parasitology

1. • 16-18 million infected
• 100 million at risk
• 50,000 deaths annually
• leading cause of cardiac disease
in S. and Central America
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

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

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

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

10. SOURCE COMMENTS
Vector
Natural transmission by triatomine bugs
through contamination with infected feces.
Transfusion
A prevalent mode of transmission in urban
areas. Gentian violet treatment (24 hr)
eliminates parasites in blood.
Congenital
Occurs during any stage of T. cruzi
infection. Can result in premature labor,
abortion neonatal death.
Accidental
Ingestion of food contaminated with
metacyclic trypomastigotes. Laboratory
accidents.
Modes of Transmission

11. Types of Vector Transmission
Salivarian Stercorarian
 transmission via
mouth parts
 very efficient
 infection rate in
vector is low
 hind gut station
 acquired from feces
or eating vector
 inefficient
 infection rate in
vector is high

12. • ‘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
Factors Influencing
Human Transmission

17. • 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
Trypanosoma cruzi in the U.S.
inefficient transmission
+
limited vector-human contact

18. • 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
Chagas Control

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. • 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
Chronic Chagas' Cardiomyopathy

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

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

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

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

27. Basis of Pathogenesis
autoimmunity?
parasite-mediated
destruction?
 few (if any) parasites
 anti-self responses
(humoral and cellular)
 slow development
 organ specificity
 persistent low level
parasitemia (PCR)
 inflammation correlates
with parasites
 disease exacerbated by
immune suppression
 successful treatment of
chronic patients (?)
• altered immune response? (Th1Th2 switch
correlated with severe disease)
• chagasic factor or toxin? (proposed by not found)

28. • 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)
DIAGNOSIS

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

30. • acute stage
–nifurtimox (8-16 mg/kg/day,
60-90 days)
–benzidazole (5-7 mg/kg/day,
30-120 days)
–allopurinol (experimental)
–azole antifungal agents
(experimental)
• chronic stage
–treat symptoms
TREATMENT

31. Viotta et al (1994)
Am. Heart J. 127:151
 benznidazole treatment (5 mg/kg/day, 30 d)
 followed for 8 years
% of patients exhibiting
treated (131) control (70)
electrocardiogram
changes
4% 30%
deterioration in
clinical condition
2% 17%
sero-negative
conversion
19% 6%

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