all possible.
Australian bat lyssavirus
In 1996 a rhabdovirus related to rabies, now known as Australian bat
lyssavirus, was found in a sick bat. A bat handler died after being infected
with this pathogen in 1996, and in a separate incident in 1998 a further
human fatality occurred. It has been found sporadically since in bats, but no
other human cases have been seen.
Case histories
Classic rabies
A rabid kitten that had been handled by members of 60 female softball
teams at an interstate competition in July 2007 held in Spartanburg, South
Carolina, led to a multistate health alert. The kitten was taken home by one
of the team coaches, where it became ill and later died. On investigation it
198 | Zoonoses
was found to have been rabid. Following tracking and investigation of people
exposed to the kitten, 27 were given prophylaxis: 1 from South Carolina, 15
from Georgia and 11 from North Carolina. No clinical cases of rabies
followed.
Bat rabies (non-EBLV)
There have been a number of incidents of human rabies after exposure to
infected bats since 2000 in the USA. In March 2002, a 28-year-old man
from Glenn County, California died of rabies after exposure to a Mexican
free-tailed bat, probably from a colony in his home. A previous case in
Amador County, California in September 2000 was associated with the
same species. Also in 2002, a 20-year-old man in Iowa died after exposure
to either infected silver-haired or pipistrelle bats. This was the first case of
rabies in Iowa since 1951. A boy from Tennessee, aged 13, died in the same
year in a case also associated with silver-haired or pipistrelle bats.
Since 2002, there have been on average one or two cases each year in the
USA across a number of states.
In Alberta, Canada, a 73-year-old man died of rabies in April 2007 after
a bite from a silver-haired bat.
Imported cases
There have been a number of cases of imported rabies in Europe, the UK
and the USA in the last decade.
In 2003, a 3-year-old child died in France after returning from Gabon
having been bitten by an infected dog. The following year there were three
separate incidents, with an Austrian tourist dying after being bitten in
Morocco, a young German girl died in Germany after holidaying in India
(see below), and a 41-year-old man died in Florida of canine rabies after
visiting Haiti on holiday.46,47
The latest case of imported rabies in a human in the UK was in 2005,
and followed a bite from a dog in Goa, India, while the patient was on
holiday. Vaccination was not sought post-exposure and the patient subsequently died after returning to the UK. There had been three previous cases
of imported rabies: the first in 1996 after a bite from a stray dog in Nigeria,
the second from a dog bite in the Philippines in 2001 and the third also from
a bite in Nigeria.48
In November 2006, an 11-year-old boy in California died of rabies, from
a virus type associated with canine-borne rabies in the Philippines. His
family had immigrated from the Philippines 2 years earlier, with the child
being bitten just before their departure for the USA.
In 2007, another German national died after being bitten by a stray dog
in Morocco.
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All of the victims were unvaccinated and all cases were fatal. These cases
highlight the need for travellers to be educated about this disease, and to
realise that a bite from an animal requires medical attention as soon after it
occurs as possible.
Organ transplantation
In June 2004, an organ donor from Arkansas died (of undiagnosed rabies);
his liver and two kidneys were used in three subsequent transplantations in
Alabama, Oklahoma and Texas, with all the recipients dying of rabies.
Rabies has also followed corneal transplantations in eight people across five
countries.49
In similar circumstances, in February 2005, German officials reported
that three of six patients who received organs transplanted from a single
donor who died in December 2004 were infected with rabies. The donor
appears to have been infected while on holiday in India (see above), but was
symptom free when she died from cardiac arrest. Two of the three infected
died; the other was in a critical condition but later survived; the other three
who had received corneal and liver transplantations remained disease free,
but received PEP.50
UK guidelines state that individuals must not donate blood or tissue for
12 months (and until fully cleared by a clinician) after a known exposure to
an infectious disease. Although rapid diagnosis tests are available, accurate
travel and clinical history as well as exact identification of causes of death
remain essential to reduce the risk of disease transmission.
Prevention
As mentioned previously, part of the protection and prevention measures in
place in the UK and the USA is a strict quarantine system. Recently this has
undergone a slight modification in the UK to allow a pet passport scheme
to undergo trials (see below). The effectiveness of the quarantine system in
the UK was demonstrated in April 2008, when a social worker involved in
bringing Sri Lankan street dogs into the UK was bitten by a puppy that later
died of rabies while in quarantine. She and two kennel workers were given
PEP. No further cases occurred.
In the USA, it is recommended by the CDC that all cats be vaccinated
against rabies because they are more frequently seen with clinical disease than
dogs (269 cases in cats in 2005 compared with 76 in dogs in the same year).
Imported dogs must be immunised in accordance with CDC vaccination
requirements.
The CDC also recommends that livestock that are particularly valuable,
especially breeding stock, should be vaccinated, as should animals used in
200 | Zoonoses
petting zoos, agricultural fairs and horses that move from state to state. All
wild animals caught for use in zoos should be quarantined for 6 months and
employees of exhibitions or zoos with animals should be immunised on a
precautionary basis.
In healthcare settings, adherence to standard infection-control precautions minimises the risk for healthcare workers’ exposure to rabies; however,
PEP should be provided to healthcare workers who care for patients with
rabies where their mucous membranes or open wounds may have been
exposed to infectious body fluids or tissue (e.g. saliva, tears, cerebrospinal
fluid or neurological tissue) from infected patients.
Children should be taught to be cautious in their interactions with
animals, especially those that are unfamiliar, to avoid potential exposures to
rabies and other infectious diseases. An apparently healthy dog, cat or ferret
that bites a person should be confined and observed daily for 10 days. If the
animal becomes ill or dies during this observation period, its brain should
be examined for evidence of rabies virus infection. If rabies is detected,
prompt administration of PEP is indicated. If the animal is unavailable for
testing, public health officials should be consulted.
In the UK, the advice on the provision of PEP has changed since the
detection of EBLV in UK bats. As classic rabies vaccine offers complete
protection to this virus, the latest guidance stresses that clinicians need to be
aware of the risk of rabies after significant exposure to bats. If a person is
bitten or scratched, or there is direct contact with a bat to mucosa or broken
skin, the area should be cleaned thoroughly with water and soap and
medical advice sought urgently and expert assessment performed. PEP
(vaccination and possibly administration of immunoglobulins) is recommended. Any member of the public finding a bat behaving abnormally,
found in an unusual place, or under unusual circumstances, should not
attempt to handle or move the animal, but contact their local bat conservation group or the Bat Conservation Trust. All bat handlers and other people
likely to be at risk of exposure through the close handling of bats should be
vaccinated against rabies and this is provided free of charge by the HPA
through the NHS.
Awareness in the general public and healthcare professionals of this
small risk needs to be addressed without creating unnecessary fear of these
endangered and protected animals.
Anyone who is bitten or scratched by a bat should contact a doctor
immediately, who should, in turn, seek expert advice. This is available
24 hours from relevant centres: in England, the HPA Virus Reference
Department (tel: ⫹44 (0)20 8200 4400) or Communicable Disease
Surveillance Centre (tel: ⫹44 (0)20 8200 6868); in Wales, the National
Public Health Service for Wales (tel: ⫹44 (0)29 20742178, out of hours
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(tel: ⫹44 (0)29 20747747. In Scotland the Scottish Centre for Infection
and Environmental Health (tel: ⫹44 (0)141 300 1100); and in Northern
Ireland, the Consultant in Communicable Disease Control in the relevant
health board or the Communicable Disease Surveillance Centre (Northern
Ireland) (tel: ⫹44 (0)28 9026 3765).
In the USA, medical services should contact local county and state health
officials and the CDC.
Pet Travel Scheme (PETS)
This scheme was introduced in the UK in April 2000. The regulations, made
under SI 1999 no. 3443 The Pet Travel Scheme (Pilot Arrangements)
(England) Order 1999, form the basis of the scheme. European Union (EU)
Regulation 998/2003, which has applied since July 2004, has updated the
scheme and sets the requirements for the movement of dogs, cats and ferrets
travelling within the EU, and into the EU from third countries. The rules of
entry to the UK remain largely unchanged by the Regulation. The scheme
aims not only to prevent rabies entering the UK, but also to prevent establishment of Echinococcus multilocularis and certain tick-borne diseases
endemic elsewhere in Europe and the rest of the world. It does not replace
the quarantine system; however, it does allow cats, ferrets and dogs, especially hearing dogs for the deaf, or guide dogs for the blind, to accompany
their owners abroad. The scheme allows owners and their animals to travel
to a number of EU and non-EU destinations and return without needing
formal quarantine.
To enter an animal into the scheme, it must have a microchip inserted to
identify it permanently, and be verifiably and effectively vaccinated against
rabies. A certificate is then issued under the scheme. This allows the animal
to enter or leave the UK by specified routes and carriers. Details can be
found on the DEFRA website (http://maff.gov.uk/defra). Booster injections
have to be given as recommended by the rabies vaccine manufacturer to
maintain immunity and validity of the certificate.
In addition to this certificate, there is a requirement for the animal to be
treated for ticks and tapeworms between 24 and 48 hours before it enters
or re-enters the UK. Again a certificate is issued by a vet to verify that the
treatment has taken place with approved products on each occasion. These
certificates must be obtained before travelling, otherwise the animal may not
be accepted by the travel company or may be turned back at the border.
During 2006, 8375 cats, 74 285 dogs and 31 ferrets successfully entered
the UK under the Scheme. In total, 362 602 pet animals have entered the UK
under the PETS since 2000 (ferrets have only been able to enter under the
Scheme since July 2004). There have been no cases of imported rabies in the
UK in animals that have used PETS.
202 | Zoonoses
Deliberate release – bioterrorism
Initial definitions
• Biological terrorism: use of biological agents or toxins (e.g. pathogenic
organisms that affect humans, animals, or plants) for terrorist
purposes.
• Deliberate release: the spreading of a pathogen or toxin deliberately to
cause casualties, fear or disruption.
• Threat: the capability of an adversary, coupled with intentions, to
undertake malevolent actions.
Background
Following almost immediately after the attacks on the World Trade Centre
in September 2001, the anthrax letters in the USA prompted the WHO,
CDC, HPA and other healthcare bodies to explore for the first time, in the
public domain, the issue of bioterrorism.51
Biological warfare is not new, but it was not until the twentieth century
that state-sponsored programmes to develop biological weapons began to be
established, reaching their zenith in the latter years of the Cold War. By then
many nations had either established or sought to establish biological weapon
programmes, often known as the ‘poor man’s atom bomb’ (a reflection of the
likely level of fatalities and casualties that such attacks might cause).
Estimates vary as to the level of casualties a deliberate release would
cause; however, a study at Stanford University in California in 2003, using
a computer model, estimated that a kilogram of anthrax spores released efficiently in a city of 10 million people could cause as many as 123 000 victims
if antibiotic treatment was not administered within 48 hours. This was
almost identical with UK estimates made in the 1970s.
As the threat increased a Biological and Toxin Weapons Convention
(BTWC) was proposed, being initially signed in 1972, and ratified by more
than 100 nations in 1975, in an attempt to control the spread of such
weapons.
Many nations have since chosen to destroy their stockpiles of these
weapons and scale down or cease their offensive programmes in accordance
with the BTWC, retaining only a defensive or protective programme. Since
then the UN has sought to prevent proliferation of the technology, materials
and information that would allow other nations or organisations to develop
such programmes and destroy bioweapon programmes and stockpiles.
The Australia Group
The Australia Group grew out of the BTWC in 1985, being an informal
arrangement aimed at reducing the proliferation and export or tranship-
Pandora’s box | 203
ment of biological warfare materials or production techniques. It currently
has 40 members plus the EU. It develops and updates lists of organisms and
toxins that it considers to be of concern. Although not all the organisms that
are listed under the Australia Group, or covered by the legislation such as
the UK Anti-terrorism, Crime and Security Act (ATCSA) 2001 and the associated orders, or the Public Health Security and Bioterrorism Preparedness
and Response Act of 2002 and the Uniting and Strengthening America by
Providing Appropriate Tools Required to Intercept and Obstruct Terrorism
(USA PATRIOT) Act of 2001 in the USA, are zoonotic pathogens, many
are. Many of the moieties known to have been developed within state
programmes were also zoonoses, because they had the essential attributes
necessary for warfare agents, being easily transmissible to humans, aggressive
in terms of pathogenicity, and capable of both causing massive fatalities or
severely ill casualties and fear or panic among the ‘worried well’.
The Global Health Security Initiative
Since 2001, although there are still concerns over state programmes, such as
those of Iran and North Korea, the main emphasis has shifted to an act of
bioterrorism or a deliberate release resulting from malicious activity by a
terrorist or terrorist-related organisation.
Part of the international response to this threat has been the establishment of the Global Health Security Initiative (GHSI), an informal, international partnership focused on strengthening health preparedness and
coordinating the global response to threats of biological, chemical or
radionuclear terrorism (CBRN) initially. Its remit has since been widened to
include in addition planning and response to pandemic influenza.
Launched in November 2001 by Canada, the EU, France, Germany,
Italy, Japan, Mexico, the UK and the USA, the GHSI has appointed the
WHO as an expert adviser on health and has started a series of initiatives,
including exploring and encouraging joint projects to procure and develop
vaccines and antibiotics to counter biological agents, share emergency
response plans, collaborate on risk assessment and management, and agree
frameworks for countries to share expertise and laboratory linkages.
Surveillance of data and epidemiological information are seen as key
indicators in detecting a deliberate release or bioterrorism incident, so the
GHSI also seeks to ensure that such data is rapidly shared so that a speedy
response can be mounted.
Likely agents
The literature on state-sponsored biological warfare is now extensive and
identifies anthrax, Ebola virus and other haemorrhagic fevers (Marburg,
Crimean–Congo haemorrhagic fever or CCHF), botulinum toxin, plague,
204 | Zoonoses
tularemia, Q fever, brucellosis, Lassa fever and associated arenaviruses as
organisms that have been investigated and in some cases fully developed
into bioweapons.
Luckily obtaining and developing the majority of these organisms is
currently believed to be beyond the capability of terrorist groups according
to the CDC; however, the main fear is that a terrorist group might attempt
to use a bioweapon.
Historically, terrorists or other extreme groups have attempted to use
deliberate releases. In 1984, followers of the Bagwan Shree Rajneesh, in
Oregon, attempted to influence the outcome of a local election by contaminating salad bars with pathogenic Salmonella spp.52 In a similar incident at
a medical centre in Dallas, Texas in 1996, 12 people were severely ill after
a disgruntled colleague deliberately contaminated cakes with a Shigella spp.
Anthrax in particular has attracted the attention of terrorists, with Al
Qaeda allegedly attempting to develop the bacterium into a viable weapon
at a number of sites in Afghanistan before the invasion in 2002. After the
invasion of the country and the destruction of a number of sites, it is unclear
whether they are currently attempting to reconstitute this programme.53
Slightly more unusual were the attempts by the Aum Shinrikyo cult in
Japan to use botulinum toxin on a number of occasions in the early 1990s.
They also cultured anthrax, which they attempted to disseminate. There is no
evidence that there were any casualties from their efforts, unlike their
successful attack with sarin nerve gas in 1995 on the Tokyo underground,
where 12 people died and thousands required medical or hospital treatment.54
In the USA, the CDC has classified likely agents into three categories: A,
B and C (see list below – zoonotic diseases in bold). In essence those agents
in category A are considered to pose the highest risk in terms of ease of
dissemination and should be treated as the highest priority in terms of both
risk to human health and secondary spread, category B are the second
highest priority and category C the third priority, and include pathogens
that are emerging and might be engineered in the future to become capable
of mass spread.55
Category A
Anthrax (Bacillus anthracis)
Botulism (Clostridium botulinum toxin)
Plague (Yersinia pestis)
Smallpox (variola major)
Tularemia (Francisella tularensis)
Viral haemorrhagic fevers (filoviruses, e.g. Ebola, Marburg and arenaviruses,
e.g. Lassa, Machupo).
Pandora’s box | 205
Category B
Brucellosis (Brucella spp.)
Epsilon toxin of Clostridium perfringens
Food safety threats (e.g. Salmonella spp., Escherichia coli O157:H7, Shigella
spp.)
Glanders (Burkholderia mallei)
Melioidosis (Burkholderia pseudomallei)
Psittacosis (Chlamydia psittaci)
Q fever (Coxiella burnetii)
Ricin toxin from Ricinus communis (castor beans)
Staphylococcal enterotoxin B
Typhus fever (Rickettsia prowazekii).
Viral encephalitis (alphaviruses, e.g. Venezuelan equine encephalitis, eastern
equine encephalitis, western equine encephalitis)
Water safety threats (e.g. Vibrio cholerae, Cryptosporidium parvum)
Category C
Emerging infectious diseases such as Nipah virus and hantavirus.
Public health dimension
A deliberate or accidental release of a biological pathogen poses a threat to
the public, and therefore it is unsurprising that in the UK, the USA and the
EU there have been measures taken to try to put plans in place to tackle any
incident. It is also complex, because it requires, subsequent to the realisation
that an incident has occurred, a coordinated approach from health services
(primary and secondary care, government, public health authorities and
voluntary organisations such as the Red Cross), police and emergency
services, and also the media.
In the UK and the USA, the police will always have the lead in such situations, because it is likely to stem from a criminal act; however, emergency
preparedness, and the mitigation of such an attack, is a civil authority
responsibility within national guidelines, so health authorities and administrations should have a plan in place to deal with any incident quickly and
appropriately.56
The HPA is pivotal to the response to any such incident in the UK, and
has issued guidance (which can be found on its website) for health
professionals and public bodies, including the recent update of the HPA’s
CBRN Incidents – Clinical Management and Health Protection manual in
September 2008.57 Importantly the response in the UK relies on health
workers recognising new or unusual clusters of infections, where a number
of people becoming ill, at or around the same time, especially where associated with unusually high morbidity or mortality, or where a single case is
206 | Zoonoses
seen that demonstrates unusual or particularly severe symptoms, where there
is no associated history to suggest an explanation of the illness. Where such
cases are seen contact should be made immediately with the medical microbiologist or infectious disease consultant at the local hospital. Failing this,
contact the Director of Infection Prevention and Control, the local health
protection unit or the HPA direct on ⫹44 (0)20 8200 4400. Full details may
be found on the HPA website at www.hpa.org.uk.
In the USA, the county and then state and federal health authorities
should be contacted along with the CDC. More information can be found
on the CDC website – bioterrorism links (see Appendix 1).
Preparedness
In both the USA and the UK, emergency preparedness plans are exercised
regularly, sometimes using simulated casualties. Stockpiles of antibiotics,
protective clothing and decontamination materials are also maintained. As
healthcare professionals, the main role is to initially identify that an event
has occurred and be prepared to support the response to such an event with
the knowledge of treatment, prevention and infection control.
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7
Viral zoonotic diseases
This chapter describes viruses that have shown their zoonotic potential
dramatically by causing human illness, usually with associated fatalities.
Notes on arrangements of monographs
A decision has been made to use viral classification to group the following
conditions, as viral taxonomy has moved on dramatically since the first
edition of this book. Readers should be aware that there are other
classification methods.
One of these methods that may be seen in current literature is the overall
grouping of viral pathogens into a heterogeneous generalised classification of
arboviruses. An arbovirus is defined as any arthropod-borne virus transferred
from its normal reservoir (either animal or human) to humans via biting insect
vectors. The usual arthropods involved in transmission of the viral pathogen
from one host to another are either mosquitoes or ticks, both soft and hard
bodied.1 Most arboviruses can be classified as either dengue fever like or
encephalitides. They can be further subdivided into mosquito- and tick-borne
groups.
Alphaviruses
Chikungunya
Caused by an alphavirus, Chikungunya fever is transmitted to humans by the
bite of infected mosquitoes. It is found in west, central and southern Africa
and many areas of Asia. The animal reservoir is considered to be monkeys.
Following recent epidemics of the disease in Africa and Reunion, the disease
has been seen in returning travellers. There have been clusters of cases in
Italy, and there are fears that the disease has now adapted to indigenous
European species of mosquito, which may lead to further outbreaks.
210 | Zoonoses
Initial non-specific symptoms are followed by a debilitating illness, with
muscle pain, rash and extreme fever. Incapacitating joint pain and arthritis
may continue after clinical recovery from the acute phase, but is not similar
to that seen in dengue fever.
Treatment is symptomatic, but aspirin should be avoided because there
are risks of haemorrhagic sequelae. Chloroquine phosphate has also been
used, but opinion still remains divided as to its efficacy.2
Eastern equine encephalomyelitis
An alphavirus, eastern equine encephalomyelitis virus (EEEV) is mosquito
borne, and usually infects wetland birds and horses. Western equine
encephalomyelitis virus (WEEV) and Venezuelan equine encephalomyelitis
virus (VEEV) are related but genetically distinct alphaviruses. EEEV and
VEEV are lethal in up to 90% of horses showing clinical symptoms,
whereas WEEV is least virulent in horses, which have a mortality rate of
approximately 40%. EEEV is also capable of causing fatal encephalitis in
humans with a case mortality rate between 50% and 75%.
In the USA, EEEV occurs mainly from New England to Florida and
along the Gulf Coast, with rare reports of foci as far inland as Michigan and
South Dakota. The virus is maintained in mosquito pools, and then amplifies in birds. Subsequent transmission to horses occurs, and human cases
usually follow equine outbreaks. Human survivors are frequently left with
persistent neurological damage, including epilepsy and focal damage in
portions of the brain tissue. Initially starting with flu-like symptoms,
patients rapidly pass into a coma and are often severely disabled if they
survive.
Recent cases
The first case of eastern equine encephalitis in the UK occurred in early
October 2007. A man who had been to New Hampshire in the USA on a
fishing holiday developed symptoms after his return to the UK.
In late summer 2005, 11 laboratory-confirmed cases of EEEV disease
were reported in New Hampshire and Massachusetts, of whom 4 subsequently died. All the patients worked or socialised in areas near swamps,
cranberry bogs or other wetlands capable of supporting mosquito vectors,
and had potential exposure at dawn or dusk in the fortnight before the onset
of clinical disease. Investigations confirmed the presence of the virus in
mosquito populations in the vicinity of the patients.3
The virus was also found in wild birds, horses, alpacas, two emus and a
llama in New Hampshire, and in horses and an emu in Massachusetts.
During 2005, 21 confirmed cases of EEEV were reported across the USA to
Viral zoonotic diseases | 211
the Centers for Disease Control and Prevention (CDC), a distinct rise over
the annual average between 2000 and 2004 of 8.2 cases per year. The reason
for the rapid rise in cases numbers remains unknown.
Mayaro virus
Mayaro virus is a zoonotic alphavirus found in Latin America, transmitted
from its reservoirs of primates (monkeys and sloths), rodents and birds by
mosquitoes. Little is known of its clinical course in humans, but it can cause
an influenza-like disease and possibly encephalitis.4
Arenaviruses
Arenaviruses are normally associated with a range of rodent vectors, mostly
species of rats and mice. The first arenavirus to be identified was lymphocytic choriomeningitis virus in 1933. Since then, approximately 20 other
arenaviruses, some of which cause human disease, have been identified.
They are split into two main groups: the Old World (Lassa), and New World
(Tacaribe) complexes. The Lassa complex includes Ippy, Lassa, lymphocytic
choriomeningitis, Mobala, Mopeia and Mozambique viruses. The Tacaribe
complex consists of Allpahuayo, Amapari, Bear Canyon, Flexal, Guanarito,
Junin, Latino, Machupo, Oliveros, Parana, Pichinde, Pirital, Sabia, Tacaribe,
Tamiami and Whitewater Arroyo viruses.5
Infected rodents are asymptomatic, and may acquire the virus by
maternal transfer, traumatic injury such as bites or scratches or faecal–oral
transfer. Human infection follows inhalation or contamination of
wounds/abrasions by rodent faeces, saliva or urine. Contaminated food may
also cause infection.6
Once across the species barrier, some of the arenaviruses such as Lassa,
may spread by human-to-human or fomite transfer.
Zoonotic arenaviruses
Guanarito virus
A zoonotic arenavirus, this virus has been found only in the Guanarito
municipality of Barinas state, Venezuela. The reservoir is cane rats, with the
disease being transmitted either via a vector or by direct contact with rats or
their body fluids. In humans it can cause severe disease, characterised by
fever, malaise and sore throat, followed by abdominal pain, diarrhoea,
haemorrhagic manifestations, convulsions and death.
Diagnosis is confirmed only by viral isolation and treatment is purely
symptomatic.7
212 | Zoonoses
Junin virus
Also known as Argentinian or South American haemorrhagic fever, cases of
Junin virus are seen only in the Junin region, east of Buenos Aires. Disease
outbreaks are normally seen between February and August during the agricultural growing season, when agricultural workers become exposed to
infected rodents or their urine and faeces in soil or aerosols. Person-toperson transmission has also been reported. Symptoms are similar to Lassa
fever and other arenavirus infections. There is no treatment, and fatality
rates range from 3% to 30% depending on lethality of the strain prevalent
in the outbreak.
Lassa virus
Lassa virus causes Lassa fever, an acute viral haemorrhagic fever first
described in 1969 in the town of Lassa, Nigeria. It is endemic in west Africa
with approximately 300 000 cases annually, of which up to 5000 are fatal.
Cases have been seen elsewhere in the world due to the movement of
infected patients during the incubation period via airlines.8
Following infection, by exposure to infected rodent faecal matter or
urine, or by patient-to-patient spread often through contaminated blood,
there is an incubation period of 6–21 days during which the virus initially
colonises the mucosa, intestines, lungs and urinary tract, followed by spread
into the vascular system.
Most infected patients are asymptomatic, but in about 20% of cases it
can cause severe disease. Generalised symptoms include fever, facial swelling,
fatigue, conjunctivitis and mucosal bleeding with bloody vomiting or
diarrhoea. There may be involvement of the vascular system, with cardiac
complications, respiratory difficulty, and encephalitis or meningitis with
associated seizures. Clinical cases may not be easy to differentiate from those
caused by Ebola or Marburg virus or malaria. Clinical cases in pregnant
women usually require abortion, because the virus has a particular affinity
for the placenta, and only 10% of infected fetuses survive.9
The overall mortality rate is approximately 1% of cases, although in
some case clusters this can reach 50%, especially where early therapy or
supportive measures are unavailable.
There is no vaccine currently available for Lassa fever; however,
development is being undertaken, with the closely related, but less virulent,
Mozambique virus being considered as a possible candidate because it
shows cross-reactivity without the lethality.
Case of imported Lassa fever, New Jersey, 2004
In August 2004, a New Jersey resident died of Lassa fever following travel
to west Africa. He had been in Liberia (where he had been born) and Sierra
Leone, and had returned to the USA via England. Luckily none of the fellow
Viral zoonotic diseases | 213
travellers who were traced and tested was infected in either the USA or the
UK. About 20 cases of imported Lassa fever have been reported worldwide.
Lymphocytic choriomeningitis virus
Lymphocytic choriomeningitis virus (LCMV) is endemic in house mice
worldwide. Pet rodents such as hamsters, guinea-pigs or rats may acquire
the infection by contact with infected mice. Normally LCMV in humans is
asymptomatic, causes a mild, self-limiting viral infection similar to influenza
or in rare cases causes an aseptic meningitis that is occasionally fatal, following
a pre-patent period of 7–14 days. However, in patients who are already
immunocompromised, LCMV may result in serious infection leading to death.
LCMV infection during pregnancy, although uncommon, can cause abortion
or severe birth defects, and fetuses may be infected from birth by maternal
transfer. A study undertaken in the USA indicated that 5% of the human
population had immune system markers for LCMV, indicating widespread
infection.10
Pregnant women and immunocompromised patients should reduce their
exposure to rodents whenever possible. Children and the owners of pet
rodents should adopt hygiene procedures such as hand washing, and not
allowing faecal matter, saliva or urine to be inhaled, or come into contact
with wounds or abrasions. Wild rodents should be controlled routinely in
all domestic and industrial premises.
LCMV in transplant recipients
In April 2005, LCMV infection was passed to four transplant recipients from
an infected donor who had acquired the infection from an infected hamster.
Three of the four died. The investigation after the incident demonstrated that
LCMV-infected pet rodents were extant across pet shop distribution chains.11
Machupo virus
Found in Bolivia and first identified in 1959, Bolivian hemorrhagic fever or
black typhus is caused by Machupo virus, a group V arenavirus related to
Junin virus of the Old World arenavirus group.12
Infection is caused by inhaling aerosols of rodent urine or droppings
specifically from the vesper mouse. It may also follow contamination of
open wounds with infected material. Infected rodents are asymptomatic.
The incubation period is between 7 and 16 days. The infection is of slow
onset with fever, lethargy, headache and muscular pains. Facial flushing and
reddening of the throat may follow, with bleeding from the nose and gums,
vomiting of blood and blood blisters as the disease progresses into the
haemorrhagic phase, usually within 7 days of onset. The mortality range is
between 3% and 30% of cases. Person-to-person transmission has been
reported especially in healthcare settings.
214 | Zoonoses
Reducing contact between infected rodents and humans has been effective,
with few recent cases being reported. A vaccine developed for Junin virus has
shown cross-immunisation potential and could be used in individuals at risk
of infection.
Mobala virus
A novel arenavirus found only in the Central African Republic, and possibly
Argentina, the natural reservoir is rodents, and in particular soft fur rats.
The disease caused is similar to Lassa fever or Ippy virus. The transmission
pathway is unclear, but it is possibly via aerosol or vector routes. Diagnosis
follows isolation of viral particles and classification using antigen test
methods.
Sabia virus (Brazilian haemorrhagic fever)
An arenavirus that has been found naturally in only one clinical case in
Sabia, Sao Paulo, Brazil (1990). Only three clinical cases have ever been
recorded: the index case, the physician who examined clinical samples from
the index case and the third case after a laboratory accident at a reference
collection. The animal reservoir is as yet unknown, but believed to be
rodents. Transmission is believed to be by aerosolised infected body fluids.
In humans it presents with fever headache, myalgia, nausea, vomiting,
conjunctivitis, acute hepatitis, diarrhoea and gastrointestinal haemorrhage.
Bunyaviruses
Crimean–Congo haemorrhagic fever
The causative agent of Crimean–Congo haemorrhagic fever (CCHF) is a
bunyavirus carried by Ixodes ticks. It is found in eastern Europe, the
Balkans, Greece, Turkey, central Asia, Africa, China, the Middle East, India
and the former Soviet Union.13
In 1944, an outbreak occurred in the Crimea; this together with a further
outbreak in 1969 in the Congo led to the naming of the disease. Infected ticks
act as both a vector and a reservoir for the disease, with transovarial spread
occurring. Wild and domestic animals such as cattle, goats, sheep, rabbits and
hares act as both a reservoir and an amplifying host for the pathogen.
In humans, following a bite from an infected tick, there can be an acute
onset of symptoms, with severe headache, rapidly elevating temperature,
arthralgia, muscle pain and gastrointestinal disturbance. Eyes may become
bloodshot, the throat inflamed and reddened, with focal blood blisters. As
the disease progresses there may be altered mental states, jaundice, massive
haematomas and bleeding from the nose and throat. This may continue for
14 days, if the patient survives, with fatalities ranging from 9% to 50% in
Viral zoonotic diseases | 215
some outbreaks. Agricultural workers in regular contact with animals in
endemic areas are at risk. Person-to-person transmission is possible because
infected blood or fluids can cause nosocomial spread.
Diagnosis is by polymerase chain reaction (PCR) or enzyme-linked
immunosorbent assay (ELISA). There is no specific treatment and treatment is usually symptomatic; however, ribarvin has undergone trials as a
treatment and, as a result of the severity of the side effects, a case-by-case
assessment must be made before treatment. A vaccine has been developed
but it is not licensed in the UK or the USA.14
Hantaviruses
The first occasion on which a hantavirus was recognised as a cause of
human fatality occurred in Hantaan, Republic of Korea, in 1978. A
bunyavirus, approximately 14 species of closely related viruses have since
been identified within the genus Hantavirus, named for the locations in
which they were first identified.
Rodents form the natural reservoir for these viruses, and different species
of rodent are linked to specific geographical areas and viral species. Infected
rodents do not generally show clinical symptoms of the disease. The virus
has also been found in birds in Russia and cats in China.
There are approximately 150 000–200 000 cases of hantavirus-related
disease reported annually, with about 50% occurring in the People’s
Republic of China. Classic hantavirus infection usually presents with renal
involvement and haemorrhagic features. Hantaviruses cause haemorrhagic
fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary
syndrome (HPS) in the Americas. In both Eurasia and the Americas, people
with occupational exposure to rodents are considered to be at greater risk
than the general population.
Human disease
After infection, clinical symptoms may appear between 7 and 28 days.
Initial symptoms mirror those of many viral diseases, with fever, headache
and non-specific gastrointestinal symptoms. Later, cough, breathing difficulties and circulatory collapse may follow, particularly in HPS. Kidney failure
may occur in HFRS after renal inflammation or destruction. Patients who
survive normally recover fully.
HFRS
HFRS is endemic in Eurasia. In Europe, three hantaviruses have been
identified as causative: Puumala virus (PUUV), Dobrava virus (DOBV) and
Saaremaa virus (SAAV).
216 | Zoonoses
The Balkan area has two forms of HFRS, with the less severe causing
virtually no fatalities, and a severe form in which more than 10% of patients
die. In Denmark, Estonia, Germany Latvia, Lithuania, Slovakia and other
European countries, no fatal cases have been reported.15
There was a large outbreak in Serbia and Montenegro in 2002, with 128
confirmed cases; subsequently, in 2003, there were 34 cases in the same area
and 31 in 2004. This may have been caused by climatic conditions, the
increase in the rodent population and the years of armed conflict, which had
led to drastic alterations in social and environmental conditions.
In 2005, there was a large increase in confirmed hantavirus infections in
Germany, with 448 confirmed cases from both rural and urban areas. This
was almost three times the number of patients recorded in previous years
and appeared to be associated with an explosion in the population of bank
voles, the rodent reservoir of PUUV.16
A similar marked increase of hantavirus infection was observed in
Belgium and France in the same year, although patients living in densely
populated urban areas were reported only from Germany.
HPS
HPS was first recognised in 1993 after an outbreak of severe respiratory
disease in the Four Corners Region of the USA; of 42 confirmed cases, 26
died. The Sin Nombre virus (SNV) was identified as the hantavirus responsible. The hantavirus disease symptoms associated with Sin Nombre virus
are atypical, with fever; headache, diarrhoea, muscle pain and respiratory
symptoms gradually worsen into acute respiratory distress.17
Since then a clade (group of viruses with common genetic ancestry) of
four other hantaviruses – Bayou virus, Black Creek Canal virus, New York
virus and Monongahela virus – has been identified as responsible for HPS
in the USA. HPS cases have also been reported in Argentina, Bolivia, Brazil,
Canada, Chile, Panama, Paraguay and Uruguay.
North America
Between 1993 when the disease was recognised, and early 2006, the CDC
has confirmed 438 cases of HPS across 30 US states, with a 35% fatality
rate. In early 2006, nine cases of HPS occurred in Arizona, New Mexico,
North Dakota, Texas and Washington.17
South America
In late 1996, there were 18 cases of HPS in El Bolson, Argentina. A new
hantavirus, subsequently named Andes virus, was identified. All the patients
were either local residents or had visited the area. Three doctors who had
treated patients also became ill, probably from the first recorded instance of
Viral zoonotic diseases | 217
person-to-person transmission. Andes virus is responsible for most of the
cases recorded in Argentina, Chile and Uruguay.
An outbreak of HPS occurred in Chile in 1997; of a total of 25 cases,
there were a number of family clusters, in which nosocomial spread may
have occurred.18 In addition during mid-January 1999, an outbreak of HPS
occurred in Panama. The causative hantavirus was designated Choclo
virus.19
In 2000, a total of six male patients in Bolivia (aged 15–49 years) were
serologically confirmed to have HPS; five died. Five of the six cases occurred
between April and July, the sixth in November. All the patients lived and
worked in rural areas in a 70-km radius around Bermejo. The hantavirus
responsible is closely related to Andes virus and is now known as Bermejo
virus.20
Transmission
Transmission is not by arthropod vector, but usually follows inhalation of
infected aerosols of rodent saliva, urine or faecal material. Cases have been
reported after rodent bites or wound inoculation with infected material.
Human-to-human transmission has been seen in HPS, and may be
possible in patients with HFRS, where infected blood or body fluids could
cause nosocomial transmission.
Diagnosis
Diagnosis follows PCR or ELISA testing of clinical samples.
Treatment
Supportive treatment is essential to maintain organ function. HPS cannot be
effectively treated with antibiotics; however, in early disease patients should
be placed on broad-spectrum antibiotics until the diagnosis of HPS is well
established, because differential diagnosis between bacterial shock and
hantaviral shock may be difficult. Ribarvin is effective in HFRS but it has
shown no clinical effectiveness in HPS cases.21
Prevention
Prevention revolves around reducing exposure to infected rodents and their
faeces or urine. For some areas in the USA, the problem is complicated by
the range of infected rodents coinciding with natural plague foci, and the
demise of rodents may lead to associated, possibly infected, fleas seeking
alternative hosts and provoking a plague outbreak.
218 | Zoonoses
Cache Valley virus
Cache Valley virus (CVV) disease is caused by a mosquito-borne bunyavirus
and is widespread in North America, where its animal reservoir consists of
deer, sheep, cattle and horses.
Only two human cases have been seen, probably because it is seldom
tested for; one of the patients died of acute encephalitis. The other case
presented with severe headache, nausea, vomiting and generalised fatigue.
The illness then progressed to an aseptic meningitis. Therapy was purely
supportive and the patient made a full recovery. The route of infection is
unknown.22
The closely related Ngeri virus caused an outbreak of haemorrhagic
fever in Africa in 2004.
La Crosse virus
The bunyavirus that causes La Crosse (LAC) virus encephalitis, which
mainly affects children, is widespread in the mid-western and south-eastern
USA, and was first identified in La Crosse, Wisconsin. Approximately 75
cases are seen annually. It is transmitted by mosquito bite, and the virus can
be transferred from mosquito to offspring via the transovarial route. The
animal reservoir is squirrels and chipmunks, with transmission by mosquito
bite.23
Symptoms are often non-specific and progress to coma, paralysis and
permanent brain damage in severe cases. Treatment is purely symptomatic.
Oropouche virus
A bunyavirus, Oropouche virus causes a febrile illness known as Oropouche
fever. Transmitted by mosquitoes to humans from sloths, it occurs in the
Amazon region of South America, the Caribbean and Panama. First isolated
in Trinidad and Tobago, it has since been responsible for several large
epidemics in Brazil in the 1970s and 1980s.24
The illness presents with a fever of abrupt onset, with other generalised
symptoms of chills, headache, anorexia, muscle and joint pain, and
vomiting, which may progress to meningitis. Diagnosis follows detection of
viral antibody in serum samples.
Treatment is non-specific with anti-inflammatory drugs or other symptomatic relief. Aspirin should be avoided because there is a summative risk
of haemorrhagic complications. The illness is usually self-limiting with most
patients making a full recovery.
Viral zoonotic diseases | 219
Rift Valley fever
The causative is a bunyavirus, and the virus is passed to humans via the
bites of infected arthropod vectors, which have previously fed upon
infected animals, usually cattle, sheep, camels or goats. The virus may also
be transferred by direct contact with infected animals, slaughtering or
butchering beasts, or the consumption of infected meat or milk.
First recorded in Kenya in 1930, it is widespread in east Africa;
epidemics are often associated with high rainfall, because this increases the
mosquito population which is the prime vector for the spread of the disease.
In animals the disease often causes abortion and death, especially in young
animals.
In humans, the initial symptoms resemble influenza, but onset of severe
disease (usually in only about 8% of cases) is manifested by the onset of
acute fever, associated with severe headache, arthralgia and myalgia; there
may also be unexplained bleeding, visual disturbance and alteration in
mental state, with meningoencephalitis.
Survivors of severe disease may have permanent visual impairment and
may never fully recover. Animals can be vaccinated against the disease, but
there is no treatment and, although a vaccine for humans has been developed,
it is not yet licensed.
Outbreaks
The largest recorded outbreak was in Kenya in 1997–8 with an estimated
89 000 cases and 478 deaths. In 2000, the disease appeared in Saudi Arabia
and Yemen, possibly following the importation of infected livestock with
800 and 1000 cases, respectively.25
An outbreak of Rift Valley fever occurred in Kenya between November
2006 and January 2007. There were a total of 404 confirmed cases with 118
fatalities. The outbreak was controlled by banning the slaughter and movement of animals, with immunisation of apparently healthy animals in the
areas unaffected but contiguous with the infected area, and a widespread
spraying programme to reduce mosquito populations and breeding rates.26
In October 2007, an outbreak occurred in Sudan which, by November
2007, had 125 confirmed cases with 60 fatalities.
Coronaviruses
SARS
In November 2002, an outbreak of a pandemic of coronavirus that caused
severe acute respiratory syndrome, or SARS, occurred. The outbreak was
220 | Zoonoses
brought under control in July 2003, although sporadic outbreaks were
reported from the People’s Republic of China, where the original outbreak
had occurred in late 2003 and early 2004. During the initial outbreak the
virus spread to 33 countries in 5 continents and caused at least 8000 cases,
of which more than 700 were fatal.
The causative coronavirus was later discovered to have a natural reservoir
in several species of horseshoe bats, along with a number of other novel
viruses from the same genus.27
The SARS virus is capable of infecting a number of animal species and
humans, with virus being detected in live animal markets and in the wider
environment in rats, palm civets, raccoon dogs and ferret badgers. It is unclear
if bats transmitted the virus direct to the initial human cases, or whether the
route was via other animals including the masked civet or other susceptible
intermediary species; however, it would appear that the infective reservoir is
species of bats, in a manner similar to Nipah and Hendra viruses.28
The transmission route for SARS is unknown and there is still debate as
to whether this is from infected aerosols, blood, urine or faeces.
The discovery of SARS-like coronaviruses in bats highlights the
increasingly recognised importance of bats as reservoirs of emerging viruses.
Filoviruses
Marburg virus
Marburg virus is caused by a filovirus closely related to but distinct from
Ebola virus. It causes a haemorrhagic fever similar to Ebola fever, and has
been isolated from fruit bats. The main range for the disease is Uganda and
eastern Congo.29
The animal host is now believed to be bats, following the detection of
antibodies/isolation of the virus from bats and fruit bats living in underground mines in The Democratic Republic of Congo (DRC). It still needs to
be determined whether the bats are either infected by parasites or by
consuming infected arthropods, or the primary reservoir.30
The bats are believed to shed the virus in their blood, saliva, faeces and
urine, in a manner similar to many other bat-borne viruses. The initial
outbreak among laboratory primates, which then spread to humans in
Marburg, Germany in 1967, is believed to have arisen after the monkeys
were held in a holding facility in Uganda where they were exposed to fruit
bats that may have been infected.
Outbreaks
There were isolated cases of Marburg haemorrhagic fever in 1975 (South
Africa), 1980 and 1987 (Kenya). There was a protracted outbreak of
Viral zoonotic diseases | 221
Marburg virus in the village of Durba in the DRC between late 1998 and
late 2000. There were 154 patients with a fatality rate of 83%. The primary
cases were seen in young male miners; secondary spread occurred to families
and healthcare workers.
In 2004–2005, there was a major outbreak in Angola, with an
unrecorded number of cases, which led to more than 300 deaths.
Disease in humans
Human infection follows exposure to infected blood, saliva or faeces, probably from the animal host in primary infections, and then from primary
patients in secondary cases. The incubation period is between 3 and 9 days,
initial symptoms are non-specific and early differential diagnosis is almost
impossible. Five days after the initial symptoms a maculopapular rash
appears on the trunk, which may be followed by organ involvement, causing
hepatitis, jaundice, pancreatitis, anorexia and altered mental states, with
haemorrhage, fluid loss and organ failure. The clinical course lasts from
1 week to 3 weeks when the infection regresses or kills the patient. Full
recovery in survivors may be prolonged.
Treatment is purely supportive, with administration of intravenous fluids
to prevent hypotension and volaemic shock as a mainstay; however, patients
with symptoms of haemorrhagic fever may respond poorly, and pulmonary
oedema can occur. A vaccine is under development in both the USA and
Canada.
Patients must be barrier nursed with strict controls on use of protective
clothing at all times. In 2007, there were two cases in Uganda with the
primary case being a male miner, who survived, and the second one of his
co-workers who cared for him during his illness, and who subsequently died.
Paramyxoviruses – henipaviruses
Hendra virus
This pathogen was first identified after a respiratory tract illness was seen in
20 horses and 2 humans in Hendra (a suburb of Brisbane), Queensland,
Australia, during September 1994. The resulting fatalities included 13 of the
horses and their trainer. A stable hand who became infected survived. A
second unconnected outbreak was identified as having occurred in Mackay,
Queensland, in or about August 1994. The Mackay outbreak was much
smaller – only two horses died and one human was infected, and later died.
The outbreak was identified only retrospectively after the death of the man,
14 months after his exposure to infected horses. There have been four more
outbreaks, each of which resulted in the death of one horse, the first in
January 1999 in Cairns and the latest on the Sunshine Coast in June 2006.
222 | Zoonoses
The only human case seen was in a vet involved in the postmortem
examination of the horse in 2004, who recovered.31
Initially the causative virus was named equine morbillivirus; this was
later changed to Hendra, after the geographical site of the first-documented
outbreak. A paramyxovirus, closely related to measles and rinderpest, it had
not been identified previously as responsible for disease in either humans or
horses.
Disease in animals
In horses, the disease causes respiratory distress, fever, pulmonary oedema,
and nasal and oral discharge with blood present. As the disease progresses,
there is central nervous system (CNS) involvement. Serologically positive
fruit bats, which are usually asymptomatic, have been found in Australia
and Papua New Guinea. Experimentally the virus can cause severe disease
in cats, which can pass viable organisms in their urine, as can horses. Horses
could be initially infected by consuming feed contaminated with the virus,
but the route of infection is unknown.32
Transmission
The route of transmission from horse to human initially seemed to be by
contact with infected blood or secretions. Investigations since have shown
the presence of the causative pathogen in fruit bats, which seem to form the
normal reservoir in which no clinical signs of disease are seen.
Close contact seems to be sufficient for horse-to-horse spread; however,
the route of transmission from bat to horse is believed to be from aerosols
of infected urine, amniotic fluid from pregnant bats or nasal discharge.
There has been no evidence of bat-to-human spread, or human-to-human
spread in this disease.
Disease in humans
The virus is not deemed to be highly contagious. Clinical presentation starts
as a flu-like illness with fever and aching muscles. Sore throat, dizziness,
drowsiness and confusion follow. Haemorrhage into or oedema of the lungs
may follow, with meningitis. Death usually follows respiratory and renal
failure.
Prevention
Good hygiene practice and quarantine of infected animals help control
outbreaks.
Nipah virus
In the period between late 1998 and mid-1999, there were cumulative
reports of a novel form of encephalitis causing fatalities and neurological
Viral zoonotic diseases | 223
damage in pig workers in Malaysia. Three major clusters of cases were seen.
The first was near Ipoh in the state of Perak, the second in Sikamat in Negri
Sembilan, and the third and largest in Bukit Pelandock, also in Negri
Sembilan.33
At first the disease was considered to be Japanese encephalitis. However,
the pattern of infection, the scale of the outbreak and the predominance of
mature male Chinese pig farm workers led to the conclusion that a novel
zoonotic agent was implicated.
Transmission
A novel paramyxovirus related to but not identical with Hendra virus was
identified as the causative organism. Most victims were of Chinese ethnicity
– an important factor in determining the animal origin of the virus. In
Malaysia, where there is a diverse ethnic mix, ethnic Malays are predominantly Islamic and are therefore not involved in the pig industry. No cases
were seen in this group. If a widespread environmental vector such as a
mosquito had carried the pathogen responsible for the disease, this distinct
identification of victims by ethnicity and employment would not have been
seen.34
Of the patients identified as suffering from the disease, 93% were
involved in pig farming or associated activities. When histories were taken
from those patients who were able to respond to questioning, the majority
reported contact with swine before developing symptoms, and a large
proportion of these patients stated that they had contact with pigs that were
already ill. This evidence strongly indicated that pigs were the source of the
disease, particularly because, on farms where human cases were seen, the
pigs were also dying of a disease characterised by symptoms of respiratory
tract infection and airway insufficiency. This led to the conclusion that the
route of infection could be the inhalation of infected aerosols.
Disease in humans
The period between exposure to swine and overt disease was estimated to
be usually less than 14 days from the histories taken from patients or their
relatives. The main symptoms seen at the onset of clinical disease were
neurological, with drowsiness and lowered levels of consciousness, loss of
muscle tone, sensory and cerebral dysfunction, progressive disorientation,
seizures, muscle spasm and spasticity. Generalised symptoms such as
headache, dizziness and sickness were also seen in some cases, before or
associated with the onset of more serious symptoms.
The disease progressed to encephalitis, with 32% of patients dying, 53%
recovering fully and 15% surviving but with persistent neural abnormalities
and damage. In the Malaysian outbreak, of the 265 people affected 105
died.
224 | Zoonoses
No human-to-human transmission was documented, although familial
clusters were seen. This probably relates to the pattern of employment on the
pig farms, with whole families employed in the same enterprise. Healthcare
workers who cared for patients suffering from Nipah virus or who were
involved in their postmortem examinations were all monitored for disease:
none showed any clinical signs of contracting the condition.
Soldiers employed in the culling of pigs, abattoir workers and veterinary
surgeons involved in outbreak control were also screened for antibodies to
the virus.
Diagnosis
Confirmation of diagnosis was obtained by isolation of viral particles from
the blood and cerebrospinal fluid of victims, both swine and human. In
humans there were demonstrable abnormalities in both fluids. The viral
particles, later genetically sequenced, were found to be identical in both pigs
and humans, confirming the theory that the agent was zoonotic and had
arisen in humans from initial swine infection.
Treatment
The only treatment available was generalised supportive therapy using
aspirin and theophyllines. Half of the cases admitted to hospital lost
consciousness and half of these patients required intubation and respiratory
support. No intervention appeared to show any influence on the eventual
mortality rate. On postmortem examination, damage was found in the
CNS, lungs and kidneys. Using staining techniques, the virus was found to
be present in neural and endothelial cells in the brain.
Prevention
It was decided that the main method of preventing further cases should be
a comprehensive cull of all pigs in the Malay states of Negri Sembilan, Perak
and Selangor. Approximately 890 000 pigs were slaughtered. Measures
were put in place to prevent pig movements, to implement a health education programme, and to provide protective clothing and equipment to pig
farmers. A system for national surveillance to identify and destroy any other
herds identified as being infected was established. Following the cull, no
new cases of the disease were seen.35
In Singapore, by mid-March 1999, there were 11 cases of acute symptoms associated with the disease in abattoir workers reported to healthcare
officials, of whom one subsequently died. All the infected individuals had
handled imported pigs. A decision was swiftly taken to stop all imports
of pigs from peninsular Malaysia and to close all abattoirs on 19 March
1999. Subsequent to these decisions no further cases were reported. Singapore
Viral zoonotic diseases | 225
also banned racehorses and other horses from entering or returning from
any of the constituent states of Malaysia.
Retrospective analysis of the infective pattern associated with the
outbreak led to the conclusion that the spread of the disease was related
to the transportation of infected pigs, either from farm to farm or from
farm to abattoir. A dead dog was found to have the virus post mortem;
however, this was an isolated case. It is now believed that, in common
with Hendra virus, the viral reservoir is fruit bats. Cats are susceptible to
Nipah virus and can shed the virus in urine and nasal mucus, but research
has shown that they are rarely exposed in nature by contact with fruit
bats. The cats found to be infected in the Malaysian outbreak had probably been infected by contact with pigs that were dead or dying from the
disease.
One of the less important but still publicly significant effects of this
outbreak was the lack of pork available for Chinese cookery, reducing the
variety of dishes available in restaurants across the Malay peninsula.
The Nipah virus outbreak prompted much research and investigation
work to be undertaken into the normal host for the virus, and to map its
geographical spread.
An outbreak of encephalitis in Faridpur, Bangladesh in April–May 2004
was identified as being caused by Nipah virus which appears now to be
endemic in the region. Of 36 cases, 75% died. Analysis of the outbreak
confirmed person-to-person transmission which was suspected following
outbreaks of the same pathogen in Siliguri, India and Mehrepur, Bangladesh
in 2001; further outbreaks followed in Naogoan, Bangladesh in January
2003 and in Rajbari and Faridpur, Bangladesh in January–February 2004.
The lack of transmission during the Malaysian outbreak is probably linked
to different healthcare and social practices. There are other paramyxoviruses
that spread easily from person to person, and Nipah virus has now been
isolated from respiratory mucus.36
There was another outbreak in Tangail, Bangladesh from late 2004 until
early 2005; of 12 clinical cases, 11 died (92%). Two-thirds of the victims had
drunk raw date palm sap, which fruit bats could have contaminated (as it was
being collected) with saliva, faeces, urine or by drowning in the collection
containers.
The latest outbreaks were between February and May 2007 in Nadia,
India and Kushtia, Bangladesh. In both outbreaks there were approximately
50 cases with a 10–12% fatality rate.
Eleven isolated cases of Nipah virus encephalitis have also been
documented in Bangladesh since 2001.
226 | Zoonoses
Other unusual paramyxoviruses in fruit bats
As a result of the emergence of Hendra virus, a research and investigation
programme was set up to monitor diseases associated with fruit bats. Within
the first 4 years two other viral diseases capable of zoonotic activity were
identified in Australia.
Another paramyxovirus, now named Menangle virus after its first place
of identification, caused an outbreak of disease at a piggery in New South
Wales, Australia, in 1997. The pigs suffered illness, and sows spontaneously
aborted. Human workers showed symptoms similar to influenza. Serological
testing showed the virus to be the same in pigs and humans. The suspected
reservoir is also fruit bats.
Tioman virus is another group V Mononegavirales paramyxovirus. It was
first isolated from the urine of fruit bats on Tioman Island, Malaysia in 2000
while efforts were being made to identify the natural host of Nipah virus.
Related to Menangle virus, there is no evidence that Tioman virus can
cause human illness; however, as it is closely related to other zoonotic
paramyxoviruses, continuing monitoring of any suspected cases is required.37
Range
Fruit bats across Malaysia, Thailand and Cambodia have tested positive for
Nipah virus infection, although it is possible that the virus circulating in
Cambodia may be another closely related henipavirus. Nipah, Hendra and
Tioman viral antibodies have been found in fruit bats from Madagascar. It
is possible that these viruses are prevalent in fruit bats across their whole
geographical range including Africa. No human cases of henipavirus infection
has been seen outside Malaysia, Australia or Bangladesh.38,39
Flaviviruses
Apart from the diseases listed in the following section, the flavivirus group
also includes Ebola (see Chapter 6) and yellow fever (found in wild
primates, transmitted by mosquito, but not considered to be zoonotic,
although possibly reverse zoonotic, i.e. humans to animals, because the
main reservoir is now believed to be humans).
West Nile virus/Kunjin virus
West Nile virus (WNV) was first identified in the West Nile province of
Uganda in 1937. A flavivirus, closely related to the causative pathogens of
Japanese encephalitis and St Louis encephalitis, historically it has been
confined to Africa, the Middle East and the Mediterranean coast. In the
biggest outbreak recorded in 1974 in the Cape Province of South Africa,
Viral zoonotic diseases | 227
almost 3000 people were infected. Kunjin virus, which is very closely related
and is believed to be a subtype of WNV, is found in Australasia and south-east
Asia.40
In Europe, WNV was first detected in Albania in 1958. The pathogen
has since been detected in Portugal, France, Italy, the Czech Republic,
Slovakia, Hungary, Romania, Moldavia, the Ukraine and Belarus. Most
cases have coincided with periods of maximum activity for mosquitoes,
usually July to September, when adjusted for the infectious pre-patent period.
Work in the USA has now demonstrated that the virus can over-winter in
adult mosquitoes. Reintroduction into previously disease-free or quiescent
areas may follow an influx of infected migrating birds.
Disease in animals
The natural reservoir for the virus is wild birds, where its presence is especially significant in migratory species, because this forms a highly mobile
infectious reservoir. Birds that become infected are believed to suffer from
clinical symptoms of disease. As most are wild species, the course of infection
is not easily determined, although it is believed that the outcome is either
death or survival. Birds that survive can become carriers.
The introduction of a carrier into a susceptible population of birds at a
time when there is high seasonal mosquito activity can produce widespread
infection, with a resulting ‘die-off’ of birds similar to that associated with
the introduction of plague (Yersinia pestis) in susceptible rodents. Once the
virus enters the mosquito population, it is also spread into any other
mammals, including humans, that the insect bites. Transfer vertically through
a generation of mosquitoes occurs by transfer from female adults to eggs laid
post-infection. The other mammals usually affected include horses, bats,
rodents, cats and raccoons.
Transmission
The disease is spread from bird to bird, and from bird to human, by a variety
of mosquito species, depending on the geographical area involved (Figure
7.1). The spread of the disease into either local bird or human populations
is solely dependent on the presence or absence of suitable vectors if infected
or carrier birds are present. Much work has been done to identify the main
species involved; however, the spectrum is so diverse that it is best to assume
that all migratory birds under suitable conditions can suffer from or carry
the pathogen.
Incidence
There were a series of notable outbreaks in the late twentieth century, with
Senegal in 1993, Romania in 1996 (of 500 reported cases approximately
10% were fatal), Israel and Kenya in 1998, and Volgograd, Russia, in 1999
228 | Zoonoses
Domestic birds
Migratory birds
Transovarian
spread
‘Die-of’
‘Die-of’
Figure 7.1 Cycle of infectivity and maintenance for West Nile virus in bird and vector
populations.
with 826 cases, of which 84 progressed to meningitis, with approximately 40
fatalities. Cases have also been seen in the Camargue region of southern
France, where an outbreak killed 20 partially feral horses in 2000, although
no human cases were reported. Case distribution follows migratory bird
patterns.
Although endemic in several regions of the globe, the disease did not
receive any particular media attention until 1999, when an outbreak
occurred affecting the eastern seaboard of the USA. Between August and
October there were 62 human cases reported and confirmed, with 7 deaths.
The centre of the outbreak was in Queens, New York City, where a large
‘die-off’ of birds, particularly crows, was seen shortly before the first human
cases. Many birds across a wide variety of species in the Bronx Zoo also
died. Once confirmed by serological testing, the outbreak was determined to
be the first outbreak ever seen in the USA.
This outbreak seems to have arisen as a result of the coincidence of a
number of environmental changes. The mosquito population had increased
markedly, partially due to prevalent climatic conditions during the previous
Viral zoonotic diseases | 229
year, and also as a result of the cessation of insecticide treatments on areas
of standing water in public parks. The cases in humans coincided with the
active feeding phase of the mosquito life cycle.
Subsequent to this outbreak the virus seems to have managed to establish
a presence in the mosquito population, with further outbreaks occurring on
an annual basis. In 2000, 18 cases, including one fatality and one patient left
in a permanent vegetative state, were seen in New York and New Jersey. The
virus was detected in mosquitoes and birds before the cases occurred. In
2007, there were 3304 cases of WNV reported from 43 states across the
USA, of which 93 were fatal; 286 viral positive blood donors were identified,
of whom 2 later progressed to neuroinvasive disease and 59 to clinical fever.
Since 2000 the WNV Surveillance System, set up in response to the 1999
outbreak in the USA, has demonstrated an increase in the geographical
range of WNV activity. Surveillance included monitoring mosquitoes,
sentinel chicken flocks, wild birds and potentially susceptible mammals (e.g.
horses and humans). In 1999, WNV activity was detected in only four areas:
Connecticut, Maryland, New Jersey and New York.
In 2007, across 34 states, nearly 1600 dead crows and 500 other birds
were reported as testing positive for the virus. Horses across 33 states tested
positive for WNV, along with dogs in 3 states and squirrels in 2 states.
Seroconversion to WNV was reported in 764 sentinel chicken flocks in 11
states. A total of 7772 WNV-positive mosquito pools have been reported
from 36 states, the District of Columbia and New York City.41
Since the arrival of WNV in the USA, monitoring in the Caribbean and
Central and South America has shown the presence of the virus across a
wide geographical area. Surveillance in sub-Saharan and west Africa has
shown that the virus is endemic.
Disease in humans
After an infective bite there is a short pre-patent period of about 3–14 days,
followed by generalised symptoms similar to influenza. There may also be a
widespread rash, conjunctivitis, diarrhoea, localised lymph node swelling
and respiratory difficulty; this seems to be related to the particular strain of
WNV responsible. The acute phase of the disease follows swiftly, with stiffness of the neck, high fever, vomiting and headache. There may be onset of
either meningitis or encephalitis, with fatalities in more than 40% in cases
where symptoms are most severe and where onset is swiftest. Neurological
symptoms of confusion, altered states of consciousness, tremor, convulsions
and coma may be seen related to the onset and progression of CNS infection. The highest mortality is associated with cases in elderly patients. Loss
of coordination, tremor and neurological symptoms may persist for more
than a year after the initial infection resolves. The disease may also lead to
flaccid paralysis associated with Guillain–Barré syndrome. On postmortem
230 | Zoonoses
examination, findings include extensive tissue haemorrhage, cardiac damage
and brain damage with cerebral oedema and neural degeneration.
Risk factors for the neuroinvasive form of the disease include pre-existing
hypertension or diabetes, heart disease or lung disease.
Treatment
There is no specific treatment, with supportive and symptomatic care being the
mainstay of therapy. A variety of drug therapies have been tried with varying
success, including ribarvin, interferon-alfa, antiepileptics, immunoglobulin
and corticosteroids.
Transmission to humans by other means
In September 2005, WNV infection occurred in three of four recipients of
organs transplanted from a common donor who was infected with WNV.
Two of the four were found to have the neuroinvasive form of the
disease. One was uninfected and the other was asymptomatic. A similar case
was reported in 2003.42
Transmission has also been recorded via contaminated blood products.
Despite a negative test at donation, two clinical cases of WNV occurred in
two immunosuppressed patients in Wisconsin in 2006, both of whom
received blood from the same donor. WNV transmission through blood
transfusion was first reported in 2002, prompting rapid implementation of
nationwide screening of blood donations for WNV by 2003. This has been
refined since.43,44
Transmission may also be possible via breast milk; following a transfusion of possibly contaminated blood, a mother developed symptoms of
WNV, and a breast milk sample tested positive for the virus. The infant
remained asymptomatic, but antibodies to WNV were demonstrated in a
blood sample from the infant 25 days after delivery, when the mother had
recovered. The infant had not as far as can be ascertained been exposed to
any other source of infection.45
Occupational exposure
In 2002, two poultry workers working on a turkey farm in Wisconsin were
diagnosed as having contracted WNV. The birds and workers on the farm
were found to have a high incidence of antibodies to the virus. After investigation it became apparent that the transmission may not have been
mosquito mediated, but through occupational exposure in both birds and
humans. The use of insect repellents, masks and gloves for workers at risk
is recommended.46
Laboratory workers are also at risk and at least two clinical WNV cases
have followed accidental inoculation with contaminated material.
Viral zoonotic diseases | 231
Prevention
A vaccine to protect animals, especially horses, against WNV has been developed and is in widespread use in the USA. The vaccination of susceptible feral
or domesticated animals could reduce the infective reservoir and, coupled
with mosquito control programmes, may drastically reduce transmission rates
in endemic areas. It is hoped that a vaccine for human use may soon become
available.
The states of the eastern seaboard of the USA have instituted a major
programme of detection and monitoring aimed at reducing the impact of any
further disease outbreaks. Seventeen states are involved plus New York City
and the District of Columbia (Washington State). The programme uses populations of tame birds, which are monitored for the appearance of the virus
during the period when the mosquitoes are actively feeding, and transmission
is most likely.
All mass ‘die-offs’ are monitored and viral testing is carried out on recovered corpses as part of epidemic prediction routines. Birds entering the USA
as planned imports for the pet trade must be tested for the virus before they
are allowed past quarantine.
Attempts are also being made to reduce mosquito populations, using
sterilised females, insecticides and other measures. People are encouraged to
avoid bites wherever possible, using repellents, nets or screens to reduce the
number of insects entering houses or other buildings.
Japanese encephalitis
Japanese encephalitis is also caused by a flavivirus, and is endemic in most
rural areas of south-east Asia, especially China, Japan, North and South
Korea, and the eastern areas of the former Soviet Union.
Disease in animals
Pigs and some bird species act as the animal reservoir for the disease,
usually in rural areas with extensive paddy field cultivation, where the
mosquito vectors can breed. The conditions for the disease also exist on the
fringes of urban centres, where there is waste land or sites under development. The disease is seasonal, and the infective peak is usually seen
between June and September when the mosquitoes are actively feeding,
although this will vary from area to area depending upon the prevalent
climatic conditions.47
Transmission
Transmission to humans follows the bite of a previously infected mosquito.
232 | Zoonoses
Disease in humans
Most cases are subclinical and asymptomatic and follow a pre-patent period
of between 5 and 15 days; however, in cases where clinical signs are seen
there is a high incidence of mortality, with up to a third of patients dying.
The clinical course begins with high fever, and neurological symptoms
rapidly follow with altered perception, confusion and coma. About 30% of
patients who survive demonstrate long-term neural and psychiatric damage
associated with neural loss.
In endemic areas, children and elderly people are at the greatest risk.
Elderly patients have a high mortality, and children, although surviving the
illness, display long-term sequelae. Travellers are unlikely to contract the
disease if they are visiting solely urban centres, but there may be a risk of
the disease if they are visiting rural areas or are likely to stay in an area for
prolonged periods of time.
Treatment and prevention
Treatment is purely symptomatic and supportive. A vaccine is available and
those people considered to be at risk while visiting endemic areas should
receive a programme of three injections at discrete intervals. A full risk–benefit
analysis should be conducted before immunisation takes place because the
vaccines are not fully licensed. Vaccine can be obtained through MASTA or
Sanofi Pasteur MSD in the UK, and through the CDC in the USA.
While travelling, wherever possible staying in air-conditioned accommodation or using a mosquito net is recommended, coupled with appropriate
use of insecticides and repellents.
St Louis encephalitis
St Louis encephalitis is also caused by a flavivirus, widespread in the Americas,
and isolated from northern Canada to southern Argentina: 4651 cases were
reported across the USA between 1964 and 2005, with most cases being
reported in the central and eastern states.48
The natural reservoirs are birds and bats, although the pathogen has also
been isolated from horses and other mammals. The animals do not display
any symptoms. In humans the disease develops after inoculation by infected
mosquito bites. The pre-patent period is between 4 days and 3 weeks and,
as with many other flavivirus infections, symptoms start with fever. Most
cases do not progress to encephalitis, although this is possible, and fatalities
have occurred, especially in elderly patients. In Brazil it has also caused
haemorrhagic fever in some patients.
There is no treatment, and symptomatic control is the only possible
therapeutic intervention.
Viral zoonotic diseases | 233
Other flaviviruses
Powassan virus is another flavivirus found only in North America. The reservoir is believed to be rodents, especially skunks and woodchucks with Ixodes
tick species acting as vectors for transmission to humans. Few cases have ever
been recorded in humans, although approximately 10–15% were fatal. A
recent cluster of cases occurred between 1999 and 2001 in Maine and Vermont
and were the latest since 1994. Luckily, the ticks that spread the disease
between the normal animal reservoir of rodents and their mammalian predators do not preferentially bite humans. Symptoms include gastrointestinal
disturbances, decreased kidney function, anaemia, altered mental states, joint
stiffness and generalised muscle weakness, with encephalitis. Diagnosis
follows isolation of virus from blood or cerebrospinal fluid or positivity for
Powassan-specific IgM and neutralising antibody. The CDC recommends
that Powassan virus should be included in the differential diagnosis of all
encephalitis cases occurring in the northern USA, and particularly in the north
east.49
As there is no vaccine or specific therapy, prevention of tick bites or
removing them as quickly as possible after attachment is the main protection
from the disease. Pets should be checked for ticks before they enter the house
in at-risk areas.
Kyansur and Omsk haemorrhagic virus are also flaviviruses. Kyansur
has been found only in the Kyansur Forest area of Karnatha, India. The
natural reservoir may possibly be monkeys, but they may also be victims of
the disease, rather than the actual primary host. Transmission follows tick
bites. The disease has an abrupt onset, with a biphasic pattern consisting of
febrile and haemorrhagic phases followed by CNS involvement, similar to
other tick-borne encephalitises. Symptoms include rash, conjunctivitis and
pneumonia. Diagnosis is by PCR/ELISA tests.
Omsk haemorrhagic virus is found only in western Siberia, the natural reservoir being rodents, especially muskrats. Transmission is by dermacentor ticks
and mosquitoes; it is also possibly capable of being water borne. The diesease
that it causes is very similar to cases of Kyansur virus, with an abrupt onset and
a biphasic pattern, followed by CNS involvement. The symptoms show the
same pattern as Kyansur, including rash, conjunctivitis and pneumonia.
Borna disease
Described more than 200 years ago in the town of Borna, Germany, this is a
fatal neurological disease primarily of sheep and horses, caused by an RNA
virus of the Mononegavirales order, family Bornaviridae. It is interesting that
the Monenegavirales order contains the following viral families: flaviviruses
(WNV, St Louis encephalitis, Japanese encephalitis), paramyxoviruses (Nipah,
Hendra) and rhabdoviruses (rabies, bat lyssa).50
234 | Zoonoses
Borna disease is unusual in that it appears that the virus itself is not
the cause of the symptoms seen – it is the immune response of the victim
that causes the underlying damage, which produces the characteristic
symptoms.
Disease in animals
The disease occurs in animals in sporadic outbreaks, primarily in central
Europe. There is also antibody evidence of infection occurring in Israel,
Japan, Iran and the USA in horses. In animals the disease is usually subclinical, although more virulent forms may arise and produce fatalities. It is
also found in sheep, cattle, rabbits and some exotic species such as llamas
and hippopotami. Rodents probably form the wild animal reservoir, especially shrews. It is currently not believed to be present in the UK; however,
the Department for Environment, Food and Rural Affairs (DEFRA) is undertaking monitoring of horses and sheep for the presence of this pathogen.
The Health Protection Agency is also taking an active interest in monitoring
human cases of mental illness where other factors are suspected.51
Transmission
The virus is transmitted via nasal secretions, saliva or tears, either directly
or by contamination of food or water. There is a pre-patent period of
approximately 4 weeks in horses with the disease presenting with nonspecific symptoms, usually of fever, loss of appetite, colic and constipation.
This can progress to neurological symptoms with loss of coordination,
muscle weakness, gait and posture abnormalities, repetitive movements and
paralysis as encephalitis develops. The virus invades the CNS by migrating
from peripheral initial infection sites down neurons. The illness normally
lasts for 1–3 weeks, and those horses displaying the CNS symptoms have up
to 100% fatality. Survivors can relapse if stressed.
The disease occurs seasonally in spring and summer and, although this
could indicate a possible spread by arthropod vectors, no vector has been
identified in Europe, although it has been found in ticks in the Near East.
Disease in humans
There is a possible link with psychiatric illness in humans. The clinical course
of infection in humans is not documented, although surveys of patients have
demonstrated a correlation between psychiatric disease in humans and the
serological evidence of Borna disease virus antibodies showing either active
or recent infection. The relationship is most frequent in cases where gait or
postural abnormalities are present. Some psychiatric patients who develop
fatal meningoencephalitis have also been shown to be Borna disease virus
positive.52
Viral zoonotic diseases | 235
Treatment
Both ribarvin and amantadine have been used in the treatment of Borna virus.
It is unclear if amantadine kills the virus or simply has an antidepressant
effect.
Closing comments
Between the first and second editions of this book, the number of zoonotic
viruses identified and classified have increased dramatically. The conditions
for humans to encounter novel viruses, carried by animals or infected vectors,
will continue to occur in the future and, as detection methods change and
improve, new pathogens can be identified, and the causatives of previously
unidentified or unclassified diseases defined. Just watch this space.
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8
Zoonoses of exotic, feral
and wild animals
Not all the animals in the world are domesticated. Our domesticated species
were once wild and, although in many parts of the world the wild species
that were their common ancestor are now extinct, the animals that we now
keep as pets or for profit once lived without human intervention. Selective
breeding has altered them externally, but genetically they are still very close
to their wild cousins, and thus can be susceptible to the same diseases.
Domesticated species may also revert to living in the wild, or as close to it as
an urban environment allows. These feral species are especially important
infective reservoirs, not only for zoonoses, but also for other significant
animal diseases.1
In the case of feral species the difference between them and domesticated
animals, often of exactly the same species, is solely a matter of geography.
Some may be escapees, such as racing pigeons that fail to return to their
roosts after a race. The large flocks of pigeons encountered in urban centres
have been implicated as a reservoir for Chlamydophila psittaci, and also
cause a significant nuisance with faeces fouling. Cats and dogs can also live
a feral existence and are usually reservoirs of the afflictions of their own
species, which may not all be zoonoses, such as parvovirus.
The term ‘exotics’ has been coined to cover species that have been introduced, usually for commercial purposes, into areas or regions where they
are not native. Some of these will be kept as pets, ranging from the expected
such as caged birds and some rodents (many of which are now bred in
country, rather than being imported) to the unusual, such as apes, reptiles,
large cats (tigers, etc.) or pygmy hedgehogs. Others will be kept for fur
(mink), as curiosities (coypu and edible dormice) or for sport (muntjac
deer), or were introduced for other reasons (grey squirrels, catfish, etc.).2
Initially confined to farms, estates or other limited and controlled locations, they inevitably escape. With a lack of domestic predators, or with a
Zoonoses of exotic, feral and wild animals | 239
reproduction rate that far outstrips predation or control strategies, these
animals can adapt to the environment, find an ecological niche and establish a wild living population, often to the detriment of native wildlife. Often
introduced with less than current standards of quarantine (and therefore
capable of carrying unusual bacterial or viral flora), or susceptible to the
diseases associated with their closest wild relatives or environmental
pathogens, they can form a disease focus.
Some animals have never been domesticated, and can be classed as fully
wild or sylvan. Of these some will inhabit only rural or wilderness areas;
others will have adapted their mode of survival to living in or around the
encroaching urban environment. There are probably now more urban foxes
in towns and cities than there are in the countryside.
Wild animals such as foxes, badgers, rats and squirrels have their own
associated diseases, some of which are zoonotic. They may also act as
amplifying hosts for pathogens, or for the parasites, such as ticks or fleas,
that carry zoonotic organisms. Many of these diseases are those of their
closest domesticated counterparts, although there are some that are species
specific, such as racoon roundworm which given the right conditions may
be marginally zoonotic (i.e. rare reported cases in humans).3
Currently in the UK, badgers as a reservoir of bovine tuberculosis
(Mycobacterium bovis) are of particular concern to dairy farmers, although
the scientific evidence relating to transmission into cattle is conflicting. As
the pathogen has also been found in roe and fallow deer, controlling infected
badgers may have no effect, and recently a decision has been made by the
British government that, at present, no badger cull will be authorised in
endemic areas.
In most urban areas across the UK and the USA, foxes or other wild
canids are on the increase and, as they become established in urban areas,
they form a potential reservoir for canine zoonoses, especially as they not
only hunt but also scavenge, and consumption of other mammalian corpses
or food waste is a potential route of spread in certain infections. Rodents as
a reservoir for leptospirosis are well recognised, and the emergence of
animals resistant to the rodenticides in normal widespread use poses an
increasing problem, especially in urban areas. The need to control populations of pest animals and their associated arthropod or intestinal parasites in
urban areas is a significant part of the local authorities’ focus on maintaining
environmental and public health.
Foxes in Europe are known to form a sylvatic focus for Echinococcus
multilocularis, Toxocara canis and Trichinella spp.4 The UK remains at
present free of E. multilocularis, but it is endemic in Europe and is a significant causative of fatal hydatid disease. The pet passport system (see Chapter
6) is geared to preventing this pathogen among others entering the UK, as is
the quarantine regimen in North America.
240 | Zoonoses
Other wildlife can also carry some unusual pathogens. In the UK, otters
(Lutra lutra) and a variety of marine mammals (porpoises and dolphins)
have tested positive for atypical Brucella spp. Otters have also been found
to be carrying liver fluke (Fasciola spp.) in southern England. The parasite
is potentially zoonotic and believed to have been contracted from imported
freshwater fish which have then become naturalised, after escape or release.5
Pasteurella multocida has been found in a variety of species including
swans, hedgehogs and foxes, and avian botulism has been found in gulls in
Scotland.
Other species of wild birds have been found to carry potentially zoonotic
pathogens with Chlamydophila spp. and trichomoniasis in feral pigeons,
and Clostridium perfringens having been detected in jackdaws.
There is also a considerable risk that wild animals of similar or related
species to domesticated varieties can act as reservoirs of important economic
pathogens. Testing by the Veterinary Laboratories Agency (VLA) in the UK
has shown that deer can act as reservoirs for such animal diseases as footand-mouth disease and bluetongue. A variety of potentially dangerous
Salmonella spp. have also been found in rodents, wild birds and badgers with
Salmonella dublin being isolated from fallow deer (Dama dama) and foxes
(Vulpes vulpes). Strains of Salmonella typhimurium have been detected in
garden birds.5
Wildlife are also not static or confined to specific areas as domesticated
species are, where the bounds of movement are normally set by agricultural
practice. Wild birds migrate, often large distances, carrying with them a
variety of pathogens, including importantly viruses such as West Nile or
pathogenic influenza such as H5N1.
Transmission pathways
Most feral or wild animals shun human contact, so infections by zoonoses
associated with wildlife normally follow changes in circumstance or cultural
practice. Natural or man-made disasters such as conflicts may displace people
or alter normal life patterns, so that exposure to infected animals or material
increases. This pattern is seen in emerging diseases as discussed in Chapter 7.
Many of the outbreaks of serious zoonotic disease seen in sub-Saharan Africa
have been linked to conflict, e.g. plague and Ebola in The Democratic
Republic of Congo (DRC) or Marburg in Angola.
The acronym WIREDs (wildlife-related emerging diseases) has been used
for these conditions. It recognises the role of wildlife as a reservoir for
pathogens potentially capable of posing a risk to humans or domesticated
animals.
Expansion of urbanisation into previously wild environments may lead
to unexpected exposures to pathogens, with the emergence of bat-mediated
Zoonoses of exotic, feral and wild animals | 241
rabies in South America being a particularly unpleasant manifestation of
this effect. Alternatively deforestation and agricultural activity on cleared
land or other changes in environmental practice can also produce dramatic
disease events, as exemplified by the emergence of Nipah virus in Malaysia.
Hunters, ecotourists, animal trappers or handlers, zookeepers, customs
officials, quarantine facility or wildlife sanctuary workers can all be exposed
as a result of their work or activities. Hunting in the UK is not a mainstream
activity, and is normally confined to species bred specifically as game, such
as deer or pheasants; however, in Europe it is estimated that there are
approximately 10 million people who hunt, generating an annual income of
10 billion euros. In the USA, hunting is both a leisure activity and a way of
life, with 700 000 people being employed in hunting-associated enterprises
and with an incalculable number of hunters. As discussed elsewhere, hunting
can expose hunters to zoonotic infections such as tularaemia, Lyme disease
and others that may carry currently unknown risks such as chronic wasting
disease (CWD).
Wildlife tourism such as safaris or bush walks are major income generators in many African states such as Kenya or Tanzania, and these can expose
participants to a variety of wildlife pathogens.
Bushmeat and the live animal trade
There are also two commercial drivers that appear to increase the risks of
wildlife zoonosis spread: the trade in bushmeat and the live animal trade.
Bushmeat is defined as meat derived from wild animals, and in Africa and
South America it is a major source of dietary protein. In Africa, in particular,
the meat may be derived from a variety of species including apes, rodents and
birds, some of which are listed under the Convention on the International
Trade in Endangered Species of Wild Fauna and Flora (CITES). Among
immigrant populations elsewhere in the world, bushmeat is seen as a delicacy, and returning or visiting nationals or their relatives may bring bushmeat into their new country of residence. Ecologically the trade is also of
concern, because, driven by demand from expatriate communities who have
the income to pay high prices for bushmeat, it may lead to over-hunting of
species, carrying with it risks of extinction.6
In the UK approximately 12 000 tonnes of illegally imported meat are
seized annually, including bushmeat. To try to estimate the percentage of the
seizures that originate from bushmeat sources such as apes or rodents, meat
is DNA tested after seizure. In 2007, there were 35 000 seizures, only one
of which could be taken to prosecution, with an Egyptian woman being
found guilty of the illegal importation of 83 kg of meat and dairy products;
she was fined £300. The damage that such imports can cause can be estimated; if the theory that the material that initially caused the devastating
242 | Zoonoses
foot-and-mouth disease outbreak in the UK during 2001 was illegally
imported meat or meat products, it is accepted at £1.2 billion.
In January 2008, the Department for Environment Food and Rural
Affairs (DEFRA) in the UK relaunched a campaign to reduce black and
minority ethnic (BME) personal food importation under the banner ‘Don’t
break the law, check the rules before travel’. Run by DEFRA in association
with Her Majesty’s Revenue and Customs (HMRC) and the Food Standards
Agency (FSA), the aim is to remind people that it is illegal to bring meat and
dairy products from countries outside the EU into the UK. It also aims to
explain why the restrictions are in place (prevention of animal and plant
diseases), and that many of the products are available legally and safely in
the UK. It also highlights the legal penalties that can be applied.
There are concerns that bushmeat seized by customs officials in western
Europe or the USA could carry zoonotic or other pathogens such as Ebola;
luckily, however, this is probably unrealistic in the case of this virus, because
it is likely to have died in meat transported these distances from source. As
to other pathogens the picture is less clear and due to the method of preparation, transport method (usually in personal unrefrigerated luggage) and
duration of transit, the meat usually carries a large bacterial burden of foodborne pathogens associated with poor butchery techniques or ongoing
decomposition.
In fresh bushmeat the risk is higher, with Ebola, simian foamy virus,
lymphotrophic viruses and other zoonotic pathogens posing a real risk to
consumers. People living in sub-Saharan Africa have been shown to have
antibodies to several chimpanzee-borne adenoviruses, probably after
infection associated with the butchering or consumption of bushmeat.7
This is also true of the legitimate, rather than the illicit, trade in exotic
foodstuffs with legally imported meat from reptiles, and other species being
identified as capable of infecting consumers, with a variety of pathogens and
parasites such as Toxoplasma spp., liver fluke, tapeworms and intestinal
roundworms.
As a subset of bushmeat, there are also concerns that traditional ethnic
medicines, where animal products may be used for therapeutic reasons,
could form a source of infection.
The live animal trade in wildlife is now worldwide and is estimated to
generate in the region of $US6 billion per annum.8 It has been implicated in
the appearance of zoonoses outside their usual geographical range, such as
the outbreak of monkeypox in the USA in 2003 (see below), and also the
emergence of diseases such as severe acute respiratory syndrome or SARS
(see Chapter 7). The legal trade at least can be regulated, and animals quarantined. No such safeguards are applicable to illicit trading in wild animals;
the illegal trade has led to the infection of customs officials with psittacosis
and the detection of H5N1 in smuggled birds of prey.9,10
Zoonoses of exotic, feral and wild animals | 243
Escapees and releases
Animals may be kept for a variety of reasons outside their normal ecosystem,
usually for commercial reasons, such as fur or meat farming. These animals
do not normally have predators in the external environment outside their
area of captivity, and this can be of concern in both animal and zoonotic
disease terms, e.g. raccoon dogs, bred in captivity for their fur, escaped from
fur farms and now form an important zoonotic reservoir for rabies in eastern
Europe. Muntjak deer, once confined to deer parks as an ornamental and
game species, are now widespread across the British Isles, and are capable of
forming a reservoir for a number of commercially important diseases such as
M. bovis tuberculosis, foot-and-mouth disease and other diseases.
Paradoxically, animal rights protesters can be responsible for damage to
the environment, or altering the zoonotic risk, when they release species into
habitats that they do not normally occupy. A release of mink from a fur
farm in the West Midlands of the UK led to unquantifiable and continuing
predation of mammalian and bird species.
Releases of animals to repopulate areas from which they have withdrawn
or become extinct, or for game hunting, has also led to the emergence of
animal diseases, some with zoonotic potential, with wild boar forming a
reservoir for Brucella suis and Trichinella spp. which may then be transmitted
to outdoor raised commercial pigs.
Zoological parks, circuses and city farms
Zoos, circuses and city farms exist in most countries, often in major cities.
Many now have petting areas, where children can interact closely with
domestic animals or captive wildlife, either touching or feeding the
animals. For many children, and their parents, this will be often the sole
contact that they have with animals not kept as pets. Both children and
adults may not adhere to good hygiene precautions, and a potential exists
for the transmission of zoonoses, including those associated with wildlife
or farm animals from this contact.11
There have been recurring outbreaks, particularly of Escherichia coli
O157, across the UK, the USA and many other parts of the world, that have
followed visits to petting farms/zoos. An outbreak of E. coli infection associated with a petting zoo in Pennsylvania in 2000 led to 55 confirmed cases,
with one child requiring a kidney transplantation. E. coli is not the only
risk; cases of Salmonella and Cryptosporidia infection have also followed
such visits. The incident in 2000 is not the only example; on an annual basis
there is at least one report that will reach national media levels of disease
outbreaks following such visits. Some further details can be found in
Chapter 4.12
244 | Zoonoses
Many of these outbreaks could be prevented had some simple precautions been taken. Prevention strategies are discussed in Chapter 9, but it is
worth reiterating that good hygiene, including hand washing, preventing
children from kissing animals, putting objects or fingers in their mouths,
especially before washing after contact with animals, will prevent many cases
of infection. Proper shoes, appropriate clothing and vigilance by responsible
adults are necessary. Guidance can be found for parents, teachers and
farmers in the Health and Safety Executive (HSE) Information Sheet AIS 23
(revised).13
Exotic pets
Other chapters of this book have already examined some of the more
unusual pathogens that exotic pets such as reptiles can carry, including a
wide variety of Salmonella spp.
As with other aspects of modern life, there are fashions in pet ownership
and these can produce some interesting disease risks.
Among the exotic pets currently kept in the USA and Europe are several
species of hedgehogs, including Asian, African pygmy and European species.
Hedgehogs are known to be reservoirs for foot-and-mouth disease, and
therefore in the USA the importation of African species has been banned
since 1991.14
Hedgehogs have also been identified as hosts for a variety of arboviruses,
such as Tahyna, and Bhanja. European hedgehogs (Erinaceus europaeus) in
Germany have been identified as carriers and amplifying hosts for Borrelia
spp., the causative organism of Lyme disease, and can be hosts for Ixodes
ticks, which are capable of spreading the disease to other species including
humans.
Among the diseases that they are known to carry are unusual Salmonellae,
Mycobacteria, Coxiella burnetii, Chlamydophila, Cryptosporidia spp.,
and Toxoplasma gondii. Humans exposed to hedgehogs have presented with
ringworm.
Prairie dogs are an unusual but popular pet in the USA, although their
popularity has declined since the outbreak of monkeypox in 2003; however,
they have also been shown to be capable of carrying tularaemia and plague,
so, although furry and ‘cuddly’, they might best be avoided, especially for
people in groups at high risk for zoonotic disease.15
Examples of diseases associated with wildlife
The following covers some of the better known disease states associated
with wildlife. It is not comprehensive but gives a flavour of those pathogens
that wildlife can carry.
Zoonoses of exotic, feral and wild animals | 245
Raccoon roundworm
An intestinal roundworm found mostly in raccoons, Baylisascaris procyonis,
causes rare but severe and sometimes fatal encephalitis in a number of other
species, including humans.16
Transmission follows the ingestion of soil or other material containing
raccoon faeces contaminated with worm eggs. Young children are at particular
risk.
As human cases are rare, or go undiagnosed, the true prevalence of the
disease cannot be estimated, although it is a widespread parasite of raccoons
across the USA and Canada. Children presenting with severe encephalitis
should be screened for the parasite; however, once clinical symptoms are
seen, severe damage or death usually follows.
Treatment with anthelmintics and steroids is usual, and would be
decided on a case-by-case basis, although it may not improve clinical
outcomes in established infection. Immediate treatment with anthelmintics
is recommended in cases of probable infection.
Rat-bite fever (Haverhill fever, Soduku)
Rat bite fever may be caused by two different pathogens: Streptobacillus
moniliformis or the spirochaete Spirillium minus. S. moniliformis is seen in
North America, whereas S. minus is the pathogen responsible for the form
seen in Africa and Asia (known as Soduku).
The pathogens are commonly found in the nasal passages of rats and
other rodents such as gerbils. Transmission follows ingestion of infected
material (specifically known as Haverhill fever when associated with milk or
water contaminated with rat urine), handling, or being bitten or scratched by
an infected rat, but clinical cases in humans are rare. The organism can also
be carried by other animals such as cats, dogs, ferrets and weasels that have
been in contact with infected rodents.17
After a pre-patent period of 2–10 days (4–28 in S. minus), a fever of
abrupt onset occurs, associated with rash, joint and muscle pain, headache,
diarrhoea and vomiting, often associated with peripheral rash. This can
progress to systemic disease with septicaemia, arthritis, anaemia, hypoxia,
endocarditis, and liver and kidney failure. If untreated death occurs in
7–10% of cases.18
S. minus may also cause an undulant fever, which may recur for months
or years if untreated.
It affects children usually more acutely than adults, although there
have been fatal adult cases in the USA and Canada, usually in people
occupationally exposed to rodents.19
246 | Zoonoses
Intravenous penicillin is the treatment of choice, and macrolides such as
erythromycin have been shown to be effective in penicillin-allergic patients.
Tests to identify the causative agent may not be rapid enough to prevent
mortality, so presumptive diagnosis and empirical treatment may be necessary
in patients with a history of exposure to rodents.
Individuals who handle rodents routinely should adopt safe working
practices, including wearing gloves, hand washing after contact, and
avoiding accidental inhalation or ingestion of infected material. Wounds
inflicted by rodents should be cleaned thoroughly and medical advice
promptly sought.
Typhus fever
Cases of typhus fever caused by Rickettsia prowazekii have been seen in the
USA related to exposure to flying squirrels (Glaucomys spp.) or their nests.
Classically this is a disease associated with cold mountainous regions of
Africa and South America, although historically it has also been seen in
Europe, especially after World War II, when there were epidemics associated
with increased populations of ectoparasites, especially the human louse
(Pediculus humanus) in prison camps, or in areas where displaced people
were crowded in unsanitary conditions.
Only a few clinical cases have been seen in the USA over the past decades,
with approximately 40 being seen in the last quarter of the twentieth century
in patients who had no extant human lice, or who could be confirmed as
having been in contact with other people who had body lice. They had,
however, all had contact with flying squirrels or their nests. It is possible that
the infection was transferred by transient contact with squirrel lice or fleas.
Infection could also follow contact with infected faeces.20
After a prodromal period of 10–15 days, symptoms appear including
headache, acute fever, haematuria, joint pain and vomiting.
Treatment is with doxycycline and may have to be prolonged.
Zoonoses of deer
The following two diseases relate to deer. Lyme disease is endemic in certain
areas in the UK and the USA. It poses a threat to people exposed to
the causative spirochaete Borrelia burgdorferi. The second condition,
tularaemia, has not been detected in the UK but it is endemic in the rest of
western Europe, and the Pet Travel Scheme (PETS) passport regulations insist
that animals licensed under the scheme should be treated for ectoparasites to
prevent Lyme disease, as well as other tick- and flea-borne diseases.
Zoonoses of exotic, feral and wild animals | 247
Lyme disease
Tick-borne borreliosis
Lyme disease is caused by spirochaetes of various Borrelia spp. The disease
is named after the town of Old Lyme, Connecticut, USA, where a cluster
of juvenile arthritis cases in the 1970s were first linked to infection by
B. burgdorferi. Studies of collected insects and literature surveys on both
sides of the Atlantic have identified the organism and the disease was clinically described in the late nineteenth century. Lyme disease is notifiable
under public health legislation in Scotland. In England and Wales it is
reportable under RIDDOR (Reporting of Injuries, Diseases and Dangerous
Occurrences Regulations) 1995 for ‘work involving exposure to ticks’.21
Transmission
The infection is transmitted by the bite of an ixodes tick, mainly Ixodes
scapularis or I. dammini in North America, which normally preys on deer.
In the UK, I. ricinus has been identified as the main tick vector and infectious reservoir. Ticks of Ixodes spp. are much smaller than common dog or
cattle ticks. In their larval and nymphal stages they are no bigger than a
pinhead. Adult ticks are slightly larger. Other biting insects, such as mosquitoes and fleas, have also been implicated in transmission, but they are not
believed to be an infectious reservoir. They are rather an incidental vector
infected by feeding on an infected vertebrate.
Incidence
Reported incidents of Lyme disease have risen in England and Wales in recent
years. This probably arises from better recognition of the disease and more
thorough reporting. Incidence and prevalence are related to environmental
factors. Certain weather conditions, such as drought or high rainfall, can kill
the tick before maturation.22
During 2006, there were a total of 945 reported cases in the UK, with
768 serologically confirmed cases of Lyme disease in England and Wales and
177 confirmed cases in Scotland. Of the 768 cases in England and Wales,
677 had been acquired in the UK and 91 abroad. The annual figure has
increased over the last decade, reflecting greater awareness of the disease,
and also greater access by the public to areas where the disease is endemic,
both domestically and overseas.
In England and Wales, surveillance by the Health Protection Agency
(HPA) has demonstrated that approximately 70% of indigenously acquired
infection occurred in the southern counties of England. The main affected
areas are the New Forest, Salisbury Plain, Exmoor, the South Downs, parts
of Wiltshire and Berkshire, and Thetford Forest. Other endemic areas
248 | Zoonoses
include the Lake District, the North and West Yorkshire moors, and the
Scottish Highlands and Islands.
The HPA has also identified that many of the cases reported in the
UK have been acquired abroad, mainly in the USA, Russia, Scandinavia,
France, Germany, and other European countries including Poland, the
Czech Republic, Slovenia and Slovakia.
Life cycle
The life cycles of the tick and Borrelia spp. are closely linked. The female
tick lays eggs during the spring of the first year, which hatch into larvae in
early summer. The larvae then seek out rodents and birds as hosts. These
hosts, being highly mobile, help disseminate the tick over a wider geographical area. The larvae continue to feed over the summer and become dormant
In early summer,
the adult
female tick
attaches and
feeds on large
mammals,
including
humans
Adult
Second year:
feeds on small/
medium birds
and mammals
First year:
feeds on small
birds and
mammals
Nymph
Figure 8.1 Lyme disease: transmission cycle.
Zoonoses of exotic, feral and wild animals | 249
in the autumn. The following spring the larvae moult into nymphs which
attach themselves to small rodents and other small mammals; in the USA the
white-footed mouse plays a significant role as both an interim host for the
tick and a reservoir for the disease.23 In the autumn of the second year they
moult again into adults. At this time ticks will attach to a large mammalian
host, feeding persistently and mating. The female will then drop off and lay
her eggs, starting the cycle again (Figure 8.1).
Borrelia spp. are present in all stages of the tick, acquiring the infection
from infected rodents when feeding commences. As the larvae are the most
voracious and aggressive of feeders, these actively spread the organism. This
correlates with the incidence of infection. Most tick bites that lead to clinical manifestations occur in the period May to July when the larvae and
nymphal stages are actively biting. Deer are the preferred host; humans, cats
and dogs are incidental hosts, as are cattle and horses. Dogs suffer badly
from the arthritic form of the disease.
Disease in humans
In humans, as with other spirochaetal diseases, the course of the disease is
undulant, with acute and chronic phases interspersed with long asymptomatic
periods. After the initial manifestation there can be a latent period of up
to 4 years before further clinical signs are seen.24
Initial infection follows a tick bite; it is now believed that the tick must
stay attached for a period for transmission to occur. This period can be less
than 16 hours: 24–72 hours is believed to give optimal transmission. A
localised skin reaction appeared in 60% of English cases. This occurs at the
bite site, usually about 9 days after infection due to spirochaetal invasion.
This is called erythema migrans and it presents as an expanding reddened
area. It usually has reinforced borders and can be solid or annular. It may
be warm to touch but is rarely itchy or painful.
Later some patients will have flu-like symptoms with fever, malaise and
headache. A transient lymphadenopathy may be seen, as may organ involvement with transient hepatitis. Eye problems, including conjunctivitis or optic
nerve damage, have been reported.25 A widespread erythema migrans with
multiple lesions can occur, often together with other more serious symptoms
of neurological damage, cardiac involvement or arthritis. A condition called
acrodermatitis chronica atrophicans (ACA) is occasionally seen. This is a
serious condition, passing from an initial inflammatory stage to atrophy and
pigmentation disturbances of the skin on extensor surfaces of the limbs.
Accompanying symptoms include pain, itching and paraesthesia.
Neurological complications may manifest at any time: the incidence in
patients aged under 14 years of neurological symptoms is higher than in
other age groups. Symptoms range from meningitis, cranial nerve damage
and facial palsy to peripheral neuropathies. Subarachnoid haemorrhage and
250 | Zoonoses
seizures have also been reported. A chronic form of the disease with
memory loss, loss of motor skills and dementia is reported, although the
linkage to Borrelia infection is currently unproven.25
Up to 10% of infected individuals in the USA present with associated
cardiac problems. These include atrioventricular block, heart failure and
myocarditis that resolves on treatment with antimicrobials.
In the USA it is estimated that 14% of sufferers develop arthritis, and in
some cases seen in the UK this has been the first symptom resulting in clinical diagnosis. The first symptoms may appear 3–6 weeks after first infection,
usually with a single joint involvement, commonly the knee. The jaw, ankles,
shoulders, elbows and wrists are also common sites.26
The variation in symptoms seen between the USA and the UK seems to
be related to a difference in the genus species of the pathogen. In the USA
B. burgdorferi predominates, whereas in Europe B. afzelii and B. garinii are
more common. Different clinical manifestations are species related, with
B. afzelii being associated with dermatological symptoms and B. garinii
with neurological disorders.
Diagnosis
Diagnosis is not easy, because not all patients present with erythema migrans,
or can remember being bitten by a tick – often the tick will be concealed
within clothing when attached and may disengage before detection. Laboratory tests have been notoriously unreliable, due to its genetic ability to vary
its outer surface proteins, thus altering its immunological signature. This
leads to false-negative test results for enzyme-linked immunosorbent assay
(ELISA), polymerase chain reaction (PCR) tests or western blot testing. The
Centers for Disease Control and Prevention in the USA (CDC) recommends
enzyme immunoassay (EIA) or immunofluorescent assay (IFA) as more
accurate.27
Treatment
Treatment consists solely of antibiotic therapy. Patients with severe multisystemic involvement, especially where neurological symptoms are present,
can be treated with intravenous cephalosporins. Tetracyclines, especially
doxycycline, and penicillins, particularly amoxicillin, demonstrate efficacy
against most Borrelia infections. b-lactams are relatively inefficient and
should be used only when other agents are not suitable.23
The British National Formulary (BNF) recommends that Lyme disease
should generally be treated by those experienced in its management.
Doxycycline is the antibacterial of choice for early Lyme disease. Amoxicillin
(unlicensed indication), cefuroxime axetil and azithromycin (unlicensed
indication) are alternatives if doxycycline is contraindicated. Intravenous
administration of cefotaxime, ceftriaxone or benzylpenicillin is recom-
Zoonoses of exotic, feral and wild animals | 251
mended for Lyme disease associated with moderate-to-severe cardiac or
neurological abnormalities, late Lyme disease and Lyme arthritis. The
duration of treatment is generally 2–4 weeks; Lyme arthritis requires longer
treatment with oral antibacterial drugs.
Prevention
Prevention strategies can be divided into environmental and personal. Many
prevention regimens aim to break the ability of the organism to maintain a
rodent reservoir, and prevent tick attachment to large mammals or humans.
Controlling undergrowth around footpaths, and inspecting and treating livestock for ticks, can reduce the tick population. Controlling access of rodents
to commercially farmed deer can reduce infection risks both for animals and
for associated human workers.
Personal protection, especially for individuals employed in forestry or
other business in endemic areas, consists of wearing long trousers and boots,
with the trousers tucked into the socks. Lighter-coloured clothing allows
ticks to be spotted before they can establish a potentially infective bite.
Prompt removal of any ticks is also important, and examination of the
groin, armpits and scalp is particularly important. Outdoor enthusiasts
should take similar precautions, especially if camping in areas where ticks
are known to be endemic.28
Vaccination
Although a vaccine for the prevention of Lyme disease in humans has been
developed, it has not been adopted because it is not considered to be costeffective except for those individuals who live in areas where Lyme disease
is endemic and who are frequently exposed to ticks. The associated risks of
possible adverse reactions also mitigate against its use, except in exceptional
cases where significant benefit can be demonstrated.29
Tularaemia
Francis’ disease, deer-fly fever, rabbit fever, O’Hara disease
Tularaemia is caused by Francisella tularensis, a small Gram-negative
coccobacillus. An intracellular pathogen, it can also survive in the environment for extended periods. It has now been found to be able to parasitise
life forms as lowly as amoebae and other protozoans. The organism is
named after Sir Edward Francis who initially isolated and studied the
causative organism at Tulare in California, USA. It occurs in a number of
subspecies. Francisella tularensis subspecies tularensis (type A) also occurs
in two distinct subpopulations – A I and A II – with the two subpopulations’
distribution being geographically different and linked to the presence of
specific vectors and animal hosts (such as different populations of rabbits).
252 | Zoonoses
The A I population is mostly seen in central USA and the A II in the western
USA.30
F. tularensis subsp. holoarctica (type C) is distributed across most of the
northern hemisphere, with another subspecies, mediasiatica, being seen in
central Asia and the former Soviet Union; it appears to have less affinity for
humans and more for aquatic mammals.
The final subspecies is much rarer and is designated subsp. novicidia; so
far only a single case has been identified in Australia, outside its normal
range of the northern USA.
Francisella spp. appear to produce an endotoxin similar to those
produced by other Gram-negative enteric bacilli. An additional twist to the
organism is that F. tularensis has also been suggested as a possible agent for
biological terrorism or warfare. There is some evidence that Israel and
Russia have attempted to develop resistant strains for use as weapons.
The organism can also survive in water and penetrate intact skin. As the
estimate of inoculum necessary to initiate disease in humans has been set at
only 10 organisms, the disease is classified as highly infective. Although not
reported in the UK, with the increasing popularity of adventure holidays
where trekking or living in wilderness areas forms part of the itinerary, there
is a risk of exposure and disease for tourists who might then return home
before clinical signs are seen.
There was a recent outbreak in Turkey in 2008, following on from
previous ones in the country in 2004 and 2005.31 A serious outbreak
occurred in Kosovo from November 2001 to February 2002, with 715
reported cases. Of those, 170 cases were confirmed as type B tularaemia,
and were linked to rodents. Spread to humans was linked to rat-associated
ticks, fleas or lice as vectors. There were no cases in peace-keeping or aid
workers and no fatalities, as all cases resolved on treatment. An outbreak of
long duration occurred in Bulgaria between 1997 and 2005 and affected
285 people.
In the former Soviet Union routine vaccination is carried out, because the
disease is considered to be endemic. The disease occurs in sporadic outbreaks
across a wide geographical range in western Europe from Scandinavia to
Spain. In many of these outbreaks a small and increasing number of cases is
seen over a period of time, reaching a peak in incidence and then declining.
The same pattern has been seen in the USA where the disease was very
prevalent in the 1950s, but has decreased markedly over time, although
sporadic outbreaks still occur.
It is not known why the incidence has declined but the use of insecticides, changes in agricultural practice and habitat destruction have all been
suggested as factors. Outbreaks such as the Kosovan incident may be
associated with boom years for the population of vermin hosts such as
rabbits or rats, and thus the blood-sucking parasite population.
Zoonoses of exotic, feral and wild animals | 253
The prevalence of the disease shows a marked seasonal bias related, as
with Lyme disease, to the life cycle of the ticks that can be the main vector
for its spread in certain areas. Most cases reported between May and
October are associated with parasite bites. Another peak is seen in the
winter relating to hunting, where there is no vector spread but there is direct
contact between humans and animals during the skinning and preparation
of prey animals. This may explain why most cases are seen in adult males –
over 75% of American cases are seen in male hunters.
The reservoir for the disease consists of both wild and domestic animals.
It has been found in rabbits, hares, squirrels, deer, snakes, rodents, cats,
dogs, cattle, pigs, sheep and goats.32 The organism has also been isolated
from all the life stages of various ticks, and Dermacentor reticulatus (dog
tick) and Ixodes ricinus (castor oil bean tick) are the major European species
involved. The organism can persist for many months or years in the tissues
of the tick and is carried through moults and can be transferred from
mother to offspring. The organism has been isolated from tick saliva and
faecal matter, so inoculation of a wound with either substance can provide
sufficient inoculum to produce clinical disease. Luckily, not all ticks within
a population are infected. Mosquitoes, deer- and horseflies, and fleas have
also been found to carry the organism. Whether they are competent vectors
of transfer is not proven in all species, although in the USA deer flies are
known to be a major vector. It has also been demonstrated that cats are able
to transmit the bacterium on their claws, after catching infected prey.33
Disease in animals
In animals, the main clinical manifestation of the disease is septicaemia,
with high fever, stiffness and loss of appetite. Respiratory involvement may
also manifest with symptoms similar to pleurisy. Death follows frequently
and rapidly. On postmortem examination, necrotic lesions may be found in
the main organs.
Transmission
Humans are susceptible to infection with the organism and it can affect any
age or social group.
Infection in humans follows a vector bite, physical contact with an
infected animal or an ingested inoculum from water or meat. Human-tohuman spread does not occur. As has been previously stated, the organism
can also penetrate intact skin and be spread by the inhalation of infected
aerosols.
Case history
In February 2004, a 3-year-old boy in Colorado, USA contracted the disease
after being bitten by a pet hamster. The boy originally had six hamsters, but
254 | Zoonoses
they all died shortly after being purchased from a Denver pet store; one of
them bit the boy, causing him to become infected. There have been previous
cases recorded among hamster hunters in Russia.
Disease in humans
Following infection there is a pre-patent period of 2–10 days before clinical
signs are seen. An ulcer appears at the inoculation site and local lymph gland
swelling is seen in the lymph nodes nearest to the ulcer as the organism multiplies and proliferates. Initially there may be a high fever, which then subsides
and recurs in a cyclical manner. Chills, headache, malaise, anorexia and
fatigue are quite common.
Antibody production begins during the second or third week of infection
but is usually insufficient to protect against infection.
The disease presents in a variety of forms depending on the route of
infection. The CDC classification in the USA recognises six main forms:
glandular, ulceroglandular, oculoglandular, oropharyngeal, pneumonic and
typhoidal. The classification is useful; however, the clinical symptoms
associated with various forms of the disease often present at the same time
in the same patient, leading to confusion. The mortality rate for untreated
tularaemia is about 8%; early diagnosis and treatment can reduce that rate
to below 1%.
The most common type, seen in over 75% of cases, is classified as
ulceroglandular following cutaneous inoculation. When the initial ulcers are
seen, their location may help to identify the mode of transmission. Ulcers on
the upper limbs usually result from exposure to infected animals, whereas
ulcers on the lower limbs, back or abdomen usually result from parasitic
bites. Glandular swelling follows the appearance of the ulcer, with primary
sites again related to mode of transmission. Untreated ulcers can take a long
time to heal, with associated persistent lymph node swellings. Most cases
will take 3–5 weeks to resolve without treatment; however, symptoms can
persist for up to 3 years after the appearance of the disease. Many cases will
need a lengthy period of convalescence.30
The glandular form presents in a similar manner to the ulceroglandular
disease but without skin ulceration, and is responsible for 15–20% of the
cases in the USA. Glandular involvement can be acute and severe.
Fortunately, the oculoglandular type of infection is rare. It occurs in no
more than 4% of cases in most outbreaks, and less than 1% over a series of
outbreaks, although it may appear in single case occurrences where there is
only one individual infected. Infected material, e.g. blood, meat, dust or
bodily fluids, is splashed into the eye. Following infection the eyelids swell
and there is ulceration in the conjunctiva and surface of the eyeball.
Localised glandular swelling in the neck may also be present.
Zoonoses of exotic, feral and wild animals | 255
Ingestion of contaminated meat or water can lead to the oropharyngeal
form. In recent outbreaks, 4–18% of cases have presented with sore throat
and pharyngitis. In some individuals, the throat does not appear to be
infected on examination. Others show severe inflammation with involvement
of the tonsils and swelling to almost total closure. Swelling is seen in the
glands of the jaw, throat and neck.
The pneumonic form follows inhalation of infected aerosols; the symptoms and findings in this form vary. As in the other forms, fever and glandular
swellings are usually present. Lung involvement may mimic a chest infection
or pleurisy.
The last in the list of forms is the typhoidal type. Onset is usually abrupt
and follows ingestion of infected material. High fever is seen, with aching
joints and muscles, vomiting and diarrhoea. Liver and splenic enlargement
is sometimes seen, and usually develops gradually after the acute phase. Skin
rashes may also be present.
In all types of infection, some of which will fall into one or more
categories, long-term immunity will usually follow infection.
Diagnosis
Confirming a diagnosis is made using clinical samples. The organism is difficult to culture in a laboratory, and also poses a risk to laboratory personnel.
Immunofluorescence or PCR methods and serological testing are preferable,
and recent advances have been made in producing rapid reliable test
methods.
Treatment
The treatment of tularaemia depends on rapid diagnosis and the commencement of antibiotic therapy as soon as possible after clinical signs are seen.
Antibiotic use is the only therapy, using single or combination therapy.
Streptomycin with or without the addition of a tetracycline has historically been the mainstay of treatment. Streptomycin is usually given intramuscularly in two divided doses for a duration of 7–14 days. An alternative
regimen is 15 mg/kg per day in two divided doses for 3 days followed by a
period of 4 or more days at half the previous dose twice daily. Gentamicin
has been substituted for streptomycin in a dosage of 3–5 mg/kg per day by
intravenous infusion in divided doses for 7–14 days, with the length of the
course being linked to patient response. Clinical monitoring of blood chemistry is essential with the use of these aminoglycosides. Chloramphenicol has
also been used in the past, but the serious associated side effects have to be
weighed against clinical need.34
Tetracyclines are effective, but, as they are bacteriostatic rather than
bactericidal, the duration of therapy needs to be longer. Doxycycline is given
256 | Zoonoses
by mouth at a dosage of 100 mg every 12 hours for 10–14 days. Some
studies have shown that high-dose erythromycin is suitable for type A infections; however, both type A and B serotypes have demonstrated resistance.
Ciprofloxacin has become the treatment of choice in some countries. In an
outbreak in Sweden, ciprofloxacin was given by mouth for 10–14 days at a
dosage of 15–20 mg/kg daily in two divided doses in children under 10, and
at a dosage of 1000–1500 mg daily in two divided doses to adults and
children over 10. Norfloxacin 400 mg/day in divided doses for 12 days was
used in a single patient in the same outbreak and proved effective. Both
ciprofloxacin and doxycycline have the advantage of allowing community
treatment because they can be effectively given by mouth, rather than
requiring an injection programme, and the use of secondary healthcare
resources.34
Prevention
A vaccine is available for people considered to be at high risk or where the
disease is seen as a public health issue, such as in the former Soviet Union.
Vaccination has also been used where the disease is a possible health and
safety hazard of employment, e.g. in park rangers and field naturalists in
endemic areas. The main human groups at risk of occupational exposure are
farmers, shepherds, hunters, veterinary surgeons, meat handlers, cooks and
the partners of hunters.
Prevention is the best policy. Avoiding insect bites and implementing
hygiene procedures when living or travelling in areas where there is a high
prevalence of the disease are essential measures. Use of insecticides and
wearing suitable clothing in forested areas – trousers rather than shorts –
will prevent many tick bites. Any ticks that succeed in attaching should be
removed carefully without crushing them, and whenever possible not with
bare hands. Domestic animals suffering from the disease should be treated
or culled to prevent spread.
As with leptospirosis, drinking, washing or swimming either by choice or
accidentally in infected water should be avoided wherever possible. Hunters
and others who handle or butcher wild animals should be advised to wear
suitable protective clothing. Wild game should be thoroughly cooked and,
as the organism can survive prolonged freezing, suitable precautions should
be taken when handling any raw game meat. Antibiotic prophylaxis is not
recommended in any risk group.
Viruses associated with primates
The following diseases are included because they pose a risk to humans
exposed to them, especially in areas where humans regularly interact with
primates, including activities such as hunting, butchering and eating apes.
Zoonoses of exotic, feral and wild animals | 257
They also pose a risk for laboratory workers and people who keep this class
of animals as pets.
Herpes B virus
Herpes B virus (Cercopithecine herpesvirus 1) is found in Asian macaques
and other primates, which can be asymptomatic carriers of the pathogen. If
transmitted to humans it can cause a fatal encephalitis or severe neurological
damage. Cases have occurred in laboratory settings after exposure to infected
faeces. In one case death followed infection by material being splashed into
the eye of the victim, though the more frequent cause of infection is by
inoculation through bites or scratches.35
In a survey carried out on free-roaming macaques and workers at a
Balinese temple, over 80% of the macaques had antibodies to the virus, and
contact between the macaques and workers or tourists was likely to allow
transmission to occur (i.e. bites, scratches).36
The pre-patent period can be as short as a few days, although it is more
normally 2–5 weeks. Neurological symptoms are seen which can progress
through paralysis to respiratory collapse and coma. Treatment has to be
aggressive using either aciclovir or ganciclovir.37
Primate handlers should use eye protection and other protective equipment such as gloves, especially when working with wild-caught primates,
and tourists should be encouraged not to come into close contact with
monkeys whenever possible.
Monkeypox
First identified in 1958, monkeypox is caused by an Orthopoxvirus (designated monkeypox virus [MXPV]), closely related to smallpox and cowpox.
It is capable of infecting a range of animals in addition to its normal host of
apes and monkeys, especially rodents including squirrels, rats, mice and
rabbits. The first confirmed zoonotic case in humans was documented in the
1970s, although it is believed that the virus had previously infected humans,
but that the infection was probably mistaken for smallpox.
Most cases are seen in Africa, with The Democratic Republic of Congo
and Sudan reporting outbreaks, although the disease probably occurs elsewhere.38,39 In June 2003, the first and only outbreak so far in the USA began.
The primary source of the outbreak was a Texan animal importer, who had
purchased from Ghana a mixed group of approximately 800 small
mammals in April 2003, composed of a number of species including squirrels, mice, rats, dormice and porcupines; some of these were later identified
as being infected with or carrying monkeypox. These animals came into
contact with approximately 200 prairie dogs, which were passing through
258 | Zoonoses
the same facility at the same time. Of the prairie dogs approximately 100
became infected.40
The prairie dogs were sold on to an Illinois-based animal distributor, and
were subsequently traded on. Following contact with the infected prairie
dogs, a number of people who handled or were in contact with these animals
became infected with monkeypox. By the time the outbreak was declared
over by the CDC in July 2003, 72 cases of suspected monkeypox had
been reported with 37 being laboratory-confirmed across 6 states (Illinois,
Indiana, Kansas, Missouri, Ohio and Wisconsin). The rapid spread of the
disease over a wide geographical area was due to the nature of the animal
trade and the holding and distribution mechanisms associated with it.
Prevention of further spread and control of the outbreak was gained by
forbidding interstate animal shipments and trade, quarantining premises
where infected animals had been found, culling infected or potentially
infected animals, and pre- and post-exposure vaccination of at-risk people
using smallpox vaccine derived from cowpox (vaccinia).
The main aim was to prevent the establishment of an indigenous focus
of infection in wild or captive animals, to prevent a reoccurrence, and this
appears to have been successful.
In June 2003, when the outbreak was first recognised, the CDC, on
behalf of the Department for Health and Human Services (DHHS) and the
Food and Drug Administration (FDA), issued a joint order prohibiting the
import of African rodents into the USA.
In November 2003, the joint order became an interim final rule that bans
the importation of African rodents and their sale, distribution, transport
and release. In addition, the ban applies to rodents with a native habitat in
Africa, even if those rodents were captive bred or born outside Africa.
Exemption may only be obtained by gaining a permit from the CDC where
animals need to be imported for scientific or educational purposes.41
The symptoms of monkeypox seen in infected animals vary because
some may be asymptomatic, although normally there is conjunctivitis,
lymphadenopathy and skin lesions, occasionally followed by splenic and
hepatic enlargement, sepsis and respiratory complications, including
pneumonia and death.
Transmission to humans follows handling an infected animal, bites or
scratches from an infected animal, contact with infected blood or body
fluids, handling or eating infected meat or tissues, and fomite spread. Once
infected, human-to-human spread can occur by droplet inhalation or
contact with infected body fluids or fomites.42
In Africa a death rate of 1–10% of clinically infected patients has been
seen, although this is reduced by good nutritional status and supportive
healthcare. Coinfection with HIV/AIDS may also play a role in mortality
Zoonoses of exotic, feral and wild animals | 259
levels. In the US outbreak there were no fatalities, although two children
required intensive care and one patient had to have a corneal transplantation.
Symptoms in humans are variable; although they normally mimic
smallpox, the symptoms are normally milder. After a pre-patent period of
approximately 12 days (although this can range from 1 day to 31 days), a
high fever of rapid onset occurs with associated myalgia and headache,
lymph node swelling and lethargy. Within 1–3 days a vesicular rash occurs,
starting normally on the face and spreading, although it may occur on other
parts of the body initially. The vesicles burst, turn crusty, scab and then
heal normally within 2–4 weeks. In some cases, especially in children, an
encephalitis may follow, as may organ failure and death.43,44
Treatment is usually non-specific and symptomatic, although vaccination
with smallpox vaccine (cowpox derived), or cidofovir, was used to some
effect in the US outbreak.45
Simian foamy virus
Simian foamy viruses (SFVs) are retroviruses found in primates that are
capable of infecting humans.46 In central Africa and Indonesia, the virus has
been found in some humans, especially in hunters, usually after exposure to
primates, particularly after bites or scratches inflicted by an infected ape.47,48
Infection has also been recorded in zoo keepers, laboratory technicians and
animal handlers who have been occupationally exposed to primates.49,50 The
virus has been isolated from local people and tourists who have had
exposure to monkeys at temples in Bali.48
In some areas most apes are infected; however, although the viruses are
persistent, they show little or no pathogenicity in the primates, with the
animals remaining asymptomatic. The viruses are shed in the saliva, and are
also blood and meat borne.
No spread of the virus between humans by sexual contact or other
means has been demonstrated, although the virus has been detected in
donated blood, and it is likely that transfusion of infected blood could lead
to infection.51
Although no pathogenicity has been seen in infected humans, in vitro the
virus will lyse both human and monkey cells.
Simian immunodeficiency viruses
Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), which
cause acquired immune deficiency syndrome (AIDS) after a prolonged period
in humans, were originally zoonotic lentiviruses.52 Since their initial transfer
into humans, they have become capable of relatively easy human-to-human
260 | Zoonoses
transmission, and have therefore ceased to be considered zoonoses. (HIV
infection is not therefore covered further in this volume.)
Apes, monkeys and other primates found across sub-Saharan Africa carry
a variety of simian immunodeficiency viruses (SIVs) closely related to extant
types of HIV. They are genetically divergent and ‘chatter’, i.e. produce genetic
variations rapidly by swapping or altering their genetic code, so producing
diverse pathogenicity and infectivity.
It is possible that new varieties of virus capable of zoonotic transfer to
humans and with potential pathogenicity will be transferred from primates
to humans in Africa, probably during hunting for, butchery of, or
consumption of, bushmeat derived from primates, especially sooty mangabeys
or chimpanzees.53
A similar situation is observed with lymphotrophic viruses. Human T
lymphotrophic virus (HTLV) types 1 and 2 are now widely distributed
worldwide and were initially zoonotic.54 Two new HTLV-designated types 3
and 4 have recently been isolated from humans exposed to monkeys or apes
in southern Cameroon.55 These have probably arisen and crossed the species
barrier in a similar manner to the immunodeficiency viruses.
Prevention of spread of wildlife diseases
In agriculture, as a matter of good husbandry practice, feral and wild animal
contact should be kept to a minimum wherever possible to reduce disease
spread. Good agricultural practice includes reducing mammalian pest
species. This has become less routine due to the costs involved and the
concerns of the environmental lobby. Control of pests on and around farms
is vitally important in the prevention and control of spread of certain
zoonoses. It becomes even more significant when the pest and the domesticated species are very closely related; sparrows in a chicken run, or in the
feed mill associated with such a unit, would pose a significant risk for avian
disease transfer.56
Members of the public should be encouraged to be circumspect in their
handling of injured wild animals, and children should be educated not to
touch corpses of birds or mammals. Normal hygiene routines should be
observed, with the use of protective clothing and general hygiene measures.
In the event of any injury caused by a wild animal, medical attention should
be sought as soon as reasonably practicable. Direct zoonotic transmission is
also possible at specialist sanctuaries or rescue units (see Rabies in Chapter
6). Most of these units have standing procedures under which all animals
are treated as suspect and as possible biohazards, thus preventing untoward
incidents of injury or infective transfer.57
Tackling these problems requires a consensus, with healthcare workers,
vets and government agencies, at both legislational and practical levels,
working in cooperation.58
Zoonoses of exotic, feral and wild animals | 261
In the USA, an initiative by the American Veterinary Medical Association
(AVMA) has led to the establishment of a ‘One Medicine Initiative’ bringing
wildlife, environmental, human and domestic animal health issues together.
Supported across professional organisations and government agencies, this
coordinated approach aims to prevent and pre-empt disease outbreaks
rather than being solely reactive.59
Surveillance
In the UK, the VLA has provided surveillance of wildlife diseases since 1998
under the Diseases of Wildlife Scheme (soon to be renamed the Wildlife
Health Strategy to be incorporated into the Veterinary Surveillance Strategy,
which forms part of the overarching Animal Health and Welfare Strategy
launched in 2004). The scheme is government funded and mirrors a scheme
run in Scotland and Northern Ireland, with a shared diagnostic database.
The scheme has 16 regional laboratories and investigates and monitors
zoonoses, emerging and exotic diseases (such as West Nile virus) and mass
mortalities (‘die-offs’) of birds and animals. It provides DEFRA and other UK
government agencies with information and statistics on wildlife diseases.60
In Europe, the Office International des Epizooties (OIE) has undertaken
surveillance of animal diseases including zoonoses since 1993. The OIE have
developed lists of reportable diseases including wildlife diseases, some of
which are zoonoses.61 In general the list contains any disease found in the
wild considered to be of an infectious nature that can infect mammals,
birds, reptiles or amphibians.
In the USA there are a number of government departments that are
involved with the surveillance and response to wildlife diseases. The Wildlife
Services unit of the US Department of Agriculture (USDA) Animal and
Plant Health Inspection Service (APHIS) aims to support federal and state
agencies when a threat to animal or human health is identified that stems
from wildlife disease. It has strategic partnerships with many other government departments (such as the Department of Health, CDC, etc.) and also
extra-territorial partnerships with geographical neighbours (Canada and
Mexico).62
Of particular interest is the Wildlife Center of Virginia, and its participation in Project Tripwire. The Wildlife Center of Virginia, a wildlife care
centre, had monitored and studied wildlife diseases for some years, and had
demonstrated the significance of these conditions for human and domesticated animal health. Project Tripwire began as a cooperative effort to
exchange data between wildlife care services to enhance analysis of illness in
animals, allowing rapid identification of outbreaks so that appropriate
measures can be put in place rapidly. After 11 September 2001, there were
concerns over the use of biological weapons, many of which are pathogens
that could be carried or infect wildlife. As part of a project to reduce
262 | Zoonoses
response time to biological incidents a system of epidemic outbreak surveillance (EOS) was developed by the US Air Force Research Laboratory; this
was further developed by the Institute of Homeland Security (IHS) which
has evaluated and developed Project Tripwire together with the Wildlife
Center to produce a system that could monitor patients, diseases and
outbreaks.63
In Canada, Environment Canada has developed a strategy for wildlife
disease. This brings together multiple government and private partners
across many disciplines, to produce a coordinated response to the threat of
wildlife disease.
Elsewhere in the world there are a variety of schemes that aim to prevent
the spread of diseases from wildlife. All these initiatives have one thing
in common: they aim to highlight and address the important issues
surrounding wildlife as a reservoir of potential pathogens for both humans
and domesticated animals, and to prevent or control outbreaks.
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9
Implications for healthcare
The other chapters in this book have explored the details of zoonotic infection
and disease. This chapter explores why these conditions pose a challenge for
healthcare professionals and how an understanding of these conditions helps
in identifying, treating and offering advice on prevention strategies to patients.
Significance of zoonotic disease
Although some of the zoonotic diseases in this volume are not dramatically
significant in daily practice, there are others that cause serious disease, or their
prevention complicates the management of severely or chronically ill patients.
The estimate from the Health and Safety Executive (HSE) that 300 000 people
are potentially exposed to risk of zoonotic disease annually is not insignificant
when viewed in terms of economic loss or personal misery.1
Zoonoses carry with them a cost, not just in purely monetary terms, and
many of them are preventable. It is therefore important that, whenever
possible, strategies are implemented to treat appropriately, or prevent these
diseases, in order to safeguard scarce resources and thereby benefit patients.
One of the key objectives of this book is to provide a knowledge base to
assist assessment of patients seen in pharmacies and other healthcare
settings. Information informs and shapes all healthcare practice, and knowledge of these conditions forms a part of the body of skills necessary in
primary care. Healthcare practice is changing and there is an increased
emphasis on a team approach to dealing with patients. The numbers of
patients accessing healthcare services other than through a doctor’s surgery
is greater than ever before, and the skills and knowledge needed to signpost
these patients accurately so that they obtain the best, most appropriate
treatment for their conditions are also changing. There is a growing need for
practitioners to obtain the widest skills and knowledge base possible to
benefit both patients and colleagues.
266 | Zoonoses
The majority of zoonoses are untreatable at community pharmacy level,
or at other first-contact sites such as walk-in centres or through telephone
counselling services. Nor do the healthcare professionals involved at these
first-contact sites have comprehensive right of diagnosis and, at present,
prescribing rights necessary to treat these conditions effectively. Therefore,
after an oral history has been taken or physical symptoms have been noted,
all patients who are suspected of being victims of these conditions should be
referred to a medical practitioner as soon as possible. It may well be of
benefit to write a referral note, especially where there is suspicion of a serious
condition, so that the information and observations can be communicated to
the medical practitioner. This is especially essential where there may be a
period of time between the patient’s presentation and the next available
appointment at the doctor’s surgery, or where it is possible that the symptoms
displayed may be transitory, e.g. in the tick bites or tick attachment and
erythema associated with Lyme disease.
Pharmacists and other healthcare professionals who undertake domiciliary visiting or have regular contact with patients over a prolonged period of
time will often have an extensive knowledge not only of the patient but also
of his or her domestic situation. This can be a key to understanding either a
chronic or an acute exacerbation of a patient’s condition, in which a zoonotic
disease derived from a companion animal, work or immediate environment
may be responsible. There is also an increasing call for health information
and activity relating to either health improvement or prevention of illness.
For at-risk patients with chronic conditions or who are on continual therapies,
a requirement to initiate or enable a risk- or harm-reduction programme is
desirable if not yet mandatory.2
Disease prevention strategies
There is a body of literature relating to risk–benefit analysis in health issues.
Zoonotic disease falls readily into this framework. Many of the risks have
already been covered in some detail, so to set the scene for the rest of this
chapter it is necessary to consider the benefits associated with animals in a
social and domestic context.3,4
Benefits of companion animal ownership
Most cat owners, when asked, state that they keep cats for companionship
and affection. This group is not alone: other groups of companion animal
owners will express similar sentiments, even if their companion animal of
choice is a reptile or other creature that is perhaps less cuddly or less
demonstrative.
Implications for healthcare | 267
Studies undertaken across the world have shown that bereaved, socially
deprived, mentally ill and house-bound individuals all exhibit lower
symptom levels, or improvements in their condition, if they have contact with
a companion animal. Reductions in blood pressure and improved recovery
rates have been demonstrated in male participants in one study. The charity
Pets as Therapy (PAT), which takes dogs into residential homes and other
long-term care settings, justifiably claims to improve the quality of life of
many patients.5
Children and adults who have behavioural difficulties or psychiatric
conditions have been shown to improve if they have to care for another
creature that in return demonstrates affection for them. The evidence
appears to be convincing that the benefits are real, and not imagined, with
far-reaching implications.6,7
These benefits may come at a price, because there may be a risk to a
patient from contracting a zoonotic disease. The next part of the process is
the risk assessment and, if appropriate, implementation of a harm-reduction
strategy.8
The assessment process also needs to focus on the already unwell or atrisk patient. It must be remembered that nobody is completely safe, and that
individuals who are on their gap year, off to far-flung places to do voluntary
service overseas, or outdoor pursuits, may require some health advice,
although a full risk assessment and harm-reduction programme are usually
inappropriate.
Benefits from domesticated animals
There is another aspect to be considered before passing on to the assessment
stage. Domesticated, agricultural and other animals also have a societal role.
Traditionally, animals have been kept for their products, be they eggs, meat,
milk and milk products, hides for leather, wool, or a wide variety of byproducts such as gelatin, glycerin, hair or fats and oils. Although the number
has reduced markedly over past decades due to social changes and higher
costs, there are also individuals who work with wild or part-domesticated
animals, such as pheasant and other game birds or deer, kept solely for
hunting.
In social terms, a large number of people derive their employment from
involvement in the rearing, husbandry, harvesting and processing of animals
and their products. As in many other areas of human endeavour, this carries
its own associated risks. Employment in this industry carries with it an
enhanced risk from certain pathogens, including some zoonoses. Individuals
who have other predisposing factors, which make them more susceptible to
contracting disease, may have some difficult choices to make if reducing
their risk involves losing the benefit of continued employment.
268 | Zoonoses
There are also a number of occupations where exposure to animals is
part of the daily routine, but where exposure might be less obvious. Dog
wardens, animal rescue workers, roofers, especially when working on roofs
where pigeons or other birds have roosted, and zoo and circus employees all
stand at greater risk of exposure to zoonotic pathogens than members of the
general public.9
Risk assessment
In both primary and secondary care settings healthcare workers often gain
knowledge relating not only to the medication and/or physical condition of
their patients, but also sometimes to their domestic situation, especially
when domiciliary visits are undertaken. The presence of a companion
animal and a basic knowledge of the likely zoonotic conditions associated
with that species might assist in assessing the patient’s risk.
A few years ago, a doctor told me that another partner in the practice had
been treating an elderly woman for a prolonged period for a recurrent chest
infection and persistent dry cough. A home visit had to be made after the
woman had become acutely ill and an emergency call had been made. On
examination, the woman was found to have a severe pulmonary infection
again. It was only as the doctor prepared to leave that the elderly woman said
that her cockatoo had been off-colour for a while, and that the vet was now
treating it for its wheeze. Serological tests showed the woman to be suffering
from psittacosis, and the condition resolved on prolonged antibiotic therapy.
The moral for all healthcare workers that can be drawn from this story is
that it is essential, especially when carrying out a risk assessment, to have a
comprehensive knowledge of patients and their lifestyle and circumstances. It
is necessary to concentrate not just on the disease state, but on the individual
as a body with an interesting condition attached.
Accurate observations, asking the right questions and building a picture of
the patient’s condition are skills that all healthcare workers should develop.
There must also be some knowledge of the likely pathogens associated with
particular animals and the patient’s circumstances.
A risk assessment for other reasons may form part of a patient’s discharge
procedure from secondary care, and it is essential for the risk of zoonotic
disease to be included in an appropriate manner for certain patients. When a
patient’s history is being taken either formally or informally, any mention of
a close association with animals should raise this issue, if only in the mind of
the healthcare worker concerned.
To recap, the main identifiable risk groups are children, pregnant women,
immunocompromised patients, agricultural and food-industry workers, and
elderly or infirm people. The main diseases associated with these groups are
summarised in Table 9.1.
Implications for healthcare | 269
Table 9.1 Summary of diseases by risk group
Risk group
Main disease threat
Animal handlers
Leptospirosis
Pasteurella
Rabies
Salmonella
Tetanus
Neonates and children
Cutaneous larva migrans
Escherichia coli
Hookworm
Salmonella
Scabies
Tetanus
Toxocara
Toxoplasmosis
Elderly and infirm people
Escherichia coli
Influenza
Listeria
Psittacosis
Salmonella
Tetanus
Agricultural and food industry workers
Anthrax
Brucellosis
Echinococcus
Escherichia coli
Leptospirosis
Orf
Pasteurella
Q fever
Salmonella
Tetanus
Tuberculosis (Mycobacterium bovis)
Immunosuppressed or immunocompromised individuals
Campylobacter
Cat scratch disease
Cryptococcosis
Cryptosporidia
Escherichia coli
Listeria
Mycobacterium avium complex
Psittacosis
Salmonella
Toxocara
Toxoplasmosis
Tuberculosis (M. bovis)
Pregnant women
Gestational psittacosis
Listeria
Salmonella
Toxocara
Toxoplasmosis
270 | Zoonoses
Having identified the animals with which the patient comes into regular
contact, a review of the possible disease states related to the animal is needed.
Detailed information on these diseases can be obtained from the appropriate
sections in previous chapters. Listing the diseases can help identify insertion
points for control measures to stop transmission or reduce pathogen
burdens.
When carrying out an assessment, it is important to remember that it
appears that the absolute risk of contracting a zoonotic infection is
dependent on additive risk factors. Children on farms, immunocompromised
agricultural workers and pregnant food-industry operatives have a greater
risk than a similar individual who does not have the additional risk factor.
Absolute risk is also dependent upon other factors, such as regular
consumption of unpasteurised dairy products; frequent close contact with
animals or poor personal hygiene practice adds a further layer of risk.10
It should be remembered that patients whose immune system is
compromised or inadequate might not be solely those individuals suffering
from human immunodeficiency virus/acquired immune deficiency syndrome
(HIV/AIDS). This category applies also to patients who are alcoholic, especially if cirrhosis is present, individuals with certain neoplastic diseases
where chemotherapy, radiotherapy or high levels of steroids are being used,
patients with renal, hepatic or splenic failure, people with diabetes, individuals with certain congenital conditions including cystic fibrosis, those with
autoimmune conditions such as systemic lupus erythematosus where
immunosuppressant therapy may be used, organ transplant recipients with
concomitant immunosuppressant therapy, people who are malnourished
and haemodialysis patients.
Patients on high-dose steroids or receiving long-term low-dose steroid
therapy also show some loss of immunocompetence. The side effects of such
therapy pose a risk to the patient from many pathogens, and from physical
damage that may lead to infection. Zoonoses are not the only risk to these
patients; however, they should not be ignored.11
In essence, an elderly, immunocompromised agricultural worker who
keeps pet cats in the kitchen, sleeps with the dogs, does not wash and
regularly consumes pints of unpasteurised milk is either lucky or dead.
Harm reduction and prevention
The gold standard for all healthcare has always been preventing a condition
from establishing itself, so that therapeutic intervention in clinically
advanced symptomatic disease is rendered unnecessary. In zoonotic infection the old adage that ‘Ten parts of prevention are better than one part of
cure’ holds very true. Once contracted there are certain zoonoses that are
impossible or extremely difficult to eradicate. Toxocariasis, toxoplasmosis,
Implications for healthcare | 271
tuberculosis and psittacosis all pose immense problems in ensuring that a
sufferer does not relapse with a further attack after a course of therapy. In
some individuals continuous or periodic treatment may be necessary to
maintain a cure.8
However, prevention, with the implied complete protection that it offers,
may be unachievable for a variety of reasons, and often the best that can be
attained is a diminution of risk, or a reduction in the harm that an infection
may cause. For identified risk groups reducing the risk of contracting
zoonotic infections forms an important part of the healthcare professional’s
role. The usual premise for harm reduction is that an attempt must be made
to maintain patients’ health, while seeking to alter their overall quality and
style of life the least. Realistically, to achieve this end, there is a need for
patients to receive as much education and information relating to the risks
that they face, and the means of reducing those risks from exposure to
zoonotic agents. This can be as simple as promptly cleaning up the cat litter
tray, or getting somebody who does not have any predisposing condition to
empty the tray. The information provided has to be geared to the patient’s
comprehension and there may be a corresponding need for counselling or
support.
The main plank of any strategy is prevention of exposure or reduction of
risk associated with exposure to a pathogen (Figure 9.1). Achieving this in
patients who are already ill can be extremely difficult, because there often is
a need to change long-standing habits, while trying to hold relationships,
employment and private life together. This can be particularly difficult for
patients where their condition is unlikely to improve unless they cease to
own pets, especially if one of their main sources of emotional comfort is a
companion animal, rather than relatives or friends. Harm reduction
becomes much less easy in patients who may have an occupational exposure
to zoonotic pathogens, where changing employment may be difficult or
impossible.
With the current economic and other difficulties that agricultural enterprises face, the last straw may be the loss of a worker, especially in a small
operation. The effects for an individual can also be catastrophic, with loss
of income leading to far-reaching lifestyle changes.12
It is essential that any portion of an overall strategy or measure that can
be achieved is seen as a bonus. However resistant the patient may be, and
however ill, there is usually something that can be done to reduce risk.
In a chronically ill patient, measures may have to be introduced gradually over long periods. The full spectrum of applicable measures may be
attained only as the patient becomes comfortable with the necessary
changes. The rate of change has to be driven by the patient, not the health
professional, as that could lead to conflict and refusal of the patient to adopt
or maintain the necessary measures.
272 | Zoonoses
Parlour hygiene
Refrigeration
Pasteurisation
Sell-by dates
Personal hygiene
Antibiotics
Anthelmintics
Drug prophylaxis
Lifestyle changes
Protective clothing
H
HOSPITAL
Immunise
Worm
Treat infections
Refrigeration
Good housing
Correct storage
Clean food
and water
Abattoir procedures:
Good hygiene
Adequate
cooking
Pre- and
postslaughter
inspections
Figure 9.1 Prevention points and strategies for food-borne zoonoses.
It is also essential that this be viewed as a multidisciplinary issue. The
traditional core team in community care is expanding. Issues relating to
zoonotic infection may cross the boundaries of social work, veterinary care,
nursing, pharmacy and medical services. If one practitioner identifies an
issue, then communication to other parties is essential. This becomes particularly true when dealing with patients whose condition may be chronic, and
who require a large alteration to their lifestyle for risk reduction. The
involvement of a veterinary surgeon, employment service advisers or benefit
agency personnel – all classes of professionals not traditionally seen as
healthcare workers – may be indispensable.11
Constituent measures for prevention strategies
Having identified what appear to be the main risk pathogens, the next step
is to develop the components for a successful strategy. Table 9.2 provides a
Implications for healthcare | 273
Table 9.2 Summary of prevention measure
Mode of transmission
Prevention measures
Pica/faecal contamination of
food, water, clothing or skin
Education and personal hygiene
Anthelmintics or antibiotics for animals and humans
Prompt removal of faecal matter
Disinfection of contaminated areas or items
Thorough cleaning and cooking of food
Ensuring that water is clean by filtration or chlorination
Aerosol
Use of facemasks (personal protective equipment or PPE)
Saliva
Avoid animal bites and disinfect wounds promptly
Vaccinate animals and humans
Avoid direct contact with animal’s face
Muzzle aggressive animals
Educate owners not to kiss their pets
Blood
Cover open wounds
Vector mediated
Use repellents
Control life cycle at breeding sites
Use insecticides/parasiticides
Wear suitable clothing
Fomite contact
Clean surroundings thoroughly, and disinfect as appropriate
Wear suitable protective clothing while undertaking risk activities
Food
Cook meat and eggs thoroughly
Consume pasteurised milk and cheese
Wash or clean food thoroughly
Refrigerate items correctly. Do not consume past ‘best before’ or out-ofdate items
Use common sense and practise personal hygiene
In chronic or extreme cases
Consider drastic changes to lifestyle, including:
changing employment
avoiding contact with animals
permanent removal of animals from domestic environment by
rehoming or euthanasia
controlling feral or pest animals in vicinity
sterilising foodstuffs
summary of the threat posed from method of transmission, mode of infection
and the appropriate prevention measures.
The framework shown in Table 9.2 can be used to assemble a list of
possible measures, which can in turn be used to reduce transmission and
infective risk. It is only a starting point and does not exclude innovation or
imagination. Be aware that most of the measures listed are voluntary; there
is no legislation that forces companion animal owners to adopt any or all of
the recommendations.
274 | Zoonoses
This is not true for workers in the agricultural or food industries, or in
any other occupation where contact with animals or their products forms
part of the normal work routine. People employed in this way have a
greater duration and frequency of contact with animals, and therefore an
increased likelihood of being exposed to zoonotic pathogens. The protective measures recommended for this group are already enshrined either in
statute or in best custom or practice within the associated industry, usually
under provisions of established legislation. These are explored at the end of
this chapter.1
There is also a risk group that falls between the companion animal
owner and the commercial extremes. These are people who are employed as
animal keepers in zoos and circuses and also the workers in protection societies and animal refuges or rescue centres, who may be volunteers or casual
workers. There is a possibility that they can, because of the nature of their
work, fall outside the scope of regulatory protection. Best practice would be
for these individuals to adopt the measures required in industry; however,
this may not be possible. For this group a mix-and-match approach to
prevention measures is probably best. Where any doubt exists as to the
hazards associated with a particular animal or procedure it is best to err on
the side of caution.
Health promotion and education
So far the focus of this chapter has been upon the patient who is already
unwell. What of the worried well or the population in general? Healthy pets
mean healthy people and vice versa. In general a companion animal that is
regularly wormed, properly fed and bedded down will be less likely to
harbour infection. The control of ectoparasites, regular veterinary care and
domestic hygiene routines with the use of disinfectants, wearing protective
gloves when handling faecal matter and preventing the animal biting, licking
or scratching any human go a long way to reducing accidental infection
rates.13
As a prevention measure, the early education of children about the care
of animals and good personal hygiene is important in preventing not only
immediate disease, but also the establishment of an infective focus (such as
toxoplasmosis) which, once contracted, may recur at a later juncture.
General advice is usually available from veterinary surgeons, animal charities
and other bodies, many of whom provide online advice or information
leaflets.
The information relating to prevention measures for patients, their
carers, friends and relatives, or healthcare professionals is also not difficult
to access. As in many other fields of medicine, there is a great body of information available, particularly on the internet, which is often overwhelming
Implications for healthcare | 275
in its quantity, if not its quality. Some of the websites in Appendix 1 provide
starting points of proven probity.
As with most medical conditions, many self-help groups are able to
provide literature for use in patient education on the risk of zoonotic
diseases and the appropriate management of companion animals either to
prevent these diseases or to develop harm-reduction strategies.
This is an important field of health promotion where healthcare professionals are well placed to be effective advocates for both patients and their
pets. There is a profound need for the void between veterinary care and
traditional GP-led community services, where there may be little linkage
between the pet and the patient, to be bridged. The problem of health
education relating to zoonotic disease is an issue that must be grasped to
protect the health of all owners of companion animals.
Healthcare professionals not belonging to the medical profession should
consider rapid referral of any patient suspected of having a zoonotic condition to a doctor as soon as is practicable, because most of these conditions
will not respond to self-medication.
Treatment
If the disease cannot be prevented, or the risk-reduction strategy fails, the next
option is treatment. This is usually with a therapeutic agent, be it an antibiotic, antifungal, anthelmintic or insecticide, although in some conditions
(e.g. hydatid disease) surgical intervention may also be necessary.
Resistance, especially in antimicrobial treatment, affects the effectiveness
of any drug therapy, and this is becoming an increasing concern. Extensive
studies have been undertaken by the Department for Environment, Food
and Rural Affairs (DEFRA) and the Department of Health (DH) in the UK,
with input from the Health Protection Agency (HPA), to ascertain the extent
and significance of the problem. The World Health Organization (WHO)
has issued guidelines on prescribing and supplying antibiotics and is also
carrying out continuing investigations of its own. The issue is significant
when related to zoonoses, because animals are treated with the same antibiotics as humans. Any resistance developing in the animal population can
spread into the food chain and thus affect the usefulness of these agents. The
display of resistance to certain insecticides and anthelmintics should also be
borne in mind when choosing an agent, and monitoring may be necessary
to determine the chosen drug’s efficacy.14
Many cases of zoonotic infection will never reach the stage of symptomatic
disease, or be diagnosed, and are resolved by empirical general antibiotic
treatment by a patient’s GP before full-blown clinical symptoms can manifest.
More cases may be seen of certain diseases as blind use of wide-spectrum
antibiotics declines.
276 | Zoonoses
In many cases of infection where a zoonotic disease is suspected, the rapid
use of antibiotics is often imperative. Susceptibility testing may be necessary.
Broad-spectrum blind usage, although not desirable, can be the fastest
method to prevent progression. Combination therapies or progression to
‘reserved’ moieties may be necessary, especially if the course of the disease is
rapid or morbidity is feared, although this normally requires diagnosis using
appropriate tests.
Certain infections may require extended antibiotic therapy with the
concomitant problems associated with interactions and choice of a suitable
agent for sustained use. In immunocompromised patients there will be a
requirement for specialist support in choosing, monitoring and supplying
some drugs required for eradication or control of certain organisms, especially resistant strains of tuberculosis and Cryptosporidia spp. There may
also be a need to keep latent infection suppressed for a patient’s lifetime, as
in toxoplasmosis, so expert advice is essential.
When choosing anthelmintics for worm infestations, the more unusual
parasites may require drugs that are not in routine use and/or available on a
named-patient basis only. In these cases support from specialised units can be
invaluable. In the UK, IDIS Ltd can provide many of these specialised drugs
(see Appendix 2 for details); in the USA the Centers for Disease Control and
Prevention (CDC) will provide advice and have a scheme that allows drugs
not normally available in continental USA, or not normally used for human
treatment, to be supplied. There may also be an issue, where the parasite load
is heavy, of the use in a domestic situation of certain products, because rapid
death of the parasites can lead to systemic toxicity and allergic reactions.
The use of unlicensed products is a thorny issue, and the initiation of
such drugs at primary care level may pose a serious clinical dilemma. It may
be necessary to refer a patient to another healthcare provider, if practicable.
In cases of more unusual organisms, especially if the condition has been
contracted abroad, hospitals specialising in tropical diseases may be the best
informed and best placed to undertake treatment. Specimen addresses and
contact telephone numbers may be found in Appendix 2.
General supportive therapies may also be needed for symptom control.
The use of anti-inflammatory drugs, painkillers, rehydration therapy or
antiemetics may be appropriate. In specific conditions, i.e. hydatid disease,
surgery may be necessary, requiring unusual drugs or adjuncts depending
upon the severity or extent of infection, the organism responsible and the
stage in its life cycle. Specialist support can again be invaluable.
The choice of pesticide in arthropod infestations needs to be carefully
considered to ensure that no underlying medical conditions are exacerbated.
Press coverage of Gulf War syndrome has heightened public fear of pesticide
use, but not in a balanced way. This has led to unreasoning fear of all insecticides. On that basis it is necessary to be careful in choosing an agent that
Implications for healthcare | 277
will not only eliminate the arthropod concerned, but also not cause or
increase the anxiety of patients or their carers.
Hypersensitivity to organophosphates and the emergence of resistant
strains of arthropods are matters of concern, and influence the choice of
agent. The formulation may also be important; the use of alcohol-based
lotions or solutions is contraindicated in people with asthma, and other
formulations may be unacceptable to some patients because of odour or
consistency.
Wherever possible, detailed information on treatments has been given in
the appropriate single-disease sections. However, not all of these therapies are
officially approved, so treatment must follow local or national policies or
guidelines. The overriding authority is either the national or local formularies
when therapeutic choices are to be made, unless the condition is so unusual as
to require empirical treatment.
Antimicrobial resistance
The ability of microorganisms to adapt to any conditions and challenges is
remarkable. Their ability to develop resistance to currently available antibiotics has become of increasing concern. The emergence of methicillinresistant Staphylococcus aureus (MRSA) and other organisms with multiple
resistance to whole classes of antibiotics threatens to return the management
strategies for certain diseases to the pre-penicillin era.
Concerns arose over the use of antibiotics related to their use in animals,
both in feed as additives either to preserve health or to increase weight gain,
and within herd management programmes as routine interventions. In July
1998 a comprehensive review of the issues and data related to antibiotic
resistance in the food chain was undertaken by the then Ministry of
Agriculture, Food and Fisheries (MAFF; now DEFRA). The House of Lords
Select Committee on Science and Technology also reported on resistance to
antibiotics and other antimicrobial agents in 2001.15
The Advisory Committee on the Microbiological Safety of Food
(ACMSF) also reported in 1999, and this led to the establishment by DEFRA
of an Antimicrobial Resistance Co-ordination Group (DARC). All of these
reports and working groups highlighted the threat to human health, and a
report The Path of Least Resistance from the Standing Medical Advisory
Committee,16 as well as recommendations made in the UK Antimicrobial
Resistance Strategy and Action Plan produced by the NHS Executive in June
2000, led to health authorities being required to develop local prescribing
guidelines, and also to the first tranche of animal growth promoters being
banned in 1999 (bacitracin, spiramycin, tylosin and virginamycin). The
second and final tranche were banned in 2006 (avilamycin, monensin,
fluorophospholipol and salinamycin).17
278 | Zoonoses
A Veterinary Medicine Directorate (VMD) report has also led to the
development of guidelines for responsible practice for the use of antibiotics
in animals. This is supported by a voluntary scheme endorsed by RUMA – the
Responsible Use of Medicines in Agriculture Alliance.
The VLA in cooperation with the Food Standards Agency (FSA) and the
HPA continues to survey food-borne pathogens to determine the prevalence,
resistance and subtypes of pathogens present in the food chain.
In Europe, in 2001, the European Commission (EC) introduced a
‘Community Strategy against Antimicrobial Resistance’. There are 15
actions in 4 key areas: surveillance, prevention, research and product development, and international cooperation. There are also EC recommendations on the prudent use of antimicrobials, and an agreement on the phasing
out of growth promoters in animals. The European Union (EU) also has an
industry scheme run through the EMEA (European Agency for the Evaluation
of Medicinal Products), which seeks to address the need to promote new
effective antibiotics.
The European Antimicrobial Resistance Surveillance System (EARSS)
consists of 700 laboratories in 28 countries. There are also a variety of
schemes under EU or EC auspices; these include Enternet, the European
surveillance system for enteric disease which also provides susceptibility
testing on salmonella and VTEC (E. coli) isolates, EuroTB which undertakes
surveillance of tuberculosis (both Mycobacterium bovis and M. tuberculosis)
and developing drug resistance, and the ESAC or European Surveillance of
Antimicrobial Consumption, ARPAC (Antibiotic Resistance Prevention and
Control) project aimed at the prevention and control of resistance.
The EC also has an outreach programme – Antibiotic Resistance in the
Mediterranean (ARMed) – which covers not only European countries in the
Mediterranean littoral, but also a wider extended area including Malta,
Cyprus, Turkey, Tunisia, Egypt, Morocco and Jordan. The EC and the
WHO have a Memorandum of Understanding (MOU) on health including
strategies against antibiotic resistance.
From the research available, it would appear that resistance to antibiotics in animal pathogens that may be zoonotic is selected after the
introduction of veterinary medicines or growth promoters. This produces
bacteria capable of being transmitted to humans by food; these bacteria are
resistant to related human antimicrobial moieties, which can then lead to difficulties in successfully treating any disease thus caused. The use of antibiotics
in agriculture is of particular concern in zoonotic disease, because the
pathogens, by definition, are from animal sources.
The issue is not trivial, as some of the organisms in which resistance has
been identified are not resistant to solely one antibiotic class but exhibit
resistance across a range of antimicrobial groups. Multi-antibiotic-resistant
pathogens of particular concern are those resistant to fluorinated quinolones
Implications for healthcare | 279
(Salmonella and Campylobacter spp.), macrolides (Campylobacter spp.),
virginamycin (enterococci) and avoparcin (enterococci).
There is also evidence that resistance has increased. Recent reports from
UK government agencies show that E. coli resistance to ciprofloxacin has
increased up to 23% in 2006, up from 1% in 1993; resistance in the same
organism to third-generation cephalosporins has risen to 11% in 2006, up
from 2% in 2001. Resistance to cephalosporin is also up from 2.2% in
2001–3 to 12% in 2006, and resistance to ampicillin/amoxicillin has gone
from 52% in 1993 to 60% in 2006. Resistance to gentamicin, which was 1%
of isolates in 1993, has reached 8.5% in 2006. Most of Europe demonstrates
the same or in some cases higher levels.
In 2006 Campylobacter jejuni was 30% resistant to ciprofloxacin and
C. coli was 37% resistant. Erythromycin resistance is low in C. jejuni and
runs at 38% in C. coli.
The other food-borne zoonotic pathogens considered to be of significance are the Salmonella spp., still deemed to be responsible for most
serious food-poisoning cases. Salmonella typhimurium DT104 and other
strains of S. typhimurium and S. virchow have been isolated that are fluoroquinolone resistant. In addition, 58% of Salmonella DT104 isolates are
resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides and
tetracyclines. The R serotype of this pathogen is additionally resistant to
trimethoprim and quinolones, posing a real problem in treatment terms. In
non-typhoidal salmonellae the most worrying is the resistance to nalidixic
acid coupled with decreased susceptibility to ciprofloxacin.18
The fear is that resistance may be transferable from animal to human
enterococci, which continue to pose problems in immunocompromised
patients. Plasmid-transferred resistance has been demonstrated in two
strains isolated in Madagascar of Yersinia pestis, the zoonotic causative
pathogen of plague, and of considerable concern and significance in terms
of world health, especially in the developing world. One strain is streptomycin resistant – previously the main drug of choice for treating plague –
and the other is resistant to chloramphenicol, tetracyclines and
sulphonamides – the second-line alternatives.
The WHO believes that there is evidence for arguing that, wherever
possible, antibiotics should not be extensively used in agriculture, especially
where the use is purely to accelerate animal growth to market weight, rather
than to treat clinical disease. The emergence of vancomycin-resistant
bacteria shows links to the use of the related compound avoparcin, and the
introduction of pristinamycin into human therapy has been compromised
by the past use of virginamycin in animal feed.
The WHO has set out a document containing global principles for the
containment of antimicrobial resistance in animals intended for food. This
suggests that all antimicrobials used for growth promotion should be
280 | Zoonoses
phased out as soon as possible. Governments are exhorted to refuse or
revoke licences for these products. There is also a recommendation that
antibiotic use in animals should not be seen as a replacement for good
husbandry.14
Direct impact of antibiotic resistance on healthcare
This issue is of considerable concern in a secondary care setting where seriously ill patients are treated regularly, and where health policy, especially on
prescribing practice, is pioneered. The emergence of MRSA and Clostridium
difficile, in particular, along with other resistant pathogens in hospital premises, has provoked a measured response with the introduction of antibiotic
policies in these establishments. With the move to primary care trusts (PCTs)
and the introduction of regional or area formularies, consideration has been
given to issues of seamless care and antibiotic hierarchies. Coordinated
policies for primary and secondary care on antibiotic prescribing may slow
the emergence of resistant pathogens.19
The situation in the USA is similar, with the CDC driving the prudent use
of antibiotics, and a cross-governmental consensus across a wide range of
national, and state, bodies working towards rational and agreed strategies
to prevent resistance in both human and veterinary spheres.
Antimicrobial resistance in therapy for immunocompromised patients
has also become an issue. Regimens for the treatment and continued
prophylaxis of the main zoonotic pathogens seen as a threat to these
patients must be decided through specialist units, with the support of microbiological laboratories and consultants to ensure that moieties can continue
to be effective and available.
In conclusion, there is a need for coordination between not only
secondary and primary care, but also animal and human health specialists
and governmental bodies to ensure that, in the future, the therapeutic gains
derived from antibiotic use are not lost.
UK legislation
A brief mention has previously been made of the HSE/COSHH (Health and
Safety Executive/Control of Substances Hazardous to Health) regulations.
As in any other realm of healthcare, practice goes hand in hand with the law.
It is almost inevitable that some of these rules and regulations cover aspects
of zoonotic diseases. Wherever possible these regulations have been indicated in the sections or chapters relating to the condition caused by the
responsible pathogen. The following section assembles some of the more
significant measures.
Implications for healthcare | 281
The Health and Safety at Work etc. Act 1974
This act and the statutory instruments and regulations made under it confer
a duty of care on employers to ensure that they do not expose their
employees to risks in the work place. It requires all employers to draw up a
health and safety policy statement, and to provide protective clothing or
equipment as required by health and safety law. Likewise, all employees
must ensure, as far as possible, their own safety when working.1
There is also a requirement to report injuries and certain diseases
(including zoonoses) to the HSE. This is covered by the Reporting of Injuries,
Diseases and Dangerous Occurrences Regulations (RIDDOR) 1995. These
replaced the previous regulations, and came into force in England, Scotland
and Wales on 1 April 1996. Under these rules there is a responsibility for an
employer or self-employed person to report a case of any disease listed in
Schedule 3 of the regulations, once it has been diagnosed in writing by a
doctor, and when the person concerned is currently employed in an associated
work activity.
The following zoonotic diseases are included in the Schedule:
•
•
•
•
•
•
•
•
•
Anthrax
Avian and ovine chlamydiosis
Brucellosis
Leptospirosis
Lyme disease
Q fever
Rabies
Streptococcus suis
Tuberculosis.
In addition there is a catch-all clause, where any disease that may have
stemmed from work activities has to be reported, including those possibly
contracted from handling dead bodies or tissues of animals or humans. The
section on work-induced lung disease also covers such pathogens as
Chlamydophila psittaci, Mycobacterium avium complex and Cryptococcus
neoformans.
Management of Health and Safety at Work Regulations 1992
These regulations are made under the Health and Safety at Work etc.
(HASAW) Act 1974, and require employers to carry out an assessment of the
risks in their work place, implement suitable risk control measures and carry
out health surveillance on employees. They must also inform employees of
any risks in the work place (including zoonoses) and give suitable and
282 | Zoonoses
adequate training to educate their workers in good practice and prevention
measures.
Control of Substances Hazardous to Health Regulations 1999
The COSHH regulations are also made under the HASAW Act 1974. They
classify the pathogens that cause zoonoses as hazardous substances. Under
these rules employers and self-employed people are required to assess the
risks to health from work activities that involve hazardous substances and
prevent or, where this is not reasonably practicable, adequately control
exposure to the hazardous substances.
Employers must promote good occupational hygiene, with the emphasis
on safe working practices, personal protective equipment (PPE) and personal
hygiene. Safe working practices include avoiding injury from tools or equipment, correct disposal of contaminated sharps, and avoiding other high-risk
activities such as handling placental matter or dead animals with the bare
hands. PPE should be used whenever necessary, and must be adequate and
appropriate for avoiding infection. The use of gloves, respirators, waterproof
aprons, face shields, special overalls or other clothing and footwear, when
carrying out tasks such as examining animals or assisting at birth, is
recommended. All PPE should be CE marked and to the appropriate British
Standard (BS).
Personal hygiene should be promoted with adequate washing facilities,
provision of hot water and soap, and a means of drying the hands.
The regulations also lay emphasis on the need for common-sense precautions regarding wound care, first aid, disinfection of animal bedding and
housing, mucking out regularly and other precautions that prevent disease
transmission. Good husbandry practice of regular worming, prompt vaccination and high standards of care and cleanliness are suggested as appropriate
measures to assist disease prevention.
Leaflets, advice and information on the HASAW Act and the other
legislation made under it can be obtained from http://www.hse.gov.uk.
Notifiable disease legislation
There are measures separately enacted that require disease notification for
animals or humans. As zoonoses affect both categories, the main legislation
for both is discussed below.
Statutory notifications of infectious diseases (human)
The requirement to notify cases of certain infectious diseases first came into
force in the late nineteenth century. It is tackled by two strands. The first,
Implications for healthcare | 283
health and clinically based aims to undertake disease surveillance, works
through the HPA; the second is based around a network of public health
‘proper officers’ (who may not be health based) appointed by local authorities
who collect and collate information which is passed to the Office for National
Statistics.
The health-based system is geared to providing rapid detection of
epidemics or mass outbreaks of potentially serious disease. The system is
currently administered by the HPA Centre for Infections, and other regional
surveillance centres, and is known as Notification of Infectious Disease
System (NOIDS). Based on clinically based activity through diagnostic
laboratory reporting, and clinical reports of disease through the Local and
Regional Service (LARS) of the HPA, it is fed by the responsibility for notification which rests upon ‘the attending medical practitioner’, who may
range from any doctor in any care setting to the proper officer of the local
authority. To gain the speed necessary to prevent epidemics, notification
does not rely on clinically proven diagnosis; a presumptive diagnosis is
enough, with later confirmation or cancellation.
Under this legislation food poisoning should also be notified. This was
defined in respect of the regulations using a DH definition, which states that
food poisoning is ‘any disease of an infectious or toxic nature caused by or
thought to be caused by the consumption of food or water’.
Although this is a wide definition, it does cover all cases; however, it does
not permit differentiation between causative organisms, but the resulting
notification allows some statistical work to take place.
In the public health arena, there is a formal reporting system covering a
number of diseases under the Public Health (Infectious Diseases) Regulations
1988. In Scotland the Public Health (Notification of Infectious Diseases)
(Scotland) Regulations 1988 require similar notification but also include
Lyme disease and toxoplasmosis. In Northern Ireland the equivalent
legislation is the Public Health Notifiable Diseases Order (Northern
Ireland) 1989.
Diseases notifiable under the Public Health (Infectious Diseases)
Regulations 1988, which are considered to be zoonoses, are (in alphabetical
order):
•
•
•
•
•
Acute encephalitis
Anthrax
Food poisoning
Leptospirosis
Meningitis caused by Haemophilus influenzae, or other viruses either
specified or unspecified
• Plague
• Rabies
284 | Zoonoses
•
•
•
•
•
•
Relapsing fever
Tetanus
Tuberculosis (M. bovis and M. tuberculosis)
Typhus fever
Viral haemorrhagic fever (i.e. Ebola)
Viral hepatitis.
Note: because of advances in diagnosis and symptom classification, some of
the categories framed at the time of the regulations now include under their
general headings conditions that might be caused by zoonotic agents. In
those cases the heading has been left open.
Notifiable disease in animals
A variety of measures is in place that requires notification of cases of certain
infectious diseases in animals. As in human cases, the notification is based
on presumption, not necessarily clinical proof, and the diagnosis may be
confirmed or cancelled after examination of suitable samples by the Veterinary
Laboratory Service.
Cases of notifiable diseases must be reported on suspicion to the divisional veterinary manager of DEFRA. Once confirmed, action will be taken
in accordance with animal health or other legislation.
Many of the measures relating to notifiable diseases in animals overlap,
and relate to previously endemic conditions that have now been eradicated
or controlled. Others relate to organisms that are classified as emerging, or
are seen as posing a significant threat were they to arrive in the UK. Examples
are Hendra virus and Echinococcus multilocularis. The latter condition is
specifically mentioned in the legislation and procedures underpinning the
Pet Travel Scheme (PETS), which defines specific measures to prevent the
introduction of this pathogen into the UK (see p. 201).
It should be noted that, in addition to the statutory reporting legislation,
there are a number of industry or trade association schemes for voluntary
reporting of diseases that may not be covered by legislation, but which
could cause economic loss to the agricultural industry.
Concerns that zoonotic pathogens could emerge or re-emerge also
underpin the following legislation:
• The Specific Animal Pathogens Order (1998) and the Specified Animal
Pathogens Order (Northern Ireland) 1999 cover three zoonotic
pathogens that are not currently seen in the UK, but that could cause
considerable damage were they to be introduced, namely Trichinella
spiralis, equine morbillivirus and Echinococcus multilocularis.
Implications for healthcare | 285
• The Zoonoses Order 1989 and the Zoonoses Order 1991 (Northern
Ireland) are specifically framed to cover the monitoring of Salmonella
and Brucella spp. from food-producing animals, their products,
environment or feeding stuffs.
• The Zoonoses (Monitoring) (England) Regulations 2007 came into
force on 1 October 2007, and are aimed at controlling zoonotic
outbreaks (and specifically highly pathogenic or HP H5N1). They
allow designated inspectors to enter any premises at all reasonable
hours to determine if an outbreak has occurred. In addition it has a
provision relating to wild animals, allowing samples to be taken that
might otherwise be in contravention of legislation protecting wildlife
species from any sampling or disturbance.
Notifiable diseases in the USA
In the USA, the CDC have responsibility for the National Notifiable
Diseases Surveillance System. Surveillance of infectious disease started in
the USA in the late 1800s, and by the early twentieth century an annual
summary of serious notifiable diseases was being produced. In 1961, the
CDC was given the mandate to collect and publish data relating to notifiable diseases; however, state reporting to the CDC still remains voluntary,
although reporting to state authorities is mandatory at state and county
level.
The list of diseases that are considered notifiable varies slightly by state;
however, every state reports the internationally quarantinable diseases in
compliance with the WHO regulations. The CDC publishes statistics and
data relating to notifiable infectious diseases in the Morbidity and Mortality
Weekly Report (MMWR). Of the diseases included in the list, which alters
periodically, many are zoonotic, but not all.
Nationally Notifiable Infectious Diseases List, United States 2008 (Zoonoses
only)
•
•
•
•
•
•
•
•
•
•
Anthrax
Arboviral neuroinvasive and non-neuroinvasive diseases
Eastern equine encephalitis virus disease
Powassan virus disease
St Louis encephalitis virus disease
West Nile virus disease
Western equine encephalitis virus disease
Botulism
Botulism, food borne
Botulism, infant
286 | Zoonoses
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Botulism, other (wound and unspecified)
Brucellosis
Cryptosporidiosis
Giardiasis
Hantavirus pulmonary syndrome
Haemolytic–uraemic syndrome, post-diarrhoeal
Listeriosis
Lyme disease
Novel influenza A virus infections
Plague
Psittacosis
Q fever
Rabies
Rabies, animal
Rabies, human
Rocky Mountain spotted fever
Salmonellosis
Severe acute respiratory syndrome-associated coronavirus (SARS-CoV)
disease
Tetanus
Trichinellosis (trichinosis)
Tuberculosis
Tularaemia.
Other US legislation
Non-Americans looking at the plethora of rules and regulations made at a
variety of levels within the US system (i.e. national, state, county, etc.) soon
become very confused because the system varies from state to state, and
some standards are voluntary whereas others are mandatory. National
governmental organisations such as USDA (US Department of Agriculture),
the FDA (Food and Drug Administration) and the health departments set
rules where possible, and enforce them nationally; however, because of the
complexity and size of the physical area of the USA, and the strength of state
legislatures, there may be other standards and regulations in addition to
national law. Readers are advised to check both national and local statutes
to ascertain what rules and legislation apply locally, and which diseases are
notifiable in both animals and humans, along with quarantine rules, etc.
Points to ponder
To round off this chapter and the book, there are a few random topics
relating to medical aspects of zoonoses that need some consideration.
Implications for healthcare | 287
Choice of companion animal
When individuals choose a pet, they do not routinely consult either a vet or
a doctor. In most cases, the decision may not have any significant consequences for the health of the pet owner or family; however, where there is a
seriously ill or potentially at-risk individual in the equation, either as a sole
owner or within a family group, the decision process may be more crucial.
The more exotic the pet, the more unusual the range of bacteria and other
pathogens that it can carry.
As discussed elsewhere in this book, reptiles and other exotic pets are
recognised as carrying unusual strains of Salmonella spp., stray kittens can
carry a variety of very interesting pathogens and a bird from a pet shop
could be the last straw for an already distressed respiratory patient. The
other aspect is that a young animal may be tractable and adorable, but the
adult may be less appealing and a lot more difficult.11
Guidance as to the suitability of a pet is readily available, usually from
veterinary surgeons or groups such as the Pet Health Council. When knowledge is gained that a patient or family is contemplating obtaining a new
companion animal, it is essential that they be encouraged to seek the available
advice before they take on a creature that could pose a health risk.
Xenotransplantation and transgenic animals
One of the dreams of the late twentieth century was the availability of an
inexhaustible supply of organs, especially hearts and kidneys, for transplantation from genetically engineered animals. Although still a matter of
science future rather than pure science fiction, the realisation of this dream
is still probably some years away. The ability of a company to produce Dolly
the Sheep and Percy the Pig was certainly impressive.
The scientific application of cloning technology, with the possibility of
manipulating the genetic material of animals to achieve therapeutic breakthroughs, has become more accepted. The existence of transgenic sheep
capable of producing human insulin or growth hormone gives hope for
many patients and opportunities for profit for drug companies. The use of
hearts from transgenic pigs has been suggested as a solution for the chronic
shortage of these organs from human donors.20
In any of these future initiatives it is necessary to exclude all zoonotic
pathogens from the material or organs used. The risks are greater than accidental exposure to the pathogen, because there will be a deliberate introduction of a quantity of animal tissue or material by surgery, or possibly injection.
In natural transplantation with human organs, the same risks apply, demonstrated graphically by the development of rabies in patients who received
infected organs. After the emergence of variant Creutzfeldt–Jakob disease
288 | Zoonoses
(vCJD), it has been demonstrated that under laboratory conditions prions
have been transferred to unrelated species by tissue transplants.
In the USA, transplants from non-human primates have been banned,
not only to preserve primate numbers, but also to prevent the spread of
zoonotic pathogens, especially viruses, because of these concerns. These
organisms may be benign in the normal host but could be pathogenic in
humans. Of concern is that any pathogen once across the species barrier
could modify to pass from person to person if there is a process such as viral
recombination, a process that probably occurred in the emergence of HIV.21
The other closest animal source to humans of organs are those derived
from pigs; these are also capable of carrying porcine endogenous retroviruses,
which are not known to be pathogenic in humans, but might become so.
This has led to a number of bodies passing policies and making recommendations including the EU and the WHO to reduce or prevent xenotransplantation. Thus, sadly, it appears that turning science fiction into science
fact still remains a distant, if not unrealistic, dream in this field of
endeavour, until safety concerns can be addressed.
References
1. Anonymous. Farmwise. London: Health & Safety Executive, 2005.
2. Zinsstag J, Schelling E, Wyss K, Bechir M. Potential of cooperation between human and
animal health to strengthen health systems. Lancet 2005; 366: 2142–5.
3. En Health. Environmental Health Risk Assessment – Guidelines for assessing human
health risks from environmental hazards. Department of Health and Ageing and
enHealth Council, Canberra, 2002.
4. European Academies Science Advisory Council (EASAC). Combating the Threat of
Zoonotic Infections. London: Royal Society, 2008.
5. Wells DL. Domestic dogs and human health: An overview. Br J Psychol 2007; 12:
145–56.
6. Schoen AM. The healing power of pets. In: Gorrel C (ed.), Kindred Spirits. New York:
Broadway Books, 2001.
7. Siegel JM, Angulo FJ, Detels R, Wesch J, Mullen A. AIDS diagnosis and depression in the
Multicenter AIDS Cohort Study: the ameliorating impact of pet ownership. AIDS Care
1999; 11: 157–70.
8. Guay DR. Pet-assisted therapy in the nursing home setting: potential for zoonosis. Am J
Infect Control 2001; 29: 178–86.
9. Bender JB, Shulman SA. Reports of zoonotic disease outbreaks associated with animal
exhibits and availability of recommendations for preventing zoonotic disease transmission
from animals to people in such settings. JAVMA 2004; 224: 1105–9.
10. CDC. Compendium of measures to prevent disease associated with animals in public
settings, 2005: National Association of State Public Health Veterinarians, Inc.
(NASPHV). MMWR 2005; 54(RR-4): 1–13.
11. Kahn LH. Confronting zoonoses, linking human and veterinary medicine. Emerg Infect
Dis 2006; 12: 556–61
12. Department for the Environment, Food and Rural Affairs (DEFRA). Zoonoses Report
UK. London: Defra, 2006.
13. Wong S, Gorczyca K, Forrow L, Angulo F. The healthy pets, healthy people project: A
collaborative effort between medical and social communities for persons with AIDS and
HIV. International Conference on AIDS, 9–14 July 2000. 13: abstract WePeD4495.
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14. World Health Organization. Overcoming Antimicrobial Resistance – World Health
Report on Infectious Diseases. Geneva: WHO, 2000.
15. Report of the House of Lords Select Committee on Science and Technology. Resistance
to Antibiotics, 3rd report. London: House of Lords, March 2001.
16. SMAC (Standing Medical Advisory Committee), Department of Health. The Path of
Least Resistance. London: HMSO, 1998.
17. Advisory Committee on the Microbiological Safety of Food. Report from the Defra
Antimicrobial Resistance Co-ordination Group (DARC) on the Government’s Actions to
address the Recommendations of the ACMSF report on Microbial Antibiotic Resistance
in Relation to Food Safety – ACM/730 March 2005.
18. Collignon P, Angulo FJ. Fluoroquinolone-resistant Escherichia coli: food for thought.
J Infect Dis 2006; 194: 8–10.
19. Powers JH. Antimicrobial drug development – the past, the present, and the future. Clin
Microbiol Infect 2004; 10(suppl 4): 23–31.
20. World Health Organization. Animal to human transplantation – future potential, present
risk. Press release. Geneva: WHO, 2 May 2005
21. Muir DA, Griffin GE. Infection Risks in Xenotransplantation. London: Department of
Health, 2001. Available at: http://www.doh.gov.uk/pub/docs/doh/76035_doh_infection_
risks.pdf.
Appendix 1
Web resources
Without access to the literature resources available through the internet, it
is unlikely that this book would ever have been written. The world-wide
web offers the resources of a comprehensive library, with access to a wide
range of peer-reviewed scientific papers, at the touch of a keyboard or the
click of a mouse.
It is not just technical texts that are available. Many government departments, both at home and abroad, have their own websites, where information
on legislation, statistics and breaking news can be found.
The uniform resource locators (URLs) listed below represent a brief selection of those sites that were used in the research for this publication. The
addresses offer the opportunity for students to locate additional information
or research topics in depth.
Some of the sites listed require visitors to register before they are able to
use all of the facilities. At the time of writing none requires any fee for access.
An attempt has been made to arrange the sites in a semblance of order;
however, the list is not exclusive or necessarily comprehensive, as new sites
appear daily. These sites offer a jumping-off point for further investigation.
European
Council of Europe
European Centre for Disease
Control and Prevention
European Food Safety Authority
(EFSA)
Institut Pasteur
MedVetNet
http://www.coe.int
http://www.ecdc.europa.eu
http://www.efsa.europa.eu
http://www.pasteur.fr
http://www.medvetnet
Web resources | 291
International
Arabian Horse Association
Emedicine
Food and Agriculture Organization
(FAO) of the United Nations
International Association for
Paratuberculosis
Merck Manual
Office International des Epizooties
(OIE)
ProMED reports
Eurosurveillance
World Arabian Horse Association
World Health Organization (WHO)
http://arabianhorses.org
http://www.emedicine.com
http://www.fao.org
http://www.paratuberculosis.org
http://www.merckvetmanual.com
http://www.oie.int
http://www.promedmail.org
http://www.eurosurveillance.org
http://www.waho.org
http://www.who.int
The UK
Animal Health Distribution
Association (AHDA)
Animal Medicines Training
Regulatory Association (AMTRA)
Association of British Pharmaceutical
Industry (ABPI)
British Association for Pure Bred
Spanish Horses
British Broadcasting Corporation
(BBC) news
British Equine Veterinary
Association (BEVA)
British Horse Society
British Medical Association (BMA)
British Medical Journal (BMJ)
British Small Animal Veterinary
Association (BSAVA)
British Veterinary Association (BVA)
British Veterinary Poultry
Association (BVPA)
Central Scientific Laboratory (CSL)
Chartered Institute for
Environmental Health (CIEH)
CJD Surveillance Unit
http://www.ahda.org.uk
http://www.amtra.org.uk
http://www.abpi.org.uk
http://bapsh.co.uk
http://news.bbc.co.uk
http://www.beva.org.uk
htttp://bhs.org.uk
http://www.bma.org.uk
http://www.bmj.com
http://www.bsava.com
http://www.bva.co.uk
http://www.bvpa.freeserve.co.uk
http://www.csl.gov.uk
http://www.cieh.org.uk
http://www.cjd.ed.ac.uk
292 | Zoonoses
Department of Agriculture and Rural
Development (Northern Ireland)
(DARDNI)
Department for Environment, Food
and Rural Affairs (DEFRA – formerly
MAFF)
Department of Health (DH)
Department of Health, Social
Services and Public Safety
(Northern Ireland)
Department for Transport (DfT)
Department of Trade and Industry
(DTI)
Farmers’ Weekly
Food and Drink Federation
Food Standards Agency (FSA)
Foreign and Commonwealth Office
(FCO)
Health Protection Agency (HPA)
Health Protection Agency
Communicable Disease Surveillance
Centre (Northern Ireland)
Health Protection Scotland (HPS)
Health and Safety Executive (HSE)
Institute for Animal Health (IAH)
Institute of Food Science and
Technology (IFST)
The Lancet
Meat and Livestock Commission
(MLC)
Medicines and Healthcare products
Regulatory Agency (MHRA)
Milk Development Council
National Farmers’ Union (NFU)
National Institute for Health and
Clinical Excellence (NICE)
National Office of Animal Health
(NOAH)
National Pig Association (NPA)
National Public Health Service for
Wales
National Sheep Association (NSA)
http://www.dardni.gov.uk
http://defra.gov.uk
http://www.doh.gov.uk
http://www.dhsspsni.gov.uk
http://www.dft.gov.uk
http://www.dti.gov.uk
http://www.fwi.co.uk
http://www.fdf.org.uk
http://www.food.gov.uk
http://www.fco.gov.uk
http://www.hpa.org.uk
http://www.cdscni.org.uk
http://www.hps.scot.nhs.uk
http://www.hse.gov.uk
http://www.iah.bbrsc.ac.uk
http://www.ifst.org
http://www.thelancet.com
http://www.mlc.org.uk
http://www.mhra.gov.uk
http://www.mdc.org.uk
http://nfuonline.com
http://www.nice.org.uk
http://www.noah.co.uk
http://www.npa-uk.net
http://www.nphs.wales.nhs.uk
http://www.nationalsheep.org.uk
Web resources | 293
North West Zoonoses Group
The People’s Dispensary for Sick
Animals (PDSA)
Pet Food Manufacturers’
Association (PFMA)
Pet Health Council (PHC)
Royal College of Physicians
Royal College of Veterinary
Surgeons (RCVS)
Royal Pharmaceutical Society of
Great Britain (RPSGB)
Royal Society for the Prevention
of Cruelty to Animals (RSPCA)
Scottish Executive Rural Directorate
Scottish Environment Protection
Agency (SEPA)
Scottish Farmers’ Weekly
Society for Companion Animal
Studies
Society of Practising Veterinary
Surgeons (SPVS)
Veterinary Laboratory Agency (VLA)
Veterinary Medicine Directorate
(VMD)
Veterinary Products Committee
Welsh Assembly Government
http://www.northwest-zoonoses.
info
http://www.pdsa.org.uk
http://www.pfma.org.uk
http://www.pethealthcouncil.co.uk
http://www.rcplondon.ac.uk
http://www.rcvs.org.uk
http://www.rpsgb.org.uk
http://www.rspca.org.uk
http://www.scotland.gov.uk
http://www.sepa.org.uk
http://www.nfus.org.uk
http://www.scas.org.uk
http://www.spvs.org.uk
http://www.defra.gov.uk/corporate/
vla
http://www.vmd.gov.uk
http://www.vpc.gov.uk
http://www.wales.gov.uk
The USA
American Veterinary Medical
Association (AVMA)
American Association of Wildlife
Veterinarians
American Horse Council Foundation
(AHCF)
American Quarter Horse Association
Animal and Plant Health Inspection
Service
Centers for Disease Control and
Prevention (CDC); includes National
Institute for Occupational Safety and
http://avma.org
http://www.aawv.net
http://www.horsecouncil.org
http://www.aqha.com
http:/www.aphis.usda.gov
http://www.cdc.gov
294 | Zoonoses
Health (NIOSH), Emerging Infectious
Diseases (EID) and Morbidity and
Mortality Weekly Report (MMWR)
Center for Food Safety and Applied
Nutrition (CFSAN)
Department of Agriculture (USDA)
Department of Health and Human
Services
Food and Drugs Administration
(FDA)
Food Safety and Inspection Service
(FSIS) – part of USDA
Medscape
Nature
New England Journal of Medicine
Pan American Health Organisation
Pets as Therapy (PAT)
Pets are Wonderful Support (PAWS)
Pubmed (National Library of
Medicine and National Institutes of
Health)
Science
Scientific American
Therapet
Wildlife Disease Association
http://vm.cfsan.fda.gov
http://www.usda.gov
http://www.hhs.gov
http://www.fda.gov
http://www.fsis.usda.gov
http://www.medscape.com
http://www.nature.com
http://www.nejm.com
http://www.paho.org
http://www.petastherapy.org
http://www.pawssf.org
http://www.pubmed.gov
http://www.sciencemag.org
http://www.sciam.com
http://www.therapet.com
http://www.wildlifedisease.org
Canada
Canadian Association of Zoo and
http://www.cazwv.org
Wildlife Veterinarians Health Canada
Appendix 2
Useful addresses
BCM Specials Manufacturing
D10 First 114, Nottingham NG20 2PR, UK
Tel: ⫹44 (0)800 952 1010
Bio Products Laboratory (BPL)
Dagger Lane, Elstree, Herts WD6 3BX, UK
Tel: ⫹44 (0)20 8905 1818
Centers for Disease Control and Prevention
1600 Clifton Road, Atlanta, Georgia 30333, USA
Tel: ⫹1 (0)888 232 6348
Website: http://www.cdc.gov
The Hospital for Tropical Diseases
Mortimer Market, London WC1E 6AU, UK
Tel: ⫹44 (0)845 155 5000 or ⫹44 (0)207 7387 4411
Website: http://www.thehtd.org
IDIS Ltd
IDIS House, Churchfield Road, Weybridge, Surrey KT13 8DB, UK
Tel: ⫹44 (0)1932 824 100
Website: http://www.idispharma.com
US contact tel: ⫹1 (0)651 503 7327
Scottish National Blood Transfusion Service (SNBTS)
Protein Fractionation Centre, Ellen’s Glen Road, Edinburgh EH17 7QT, UK
Tel: ⫹44 (0)131 536 5700
Tommy’s, the baby charity
Nicholas House, 3 Laurence Pountney Hill, London EC4R 0BB, UK
Tel: ⫹44 (0)870 777 30 60
Email: info@tommys.org
296 | Zoonoses
Creutzfeldt–Jakob disease and variant Creutzfeldt–Jakob
disease
The National CJD Surveillance Unit
Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
Tel: ⫹44 (0)131 537 3073
Fax: ⫹44 (0)131 343 1404
CJD Resource Centre
National Institute for Biological Standards and Control, Blanche Lane,
South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK
Tel: ⫹44 (0)1707 641 000
Fax: ⫹44 (0)1707 641 050
CJD Support Network
PO Box 346, Market, Drayton, Salop TF9 4WN, UK
Tel: ⫹44 (0)1630 673993
Helpline: ⫹44 (0)1630 673973
National Prion Disease Pathology Surveillance Center (NPDPSC)
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road,
Room 418, Cleveland, Ohio 44106, USA
Tel: ⫹1 (0)216 368 0587
Index
abattoir fever see Q fever
acepromazine, 151
aciclovir, 64
acrodermatitis chronica atrophicans, 249
African haemorrhagic fever see Ebola
agricultural livestock, 61–107
agricultural practices, 15, 16, 260
use of antibiotics, 15–16, 277, 279–80
agricultural workers, 268, 269
albendazole, 39, 42, 85–6, 100, 107
alphaviruses, 209–11
amantadine, 69, 72, 235
amnesic shellfish poisoning, 112
amoxicillin, 165, 166, 168, 171, 250, 279
ampicillin, 119, 123, 166, 279
Ancylostoma spp., 40, 41
ancylostomiasis, 40–1, 42
Andes virus, 216–17
animal growth promoters, 277, 279–80
animal handlers, 267–8, 269, 274
antacids, 119
anthrax, 7, 12, 16, 160, 161, 162–72, 281,
283, 285
cutaneous, 12, 162, 163, 164–5, 167
deliberate release/biological warfare
agent potential, 163, 167, 170–2,
202, 203, 204
US mail case (Amerithrax), 165, 171–2
in drum makers, 161, 162, 169–70
inhalational/pulmonary, 12, 163, 164,
165, 166–7
intestinal, 164, 165
meningitis, 165, 166
prophylaxis, 167–8
treatment, 165–7
antibiotic therapy, 275–6
antimicrobial resistance, 15–16, 275,
277–80
Aravan virus, 196
arboviruses, 209, 244
arenaviruses, 211–14
armadillos, 17, 58–9
arthropod vectors, 12–13, 209
ascariasis, 98–100
Ascaris spp., 98
Australia Group, 202–3
Australian bat lyssavirus, 197
avian chlamydiosis see psittacosis
avian influenza H5N1, 27, 63, 65–75, 161
current outbreak, 67, 70–72
avian paramyxovirus type 1, 63
avoparacin resistance, 279
azithromycin, 31, 33, 36, 72, 250
bacillary angiomatosis, 36
Bacillus anthracis, 7, 162
Balkan influenza see Q fever
Bartonella henselae, 12, 35, 36
Bartonella quintana, 35
bat-borne viruses, 220
Australian bat lyssavirus, 197
coronaviruses, 220
European bat lyssavirus (bat rabies),
197, 200
298 | Index
fruit bat paramyxoviruses, 222, 226
lyssavirus rabies-like disease, 196–7
rabies, 189, 190, 191, 193, 197, 198,
240–1
Baylisascaris procyonis, 245
Bayou virus, 216
BCG vaccine, 91
Bermejo virus, 217
Biological and Toxic Weapons Convention
(BTWC), 202
biological warfare/bioterrorism agents, 162,
202–6, 252
infection of wildlife, 261–2
public health issues (forward
planning), 205–6
see also anthrax
birds, 238, 240
agricultural livestock, 62–74
companion animals, 27–33
migratory, 5, 6, 13, 70, 161, 227, 240
Black Creek Canal virus, 216
Black Death, 161, 176, 183
Bolivian haemorrhagic fever (black typhus),
213
Borna disease, 233–5
Borrelia spp., 244, 246, 247, 248, 249, 250
botulinum antitoxin, 129, 130
botulinum toxin, 127, 128, 129, 130, 131
deliberate release/bioterrorism, 203,
204
botulism, 127–31, 285
food-borne, 128–30, 285
infant, 128, 130–1, 285
inhalation, 128
wound, 128, 131, 286
bovine spongiform encephalopathy, 10–11,
16, 18, 20, 22, 23, 75, 110, 143, 144–5
government-led enquiry, 152
prevention, 153–6
variant Creutzfeldt–Jakob disease
linkage, 147–8
Brazilian haemorrhagic fever, 214
brevitoxins, 112
Brucella abortus, 76, 126
Brucella melitensis, 75, 76, 126
Brucella spp., 76, 240, 285
Brucella suis, 76, 243
brucellosis, 16, 74, 75–8, 281, 286
deliberate release/bioterrorism, 204,
205
bunyaviruses, 214–15, 218–19
Burkholderia mallei, 9, 54
bushmeat, 241–2
Cache Valley virus, 218
Campylobacter coli, 133, 279
Campylobacter jejuni, 133, 279
Campylobacter spp., 133–4
antimicrobial resistance, 279
canola fever (Leptospira canicola), 56
Cat Scratch Disease, 12, 34, 35–6
cats, 33–4, 40, 41, 49, 51, 52–3, 238
hygiene measures, 42, 48, 52
Pet Travel Scheme (PETS), 201
cattle, 75–91
tracing system, 155
causative pathogens, 1–4
Centers for Disease Control and Prevention
(CDC), 14
cephalosporins, 54, 72, 101, 166, 185, 250
resistance, 123, 279
Cercopithecine herpesvirus 1 (herpes B
virus), 257
cetacean brucellosis, 76, 78
charbon see anthrax
Chikungunya fever, 209–10
children, 18, 268, 269
Chlamydia, 4, 19
chlamydiosis, 92–4
Chlamydophila abortus, 92, 93
Chlamydophila felis, 92, 94
Chlamydophila pecorum, 92
Chlamydophila psittaci, 8, 9, 31, 32, 238,
281
Chlamydophila spp., 92 , 240, 244
chloramphenicol, 54, 64, 83, 134, 166, 185,
186, 255
resistance, 123, 279
chloroquine, 83, 210
chlortetracycline, 94
Choclo virus, 217
cholera, 111
Index | 299
chronic wasting disease, 144, 158, 241
cidofovir, 258
ciguatera, 111–12
cimetidine, 119
ciprofloxacin, 54, 123, 165, 166, 167, 168,
171, 185, 186, 187, 255
prophylactic use, 167, 168, 186, 187
resistance, 279
circuses, 243–4
clarithromycin, 31
clindamycin, 52, 166, 167
Clostridium botulinum, 126, 127–31
Clostridium difficile, 280
Clostridium perfringens, 8, 126–7, 240
toxin, 126, 127, 205
clotrimazole, 44
companion animals, 16–17, 26–59, 287
benefits of ownership, 27, 266
exotics, 17, 244
contagious pustular dermatitis (orf), 96–7
Control of Substances Hazardous to Health
Regulations (1999), 282
coronaviruses, 219–20
co-trimoxazole, 119, 186
Coxiella burnetti, 10, 81, 83, 244
creeping eruption see cutaneous larva
migrans
Creutzfeldt–Jakob disease, 146
see also variant Creutzfeldt–Jakob
disease
Crimean–Congo haemorrhagic fever, 203,
214–15
critical control points, food
production/handling, 136
Crohn’s disease, 3, 30
cryptococcosis, 27, 28–9
Cryptococcus neoformans, 27, 281
cryptosporidiosis, 19, 132–3, 286
Cryptosporidium parvum, 132
Cryptosporidium spp., 132, 244, 276
cutaneous larva migrans (creeping
eruption), 40, 41–2
cysticercosis, 85, 86, 87
dairy-worker fever (Leptospira hardjo), 56
deer, 240, 243, 246–56
deer-fly fever see tularaemia
deliberate release, 202
see also biological warfare/bioterrorism
agents
Dermacentor reticulatus, 253
diarrhoeic shellfish poisoning, 112
dinoflagellate toxins, 111, 112, 113
direct contact transmission, 11–12
Dobrava virus, 215
dogs, 34, 37, 38, 39, 40, 41, 42, 188, 190,
238
hygiene measures, 42, 48
Pet Travel Scheme (PETS), 201
domoic acid, 112
doxycycline, 33, 54, 58, 77, 83, 165, 166,
167, 168, 171, 185, 186, 187, 250, 255,
256
prophylatic use, 168, 186, 187
Duvenhage virus, 196–7
Eastern equine encephalomyelitis, 210–11,
285
EBLV-1/2 (European bat lyssavirus), 197
Ebola, 2, 160, 172–6, 226, 240, 242, 284
deliberate release/bioterrorism
potential, 203
outbreak statistics, 174–5
echinococcosis, 36–40
Echinococcus granulosus, 36, 37
Echinococcus multilocularis, 36, 37, 40,
201, 239, 284
eggs, 62, 137
Salmonella contamination, 122, 124,
125
elderly people, 18, 74, 268, 269
emergent pathogens, 4–7
enzootic abortion, 92, 93
equine influenza, 65
erythema migrans, 249
erythromycin, 33, 36, 93, 103, 119, 246,
255
Escherichia coli, 22, 110, 113–17
antimicrobial resistance, 279
Escherichia coli O157:H7, 11, 16, 113–14,
205, 243
Pennington report, 117
300 | Index
toxin, 114, 115
Wishaw outbreak (Scotland), 11,
115–17
ethambutol, 90
European bat lyssavirus (bat rabies), 197,
200
exotic Newcastle disease (pseudo-fowl pest),
63–5
exotics, 17, 238–9, 244
escapes/releases, 243
false cowpox (pseudo-cowpox), 80–1
farcy see glanders
farm visits, 140, 243–4
fatal familial insomnia, 147
feline keratoconjunctivitis, 94
ferrets, Pet Travel Scheme (PETS), 201
filoviruses, 220–1
fish, food-borne zoonoses, 111
flaviviruses, 226–35
flea vectors, 12, 13, 18, 35, 239
plague, 176, 177, 179, 180, 181, 182,
188
flucloxacillin, 42
fluoroquinolones resistance, 123
flupirtine, 151
fomite spread, 8, 12
food poisoning, 8, 10, 110, 283
deliberate release/bioterrorism, 204,
205
food production, 20–1, 139–40
food safety, 110
general hygiene recommendations,
138–9
industrial issues, 20
public confidence, 22
Food Safety Inspection Service, 135, 138
food scares, 21, 22–3, 110, 122
Food Standards Agency (FSA), 11, 117,
135, 138
food sterilisation, 139
food-borne transmission, 8, 9–11, 14–15,
16, 110–40
prevention, 135–40
transmission pathways, 111
food-industry workers, 268
disease risk, 269
foot-and-mouth disease, 3, 21–2, 78–80,
140, 240, 242, 243, 244
fowl cholera (Pasteurella), 100–2
fowl plague, 65
foxes, 37, 40, 188, 190, 239, 240
Francis’ disease see tularaemia
Francisella endotoxin, 252
Francisella tularensis, 251, 252
subspecies, 253
fusidic acid, 64, 94
Gambierdiscus toxicus, 111
genetic susceptibility, 19–20
gentamicin, 54, 119, 134, 166, 167, 185,
186, 255
resistance, 279
Gerstmann–Strässler–Schenker syndrome,
147
gestational psittacosis (chlamydiosis), 92–4
Giardia lamblia, 94
giardiasis, 94–6, 286
glanders (farcy), 9, 53, 54–5, 205
Global Health Security Initiative, 203
griseofulvin, 44
Guanarito virus, 211
Guillain–Barré syndrome, 134–5, 229
HACCP process, 136
haemolytic–uraemic syndrome, 114–15, 286
haemorrhagic colitis, 114
haemorrhagic fever with renal syndrome
(HFRS), 215–16, 217
haemorrhagic jaundice (Leptospira
icterohaemorrhagiae), 56
hantavirus, 205, 215–17
hantavirus pulmonary syndrome, 215, 216,
217, 286
Haverhill fever (rat-bite fever), 245–6
hazard analysis, food production/handling,
136
health promotion/education, 274–5
Health and Safety at Work etc. Act (1974),
281
healthcare implications, 265–88
hedgehogs, 244
Index | 301
Hendra virus, 220, 221–2, 284
henipaviruses, 221–6
hepatitis A, 58
hepatitis B, 58
herpes B virus (Cercopithecine herpesvirus
1), 257
HIV/AIDS, 27, 28, 30, 34, 36, 104, 259–60,
270, 288
BCG vaccine contraindication, 91
bovine tuberculosis, 90
Campylobacter septicaemia, 134
cryptosporidiosis, 132
giardiasis, 95, 96
monkeypox, 258
Pasteurella infection, 101
salmonella septicaemia, 123
toxoplasmosis, 51
hookworm, 40–2
horses, 53–8
Human Animal Infections and Risk
Surveillance (HAIRS) group, 14
human diploid cell rabies vaccine (HDCV),
194
human rabies immunoglobulin, 193, 195
human T lymphotrophic virus (HTLV), 260
hunting, 241
hydatid disease (hydatidosis), 36–7, 38
hydatid sand, 38
hydrophobia see rabies
ibuprofen, 69
imipenem, 54, 166
immunocompromised individuals, 19, 268,
270
Cat Scratch Disease, 34, 35
cryptococcosis, 28, 29
cryptosporidiosis, 132
disease risk, 269
Escherichia coli O157:H7, 115
giardiasis, 95, 96
influenza vaccination, 74
listeriosis, 118, 120
lymphocytic choriomeningitis virus,
213
Mycobacterium avium complex, 30
psittacosis, 33
ringworm, 43
salmonellosis, 123
toxoplasmosis, 48, 51
importance of zoonoses, 14–18, 265–6
infective dose, 7–8
influenza, 65–75
antigenic drift, 65
haemagglutinin (H), 65
neuraminidase (N), 65
vaccines, 67, 73–4
influenza A, 65, 66, 67, 69, 70, 74, 286
antigenic shift, 65
influenza B, 65, 69
influenza C, 65
influenza H1N1 subtype, 67–8
influenza H3N2 subtype, 67
influenza H5N1 subtype, 67, 68–74, 161,
240, 242
control protocols, 71, 75
current outbreak, 70–2
see also avian influenza H5N1
influenza H7N7 subtype, 67
Irkut virus, 196
isoniazid, 90
ivermectin, 42, 45, 48
Ixodes spp., 13, 247, 253
Japanese encephalitis, 231–2
Johne’s disease, 3
Junin virus, 212, 214
ketoconazole, 44
Khajard virus, 196
Kunjin virus, 226, 227
kuru, 147
Kyansur haemorrhagic virus, 233
La Cross virus, 218
Lagos bat virus, 196
Lassa fever, 212–13
deliberate release/bioterrorism, 204
legislation
UK, 20, 23, 280–5
US, 285–6
leprosy, 17, 58–9
Leptospira spp., 56, 57
302 | Index
leptospirosis, 10, 53, 56–8, 239, 281, 283
levamisole, 99
levofloxacin, 169, 185, 186
Listeria monocytogenes, 19, 118
listeriosis, 118–22, 286
loperamide, 123
Lyme disease, 4, 241, 244, 246, 247–51,
281, 286
transmission, 13, 248–9
lymphocytic choriomeningitis virus, 211,
213
lyssaviruses, 188, 196–7
Machupo virus, 213–14
malignant oedema see anthrax
malignant pustule see anthrax, cutaneous
Malta fever see brucellosis
mammalian-derived meat and bone meal
(MMBM), 155
Management of Health and Safety at Work
Regulations (1992), 281–2
Marburg virus, 58, 203, 220–1, 240
Mayaro virus, 211
meat, 10–11, 16
bushmeat, 241–2
contamination reduction at harvesting,
137
food-borne zoonoses, 113–17
meat and bone meal (MBM), 144, 145
mebendazole, 39, 41, 48, 100, 107
medical practitioner referral, 266
Mediterranean fever see brucellosis
Menangle virus, 226
mepacrine, 95
meropenem, 166, 167
metronidazole, 95, 100
miconazole, 44
Microsporum canis, 43
Microsporum spp., 42
milk-borne diseases, 9–10, 126, 137
milkers’ nodule/wart (pseudo-cowpox),
80–1
Mobala virus, 214
Mokala virus, 196
monkeypox, 242, 244, 257–9
Monongahela virus, 216
mosquito vectors, 5, 6, 12, 13, 209, 210,
218, 219, 231
West Nile virus, 227, 228, 231
mycobacteria, 29, 58, 244
Mycobacterium avium complex, 3, 27,
29–31, 281
Mycobacterium bovis, 9–10, 29, 87, 88,
239, 243
Mycobacterium intracellulare see
Mycobacterium avium complex
Mycobacterium marinum, 29
Mycobacterium tuberculosis, 29, 87
Necator americanus, 40
necrotic enteritis (pigbel), 8, 127
neurotoxic shellfish poisoning, 112
New York virus, 216
Newcastle disease, 63–5
niclosamide, 86
Nipah virus, 205, 220, 222–5, 241
norfloxacin, 255
Notedres cati, 45
notifiable disease
UK, 282–5
USA, 285–6
occupational exposure, 19, 20–1, 39, 54,
56, 58, 268, 269
preventive measures, 274
ocular larva migrans, 47–8
ofloxacin, 186
O’Hara’s disease see tularaemia
okadaic acid, 112
Omsk haemorrhagic virus, 233
orf, 96–7
Oropouche virus, 218
oseltamivir, 67, 72
paracetamol, 69
paralytic shellfish poisoning, 112, 113
paramyxoviruses, 221–6
parapoxvirus, 96, 97
Pasteurella multocida, 100, 101, 240
Pasteurella spp., 100–2
penicillin, 54, 57, 101, 103, 119, 166, 185,
246, 250
Index | 303
Pennington report, 117, 135
pentosan polysulphate, 151
personnel loss, 20–1
pest control, 18, 260
pesticides, 45, 276–7
Pet Travel Scheme (PETS; pet passports),
188, 193, 199, 201, 246, 284
Pets as Therapy (PAT), 27, 267
pica, 10
pigbel (enteritis necroticans), 8, 127
pigs, 98–107
piperazine, 100
plague, 13, 17, 18, 160, 161, 176–88, 240,
244, 283, 286
animal reservoir/maintenance hosts,
181–2
biological warfare potential, 177, 203,
204
bubonic, 176, 182–3
historical pandemics, 176–7
international initiatives, 178–9
meningitis, 183, 186
pharyngeal, 183–4
pneumonic, 176, 177, 179, 180, 184,
185
prevention, 187–8
prophylaxis, 186–7
septicaemic, 183
transmission, 178, 182
treatment, 185–6
vaccination, 187
wild foci, 177–8, 180–1
poultry production, 62–3
Powassan virus, 233, 285
praziquantel, 39, 86
pregnant women, 9, 19, 268
chlamydiosis (gestational psittacosis),
93, 94
disease risk, 269
listeriosis, 118, 120, 121
lymphocytic choriomeningitis virus,
213
plague prophylaxis, 186, 187
toxoplasmosis, 48, 50, 51, 52
prevention, 266, 268, 270–2
strategies, 272–4
primates, 58
viruses, 256–60
prion disease, 10–11, 18, 19, 75, 143–58,
288
pseudo-cowpox, 80–1
psittacosis (ornithosis), 8, 9, 19, 27, 31–3,
205, 242, 268, 271, 281, 286
public impact of zoonoses, 21–4
Puumala virus, 215
pyrantel, 100
pyrazinamide, 90
pyrimethamine, 51, 52
Q fever, 10, 81–4, 126, 281, 286
deliberate release/bioterrorism
potential, 204, 205
quarantine, 161, 175, 188, 193, 199, 200,
201
Query fever see Q fever
quinolones resistance, 123, 279
rabbit fever see tularaemia
rabies, 12, 17, 160, 161, 188–201, 281,
283, 286
bat-mediated, 197, 198, 200, 240–1
Europe, 188–9, 198
North America, 189–90, 198
organ transplant patients, 199
prevention, 199–201
prophylaxis, 193–4
treatment, 192–3
UK, 188, 198
vaccination, 200
animals, 189, 190, 193,
199–200
post-exposure prophylaxis, 188,
189, 190, 192–3, 194, 197, 199,
200
pre-exposure, 194, 195
regimens, 194–6
raccoon dog (Nycterentes procyonides),
rabies transmission, 188, 243
raccoon roundworm, 245
raccoons, rabies transmission, 190
rat-bite fever, 245–6
re-emerging zoonoses, 6
304 | Index
Reporting of Injuries, Diseases and
Dangerous Occurrences Regulations
(RIDDOR) (1995), 281
reptiles, 58, 125
ribavirin, 193, 217, 235
Rickettsia prowazekii, 246
rifabutin, 31
rifampicin, 76, 77, 90, 166, 167
rifamycin, 31, 44
Rift valley fever, 219
ringworm, 12, 42–4, 244
risk assessment, 268, 270
risk groups, 18–19, 268, 269
rodent vectors, 239, 240
arenaviruses, 211, 213, 214
hantaviruses, 215, 217
plague, 176, 177, 178, 179, 180, 181,
182, 188
roundworm, large, 98–100
Saaremaa virus, 215
Sabia virus, 214
St Louis encephalitis, 232, 285
Salmonella dublin, 240
Salmonella enteritidis, 122, 124, 125
Salmonella kingabwa, 125
Salmonella newport, 124
Salmonella paratyphi var. Java, 122, 125
Salmonella pomona, 125
Salmonella spp., 17, 58, 204, 205, 240,
244, 279, 285, 286, 287
Salmonella typhi, 58
Salmonella typhimurium, 122, 124, 125,
240, 279
Salmonella typhimurium DT104, 123, 279
R serotype, 15, 123, 279
Salmonella virchow, 122, 279
salmonellosis, 122–6
Sarcoptes scabiei, 44
saxitoxin, 112
scabies, 44–5
scrapie, 19, 143, 144, 145–6
seals, brucellosis, 76, 78
severe acute respiratory syndrome (SARS),
219–20, 242, 286
sheep, 37, 38, 49, 50, 53, 91–7
shellfish poisoning, 111, 112–13
Shigella spp., 204, 205
shipping fever (Pasteurella), 100–2
simian foamy virus, 259
simian immunodeficiency virus, 259–60
Sin Nombre virus, 216
Soduku (rat-bite fever), 245–6
specified bovine material (SBM), 145
specified risk material, 156, 157
spiramycin, 52
Spirillium minus, 245
splenic fever see anthrax
Streptococcus suis, 102–4, 281
streptomycin, 54, 77, 91, 185, 186, 255
resistance, 123, 279
Stroptobacillus moniliformis, 245
sulfadiazine, 54
sulfamethoxasole, 51
sulphonamides resistance, 123, 279
supportive therapy, 276
surveillance, 7, 14
antimicrobial resistance, 278
influenza, 71, 72–3
notifiable disease legislation, 283, 285
Salmonella spp., 123–4
variant Creutzfeldt–Jakob disease, 150,
157–8
West Nile virus, 229, 231
wildlife/exotic diseases, 261–2
swine influenza, 65
current outbreak (Mexican swine flu),
67–8
Taenia saginata (Cysticercus bovis), 84
Taenia solium, 84
tapeworm (beef/pork tapeworm), 84–7
terbinafine, 44
tetanus, 16, 53, 284, 286
tetracyclines, 33, 54, 57, 83, 93, 101, 134,
185, 186, 250, 255
resistance, 123, 279
thrombocytopenic purpura, 115
tiabendazole, 42, 48, 107
ticarcillin, 54
tick vectors, 13, 201, 209, 214, 239, 244,
252, 253
Index | 305
tick-borne borreliosis see Lyme disease
tinidazole, 95
Tioman virus, 226
Toxocara canis, 45, 239
Toxocara cati, 45
Toxocara felis, 19
toxocariasis, 34, 45–8, 270
Toxoplasma gondi, 3, 10, 48, 49, 244
Toxoplasma spp., 4, 10, 242
toxoplasmosis, 19, 34, 48–53, 270
congenital infection, 50
transgenic animals, 287–8
transmissible mink encephalopathy, 144
transmissible spongiform encephalopathies,
143
animal diseases, 144–6
human disease, 146–58
transmission routes, 7–13, 111
preventive measures, 273
transplant patients, 199, 213
trench fever, 35
Trichinella britovi, 104, 105
Trichinella nativa, 104
Trichinella pseudospiralis, 104, 105, 107
Trichinella spiralis, 104, 105, 284
Trichinella spp., 239, 243
trichinosis (trichinellosis), 104–7, 286
Trichophyton spp., 42
Trichophyton verrucosum, 43
trimethoprim, 123, 279
resistance, 123
tuberculosis, 7, 19, 29, 30, 271, 276, 281,
284, 286
bovine, 9–10, 16, 75, 87–91, 126
surveillance and control, 88–9, 91
tularaemia, 241, 244, 246, 251–6, 286
deliberate release/bioterrorism
potential, 204, 252
glandular, 254
oculoglandular, 254
oropharyngeal, 255
pneumonic, 255
typhoidal, 255
ulceroglandular, 254
vaccination, 252, 255
typhus fever, 246, 284
undulant fever see brucellosis
vancomycin, 166, 167
resistance, 279
variant Creutzfeldt–Jakob disease, 10–11,
16, 18, 22, 23, 143, 144, 147–51, 156,
157–8, 287
associated genetic modification, 148–9
epidemiological clusters, 152–3
prevention, 153–4
vectors, 5, 12–13
Venezuelan equine encephalomyelitis, 210
viral classification, 209
viral zoonotic diseases, 209–35
virginamycin resistance, 279
visceral larva migrans, 47
water-borne disease, 10, 17
Weil’s disease see leptospirosis
West Caucasian bat virus, 196
West Nile virus, 6, 7, 13, 63, 161, 226–31,
240, 285
outbreaks, 227–9
transmission, 227, 230
Western equine encephalomyelitis, 210, 285
wild animals, 238, 239–40
bushmeat, 241–2
live animal trade, 241, 242
transmission pathways, 240–4
wildlife diseases, 244
prevention of spread, 260–1
surveillance, 261–2
WIRED (wildlife-related emerging diseases),
240
woolsorter’s disease see anthrax,
inhalational/pulmonary
xenotransplantation, 287–8
Yersinia enterocolitica, 131–2
Yersinia pestis, 7, 13, 177, 185
antimicrobial resistance, 180, 279
yessotoxin, 112
Yuli virus, 196
zanamivir, 67, 69, 72
zoological parks, 243–4