Transcript No Slide Title

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
Common Names
•
•
•
•
•
triatomine bugs
reduviid bugs
assassin bugs
kissing bugs
conenose bugs
Genera
• Triatoma
• Rhodnius
• Panstrongylus
Triatomine Vectors
• >100 species can transmit
• 3 primary vectors
• T. dimidiata (central Am.)
• R. prolixis (Colombia and
Venezuela)
• T. infestans (‘southern cone’
countries)
•metacyclic trypomastigotes
excreted in triatomine feces
•entry via bite wound,
mucous membranes (eg.,
eyes), hair follicles
•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
• amastigotes replicate
by binary fission
• ingestion of blood-stream
trypomastigotes by
triatomine
• release of trypomastigotes
and reinvasion of host cells
• amastigotes transform
to trypomastigotes
•migration to hindgut and transformation
to trypomastigote
•conversion to epimastigotes
and replication in midgut
Modes of Transmission
SOURCE
COMMENTS
Natural transmission by triatomine bugs
Vector
through contamination with infected feces.
A prevalent mode of transmission in urban
Transfusion areas. Gentian violet treatment (24 hr)
eliminates parasites in blood.
Occurs during any stage of T. cruzi
Congenital infection. Can result in premature labor,
abortion neonatal death.
Ingestion of food contaminated with
metacyclic trypomastigotes. Laboratory
Accidental
accidents.
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
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
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
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
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 cardiomyopathy or megasyndromes
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
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
Pathology
• cardiomegaly
• hypertrophy*
• apical aneurysm
(left ventricle)
• extensive fibrosis*
•  cellular infiltration
*correlates best with
cardiac symptoms
Pathology
• cardiomegaly
• hypertrophy*
• apical aneurysm
(left ventricle)
• extensive fibrosis*
•  cellular infiltration
*correlates best with
cardiac symptoms
Megaviscerae
• prevalence varies by
geographical zones
• Chili, central Brazil
• colon and esophagus
most frequently affected
• megaesophagus
• painful swallowing
• regurgitation
• megacolon
• severe constipation
• destruction of parasympathetic
neurons  dilation
non-Chagas
C = heart
S = colon
E = esophagus
Chagas
Basis of Pathogenesis
autoimmunity?
 few (if any) parasites
 anti-self responses
(humoral and cellular)
 slow development
 organ specificity
parasite-mediated
destruction?
 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)
DIAGNOSIS
• history of living in
infested house
• bug bite, chagoma,
Romaña's sign
• cardiac or gastrointestinal symptoms
• imaging
• detection of parasite
(acute stage)
• serology (chronic
stage)
DIAGNOSIS
• parasite detection
• direct examination
• stained blood smears
• inoculation into mice
• in vitro culture
• xenodiagnosis
• PCR
• serological tests
• hemagglutination
• immunofluorescence
• ELISA
• complement fixation
TREATMENT
• 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
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
deterioration in
clinical condition
sero-negative
conversion
4%
30%
2%
17%
19%
6%
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
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