Dr. Julius R. Migrio, Jr.
BLOOD AND TISSUE
PROTOZOANS
Leishmaniasis
OVERVIEW
Outline
Overview
Leishmania parasites are named after W.B.
Leishman.
Demographics
Causative Agent
Life Cycle
Symptoms
He recognized one of the earliest strains in
1901.
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
DEMOGRAPHICS
Affects more than 12 million people!
Outline
Overview
Demographics
At risk: more than 350 million people
Causative Agent
Life Cycle
2 million new cases annually
1.5 million visceral leishmaniasis
500,000 cutaneous leishmaniasis
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
59,000 people die annually
Leishmaniasis
DEMOGRAPHICS
Endemic in 88 countries on 4 continents
Outline
Overview
Demographics
72 are developing countries
13 of which are among the least
developed
Usually targets migrants, seasonal
workers, refugees, sex workers and
truck drivers
Individual risk factors such as
malnutrition and immunosuppression
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
DEMOGRAPHICS
Endemic in 88 countries on 4 continents
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Usual targets are IV drug users
Leishmaniasis
DEMOGRAPHICS
Endemic in 88 countries on 4 continents
Cutaneous leishmaniasis cases:
Iran
Afghanistan
Syria
Saudi Arabia
Brazil
Peru
Visceral leishmaniasis cases:
Bangladesh
Brazil
India
Nepal
Sudan
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
CAUSATIVE AGENT
Parasitic protozoa of the genus Leishmania
Over 20 species and subspecies infect
humans
Eg. Leishmania donovani, L. major, L.
braziliense
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
PHOTO: Photomicrograph of Leishmania in a blood film (using Romanovski stain).
Leishmaniasis
LIFE CYCLE
Transmitted mainly by bites from sandflies
Genus Phlebotomus
About 30 species are known vectors
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Reservoir:
Dogs
Rats
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
LIFE CYCLE
Promastigotes enter the bloodstream
then are ingested by macrophages
then mature to amastigotes
then reproduce by binary fission
then burst out from the macrophage
and either infect other macrophages
or get ingested by sandflies
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
SYMPTOMS
The leishmaniases can be classified into 4
main forms:
Outline
Overview
Demographics
Causative Agent
1. Visceral leishmaniasis (VL)
2. Cutaneous leishmaniasis (CL)
3. Mucocutaneous leishmaniasis (MCL)
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
4. Diffuse cutaneous leishmaniasis (DCL)
Control
What now?
Leishmaniasis
SYMPTOMS
1. Visceral leishmaniasis (VL)
- Kala azar
- Most serious form
- Caused by L. donovani
- Mortality rate approaches 100%!
Symptoms:
- Irregular bouts of fever
- Weight loss
- Hepatomegaly
- Splenomegaly
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
SYMPTOMS
2. Cutaneous leishmaniasis (CL)
- Baghdad ulcer, Delhi boil, Bouton dOrient
- The most common form
- Caused by L. major
- Usually in Africa or Asia
Symptoms:
- Up to 200 simple skin lesions
- Wounds heal within a few months
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
SYMPTOMS
3. Mucocutaneous leishmaniasis (MCL)
- Caused by L. braziliensis
Outline
Overview
Demographics
Causative Agent
Symptoms:
- Starts as skin ulcers
- Spreads, causing dreadful and massive
tissue destruction, especially of the
nose and mouth
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
SYMPTOMS
4. Diffuse cutaneous leishmaniasis (DCL)
Outline
Overview
Demographics
- Disseminated and chronic skin lesions
- resembles leprotamous leprosy
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
DIAGNOSIS
Outline
Overview
1. Direct visualization
Demographics
Causative Agent
2. Freeze-dried Direct Agglutination Test
(DAT)
3. rK39 dipstick
Life Cycle
Symptoms
Diagnosis
Treatment
4. Latex Agglutination urine test
Prevention and
Control
What now?
Leishmaniasis
DIAGNOSIS
Outline
Overview
1. Direct visualization
- Uses tissue aspirate
- Spleen
- Bone marrow
- Lymph nodes
- Unsuitable for field use
- Invasive
- Low sensitivity
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
DIAGNOSIS
Outline
Overview
2. Freeze-dried Direct Agglutination Test
(DAT)
-Detects antibodies
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
DIAGNOSIS
Outline
Overview
3. rK39 dipstick
-Based on recombinant antigen of
leishmania parasite
-Being investigated for use in active case
detection
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
DIAGNOSIS
Outline
Overview
4. Latex Agglutination Urine Test
-Detects antigens
-Used among patients who have
compromised immune response
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
TREATMENT
Outline
Overview
Most cases of cutaneous leishmaniasis
heal without treatment
Immunity against further infection can be
attained
immunization efforts in South-west Africa
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
TREATMENT
Outline
Overview
Other forms of leishmaniasis require long
courses:
pentavalent antimony drugs
Given parenterally
Meglumine antimonate
Sodium antimony gluconate
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Resistance have been reported, prompting
the use of amphotericin B
Prevention and
Control
What now?
Leishmaniasis
TREATMENT
Outline
Overview
Miltefosine
- First oral treatment for VL
- Potential teratogen
- Possibility of developing resistance
Paromomycin
- An aminoglycoside
- Used topically for CL
- Used orally as 2nd line treatment of VL
- Injectable formulation is being
developed
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Leishmaniasis
PREVENTION & CONTROL
Outline
Overview
Vector control
Insect repellants
Insecticides
Bednets
Reservoir control
Poisoned baits
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
AFRICAN TRYPANOSOMIASIS
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
DEMOGRAPHICS
Outline
Overview
60 million people are at risk
300,000 500,000 new cases annually
Demographics
Causative Agent
Life Cycle
66,000 people die annually
Symptoms
Prevalence of more than 70% in some
areas
Treatment
Diagnosis
Prevention and
Control
What now?
African Trypanosomiasis
DEMOGRAPHICS
Outline
Overview
36 countries in sub-Saharan Africa:
7 countries: disease is highly endemic
4 countries: disease is endemic
2 countries: disease has moderate endemicity
3 countries: status is poorly understood
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
CAUSATIVE AGENTS
Protozoan parasites of the genus
Trypanosoma
- Trypanosoma brucei rhodesiense
- east and southern Africa
- T.b. gambiense
- west and central Africa
- T.b. brucei
- cattle disease only
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
LIFE CYCLE
Transmitted mainly by bites from tsetse flies
Genus Glossina spp.
Parasites mature in the salivary glands
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Reservoir:
cattle
wild animals
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
LIFE CYCLE
Metacyclic trypomastigotes enter the
bloodstream
Outline
Overview
Demographics
then transform into bloodstream
trypomastigotes
Causative Agent
then reproduce by binary fission
Symptoms
and get ingested by flies
Life Cycle
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
SYMPTOMS
T.b. gambiense
- Chronic infection
- less severe (several years)
T.b rhodesiense
- Usually acute infection
- more severe (days to weeks)
- Progresses to death!
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
SYMPTOMS
Outline
Overview
Early signs and symptoms
- fever
- headache
- malaise
- anemia
- joint pains
- enlarged lymph glands
- splenomegaly
Late signs and symptoms
- neurological symptoms
- progresses to coma
- fatal if left untreated!
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
SYMPTOMS
Outline
Overview
Pathophysiology: African Sleeping Sickness
Mainly an immune-mediated
hypersensitivity reaction
Due to parasite antigens
acting on:
o RBCs
o cardiac tissue
o brain tissue
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
DIAGNOSIS
Outline
Overview
1. Direct visualization
Demographics
Causative Agent
2. Card Agglutination Test for Trypanosomes
(CATT)
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
DIAGNOSIS
Outline
Overview
1. Direct visualization
Demographics
Causative Agent
- Can do blood smear or lumbar puncture
- Invasive
- Not suitable in the field
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
DIAGNOSIS
Outline
Overview
2. Card Agglutination Test for Trypanosomes
(CATT)
- useful for screening of T. b. gambiense
- no comparable test for T. b. rhodesiense
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
TREATMENT
Outline
Overview
Pentamidine
for early-stage T. b. gambiense sleeping
sickness
Suramin
for early-stage T. b. rhodesiense
sleeping sickness
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
TREATMENT
Outline
Overview
Melarsoprol
for late-stage disease of both forms of
sleeping sickness
Original drug of choice
Relatively toxic!
Growing resistance patterns
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
TREATMENT
Outline
Overview
Eflornithine
current 1st line drug for T. b. gambiense
sleeping sickness patients who do not
respond to melarsoprol
Resurrection drug
costs $US 300-500 per patient and has
many side-effects
Current studies (June 2009) show
Nifurtimox-Eflornithine combination
safer and as effective
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
African Trypanosomiasis
PREVENTION & CONTROL
Outline
Overview
Surveillance of at-risk populations
Clearance of tsetse fly breeding
grounds
Insecticides
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
Fly traps and screens
What now?
CHAGAS DISEASE
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
OVERVIEW
Outline
Overview
named after a Brazilian doctor, Carlos
Chagas
first described in 1909
- Illustrated the life-cycle of the parasite
- identified the insect vector
- identified small mammals as reservoir
hosts
- suggested means to help prevent
transmission
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
DEMOGRAPHICS
Outline
Overview
About 16-18 million people are infected
Demographics
Causative Agent
- 25% are symptomatic
- About 2-3 million chronic cases
More than 200,000 new cases annually
Life Cycle
Symptoms
Diagnosis
Treatment
More than 20,000 annual deaths
Prevention and
Control
About 350 million people are at risk
What now?
Chagas Disease
DEMOGRAPHICS
Outline
Overview
18 countries in 2 ecological zones:
1. Central America, Mexico, Northern South
America
2. Southern Cone of South America
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
CAUSATIVE AGENTS
Protozoan parasites Trypanosoma cruzi
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
LIFE CYCLE
Transmitted to humans in 3 ways:
1. By bloodfeeding Assassin/Reduviid
bugs (sub-family Triatominae)
2. Through transfusion with infected blood
3. Congenitally, from infected mother to
fetus
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
LIFE CYCLE
Heres how it goes
Bug bites you while it sucks blood
It poops while feeding on your blood
Feces contains
metacyclic trypomastigotes
Trypomastigotes enter through bite wound
or mucosal surfaces
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
LIFE CYCLE
Heres how it goes
They invade cells
where they develop into amastigotes
and replicate by binary fission
and burst out as bloodstream
trypomastigotes
and can:
Invade other cells
Be sucked by another bug
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
SYMPTOMS
Usually, an initial small furunculoid lesion at
the bite site
Within a few days, fever and
lymphadenopathy develops
In children and immunocompromised
patients, may lead to dissemination and
death
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
SYMPTOMS
Romaas sign
- swollen palpebrae
- due to conjunctival point of entry
- painless
- persists for up to 2 months
Outline
Overview
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
SYMPTOMS
Outline
Overview
May proceed to an asymptomatic phase
- Could last from months to years
- Dissemination of the parasites:
1. Heart
2. GI tract (intestines and esophagus)
3. Brain (?)
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
SYMPTOMS
Outline
Overview
PATHOPHYSIOLOGY:
Theory 1:
Infection-induced autoimmune disease
parasite mediated cross-reaction
Supported by paradigm of
chronic disease fewer parasites!
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Theory 2:
Parasite persistence
chronic infection leads to chronic
inflammation
Control
What now?
Chagas Disease
DIAGNOSIS
Outline
Overview
1. Direct visualization
Demographics
Causative Agent
2. Indirect test
3. Imaging tests
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
DIAGNOSIS
Outline
Overview
1. Direct visualization
- Blood smear
- observation of rapid movements of live
trypomastigotes
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
DIAGNOSIS
Outline
Overview
2. Indirect test
-Immunologic tests (ELISA, IFA)
-Hemoculture in liver infusion tryptose
medium
-Xenodiagnosis
- Uses live Triatomina bugs
- Allowed to feed on a patient
- Bug intestinal contents are then
examined
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
DIAGNOSIS
Outline
Overview
2. Imaging tests
-Abdominal x-ray
-Chest x-ray
-Esophageal imaging
-Electrocardiogram
- low-voltage QRS complexes (acute
phase)
- Ventricular premature beats, BBB, Twave inversion, low-voltage QRS,
etc. (chronic phase)
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
TREATMENT
Outline
Overview
Nifurtimox and Benznidazole
Demographics
Causative Agent
- Nitroimidazole
- Used in acute and early chronic (a few
years) phase
- No effect on chronic cases
- Side effects: hypersensitivity,
polyneuritis, neutropenia
- Category C in pregnancy
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
TREATMENT
Outline
Overview
Cardiopathy
- Class III antiarrythmics (Amiodarone,
Sotalol)
- Diuretics (if with CHF)
- Pacemakers for persistent
bradyarrythmias
- Heart transplant!
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
TREATMENT
Outline
Overview
Megaesophagus
- Balloon dilatation (but with risk of
rupture)
- Surgical treatment of achalasia
- Bowel loop interposition for late stages
Megacolon
- Laxatives for constipation
- Surgery: end-to-end anastomosis
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
PREVENTION & CONTROL
Outline
Overview
Vector Control
- Insecticides
- substituting plastered walls and a metal
roof for adobe-walled, thatch-roofed
dwellings
- Sanitation
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
Chagas Disease
PREVENTION & CONTROL
Outline
Overview
Transfusional Control
- Blood transfusion transmission is the
second main route of T. cruzi infection
- Infection rates can go up as high as
24%
- Infectivity risk: 20% for T. cruzi
- Screening should be mandatory!
Demographics
Causative Agent
Life Cycle
Symptoms
Diagnosis
Treatment
Prevention and
Control
What now?
