16-18 million infected 100 million at risk 50,000 deaths annually leading cause of cardiac disease...
TRANSCRIPT
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• 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
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Genera
• Triatoma• Rhodnius• Panstrongylus
Common Names
• triatomine bugs• reduviid bugs• assassin bugs• kissing bugs• conenose bugs
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Triatomine Vectors
• >100 species can transmit• 3 primary vectors
• T. dimidiata (central Am.)• R. prolixis (Colombia and
Venezuela)• T. infestans (‘southern cone’
countries)
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•metacyclic trypomastigotes excreted in triatomine feces
•entry via bite wound, mucous membranes (eg., eyes), hair follicles
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•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
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• amastigotes replicate by binary fission
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• amastigotes transform to trypomastigotes
• release of trypomastigotes and reinvasion of host cells
• ingestion of blood-stream trypomastigotes by triatomine
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•conversion to epimastigotes and replication in midgut
•migration to hindgut and transformation to trypomastigote
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SOURCE COMMENTS
VectorNatural transmission by triatomine bugsthrough contamination with infected feces.
TransfusionA prevalent mode of transmission in urbanareas. Gentian violet treatment (24 hr)eliminates parasites in blood.
CongenitalOccurs during any stage of T. cruziinfection. Can result in premature labor,abortion neonatal death.
AccidentalIngestion of food contaminated withmetacyclic trypomastigotes. Laboratoryaccidents.
Modes of Transmission
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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
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• ‘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
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• 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
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• 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
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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
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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
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• 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
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• cardiomegaly• hypertrophy*• apical aneurysm
(left ventricle)• extensive fibrosis* cellular
infiltration
*correlates best with cardiac symptoms
Pathology
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• cardiomegaly• hypertrophy*• apical aneurysm
(left ventricle)• extensive fibrosis* cellular
infiltration
*correlates best with cardiac symptoms
Pathology
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• prevalence varies by geographical zones• Chili, central Brazil
• colon and esophagus most frequently affected
• megaesophagus• painful swallowing• regurgitation
• megacolon• severe constipation
Megaviscerae
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• destruction of parasympathetic neurons dilation
non-Chagas
Chagas
C = heartS = colonE = esophagus
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Basis of Pathogenesis
autoimmunity?parasite-mediated
destruction? few (if any) parasites anti-self responses
(humoral and cellular) slow development organ specificity
persistent low levelparasitemia (PCR)
inflammation correlateswith parasites
disease exacerbated byimmune suppression
successful treatment ofchronic patients (?)
• altered immune response? (Th1Th2 switch correlated with severe disease)
• chagasic factor or toxin? (proposed by not found)
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• 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
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• parasite detection• direct examination• stained blood smears• inoculation into mice• in vitro culture• xenodiagnosis• PCR
• serological tests• hemagglutination• immunofluorescence• ELISA• complement fixation
DIAGNOSIS
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• 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
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Viotta et al (1994) Am. Heart J. 127:151
benznidazole treatment (5 mg/kg/day, 30 d) followed for 8 years
% of patients exhibitingtreated (131) control (70)
electrocardiogramchanges 4% 30%deterioration inclinical condition 2% 17%sero-negativeconversion 19% 6%
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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
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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