The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease

Marin-Neto, José Antônio; Rassi, Anis; Avezum, Álvaro; Mattos, AC

doi:10.1590/s0074-02762009000900042

Cited by 156 publications

(124 citation statements)

References 29 publications

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“…We anticipate that the reemergence of guinea pigs as models of human pathogens will facilitate this effort. 63 Nevertheless, the present data demonstrate that T. cruzi infection of guinea pigs recapitulates human pathology and provide a solid foundation for the use of these natural reservoirs of T. cruzi infection as laboratory models of Chagas disease.…”

Section: Discussionmentioning

confidence: 67%

“…60 -62 The guinea pig model might also be useful for drug testing, with the possibility of following cohorts of treated and untreated guinea pigs for development and progression of cardiac abnormalities, similar to the design of the ongoing benznidazole trial for chronic Chagas disease in humans. 63 No gastrointestinal disease was observed in the guinea pigs used in this study. However, only a few patients with clinical Chagas disease have digestive involvement.…”

Section: Discussionmentioning

confidence: 69%

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Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Castro-Sesquen

Gilman

Yauri

et al. 2011

The American Journal of Pathology

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The guinea pig (Cavia porcellus) is a natural reservoir for Trypanosoma cruzi but has seldom been used as an experimental infection model. We developed a guinea pig infection model for acute and chronic Chagas disease. Seventy-two guinea pigs were inoculated intradermally with 10 4 trypomastigotes of T. cruzi strain Y (experimental group); 18 guinea pigs were used as control group. Eight animals from the experimental group and two from the control group were Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is one of the most important parasitic infections of the Americas. Despite successful vector control programs in many countries, the disease remains a major public health problem in Latin America, with 8 to 10 million people currently infected, an annual incidence of 65,000 new cases in 15 countries, and 14,000 deaths associated with the infection per year. 1 Transmission to the mammalian host occurs when a T. cruzi-infected triatomine vector deposits infectious trypomastigotes in feces during a blood meal and the parasites invade through the bite wound or intact mucosal membranes. 2 Trypomastigotes can infect virtually any nucleated cell, where they transform to amastigotes and replicate in the host cell cytoplasm. Amastigotes convert back to trypomastigotes inside the cell and then rupture the cell and circulate in the bloodstream. After weeks, the host immune response usually controls the acute infection but does not completely clear the parasite. This results in lifelong chronic infection of the host.The initial weeks after T. cruzi infection are characterized by a high-level parasitemia and symptoms that vary from mild nonspecific febrile illness to life-threatening myocarditis and/or meningoencephalitis. 2 Acute symptoms and detectable parasitemia resolve spontaneously within 2 to 3 months, and the infected individual passes into the chronic phase of the disease. Nearly all individuals in the early period of chronic infection are asymptomatic and are said to have the indeterminate form of the disease. In most individuals, the infection remains silent for life and is detectable only by anti-T. cruzi serologic tests and, in a proportion of individuals, by molecular Supported by NIH training grant in infectious and tropical diseases 5 T35 AI065385 and NIH grant 1R01AI087776-01.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 69%

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Castro-Sesquen

Gilman

Yauri

et al. 2011

The American Journal of Pathology

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“…Sin embargo, al plantear el hecho que parte de los individuos afectados adquirieron la infección durante la edad lactante y pre-escolar, implica que el hábito de consumir chimó se inicia en etapas tempranas de la edad escolar, en este sentido ha sido reportado en Venezuela que la edad promedio de iniciación en el hábito es 11,6 años 23 . De esta manera, la nicotina mantendría una respuesta inmune robusta en el tiempo, disminuyendo la tasa de seronegativización espontánea en los individuos consumidores de chimó 24 .…”

Section: Discussionunclassified

Seroprevalencia de la infección por Trypanosoma cruzi y factores asociados en un área endémica de Venezuela

et al. 2011

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Determinamos factores de riesgo asociados a la seropositividad para anticuerpos anti-Trypanosoma cruzi en 26 poblaciones rurales, 905 viviendas, 2.156 individuos y 333 caninos en el Estado Lara, Venezuela. La seropositividad fue determinada mediante ELISA y MABA. Los datos fueron obtenidos mediante encuestas entomológicas, demográficas y médicas. Los factores de riesgo fueron establecidos mediante regresión logística binaria. La seroprevalencia humana fue de 7,24% y la canina 6,9%. La seropositividad estuvo asociada positivamente al Rhodnius prolixus, la edad, madre con antecedentes de Chagas, consumo de chimó, presencia de mamíferos y aves en la vivienda, desorden en el domicilio, y anexos de bajareque, nidos y cuevas en el peridomicilio. Negativamente con hábitos de consumo de tabaco y alcohol, antecedentes de cáncer y a depósitos en el peridomicilio. En conclusión, la enfermedad de Chagas en el área rural estudiada es un fenómeno remoto transmitida por R. prolixus y vía transplacentaria, asociada a hábitos socioculturales relacionados con la pobreza, a entornos selváticos y antecedentes médicos del huésped.

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“…The average cure rate among acute and recent cases is 80%, while it is less than 20% among chronic cases [23][24][25] . A pilot study, the Benefit project -Benznidazole Evaluation for Interruping Trypanosomiasis -an international, multicenter, double-bind, placebo-controlled trial of tripanocidal chronic Chagas heart disease is in course 40,41 .…”

Section: Drugs In Use and New Strategies For Treating Chagas Diseasementioning

confidence: 99%

Chagas disease: What is known and what should be improved: a systemic review

Coura

Borges-Pereira

2012

Rev. Soc. Bras. Med. Trop.

116

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This study consists of a broad review on what is known and what should be improved regarding knowledge of Chagas disease, not only through analysis on the main studies published on the topics discussed, but to a large extent based on experience of this subject, acquired over the past 50 years (1961-2011). Among the subjects covered, we highlight the pathogenesis and evolution of infection by Trypanosoma cruzi, drugs in use and new strategies for treating Chagas disease; the serological tests for the diagnosis and the controls of cure the infection; the regional variations in prevalence, morbidity and response to treatment of the disease; the importance of metacyclogenesis of T. cruzi in different species of triatomines and its capacity to transmit Chagas infection; the risks of adaptation of wild triatomines to human dwellings; the morbidity and need for a surveillance and control program for Chagas disease in the Amazon region and the need to prioritize initiatives for controlling Chagas disease in Latin America and Mexico and in non-endemic countries, which is today a major international dilemma. Finally, we raise the need for to create a new initiative for controlling Chagas disease in the Gran Chaco, which involves parts of Argentina, Bolivia and Paraguay.

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The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease

Cited by 156 publications

References 29 publications

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Seroprevalencia de la infección por Trypanosoma cruzi y factores asociados en un área endémica de Venezuela

Chagas disease: What is known and what should be improved: a systemic review

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