Randomized Trial of Benznidazole for Chronic Chagas' Cardiomyopathy.

BACKGROUND: The role of trypanocidal therapy in patients with established Chagas' cardiomyopathy is unproven. METHODS: We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event. RESULTS: The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P=0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons). The effect of treatment on PCR conversion varied according to geographic region: in Brazil, the odds ratio for PCR conversion was 3.03 (95% CI, 2.12 to 4.34) at 2 years and 1.87 (95% CI, 1.33 to 2.63) at 5 or more years; in Colombia and El Salvador, the odds ratio was 1.33 (95% CI, 0.90 to 1.98) at 2 years and 0.96 (95% CI, 0.63 to 1.45) at 5 or more years; and in Argentina and Bolivia, the odds ratio was 2.63 (95% CI, 1.89 to 3.66) at 2 years and 2.79 (95% CI, 1.99 to 3.92) at 5 or more years (P<0.001 for interaction). However, the rates of PCR conversion did not correspond to effects on clinical outcome (P=0.16 for interaction). CONCLUSIONS: Trypanocidal therapy with benznidazole in patients with established Chagas' cardiomyopathy significantly reduced serum parasite detection but did not significantly reduce cardiac clinical deterioration through 5 years of follow-up. (Funded by the Population Health Research Institute and others; ClinicalTrials.gov number, NCT00123916; Current Controlled Trials number, ISRCTN13967269.).

Human infection by Fasciola hepatica in Venezuela: report of a geriatric case.

A new case of human infection due to Fasciola hepatica is reported in the Venezuelan parasitological literature. The patient is an 81-year-old female asymptomatic, with an eosinophilia of 21% and critrosedimentation rate of 26 mm/h and was found during a routine check up. These values were normal at the time of treatment (4 months later), as were several tests of hepatic function, blood chemistry and peripheral blood haematological values. The number of eggs of the parasite were between 90 and 130/g of facees. The patient was successfully treated with the human formulation of trielabendazole at 2 single doses of 10 mg/kg, each separated by 24 h. The same laboratory tests mentioned above did not show modifications, except for a slight increase in the cosinophil counts at 2 and 11 days and erythrosedimentation rate at 11 days post-treatment. Coproparasitological observations carried out at 12, 18, 60 and 120 days post-treatment were negative. No clinical symptoms were registered up to 2 months after treatment. The patient most probably acquired the infection at home through the ingestion of commercially available lettuce from an endemic area of bovine fascioliasis, very distant from home, and between 4 and 7 months previous to treatment. We stress the need to investigate F. hepatica infections which he been neglected, probably because of limited knowledge by health workers, lack of specific symptoms and absence of more sensitive diagnostic procedures.

Human infection by fasciola hepatica in Venezuela: report of a geriatric case

Se reporta para la literatura parasitológica venezolana, un nuevo caso de infección humana por Fasciola hepatica. Se trata de una paciente de 81 años, asintomática, quien presentó durante exámenes de rutina, una eosinofilia de 21 por ciento y una eritsedimentación de 26 mm/h. Estos valores fueron normales para el momento del tratamiento (4 meses después), así como también lo eran varias pruebas de funcionamiento hepático, química sanguínea y valores hematológicos. El número de huevos del paciente fue de 90 a 130/g de heces. La paciente fue exitosamente tratada con la formulación humana de triclabendazol en 2 dosis simples de 10 mg/kg cada una separadas por 24h, resultado negativas las evaluaciones coproparasitológicas realizadas a los 12,18,60 y 120 días post-tratamiento. Los mismos tests de laboratorio arriba mencionados no mostraron modificaciones excepto por un incremento leve en el contaje de eosinófilos en los días 2 y 11, así como un incremento en los valores de eritrosedimentación al día 11 post-tratamiento. Así mismo, no.

Strategic emphases for tropical diseases research: a TDR perspective.

Setting priorities for health research is a difficult task, especially for the neglected diseases of the poor. A new approach to priority setting for tropical diseases research has been adopted by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (known as the TDR). Priorities are defined on the basis of a comprehensive analysis of research needs and research opportunities for each of the ten major tropical diseases in the TDR portfolio. The resulting strategic emphases matrix reflects the priorities for tropical diseases research from the perspective of the TDR. Its purpose is not to impose global research priorities, but we believe the results could be useful to other organizations.

Strategic emphases for tropical diseases research: a TDR perspective.

Setting priorities for health research is a difficult task, especially for the neglected diseases of the poor. A new approach to priority setting for tropical diseases research has been adopted by the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (known as the TDR). Priorities are defined on the basis of a comprehensive analysis of research needs and research opportunities for each of the ten major tropical diseases in the TDR portfolio. The resulting strategic emphases matrix reflects the priorities for tropical diseases research from the perspective of the TDR. Its purpose is not to impose global research priorities, but we believe the results could be useful to other organizations.

Developments in the treatment of leishmaniasis and trypanosomiasis.

The leishmaniases and trypanosomiases are diseases caused by related parasites belonging to the kinetoplastidae family. They share common biological traits, which are comparatively better known than for other parasites, and which would favour the identification of common targets. Yet, very few new drugs are on the horizon and treatment relies on old, often toxic and ineffective drugs. Miltefosine may soon become the first oral drug registered for Leishmaniasis. Other compounds in clinical trials are paromomycin, sitamquine and lipid formulations of amphotericin B. For African trypanosomiasis old drugs primarily indicated for Chagas disease are being considered (nifurtimox, megazole). Earlier projects are berenil, bisamidines and triazines for African trypanosomiasis, and novel azoles and cruzipain inhibitors for Chagas disease.