1. Trypanosoma cruzi causative agent of Chagas disease
discovered by Carlos Chagas
named organism after mentor, Oswaldo Cruz
determined life cycle
described salient features of disease
16-18 million infected
100 million at risk
50,000 deaths annually
leading cause of cardiac disease in S. and Central America

2. Common Names Genera triatomine bugs reduviid bugs Triatoma
assassin bugs
kissing bugs
conenose bugs
Genera
Triatoma
Rhodnius
Panstrongylus

3. Triatomine Vectors >100 species can transmit 3 primary vectors
T. dimidiata (central Am.)
R. prolixis (Colombia and Venezuela)
T. infestans (‘southern cone’ countries)

4. metacyclic trypomastigotes excreted in triatomine feces
entry via bite wound, mucous membranes (eg., eyes), hair follicles

5. metacyclic trypomastigotes excreted in triatomine feces
entry via bite wound, mucous membranes (eg., eyes), hair follicles
blood-stream trypomastigotes are non-dividing
trypomastigotes invade host cells and convert to amastigotes

6. amastigotes replicate by binary fission

8. ingestion of blood-stream trypomastigotes by triatomine
release of trypomastigotes and reinvasion of host cells
amastigotes transform to trypomastigotes

9. migration to hindgut and transformation to trypomastigote
conversion to epimastigotes and replication in midgut

10. Modes of Transmission

12. Factors Influencing Human Transmission
‘early’ defecation (i.e., during triatomine feeding)
colonization of human habitats
adobe walls
thatched roofs
para-domiciliary cycles
animal stalls adjacent to domicile
proximity to sylvatic cycle

17. Trypanosoma cruzi in the U.S.
triatomine bugs found in U.S.
parasite common in wild animals
5 confirmed autochthonous cases
why no autochthonous transmission?
late defecaters
zoophillic vectors
better houses
inefficient transmission +
limited vector-human contact

18. Chagas Control improvement of human dwellings
separation of animal stalls from house
health education
insecticides
synthetic pyrethroids
eg., Southern Cone Initiative
major  in Chagas (T. infestans)
little affect with R. prolixis
gentian violet in blood for transfusions

19. Clinical Course of Chagas
Acute Phase
active infection
1-4 months duration
most are asymptomatic (children most likely to be symptomatic)
Indeterminate Phase
10-30 years of latency
relatively asymptomatic with no detectable parasitemia
seropositive
Chronic Phase
10-30% of infected exhibit cardio-myopathy or megasyndromes

20. Acute Phase Features 1-2 week incubation period local inflammation
Romaña’s sign
chagoma
symptoms can include: fever, malaise, lymphadenopathy, hepatosplenomegaly, nausea, diarrhea
acute, often fatal, myocarditis develops in a few individuals
high parasitemias in myofibrils

21. Chronic Chagas' Cardiomyopathy
long latency characterized by seropositivity and no parasitemia
higher prevalence of ECG abnormalities in asymptomatic seropositive persons
progressive development of abnormalities
right bundle branch block
left anterior hemiblock
clinical presentations include:
arrhythmias and conduction defects
congestive heart failure
thromboembolic phenomenon

22. Pathology cardiomegaly hypertrophy* apical aneurysm (left ventricle)
extensive fibrosis*
 cellular infiltration
*correlates best with cardiac symptoms

23. Pathology cardiomegaly hypertrophy* apical aneurysm (left ventricle)
extensive fibrosis*
 cellular infiltration
*correlates best with cardiac symptoms

24. Megaviscerae prevalence varies by geographical zones
Chili, central Brazil
colon and esophagus most frequently affected
megaesophagus
painful swallowing
regurgitation
megacolon
severe constipation

26. destruction of parasympathetic neurons  dilation
non-Chagas
Chagas
C = heart
S = colon
E = esophagus

27. Basis of Pathogenesis
altered immune response? (Th1Th2 switch correlated with severe disease)
chagasic factor or toxin? (proposed by not found)

28. DIAGNOSIS history of living in infested house
bug bite, chagoma, Romaña's sign
cardiac or gastro-intestinal symptoms
imaging
detection of parasite (acute stage)
serology (chronic stage)

29. DIAGNOSIS parasite detection serological tests direct examination
stained blood smears
inoculation into mice
in vitro culture
xenodiagnosis
PCR
serological tests
hemagglutination
immunofluorescence
ELISA
complement fixation

30. TREATMENT acute stage chronic stage
nifurtimox (8-16 mg/kg/day, days)
benzidazole (5-7 mg/kg/day, days)
allopurinol (experimental)
azole antifungal agents (experimental)
chronic stage
treat symptoms

31. Viotta et al (1994) Am. Heart J. 127:151
benznidazole treatment (5 mg/kg/day, 30 d)
followed for 8 years

32. Lauria-Pires et al (2000) AJTMH 63:111
Brasília street cleaners  treatment
standard treatment with nifurtimox or benznidazole
10 year follow up
treated vs. untreated:
no parasitiological cure (PCR)
no sero-negative conversion
no ECG improvements
administration of nitroderivatives
severe side effects
compliance problems

33. Trypanosoma rangeli can be confused with T. cruzi
non-pathogenic for humans
pathogenic for triatomines
mode of transmission?
found in both salivary glands and feces