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 Genera triatomine bugs reduviid bugs Triatoma 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

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 cardio-myopathy 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 Chagas C = heart S = colon E = esophagus

Basis of Pathogenesis 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 gastro-intestinal symptoms imaging detection of parasite (acute stage) serology (chronic stage)

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

TREATMENT acute stage chronic 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

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