Placebo

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.) abstr act

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1507574

Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy

Background— Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. Methods and Results— A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damag...

Pathogenesis of Chronic Chagas Heart Disease

American trypanosomiasis (Chagas disease).

A 42-year-old woman presents after donating blood and receiving a report that she is positive for Chagas' disease. Chagas' disease is caused by a parasite and is endemic in many parts of Latin America.

Antitrypanosomal Therapy for Chronic Chagas' Disease

BACKGROUND: Prior guidelines stated that trypanocidal therapy should not be used for treating chronic asymptomatic Trypanosoma cruzi infections. However, the recent availability of clinical trials reporting high rates of parasitologic cure in children with early chronic T. cruzi infection have produced changes of these recommendations in some countries. Because of the uncertainty regarding best treatment for this stage of T. cruzi infections, the literature was reviewed systematically for a synthesis of the available evidence. OBJECTIVES: To assess the effects of trypanocidal therapy for chronic asymptomatic T. cruzi infection. SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register (Issue 1, 2000), MEDLINE (start-Nov 1999), EMBASE (start - Feb 2000), LILACS (start - Feb 2000) and the Tropical Diseases Research Division of WHO database (Start - Feb 2000). Reference lists of articles were searched for relevant material. SELECTION CRITERIA: Published RCTs of trypanocidal therapy for people with chronic, asymptomatic T. cruzi infections DATA COLLECTION AND ANALYSIS: Two reviewers independently screened papers for inclusion criteria, quality assessment and data extraction. Forms were used to collect data. Reviewers resolved differences by discussion then a third reviewer if necessary. MAIN RESULTS: Of 43 papers assessed for inclusion, five RCTs (total population=756) met the inclusion criteria. The quality of the trials was rated as low (n=3) or intermediate (n=2). Two RCTs tested benznidazole in school children and three tested different agents in adults. The Odds Ratios and their 95%CI (Fixed models) were: Incidence of ECG abnormalities: 0.41 (0.09, 1.85); Negative seroconversion (AT ELISA): 10.91 (6.07, 19.58); Negative xenodiagnosis during the follow up: 5.37 (3.34, 8.64); Standardised mean reduction of antibody titres: 0.54 (0.31, 0.84). Nitroimidazolic derivatives substantially and significantly modified parasite-related outcomes compared to placebo. Other agents showed borderline or not significant effect. REVIEWER'S CONCLUSIONS: Despite major public health importance, trypanocidal.therapy for chronic asymptomatic T. cruzi infection has been tested in few, small size RCTs which were designed to assess parasitic-related, but not clinical outcomes. Therefore, the potential of trypanocidal therapy to prevent Chagas' disease among asymptomatic, chronically infected subjects is promising, but remains to be evaluated. trypanocidal therapy, particularly nitroimidazolic derivatives given to children or adults with positive xenodiagnosis improve parasite-related outcomes. The large contrast between the burden of Chagas disease and the existing evidence on its prevention points the need to test these or newer agents in more and larger RCTs that include clinical endpoints.

/pdf/trypanocidal-drugs-for-chronic-asymptomatic-trypanosoma-3hwcxtoc8y.pdf

Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection

Chagas (CH) disease, found throughout Latin America, is caused by the parasite Trypanosoma cruzi. Heart failure is a common (i.e. 10-30%) late outcome for people who develop symptomatic Chagas disease. Studies show that patients with Chagasic heart failure have a worse prognosis than patients with heart failure from other aetiologies. As most people living with CH are from lower socioeconomic backgrounds where access to quality medical care can be limited, the study investigated the equality of patient care between Chagas and nonChagas heart failure patients in La Fundacion Cardioinfantil (FCI), Bogota, Colombia. Methods The study was a retrospective cohort study, compiling data from medical files of patients hospitalized for heart failure between 2001-2011. Each CH patient (n=41) was matched with 1-2 comparable non-Chagas (no-CH) patients (n=77). Results/Projected Outcomes At the FCI, no differences were observed between care given to CH and no-CH patients, concluding that patients with CH receive a similar standard of care to patients with no-CH. Because this report is not inclusive of other health institutions in Colombia, the FCI is recommended as a model institution for equal patient treatment.

Micah Rae Pepper

Papers

Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection

Treatment Patterns and their Relation to the Diagnosis of Chagas Disease in Patients with Heart Failure, 2001-2011: Bogotá, Colombia