971

W H O Te c h n i c a l R e p o r t S e r i e s

971

Research Priorities for Zoonoses and Marginalized Infections

Research Priorities for Zoonoses and Marginalized Infections

This report provides a review and analysis of the research

landscape for zoonoses and marginalized infections which
affect poor populations, and a list of research priorities to
support disease control. The work is the output of the Disease
Reference Group on Zoonoses and Marginalized Infectious
Diseases of Poverty (DRG6), which is part of an independent
think tank of international experts, established and funded by
the Special Programme for Research and Training in Tropical
Research Priorities
Diseases (TDR), to identify key research priorities through
review of research evidence and input from stakeholder for Zoonoses and
Marginalized Infections
consultations.
The report covers a diverse range of diseases, including
zoonotic helminth, protozoan, viral and bacterial infections
considered to be neglected and associated with poverty.
Disease-specific research issues are elaborated under individual
disease sections and many common priorities are identified
among the diseases such as the need for new and/or improved Technical report of the TDR Disease Reference Group on Zoonoses
drugs and regimens, diagnostics and, where appropriate, and Marginalized Infectious Diseases of Poverty
vaccines. The disease-specific priorities are described as micro
priorities compared with the macro level priorities which will
drive policy-making for: improved surveillance; interaction
between the health, livestock, agriculture, natural resources
and wildlife sectors in tackling zoonotic diseases; and true WHO Technical Report Series
assessment of the burden of zoonoses.
This is one of ten disease and thematic reference group reports
that have come out of the TDR Think Tank, all of which
have contributed to the development of the Global Report
for Research on Infectious Diseases of Poverty, available at:
www.who.int/tdr/capacity/global_report.
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 W H O Te c h n i c a l R e p o r t S e r i e s

Research Priorities
for Zoonoses and
Marginalized Infections
Technical report of the TDR Disease Reference Group on Zoonoses
and Marginalized Infectious Diseases of Poverty

This report contains the collective views of an international group of experts and
does not necessarily represent the decisions or the stated policy of the World Health Organization
WHO Library Cataloguing-in-Publication Data
Research priorities for zoonoses and marginalized infections.
(Technical report series ; no. 971)
1. Zoonoses. 2. Research. 3. Neglected diseases. 4. Poverty. 5. Developing countries.
I.World Health Organization. II.TDR Disease Reference Group on Zoonoses and Marginalized
Infectious Diseases of Poverty. III.Series.
ISBN 978 92 4 120971 7 (NLM classification: WC 950)
ISSN 0512-3054

© World Health Organization 2012

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Contents
WHO/TDR Disease Reference Group on Zoonoses and Marginalized
Infectious Diseases of Poverty (DRG 6) 2009–2010 v
Abbreviations vii
Executive summary ix
1. Introduction 1
1.1 Rationale and context 1
1.2 Zoonoses and the Millennium Development Goals 3
1.3 Challenges 4
1.4 Scope of the report 6
1.5 Group membership 7
1.6 Host country 7
1.7 Think tank members 7
2. Methodology and prioritization 9
2.1 Informal consultation 9
2.2 Selection of DRG members 9
2.3 First DRG meeting 10
2.4 Stakeholders' consultations 10
2.5 Second DRG meeting 11
2.6 Prioritization process 11
2.7 Transformation of DRG report to TRS 12
3. Burden of disease 13
3.1 Estimating the burden of parasitic zoonoses: approaches and challenges 13
3.1.1 Measures of mortality, morbidity and health-associated life years 15
3.1.2 Economic (monetary) burden of zoonotic disease 18
3.1.3 Case-studies 19
3.2 Disease-specific issues and burden 22
3.2.1 Helminths 22
3.2.2 Protozoan infections 31
3.2.3 Bacterial infections 34
3.2.4 Viral infections 44
4. Intervention-oriented research issues 47
4.1 Community-led or community-directed interventions 47
4.1.1 Community-led Total Sanitation 48
4.1.2 CLTS and zoonotic diseases 49
4.2 The human/animal interface: “One Health” as a concept 53
4.3 Chemotherapy and immunization 58
4.3.1 Mass chemotherapy (mass-targeted, humans-animals) 58
4.3.2 Immunization against rabies 59
4.4 Vector and intermediate host control 60
4.5 Vaccination as a control option for zoonotic diseases 61
4.5.1 Animal-targeted immunization 61
4.5.2 Echinococcus granulosus 63
iii
 4.5.3 Vaccine against Taenia solium 64
4.5.4 Foodborne trematode vaccines 64
4.6 Human-targeted vaccines 64
4.6.1 Enteric infections 64
4.7 Animal reservoirs 66
4.8 Health education and health literacy 67
4.9 Development of human resources 71
4.10 Integrated approaches 71
4.11 New products and strategies 72
4.12 Health systems and interactions with other sectors: intersectoral dialogue 74
4.13 Cost−effectiveness analysis 74
5. Disease-specific and intervention-specific priorities for research 77
5.1 Disease-specific research priorities 77
5.1.1 Cysticercosis and taeniasis 77
5.1.2 Echinococcosis 78
5.1.3 Asian schistosomiasis 78
5.1.4 Foodborne trematodiases 79
5.1.5 Toxoplasmosis 80
5.1.6 Cryptosporidiosis 80
5.1.7 Rabies 81
5.1.8 Bacterial zoonoses 82
5.1.9 Enteric infections 84
5.2 Intervention-specific research priorities 85
5.2.1 Community-led Total Sanitation 85
5.2.2 Animal/human interface 86
5.2.3 Epidemiological studies 86
5.2.4 Health education and promotion 87
6. Cross-group issues and priorities 89
6.1 Interactions with Disease and Thematic Reference Groups 89
6.2 Priorities for policy-makers 90
7. Conclusions 91
Acknowledgements 93
References 95
Appendices 109

iv
WHO/TDR Disease Reference Group on Zoonoses
and Marginalized Infectious Diseases of Poverty
(DRG 6) 2009–2010
Reference Group Members
Dr H. Carabin, University of Oklahoma Health Sciences Centre, Oklahoma, OK, USA
Dr S. Cleaveland, Reader, Division of Ecology and Evolutionary Biology, University of
Glasgow, Glasgow, Scotland
Dr A. Garba, Director, Réseau International Schistosomose, Environnement, Aménagement
et Lutte (Riseal), Niamey, Niger
Dr E. Gotuzzo, Director, Instituto de Medicina Tropical "Alexander von Homboldt",
Universidad Peruana Cayetano Heredia, Lima, Peru
Dr Z. Hallaj, Senior Consultant on communicable diseases, WHO/EMRO, Cairo, Egypt
(co‑Chair)
Dr K. Kar, Chairman, CLTS Foundation, Calcutta, India
Professor G.T. Keusch, Professor of International Health and of Medicine, Boston University,
Boston, USA
Professor D.H. Molyneux, Senior Professorial Fellow, Liverpool School of Tropical Medicine,
Liverpool, England (Chair)
Professor D.P. McManus, National Health and Medical Research Council of Australia Senior
Principal Research Fellow, Head of Molecular Parasitology Laboratory, Queensland
Institute of Medical Research, Brisbane, Australia
Dr H. Ngowi, Department of Veterinary Medicine and Public Health, Sokoine University
of Agriculture, Morogoro, United Republic of Tanzania
Dr P. Ramos-Jimenez, Philippine NGO Council on Population Health and Welfare, Pasay
City, Philippines
Dr A. Sanchez, Associate Professor, Department of Community Health Sciences, Brock
University, St. Catharines, Ontario, Canada

Career Development Fellow

Dr H.M. Abushama, Assistant Professor in Immunogenetics, Department of Zoology,
Faculty of Science, University of Khartoum, Khartoum, Sudan

Secretariat
Dr A. Bassili, TB Surveillance Officer and Focal Point, Tropical Disease Research,
Communicable Disease Control, WHO Regional Office for the Eastern Mediterranean,
Cairo, Egypt
v
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Dr C.L. Chaignat, Medical Officer, Water, Sanitation and Hygiene, Protection of the
Human Environment, WHO, Geneva, Switzerland
Dr D. Kioy, Scientist, Special Programme for Research and Training in Tropical Diseases,
WHO, Geneva, Switzerland (Manager)
Dr F.X. Meslin, Coordinator, Neglected Zoonotic Diseases, Neglected Tropical Diseases,
WHO/HQ, Geneva, Switzerland
Dr A.L. Willingham, Scientist, Special Programme for Research and Training in Tropical
Diseases, WHO, Geneva, Switzerland
WHO Technical Report Series, No. 971, 2012

vi
Abbreviations
AE alveolar echinococcosis
BNP Blue Nile Health Project
CE cystic echinococcosis
CLTS Community-led Total Sanitation
CNS Central Nervous System
CT Computerized axial Tomography
DALY disability-adjusted life year
DRG Disease Reference Group
EMRO WHO Regional Office for the Eastern Mediterranean
EPEC enteropathogenic E.coli
ETEC enterotoxigenic E.coli
FAO Food and Agriculture Organization of the United Nations
FBT foodborne trematodiasis
GAVI Global Alliance for Vaccines and Immunization
GBD global burden of disease
GFATM Global Fund to Fight AIDS, Tuberculosis and Malaria
GMP Good Manufacturing Practice
HAART highly active antiretroviral therapy
HALY health-adjusted life years
IMCI Integrated Management of Childhood Illness
MDA mass drug administration
MDGs Millennium Development Goals
MRI Magnetic Resonance Imaging
NCC neurocysticercosis
NTD neglected tropical disease
NZD neglected zoonotic disease
ODA Official Development Assistance
ODF open defecation free
vii
OIE Office International des Epizooties (World Organization for Animal
Health)
OVD oral vaccination of dogs
PCR Polymerase chain reaction
PEP post-exposure prophylaxis
QALY quality-adjusted life years
TDPS Target-driven Partial Sanitation
TRG Thematic Reference Group
USDA Unites States Department of Agriculture

Details on The Global Report for Research on Infectious Disease of Poverty can be found at http://www.who.
int/tdr/stewardship/global_report/en/index.html
Executive Summary
The Disease Reference Group on Zoonoses and Marginalized Infectious Diseases
of Poverty (DRG6) was part of an independent think tank of international
experts, established by the Special Programme for Research and Training in
Tropical Diseases (TDR) to identify key research priorities through the review of
research evidence and input from stakeholder consultations.

Context
There has been limited recognition by the global health community that
zoonoses and marginalized infectious diseases are major causes of poverty and
thus constraints on development. A Disease Reference Group (DRG) was created
to review the zoonotic diseases and these marginalized infectious diseases and
to provide an analysis of research priorities. The report emphasizes that the
diseases discussed are diverse and cover the spectrum of infectious agents, from
viruses to worms. The infections display a variety of transmission patterns,
have a global geographical distribution throughout the tropics and subtropics,
and exist in different ecological environments and in different health system
settings. However, this complexity is compounded, compared with non-zoonotic
infections, by the need to involve other sectors (for example livestock services,
education, environment, water and sanitation, and wildlife) when decisions
on policy for control, financing for control across sectors, defining research
priorities and implementing research findings are made.
The Group also highlighted cross-disease and thematic issues following
interaction between members, stakeholders and the WHO Secretariat. A series
of matrices was developed to evaluate the priorities from the perspective of
cross-cutting themes for research. This approach was designed to recognize
the complexity of the priority-setting task and to highlight the challenges of
implementation of research findings where zoonotic diseases are not accorded
high priority as they primarily affect marginalized populations with limited
access to government services. The Group also recognized that two levels of
prioritization were necessary. Firstly, disease-specific and focused priorities
were addressed, driven by the appropriate biomedical or social paradigm. These
recommendations are extensive and relevant to disease-focused scientific
constituencies. Secondly, broader priorities emerged that are relevant to the
different diseases considered in this report and infectious diseases in general.

Disease-specific priorities
Biomedical priorities were identified for specific diseases and drew on the expert
opinions of the DRG and stakeholder discussions, as well as existing published
ix
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

material from WHO and other authoritative groups, including disease-specific

partnerships. These priorities were grouped into the needs for new drugs,
diagnostics, and human and animal vaccines.

Macro priorities for policy-makers

Common priorities emerged irrespective of the disease entity or infectious
agent being addressed. Stakeholders highlighted significant issues that require
emphasis. For example, in many countries a large proportion of the population
is dependent on livestock for its social and economic well-being, and in these
countries a high proportion of the Gross Domestic Product is derived from
livestock production. Therefore, the report identified what it termed macro
priorities, covering all the diseases included in the analysis. These are:
■■ expand the surveillance for zoonotic diseases in humans and animals;
■■ re-attribute the burden of morbidity and mortality attributed to
diseases and conditions (cancers, neurological conditions, injuries)
to the neglected parasitic/zoonotic diseases;
■■ re-evaluate the societal burden of disease for zoonoses;
■■ expand systems research to determine how best the different sectors
can interact;
■■ evaluate the effectiveness of community-led approaches, including
the Community-led Total Sanitation approach, in the control of
zoonotic infectious diseases;
■■ integrate animal and human disease expertise with social science
perspectives;
■■ conduct more extensive studies on the costs of intervention, the
cost−benefits and cost−effectiveness;
■■ scale up research training to increase human resources in the area
WHO Technical Report Series, No. 971, 2012

of public health, including veterinary and livestock services, for

addressing zoonoses;
■■ create opportunities to evaluate and modify control strategies as
experience is gained in implementation;
■■ combine interventions allied to improved water and sanitation, and
health education and promotion, and deploy them for the human
and animal diseases in parallel;
■■ expand research on the use of new communication technologies such
as smart phones to enhance surveillance, reporting and evaluation.
The conclusions and deliberations of the DRG are summarized in Figure 1.
They specify the disease-specific priorities versus the broader macro priorities.
x
 Executive Summary

Figure 1
Research priorities for zoonotic diseases

xi
1. Introduction
As part of its ten-year strategy 1 to foster “an effective global research effort on
infectious diseases of poverty in which disease-endemic countries play a pivotal
role”, TDR established a global research think tank of 125 international experts
to continually and systematically review evidence, assess research needs and,
following periodic national and regional stakeholder consultations, set research
priorities for accelerating the control of infectious diseases of poverty. Working in
ten disease-specific and thematic reference groups (DRGs/TRGs), these experts
were crucial contributors to TDR's stewardship mandate for the acquisition and
analysis of information on infectious diseases of poverty 2. Their work is ultimately
intended to promote control-relevant research, achieve research innovation
and enhance the capacity of disease-endemic countries to resolve public health
problems related to the disproportionate burden of infectious diseases among
the poor.
This report addresses the research needs of zoonotic diseases (the diseases
of animals that also affect humans) as well as other marginalized infections of
some of the world’s poorest people and communities, often living beyond the
reach of the formal health system. Research priorities identified by the Reference
Group on Zoonoses and Marginalized Infectious Diseases (DRG6) are presented
in this report.

1.1 Rationale and context

The majority of infectious diseases mainly affect poor and marginalized
populations that lack access to health services and are readily ignored. As a
result, these populations are subjected to a cycle of ill-health and poverty
that aggravates their burden of infectious diseases. Of some 1400 species of
infectious disease pathogens of humans, nearly 60% are derived from animal
sources, hence the importance of recognizing the role of livestock, companion
animals and wildlife in the interactions between animals and humans (1, 2). In
addition two thirds of emerging pathogens are of zoonotic origin (1, 2). Only
by recognizing the importance of these human−animal interactions can we fully
understand how to control these infections.
Zoonotic diseases, although biologically diverse, share common
characteristics associated with the conditions under which poor people live
in the world’s poorest countries. These features are usually the result of social,
economic, geographical and political forces. We have an excellent understanding

1
Details on TDR's strategy can be found at: http://www.who.int/tdr/about
2
Details of TDR's research priority reports can be found at: www.who.int/tdr/capacity/gap_analysis
1
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

of the biological features of the etiology, transmission and epidemiology of a

particular infection, but reducing the burden of disease must be undertaken in
communities and populations within the framework of local or national settings
and through coordinated policy.
Recent pandemic threats have raised concern in developed countries,
as their populations and economies are threatened. In response, developed
countries have provided significant resources for targeted surveillance and
control of these emerging global problems. Most of these intermittent global
threats have emerged from animal sources. However, many marginalized
populations are living in close contact with animals on a daily basis since they are
dependent on livestock as a critical resource for survival. They are thus exposed,
together with their livestock, to debilitating infections through the frequency
of their contacts. History has shown that infections constantly emerge from
animal populations. Such threats have always provoked fear, fueled in recent
years by the emergence of HIV, Ebola, Nipah, Lassa, SARS, H5N1 and H1N1
influenza viruses, and E. coli O157:H7, all of animal origin.
The number of people who are directly dependent on livestock is
estimated at some 600 million, nearly a tenth of the world’s population, and
in more marginal lands of the tropics the proportion of the population so
dependent can be as high as 70%. However, for effective disease control, the
zoonotic diseases need multisectoral collaboration between the human and
veterinary health, agricultural, and water and sanitation sectors.
A further feature of zoonotic and marginalized diseases is that they
predominate among populations living in conflict and war zones, internally
displaced populations, refugees, and those affected by natural disasters
(earthquakes, volcanoes and tsunamis). In such situations, already weak
infrastructures for health and limited resources cannot cope with the increased
burden of infectious diseases, even though the pattern of emergence of diseases
in these situations is well known.
WHO Technical Report Series, No. 971, 2012

In environments where zoonotic diseases represent a high burden, health

systems are weak, fragmented or not accessible to populations living “beyond
the end of the road”. Hence there is inadequate surveillance and reporting of
disease outbreaks, a situation compounded by inadequate diagnostic and
therapeutic services. In addition, the efficacy of drugs for both humans and
animals is not effectively monitored as a result of lack of control of imports and the
widespread sale of ineffective or counterfeit products through an unregulated
private sector.
A sizeable proportion of the burden of zoonotic disease seems likely
to result from endemic, chronic, disabling, frequently misdiagnosed and often
unreported infections of remote populations that are dependent on livestock
for their survival and asset base. Such populations, often nomadic, have limited
contact with or access to formal health services and live beyond the reach of
2
 Introduction

surveillance systems. This report seeks to bridge this human−animal interface by

linking research knowledge to the control of zoonoses of human public health
and veterinary public health importance. It seeks to provide stakeholders with
a greater understanding of the opportunities of a strategic vision of the research
needed to diminish the impact of these infections. The report emphasizes that,
in many low-income countries, a high proportion of the total population is
dependent on livestock and that a significant proportion of the Gross Domestic
Product is derived from livestock. In the humid savannas and forests of sub-
Saharan Africa, the consumption of game meat or “bushmeat” represents a
major source of protein, with the attendant risks of the acquisition of a variety
of pathogens due to the exposure of humans to animal species ranging from
rodents and bats to non-human primates.
Infectious diseases affect the poorest people on the planet, those who
have been called “the bottom billion” (3, 4). Addressing one disease at a time
means that attention to their control has depended on donor priority ratings on
the one hand and on the power of advocacy constituencies on the other. As a
result the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM) was
established as a financing mechanism to coordinate donor efforts and to ensure
efficient distribution of financial resources. One consequence has been greater
overall resources for these three diseases, at the potential expense of stagnant
investments in other highly prevalent diseases of poverty with arguably a higher
overall burden than the specific diseases addressed by GFATM (4).

1.2 Zoonoses and the Millennium Development Goals

Zoonoses are not overtly mentioned in the Millennium Development Goals
(MDGs) and therefore are relegated to the basket of “other diseases” included
in MDG 6, which is primarily focused on HIV and malaria. However, as this
report shows, the zoonotic diseases have a profound impact on the health of
the poorest, whose sole source of income and only asset is often their livestock.
A stakeholder meeting in Cairo, Egypt, highlighted the arid zones of sub-
Saharan Africa and the Eastern Mediterranean Region, where the loss of the
traditional systems of livestock husbandry through drought, animal or human
disease, ecological stress or civil unrest has threatened the very existence of
these communities, which are critically dependent on the well-being of their
livestock. These communities are often marginalized not only through the
stresses described above but also by political, social, cultural and economic
forces. They are often minority ethnic groups, are migratory and traditionally do
not participate in mainstream education, and they lack access to any government
service. Although the zoonotic diseases themselves are not specified within the
framework of the MDGs, addressing diseases of poverty, both in humans and
animals, will have an impact on the success of ongoing and future attempts to
improve the lives of the poorest populations in the poorest countries. Ensuring
3
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

the health of the livestock has further implications for the maintenance of
the rural economy, as many infections of livestock have an impact on their
productivity in terms of milk or meat output, animal value at slaughter, loss of
manure as a fertilizer, and reduced income from sale of livestock. In addition,
in many societies, smallholder farming is under the control of women, who
can suffer disproportionately from the adverse consequences of human and/
or animal disease, through loss of income and hence loss of independence.
The benefits in the context of MDGs relating to maternal and child health and
access to health and education can thus be traced to the effective maintenance
of the traditional way of life, assured through the health of livestock in these
populations, particularly in arid environments.
The “other diseases” of MDG 6 which include the even more neglected
zoonoses, need to be re-addressed in the context of what may be gained in terms
of poverty alleviation through implementation of cost-effective interventions on
the one hand and more focused research on the other. The “other diseases” (except
tuberculosis, which was included in GFATM) and perhaps polio eradication
have remained secondary priorities, despite accumulating evidence for the
effectiveness of control measures that can be deployed at the population level and
the knowledge that over one billion people are infected and some 2.7 billion are
probably at risk of “other diseases” besides the “big three” (3−5). For the zoonotic
diseases, there is a need for stronger advocacy and for a focused research agenda
directed at improved approaches to control. As suggested by Molyneux (4),
while the 10/90 gap in research efforts (referring to the fact that less than 10% of
global funding is devoted to 90% of the world’s health problems) is well defined,
this gap for the most neglected diseases is probably closer to 1/99. Such a ratio
certainly applies to the zoonotic diseases where the burden:research ratio was
not calculated by a study of the research spending on neglected diseases (6).
The comparative lack of research investment in diseases other than the
“big three” diseases of poverty, and the disparity between burden of disease
WHO Technical Report Series, No. 971, 2012

and investment has been well documented (6). It has been calculated that the
total investment in neglected tropical disease control (excluding HIV/TB and
malaria) is only 0.6% of total Official Development Assistance (ODA) funding for
health, despite the large population of infected and very poor people at risk (7).

1.3 Challenges
The most important initial observation is that there is limited reliable qualitative
and quantitative information on the burden of zoonotic diseases, as well as a
lack of information on their geographical (regional) distribution in endemic
countries. One of the challenges in estimating burden of disease is the weak
health and agricultural information systems in endemic countries, including the
lack of reporting (or underreporting) of infectious diseases. Similarly, because
4
 Introduction

of limited national government expenditures for health, surveillance remains

particularly underfunded, which limits the ability to estimate reliably the burden
of these infections. Limited funding also handicaps control of zoonotic diseases
as the interaction between those responsible for human health, animal health and
wildlife services is impeded, leading to the failure to identify disease outbreaks
and contributing to the limited awareness of zoonotic infections at the policy
level. Because zoonotic diseases often occur in communities beyond the reach of
the formal health facilities, education systems and livestock services, reporting
and certification of deaths may not be possible. This information is a prerequisite
for the acquisition of accurate data upon which the Global Burden of Disease
Studies depend.
Inadequate surveillance and reporting are characteristic of zoonoses,
and many zoonotic infections have clinical manifestations, being characterized
only by febrile episodes. Some diseases, however, can be stigmatizing and are
hence kept hidden. For example, neurocysticercosis is associated with a range
of symptoms, such as epileptic seizures and severe chronic headaches, while
liver fluke infections with opisthorchiasis and clonorchiasis can lead to bile duct
carcinomas. Moreover, the definitive diagnosis for several of these helminth
infections requires advanced techniques such as imaging, which are rarely
available and are unaffordable in the settings where the zoonoses are a major
burden. Clusters of cases and their true etiology may also go unrecognized,
especially if they occur in isolated areas. This leads to a further underestimation
of their incidence, the starting point for assessing disease burden. The lack of
information on the social and economic outcomes of zoonoses, including the
direct (treatment costs) and indirect (productivity losses) costs in both humans
and animals, and the indirect impact of reduced productivity in livestock (meat,
milk, manure), remain a serious deficit. The fact that zoonoses can affect in turn
the cash value of animals and reduce the availability of protein, contributing to
malnutrition, growth reduction and cognitive deficits, remains a serious and
systemic deficit.
At the national level, countries where zoonoses are endemic have limited
qualified human resources to deal with the challenges of control of infectious
diseases. In ministries of health, the personnel dealing with surveillance and
research may have limited experience with zoonoses. In addition, epidemiologists
and health economists who work in local academic institutions, have other
responsibilities that limit the time they can devote to collaboration with
governmental agencies.
At the international level, considerable resources are now devoted to
combating HIV, malaria, tuberculosis, poliomyelitis and vaccine-preventable
diseases through GFATM, the Global Polio Eradication Initiative and the Global
Alliance for Vaccines and Immunization (GAVI). In contrast, until recently,
there has been little attention to the neglected tropical diseases (NTDs) that
5
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

are most prevalent among the bottom billion on the socioeconomic ladder (3).
In addition, in most of the disease-endemic countries, research agendas do not
prioritize the challenges faced by the disease control programmes, in large part
because they are usually set by academic institutions without addressing or
seeking to influence the national priorities in disease control.

1.4 Scope of the report

The comparative lack of research investment in neglected diseases other than
the “big three” diseases of poverty, and the disparity between burden of disease
and investment have been documented (6). It has been calculated that the
total investment in neglected tropical disease control (excluding HIV/TB and
malaria) is only 0.6% of total Official Development Assistance (ODA) funding
for health, despite the over one billion people considered to be at risk (7). This
report examines zoonotic and marginalized diseases caused by an array of
diverse infective agents, from viruses to worms, with very different transmission
mechanisms, epidemiology, geographical distribution, control interventions,
evaluation and surveillance procedures. This diversity of agents creates a further
dimension – the need to bring together new constituencies of stakeholders
working across the animal-human interface and provides a unique challenge in
priority setting.
This report focuses on the following specific infections:
1) Helminth infections
- taeniasis/cysticercosis
- echinococcosis
- zoonotic schistosomiasis
- foodborne trematodiases
2) Protozoan infections
WHO Technical Report Series, No. 971, 2012

- toxoplasmosis
- cryptosporidiosis
3) Bacterial infections
- brucellosis
- enteric infections
- bovine tuberculosis
- anthrax
4) Viral infections
- rabies
This report did not consider rotavirus infection because, while it is
a cause of high morbidity and mortality, it is already receiving considerable
6
 Introduction

attention elsewhere. Effective vaccines are now available and will probably be
deployed widely in the coming years. The remaining diarrhoeal diseases are
particularly linked to poverty with its attendant limited access to safe water and
sanitation facilities, and inadequate access to health services. These infections
are considered in this report, particularly as they relate to and enhance the
cost−effectiveness of ecosystem, water supply and sanitation improvements
that can reduce the burden of diarrhoeal and other infectious agents, whether
zoonotic in nature or not.

1.5 Group membership

The Disease Reference Group on Zoonoses and Marginalized Infectious Diseases
of Poverty (DRG 6) consisted of 13 experts in the area of zoonotic diseases and
cross-cutting themes (Appendix 1). Members were identified from research
institutions, international organizations, bilateral institutions, health and
medical organizations, and governmental and inter-governmental organizations
worldwide. Particular attention was paid to the geographical distribution, to
ensure disease-endemic country and regional input as well as technical input,
and gender balance of the membership. Members were formally appointed by
the Director, TDR, for an initial period of two years. All members were obliged
to declare any conflict of interest and confidentiality.
The Chair and co-Chair of the group were selected on the basis of their
internationally-recognized research and control experience in disease-endemic
countries.

1.6 Host country

To ensure that the countries most affected by diseases of poverty contribute to,
and share ownership of the research agenda emerging from this initiative, the
Reference Groups were hosted by disease-endemic countries, in partnership with
WHO country and regional offices (Appendix 2).
The DRG was hosted in the WHO Regional Office for the Eastern
Mediterranean (EMRO), Cairo Egypt.

1.7 Think tank members

The think tank was designed to draw on the best expertise internationally
(Appendix 3), and to maximize partnerships with countries most affected by
diseases of poverty. The 10 Reference Groups making up the think tank included
researchers and public health experts from the most affected countries, and
these countries also hosted the Groups. WHO country and regional offices
supported both the Reference Groups and broad-based stakeholder consultations
(Appendix 4).
7
2. Methodology and prioritization
A preliminary informal consultation was convened by TDR in Geneva to discuss
the broad issues of the diseases that the DRG, when formally established, would
address. This meeting was necessary as TDR had not previously been involved in
these diseases, yet zoonotic diseases represented significant challenges in terms
of their impact and burden on the poor in endemic countries. The DRG on
Zoonoses and Marginalized Infectious Diseases (DRG 6) was thus established to
prepare a status report on research into these infections and provide input for
the Global Report for Research on Infectious Diseases of Poverty 1.
The purpose of DRG 6 was to systematically review research evidence and
evaluate its relevance to control needs, assess challenges in control and highlight
new and significant scientific advances. It was also to provide independent advice
and guidance on priority areas and critical research gaps as a contribution to the
Global Report. It is recognized that there are many ways to identify priorities
based on expected outcomes. DRG 6 followed a sequential strategy, starting
with initial informal consultation, semiquantitative prioritization exercises by
members followed by a further stakeholders’ consultation, proceeding to the
development of a series of matrices based on specific indicators of identified
research priorities. The DRG also drew on authoritative reports, some of which
were convened under the auspices of WHO and TDR, which had also identified
priorities for some of the diseases discussed.

2.1 Informal consultation

An informal consultation to discuss the scope, framework and membership of
a DRG on infectious diseases associated with poverty including zoonoses other
than those in the “traditional” TDR disease portfolio was held 2–3 June 2009 in
Geneva. The consultation had the following specific objectives: 1) to define and
agree on criteria for selecting the infectious diseases and research areas of the
DRG; 2) to determine the scope of the DRG (diseases and research areas), and
3) to recommend potential membership of the DRG based on the scope of the
mandate, skill sets and expertise required. Members of the informal consultation
included experts on a variety of relevant diseases and specialities from WHO and
countries (representative of all WHO regions). The Group then discussed and
defined the disease scope and categories for the thematic analytical work.

2.2 Selection of DRG members

Potential members were identified from research institutions, international
organizations, health and medical organizations, and governmental and inter-

1
http://www.who.int/tdr/capacity/global_report
9
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

governmental organizations worldwide. An initial list of 45 experts selected on

the basis of the following required matching expertise: veterinary public health,
veterinary laboratory science, wildlife biology, health social sciences (medical
anthropologist/community health), clinical medicine (infectious diseases experts),
water and sanitation, parasitology/microbiology/genomics and genetics, health/
agriculture economics and diagnostics, was prepared and subjected to voting by
a panel of WHO internal and external researchers. Particular attention was paid
to the geographical distribution, to ensure disease-endemic country and regional
input as well as technical input, and gender balance of the membership. The final
list of 13 members was formally appointed by the Director, TDR for an initial
period of two years. All members were obliged to declare any conflict of interest
and confidentiality.

2.3 First DRG meeting

Following the selection of DRG members and in preparation for the first meeting
in November 2009, members were asked to prepare and present the research
issues in their areas of expertise. All the identified areas were discussed in detail
and a list of diseases on which to focus was identified. Following the first meeting
of the DRG, members initiated report writing within their areas of expertise,
and a draft report was created to be discussed at a stakeholders’ consultation.

2.4 Stakeholders' consultations

Periodic regional and national stakeholders’ consultations are an essential part
of the analytical process, enabling validation, endorsement and uptake of final
research priorities, and ensuring that the work of the DRG is authoritative,
scientifically credible and relevant for policy.
The stakeholders’ consultation was organized by WHO/EMRO, the DRG
host, to discuss the scope, relevance, research gaps and validation of research
WHO Technical Report Series, No. 971, 2012

priorities. It was held in Cairo, Egypt, on 29 March 2010. Regional and national
stakeholder consultations based in endemic countries represented an essential
part of the analytical process.
Key stakeholders included the ministers of health, other representatives
of the ministries of health, ministers of agriculture and animal resources of
Egypt, Sudan and Yemen, who emphasized the importance of research in these
diseases where there is an interface between humans and animals. They endorsed
the concept note and provided input in the identification of research priorities in
relation to real needs in their countries. Other participants included international
organization (OIE), academic institutions (Imperial College London, University
of KwaZulu-Natal, University of Costa Rica, the National Autonomous University
of Honduras) and representatives of WHO regions.
10
 Methodology and prioritization

2.5 Second DRG meeting

As a result of the stakeholders’ consultation discussions, a semiquantitative
matrix system was developed during the second DRG meeting in order to ensure
that cross-cutting issues relevant to each specific disease were considered and
to indicate a priority rating. The meeting took place in Cairo, Egypt, the DRG’s
host country, from 30 to 31 March 2010.

2.6 Prioritization process

The disease-specific priorities were derived from expert opinion of the DRG, as
formulated by previous relevant WHO/HQ and regional meetings and WHO/
TDR meetings on the different disease groups, from peer-reviewed papers from
experts and from prominent publications that had policy relevance. The DRG was
also cognizant of funding bodies that had an interest in the diseases considered
by the group, including disease-specific regional working groups, the OIE and
the research focus of these organizations.
During its meetings and via electronic communication, the DRG
identified research priorities for both individual diseases and the broader
intervention-based approaches, which require cross-cutting social science
research particularly in areas of health education and promotion, community-
based approaches and operational research required to scale up existing strategies
for zoonotic disease control. The stakeholders’ consultation was also presented
with the initial broad conclusions of the DRG and endorsed the approach the
DRG had taken and the initial view of the priorities identified. The DRG also
highlighted a multiplicity of cross-disease and thematic issues that emerged
during intensive debate and interaction between members, stakeholders and
the Secretariat.
Following its initial scan of priorities during and after its first meeting,
the DRG developed a structured approach and methodology for addressing
priorities based on the experience of the members and the feedback from wider
discussions. The report is based on this accumulated experience and knowledge
of the health, livestock and education sectors from both a research and an
implementation perspective. The priorities were examined in a semiquantitative
way. This allowed a multidimensional approach where the diseases, the cross-
cutting topics and the interventions could be addressed and prioritized. This
enabled scores to be analysed and rated on a scale of 1-5 (5 being the highest
priority level). The analysis led to the identification of priorities shown in
Figure 1 as macro and disease-specific priorities. At the end of the process, the
DRG published a summary of priorities identified for zoonoses and marginalized
infectious diseases of poverty (8).
11
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

2.7 Transformation of DRG report to TRS

The process of finalization of the report and its transformation into a publication
in the WHO Technical Report Series was carried out through electronic
communication between the Chair, co-Chair, DRG members and the Secretariat.
The Secretariat undertook the organization of external and internal reviews of
the report, and comments on structure and content were addressed in the final
version of the report.
This report was assessed by the WHO Guidelines Review Committee,
which recommended that it be published as an Expert Report.
WHO Technical Report Series, No. 971, 2012

12
3. Burden of disease
Disease burden is defined as the “size of a health problem in an area, measured
by cost, mortality, morbidity or other indicators”. This definition clearly shows
that disease burden may be captured by different measures, which are described
in the following section.

3.1 Estimating the burden of parasitic zoonoses:

approaches and challenges
The various methods that may be used to estimate disease burden in animals
and humans are summarized in Table 1 (9).

Table 1
Comparisons of the main measures of disease burden

Measure Items Availability / quality of data

of burden
Humans Animals
Mortality Cause-specific Quality highly variable Rarely available except
death rates between countries for notifiable diseases.
Morbidity Disease-specific Notifiable / registry Research studies only
incidence rates disease data Acute, non-recurrent
Quality / completeness and notifiable
highly variable. diseases (i.e. rabies) if
denominator known
Disease-specific National / special Slaughterhouse
prevalence survey data data where home
Special survey slaughtering is rare
data often provide Special survey
overestimate data often provide
overestimate
QALYs Cause-specific Quality highly variable Not applicable
death rates between countries
Life expectancy Largely available
Disease-specific Notifiable / registry
incidence rates disease data.
Quality / completeness
highly variable.
continues
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Table 1 continued
Measure Items Availability / quality of data
of burden
Humans Animals
QALYs Time evolution of Knowledge of natural Not applicable
disease states history of disease
needed
Quality of life Special studies.
measure at various Place/time specific
disease states

DALYs Cause-specific Quality highly variable Not applicable

death rates between countries
Disease-specific Notifiable / registry
incidence rates disease data.
Quality / completeness
highly variable.
Distribution Knowledge of natural
of sequelae history of disease
associated needed
with disease in
treatment-free
individuals
Duration of Knowledge of natural
each sequela in history of each sequela
treatment-free needed
individuals
Distribution Special studies required
of sequelea
associated with
WHO Technical Report Series, No. 971, 2012

disease among
people under
treatment
Duration of each Special studies required
sequela under
treatment
Disability weights Available from GBD
for each sequela initiative.
(treated / non- Not all sequelae
treated) have been attributed
disability weights
continues
14
 Burden of disease

Table 1 continued
Measure Items Availability / quality of data
of burden
Humans Animals
Monetary Cause-specific Quality highly variable Rarely available except
burden death rates between countries for notifiable diseases.
Disease-specific National / special Slaughterhouse
prevalence survey data data where home
Special survey slaughtering is rare
data often provide Special survey
overestimate data often provide
overestimate
Distribution Knowledge of natural Knowledge of natural
of sequelae history of disease history of disease
associated with needed needed
disease
Frequency of Special studies Special studies
care / treatments / Expert opinion Expert opinion
diagnoses and
productivity losses
for each sequela
Costs associated Country-level health / Agricultural statistics
with care / labour statistics Special surveys
treatments / Special surveys
productivity losses
of each sequela
By permission of Oxford University Press.
p.33 Table 4.2: Comparisons of the main measures of Disease burden from Ch.4 'Health Impact Assessment
and burden of zoonotic diseases' by C.M.Budke, H.Carabin, Torgerson, P.R. from "Oxford Textbook of Zoonoses:
Biology, Clinical Practice and Public Health Control" edited by Palmer, S.R., et al (2011).
Free permission Author's own material.

3.1.1 Measures of mortality, morbidity and health-

associated life years
3.1.1.1 Measures of mortality and morbidity in humans
Several methods have been proposed to compare the burden of human diseases
worldwide. The traditional method has been to use cause-specific death
rates (10). The reported advantage of this approach is the availability of death
certificates worldwide. However, the determination of the cause of death as listed
on death certificates has been shown to be poor in a number of countries (11).
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Many demographers would dispute the claim that death certification is available
widely. In remote communities where zoonoses are prevalent, the existence of a
death certification process and/or an accurate assessment of the cause of death
is unlikely. This is particularly the case where death is followed traditionally by
burial within 24 hours. Moreover, in cases of death reporting, other errors can
arise, such as;
1) ignorance of all diseases that are not fatal but may contribute to a
fatal outcome due to another cause;
2) underestimation of the prevalence of common diseases that are
rarely fatal;
3) underestimation of the distal rather than proximal causes of death,
such as underlying nutritional status, reduced immunological
status or co-morbidity.
Another option is to measure the frequency of occurrence of each disease.
Such data can originate from surveillance systems, public health records or
specific studies where medical charts are reviewed. The most commonly available
data are those from surveillance systems. Surveillance systems, however, have
several limitations. These include:
1) variation in the quality and completeness of the data from country
to country and within a country from region to region;
2) the limited number of diseases under surveillance and covered by
the reporting systems;
3) inclusion of only those cases that are reported to the authorities.
This leads to a poor representation of the true frequency of specific
diseases and prevents the development of accurate maps of disease prevalence.
WHO Technical Report Series, No. 971, 2012

3.1.1.2 Measures of health-associated life years in humans

Measuring the prevalence of a particular disease does not capture associated
duration, suffering and subsequent disability. Such impacts of disease can be
measured with health-adjusted life years (HALYs). The two most common
HALYs are quality-adjusted life years (QALYs) and disability-adjusted life years
(DALYs). Several multi-attribute measurement tools have been developed to
link a health measurement scale to utility of health values. The most commonly
used measurement scales are the Quality of Health Being (QHB), the Health
Utilities Index (HUI), the Short Form series (SF) and the Euro-Qol series (12).
These scales measure several aspects of functioning (i.e. physical, social, mental).
Questionnaires are used to calculate a score, which is correlated with utility
values, used to compare the impact of diseases.
16
 Burden of disease

QALYs are designed to reflect an individual-level impact and are difficult

to compare internationally. DALYs combine four elements: the number of years
of life lost due to the disease-associated death rate, the age−gender specific
incidence rate of the disease, the distribution and duration of the sequelae of the
disease and the disability associated with those sequelae. DALYs aim at being
interchangeable and equivalent across locations and cultures and at measuring
limitations in functional status regardless of environment (13). However, since
accurate data on the prevalence of zoonotic infections in humans are rarely
available, DALYs associated with such diseases are difficult to estimate.
An assessment of the DALY burden of five zoonotic diseases was
initiated by WHO in 2006. For echinococcosis and rabies the existing published
estimates were used (14, 15). For those diseases with both anthroponotic and
zoonotic components (schistosomiasis, trypanosomiasis and leishmaniasis)
the DALY burden of each component was estimated from a range of sources
(including expert opinion and WHO GBD 2004 data), and assumptions
were made for each of the diseases. The total DALY burden of the zoonotic
component of these five diseases was conservatively estimated at 5.3 million
DALYs (16).

3.1.1.3 Measures of mortality and morbidity in animals

The impact of infections in animals can be captured through the determination
of associated mortality and morbidity or by its monetary impact. There are rarely
reliable data on the frequency of neglected zoonoses in poor countries except
for those infections that are under surveillance through the OIE. Abattoir data
can be used to estimate the prevalence of some infections if macroscopic lesions
can be detected at slaughter. However, such data are only useful in areas where
animals are consistently inspected at slaughter. This is rarely the case in areas
where neglected zoonoses are endemic and slaughter practices are traditional
and not supervised by veterinary authorities. Decline in national government
support for national veterinary services has reduced the information available
from formal sources. The estimate of the monetary impact of animal zoonotic
infections requires the same information as that collected in human populations.
This includes the prevalence of the infection and the distribution and duration of
sequelae and their impact on livestock productivity.
Estimating the burden of zoonoses in animals is particularly challenging
(17). There are several reasons for this:

1) Zoonotic infections are neglected and underreported as causes

of death. They are rarely diagnosed or included on the list of
notifiable diseases.
17
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

2) Information on the spatial distribution of the prevalence of

zoonotic infections is limited.
3) Zoonotic infections often present with a variety of non-
specific symptoms that are easily misdiagnosed, leading to an
underestimation of the frequency of zoonoses.
4) Because most zoonoses are chronic infections, the sequelae may
be delayed and develop over several years. Thus they may not be
perceived as connected to the original infection.
5) Zoonoses affect animals as well as humans, hence the total burden
of an infection should be calculated to include the losses occurring
as a consequence of their impact on animals. Livestock-dependent
populations rely on animals for survival and the impact of disease
on reduced milk production, condemned meat or lost proteins
due to loss of livestock from disease and reduced manure for soil
fertility are contributory factors to disease burden estimates.
6) Animals as well as humans may suffer from more than one
infection at the same time, thus complicating the diagnosis and
attribution of the burden to a specific infectious entity.
Measuring the true extent of all neglected zoonotic diseases requires the
recognition of the problems of access, insufficient surveillance and misdiagnosis.

3.1.2 Economic (monetary) burden of zoonotic disease

A further method that can be used to measure the burden of disease is to calculate
its societal monetary impact. Monetary losses associated with zoonoses can be
calculated by a mathematical approach (18). In human disease, the direct costs
incurred correspond to health-care spending (i.e., diagnosis, treatment, etc.) and
indirect costs to resources foregone due to the disease (i.e., productivity losses,
transportation, over-the-counter drugs purchased). In animals, the direct costs
WHO Technical Report Series, No. 971, 2012

are related to condemnation of whole (or parts of) carcasses, while indirect costs
as a result of animal diseases are more difficult to capture, but can be classified in
the following broad categories.

Agricultural and other products

Animals in many low-income settings, in addition to contributing to the
availability of dietary protein, provide transport, draught power, fuel and clothing.
Crop production and harvesting may be adversely affected through the reduction
in both traction capacity and the manure output essential for soil fertility and an
efficient productive nutrient cycle. Transport, including mobilization of essential
water supplies can also be severely affected. This impact is difficult to quantify
and may be grossly underestimated.
18
 Burden of disease

Food safety issues and restrictions to trade

Outbreaks of zoonotic diseases can lead to disruption in local markets and may
result in the restriction of movement of animals (2). Barriers to export markets
have less impact on most rural communities. However where goods are exported
there is a multiplier effect on employment and auxiliary sectors leading to a
much amplified effect on whole communities (2).

Conservation issues
Neglected zoonotic disease (NZD) may cause mortality in wild animals leading
to extinction of endangered species (e.g. African wild dogs from rabies). This
could also have an impact on the ability to generate income in communities that
rely on tourism.

3.1.3 Case-studies
3.1.3.1 The monetary burden of cysticercosis
There are significant agricultural losses related to Taenia solium infection of pigs
caused by cystic stages of the parasite. Porcine cysticercosis often results in total
condemnation of pig carcasses since pigs can harbour thousands of cysts, making
the meat from these animals unsafe to eat. Pig traders, aware of the disease, may
detect infection during a pre-purchase examination and then refuse to buy a
suspect pig. Farms and whole communities may become stigmatized when they
are known to sell infected pigs and/or cyst-contaminated meat. Several studies
have assessed the monetary burden due to cysticercosis infection, as shown in
Table 2 (19–22). A pig carcass infected with cysticercosis is sold at a decreased
price, which can vary from 25% of the usual market price in Benin to 50% in
Rwanda (20). There is also a loss of profit when farmers do not sell their meat to
official markets (17).
The combined cost of cysticercosis in humans and animals has been
estimated in two countries (17, 23). The proportion of epilepsy cases attributable
to neurocysticercosis (NCC) and the proportion of working time lost were found
to have the most influence on the estimated monetary burden (23).

3.1.3.2 The monetary burden of cystic echinococcosis

The combined human and animal monetary burden of cystic echinococcosis
has been estimated from several countries. One limitation mentioned in all
the studies has been the lack of knowledge of the impact of infection in people
without obvious symptoms and the estimates of the reduction in productivity in
animals. The monetary impact of cystic echinococcosis has been evaluated in a
number of countries; the results are reported in Table 3. Although these studies
vary in the methods used, they provide a broad estimate of the costs of cystic
echinococcosis.
19
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Table 2
Summary of monetary burden of cystcercosis

Monetary Loss Country Cause Equivalent Reference

≥ US$ 120 China cysticercosis Amount of (22)
million annually infection pork discarded
200 million kg
US$ 9.0–32.3 Eastern NCC-associated 5–10% of the (17)
to US$ 12.8– Cape epilepsy, benefits annual health
70.0 million Province, from pork not sold expenditures
depending on South Africa in slaughterhouses (US$ 41.3 per
the methods (2004) capita)
used
€6.9–14.8 West NCC-associated 5.6% of (23)
million Cameroon epilepsy and per capita
30% loss of value expenditure on
for infected pig health (2004)
carcases (year (US$ 44)
unknown)
US$ 996 per Lima, Peru 49 NCC patients 54% of (24)
case for the residing in Lima minimal wage
first 2 years of treated in a during the
treatment neurological first year of
reference hospital treatment;
(1999-2002) 16% of
minimal wage
during the
second year of
treatment
US$ 174.7 per Andhra Solitary Cyst 50.9% of per (25)
WHO Technical Report Series, No. 971, 2012

patient Pradesh, Granuloma NCC- capita GDP

India associated new
onset seizures
patients in a seizure
clinic (1997)
US$ 2.1– Los Angeles, 3,618 hospitalized Average (26)
14.0 million per CA, USA NCC adult cases per NCC
year; average (1991–2002) hospitalization
$56 500 per almost twice
hospitalization) average US
hospitalization
(US$ 24 000)

20
 Burden of disease

Table 3
Summary of monetary burden of cystic echinococcosis

Country (year of Estimated annual % agricultural References

valuation) societal monetary monetary
burden burden
Jordan (unknown) US$ 3.9 million 92% (27)
Wales, United
US$ 1.1–6.7 million 73–76% (28)
Kingdom (1997)
Uruguay US$ 2.9–22.1 million 16–70% (29)
(unknown)
Tunisia (2000) US$ 10.7–14.7 million 56–57% (18)
China (unknown) US$ 0.94 million 97% (30)
Spain (2005) US$ 19.5–184.6 million 10–95% (31)
Global burden US$ 4.1 billion 46% human http://www.who.
treatment, int/neglected_
54% animal diseases/2010report/
health costs en/index.html

3.1.3.3 The monetary burden of rabies

The monetary burden of rabies has been estimated for Africa and Asia, including
data on the costs of post-exposure prophylaxis (PEP), costs relating to the control
of dog rabies (dog vaccination and population control), rabies surveillance costs
and livestock losses (15). In this analysis, the direct medical costs include the
cost of biological reagents (rabies vaccines and immunoglobulin) and their
administration (including materials and staff salaries). Indirect costs represent
50% of total costs (32) and include transport costs to and from treatment centres
and loss of income while receiving treatment in the case of both bite victims and
their accompanying adults.
The monetary burden of rabies in Africa and Asia was estimated as
US$ 583 (90% CI: 540–626) million (33), but this is considered an underestimate
for several reasons. Firstly, it is recognized that the number of vaccine doses used
has been widely underestimated owing to a lack of data from many countries.
Secondly, vaccine and travel costs have been estimated conservatively (US$ 40
per PEP course in Africa and US$ 49 in Asia). Moreover, shortages of PEP, which
occur frequently, increase costs as bite victims are required to travel elsewhere
for treatment (34).
Thirdly, livestock losses have been estimated on the basis of laboratory
sample submissions, which are also likely to be a gross underestimate, even with
21
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

correction for assumed underreporting. In a detailed contact-tracing study in

northern United Republic of Tanzania, livestock deaths were 2−5 times higher
than figures used in an analysis, with an incidence of 12−25 deaths/100 000
cattle/year (15, 32). Finally, this analysis did not include income loss resulting
from premature deaths, which dominates any evaluation of economic burden
due to the high childhood mortality associated with rabies. According to these
estimates, the economic burden of rabies for Africa and Asia is more than US$
3 billion. The monetary burden of rabies is summarized in Table 4.

Table 4
Summary of monetary burden of rabies

Monetary loss Country Cause Reference

In US$
563 (520–605.8) Asia Post–exposure (15, 32)
million treatment and dog
rabies control costs
20.5 (19.3–21.8) Africa Post–exposure (15 ,32)
million treatment and dog
rabies control costs
300 million USA Prevention (33)
> 4 billion Global Prevention and control, http://www.rabiescontrol.
plus income loss due to net/news/news-archive/
premature deaths global-surveys-on-rabies-
in-progress.html

These three case-studies highlight several key issues that argue for more
WHO Technical Report Series, No. 971, 2012

research on the burden and the costs to humans and to the agricultural/livestock
sectors of zoonotic infections. While individual disease studies are useful in
quantifying such losses, given that there may be several co-endemic zoonoses, the
overall costs of animal-associated infections can be predicted to be much higher,
in view of underestimates also from incorrect diagnosis and underreporting.

3.2 Disease-specific issues and burden

3.2.1 Helminths
3.2.1.1 Cysticercosis/taeniasis
Cysticercosis is caused by the tapeworm Taenia solium and is transmitted
between humans (definitive hosts) and pigs (intermediate hosts). The adult
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 Burden of disease

T. solium causes an intestinal infection, taeniasis in humans, whereas the larval

stages cause cysticercosis in both humans and pigs. Owing to conditions related
to poverty, such as inadequate sanitation, poor pig management practices, and
lack or absence of meat inspection and control, cysticercosis/taeniasis remains
an important public health and veterinary problem in many poor countries.
In humans, cysticercosis is particularly important as it can lead to a range of
neurological disorders and sometimes death. Cysticercosis is also a serious
constraint for the nutritional and economic well-being of smallholder farming
communities in many countries of Africa, Latin America and Asia as it reduces
the market value of pigs and renders pork unsafe to eat. Neurocysticercosis
(NCC in humans) occurs when an immature larval stage of the parasite migrates
to the brain. It is considered the most common parasitic infection of the human
nervous system and the most frequent and preventable cause of epilepsy in the
developing world (35−37).
In a meta-analysis, lesions of NCC were reported in about 30% of
people with epilepsy in endemic countries (38). This estimate was similar in
both children and adults, which supports reports from southern Africa and
India indicating that NCC is a common cause of juvenile epilepsy (39−46). In
Honduras, a clinical study revealed that 19% of epileptic patients (n=60) had
viable intracerebral cysticerci and 65% of them had calcifications compatible
with NCC (37).
Despite its frequency and severity, little is known about the societal and
economical impact of NCC. Initiatives are currently underway to determine the
burden of NCC in endemic countries of Africa, Asia and Latin America as well
as countries with many imported cases such as the USA (23, 47). Cysticercosis
is becoming a growing problem in some developed countries because of
immigration of infected individuals from endemic areas (37).
On the basis of its biological and transmission characteristics, cysticercosis
was declared eradicable in 1993 by the International Task Force for Disease
Eradication (48, 49). But since its eradication is dependent on behavioural
changes in endemic populations as well as on implementation of the appropriate
biomedical control measures, the disease remains prevalent among impoverished
populations. Other factors contributing to the lost opportunity to eradicate the
disease are the chronic nature of the infection in humans, the variety of symptoms
associated with NCC, the lack of information and awareness about the burden
and transmission of the disease, and the lack of field-applicable diagnostic tools
for NCC. Despite the 1993 Task Force recommendation, cysticercosis/taeniasis
has not been eliminated from any region, no national control programmes are in
place, and limited advocacy is being undertaken despite the existence of regional
working groups.
WHO included cysticercosis/taeniasis in its Global Plan to Combat
Neglected Tropical Diseases 2008–2009 (50) and in new initiatives addressing
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

integrated control of neglected zoonotic diseases (2, 46), and in assessing the
burden of foodborne diseases (47−49). International epilepsy associations are
giving increased attention to NCC as a major preventable cause of epilepsy (50),
and international NCC/cysticercosis working groups have been formed (51−59)
to facilitate research and control efforts to combat T. solium infections.
Two randomized controlled community trials on the effectiveness
of strategies to control cysticercosis have been published (60−61). In Peru, a
randomized community trial in nine villages, split into 12 “treatment units”,
assessed the effect of combined mass human and pig chemotherapy on the
prevalence and incidence rates of porcine cysticercosis (60). The descriptive
statistics supported some reduction in prevalence and incidence of porcine
cysticercosis in the intervention villages as compared with the controls.
Another randomized, controlled community trial in 42 villages of northern
United Republic of Tanzania aimed at improving pig management through an
educational programme. The trial demonstrated that there was a reduction in the
incidence of porcine cysticercosis of 49% as measured by circulating antigens in
sentinel pigs (60). Similarly, a predictive transmission dynamics model indicated
that interventions targeting improvement in sanitation and in pig management
techniques would be more effective in the long term than treating pigs and/or
humans (61).
The social consequences of NCC, mostly as a result of epileptic seizures,
include stigmatization and incapacitation leading to decreased work productivity
(62−67). People with epilepsy are often isolated and fail to receive appropriate
treatment (68, 69). In west Cameroon it has been estimated that only 27% of
people with epilepsy marry and 39% fail to enter any professional activity
(69), while in Zambia people with epilepsy have poorer employment status,
less education, poorer housing and greater food insecurity. Adult females with
epilepsy are more likely to deliver their babies at home and are at greater risk
of rape (70). People with epilepsy are also prone to accidents during seizures,
resulting in serious burns from fires, drowning or injury due to automobile
WHO Technical Report Series, No. 971, 2012

accidents, consequences that should also be considered in estimating the burden

of NCC (71).
Modelling the expected numbers of epilepsy cases associated with NCC
revealed that between 2.8 and 20.4 DALYs per thousand persons were lost per
year, which was a higher estimate than for some other NTDs (72). The DALYs
associated with NCC are now being calculated through a systematic review of the
literature by a WHO-led initiative to estimate the global burden of foodborne
diseases (52−54).

3.2.1.2 Cystic and alveolar echinococcosis

Echinococcosis (hydatid disease) is caused by cystic stages of cestode tapeworms
belonging to the genus Echinococcus (family Taeniidae). The adult worms are
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 Burden of disease

found in carnivores, especially dogs and foxes. The two species that infect
humans are Echinococcus granulosus and E. multilocularis, which cause cystic
echinococcosis (CE, hydatidosis) and alveolar echinococcosis (AE), respectively.
Both infections are responsible for substantial morbidity and mortality.
Human CE is the most frequent and accounts for around 95% of the estimated
2–3 million global echinococcosis cases. Recent reports indicate that CE and
AE are of increasing public health concern and that both can be regarded as
emerging or re-emerging diseases (73).
Echinococcus granulosus has a worldwide geographical distribution and
is found in at least 100 countries. The highest prevalence is reported from parts
of Africa (northern and eastern regions), Eurasia (e.g. central Asia, China, the
Mediterranean region, Russia) and South America. The actual prevalence can
be from sporadic to high, and few countries can be regarded as being free of
the parasite, apart from island states such as Cyprus, Iceland and New Zealand,
where elimination campaigns have been successful. The DALYs associated with
human CE were recently estimated to be more than for onchocerciasis and similar
to African trypanosomiasis (14). The socioeconomic impact of CE has not been
well researched.
Ingestion of material contaminated with dog faeces containing
E. granulosus eggs results in the development in humans, or other intermediate
hosts, of unilocular fluid-filled bladders – hydatid cysts – mainly in the liver
and lungs but also in other organs. Cysts are often asymptomatic but as they
increase in size over time they act like tumour masses and cause symptoms
due to pressure on surrounding tissues. Cysts may rupture resulting in acute
anaphylactic shock and death if untreated. Dogs that harbour the adult worms
become infected by ingestion of offal containing viable hydatid cysts. The
populations, often pastoral communities, at risk of infection usually live in rural
areas where surveillance is difficult as the infection is asymptomatic, in both
livestock and dogs, and hence not recognized or prioritized by communities or
the local veterinary services.
Treatment for CE relies mainly on surgery or percutaneous drainage to
relieve the pressure symptoms, although the latter has been problematic because
of the risk of spilling cyst fluid and causing anaphylactic shock. Drug treatment
with high doses of albendazole alone or in combination with praziquantel is
effective and can also be used before surgery to sterilize cysts (74). Percutaneous
drainage using ultrasound guidance is better than simply puncturing a cyst.
However, ultrasound and/or surgical intervention, which is often difficult, may
not be available in resource-poor settings.
Echinococcus multilocularis which causes alveolar echinococcosis is
found in the northern hemisphere, including central Europe, most of northern
and central Eurasia (extending eastwards to Japan) and parts of North America.
The median of the total numbers of AE cases in the world has recently been
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

estimated at some 18 000 cases per year; of these 91% are believed to be in China,
particularly on the Tibetan plateau (75). The authors (75) calculated a median
global DALY of 666 434 DALYs per annum. This high rate is attributable to the
high fatality rate, resulting in many years of life lost. Adult worm infections of
E. multilocularis are maintained in a wildlife cycle, with foxes being the most
important definitive hosts and small rodents (especially microtine voles) acting
as intermediate hosts. Human AE is consequently a rarer zoonosis than CE. The
disease is regarded as an emerging disease in Europe because of increasing fox
populations. Although foxes are the principal reservoir of adult worms, dogs are
increasingly being regarded as hosts (75).
The cystic form of E. multilocularis is a tumour-like infiltrating structure
of numerous small vesicles embedded in stroma of connective tissue that
develops almost exclusively in the liver (99% of cases), although metastasis to
other organs can occur. The parasitic mass usually contains a semisolid matrix
rather than fluid and is associated with progressive disease, a poor response
to therapy, a high fatality rate and poor prognosis if managed inappropriately.
Radical surgery, which has been has been the cornerstone of treatment for AE, is
rarely available in resource-poor populations.
Early diagnosis of AE is crucial and results in a reduced rate of
unresectable lesions and less need for more radical surgery. Perioperative and
long-term adjuvant chemotherapy with albendazole (doses up to 20 mg/kg per
day) has been associated with 10-year survival in approximately 80% of cases,
compared with less than 25% in historical controls. Albendazole is parasitostatic
only against the E. multilocularis metacestode. Liver transplantation has been
performed on some AE patients.
The definitive diagnosis of most human cases of CE and AE is by imaging
methods, such as radiology, ultrasonography, computerized axial tomography
(CT) and scanning or magnetic resonance imaging (MRI). Such procedures are
not readily available in isolated communities and poor populations. The advent
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of lower-cost portable ultrasound scanners now enables community-based

surveys in rural endemic regions to be undertaken. Immunodiagnosis (detection
of anti-Echinococcus antibodies in serum) complements the clinical picture, and
is useful not only in primary diagnosis but also for the follow-up of patients
after surgery or drug treatment.
Preventive measures that have been used to control Echinococcus
infections include avoidance of contact with dog or fox faeces, hand-washing and
improved sanitation, reducing dog or fox populations, treatment of dogs with
arecoline hydrobromide or praziquantel, the use of praziquantel-impregnated
baits, incineration of infected organs and health education. Highly successful
campaigns using these approaches have eliminated the disease from island
nations such as Cyprus, Iceland and New Zealand, where control of dogs and offal
consumption is more easily monitored and boundaries for importation secure.
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However, despite the establishment of control programmes against CE in

some countries or regions, E. granulosus still has a wide geographical distribution
and the parasite continues to be the cause of substantial morbidity and mortality
in many parts of the world. Indeed, recent evidence suggests CE is a public health
problem of increasing concern, persisting or re-emerging in many areas of the
world, causing severe disease and considerable economic loss (76).
A similar situation prevails with E. multilocularis, as shown by the
increasing prevalence of AE, its distribution, which is wider than previously
thought, and the fact that the parasite can readily spread from endemic to non-
endemic areas. The greater pathogenicity, difficulty of treatment and higher
mortality risk of AE have led to intervention trials/programmes for control
in a number of endemic areas. However, effective methods for control of
E. multilocularis are not yet available, and this lends support to the argument for
more efficient prevention measures and early diagnosis of AE.
In some areas, notably western China, both human AE and CE are
co‑endemic, and combined control of these Echinococcus species may be
warranted. Guidelines should be developed for consideration of definitions
for control of CE so as to determine what levels of reduction in sheep, dog and
human infections will have a significant impact. Chemotherapy has reduced the
need for invasive surgical management of CE and AE, but there is a need for new
advances in the prevention and control of both diseases.

3.2.1.3 Zoonotic Asian schistosomiasis

Asian schistosomiasis is caused by the trematodes Schistosoma japonicum and
Schistosoma mekongi. S. mekongi infects humans in Cambodia and the southern
tip of the Lao People’s Democratic Republic, while S. japonicum infections are
endemic in China, in parts of Indonesia and in the Philippines. Even though 40
mammalian species have been shown to harbour S. japonicum (77), only 10 are
considered to contribute significantly to human infection (78–80). S. japonicum
and S. mekongi are transmitted through contact with fresh water that contains
free-swimming larval forms called cercariae released from snails, which are the
intermediate hosts. Cercariae penetrate the skin of the mammalian hosts and
develop into adult worms. Water buffalo, cattle, rodents, dogs, sheep and pigs
act as reservoirs for transmission of S. japonicum and dogs and pigs are the main
reservoirs for S. mekongi.
Male and female worms migrate to the hepatic portal system where they
mature, pair up and move downstream. The worm pairs reach mucosal branches
of the inferior mesenteric and superior haemorrhoidal veins and the females
then begin egg production. The process of migration and maturation takes
4−5 weeks. Eggs pass through the intestinal wall and are discharged in the faeces
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into freshwater. The miracidia are explosively liberated from the eggs while still
encapsulated within their sub-shell envelopes and infect receptive Oncomelania
hupensis (S. japonicum) or Neotricula aperta (S. mekongi) snails.
In humans, S. japonicum is associated with liver disease, splenomegaly
and bloody diarrhoea, malnutrition, anaemia and reduced cognition (81). In a
recent review of the literature, the disability weights associated with S. japonicum
were found to be between 7 and 46 times larger than those used in the latest
global burden of disease estimates (82).
The contribution of different animal species to infection of humans may
vary in different endemic areas. In China, studies support a major contribution
of cattle and water buffalo in the transmission of S. japonicum to humans (81).
This is in contrast to the Philippines, where studies in Samar Province found an
association between the intensity of infection in dogs and cats and infection in
humans (83). However, using a polymerase chain reaction (PCR)-based diagnostic
method (84), the prevalence of S. japonicum in water buffalo (carabao) was as
high as 60% in some communities (84). Hence the importance of their role in
disease transmission in the Philippines needs to be clarified.
A mass treatment approach with praziquantel has proved effective in
some areas of China and eliminated S. mekongi in Cambodia (85). However,
it remains less effective in other schistosomiasis-endemic provinces (86). In
both China and the Philippines, infection in the mammalian reservoir hosts
has prevented the possible elimination of schistosomiasis (87). Also, some
communities are reluctant to accept the mass distribution of praziquantel (88).
A pilot study for integrated control of schistosomiasis has recently
been undertaken in China. The study involved a multi-pronged approach
of removing bovines from snail-infested grasslands, providing farmers with
mechanized farm equipment, improving sanitation by supplying tap water
and building lavatories and latrines, providing boats with containers for faeces
WHO Technical Report Series, No. 971, 2012

disposal, and implementing an intensive health education programme (89).

This comprehensive control strategy based on interventions to reduce the rate
of transmission of S. japonicum infection from cattle and humans to snails
has been highly effective. As a result the Chinese government has adopted
the interventions used in the study as the national strategy for the control of
schistosomiasis. However, replacement of bovines with machinery may not
be feasible in many schistosomiasis-endemic areas, such as lakes/marshlands
or mountainous regions because of the difficult terrain. The cost of large-scale
implementation could prove to be prohibitive.
Additional challenges to elimination include the limited accuracy of
field diagnosis using the Kato-Katz technique, the poor compliance of some
populations with mass chemotherapy (88), the need for sustained, integrated
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control efforts (90), and acceptance of transmission-blocking vaccines in buffalo

and other reservoir hosts when they become available for future deployment (91).
Mathematical modelling has shown that integrated control strategies (including
combinations of treatment, bovine vaccination, improved sanitation and reduced
water contact) are, indeed, effective for short- and long-term control of Asian
schistosomiasis (81).
There are other important factors that have yet to be given adequate
attention for the control of Asian schistosomiasis. For example, the completion
of the Three Gorges Dam in southern China has been predicted to increase
transmission of S. japonicum (81). To reduce the impact of this massive
infrastructural project, planners and managers should integrate health impact
assessments and examine how families and communities cope with the social
and economic changes and health risks resulting from such a project (92). An
economic analysis has been conducted to evaluate the cost−effectiveness of
the 10-year programme that eliminated S. mekongi and concluded that for each
dollar invested the benefit was over 3 dollars (93).

3.2.1.4 Foodborne trematodiases

Foodborne trematodiases (FBTs) are an emerging public health problem. An
estimated 750 million people are at risk of acquiring these infections (94). The
FBTs of public health importance are the liver flukes (Clonorchis sinensis, Fasciola
gigantica, Fasciola hepatica, Opisthorchis felineus, and Opisthorchis viverrini),
lung flukes (Paragonimus spp.) and intestinal flukes (e.g. Echinostoma spp.,
Fasciolopsis buski and the heterophyids). Adult flukes are hermaphroditic and
have life-cycles that follow the typical trematode pattern, involving a mollusc
intermediate host from which cercariae are released and either encyst on grass or
water plants (F. hepatica, F. gigantica, F. buski), penetrate the skin of a secondary
intermediate fish host and encyst in the muscles of fish (C. sinensis, O. viverrini,
Echinostoma spp.), in crustaceans (e.g. Paragonimus spp.) or in frogs, snails and
tadpoles (Echinostoma spp.). Definitive hosts become infected by eating raw,
pickled or insufficiently cooked aquatic products harbouring metacercariae or
drinking contaminated water. After ingestion of the metacercariae, excystation of
the metacercariae occurs in the stomach and the released juvenile worm migrates
to the target organ.
Opisthorchis viverrini is considered a Group I carcinogen (known
to be carcinogenic in humans) and long-term infection can lead to
cholangiocarcinoma – cancer of the bile ducts. The link between fluke infection
and cholangiocarcinoma is less robust for Clonorchis spp, but may nonetheless be
real (95). Detection of eggs in faeces (intestinal flukes, liver flukes and lung flukes)
and sputum (lung flukes) is the method of diagnosis of foodborne trematode
infections in epidemiological surveys and for the monitoring of control
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interventions. Serology and ultrasound provide indirect evidence of infection.

PCR techniques have been recently introduced to diagnose Opisthorchis
infections (95, 96). Praziquantel exhibits a broad spectrum of activity against
trematodes and has an excellent safety profile. Hence it is the drug of choice for
clonorchiasis, opisthorchiasis, paragonimiasis and intestinal fluke infections (94).
Sheep, goats and cattle are the predominant animal reservoirs of Fasciola.
In humans, diagnosis of fascioliasis is by finding the eggs in stools, but may
be complemented by immunological detection of anti-F. hepatica antibodies
in sera. Other non-invasive diagnostic techniques are radiology, radioisotope
scanning, ultrasound, CT scanning and MRI (97). Triclabendazole (10–12 mg/
kg) is the drug of choice in human fascioliasis: praziquantel has no effect on
Fasciola (92). Prevention is possible by controlling ingestion of watercress and
other metacercariae-carrying aquatic plants consumed by humans, but requires
behavioral change in dietary habits (97). Triclabendazole has been donated to
WHO for the control of fascioliasis by Novartis and is currently being used in
mass chemotherapy in Bolivia and Peru.
The increasing impact of FBT infections on human health and
productivity is attributed to the rapid development of aquaculture, especially in
Asia (98). Sixteen per cent of the world’s protein consumption and around one
quarter of animal protein needs in Asia are met by aquaculture products from
backyard ponds, small farms or from industrial settings. In 1999, FAO reported
that the global output of aquatic products was 42.77 million tonnes and was
valued at US$ 47.86 billion. Ninety per cent of these products are harvested
in Asia, of which one-third are from China. Over two-thirds of the world’s
aquaculture occurs in fresh water, mostly in Asia where FBTs are endemic (99).
Populations residing near bodies of fresh water, especially in south-east Asia and
the Western Pacific region, are at the greatest risk of FBT diseases (100). One
study demonstrated the increase over a period of only one year in C. sinensis
infection in farmed fish of some 11% in the Red River Delta in Viet Nam (98).
WHO Technical Report Series, No. 971, 2012

The authors recommend that aquaculture management programmes should

address the FBT problem, given that young fish are already infected when
introduced into grow-out systems.
FBT infections are becoming increasingly common in urban areas
as a result of improvements in transportation, marketing and distribution of
freshwater fish, crustaceans and edible water plants and because of the embedded
practice in many Asian cultures of eating raw freshwater-derived food. The
demand for aquaculture-derived products is predicted to increase within the
next two decades owing to overfishing of wild fish, rising incomes, increasing
population and global demand for high-value protein (94).
Despite the availability of interventions for control and treatment of FBT
infections, many people dependent on freshwater resources continue to suffer
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from FBT diseases. Poverty, poor access to health services, lack of education,
inadequate health and sanitation facilities, use of human and animal excreta/
wastes as fish feeds, cultural beliefs, and practices concerning the consumption
of raw freshwater products are the factors that predispose communities to FBT
infections. This situation is aggravated by limited national and local policies,
regulations and health services. The participation of social scientists in FBT
control programmes is essential to address the importance of health education
in guiding people’s food habits and to develop appropriate communication and
education strategies for behaviour modification.

3.2.2 Protozoan infections

3.2.2.1 Toxoplasmosis
Toxoplasma gondii is an obligate intracellular parasite. Felines are the definitive
hosts and act as a reservoir for the parasite. Human infections are acquired by
ingestion of cysts (bradyzoites) in infected raw meat or following consumption of
food contaminated with sporulated oocysts from cat faeces. Human-to-human
transmission is through congenital infection acquired via the transplacental
route and can result in premature birth, eye damage and blindness, brain
damage causing microcephaly and mental retardation, hydrocephaly, seizures
or hepatosplenomegaly. Infection is usually asymptomatic with a low incidence
of overt disease. It presents as an acute mononucleosis-like syndrome,
chorioretinitis or chronic abortion in women. Of HIV-seropositive patients,
40% develop central nervous system (CNS) toxoplasmosis with focal abscesses
primarily located in the brain. Neurological imaging (CT or MRI) is required for
diagnosis of CNS toxoplasmosis, but early treatment and prophylaxis have been
shown to be effective in diagnosed cases.
Toxoplasmosis has a worldwide distribution, with an estimated one third
of the entire global population infected. The US Centers for Disease Control and
Prevention estimates that more than 60 million people are infected with the
parasite in the USA alone, the vast majority of whom are asymptomatic. In the
USA, between 500 and 5000 infants are estimated to be infected annually through
the congenital route. Toxoplasmosis is considered to be the third leading cause of
death attributable to foodborne illness globally. The burden of toxoplasmosis is
borne disproportionately by poor communities in which food safety is inadequate.
Limited access to routine prenatal evaluation for toxoplasmosis, which has proved
to be effective in preventing neonatal neurological and ocular damage, adds to
the burden (101). The prevalence of toxoplasmosis is strongly correlated with
socioeconomic status (102) and environmental humidity. However, the proportion
of human infections that derive from these different routes of transmission is
not known. Transplantation of infected organs can also result in fatal infection
as a consequence of immunosuppressive treatment.
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3.2.2.2 Cryptosporidiosis
Awareness of Cryptosporidium as a human pathogen began in the early period of
the AIDS epidemic, when severe persisting watery diarrhoea was identified as a
common concomitant of HIV infection in developed and developing countries
(103). There are now 18 species and 40 genotypes of Cryptosporidium recognized,
with nine species and two genotypes associated with human infection (104).
These species and genotypes are adapted to different hosts, and each species
has a variable host range. Cryptosporidium hominis is generally non-zoonotic,
i.e. humans acquire infection from other humans, whereas the primary source
of C. parvum infection in humans is zoonotic. Ruminants are the host species,
primarily young bovines, although the parasite can subsequently be directly
propagated within a human community. Consequently, data from developed
countries show that C. parvum is most commonly isolated from sporadic
human cases originating in rural areas, whereas C. hominis predominates in
urban settings (105, 106). The best evidence for the zoonotic transmission
of C. parvum comes from studies of infections among children at a farm day
camp, middle- and high-school students in an educational farm programme, and
veterinary students in contact with infected bovines (107–110).
The advent of highly active antiretroviral therapy (HAART) for HIV
patients and the ability to repair immune deficiencies has changed outcomes
in such patients (111). However, as more investigators searched for evidence of
Cryptosporidium infection in non-AIDS patients with diarrhoea, it became clear
that many self-limited episodes occur in individuals with a normal immune
system, especially young children (112). The remarkably low infectious dose, and
the importance of person-to-person direct transmission has been documented in a
human volunteer study (113), which found that 18 of 29 normal Cryptosporidium-
seronegative human adult volunteers became infected and excreted the organism
after ingestion of a mean infective dose of just 132 C. parvum oocysts. Of these
18 volunteers, 11 were symptomatic and 7 developed diarrhoea. All participants
WHO Technical Report Series, No. 971, 2012

recovered with a mean duration of symptoms of 74 hours (108). The difference

between self-limited diarrhoea in immunocompetent individuals and chronic
diarrhoea in AIDS patients is highlighted by the outcome of a massive waterborne
outbreak of infection in Milwaukee, Wisconsin, USA in 1993, when an estimated
403,000 individuals were infected (114). When the infection was stratified by HIV
status, it was clear that HIV-positive individuals experienced longer-lasting and
more severe symptoms and they were more likely to be hospitalized (115). Out of
209 children with diarrhoea who had appropriate stool examinations during the
outbreak, 49 (23%) were confirmed to be infected with Cryptosporidium. These
children were more likely to have had an underlying disease that altered their
immune status, and the clinical illness was more prolonged and associated with
weight loss and abdominal cramps compared with Cryptosporidium-negative
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children. Epidemiological data from both adults and children strongly suggest that
effective HAART therapy in AIDS patients ameliorates clinical cryptosporidiosis
as host immunocompetence is restored (116). The estimated cost of the illnesses
associated with the Milwaukee outbreak was over US$ 96 million, including
US$ 31.7 million in medical costs and US$ 64.6 million in productivity losses
(117). The implications of these data for the setting in developing countries
are obvious: 1) the size of the ruminant host population for C. parvum; 2) the
close interactions between people and livestock in rural settings, and the small
infectious dose; 3) the consequences of oocyst contamination of drinking-
water; 4) the susceptibility of young or immunocompromised individuals; 5) the
relevance of common risk reduction strategies for this and other zoonotic and
marginalized infections through improved water safety and hygienic practices.
In the USA, the most recent period of surveillance indicates a confirmed
infection rate of approximately 4/100 000 person-years (118). Infants and
children in group settings in which personal hygiene is difficult to maintain
are at higher risk of infection through direct person-to-person or person-to-
food/water-to-person transmission. In developing countries, the prevalence
is particularly high in children aged 6−36 months, associated with both
malnutrition and/or HIV infection (119). In Guinea-Bissau, West Africa,
nearly 8% of diarrhoeal stools from children were positive for Cryptosporidium
(120) and, by the age of two, 45% of children had been infected (121). In such
settings, infection is commonly associated with persistent diarrhoea, and
multiple species of the parasite may be involved, although the vast majority of
infections are due to C. hominis (87%) and C. parvum (9%) (122). Diarrhoeal
stools from 848 children under 5 years of age in urban and rural hospital
settings in Malawi were examined for Cryptosporidium oocysts (123). Of the
50 oocyst-positive samples, 43 could be amplified by PCR restriction fragment
length polymorphism. On the basis of this analysis, samples from children in
rural areas showed a wider species range than samples from children in urban
areas, suggesting the importance of zoonotic transmission in rural settings.
Diagnosis of cryptosporidiosis, especially in developing countries,
depends primarily on simple differential staining techniques and microscopy,
although sensitive and specific immunological and nucleic acid-based
diagnostics are available but are costly (124). An advantage of microscopy for
Cryptosporidium is that other infections (e.g. helminth ova) can also be detected
during microscopic examination. On the other hand, with a single specimen
examined by microscopy it is easy to miss the diagnosis, since the number of
oocysts excreted can vary during the course of symptomatic infection and at
times may be below the detectable limits (125). There is little doubt that new
sensitive, specific and inexpensive tests would be useful, particularly if they
could distinguish between C. hominis and C. parvum, thus suggesting likely
transmission routes to investigate.
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Prevention and treatment of cryptosporidiosis are problematic.

Maintaining personal hygiene for infants and toddlers is difficult. Infected
individuals may continue to pass oocysts for several weeks after a clinical
infection (125). Similarly, it can be difficult to prevent contamination of water
sources by animals. Drug treatment has been disappointing (126). The one drug
licensed to treat cryptosporidiosis in non-immunocompromised individuals,
nitazoxanide, may shorten the course and duration of excretion of oocysts.
However, it is of limited value in self-limiting infection in immunocompetent
individuals and less effective in chronic infection in the immunocompromised.
Indeed, a controlled trial in children with AIDS in Zambia demonstrated no
efficacy of the drug, and the authors concluded that the drug could not be
recommended for treatment of cryptosporidiosis in Zambian children with
AIDS (129).
There are economic consequences of Cryptosporidium infection in cattle,
primarily related to the costs of care of animals with diarrhoea and dehydration,
slower growth, and some associated mortality (128). Although a number of
investigators believe there is a significant economic cost of cryptosporidiosis
in calves (129), it is difficult to find quantitative data, especially in developing
country settings. Without these data, strategies to prevent or treat bovine
infections may be less appealing to producers, particularly small-scale farms, than
a strategy to prevent or mitigate infection in humans. This is primarily through
better agricultural practices to limit spread of oocysts in water or food crops
grown near cattle or dairy herds, or through effective filtration of drinking-water.

3.2.3 Bacterial infections

3.2.3.1 Brucellosis
Brucellosis is a bacterial zoonosis, caused by intracellular bacteria of the genus
Brucella (130). The genus includes six species producing disease in terrestrial
animals, with Brucella melitensis, Brucella abortus and Brucella suis being the
WHO Technical Report Series, No. 971, 2012

most pathogenic species. These bacteria infect a variety of domestic livestock

such as goats, cattle, camels, sheep and pigs. Brucella is a major cause of zoonotic
infections and therefore is of serious public health importance, particularly in
low-income countries where intervention strategies are almost non-existent
(130). Brucella infections are also widespread in wild mammals, including marine
mammals (131). Thus, the impact and distribution of this disease in wild animal
populations deserves attention. In the animal primary host, brucellosis induces
abortions and genital infections, which are the major sources of economic losses.
Humans are usually infected through consumption of non-pasteurized
dairy products and close-contact manipulation of infected animals. Human
brucellosis is a severely debilitating disease characterized by persistent waves
of fever (and therefore known as undulant fever) and a suite of nonspecific
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 Burden of disease

manifestations such as headache, malaise, back pain, myalgia and generalized

aches. Splenomegaly, hepatomegaly, coughing and pleuritic chest pain are
sometimes seen (132). Gastrointestinal symptoms, including anorexia, nausea,
vomiting, diarrhoea and constipation, occur frequently in adults but less often
in children. If not treated, the infection can progress to granulomatous hepatitis,
uveitis, meningitis, endocarditis or other manifestations. The nonspecific
clinical presentation of Brucella infections results in widespread misdiagnosis
and underreporting of the condition, particularly in malaria-endemic areas,
where fevers are often assumed to be malaria (133, 134). These problems are
compounded by lack of sufficient knowledge about the disease among health staff
(135), the variable performance of serological diagnostic tests (136), and delays
in health-seeking behaviour (137).
It is likely that the incidence of human disease varies considerably in
different communities, in line with the wide geographical variation in livestock
seroprevalence patterns in different agro-ecological settings (138). However,
there is no doubt that, in many areas, the disease burden is likely to be substantial.
Results from a population-based study in rural areas of the United Republic of
Tanzania indicated that 13% of people sampled in pastoral communities were
seropositive, with 43% of seropositive individuals showing at least two clinical
symptoms consistent with brucellosis (139). Although brucellosis has been
eliminated from several countries, largely as a result of test-and-slaughter
and vaccination programmes in livestock populations, the disease remains
widespread and poses public health threats throughout Africa, South America,
Asia and parts of Europe.

3.2.3.2 Enteric infections

Enteric infections are among the most common afflictions of humans. They
contribute to a high proportion of deaths in low- and middle-income countries
in all regions of the world (Figures 2 and 3). Most individuals will have an
episode of watery diarrhoea (defined as three or more liquid non-bloody stools
per day for an individual older than 3 months and five or more liquid stools for a
breastfeeding infant under 3 months of age) at least once or, more likely, several
times a year. Complicating etiological diagnosis is the fact that there are multiple
bacterial and viral pathogens, protozoa (especially Cryptosporidium hominis or
parvum, Giardia intestinalis and Balantidium coli), and intestinal helminths that
also cause occasional diarrhoea in humans. The vast majority of these episodes are
mild, self-limiting and more a nuisance than a significant illness. In developing
countries it is quite different, as the lack of safe water and effective sanitation
and household hygiene contribute to multiple episodes of more severe illness,
especially in young children. Watery diarrhoea, associated with losses of 10% or
more of body water and electrolytes, results in severe dehydration, hypotension
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

and life-threatening circulatory collapse. Vibrio cholerae and enterotoxigenic

or enteropathogenic Escherichia coli (ETEC or EPEC) are frequent causes of
dehydrating diarrhoea in children under 5 years, while cholera and ETEC
are major pathogens in those older than 5, including adults (140). In young
children, some 5−10% of watery diarrhoea episodes persist beyond 14 days.
These illnesses are associated with significant malabsorption and malnutrition,
are disproportionately associated with a fatal outcome, and require particular
attention to nutritional interventions, and for these reasons should be separately
classified as persistent diarrhoea (141).
In addition to dehydrating diarrhoea and persistent diarrhoea, however,
other enteric pathogens exhibit distinctive pathogenic mechanisms resulting
in marked inflammatory responses in the intestinal mucosa. This results in
mucosal ulcerations due to intestinal epithelial cell death which leads to bloody
diarrhoea or dysentery. The latter is a more clinically severe syndrome defined
by the triad of a characteristic small-volume bloody stool with leukocytes and
mucus, abdominal cramps, and tenesmus, a worsening of abdominal symptoms
with the urge to pass stools. The commonest cause of inflammatory diarrhoea
or dysentery is the genus Shigella, the cause of shigellosis or bacillary dysentery.
These bacteria invade the mucosa and initiate pro-inflammatory cytokine
responses with profound metabolic effects. These include anorexia and reduced
intake of food, losses of carbohydrate stores, minerals and micronutrients,
protein-losing enteropathy due to losses of serum proteins across the damaged
mucosa into the gut lumen, catabolism of muscle protein, and changes in
priorities for hepatic protein synthesis from albumin to acute-phase proteins
modulating host defence responses (142). These effects last far beyond the
period of acute clinical illness, and account for ongoing loss of lean body mass
during convalescence (143). When additional infections of any nature (enteric,
respiratory or systemic viral or bacterial infections) occur in rapid succession
(especially when accompanied by fever, which exacerbates catabolic losses) and
WHO Technical Report Series, No. 971, 2012

before nutritional deficits can be restored, a progressive decline in nutritional

status is initiated, leading ultimately to severe protein-energy malnutrition.
Without appropriate nutritional interventions, death is a frequent outcome.
Unfortunately, this is a common scenario among children under 5 years of age
in developing countries, as one infection follows another, each resulting in some
loss of nutrient stores, without the possibility to correct the loss before the next
infection occurs (144). For this reason malnutrition is associated with more
than half of childhood deaths, and is a major risk factor even when a specific
terminal illness is identified (57). Because enteric infections are such important
contributors to progressive nutritional decline, they are frequent antecedent
causes of death, regardless of the terminal event.
The delayed effects of enteric diseases, especially inflammatory diarrhoea,
can easily be underestimated in assigning causes of death, and therefore their
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 Burden of disease

impact is generally far greater than usually believed. Recent studies of inpatient
deaths indicate that use of standard anthropometric methods to assess overall
nutritional status underestimates the effect of malnutrition (145). Such studies
show that the attributable fractional risk of death due to malnutrition exceeds
50%. The original characterization of the interaction of malnutrition and
infectious diseases as synergistic (146) remains an operationally valid way to
consider the relationship. Unfortunately, prospects are not encouraging, since
population increase in many developing countries continues unabated, and the
effects of climate change and severe weather events are becoming more common,
with potential serious effects on soil quality, food supply and nutritional status.
All this undermines efforts to diminish poverty and improve nutrition and
general health status. Food insecurity is a major ongoing global crisis.
Current estimates suggest that overall mortality due to all enteric
infections in infants and children under 5 years of age is around 1.9 million
deaths per year (147), second only to acute pneumonia as a cause of death among
this age group. This estimate is derived from analysis of published reports,
mostly from facility-based studies, rather than the community. The proportion
of under-5 deaths due to diarrhoeal disease is highest in the South-East Asia and
Africa Regions of WHO (Figures 2 and 3).

Figure 2
Distribution of deaths due to diarrhoea in low- and middle-income countries
in five WHO regions

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WHO Technical Report Series, No. 971, 2012

Figure 3
Worldwide distribution of deaths caused by diarrhea in children under 5 years of age in 2000 (148)
Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Copyright © 2008, The American Society for Clinical Investigation

 Burden of disease

The reports on which these analyses are based, in general, provide no

specific information on the prevalence of watery, inflammatory or persistent
diarrhoea, and little if any information on the specific etiological causes. As
many as 25% of these deaths are thought to be due to rotavirus infection, which
occurs primarily in infants under 2 years of age, who are highly vulnerable to
rapid dehydration. A considerable but uncertain proportion of the remainder
are likely to be due to Shigella infection, which is not particularly mitigated by
effective rehydration interventions. A previous estimate of 1.1 million deaths/
year due to Shigella species (149) is now considered to be excessive, but no
better or more recent estimates are available. Persistent diarrhoea is a distinctive
syndrome, may occur in 5−15% of episodes in vulnerable populations, and is
associated with ongoing malabsorption and malnutrition rather than rapid
dehydration. Persistent diarrhoea has a higher case-fatality rate than acute
watery or inflammatory diarrhoea, and may account for as much as 30−50% of
diarrhoeal disease deaths (141).
Nonetheless, estimated mortality due to enteric infections in young
children has progressively decreased over the past 30 years. During this time
the number of children under 5 at risk in the world has increased several-fold
(140). This is a remarkable achievement, much of which can be attributed to
the success of oral rehydration to correct severe dehydration, to recognition of
persistent diarrhoea as a problem, to improvements in nutritional status through
programmes for nutritional rehabilitation and micronutrient supplements, and
to a lesser extent to the use of antibiotics to treat bloody diarrhoea and dysentery.
There are several caveats in interpreting these data. Firstly, there is only
limited information on the prevalence of inflammatory diarrhoea and dysentery.
Secondly, (in contrast to the ongoing effectiveness of oral rehydration therapy),
sustaining the impact of antibiotics for bloody diarrhoea and dysentery is a
serious concern. This is due to the continuing selection and spread of bacterial
resistance to the readily available, oral, safe and effective drugs. Thirdly, nutritional
status and access to care have improved in some parts of the developing world
and they are likely to be favourably affecting outcomes of diarrhoeal disease.
Fourthly, increasing numbers of HIV/AIDS patients are being treated with
antiretroviral therapy, which will improve the host immune response to infections
and reduce susceptibility to infections for which treatment is of limited benefit,
e.g. cryptosporidiosis. These observations suggest that the causes and responses
to enteric diseases to further reduce the mortality toll are likely to be changing
over time. Finally, there has been no reduction in the incidence of diarrhoea in
children under 5 for the past 30 years, and so any deterioration in health systems,
environmental sanitation or access to safe water, or treatment failures due to
antimicrobial drug resistance, may reverse the current overall favourable trends.
From another perspective, diarrhoeal diseases are estimated to be
responsible for 72.8 million DALYs (4.8% of all DALYs) among all ages and all
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

regions of the world, second only to respiratory diseases as a source of global

DALYs (150–154). The distribution of these DALYs, however, is highly related to
economic status. Among low-income countries, diarrhoeal diseases accounted
for 59.2 million DALYs, whereas there were just over 400 000 DALYs in high-
income countries, and only some 14 000 deaths. It is much more difficult to
assess the incidence of enteric infections. Such calculations are subject to great
variation depending on: 1) the method used and the quality of data collection;
2) the representative nature of the population studied (they are likely to over-
sample health facilities rather than the community and underestimate cases of
mild/moderate diarrhoea); 3) the infrastructure for the supply of clean water,
sanitary disposal of faeces and safe storage of food; 4) the relative prevalence
of specific agents and whether or not they are affected by chlorination or water
filtration; 5) low-inoculum pathogens that can be readily transmitted by person-
to-person contact.
Mortality rates are dependent on the frequency of all infections, as well
as on the availability of health-care facilities and access to treatment, including
rehydration, antibiotics and nutritional rehabilitation services. The difference
between high- and low-income countries is greatest for mortality and least for
incidence, with severe illness and hospitalization somewhere in between. Some
enteric pathogens, such as Vibrio cholerae O1 or O139 and Shigella dysenteriae
Type 1, also have epidemic potential, when the impact on older children and
adults is increased. Global trends for cholera tracked by WHO show a steady
increase in cholera reporting in recent years (155). Thus during the period
2004−2008 a cumulative total of 838 315 cases were reported to WHO, which
is a 24% increase over the 676 651 cases reported during the period 2000−2004.
There was a concomitant 27.5% increase in cholera deaths.
Cholera is still underreported in some regions, particularly in south-east
and central Asia, where inconsistencies in case definitions and lack of a standard
vocabulary hinder case identification. Some countries report only laboratory-
WHO Technical Report Series, No. 971, 2012

confirmed infections, and so there are large numbers of cases consistent with the
WHO standard case definition that, as a result, go unreported. Notification of
cholera also does not include cases labelled as acute watery diarrhoea in Africa
and central and south-east Asia, for which there are many causes and where
microbiological laboratory support is commonly unavailable. An unknown but
substantial proportion of the 500 000−700 000 episodes labelled acute watery
diarrhoea annually are certainly due to V. cholerae. This is supported by a recent
study from India, which substantiates the gross underreporting of cholera due
to incomplete and/or inadequate data collection (156). Over 220 000 cases
were identified by the authors over a 10 year period, which contrasts with the
nearly 38 000 cases reported to WHO during the same time period. In the case
of S. dysenteriae Type 1, carefully collected data from Bangladesh show that
S. dysenteriae Type 1 has virtually disappeared over the past 10 years (Figure 4).
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 Burden of disease

Figure 4
Estimated number of Shigella dysenteriae type 1 isolates, Hospital Surveillance,
Dhaka, 1980–2003

Permission by icddr,b
(From Figure 1: Estimated number of S. Dysenteriae type 1 isolates, Hospital Surveillance, Dhaka, 1980-2003 in
“Increasing Antibiotic Resistance of Shigella species”. Health and Science Bulletin Vol 2, No 1, March 2004)

Similar findings have been reported from Africa, where surveillance is

limited to a small number of facilities with diagnostic capabilities (157). Whether
or not this trend will be sustained cannot be predicted, in part because this
organism has remained in the background for long periods in the past before
suddenly reappearing in explosive and devastating epidemics.
Dehydrating watery diarrhoea outbreaks (e.g. cholera, ETEC) and
dysentery (e.g. S. dysenteriae Type 1) are particular problems in situations of
complex humanitarian disasters and emergencies, whether due to war and
violence or to natural disasters.
Following the devastating earthquake in January 2010 in Haiti, cholera
was reported in October 2010. By the end of 2011, over half a million cases
had occurred, with over 7000 deaths. Currently, some 200 cases a day are being
reported during the dry season, rising 5-fold during the wet season (206).
Refugees from either war and violence or natural disasters are typically gathered
in temporary camps, which are initially chaotic and lack adequate clean water or
facilities for personal hygiene and sanitary disposal of human faeces, or access
to appropriate medical care. Children and even adults are highly susceptible to
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

enteric infections under these circumstances, and history has documented waves
of watery diarrhoea followed by dysentery and malnutrition, with case-fatality
rates as high as 9% (158). In some instances enteric infections have been the
cause of more than 40% of the reported deaths, over 80% of which have occurred
in children under 2, mostly due to cholera and Shigella infection (159).
While cholera and dysentery have historically been associated with
military campaigns (160) and mass migrations, such as the annual pilgrimage to
Mecca (161, 162), attention to safe water supplies and disposal of faeces by the
Kingdom of Saudi Arabia has reduced the frequency of outbreaks in recent years,
although sporadic cases still occur (163). However, pilgrims returning home
can still initiate secondary cholera outbreaks where conditions are conducive to
waterborne spread. Even developed countries continue to report sporadic cases
of cholera acquired, in the case of the USA, through ingestion of contaminated
raw shellfish harvested from the Gulf of Mexico where V. cholerae O1 lives
in its natural coastal water habitat. Outbreak spread is effectively prevented
by access to safe chlorinated water sources and infrastructure for the sanitary
disposal of faeces.
Many of the pathogens involved in zoonotic diarrhoeal disease in
humans colonize the animal host but do not result in disease. Non-typhoidal
Salmonella, E. coli O157:H7, Campylobacter jejuni and Cryptosporidium parvum
are examples. Livestock and poultry populations can frequently be infected
but are uncommonly affected. However, foodborne illness in the USA has
been estimated to cause 76 million new cases per year, resulting in 325 000
hospitalizations and some 5000 deaths (164). A recent report (165) estimates
the cost of these illnesses at US$ 152 billion per year, not including the costs to
industry due to recalls of tainted foods or the impact of consumer avoidance of
consumption of suspect foods. The global cost of emerging epidemic infections,
including SARS, and H5N1 and H1N1 influenza virus, has been estimated
to total around US$ 200 million over the past decade in initiating targeted
WHO Technical Report Series, No. 971, 2012

surveillance, culling animals to stop spread of infection, and trade- and tourism-
related losses (166).

3.2.3.3 Bovine tuberculosis

The disease burden of zoonotic tuberculosis (caused by Mycobacterium bovis)
remains largely unknown, despite widespread recognition of its potential to
contribute to the human tuberculosis epidemic, particularly in the era of HIV/
AIDS (167–172). Problems relate both to laboratory diagnosis, which requires
specialized culture facilities that are rarely available in developing countries, and
to a lack of awareness among clinicians of the potential for species other than
M. tuberculosis to cause tuberculosis in humans. Where efforts have been made
to identify the Mycobacterium species involved in human tuberculosis, M. bovis
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 Burden of disease

has been detected as a cause of both pulmonary and extrapulmonary tuberculosis

in some, but not all, settings. One study has reported the isolation of M. bovis
and M. africanum from 13% of human tuberculosis cases in Nigeria (173). In
rural United Republic of Tanzania, M. bovis was identified in 4% of the culture-
positive pulmonary cases (174) and from 10% of extrapulmonary tuberculosis
human cases (175). It is recognized that care needs to be taken in the assessment
of country situations, as findings may differ significantly between regions and
ethnic groups (171). For example, M. bovis was isolated from 6.9% of tuberculous
patients in a pastoral community in Uganda (176), whereas a study in a different
rural community failed to detect M. bovis from 70 culture-positive cases of
pulmonary tuberculosis, despite a high frequency of raw milk consumption and
high prevalence of infection in cattle in the region (177). In Taiwan, China, only
0.5% of isolates (15 out of 3321 isolates) were characterized as M. bovis, with
almost all (14/15) derived from patients with pulmonary tuberculosis (178).
The disease burden of M. bovis, calculated as DALYs, has been estimated
in United Republic of Tanzania as approximately 1.3% of the total burden of
tuberculosis in the country (179). However, this estimate was based on limited
data and substantial efforts are still needed to provide rigorous estimates of the
burden of disease. Further research is also needed to understand the specific
risk factors for zoonotic transmission, with only limited analysis of risk factors
associated with M. bovis infection in humans carried out in United Republic of
Tanzania (175, 180) and Taiwan, China (178). Many questions remain about
the significance of other non-tuberculous Mycobacterium infections, which
are frequently isolated from both pulmonary and extrapulmonary TB patients.
For example, non-tuberculous Mycobacterium species were isolated from
50% of culture-positive cervical lymphadenitis cases in rural communities of
both United Republic of Tanzania (175) and Uganda (176) and from 25% of
mycobacterial lymphadenitis cases in children in India (181). Despite evidence
that non-tuberculous Mycobacterium may be posing a substantial, and growing,
threat to human health, virtually nothing is known about these infections in
terms of burden of disease, transmission routes, risk factors and implications for
treatment outcomes.

3.2.3.4 Anthrax
Anthrax is caused by Bacillus anthracis and is endemic in herbivorous animals in
the tropics. The bacterium lives in soil and is ingested while animals are feeding
or by exposure to heat-and desiccation-resistant spores, which can live for
decades in the environment, by entry of spores through the skin, by inhalation
or by consumption of contaminated meat. The treatment of patients is based
on the use of high-dose antibiotics, i.e. penicillins or cotrimoxazole. Although
anthrax has been ranked as a high-priority disease in terms of animal health and
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

poverty (182), little information is available about the true scale of the human
disease problem. Hospital data from Africa are largely restricted to information
on cutaneous anthrax, presumably because acute infections causing pulmonary
or gastrointestinal anthrax have high case-fatality rates and victims invariably
die at home before being able to reach hospital. Research on human anthrax
needs to address several major data gaps with studies generating information on:
(1) the incidence of human disease and deaths (for cutaneous, pulmonary and
gastrointestinal forms of the disease); (2) the DALY and economic burden; (3) risk
factors for infection and different forms of the disease; (4) the development of
appropriate methods for diagnosis and surveillance. Preliminary data from United
Republic of Tanzania indicate high anthrax seroprevalence levels in domestic
dogs in anthrax-affected areas, suggesting that dogs may have utility as proxy or
sentinel populations for disease surveillance where disease reporting is lacking,
and may be used to examine environmental risk factors for infection.

3.2.4 Viral infections

3.2.4.1 Rabies
Rabies is a viral disease that is almost always fatal within a few days once clinical
signs occur. The virus belongs to the genus Lyssavirus. Although rabies circulates
in a number of domestic and wild carnivore and bat species, infection cycles
are maintained by distinct species in different geographical areas (e.g. dogs in
much of Africa and Asia; raccoons in the eastern USA; foxes in eastern Europe;
yellow mongooses in South Africa). Infection of humans follows bites by rabid
animals. More than 90% of all human rabies cases result from contacts with
dogs in the developing world. Suspicion of infection in humans and animals
is based on symptoms and signs, supported by epizootiological information.
A confirmed diagnosis is made using standard laboratory tests carried out on
tissues, mostly of nervous system origin and usually collected post mortem.
Rabies has a wide geographical distribution and is present on all continents
WHO Technical Report Series, No. 971, 2012

except Antarctica. A number of countries (mainly islands and peninsulas,

for example in the Caribbean, the Pacific Ocean and the Mediterranean) are,
however, recognized as free of the disease. Canine rabies is present in most
of Africa, Central and South America and Asia, where the highest burden of
human rabies is found. Rabies in dogs poses a threat to more than 3.3 billion
people. It is estimated that 55 000 people die from dog-mediated rabies annually
in Africa and Asia (13).
Where rabies is a public health problem, prevention of the disease in
humans depends on a combination of interventions, including control of rabies
in the animal reservoir, primarily the domestic dog in countries where the vast
majority of human deaths still occur. Additional measures include pre-exposure
immunization of humans at occupational risk of contracting the disease and on
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 Burden of disease

the speedy delivery of post-exposure prophylaxis (PEP) to potentially exposed

patients (183). Theoretical and empirical studies suggest that the immunization
of 70% of the dog population is effective in preventing rabies outbreaks in
populations at risk (184–186). The key to the success of vaccination programmes
is knowledge of the ecology of the dog population and the nature of human/dog
interactions in the area.
To date, only a few studies of human disease incidence are available
for developing countries (34, 187), and widely cited figures for human rabies
mortality and DALY burden in Africa and Asia have relied upon estimates
generated from the incidence of animal-bite injuries and rates of post-exposure
vaccination (13). These estimates suggest that 1.8 million DALYs are attributable
to rabies, although, with the rapid growth of dog populations in Africa and Asia,
and an increasing incidence of dog rabies in many countries, revised estimates
are likely to indicate a major increase in the DALY burden.
Rabies is predominantly a disease of children, with children between 5
and 15 years at highest risk. This is because children are more often bitten than
adults and, when bitten, are more likely to incur injuries in high-risk sites on the
body, such as the head and neck.
National rabies control programmes based on mass immunization of
dogs initiated in 1983 in Latin American countries have achieved considerable
success, with human and dog rabies now eliminated from Argentina and Chile
and from major urban centres of other Latin American countries. In 20 years of
PAHO-coordinated activities, dog-transmitted human rabies cases have fallen by
more than 90% (188), although high-risk foci still remain. For example, cases
of rabies transmitted from vampire bats appear to be increasing in some areas,
which has been attributed to environmental disturbance, migration and limited
access to health care in remote regions.

45
4. Intervention-oriented research issues
4.1 Community-led or community-directed interventions
The Alma Ata Declaration in 1978, which promoted health for all and equity
through the institutionalization of primary health care paved the way for
people’s participation in health care, planning and implementation. It called on
all governments, international organizations and the global community to come
together to provide the necessary health and social support to enable people to
attain a level of health by the year 2000 that would allow them to lead a socially
and economically productive life.
Although the Alma Ata Declaration was unable to meet its promise of
attaining “health for all” by the beginning of the 21st century, it has spawned some
models of community participation in making health products, technologies
and services accessible, especially to the poorest populations in many developing
countries. For example, the World Bank and WHO launched the African
Programme for Onchocerciasis Control (APOC) in 1995 with the aim of
establishing a sustainable community-directed delivery system of ivermectin to
control human onchocerciasis (river blindness) in endemic African countries by
providing millions of annual treatments. The programme utilizes the community-
directed treatment approach, which is a sustainable and cost-effective mass drug
administration for distributing donated ivermectin to treat onchocerciasis in
areas of high and medium endemicity. This approach empowers families and
communities, instead of the health services, to assume responsibility for obtaining
and distributing drugs in their village/community settings. Local communities
decide together how they will collect the tablets from the supply sources, when
and how the drug will be distributed, who assumes responsibility for distribution
and record-keeping, and how the whole process is monitored.
It is estimated that APOC saved 3 million DALYs between 1996
and 2005, and, with a free supply of ivermectin, this gives an estimated 17%
economic rate of return on the cost of treatment delivery (189). The Programme
has also yielded other indirect benefits, which include improved overall health
in communities, deworming (an ancillary benefit of ivermectin), and improved
school attendance and food production. APOC was found to be effective not
only in controlling onchocerciasis but also in the implementation of other health
programmes particularly for malaria, tuberculosis, vaccination and micronutrient
deficiencies (190). A recent multicountry study demonstrates the value of
the community-directed approach in delivering other health interventions,
particularly in increasing bednet uptake and home-based management of
malaria (191).
In terms of improved sanitation, a key factor for many zoonotic diseases,
community participation, is essential to achieve sustainable change that will
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

translate into better quality of life and better health status. In low- and middle-
income countries, strategies to improve sanitation range from systematic
approaches, such as the provision of potable water and installation of sewage
systems and indoor plumbing, to more restricted interventions, such as the
installation of community water wells and household latrines or toilets. The latter
is a widespread intervention that has met varying degrees of success, as in many
instances, the presence of latrines or toilets alone does not secure better family
and/or environmental hygiene (192, 193). Indeed, these studies showed that
to have a positive impact in the prevention of diarrhoeal diseases in children,
water supplies and sanitation needed to be accompanied by changes in domestic
hygienic behaviour (192). Similarly, it was shown that there was a significant
association between hygienic behaviour and the presence of adequate household
excreta disposal facilities, thus demonstrating the synergistic effect of the two
factors (193). More recently, however, a report from Brazil demonstrated that,
socioeconomic factors, rather than the presence of water and sanitation, were
associated with a large proportion of the diarrhoea burden in children under
10 years of age (194). These investigators pointed to the changing epidemiology
of diarrhoea in the city of Salvador, where the expansion of the sanitation
network and other efforts make it hard to pinpoint specific risk factors for
diarrhoea such as deficient water and sanitation systems (194, 195). A recent
analysis of the literature shows that hand-washing with soap, improved water
quality and improved excreta disposal reduce the diarrhoea risk by 48%, 17%
and 36%, respectively (196). In view of this evidence, in resource-poor settings,
where access to water is minimal, immediate efforts to reduce diarrhoea should
focus on environmental sanitation and the elimination of open defecation. This
can be achieved with full community participation through the utilization of
various participatory methodologies. One strategy that focuses on this is known
as Community-led Total Sanitation, which is discussed below.

Community-led Total Sanitation

WHO Technical Report Series, No. 971, 2012

4.1.1
Nearly 2.6 billion people have no access to adequate sanitation and instead are
culturally habituated to defecate in the open. This massive faecal contamination
of the environment leads to unsafe drinking-water and, compounded by a lack
of access to health care, a serious risk to health. As a direct consequence, one
child dies every 15 seconds from diarrhoeal disease transmitted through faecal
contamination of the environment, water or food. Billions of dollars are being
spent on construction of latrines, providing safe water and teaching hygiene to
local communities. Unfortunately, these efforts often fail to produce any significant
or sustainable improvement of sanitation or any reduction in diarrhoeal disease
morbidity and mortality.
In recent years the development and scaling-up of a movement to create
local community action to improve environmental sanitation has begun to
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reverse the situation. Termed “Community-led Total Sanitation” (CLTS), the

approach was pioneered in Bangladesh and has subsequently been introduced
in 34 other countries in Africa, Asia and Latin America. Already millions of
people living in rural areas have been able to stop the practice of open defecation
and improve other collective and personal hygiene behaviours. There are two
different approaches, the “Target-driven Partial Sanitation” approach (which
focuses on prescriptive technology, introduced from outside the community,
including educational modules to improve hygienic behaviours) and the CLTS
approach which focuses on local empowerment and capacity-building in order
to motivate a community to achieve and sustain universal use of safe faecal
disposal methods. Such communities are given “open defecation free” (ODF)
status (197). The CLTS methodology facilitates the capacity of a community
to analyse its sanitation profile and practices of defecation, and to consider the
health consequences. It is oriented towards voluntary commitments to collective
action to become ODF (197). Stopping open defecation is the starting point to
sustainable hygiene and behaviour change, and can be followed up with measures
to improve sanitation system hardware and the environment, while creating
opportunities for livelihoods involved in sustaining these changes. CLTS never
teaches, prescribes technologies or subsidizes sanitation hardware. It only engages
local communities in collectively analysing their sanitation profile, identifying
the problems and taking the necessary decisions to act.

4.1.2 CLTS and zoonotic diseases

Many of the zoonotic diseases are transmitted from vertebrate animals to
humans, humans to humans, or even humans to animals via soil and water
contaminated with faeces from infected individuals. Although there is no
systematic research thus far to assess the impact of CLTS and ODF status of
communities on the incidence and prevalence of these infections, there is every
reason to believe that a cleaner environment will reduce transmission of these
infections, as well as bacterial and viral diarrhoeal infections, parasitic zoonoses
and soil-transmitted helminths. Because of the persistence of infectious forms
of some zoonotic infections and the soil-transmitted helminths, the most
immediate effects are likely to be on the frequency of diarrhoeal disease. Initial
assessments of community acceptance have been conducted by the Institute for
Development Studies at the University of Sussex (Chambers R. Going to scale
with community-led total sanitation: reflections on experience, issues and ways
forward (IDS Practice Paper 1) 1.

1
http://www.communityledtotalsanitation.org/sites/communityledtotalsanitation.org/files/Chambers_
Going%20to%20Scale%20with%20CLTS.pdf
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This summarizes the methods and challenges of implementing CLTS

in six countries. The present strategies of tackling zoonotic diseases focus on
either treating infected humans or targeting animals by segregating/treating/
vaccinating them. These approaches are often disease-specific, and reductions
in prevalence or incidence are costly and logistically difficult to sustain. Fresh
faecal contamination and continued transmission always takes place unless the
basic hygiene behaviour is changed. Although the polio vaccine eradication
programme, which relies entirely on vaccine delivery, has been highly successful,
the results could have been enhanced by triggering CLTS in communities and
encouraging them to become ODF to reduce the continued introduction of wild
polio virus into the environment. Similarly, a transmission dynamics model of
cysticercosis suggested that improved sanitation and restricting access of pigs
to human faeces would be a more sustainable approach than pig vaccination and
treatment combined with human treatment (56).
It remains to be evaluated whether the reduction in worm loads of
helminthic infections associated with oral-faecal transmission can be achieved
through cessation of open defecation and also have a definitive impact on
the transmission of diarrhoeal disease agents. These potential impacts are
summarized in Figures 5 and 6. Such evaluations should include villages that
have achieved ODF status and those that are still moving towards 100% ODF.
Full community sanitation of human faeces may not eliminate all infections,
as animals closely associated with households may continue to be the source
of human infection. However, the change in behaviour in ODF villages may
energize other hygienic practices, including hand-washing and protection of
household drinking-water and cooking water from contamination. Moreover,
even during the time before conclusive evidence is obtained about the health
impact of sanitation (196), activities to expand the CLTS approach should be
continued. It is clear that environmental interventions can have a substantial
WHO Technical Report Series, No. 971, 2012

effect on diarrhoea morbidity and mortality as well as other important benefits,

including the enhancement of human dignity (196, 198).
For rural communities that use human excreta as manure for agriculture,
it is important to include an assessment of the dangers such practices represent,
and at what stages of Eco-San (Ecological Sanitation) the manure could efficiently
and safely be used.
CLTS has already had a profound effect on many communities in
over 30 countries across three continents, enabling many millions of people
in local communities to construct affordable toilets (Figure 6). In particular, it
has reached the poorest families and communities, many of whom depend on
livestock for their livelihoods and have little or no access to safe water or basic
sanitation and health services. It fosters privacy and convenience especially for
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Figure 5
Some of the major economic, health and social impacts of Community-led
Total Sanitation

menstruating and pregnant women and among those in purdah. Furthermore,

it can be quickly mainstreamed or scaled up by the government health systems
in countries. Often the communities that achieve ODF status continue to
develop other initiatives, as natural leaders emerge to solve other problems of
rural communities. A similar experience has been seen in the onchocerciasis
programme in Africa where additional health interventions are added to the
ivermectin distribution package (190). Such approaches could include achieving
“hunger-free status”, thereby enhancing food security by eliminating seasonal
hunger from the entire community, and ensuring improved school attendance
with ensuing educational benefits, particularly for females.
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WHO Technical Report Series, No. 971, 2012

Figure 6
Potential positive impacts of Community-led Total Sanitation on human health and possible impacts on diseases of the poor
including zoonoses
Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group
 Intervention-oriented research issues

Previous vertical programmes to address diarrhoeal diseases have

given way to the Integrated Management of Childhood Illness (IMCI). This
includes broad messages on basic nutrition and micronutrient intervention
programmes, administration of the routine vaccines included in the Expanded
Programme on Immunization, and case management for acute respiratory
and diarrhoeal diseases and malaria. Community-level water and sanitation
interventions, as well as the necessary research investments in technology,
community engagement, and behavioural change, remain relatively neglected
and significantly associated with poverty.
Table 5 emphasizes the similarities and differences between three
community-led or community-directed initiatives, which can be used to develop
implementation research models of direct value to communities afflicted by
zoonotic infections.

4.2 The human/animal interface: “One Health” as a concept

While recognizing that existing approaches to the control of and research into
zoonotic diseases will continue to benefit from their current vertical or horizontal
structure, there is growing evidence for the benefits of a joint human and animal
health approach. The “One Health” concept, which involves a greater degree of
integration of human and animal health resources, should be promoted, because
many zoonoses can be better surveyed, diagnosed and controlled by considering
human and animal health together. Such an approach would greatly facilitate
detecting and addressing zoonoses. It would also ensure better access to health
inputs for poor people and recognize the needs of their livestock. Encouraging
cost-sharing in proportion to the benefits gained by each sector could be an
enabling component of a “One Health” approach.
There is a need to generate data on the societal and economic impact
of zoonotic diseases. This will require addressing the quantification of human
morbidity and mortality (DALYs), impacts on livestock production, consequences
for livestock trade (condemnation of carcasses), impacts on wildlife production
and biodiversity, and social impacts (e.g. social stigma, fear) in a comprehensive
way using examples such as cysticercosis, echinococcosis, brucellosis and rabies.
An additional component of animal diseases is the requirement to
identify and quantify the component of the burden of disease due to the potential
contribution of zoonotic diseases to non-communicable disease burdens. This is
related in particular to neurological disorders, liver disease, cancer and injuries
using case-studies of cysticercosis (epilepsy and headaches), echinococcosis
and schistosomiasis (liver disease), foodborne trematodes (biliary and hepatic
cancer), toxoplasmosis (schizophrenia, congenital/fetal abnormalities) and rabies
(injuries).
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Table 5
Comparative analysis of operational community-based interventions on health

Criteria Community-led Community-directed Community-based

Total Sanitation Intervention (CDI) Initiatives (CBI)
(CLTS) (ivermectin/albendazole)
Year of innovation Year of innovation Year of innovation
1999-2000 1995 1988
Global spread so far 34 countries across south and south- 25 African countries 17 countries in Eastern
east Asia, Eastern Mediterranean Mediterranean Region
countries, eastern, southern, central (EMRO)
and western Africa and Latin America
Adopted in the National at least five countries have adopted approach adopted as in the areas implementing
Sanitation strategy of CLTS approach in their national implementation platform in the initiatives in EMRO
the governments of sanitation strategy (Indonesia, endemic areas of onchocerciasis region
countries Ethiopia, Sierra Leone, Zambia, Eritrea) and lymphatic filariasis
Rough estimate of difficult to access but at least more 75 million for onchocerciasis 18 million (about 5% of
number of people than 10 million in Africa, and 80 million for the total population of the
benefitted lymphatic filariasis in Africa region)
Perceived benefits sharp decline in household medical improved well-being, both improved essential health
expenses mainly through reduction in physical and mental, and indicators
the incidences of diarrhoea, dysentery, improved nutritional status
cholera and typhoid
Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Disease-specific sharp reduction in the incidences of reduced blindness, skin disease, decreased infant and child
benefits diarrhoea, dysentery, cholera and intestinal worm load, anaemia mortality
typhoid and frequency of filarial fever
continues
 Table 5 continued
Criteria Community-led Community-directed Community-based
Total Sanitation Intervention (CDI) Initiatives (CBI)
(CLTS) (ivermectin/albendazole)
Rural communities their collective desire for hygiene demand for donated efficacious ownership of the
access to interventions behaviour change, starting with products driven by community community of the
depends on: stopping open defecation ownership interventions
Outsider’s role /Donor/ facilitators of a process of donor support for APOC; facilitators for creating
NGDO empowerment and change facilitators for creating awareness and process of
awareness and process of empowerment
empowerment
Insider’s role active analysis of their own sanitation realization of the need for taking active role in
situation, planner and implementer community distributor as leader managing integrated
of CLTS to achieving ODF status as of the process development
soon as possible
Expected early “open defecation free” communities community-managed drug functional community
outcome distribution system working leadership
Time needed to get the anything between 1 and 2 weeks to rapid impact of drug on skin about a year
first outcome 3 months depending on the size of itching and de-worming
community and other factors
Inputs supplied by hands-off facilitation only donated drugs, training and interest-free
outsiders Training by NGDOs partners loan
Prescriptions of nil at the outset; only on training, evaluation and CBI guidelines
technology or practice demand later reporting of coverage
Intervention-oriented research issues

continues

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WHO Technical Report Series, No. 971, 2012

Table 5 continued
Criteria Community-led Community-directed Community-based
Total Sanitation Intervention (CDI) Initiatives (CBI)
(CLTS) (ivermectin/albendazole)
Sustainability depends insiders; their collective desire for perceived value of drugs on the community
largely on: maintaining ODF status
Spread and scaling up self-spread to neighbouring advocacy at all levels; national self-spread to neighbouring
by: communities; natural Leaders and NGDO commitment villages and NGO staff
emerging from ODF villages, NGOs,
government field extension staff
Informal indicators reduction in the population of demand for continued annual
of change from flies and mosquitoes, sharp fall in drug distribution; continued
community perceptions the number of diarrhoea patients high coverage at epidemiological
visiting village doctors and health level necessary
centres, rise in the sale of sanitation
hardware in village and nearby
markets,
Social solidarity better-off members of the CDD selected by community as very high
community contribute voluntarily leaders;
to the poor to achieve ODF status,
which is a ‘public good’ and not a
‘private good’
Cost of implementation low to very low costs borne by community; relatively low
Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

principle of no remuneration
continues
 Table 5 continued
Criteria Community-led Community-directed Community-based
Total Sanitation Intervention (CDI) Initiatives (CBI)
(CLTS) (ivermectin/albendazole)
Time taken to initiate 3 to 4 hours trigger CLTS in 1-2 days training 1-3 months
the process communities and follow-up until
ODF status is reached
Chances of continuing fairly high as the local communities extensive opportunity for CDDs
with other community initiate actions in other areas of to participate in other health
led initiatives sanitation or livelihood development interventions; upscaling of
bednet uptake; home-based
malaria management
Sustainability index fairly high to medium high to medium; accessed high
through standardized process
Informal indicators reduction in the population of maintenance of commitment to
of change from flies and mosquitoes, sharp fall in collect drugs
community’s the number of diarrhoea patients
perceptions attending health facilities
Intervention-oriented research issues

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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

4.3 Chemotherapy and immunization

4.3.1 Mass chemotherapy (mass-targeted, humans-animals)
In the context of the parasitic and bacterial diseases, chemotherapy plays a
significant role in curative approaches to individual therapy and in some situations
in mass drug administration (MDA; preventive chemotherapy). Whilst these are
well known and there are tested drugs to combat trematode and cestode infections
(praziquantel in particular), there are also definitive needs for improved drugs
or drug combinations, regimens and dosages to improve efficacy or reduce the
risks of transmission. For the treatment of non-zoonotic neglected diseases, the
majority of which are based on donation programmes, WHO has developed a
handbook on preventive chemotherapy (199) recommending the strategies
required in different endemic areas where several infections may be co‑endemic
and where the treatment frequency may vary from annual to semi-annual.
However, this approach has not been applied widely to control zoonotic helminth
infections, although mass distribution of praziquantel has been used in China and
the Philippines for the control of Schistosoma japonicum and successfully for the
elimination of S. mekongi in Cambodia (80). It is also applicable for the control of
the foodborne trematodes (200), specifically for clonorchiasis, opisthorchiasis and
Paragonimus at a single oral dose of 40 mg/kg. These diseases are being targeted
in Lao People’s Democratic Republic and Viet Nam following pilot studies in
2007 (201). The challenge is the high cost of praziquantel, although in recent
years the cost has been driven down considerably and the unit cost per individual
treatment is now around US$ 0.32 (3, 202). An example of the use of the principle
of MDA for a zoonotic disease using a donated product is the distribution of
triclabendazole (donated by Novartis). This drug is used as a curative treatment
and is registered in only four countries: Ecuador, Egypt, France and Venezuela.
The recommended single dose of 10 mg/kg makes this drug useful for the MDA
approach, and mass drug distribution of triclabendazole is currently ongoing
WHO Technical Report Series, No. 971, 2012

in areas of endemic fascioliasis in Bolivia and Peru. The WHO website www.
who.int/neglectedtropicaldiseases provides information on fascioliasis and how
countries may apply for donations of triclabendazole. The WHO policy on the
control foodborne trematodes is summarized in reference 201.
For the treatment of the cystic stages of echinococcosis in humans,
there has been limited progress in improving on the current regimes of long-
term relatively high-dose treatment with albendazole (10 mg/kg per day) or
mebendazole (40 mg/kg per day). These drugs severely damage cysts but are
parasitostatic rather than parasiticidal. Albendazole is the more efficacious due
to its better absorption. A third of cystic echinococcosis patients have been
cured through chemotherapy using benzimidazole drugs and many have seen
cysts reduced in size (203). Long-term use of these drugs also inhibits larval
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development of E. multilocularis and reduces metastasis, thereby enhancing the

survival of patients.
For infections of dogs with adult tapeworms, mass treatment with
praziquantel (5 mg/kg) remains the treatment of choice (204) in combination
with other approaches as applied in successful control campaigns in Cyprus,
Iceland and New Zealand. Hydatid disease represents an excellent example of
successful integrated control to reduce a public health risk. Deworming of the
dog population contributes significantly to that end, especially when linked to
health education, control of offal disposal, carcass condemnation, and other
appropriate slaughter practices.
Chemotherapy has been used in a pilot trial in 12 villages in Peru for
the control of cysticercosis using two rounds of oxfendazole (30 mg/kg) in the
treatment of pigs to kill cysts and praziquantel (5 mg/kg) to target the adult
tapeworms in humans. Previous trials with oxfendazole at lower doses were less
effective in killing cysts and treatment coverage of the human population with
praziquantel was around 75% (54). There was a reduction in both prevalence
and incidence after the treatment, but the parasite was not eliminated and
instead it stabilized at slightly decreased rates. However, a recent study in
Cameroon using the TSOL18 vaccine in pigs and the treatment of pigs with
oxfendazole demonstrated the potential for eliminating the infection by
combined approaches (205). The study in Cameroon did not treat humans with
praziquantel for the adult T. solium but interventions targeted to both pigs and
humans should certainly have an enhanced impact on transmission parameters.

4.3.2 Immunization against rabies

Rabies differs from most other infections in that clinical disease can be
prevented through timely immunization, even after exposure to the infecting
agent. Rabies post-exposure prophylaxis (PEP) consists of local treatment of
the wound, which should be initiated as soon as possible after a bite, followed
by the administration of passive immunization with rabies immune globulin,
if indicated, and a potent and effective rabies vaccine for active immunization.
Widespread immunization of humans following exposure has significantly
reduced the number of human deaths from rabies. More than 10 million people
receive such prophylaxis annually, the majority living in China and India. In
Africa and Asia, the number of PEP regimens delivered is estimated to prevent
approximately 330 000 deaths (13).
PEP accounts for 80% of the estimated annual cost (US$ 600 million) of
rabies in Africa and Asia. In the most rabies-affected areas, patient-borne costs for
PEP account for nearly half the total costs of rabies treatment. The frequency of
PEP is expected to rise dramatically in all countries with dog rabies, particularly
in countries that are replacing vaccines derived from nervous tissue with the
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

safer and highly potent cell-culture vaccines (13, 33). Preventive immunization is
recommended for anyone at continuous, frequent or increased risk of exposure to
rabies virus, by nature of either their residence or their occupation (e.g. laboratory
workers dealing with RABV and related lyssaviruses, veterinarians, and animal
handlers). Travellers with extensive outdoor exposure in rural high-risk areas,
where immediate access to appropriate medical care may be limited, should also
be vaccinated pre-exposure. Children living in or visiting rabies-affected areas
are at particular risk.

4.4 Vector and intermediate host control

Vector control has played and continues to play a major role in the control of
both endemic diseases (for example, malaria through long-lasting impregnated
nets and indoor residual spraying) and epidemic diseases (e.g. dengue) of poverty
which are transmitted by insects as well as other arthropods (e.g. ticks for
relapsing fever). Snails may be considered the “vectors” for the transmission of
all trematodes. They play the role of obligatory intermediate hosts where complex
life-cycles result in the production of human and animal infective stages.
Historically, there has been recognition that snail control can contribute
to the reduction in exposure and transmission of snail-borne diseases, specifically
schistosomiasis, through chemical use as well as environmental modification
(207). The widespread use of molluscicides has, however, lost favour because of
environmental concerns and the costs and sustainability of the approach as mass
or targeted chemotherapy of the human definitive hosts for schistosomiasis
has been introduced. However, focal mollusciciding may still play role in
particular epidemiological settings, such as the marshlands of southern China
where geospatial methodologies can be used to predict the location of snail
habitats and hotspots of transmission. In Africa where there is limited zoonotic-
associated transmission of schistosomiasis (S. mansoni) there have been
large-scale attempts to control the disease through integrated snail control by
WHO Technical Report Series, No. 971, 2012

environmental management and the use of molluscides, although permanent

reductions in transmission have not been achieved (202).
The Blue Nile Health Project (BNP) in Sudan was initiated in 1979 to
develop better strategies for controlling the major water-associated diseases in
tropical irrigation schemes. It has been estimated that the 10-year programme cost
some US$ 154 million (1978 prices). The Gezira, Managil and Rahad irrigation
systems were selected to represent typical irrigation systems throughout Africa
and the Middle East, where malaria, diarrhoeal diseases and schistosomiasis are
endemic, and as the areas most urgently in need of disease control in Sudan.
In 1986, a study undertaken by the BNP on snail control was applied as part of
a local S. mansoni control programme in a primary health-care setting in the
Dalati and Agallu Metti areas of the Ethiopian Blue Nile Valley. Niclosamide
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was applied focally wherever infected snails were found and the monthly snail
surveillance continued until 1989. As a result, overall snail infection prevalences
were reduced from 11.2% (Dalati) and 32.0% (Agallu Metti) to zero and 2.0%,
respectively. In 1989, the human prevalence of schistosomiasis was only 8.6% in
Agallu Metti. This programme demonstrated that while it is feasible to control
S. mansoni by implementing snail control strategies through the primary
health-care system (208), maintaining the success achieved by large-scale yet
pilot projects and the extension and funding support required for national
programmes have not been forthcoming.
There have been no attempts to initiate snail control for the intermediate
hosts of foodborne trematodes (95). The methods used for control of the water-
associated diseases emphasize that permanent improvements in water supply and
sanitation, in environmental and agricultural practices, in health education and
community participation, and in primary health services can lead to a reduction
in dependence on pesticides and drugs while achieving effective control.

4.5 Vaccination as a control option for zoonotic diseases

Globally, vaccines are considered the “magic bullet” for public health interventions
in the control of infectious diseases, and this has been substantiated by the results
of the WHO Expanded Programme on Immunization.

4.5.1 Animal-targeted immunization

Injectable vaccines for mass immunization of dogs against rabies were used for
the first time in 1921 in Japan (209). Japan still enjoys the rabies-free status it
acquired definitively in 1957. Malaysia initiated a rabies control programme
in 1952 with compulsory vaccination of all dogs and rigorous destruction of
ownerless dogs, which brought rabies under control within a year. During the
second half of the 20th century, only a limited number of countries eliminated
the disease in their dog reservoir using immunization as a main tool. These
countries, in addition to those mentioned above, include Canada and the USA
(in the 1950s), Taiwan, China, and Portugal (1961), Chile (1976) and Uruguay
(1983). In 2009, the Pan American Health Organization/WHO Regional Office
for the Americas initiated a programme for dog rabies control based mainly
on mass immunization of dogs. Mexico, for example, vaccinated more than
10 million dogs a year. Dog rabies has now been eliminated from all major urban
centres in other Latin American countries and accordingly human rabies has
been reduced by more than 90%.
In China the annual number of human rabies deaths was reduced from
3300 in 2007 to about 2400 in 2008. This achievement mainly followed sustained
campaigns for dog immunization and dog population control activities in the
main infected provinces.
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Parenteral vaccination of dogs against rabies is considered the most

effective measure for controlling canine rabies. At least 70% of the dog population
should be vaccinated in areas where canine rabies is endemic. High vaccination
coverage can be achieved through swift campaigns involving intersectoral
cooperation, community participation, involvement of local authorities in
planning and execution, and media support. By the end of 2009, many developing
countries in Africa (e.g. Angola, Morocco, South Africa, Tunisia, and United
Republic of Tanzania) and in Asia (e.g. Indonesia, Philippines, Thailand and
Viet Nam) had stepped up their dog rabies immunization programmes through
vaccination to control dog rabies and thus eliminate human rabies.
North America and Europe independently proposed that mass
immunization of the principal wildlife hosts against rabies might be more
effective than culling. Oral vaccines were included in baits targeting the principal
host species. In the early 1960s foxes in the USA were successfully immunized
orally with live attenuated ERA virus. Other oral rabies vaccines were later
developed, as well as systems for their mass production. The first field experiment
was conducted in Switzerland in 1978 (210); this was followed a few years later
by Germany and Italy, and by other European countries after 1985. Many western
and central European countries that were previously rabies-endemic had been
freed of rabies by 2008 as a result of successful oral vaccination programmes,
e.g. Belgium, Czech Republic, Finland, France, Germany, Luxembourg, the
Netherlands and Switzerland. When applied using the safest vaccine baits, oral
vaccination of dogs (OVD) may increase dog vaccination coverage, particularly
when applied in combination with parenteral vaccination 1. However, OVD has
not yet become an operationalized component of any dog rabies control and
elimination programmes because of concerns over safety for humans and cost
per vaccine bait.
Since Schistosoma japonicum is a zoonotic organism, a transmission-
blocking vaccine for livestock could be implemented in countries where livestock
animals play a major role in human infection (211). Indeed, randomized, double-
WHO Technical Report Series, No. 971, 2012

blind trials in water buffalo, using DNA vaccines encoding S. japonicum antigens,
have taken place in China, resulting in approximately 50% protection (212). As
this exceeds the hypothetical level predicted by mathematical modelling (213) to
reduce transmission significantly, a transmission-blocking vaccine could well be
available and on the market within the next few years.
The recent landmark publication of the S. mansoni and S. japonicum
genomes (214, 215) takes us a step closer to the identification of further key
protective epitopes and the development and implementation of effective anti-
schistosome (non-zoonotic) vaccines. However, many research questions need

1
http://whqlibdoc.who.int/hq/2010/WHO_HTM_NTD_NZD_2010.1_eng.pdf page 15
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to be addressed if this goal is to be achieved (86). Vaccine development should

be a priority along with other avenues of research in schistosomiasis, including
the search for alternative drugs to praziquantel, as the future development of
resistance against the drug cannot be ruled out.

4.5.2 Echinococcus granulosus

The successful CE control programmes show that prevention of transmission
to either intermediate (ungulates) or definitive (dogs) hosts can reduce or even
eliminate the infection in human and livestock populations. Hence, if one or
both type of hosts could be vaccinated, an improvement in the effectiveness
and speed of control would be expected. An E. granulosus vaccine would ideally
prevent oncosphere development to hydatid cysts in sheep, and thus stop the
development of adult gravid tapeworms in dogs. Mathematical models of CE
control suggest that vaccination of sheep would be an effective control strategy,
provided that over 90% vaccine coverage of the sheep population was achieved.
This level of coverage is unlikely to be sustainable or realistic in developing
countries. However, the most effective intervention revealed by the modelling
was a combination of sheep vaccination and dog anthelminthic treatment.
A vaccination coverage of about 75% in sheep and anthelminthic treatment
of dogs every 6 months would still achieve a high level of control of disease
transmission, thereby greatly reducing the cost of a control programme and
probably also increasing compliance from dog owners.
Humoral immunity plays a major role in the natural host-parasite
relationship in echinococcosis. This antibody response was used to develop
the highly immunogenic recombinant vaccine, designated EG95, against
E. granulosus (216). The vaccine has been shown to confer a high degree of
protection against challenge with different geographical isolates of E. granulosus.
This would indicate that it could have wide applicability as an effective tool for
use in hydatid control campaigns, with the potential to prevent hydatid disease
directly through vaccination of humans. Research into vaccination against
established hydatid cysts, both as a treatment option and for use in conjunction
with oncosphere vaccines, is needed to reduce the time required to break the
transmission cycle of the dog−sheep strain (217).
Although the EG95 vaccine against ovine hydatidosis is a reality that
now requires innovative delivery strategies (217), no similarly effective vaccine
exists against canine echinococcosis. This is not because of the lack of potential
for application, because such a vaccine for dogs would be of enormous benefit
in further reducing the effective period required to stop transmission of
E. granulosus. Rather, the scarcity of vaccine candidates for immune protection
against the adult tapeworm infection reflects the lack of research on specific
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immune correlates, the lack of evidence until recently of natural immunity in

dogs, and the difficulties and cost of maintaining experimental canids (217).
Experiments to induce immunity in dogs through vaccination have been carried
out (218, 219) but have been questioned methodologically (220). Clearly, these
experiments need to be repeated, confirmed and extended, and this research area
warrants strong encouragement for the future.

4.5.3 Vaccine against Taenia solium

A prophylactic recombinant protein vaccine (TSOL18) against Taenia solium has
been developed for use in pigs. A pilot field trial of the TSOL18 vaccine was
recently undertaken in Cameroon (205). Two hundred and forty piglets 2−3
months old were distributed to 114 individual households in pairs. Vaccinated
animals received three immunizations with 200 µg TSOL18 plus 5 mg Quil A
and 30 mg/kg oxfendazole at the time of the second immunization. Necropsies
were undertaken when the pigs were approximately 12 months of age. Viable
T. solium cysticerci were identified in 20 control pigs (prevalence 19.6%) whereas
no cysticerci were found in any of the vaccinated animals (P<0.0001). Combined
application of TSOL18 vaccination and a single oxfendazole treatment in pigs has
the potential to control T. solium transmission in endemic areas and, indirectly, to
reduce the number of new cases of NCC in humans. An authoritative assessment
of all the options for control and possible eradication using the different strategies
has been provided in a summary study (221). However the cost−effectiveness,
cost−benefit and sustainability of such an approach for developing countries still
need to be determined.

4.5.4 Foodborne trematode vaccines

Recent reports indicate that fascioliasis is becoming a serious public health
problem, especially in South America, Egypt and the Islamic Republic of Iran
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(sporadic cases are also on the increase throughout Europe). Vaccines targeted
at animals could play an important role in controlling fascioliasis in animals
and, by blocking transmission of infection, have a beneficial effect on disease in
humans. A number of prototype anti-Fasciola vaccines are being developed (222,
223) but no commercial product is yet available. There has been very limited
interest in developing vaccines against other foodborne trematode diseases, such
as clonorchiasis and opisthorchiasis.

4.6 Human-targeted vaccines

4.6.1 Enteric infections
Progress in the development of operationally useful vaccines for the range of
enteric infections has been steady. However, with two notable exceptions, no
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new vaccines are ready for introduction as public health tools. One exception is
rotavirus vaccines, already marketed and used in developed countries; the second
is heat-killed whole-bacteria oral cholera vaccines, currently used in limited
settings. Recent trials of rotavirus vaccines (224) have documented a reduction
in all-cause severe dehydration by 30% and for severe rotavirus gastroenteritis
by 61% in Malawi and 77% in South Africa (pooled vaccine efficacy of 61%). Of
the 4417 infants included in the efficacy analysis, severe rotavirus gastroenteritis
occurred in 4.9% of the infants in the pooled placebo group and in 1.9% of
those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% CI: 44.0-73.2).
Although vaccine efficacy was lower in Malawi than in South Africa (49.4% vs
76.9%), the number of averted episodes of severe rotavirus gastroenteritis was
greater in Malawi than in South Africa (6.7 vs 4.2 cases per 100 infants vaccinated
per year). The pooled efficacy against all‑cause severe gastroenteritis was 30.2%.
The reduced efficacy in developing versus developed countries needs to be better
understood to optimize the impact of rotavirus vaccines. Surveillance studies in
rural China have estimated the incidence rate of rotavirus diarrhoea to be 61.4
cases per 1000 children per year in those under 5 years old. Extrapolating to
a cohort of 5000 Chinese newborns, universal rotavirus immunization would
prevent 1764 cases of rotavirus diarrhoea, with 882 hospitalizations averted
(84). At 2004 prices, net savings were calculated to be US$ 14 112 from a societal
perspective and US$ 34 751 from a patient perspective.
With subsidies from GAVI vaccine purchase funds, the price of already
marketed vaccines has been reduced to US$ 0.15−0.30 per dose (225). This is
inexpensive enough to be used in developing countries until the promising and
even less expensive rotavirus vaccines under development in China and India
are thoroughly tested and marketed (226, 227). Since there are reasons to believe
rotavirus vaccines will be widely introduced into developing countries in the
near future, this report does not discuss rotavirus in detail. However, it is an
example of the potential of highly effective vaccines to reduce morbidity and
mortality due to specific enteric pathogens.
Two oral cholera vaccines based on heat-killed vibrios, with or without
recombinant cholera toxin B subunit included as an adjuvant, have been
shown to be safe, effective in well-designed controlled field trials, and feasible
for use in the community (228). One, consisting of a killed whole cell plus
recombinant cholera toxin B-subunit (WC/rBS), has been prequalified by
WHO, and is licensed and sold in over 60 countries as Dukoral, primarily for
travellers to cholera-endemic countries. It is administered in two doses 10 days
apart and elicits protective efficacy 10 days after the second dose; the cost is
approximately US$ 40 per dose. Overall protective efficacy as high as 85−90%
has been demonstrated, lasting for at least 6 months among all age groups, but
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declining rapidly thereafter in children below 5 years of age. The second vaccine
is a similar product containing both O1 and O139 V. cholerae serotypes but no
recombinant B subunit (229). It has been produced, licensed and used only in
Viet Nam, but more recently it has been reformulated under GMP conditions by
the International Vaccine Institute (230), and this version has been submitted to
WHO for prequalification. It has been licensed in India by Shantha Biotech as
Shanchol and is now marketed in India for around US$ 6 per dose. The vaccine
has shown longer-term protection in children under 5 years, although it appears
to be less protective than Dukoral (231). Wider use of these vaccines in endemic
areas, as well as pre-emptive use when the risk of potential epidemic spread is
high, has been recommended (232). In cholera-endemic countries, vaccination
should be considered as an additional tool to control cholera and therefore
targeted at high-risk populations.
Vaccine development for shigellosis has been disappointing, as
the most effective vaccines are also the most reactogenic, and therefore no
candidate Shigella vaccine has yet been seriously considered for scale-up and
implementation. This is, in part, because there are multiple species and serotypes
of Shigella able to cause human illness. In addition, although immunity is
known to be serotype-specific, the nature of protective immunity required
for an effective vaccine remains unclear (233). Many approaches have been
investigated, including oral immunization with live attenuated Shigella or S. typhi
expressing Shigella O-antigens (234), isolated Shigella cell-surface components
(235, 236), or parenterally administered O-polysaccharide-protein conjugates
(237). To provide comprehensive protection against most Shigella species,
serotypes and subserotypes (16 in all), a limited pentavalent vaccine containing
S. dysenteriae type 1, S. sonnei, and S. flexneri 2a, S. flexneri 3a and S. flexneri 6
has been proposed (238), as the last three contain cross-reactive serotype-specific
antigens for the remaining 11 S. flexneri strains. While this approach would
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simplify the development of a broadly effective vaccine for shigellosis, targeting

the most common and most virulent species, the development of such a vaccine
remains a daunting task.

4.7 Animal reservoirs

Targeting animal reservoirs to control zoonotic diseases has been a means of
reducing transmission of infections to humans. An example of this strategy
is the use of chemotherapy to reduce the animal reservoir of human sleeping
sickness caused by Trypanosoma rhodesiense in Uganda (239). Although culling
of domestic dogs is often carried out by veterinary and public health authorities
as a response to rabies outbreaks, there is no evidence that culling operations
today have any significant effects on rabies control. In addition to numerous
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practical, financial, demographic and ethical concerns relating to indiscriminate

dog culling, major questions remain about the theoretical premise on which
culling is sometimes justified. While the assumption that disease transmission
is dependent upon host density (i.e. that disease transmission rates increase
with increasing host densities) is intuitively appealing, there is no evidence for
density-dependent transmission of rabies in domestic dog populations (186).
Similarly, culling of wildlife has never provided an effective long-term solution to
wildlife rabies control. The high reproductive potential of reservoir populations,
perturbation effects on movements and contact patterns, together with the
capacity of the environment to provide food, water and shelter, most often
render population control efforts futile. Empirical evidence from diverse settings
across the world indicates that mass vaccination of reservoir hosts, whether
domestic dog or wildlife populations, remains the single most effective approach
to rabies control and elimination.
Other examples include the use of vaccines in dogs for rabies control,
and the dispersion of baited oral vaccines for the fox population to control rabies
in Europe. Following development of a vaccine for bovines for Schistosoma
japonicum control, its use is under consideration in China and the Philippines
but will depend on the proportion of human cases derived from the buffalo
source. The effectiveness of any vaccine in such settings will depend on the
proportion of infections in other reservoir hosts that cannot be vaccinated.
For echinococcosis and cysticercosis, targeting the major animal reservoirs,
respectively sheep and pigs, has been investigated recently. In the former, the
use of ovine vaccines has been tested and, in the latter, the use of oxfendazole to
kill larval cysts, the source of human tapeworm infection. All these approaches,
however, seem to require additional interventions to reinforce the impact of the
primary intervention on the reservoir; hence the need for integrated approaches.

4.8 Health education and health literacy

Infectious diseases, particularly those in the category of neglected diseases, thrive
in conditions of poverty and associated factors such as inadequate sanitation and
lack of formal education (3). In turn, they perpetuate poverty, thus minimizing
opportunities for development and education (240).
Education leads to multiple benefits, including access to better economic
opportunities, and is strongly associated with better health outcomes such
as decreasing rates of infant, child and maternal mortality (241). Education is
thus an essential component for social change (242) and is a key strategy to end
poverty and decrease the burden of disease. In the context of the Millennium
Development Goals, “Education that reaches the poor can contribute to a more
equal society” (242).
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The World Health Organization has identified literacy as a key

determinant for reducing health inequities in both rich and poor countries (243).
Indeed, the number of years of schooling is positively associated with lower
maternal mortality, and maternal education has a strong association with child
health (242).
Studies on infectious diseases have shown that, among populations
living in endemic communities, lack of education (as measured by years of
schooling) and insufficient knowledge about the common diseases to which
people are exposed are common risk factors for increased incidence and
prevalence. For instance, in Honduras, Taenia solium infections have been found
to be more prevalent among those with fewer years of schooling (244), while in
rural Peru lack of education beyond elementary school was found to be associated
with higher levels of human T. solium seropositivity (245). In China, a review of
the socioeconomic determinants of Schistosoma japonicum found that in most
reports a higher educational level was associated with lower exposure to infected
water and therefore lower prevalence of infection (246). Equally, for enteric
diseases, studies in Brazil provide further evidence that childhood diarrhoea is
more likely in children whose mothers had a low level of schooling (194).
It is generally assumed that improvements in education and increased
awareness through access to health information would lead to change in
behaviour. However, any sustainable effect between educational strategies and
changes in behaviour has been difficult to ascertain, particularly in short-term
interventions. A study in Mexico showed that an educational intervention
was successful in increasing knowledge of the transmission of T. solium (247).
However, although some changes in behaviour were also observed, they were
variable and not statistically significant at only six months post-intervention
(247). A study on cystic echinococcosis showed that, although the vast majority
of the study population recognized hydatid cysts, the mode of transmission and
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association with human disease was largely unknown (248).

Some studies show that the possession of appropriate background
knowledge does not always predict better health outcomes or behaviour. This
has been documented widely for chronic diseases (e.g. cigarette smoking
and lung cancer) and sexually transmitted diseases, but only a few studies on
the diseases within the scope of this report have documented a disconnect
between knowledge and action. For example, a study on rabies in Sri Lanka
demonstrated that, despite awareness and knowledge about the disease, there
was no accompanying improvement in responsible behaviour with regard to
dog ownership (249). This is also true for pig owners, who understand that
their animals have more chances of acquiring cysticercosis by roaming free and
scavenging for food. In trying to explain the discrepancy between knowledge
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and action in the latter example, it has been proposed that other factors such
as economic incentives or health risk perceptions may play a prominent role
(250). The protective effect brought about by knowledge and awareness may be
minimized by environmental and infrastructural conditions and limitation of
resources. In addition, individual decisions and actions may be not as effective
if exposure is beyond the control of the individual. The power of education is
conditioned by the political, social and economic circumstances in which people
live (242).
In the example of porcine cysticercosis, the reasons why small-scale pig
holders allow animals to roam free are seldom explored. Smallholders may lack
land to set up a sty or resources to build it. An FAO report concludes that some
livestock keepers are simply too poor and their operations too small to overcome
economic and technical barriers (251). Moreover, too often smallholders struggle
to feed their families and cannot afford to feed their livestock. Under these
circumstances, keeping pigs in confinement is not a viable option. This could
explain the observation in north-western Mozambique, where the prevalence of
porcine cysticercosis among households with knowledge about the parasite was
not different from those without such knowledge (252). Other zoonotic diseases
can present an even more complex scenario where education and awareness
play only a limited role. For instance, the control of S. japonicum in China is
compounded by agricultural practices and the existence of an animal reservoir,
namely water buffalo, which spend more time in the water than cattle and thus
have more opportunities to contaminate the water. Therefore, in addition to
health education and treatment for humans, strategies that include replacement
or treatment of water buffalo and the use of a transmission-blocking vaccine will
need to be implemented to maximize control efforts (211).
A further aspect that needs to be taken into consideration when
analysing discrepancies between knowledge and action to reduce zoonotic
disease burden is that there are several infections which for ethnic and cultural
(including religious) reasons may play a more immediate role in transmission
than schooling or awareness. Such is the case of certain foodborne parasites,
for example, protozoa (e.g. T. gondii), trematodes (e.g. F. hepatica, Opisthorchis,
Clonorchis, Paragonimus) and cestodes (e.g. T. solium and T. saginata) (253,
254). Discrepancies between knowledge and action are documented in both
developing and developed countries (255).
The variable results concerning the effectiveness of health education in
communities endemic for the infectious diseases may also reflect the need for
longer-term studies and optimized educational design as well as participatory
research and innovative evaluation methodologies. For example, a 12-year pilot
study for the control of S. japonicum, focused on health education and promotion
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(complemented with treatment of infected people with praziquantel), was able to

achieve long-term positive changes towards control and adherence to treatment,
particularly in women (256). With shorter-term studies, available evidence
shows that when educational interventions are undertaken with full community
participation, their results are more effective and may lead to lasting effects (252).
In Nepal, making use of the first steps of the PRECEDE-PROCEED model (see
below), the organizers were able to engage the community in identifying practices
needing improvement to control porcine cysticercosis (257). Encouraging results
have also been reported in the United Republic of Tanzania where the PRECEDE-
PROCEED model was fully implemented (258). A health education intervention
resulted in behavioural changes and decreased incidence of T. solium infections
by nearly half 12 months post-intervention (258).
The PRECEDE-PROCEED model, widely used in health promotion,
provides a comprehensive structure for assessing needs and implementing
and evaluating interventions. It is based on the premise that health risks are
caused by multiple factors, and so efforts seeking to effect change (behavioural,
environmental, social) must be multidimensional, multisectoral and participatory
(259). This model, however, is complex, requiring a high degree of professional
involvement and an organized system. Outcome Mapping (260) can be used in a
variety of situations to engage stakeholders (groups, communities or institutions)
to define desired outcomes, implement strategies and measure progress.
An advantage of Outcome Mapping is that, in contrast with the PRECEDE-
PROCEED model that focuses on health outcomes, it allows assessing or
measuring real-time progress, not just end-results. Instead of defining success
as accomplishing the ultimate target goal (for instance the decrease in incidence
of a disease; presence or absence of diarrhoea), the success of the programme
can be monitored through the use of progress markers (e.g. changes in hygiene
practices) and by recording a gradient of changes in behaviour towards the
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ultimate goal (260). Wider recognition is needed of the constructive effects of

fostering empowerment and strengthening self-sufficiency among populations
exposed to the zoonotic diseases.
Finally, recent work has shown that beyond functional literacy (i.e. the
skills of reading and writing), health literacy is fundamental in empowering
individuals and communities to take actions conducive to improving their own
health and their social and physical environment (261, 262). An increasing
body of knowledge supports the role of health literacy in fostering positive
health behaviours and practices for the prevention of chronic diseases (262,
263) but little has been done to explore its role as an asset in ameliorating the
burden imposed by infectious disease in the poorest of the poor. The problem
is compounded when addressing zoonotic diseases, as the communities may be
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migratory, nomadic or isolated. They may have little access to formal educational
structures and concepts, and may not be catered for by traditional government
facilities.

4.9 Development of human resources

The implementation of effective, reproducible and sustainable health promotion
strategies, including health education, requires strong leadership, continuing
cooperation and a harmonized vision among different sectors in academia,
government and civil society.
A recent report from the Institute of Medicine of the US National
Academies of Sciences clearly identifies the global need for strengthening
the professional workforce capable of conducting surveillance and initiating
appropriate responses to infectious disease threats. Moreover, the report
advocates training programmes that foster inter-disciplinarity as well as the
participation of community and public health professionals (166). This training
model is essential for a broader understanding of the causality of infectious
disease and is the cornerstone of control and prevention strategies that target
an integrated approach to health and should be at the core of professional and
technical curricula (264).
In regard to the infectious diseases of poverty, health education and
health literacy can play a fundamental role in the empowerment of disadvantaged
communities in disease-endemic countries (265). By tailoring health messages to
specific populations, educators, researchers and decision-makers are more likely
to reach broader audiences and to effect change. For example, research focus
groups studied a rural community in Honduras where porcine cysticercosis was
prevalent and where pigs were roaming freely through the village. The study
showed that the small pig-holders, who were mostly women, were not only not
interested in pamphlets with health information, but also disliked pamphlets or
handouts portraying them in cartoons, as they consider this a lack of respect.
These findings were considered in the design of a communication
strategy that integrated the role of literacy, gender and daily activities, such as
going to the market, into a health message to encourage a behaviour change.
Thus, a family canvas shopping bag with a drawing of a piglet and the legend
“a pig in a pen is a healthy pig” was distributed among women. The bag was
received enthusiastically by the women and they used it proudly every day and
explained its significance to others who were curious about it (Maritza Canales,
unpublished data).

4.10 Integrated approaches

Disease control programmes are typically integrated as there is a need to link
surveillance, monitoring and reporting all activities with actions taken by
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the health system. With zoonotic diseases and the diseases of marginalized
populations, interventions typically are directed at both the human and the
animal host. Such approaches may be biomedical (drug or vaccine), vector or
intermediate host control (insects or snail), environmental, legislative (inspection
and condemnation of infected products at slaughterhouses) or educational.
Integration must also be across the human health and animal health sectors.
The recent example of integrated control of schistosomiasis in China was referred
to earlier. There are several other examples of integrated control of zoonotic
diseases that demonstrate the importance of addressing both ends of the host
spectrum, the vectors (if present), the environment and behaviour change.
Control measures already exist for several neglected zoonotic diseases
such as rabies, anthrax, echinococcosis, cysticercosis and brucellosis. Interventions
can be packaged through existing veterinary and public health structures.
Several examples of major successful control programmes indicate that national,
regional or even global control/elimination should be possible. This integrated
approach can be extended to incorporate non-zoonotic public health problems
prevalent in the same impoverished communities. However, the effectiveness
of these interventions in reducing human infection for some of the diseases
(e.g. cysticercosis, echinococcosis) remains unknown.
Depending on the characteristics of the human and zoonotic diseases
prevailing in the area, control of the zoonotic diseases can be integrated and
viewed within existing health and agricultural systems. “Control packages” for
animal diseases, similar to school-based programmes for the control of certain
human diseases in children, should be developed. These would reflect a change
from single-disease/vertical approaches to more integrated health promotion by
development of new packages addressing several disease/health problems. The
development of such packages needs to be supported by operational research to
assess their impact, safety and cost−effectiveness and by disease control and cost
WHO Technical Report Series, No. 971, 2012

modelling exercises where appropriate.

These packages should target populations such as: 1) pastoral communities
and remote sedentary rural populations in Africa and Asia; and 2) marginalized
urban livestock producers. Together these represent a substantial proportion of
the 600 million poor livestock keepers worldwide.

4.11 New products and strategies

There is universal recognition that more research should be conducted to
improve and develop new disease control tools. However, diagnostic, curative,
preventive and monitoring tools must be adapted to the conditions prevailing
in developing countries and recognize the constraints of financing, affordability
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and delivery. There is unprecedented interest in research on diseases of the poor,

although there is still only a disproportionately small amount for research on
zoonoses. However, there is a degree of optimism that this research will yield
products that can be developed rapidly, can be financed and deployed within
health systems, and can yield beneficial widespread impacts on health. The
needed research should be undertaken cooperatively at the international level,
be multidisciplinary, involve both human and animal health research groups,
and engage relevant stakeholders. It should focus on integrated interventions,
rather than target a particular and unique biological target, since it is likely
that the cost−effectiveness and cost−benefit of a broader approach will be more
favourable. The concept of the “mono-intervention” approach is not likely to be
productive in zoonotic diseases but this approach is usually the target-driven
focus of research in biomedical areas.
For most diseases there is a need for development of affordable, rapid,
reliable and robust diagnostic tools appropriate for both field and local health
facility settings in almost all of the diseases considered by this report. These
tools should also be considered in the context of surveillance and monitoring
and evaluation tools. There is a need for development of innovative strategies
for disease surveillance, including the use of sentinel populations (both human
and animal), adopting new approaches in communication technology and
analytical tools (e.g. text/data mining such as the USDA livestock disease alerts),
participatory approaches such as the use of abattoir workers for surveillance, and
mobile phone reporting (e.g. as used to report rabies exposures in Pakistan).
In any assessment of disease control there is always an interest in vaccine
development. However, in the context of zoonoses the drive to develop new
vaccines for interventions in animal populations, including multivalent vaccines,
could be justified if combination vaccines given through the same delivery strategy
were demonstrated to be effective. For example, combined rabies/echinococcosis
vaccine for dogs and a combined echinococcosis/brucellosis vaccines for sheep
would be attractive concepts for development.
From a strategic perspective, there is a need to develop community-
led initiatives for surveillance, treatment, prevention and control of infectious
diseases, recognizing the need for two existing major community-based
initiatives to share experiences since control strategies for infections are often
complementary. Specifically, the Community-led Total Sanitation project and
the African Programme for Onchocerciasis Control (although onchocerciasis is
not a zoonosis) should meet to explore lessons learned as well as the removal
of obstacles to scaling up the two approaches through communities. A recent
WHO/TDR multicountry study has provided strong evidence of the health
delivery opportunities afforded (266).
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Although both the biomedical and social sciences approaches to research

are crucial, it is important to identify effective strategies for translating research
findings into policy change and through this to generate sustainable financing
for implementation at the necessary scale. This is a significant challenge under
ordinary circumstances, but in times of global financial stress it becomes
significantly more difficult. There is also a need for research into the sustainability
of systems to identify strategies to maintain control and prevention beyond the
term of donor support.

4.12 Health systems and interactions with other

sectors: intersectoral dialogue
A significant part of the problem of neglected zoonotic diseases is the lack of
communication and shared information among the relevant communities
that need to connect with one another. The establishment of a scientific
multidisciplinary intersectoral advisory committee to share and communicate
information, especially within countries where the burden of those diseases is
high, would be a major step forward. In addition, measures should be taken to
raise awareness among policy-makers in all involved sectors and at all levels
to inform decision-makers of the importance and impact of zoonoses and
marginalized diseases. The responsible international agencies (WHO, FAO and
OIE), as well as other stakeholders, need to take leadership in the sensitization
of national governments and donor communities to the importance of zoonoses
both as endemic impediments to development and as immediate threats to
health. Given the limited resources typically available in poor countries, WHO,
FAO and OIE need to determine how to help establish international resource
centres to gather existing educational and advocacy material for zoonotic and
marginalized diseases.
WHO Technical Report Series, No. 971, 2012

Beyond the information-sharing function, a system for recognizing and

funding centres of excellence in zoonotic disease research that are linked to
local public health systems would extend the capacity of local communities to
address their own problems.

4.13 Cost−effectiveness analysis

Very few studies to evaluate the economic implications of alternative control
strategies for zoonotic diseases have been performed. Such studies need
to quantify the production losses, such as reduced fertility, milk or wool
production, poor weight gain of food animals and organ damage, as they can
impose significant financial losses on livestock keepers (267). This is essential
if the true impact of these diseases is to be evaluated. Such losses are difficult
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to quantify in developing countries, in part because they are dependent on the

type of production system in the community of interest. Often there are few
formal markets and opportunities to replace animals, which further challenges
the accurate assessment of lost revenue. Even where appropriate treatments are
commercially available, poor-quality animal health services and low compliance
will make it difficult to compensate for the cost of treatment by the subsequent
return to health of the animal and its value to the farmer.

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5. Disease-specific and intervention-specific
priorities for research
5.1 Disease-specific research priorities
This report identifies applicable and relevant priorities for each zoonotic disease
covered by the DRG, identifying the knowledge gaps in zoonotic disease research
and presenting the priorities for research.
While many disease-specific and agent-specific research needs are
detailed in the sections below, there are five common threads in the knowledge
gaps that, if addressed, will help to target interventions and bring significant
health improvement in a short time frame. These are:
■■ studies of disease burden in both humans and animals in both urban
and rural settings in a manner that brings the human and veterinary
health communities together;
■■ determination of the economic cost of these diseases for both the
human and animal populations involved;
■■ studies of the efficacy of integrated interventions that address more
than one disease and/or agent at the same time;
■■ determination of the cost-effectiveness of these interventions;
■■ studies on promotion of health literacy and social mobilization
to ensure maximal engagement of the affected populations in the
selected interventions.

5.1.1 Cysticercosis and taeniasis

The following research priorities were identified by the DRG:
■■ new drugs, rapid diagnostics, drug regimens and treatment follow-up
for taeniasis and human cysticercosis;
■■ field-based randomized clinical trials to evaluate the efficacy of
oxfendazole and its effectiveness with recombinant vaccines against
porcine cysticercosis;
■■ detailed studies to elucidate the spectrum of symptoms, including
stroke associated with NCC to inform burden of disease studies;
■■ development of immunological tests for diagnosis and biomarkers
of infection status/exposure and for differentiation of T. solium and
T. saginata;
■■ development and validation of transmission dynamics models to
assess the cost−effectiveness and cost−benefits of alternative control
strategies;
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■■ development of audience-specific health education and behaviour

change interventions; and assessment of their effectiveness together
with gender-related correlates in intervention studies.

5.1.2 Echinococcosis
The following priorities were identified for echinococcosis research:
■■ measurement of the health and economic burden of echinococcosis
caused by both E. granulosus and E. multilocularis, including
productivity losses in humans and animals and cost−effectiveness of
current control approaches;
■■ multicentric prospective evaluation of available clinical treatment
options, including surgery, ultrasound, drug regimens (albendazole,
flubendazole and ivermectin, including dosages and combinations);
■■ improved sensitive and specific diagnostics for early detection of
Echinococcus infection including:
–– methods (imaging, serology) to assess parasite viability and/or
progression of both cystic and alveolar disease;
–– comparison of the efficacy, sensitivity and specificity of copro-
DNA tests to establish strain-specific detection for E. granulosus
in dogs;
■■ further assessment of different vaccine strategies/options/combinations,
e.g. a vaccine for ovine echinococcosis and development of a vaccine
for use in definitive canine hosts;
■■ development and validation of better transmission dynamics models
to assess the cost−effectiveness of alternative control strategies.

Asian schistosomiasis
WHO Technical Report Series, No. 971, 2012

5.1.3
The zoonotic schistosomiases, Schistosoma japonicum and S. mekongi in Asia
could be locally eliminated because new tools (e.g. an effective vaccine for
buffalo) are available. However, more studies are needed to determine the role
of the variety of animals in transmission as reservoirs (buffalo or others such as
dogs, cats or rats). This is especially the case in the Philippines, where the precise
role of carabao (water buffalo) in the transmission of S. japonicum needs to be
determined.
■■ Operational research is required on the cost−effectiveness of
integrated control to establish optimum approach at scale in different
geographical settings, including the value of transmission-blocking
vaccines for use in buffalo or other mammalian hosts.
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 Disease-specific and intervention-specific priorities for research

■■ Studies on the problems of coverage and compliance related to access

to mass treatment in the Philippines (Samar province) in relation to
animal reservoir diversity to define which zoonotic sources have an
impact on the incidence of human infections.
■■ Studies on the impact of schistosomiasis on malnutrition and cognition
are required in relation to single infections and polyparasitism.
■■ Improved diagnostic methods are required where schistosomiasis
prevalence is low and as a surveillance tool in order to determine
whether effective control has been achieved.
■■ Development of appropriate and gender-sensitive tools and methods
is needed to assess the health and socioeconomic impact of control
programmes on individuals and households.

5.1.4 Foodborne trematodiases

The DRG benefited from recent WHO and TDR meetings on this topic and
review papers in constructing the following priority listing for foodborne
trematodiases (89):
■■ estimation of the global burden of foodborne trematodiases;
■■ increased interest in the discovery and development of new
diagnostic tools, vaccines and new trematocidal drugs;
■■ determination of how improved access to clean water, adequate
sanitation and sewage treatment, and enhanced food safety measures
have an impact on foodborne trematodiases;
■■ while chemotherapy-based morbidity control should serve as
the backbone of control programmes in areas where foodborne
trematodiases are highly endemic, integrated control approaches
and intersectoral collaboration between public health and veterinary
medicine warrant more attention, including considerations of
feasibility, efficacy and cost−effectiveness;
■■ operations research on integrated control (mass treatment, education
and behaviour change communication, community-directed/led
strategies for health, sanitation and aquaculture management) in
endemic communities and intersectoral collaboration between
public health and veterinary medicine and public and private sectors
in planning implementation, including food safety issues;
■■ analysis of gender (male and female) differentials on access to and
compliance with FBT treatment;
■■ development of appropriate and gender-sensitive tools and methods
to assess the socioeconomic impact of FBT on individuals,
households, communities and societies;
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■■ evaluation of national FBT disease surveillance, and its effectiveness

in tracking FBT infections. Together with the surveillance of other
zoonotic diseases, assess the impact of FBT and its control into the
health education programmes for communities and schools, and its
effect on the knowledge and practice of endemic communities to
prevent and control FBT.

5.1.5 Toxoplasmosis
The following priority research needs for toxoplasmosis were identified:
■■ development of animal vaccines;
■■ development of new economic and safe diagnostic techniques for
acute infection during pregnancy to detect toxoplasmosis in the
mother and fetus;
■■ assessment of the cost−effectiveness of integration of existing
serological test regimes into antenatal care programmes in low-
income settings;
■■ development of cost-effective diagnostic and management protocols
for CNS toxoplasmosis in high-risk HIV-seropositive patients;
■■ development of culturally acceptable health education programmes
to improve food hygiene in the home, especially for pregnant women;
■■ quantification of the impact of improved water quality and sanitation
on toxoplasmosis infection;
■■ quantification of the proportion of chronic abortions globally that
are attributable to toxoplasmosis.

5.1.6 Cryptosporidiosis
The following research priorities were identified for cryptosporidiosis:
WHO Technical Report Series, No. 971, 2012

■■ document the burden of cryptosporidiosis in young children in

developing countries;
■■ determine the extent of livestock as source of Cryptosporidium
infections in humans in the developing world;
■■ enhance surveillance of infection prevalence in humans and
livestock, and determine the short- and longer-term health and
economic consequences for both populations;
■■ assess the impact of community-level water and sanitation
improvements on the prevalence of human infection, in both urban
and rural settings;
■■ identify agricultural practices that reduce the exposure of livestock
to infection in order to interrupt transmission to humans;
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 Disease-specific and intervention-specific priorities for research

■■ develop a livestock vaccine to block animal infection and consequently

reduce the excretion of infectious cysts into the environment and
transmission of infection to humans;
■■ continue to explore new drug candidates for use in the
immunocompromised host.

5.1.7 Rabies
Human rabies incidence can be reduced by mass dog vaccination campaigns in
combination with prompt and appropriate post-exposure prophylaxis (PEP)
for people suffering animal bites and possible exposure to the rabies virus.
Cross-sectoral evaluation of this approach has clearly demonstrated the cost−
effectiveness of interventions in the domestic dog population (268). However,
challenges remain in developing sustainable strategies to resource this approach,
including cooperation between the health and veterinary sectors (269).
Surveillance also remains a major constraint throughout much of Africa and
parts of Asia. Relatively few cases of human and animal rabies are confirmed
by laboratory diagnosis because of limited laboratory diagnostic capacity and
the lack of submission of diagnostic samples from clinical cases (both humans
and animals). In addition, clinical diagnosis can be problematic, particularly
in malaria-endemic areas, where a proportion of childhood rabies deaths are
misdiagnosed as cerebral malaria (270). The priorities identified by the DRG
were both implementation policy and basic research, as these are interrelated.
The following actions are needed to reinforce the research agenda:
■■ strengthening of laboratory capacity for diagnosis and surveillance
to generate accurate data on rabies incidence in order to guide
control strategies and estimates of disease burden;
■■ prioritization and cooperation between health, veterinary and
wildlife agencies;
■■ adoption of appropriate and effective methods for collection of
samples for diagnosis of rabies in humans both post mortem (e.g.
periorbital biopsies, (270)) and antemortem (e.g. nuchal skin
biopsies (271)).
Specific research priorities identified were:
■■ more widespread use of existing techniques for field collection and
storage of samples and tests for rabies diagnosis and surveillance
(269), such as the direct rapid immunohistochemical test (272–275),
and use of preservatives/specialized paper for stabilization of virus
and RNA;
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

■■ development and evaluation of new technologies for integrated, real-

time surveillance and response (e.g. mobile computing technologies);
■■ evaluation of the cost−effectiveness of different WHO-recommended
pre and post-exposure regimens, including indirect costs associated
with hospital visits;
■■ evaluation and implementation of new biological regimens for
humans, including use of monoclonal antibodies as a cost-effective
replacement for rabies immunoglobulin (276, 277);
■■ establishment of reliable, economical and harmonized in vitro
laboratory tests to ensure the quality and in particular the potency
of rabies vaccines;
■■ development of innovative strategies for funding integrated and
sustainable dog vaccination programmes, including education and
social mobilization campaigns;
■■ development of combined approaches to dog rabies vaccination and
immuno-contraception (277);
■■ investigation of the economics of dog oral vaccination strategies
and identification of appropriate settings for implementing oral
vaccination campaigns in dogs (277).

5.1.8 Bacterial zoonoses

Owing to limited clinical laboratory infrastructure, a definitive diagnosis for
diseases such as bovine tuberculosis and brucellosis can rarely be confirmed in
routine clinical practice. Existing serological tests for brucellosis carried out in
hospital settings often perform poorly, with problems relating to both specificity
and sensitivity (278). For anthrax, an additional cause of underreporting is the
rapid onset and progression of pulmonary and gastrointestinal cases, which
WHO Technical Report Series, No. 971, 2012

means that patients often die before reaching medical facilities.

The following research priorities for bacterial zoonoses were identified.
■■ Inexpensive, robust and reliable diagnostic tests are required for use
in field and hospital settings. Where tests do currently exist, such as
the single comparative intradermal test for bovine tuberculosis and
serological tests for brucellosis, establishing locally appropriate cut-
off points is important for acquisition of valid data to inform disease
burden studies.
■■ There is a pressing need for cross-sectoral assessment of disease
burden to allow for realistic evaluation of the cost−effectiveness of
disease interventions.
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 Disease-specific and intervention-specific priorities for research

■■ A common measure of zoonotic disease burden that incorporates

human health indices, costs to the public health sector, monetary
burden for the livestock sector and costs to the private sector needs
to be developed.
■■ Ethnographic and participatory research approaches are needed
to design relevant and understandable criteria for measuring
impacts that incorporate a broader consideration of burden with
consideration of the value of livestock for human well-being and
development.
Several key questions need to be answered for zoonotic tuberculosis in
Africa. The priorities are as follows:
■■ understanding of the human disease burden, and how and why the
prevalence of human M. bovis and non-tuberculous mycobacterial
infections varies in different communities;
■■ identification of animal-related risk factors for human infection with
different mycobacterial species, including potential factors associated
with small ruminants (279);
■■ clinical research on optimal drug treatment regimens for etiologically
confirmed M. bovis and non-tuberculous mycobacterial infections;
■■ evaluation of the effectiveness of the standard DOTS regimen
administered in cases of tuberculosis caused by M. bovis and non-
tuberculous mycobacterial infections, as few cases are differentiated
on the basis of culture results;
■■ development of effective livestock vaccines and vaccination strategies
for M. bovis, as conventional test-and-slaughter approaches that
have been used to control and eliminate infection in industrialized
regions are unlikely to be feasible in most developing countries.
For both brucellosis and anthrax, livestock vaccines are available.
However there is a need to ensure immunogenicity and vaccine quality, improve
vaccine safety, and design and implement targeted vaccination strategies that will
optimize the cost−effectiveness of interventions.
The following research priorities for brucellosis were identified:
■■ critically assess the immunogenic properties of currently available
vaccines and their effectiveness in areas of high endemicity;
■■ improve the safety and immunogenicity of the current vaccines
against Brucella melitensis and Brucella abortus;
■■ design diagnostic strategies to differentiate vaccinated animals from
naturally infected animals in order to prevent unnecessary livestock
slaughter;
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■■ develop inexpensive and reliable diagnostic tests for use in local

hospital and field settings;
■■ generate data and develop methodologies to allow an accurate
estimation of the societal burden of brucellosis, focusing primarily
on burden of disease in livestock and human populations;
■■ design and evaluate cost−effective livestock vaccination strategies
and advocate “One Health” approaches to implementation at the
policy-maker level (ministries of health and agriculture);
■■ develop approaches to raise awareness among physicians of the
need for differential diagnosis of Brucella in cases of non-specific
febrile illness.
Even without a specific detailed knowledge of risk factors, several health
measures are likely to be effective in preventing transmission of bacterial
zoonoses, such as boiling milk (to prevent brucellosis and M. bovis infection)
and hygienic precautions when handling abortions and placental material (to
prevent brucellosis and Q-fever) and the carcasses, skin and hides of livestock
that have died (to prevent anthrax). Applied research is therefore needed on
the development, implementation and evaluation of appropriate preventive
health educational measures that are likely to provide a cost−effective means of
reducing the burden of a wide range of bacterial zoonotic infections.

5.1.9 Enteric infections

Current gaps in knowledge represent barriers to improving the effectiveness of
measures to interrupt the transmission of diarrhoeal and dysenteric diseases.
These gaps span the range of “upstream technical” to “downstream applied”
questions. The needs are:
WHO Technical Report Series, No. 971, 2012

■■ develop better methods for surveillance of human enteric infections,

including syndromic classification and etiology if possible, based in
representative community settings, both urban and rural, and across
the whole age range;
■■ clarify the reservoirs for animal and human enteric infections and
the pathways of transmission among animals, from animals to
humans, from humans to humans and from humans to animals;
■■ after identifying critical points in transmission, develop interventions
that will target the most effective transmission routes and markedly
diminish, if not abolish, their efficiency;
■■ develop infrastructure and capacity to identify zoonotic enteric
pathogens in the relevant animal populations;
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 Disease-specific and intervention-specific priorities for research

■■ determine the economic burden resulting from infections in

livestock, including illness and loss of markets and income from
animals and the direct and indirect economic costs of foodborne
illnesses;
■■ test simple cost-effective farming methods to prevent transmission
of zoonotic infection to animals, crops and water supplies, and to
humans, which will be applicable to small- and large-scale producers
alike;
■■ develop ways to improve the communications between veterinary and
human health professionals, to include integrated training modules
and mechanisms for exchange of information;
■■ create joint veterinary/human health outbreak investigation teams,
with access to quality laboratory capacity for diagnosis allied to
enhancement of veterinary and human grassroots public health
educational services (educational extension model) to improve
animal and human health outcomes;
■■ implement ongoing surveillance for drug resistance and determine
the most effective means to disseminate this information;
■■ develop strategies to control the delivery of drugs used for enteric
infections without restricting access when these medications are
urgently needed in order to increase appropriate use and delay the
emergence and spread of drug resistance;
■■ identify the optimal investments in livestock animal and human
primary health care capacity to ensure appropriate treatment as well
as the use of effective prevention modalities;
■■ increase investments in new drug and diagnostic test research and
development programmes;
■■ develop multivalent, low-cost, locally produced vaccines sufficiently
effective to interrupt transmission cycles;
■■ create new approaches to community sanitation measures and the
provision of clean water supplies.

5.2 Intervention-specific research priorities

5.2.1 Community-led Total Sanitation
The key research priorities emerging from the experience of CLTS to date are:
■■ measure the effectiveness of CLTS on incidence and prevalence of
zoonotic and marginalized diseases through epidemiological studies
and community-based randomized trials;
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■■ estimate the duration of “open defecation free” (ODF) status

following CLTS;
■■ estimate the cost−benefit of CLTS as compared with other approaches;
■■ study the human-animal interface to clarify the social, cultural,
behavioural, economic and gender dimensions of improving
community access to proper sanitation through CLTS;
■■ evaluate the impact of CLTS on specific communities dependent on
equines and camelines, smallholder pig farmers and those dependent
on aquaculture.

5.2.2 Animal/human interface

In the area of the animal-human interface the key research priorities identified
are:
■■ further study mechanisms for coordinated public and animal health
action within national government systems that comprise both the
public health and animal health systems as a single entity on an
equal partner basis;
■■ increase the level of priority accorded to zoonotic diseases by
increasing advocacy and undertaking research to underpin the
importance of zoonotic infections as drivers of poverty;
■■ extend the concept to cover diagnosis, data-sharing, monitoring and
surveillance systems, training, interventions and delivery.

5.2.3 Epidemiological studies

Small-scale focused epidemiological studies should be undertaken to gather basic
information for the design of control programmes and awareness generation and
to support advocacy. Such studies should focus on the following:
WHO Technical Report Series, No. 971, 2012

■■ assessment of the DALY burden borne by individuals affected by

the diseases;
■■ assessment of the monetary impact of the diseases to livestock and
human productivity;
■■ study of risk factors in both people and animals with a view to
successfully targeting at-risk groups for high-priority intervention;
■■ investigation of methods for quantifying the rate of underreporting
of these diseases in humans;
■■ development of transmission dynamics models to predict the
effectiveness of alternative control measures;
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 Disease-specific and intervention-specific priorities for research

■■ cohort studies on several zoonoses in which the symptoms in humans

appear several years after infection;
■■ randomized trials to estimate the effectiveness of alternative control
strategies, including integrated/combined strategies.

5.2.4 Health education and promotion

The priority areas for research are the following:
■■ long-term (longitudinal) studies assessing health education “multi-
packs”, i.e. for diseases with similar or overlapping bio-social
determinants;
■■ gender-sensitive approach to health education/promotion and
behaviour change, e.g. the role of women, as they more often tend to
be small livestock keepers;
■■ comparative studies on traditional versus participatory research;
■■ evaluation research (assessment of methodologies for programme/
project evaluation);
■■ assess the specific contribution of educational components within
integrated interventions.

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6. Cross-Group issues and priorities
6.1 Interactions with Disease and Thematic Reference Groups
Involvement in the meetings of Chairs and co-Chairs, attendance at the
Stewardship Advisory Committee and interactions with the Secretariat have
ensured communication with the activities of other DRGs and TRGs. However,
it was important that the DRG on Zoonoses and other Marginalized Infections
(DRG 6) was also in a position, through its expertise and focus in EMRO, to
debate the issues in a way that reflected its unique perspective, geographical,
health, and livestock and cross-sector experience, since TDR has traditionally not
been involved in this group of poverty-promoting infections where interventions
span sectors other than health. Although the interaction of most relevance was
that with the DRG addressing priorities for helminth diseases (DRG 4), the
approaches to control of the zoonotic helminthiases differ significantly from
those for non-zoonotic diseases. In addition, DRG 6 felt that more attention
should be paid to zoonotic tuberculosis because of the potential importance of
bovine tuberculosis in the epidemiology of human tuberculosis in HIV/AIDS
patients in Africa. This suggests the need for stronger interactions with the TB
DRG (DRG 2) in order to better address research needs in areas where there is
evidence of a rate of bovine-derived TB in human cases that is higher than usual.
There are also social science issues relating specifically to the various
communities that are livestock-dependent, are not amenable to mainstreaming
into society, and traditionally live a migratory and nomadic, pastoralist existence.
In this context, a gender perspective is relevant as the roles of the different sexes in
these communities are often diverse and traditionally structured. For this reason
interventions, on the one hand, and the impact of human and animal diseases,
on the other, will have different implications for males and females in these
societies. There is a clear relationship also with the TRG addressing environment
and agriculture (TRG 4). Environmental and ecological changes will have a
profound impact on the diseases covered by TRG 4. Environmental change will
lead, for example, to changed migration patterns, potentially increasing contact
between livestock-owning communities and settled farming communities
(itself a potential source of conflict), which could result in the transmission of
infections and outbreaks in farming communities and thus exposure to infections
to which people are not traditionally exposed. Environmental change itself,
in its many forms, may also result in changes in behaviour and distribution of
wildlife reservoir hosts, changed trends in vector or intermediate host biology,
and changes in water tables, thus affecting the epidemiology of diseases where
aquaculture plays a role (e.g. foodborne trematodes). This subject is an extensive
and complex one and will require co-prioritization between DRGs and TRGs.
However, as in many settings environmental and ecological change is rapid,
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constructing and developing research projects that are designed to answer more
generic questions is challenging, as many of the issues are often ecologically or
geographically specific.
Several sets of health system issues and research questions relate to
community interventions (Table 5), i.e. the need for research on interactions
at both national and subnational levels between the health sector and those
responsible for animal health, as well as other sectors where both human and
animal disease research and control can benefit from policy changes, e.g. water
and sanitation, wildlife and natural resources. This requires discussion with the
Health Systems Group (TRG 3), as it can be anticipated that zoonotic diseases
and the specific problems of the livestock-dependent communities, often beyond
the end of the road and with no access to the formal health systems, pose specific
research questions for these groups.

6.2 Priorities for policy-makers

At present the TDR Stewardship initiative provides possibly the only coordinated
global and regional leadership to promote and coordinate an integrated approach
to these diseases. As such it represents a model of how this approach may be
applied in the context of those communities and ecosystems that facilitate
transmission.
The critical factor in progressing the Stewardship agenda consists of
moving zoonotic and other marginalized diseases up the research priority agenda
while seeking to initiate at-scale implementation of control with known strategies
and testing the effectiveness of those strategies against well-monitored baseline
data via operational and applied research. However, a prerequisite will be country
prioritization and commitment from interested and committed sectors. This
approach will require budget lines from both the relevant implementing ministry
and national research commitments, stable policy and essential long-term national
and international financing.
WHO Technical Report Series, No. 971, 2012

Promotion of advocacy efforts to inform stakeholders about the societal

burden of these diseases is necessary to create demand for control at all levels of
society. However, the most serious challenge to overcome is that the diseases to
be addressed currently have limited advocacy constituencies and are very often
restricted to the most marginalized and disenfranchized communities.
First steps should be to:
■■ develop guidelines for implementing integrated surveillance to
define the problem;
■■ develop plans for prevention and control activities for these diseases;
■■ conduct, maintain and report inventories of control activities and
tools currently being deployed.
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7. Conclusions
The Disease Reference Group focused on zoonoses and marginalized infections.
These infections are characteristic of marginalized populations that have little or
no access to government services. This may be because of population movement
or migration, social or political unrest, conflict, acute natural or human-made
disasters provoking complex emergencies, urban populations and slum dwellers,
or simply neglect of poor, politically and geographically marginalized populations
by the political leadership.
The following research priorities were identified:
■■ expand the surveillance for zoonotic diseases in humans and animals;
■■ re-attribute the burden of morbidity and mortality attributed to
diseases and conditions (cancers, neurological conditions, injuries)
to the neglected parasitic/zoonotic diseases;
■■ re-evaluate the societal burden of disease for zoonoses;
■■ expand systems research to determine how best the different sectors
can interact;
■■ evaluate the effectiveness of community-led approaches, including
the Community-led Total Sanitation approach, in the control of
zoonotic infectious diseases;
■■ integrate animal and human disease expertise with social science
perspectives;
■■ conduct more extensive studies on the costs of intervention, the
cost−benefits and cost−effectiveness;
■■ scale up research training to increase human resources in the area
of public health, including veterinary and livestock services, for
addressing zoonoses;
■■ create opportunities to evaluate and modify control strategies as
experience is gained in implementation;
■■ combine interventions allied to improved water and sanitation, and
health education and promotion, and deploy them for the human
and animal diseases in parallel;
■■ expand research on the use of new communication technologies such
as smart phones to enhance surveillance, reporting and evaluation.
A need for new scientific discoveries and innovations remains, but a
more effective scale-up of existing tools is required across the range of diseases
discussed. Effective interventions to address the infections covered do exist but
are often not implemented for reasons of cost, lack of policy know-how and the
failure to recognize an intervention targeting animals as an alternative approach
to reducing the disease burden in humans.
91
Acknowledgements
Special acknowledgement was made by the DRG to Drs Deborah Kioy, Ayoade
Oduola, Johannes Sommerfeld, Lee Willingham, Edith Certain, Julie Reza, and
Margaret Harris, Special Programme for Research and Training in Tropical
Diseases (TDR), WHO, Geneva, Switzerland, who were instrumental in the
creation and management of the DRG as well as the preparation and coordination
of the meetings. Valuable support was obtained from Dr Amal Bassili, WHO/
EMRO, Cairo, Egypt for the organization and hosting of the stakeholders’
consultation.
Support from and contribution made by WHO programmes and staff
were valued: Dr François Meslin, Neglected Tropical Diseases, Dr Claire-Lise
Chaignat, Water, Sanitation and Hygiene, and Dr Antonio Montresor, Neglected
Tropical Diseases, for technical input and participation of meetings. Dr Hind
Mohamed Abushama, the TDR Career Development Fellow was involved in the
preparation of this report.
The DRG also acknowledged with thanks the valuable contributions
made to its work by the stakeholders during the stakeholders’ consultation. The
stakeholders representing governments: Dr Nasr EL Sayed, Minister’s Assistant for
Preventive Affairs & Primary Health Care & Family Planning, Ministry of Health,
Cairo, Egypt; Dr Fatouh Mostafa Darwish, Head of Central Administration of
Preventive Medicine, General Organization for Veterinary Services, Ministry of
Agriculture and Land Reclamation, Cairo, Egypt; Dr Hassan Shafik Mohamed,
Head of the Central Administration of Public Health and Abattoirs, General
Organization for Veterinary Services, Ministry of Agriculture and Land
Reclamation, Cairo, Egypt; H.E. Dr Tabita Botrous Shokai, Federal Minister of
Health, Federal Ministry of Health, Khartoum, Sudan; H.E. Dr Faysal Hassan
Ibrahim, Minister for Animal Resources and Fisheries, Ministry for Animal
Resources and Fisheries, Khartoum, Sudan; Dr Sarah Mohamed Awadalla,
Director, UN Agencies Directorate, Directorate General of External Relations &
International Health, Federal Ministry of Health, Khartoum, Sudan; Dr Nasser
Mohsen Baowm, Deputy Minister, Ministry of Public Health and Population,
Sana’a, Yemen; Dr Mansoor Mohammed Al Qadasi, Director-General, Animal
Health and Veterinary Quarantines, Ministry of Agriculture and Irrigation,
Sana’a, Yemen;
Stakeholders representing international and non-governmental organizations:
Dr Kathleen Glynn, Chargée de Mission, Scientific and Technical Department,
World Organization for Animal Health (OIE), Paris, France; Dr Tarcisse Elongo,
Médecin Épidémiologie Provincial, Coordonnateur des Pools de Surveillance,
Chef de Sous Bureau de l'OMS au Katanga, Lumbubashi, Congo; Dr Wendy
Harrison, Deputy Director, Schistosomiaisis Control Initiative, Department of
93
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Infectious Disease Epidemiology, St Mary's Campus, Norfolk Place, London,

England; Dr Aristarchos M. Seimenis, Director, Intercountry Programme,
Coordinator WHO/Mediterranean Zoonoses Control Centre, c/o Center of Athens'
Veterinary Institutions, Athens, Greece;
Stakeholders representing academic institutions: Professor Samson
Mukaratirwa, Head, Biological and Conservation Sciences School, University
of KwaZulu-Natal, Durban, South Africa; Dr Esteban Chaves-Olarte, Associate
Professor, University of Costa Rica, San José, Costa Rica; Dr Maritza Canales,
Academic Coordinator, Masters Program in Infectious and Zoonotic Diseases,
School of Microbiology, National Autonomous University of Honduras,
Tegucigalpa, Honduras.
Valuable advice and support was received from the members of the
informal consultation who helped with the identification of scope for the DRG.
These included Dr Vicente Y. Belizario, Jr Deputy Director, National Institutes of
Health, and Professor, Department of Parasitology, University of the Philippines,
Manila, Philippines; Professor Kirana M. Bhatt, Department of Medicine, College
of Health Sciences, University of Nairobi. Kenya; Dr Rosanna Lagos Z. Hospital
de Niños Roberto del Río, Santiago, Chile and Dr Nina Mattock, Editor, Bernex,
Switzerland.
Sincere thanks and appreciation to the peer reviewers, both from within
and outside WHO for their comments and contributions on the technical
accuracy of this report. Lisa Nevitt, Centre for Neglected Tropical Diseases,
Liverpool School of Tropical Medicine, Liverpool, England, provided support
with tables and figures. Dr Philip G. Jenkins was responsible for the technical
editing of this report.
The activities of the DRG, including the production of this report, were
funded by the Special Programme for Research and Training in Tropical Diseases
(TDR) and by European Commission financial support under Agreement
PP‑AP/2008/160-163.
WHO Technical Report Series, No. 971, 2012

94
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Appendix 1
Membership of Disease-specific Reference Group on Zoonoses
and Marginalized Infectious Diseases of Poverty (DRG 6)

Names Country Expertise Gender

CHAIR Professor United Parasitology/ M
David Molyneux Kingdom epidemiology
CO-CHAIR Dr Zuhair Hallaj Syria Clinical medicine/ M
epidemiology
(infectious diseases)
MEMBERS Professor USA Communicable M
Gerard Keusch diseases
Professor Philippines Health Social Siences F
Pilar Ramos-Jimenez
Dr Helena Ngowi United Veterinary/public F
Republic of health
Tanzania
Dr Sarah Cleaveland USA/United Wildlife biology F
Kingdom
Dr Don McManus United Parasitology/ M
Kingdom/ microbiology/
Australia genomics and
genetics
Dr Hélèn Carabin USA/ Health/agriculture F
Canada economics
Dr Eduardo Gotuzzo Peru Infectious diseases M
Dr Kamal Kar India Water and sanitation M
Dr Ana Sanchez Honduras/ Parasitology F
Canada
Dr Amadou Garba Niger Clinical medicine M
(infectious diseases)

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Appendix 2
Disease-specific and thematic reference groups (DRGs/TRGs),
the think tank for infectious diseases of poverty and host countries

Reference group Host institution and country

DRG1 Malaria WHO country office, Cameroon
DRG2 Tuberculosis, leprosy and Buruli ulcer WHO country office, Philippines
DRG3 Chagas disease, human African WHO country offices, Sudan
trypanosomiasis and leishmaniasis and Brazil
DRG4 Helminth infections African Programme for
Onchocerciasis Control (APOC),
Burkina Faso
DRG5 Dengue and other emerging viral WHO country office, Cuba
diseases of public health importance
DRG6 Zoonoses and marginalized infectious WHO Regional Office for the
diseases of poverty Eastern Mediterranean, Egypt
TRG1 Social sciences and gender WHO country office, Ghana
TRG2 Innovation and technology platforms WHO country office, Thailand
for health interventions in infectious
diseases of poverty
TRG3 Health systems and implementation WHO country office, Nigeria
research
TRG4 Environment, agriculture and infectious WHO country office, China
WHO Technical Report Series, No. 971, 2012

diseases of poverty

110
 Appendices

Appendix 3
Think tank members
Professor Pedro Alonso, Director and Research Professor, Barcelona Centre for International
Health Research (CRESIB), Barcelona, Spain
Professor Rose Leke, Head, Department of Microbiology, Immunology, Hematology
and Infectious Diseases, Faculty of Medicine and Biomedical Sciences, University of
Yaoundé, Yaoundé, Cameroon
Dr Joel Breman, Senior Scientific Adviser, Fogarty International Center, Division of
International Epidemiology & Population Studies, National Institutes of Health,
Bethesda, MD, USA
Professor Graham Brown, Foundation Director, Nossal Institute for Global Health,
University of Melbourne, Carlton, Victoria, Australia
Dr Chetan Chitnis, Principal Investigator, International Centre for Genetic Engineering
and Biotechnology (ICGEB), New Delhi, India
Professor Alan Cowman, Researcher, Walter and Eliza Hall Institute of Medical Research,
Parkville, Victoria, Australia
Professor Abdoulaye Djimdé, Research Scientist, Chief of Laboratory, Malaria Research
and Training Center (MRTC), University of Bamako, and Malian EDCTP Senior Fellow,
Bamako, Mali
Dr Sócrates Herrera Valencia, Director, Caucaseco Scientific Research Center (SRC),
Instituto de Inmunología del Valle, Malaria Vaccine & Drug Development Centre,
Universidad del Valle, Cali, Colombia
Professor Marcelo Jacobs-Lorena, Johns Hopkins School of Public Health, Department of
Molecular Microbiology and Immunology, Malaria Research Institute, Baltimore, MD,
USA
Dr Ramanan Laxminarayan, Director, Center for Disease Dynamics, Economics and Policy
(CDDEP), Washington, DC, USA
Professor Rosanna Peeling, Chair of Diagnostics Research, London School of Hygiene &
Tropical Medicine, Department of Infectious and Tropical Diseases, Clinical Research
Unit, London, England
Professor Akintunde Sowunmi, University College Hospital, Malaria Research Laboratories,
Institute of Advanced Medical Research and Training (IAMRAT), Ibadan, Nigeria
Dr Sarah Volkman, Senior Research Scientist, Harvard School of Public Health, Department
of Immunology and Infectious Diseases, Boston, MA, USA
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Dr Tim Wells, Chief Scientific Officer, Medicines for Malaria Venture (MMV), Geneva,
Switzerland
Professor Gavin Churchyard, Chief Executive Officer, Aurum Institute, Johannesburg,
South Africa
Professor Charles Yu, Medical Director and Vice President for Medical Services, De La Salle
Health Sciences Institute, Vice-Chancellor’s Office for Mission, Cavite, Philippines
Dr Madhukar Pai, Assistant Professor, McGill University, Department of Epidemiology,
Biostatistics & Occupational Health, Montreal, Quebec, Canada
Dr Ann M. Ginsberg, Senior Advisor, Global Alliance for TB Drug Development, New York,
NY, USA
Dr Jintana Ngamvithayapong-Yanai, President, TB/HIV Research Foundation, Chiang Rai,
Thailand
Professor Laura C. Rodrigues, Head, Department of Epidemiology and Population Health,
London School of Hygiene & Tropical Medicine, London, England
Professor Martien Borgdorff, Head, Cluster Infectious Diseases, Municipal Health Service
of Amsterdam and Professor of Epidemiology, University of Amsterdam, Amsterdam,
Netherlands
Professor Biao Xu, Director of Tuberculosis Research Center, Professor of Epidemiology and
Deputy Chair, Department of Epidemiology, School of Public Health, Fudan University,
Shanghai, China
Dr Francis Adatu Engwau, Programme Manager, National Tuberculosis/Leprosy Programme,
Kampala, Uganda
Dr Anthony David Harries, Senior Advisor, Director, Department of Research, London
School of Hygiene & Tropical Medicine. University of London, London, England
Dr Timothy Paul Stinear, Head of Research Group NHMRC, R. Douglas Wright Research
Fellow, Department of Microbiology and Immunology, University of Melbourne,
WHO Technical Report Series, No. 971, 2012

Parkville, Victoria, Australia

Dr Helen Ayles, Director, ZAMBART Project, London School of Hygiene & Tropical
Medicine, ZAMBART, Ridgeway Campus, University of Zambia, Lusaka, Zambia
Professor Diana Lockwood, Department of Infectious and Tropical Diseases, London
School of Hygiene & Tropical Medicine, London, England
Professor Ken Stuart, President Emeritus & Founder, Seattle Biomedical Research Institute,
Seattle, WA, USA
Professor Maowia M. Mukhtar, Institute of Endemic Diseases, Department of Molecular
Biology, University of Khartoum, Khartoum, Sudan
Professor Bianca Zingales, Instituto de Quimica, Universidade de São Paulo, São Paulo,
Brazil
112
 Appendices

Professor Marleen Boelaert, Head, Department of Public Health, Institut de Médecine

Tropical, Epidemiology & Disease Control Unit, Department of Public Health, Antwerp,
Belgium
Ms Marianela Castillo-Riquelme, Departamento de Economía de la Salud, DIPLAS,
Subsecretaría de Salud Publica, Ministerio de Salud de Chile, Santiago, Chile
Professor Mike J. Lehane, Professor of Molecular Entomology and Parasitology, Liverpool
School of Tropical Medicine, Liverpool, England
Professor Pascal Lutumba, Institut National de Recherche Bio-Médicale, Kinshasa University,
Democratic Republic of the Congo
Dr Enock Matovu, Senior Lecturer, Faculty of Veterinary Medicine, Makerere University,
Department of Veterinary, Parasitology and Microbiology, Kampala, Uganda
Dr David Sacks, Head, Intracellular Parasite Biology Section, National Institutes of Health,
National Institute of Allergy and Infectious Diseases, Laboratory of Parasitic Diseases,
Bethesda, MD, USA
Dr Sergio Alejandro Sosa-Estani, Head, Service of Epidemiology, Instituto de Efectividad
Clinica y Sanitaria, Buenos Aires, Argentina
Dr Shyam Sundar, Department of Medicine, Institute of Medical Sciences, Banaras Hindu
University, Varanasi, India
Professor Rick L. Tarleton, Distinguished Research Professor, Center for Tropical &
Emerging Global Diseases, Coverdell Center for Biomedical Research, University of
Georgia, Athens, GA, USA
Professor Alon Warburg, Professor of Vector Biology and Parasitology, The Kuvin Center for
the Study of Infectious and Tropical Diseases, Faculty of Medicine, Hebrew University,
Einkerem, Israel
Dr Sara Lustigman, Head, Laboratory of Molecular Parasitology, Lindsley F. Kimball
Research Institute, New York Blood Center, New York, NY, USA
Dr Boakye Boatin, Noguchi Memorial Institute for Medical Research, University of Ghana,
Legon, Accra, Ghana
Dr Guojing Yang, Vice Head, Department of Schistosomiasis Control, Jiangsu Institute of
Parasitic Diseases, Wuxi, China
Dr Rashida M.D.R. Barakat, High Institute of Public Health, Alexandria University,
Alexandria, Egypt
Dr Maria Gloria Basanez, Professor of Neglected Tropical Diseases, Department of
Infectious Disease Epidemiology, Faculty of Medicine, Imperial College, London,
England
Dr KwablahAwadzi, Onchocerciasis Chemotherapy Research Centre, Hohoe Hospital,
Hohoe, Ghana
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 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Professor Banchob Sripa, Division of Experimental Pathology, Department of Pathology,

Faculty of Medicine, KhonKaen University, KhonKaen, Thailand
Professor Warwick Grant, Head of Genetics, School of Molecular Sciences, Genetic
Department, La Trobe University, Bundoora, Victoria, Australia
Professor Roger K. Prichard, Professor of Biotechnology, Institute of Parasitology, McGill
University, Ste Anne de Bellevue, Quebec, Canada
Professor Hector Hugo Garcia, Department of Microbiology and Cysticercosis Unit,
Instituto de Ciencias Neurologicas, Universidad Peruana Cayetano Heredia, Lima, Peru
Dr James McCarthy, Group Leader, Clinical Tropical Medicine, Queensland Institute of
Medical Research, University of Queensland, Herston, Queensland, Australia
Professor Kouakou Eliezer N’Goran, Professeur de Biologie, Laboratoire de Zoologie et de
Biologie Animale, Université de Cocody, Abidjan, Côte d’Ivoire
Dr Andréa Gazzinelli, School of Nursing, Federal University of Minas Gerais, Belo Horizonte,
MG, Brazil
Dr Jeremy Farrar, Director, Oxford University Clinical Research Unit in Viet Nam, The
Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam
Professor Maria Guzman, Head, Virology Department, Instituto de Medicina Tropical
“Pedro Kouri”, Havana, Cuba
Dr Natarajan Arunachalam, Senior Grade Deputy Director, Centre for Research in Medical
Entomology, Indian Council of Medical Research, Madurai, India
Dr Duane Gubler, Professor, Director, Asia-Pacific Institute of Tropical Medicine and
Infectious Diseases, John A Burns School of Medicine, University of Hawaii, Honolulu,
HI, USA
Dr Sirirpen Kalayanarooj, Queen Sirikit National Institute of Child Health, Bangkok, Thailand
WHO Technical Report Series, No. 971, 2012

Dr Linda Lloyd, Director, Center for Research, The Institute for Palliative Medicine at San
Diego Hospice, San Diego, CA, USA
Dr Lucy Chai See Lum, Associate Professor of Paediatrics, Department of Paediatrics,
Faculty of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
Dr Amadou Sall, Chef de l’Unité des Arbovirus et Virus des Fièvres hémorragiques, Insitut
Pasteur de Dakar, Arboviruses Unit/WHO Collaborating and Conference Centre,
Dakar, Senegal
Dr Eric Martinez Torres, Instituto de Medicina Tropical Pedro Kouri, Havana, Cuba
Dr Philip J. McCall, Vector Group, Liverpool School of Tropical Medicine, Liverpool, England
Professor Derek Cummings, Assistant Professor, Department of Epidemiology, Bloomberg
School of Public Health, Johns Hopkins University, Baltimore, MD, USA
114
 Appendices

Dr Hongjie Yu, Deputy Director, Professor, Office for Disease Control and Emergency
Response, Chinese Center for Disease Control and Prevention, Beijing, China
Professor David Molyneux, Senior Professorial Fellow, Liverpool School of Tropical
Medicine, Liverpool, England
Dr Zuhair Hallaj, Senior Consultant on Communicable Diseases, WHO Regional Office for
the Eastern Mediterranean, Cairo, Egypt
Dr Gerald T. Keusch, Professor of International Health and of Medicine, Boston University,
Boston, MA, USA
Dr Pilar Ramos-Jimenez, Philippine NGO Council on Population, Health and Welfare, Pasay
City, Philippines
Professor Donald Peter McManus, National Health and Medical Research Council of
Australia, Senior Principal Research Fellow, Head of Molecular Parasitology Laboratory,
Queensland Institute of Medical Research, Brisbane, Queensland, Australia
Dr Eduardo Gotuzzo, Director, Instituto de Medicina Tropical “Alexander von Homboldt”,
Universidad Peruana Cayetano Heredia, Lima, Peru
Dr Kamal Kar, Chairman, CLTS Foundation, Calcutta, India
Dr Ana Sanchez, Associate Professor, Department of Community Health Sciences, Brock
University, St. Catharines, Ontario, Canada
Dr Amadou Garba, Director, Réseau International Schistosomose, Environnement,
Aménagement et Lutte (RISEAL), Niamey, Niger
Dr Helena Ngowi, Department of Veterinary Medicine and Public Health, Sokoine
University of Agriculture, Mongoro, United Republic of Tanzania
Dr Sarah Cleaveland, Reader, Division of Ecology and Evolutionary Biology, University of
Glasgow, Glasgow, Scotland
Dr Hélène Carabin, University of Oklahoma, Oklahoma Health Sciences Center, Oklahoma
City, OK, USA
Professor Barbara McPake, Director and Professor, Institute for International Health and
Development, Queen Margaret University, Edinburgh, Scotland
Dr Margaret Gyapong, Director, Dodowa Health Research Centre, Ghana Health Service,
Dodowa, Ghana
Professor Juan Arroyo Laguna, Profesor Principal del Departamento Académico de Salud
y Ciencias Sociales, FASPA-UPCH, Universidad Pruana Cayetano Heredia, Lima, Peru
Professor Sarah Atkinson, Reader, Department of Geography, University of Durham,
Science Laboratories, Durham, England
Professor Rama Baru, Professor, Centre of Social Medicine and Community Health,
Jawaharlal Nehru University, New Delhi, India
115
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Professor Otto Nzapfurundi Chabikuli, Regional Technical Director, Africa Region with
Family Health International (FHI360), Pretoria, South Africa
Professor Kalinga Tudor Silva, Senior Professor, Faculty of Arts, University of Peradeniya
and Executive Director, International Centre for Ethnic Studies, Kandy, Sri Lanka
Professor Charles Hongoro, Research Director, Policy Analysis Unit, Human Sciences
Research Council, Pretoria, South Africa
Professor Mario Mosquera-Vasquez, Associate Professor, Departamento de Comunicación
Social, Universidad del Norte, Barranquilla, Colombia
Professor Chuma Jane Mumbi, Research Fellow, Kenya Medical Research Institute,
Wellcome Trust Research Programme, Kilifi, Kenya Professor Helle Samuelsen, Head,
Department of Anthropology, University of Copenhagen, Copenhagen, Denmark
Professor Sally Theobald, Liverpool School of Tropical Medicine, Liverpool, England
Professor Mitchell Weiss, Professor and Head of the Department of Public Health and
Epidemiology Swiss Tropical Institute, Basel, Switzerland
Professor Yongyuth Yuthavong, Senior Researcher, National Centre for Genetic Engineering
and Biotechnology (BIOTEC), Bangkok, Thailand
Professor Simon Croft, Professor of Parasitology, Department of Infectious and Tropical
Diseases, London School of Hygiene and Tropical Medicine, London, England
Professor Rama Baru, Professor, Centre of Social Medicine and Community Health,
Jawaharlal Nehru University, New Delhi, India
Professor Sanaa Botros, Manager of Training and Consultation Unit, Theodor Bilharz
Research Institute, Imbaba, Giza, Egypt
Dr Mary Jane Cardosa, Director, Institute of Health and Community Medicine, University
Malaysia Sarawak, Kota, Malaysia
Professor Simon Efange, Professor of Chemistry, University of Buea, Buea, Cameroon
WHO Technical Report Series, No. 971, 2012

Dr Vish Nene, Director of Biotechnology Thematic Group, International Livestock Research

Institute, Nairobi, Kenya
Dr Antonio Oliveira-Dos-Santos, Medical Affairs Director, Genzyme, Rio de Janeiro, Brazil
Professor Paul Reider, Department of Chemistry, Princeton University, Princeton, NJ, USA
Dr Giorgio Roscigno, Former Chief Executive Officer, Foundation for Innovative New
Diagnostics, Budé, Geneva, Switzerland
Professor Anthony So, Director, Terry Stanford Institute of Public Health Policy, Duke
University, Durham, NC, USA
Professor Ming-Wei Wang, Director, The National Centre for Drug Screening, Shanghai,
China
116
 Appendices

Dr Miguel Angel González-Block, Executive Director, Centre for Health Systems Research,
National Institute of Public Health, Cuernavaca, Mexico
Professor Olayiwola Akinsonwon Erinosho, Executive Secretary at Health Reform
Foundation of Nigeria (HERFON), Abuja, Nigeria
Dr Charles Collins, Honorary Senior Research Fellow, University of Birmingham,
Birmingham, England
Dr Dyna Arhin, Associate Consultant, Public Health Action Support Team (PHAST), Faculty
of Medicine, Imperial College London, England
Dr Abbas Bhuiya, Senior Social Scientist, Head, Poverty and Health Programme and Social
and Behavioural Sciences Unit, Public Health Sciences Division, ICDDR,B, Mohakhali,
Dhaka, Bangladesh
Dr Celia Maria de Almeida, Senior Researcher and Professor in Health Policy and Health
Systems Organization, Health Administration and Planning Department, Escola
Nacional de Saude Publica-ENSP/Fiocruz, Rio de Janeiro, Brazil
Professor Barun Kanjilal, Professor, Indian Institute of Health Management Research,
Jaipur, India
Dr Joseph Kasonde, Executive Director, Zambia Forum for Health Research, Lusaka, Zambia
Dr Dorothée Kinde-Gazard, Minister of Health, The National AIDS Control Probramme
(PNLS), Cotonou, Benin
Dr Samuel Wanji, Research Foundation for Tropical Diseases and the Environment, Buea,
Cameroon
Professor Anthony McMichael, Professor, National Centre for Epidemiology and Population
Health, Australian National University, Canberra, ACT, Australia
Professor Xiao-Nong Zhou, Director, National Institute of Parasitic Disease, China Centers
for Disease Control, Shanghai, China
Professor Corey Bradshaw, Director of Ecological Modelling, The Environment Institute
and School of Earth & Environmental Sciences, University of Adelaide, Adelaide,
Western Australia, Australia
Dr Stuart Gillespie, Director, RENEWAL, Coordinator, Agriculture and Health Research
Platform, International Food Policy Research Institute (IFPRI), c/o UNAIDS, Geneva,
Switzerland
Dr Suad M. Sulaiman, Health & Environment Adviser, Khartoum, Sudan
Professor James A. Trostle, Professor of Anthropology, Anthropology Department, Trinity
College, Hartford, CT, USA
Dr Jürg Ützinger, Assistant Professor, Department of Public Health and Epidemiology,
Swiss Tropical Institute, Basel, Switzerland
117
 Research Priorities for Zoonoses and Marginalized Infections Report of the TDR Disease Reference Group

Professor Bruce Wilcox, Professor and Director of the Global Health Program at the
University of Hawaii, Honolulu, HI, USA
Dr Guojing Yang, Assistant Professor (Principal Investigator), Dept. Schistosomiasis Control,
Jiangsu Institute of Parasitic Diseases, Jiangsu Province, China
WHO Technical Report Series, No. 971, 2012

118
 Think tank co-chairs and host countries

Appendix 4
Distribution of the Think Tank leadership (co-Chairs)

TRG: Thematic Reference Group

Appendices

DRG: Disease-specific Reference Group

119
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W H O Te c h n i c a l R e p o r t S e r i e s

971

Research Priorities for Zoonoses and Marginalized Infections

Research Priorities for Zoonoses and Marginalized Infections

This report provides a review and analysis of the research

landscape for zoonoses and marginalized infections which
affect poor populations, and a list of research priorities to
support disease control. The work is the output of the Disease
Reference Group on Zoonoses and Marginalized Infectious
Diseases of Poverty (DRG6), which is part of an independent
think tank of international experts, established and funded by
the Special Programme for Research and Training in Tropical
Research Priorities
Diseases (TDR), to identify key research priorities through
review of research evidence and input from stakeholder for Zoonoses and
Marginalized Infections
consultations.
The report covers a diverse range of diseases, including
zoonotic helminth, protozoan, viral and bacterial infections
considered to be neglected and associated with poverty.
Disease-specific research issues are elaborated under individual
disease sections and many common priorities are identified
among the diseases such as the need for new and/or improved Technical report of the TDR Disease Reference Group on Zoonoses
drugs and regimens, diagnostics and, where appropriate, and Marginalized Infectious Diseases of Poverty
vaccines. The disease-specific priorities are described as micro
priorities compared with the macro level priorities which will
drive policy-making for: improved surveillance; interaction
between the health, livestock, agriculture, natural resources
and wildlife sectors in tackling zoonotic diseases; and true WHO Technical Report Series
assessment of the burden of zoonoses.
This is one of ten disease and thematic reference group reports
that have come out of the TDR Think Tank, all of which
have contributed to the development of the Global Report
for Research on Infectious Diseases of Poverty, available at:
www.who.int/tdr/capacity/global_report.