American Trypanosomiasis

Chagas Disease
New World Trypanosomiasis
South American Trypanosomiasis
Mal de Chagas
Chagas-Mazza Disease
 Overview
• Organism
• History
• Epidemiology
• Transmission
• Disease in Humans
• Disease in Animals
• Prevention and Control
• Actions to Take
Center for Food Security and Public Health, Iowa State University, 2012
ORGANISM
 The Organism
• Protozoan parasite
– Trypanosoma cruzi
• Cause of American
trypanosomiasis
(Chagas disease)
• Susceptible to:
– Disinfectants, direct
sunlight,
other harsh
environments Center for Food Security and Public Health, Iowa State University, 2012
HISTORY
 History of Chagas
• 1907: Dr. Carlos Chagas
first becomes aware
of the barbiero (a blood
sucking bug)
• 1909: First publications on
newly discovered
trypanosome
• 1930s: Public health
importance becomes
known
Center for Food Security and Public Health, Iowa State University, 2012
EPIDEMIOLOGY
 Geographic Distribution
• Americas
– South America
– Central America
• United States
– Endemic in Southern
half and California
• 8 to 11 million people
infected worldwide

Center for Food Security and Public Health, Iowa State University, 2012
 Populations at Risk
• Neglected Infection of Poverty (NIP)
– Disproportionately affects
impoverished people in the U.S.
• Occupational groups
– Veterinarians, laboratory personnel
• Wildlife handlers
• Hunters
• Travelers to endemic areas
Center for Food Security and Public Health, Iowa State University, 2012
 Species Affected
• Many mammals in the Americas
• Frequent hosts in the U.S.
– Opossums
– Armadillos
– Raccoons
– Coyotes
– Rats, mice, squirrels
– Dogs
– Cats
Center for Food Security and Public Health, Iowa State University, 2012
TRANSMISSION
 Transmission
• Vector-borne
– Triatomine insects
(blood sucking insects)
• Reduviid insects,
kissing beetle/bug,
assassin bug
– Multiple species
capable of transmission
• Triatoma
• Rhodnius
• Panstrongylus

Center for Food Security and Public Health, Iowa State University, 2012
 Transmission
• Three transmission cycles
– Sylvatic (wild)
• Wildlife-insect transmission
• Human infections rare
– Domestic
• Human-insect transmission
– Peridomestic
• Insect – domesticated transmission
• Transmitted via:
– Blood, organs, ingestion, in utero, milk
Center for Food Security and Public Health, Iowa State University, 2012
Center for Food Security and Public Health, Iowa State University, 2012
Center for Food Security and Public Health, Iowa State University, 2012
 Trypanosomatidae

• Kinetoplast:
DNA containing organelle from which a
mitochondrion arises; Mitochondrial
compartment packed with minicircles
and maxicircles of DNA; self-replicating.

• 1 flagella
• 1 nucleus
• 1 mitochondrion
• leaf-like or rounded body
• all parastitic
• change body form depending on host
and tissue
• cyclic development (6 different stages)
 Genus Trypanosoma
• some of the most economically important human and animal parasites
• parasites of invertebrates and all classes of vertebrates
• blood or tissue fluids; intracellular
• mostly transmitted through invertebrate vectors

Development:
Anterior station - Salivaria
• division of trypomastigotes in midgut of vector
• migration of parasite forward into the upper digestive
tract (eg. salivary glands)
• metacyclic trypomastigotes passed to vertebrate
host when the vector feeds.
• Salivarian (eg.T. brucei gambiense) by tse-tse fly.

Posterior station - Stercoraria

• parasite in the hindgut transforms into epimastigotes
and metacyclic trypomastigotes
• move back through the digestive tract
• metacyclic trypomastigotes are passed to the vertebrate
host in the vector feces.
• Stercocarian (eg. Trypanosoma cruzi) by kissing bugs.
DISEASE IN HUMANS
 Chagas Disease
• Incubation period
– 5 to 14 days after exposure
to triatomine insect feces
– 20 to 40 days after blood transfusion
– 5 to 40 years after infection
• Chronic stage

Center for Food Security and Public Health, Iowa State University, 2012
 Symptoms of Chagas
Disease
- start with fever, headaches, and joint
pains; not uncommon symptoms of
many parasitical diseases.
- However, as the parasites enter
through both the blood and lymph
systems, the lymph nodes swell up
to tremendous size.
- If left untreated, symptoms spread
and attack the kidneys and heart and
eventually enters a neurological
phase.

Center for Food Security and Public Health, Iowa State University, 2012
 Symptoms of Chagas
Disease
- Easily the most life-threatening stage,
when symptoms pass the blood-brain
barrier, confusion, reduced
coordination, and sleep cycle (which
gives the disease it’s name) is
disturbed.
- Fatigue punctured with manic periods
increases daytime slumber and
nighttime insomnia. Without the
treatment, the disease is fatal, and the
neurological phase is irreversible.

Center for Food Security and Public Health, Iowa State University, 2012
 Chagas Disease
• Acute phase
– Parasites found in blood
– Most adults asymptomatic
– Chagoma
• Localized painless induration
– Romaña’s sign
• Edema of eyes, conjunctivitis
• Usually resolves in weeks to months

Center for Food Security and Public Health, Iowa State University, 2012
 Chagas Disease
• Indeterminate phase
– Asymptomatic phase of varying length
– Parasites disappear from blood
– Most patients enter chronic phase
within 5 to 15 years

Center for Food Security and Public Health, Iowa State University, 2012
 Chagas Disease
• Chronic phase
– Characterized by organ failure
• Heart disease
– Most common form of chronic Chagas
– Many manifestations may occur
• Digestive system abnormalities
– Megaesophagus
– Megacolon

Center for Food Security and Public Health, Iowa State University, 2012
 Chagas Disease
• Immunocompromised people can be
severely affected
• Pregnant women
– Congenital infection,
premature birth
• AIDS patients
– Brain abscesses
– Higher likelihood of reactivation

Center for Food Security and Public Health, Iowa State University, 2012
 Diagnosis
• Microscopy
– Blood, CSF, tissues
– Acute stage
• Parasite isolation
• Serology
– Indirect immunofluorescence, ELISA
– Chronic stage
• Molecular techniques
Center for Food Security and Public Health, Iowa State University, 2012
 Treatment
• Antiparasitic drugs
– Treat acute or congenital cases
to prevent chronic disease
– Administer long term
– Significant side effects
• Chronic stage
– Symptomatic treatment of cardiac
and digestion disease

Center for Food Security and Public Health, Iowa State University, 2012
 Morbidity and Mortality
• Acute symptoms: 5%
• Case fatality rate: 5 to 8%
– Deaths mostly in children
– Acute myocarditis, meningoencephalitis
• Chronic disease: 20 to 30%
– Exact causes for disease
progression unknown

Center for Food Security and Public Health, Iowa State University, 2012
DISEASE IN ANIMALS
 Disease in Animals
• Incubation
– Dogs: 5 to 42 days
– May be asymptomatic until chronic
stage years later
• Hosts
– Dogs, cats commonly affected
– Birds, reptiles, fish not susceptible

Center for Food Security and Public Health, Iowa State University, 2012
 Clinical Signs: Dogs
• Acute phase
– Lymphadenopathy, ataxia,
diarrhea, weakness
– Acute myocarditis develops
2 to 3 weeks post-infection
• Chronic phase
– Congestive heart failure,
cardiac dilatation, sudden
death

Center for Food Security and Public Health, Iowa State University, 2012
 Disease in Other Species
• Cats
– Usually asymptomatic
– Rarely fever, edema, weight loss,
neurological signs
• Other species
– Mostly unknown
– Myocarditis reported in wildlife
– Cardiac, reproductive disease in
rats and mice
Center for Food Security and Public Health, Iowa State University, 2012
 Post Mortem Lesions
• Right side cardiac
lesions
– Dilation, hemorrhages,
paleness, pericardial
effusion
• Pulmonary edema
• Peritoneal transudate
– Liver, spleen, kidney
congestion
Center for Food Security and Public Health, Iowa State University, 2012
 Diagnosis and Treatment
• Diagnosis
– Microscopy
– Parasite isolation
– Serology
• Indirect immunofluorescence
– Molecular techniques
• Treatment
– Antiparasitic drugs

Center for Food Security and Public Health, Iowa State University, 2012
 Morbidity and Mortality
• Prevalence in wildlife
– 2 to 62% in raccoons and opossums
• Prevalence in dogs
– 1.1 to 8.8% (U.S.)
– 10 to 17% (Mexico)
• Mortality
– High in experimentally infected animals

Center for Food Security and Public Health, Iowa State University, 2012
PREVENTION AND
CONTROL
 Recommended Actions
• Chagas is NOT a nationally
notifiable disease
• Reportable by state mandate in:
– Arizona
– Massachusetts
– Tennessee

Center for Food Security and Public Health, Iowa State University, 2012
 Prevention in Humans
• Prevent contact with triatomine
insects and their feces
– Improve substandard housing
– Use screens/bed nets (permethrin-
impregnated bed net) when sleeping
– Spray homes with
insecticides
– Cook contaminated
foods
 Prevention in Humans
• Screen blood and organ donors
• Occupational risk groups
– Wear gloves, other PPE
– Dispose of sharps properly
• Travelers
– Wear thick clothing
– Avoid substandard housing
• Vaccine not available
Center for Food Security and Public Health, Iowa State University, 2012
African Trypanosomiasis
(Sleeping Sickness)
 Background
- Human African trypanosomiasis (HAT), also called sleeping
sickness, is an illness endemic to sub-Saharan Africa.

- It is caused by the flagellate protozoan Trypanosoma

brucei, which exists in 2 morphologically identical
subspecies:
- Trypanosoma brucei rhodesiense (East African or
Rhodesian African trypanosomiasis) and

- Trypanosoma brucei gambiense (West African or Gambian

African trypanosomiasis).

- Both of these parasites are transmitted to human hosts by

bites of infected tsetse flies (Glossina palpalis transmits T
brucei gambiense and Glossina morsitans transmits T
brucei rhodesiense), which are found only in Africa.
 Causes

• A bite from an infected tsetse fly

causes African trypanosomiasis .
• Blood transfusions are a rare cause
of parasitic transmission.
• In rare cases, accidental
transmission in the laboratory has
been implicated.
•The reservoirs of infection for these
vectors are exclusively human in West
African trypanosomiasis.

•However, East African

trypanosomiasis is a zoonotic infection
with animal vectors.
 Life cycle
• Trypanosomes are parasites with a 2-host life
cycle: mammalian and arthropod.
• The life cycle starts when the trypanosomes are
ingested during a blood meal by the tsetse fly
from a human reservoir in West African
trypanosomiasis or an animal reservoir in the
East African form.
• The trypanosomes multiply over a period of 2-3
weeks in the fly midgut; then, the trypanosomes
migrate to the salivary gland, where they
develop into epimastigotes. The metacyclic
trypomastigotes infect humans.
Type of Stage 1 Stage 2
Trypanosomiasis
(Hemolymphatic (Neurologic [CNS]
Stage) Stage)

East African Suramin 100-200 mg IV Melarsoprol 2-3.6

trypanosomiasis (caused test dose, then 1 mg/kg/d IV for 3 d; after
by T brucei rhodesiense) g(20mg/kg) IV on days 1, 1 wk, 3.6 mg/kg/d for 3
3, 7, 14, 21 d; after 10-21 d, repeat
the cycle
West African Pentamidine isethionate 4 Melarsoprol 2-3.6
trypanosomiasis (caused mg/kg/d IM for 10 d mg/kg/d IV for 3 d; after
by T brucei gambiense) 1 wk, 3.6 mg/kg/d for 3
days; after 10-21 d,
repeat the cycle
or
or
Suramin 100-200 mg IV
test dose, then 1 Eflornithine 400 mg/kg/d
g(20mg/kg) IV on days 1, IV in 4 divided doses for
3, 7, 14, 21 14 d
The two drugs used to treat infection
with Trypanosoma cruzi are
nifurtimox and benznidazole.
Common side effects of benznidazole
treatment include:
• allergic dermatitis
• peripheral neuropathy
• anorexia and weight loss
• insomnia
The most common side effects of
nifurtimox are:
• anorexia and weight loss
• polyneuropathy
• nausea
• vomiting
• headache
• dizziness or vertigo

Contraindications for treatment include

severe hepatic and/or renal disease.
Drug Age group Dosage and duration

Benznidazole < 12 years 10 mg/kg per day orally

in 2 divided doses for 60
days.
12 years or older
5-7 mg/kg per day
orally in 2 divided doses
for 60 days

Nifurtimox ≤ 10 years 15-20 mg/kg per day

orally in 3 or 4 divided
doses for 90 days

11-16 years 12.5-15 mg/kg per day

orally in 3 or 4 divided
doses for 90 days

17 years or older 8-10 mg/kg per day

orally in 3 or 4 divided
doses for 90 days