nifurtimox and Cardiomyopathies

Chagas disease is a neglected disease that remains a public health threat, particularly in Latin America. The most important treatment options are nitroimidazole derivatives, such as nifurtimox and benznidazole (BZN). Some studies suggest that for adults seropositive to T. cruzi but without clinically evident chronic Chagas cardiomyopathy (CCC), a simple fixed-dose scheme of BZN could be equivalent to a weight-adjusted dose. We compared the efficacy and safety of a fixed dose of BZN with an adjusted dose for T. cruzi seropositive adults without CCC. We used the Cochrane methods, and reported according to the PRISMA statement. We included randomized controlled trials (RCTs) allocating participants to fixed and/or adjusted doses of BZN for T. cruzi seropositive adults without CCC. We searched (December 2019) Cochrane, MEDLINE, EMBASE, LILACS, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP), and contacted Chagas experts. Selection, data extraction, and risk of bias assessment, using the Cochrane tool, were performed independently by pairs of reviewers. Discrepancies were solved by consensus within the team. Primary outcomes were parasite-related outcomes and efficacy or patient-related safety outcomes. We conducted a meta-analysis using RevMan 5.3 software and used GRADE summary of finding tables to present the certainty of evidence by outcome. We identified 655 records through our search strategy and 10 studies (four of them ongoing) met our inclusion criteria. We did not find any study directly comparing fixed vs adjusted doses of BZN, however, some outcomes allowed subgroup comparisons between fixed and adjusted doses of BZN against placebo. Moderate-certainty evidence suggests no important subgroup differences for positive PCR at one year and for three safety outcomes (drug discontinuation, peripheral neuropathy, and mild rash). The same effect was observed for any serious adverse events (low-certainty evidence). All subgroups showed similar effects (I2 0% for all these subgroup comparisons but 32% for peripheral neuropathy), supporting the equivalence of BZN schemes. We conclude that there is no direct evidence comparing fixed and adjusted doses of BZN. Based on low to very low certainty of evidence for critical clinical outcomes and moderate certainty of evidence for important outcomes, fixed and adjusted doses may be equivalent in terms of safety and efficacy. An individual patient data network meta-analysis could bette

Topics: Adult; Cardiomyopathies; Chagas Disease; Databases, Factual; Humans; Nifurtimox; Nitroimidazoles; Patient Safety; Randomized Controlled Trials as Topic; Treatment Outcome; Triazoles; Trypanosoma cruzi

Chagas disease is a parasite infection primarily transmitted to humans via the bite of triatomine insect vectors. Up to 8 million people are estimated to be infected with Chagas disease in the Americas. Patients who do not receive treatment can develop severe cardiac debility, gastrointestinal organ dysfunction, and may die. The changing demographics of the United States, a consequence of changing immigration patterns, means that healthcare providers are more likely to encounter patients with Chagas disease, and must understand its cause, pathogenesis, diagnosis, and treatment.

Topics: Acute-Phase Reaction; Cardiomyopathies; Chagas Disease; Chronic Disease; Diagnosis, Differential; Female; Humans; Male; Megacolon; Nifurtimox; Nitroimidazoles; Trypanocidal Agents; Trypanosoma cruzi; United States

We investigated the relationship between potentially pathogenic antibodies against a Trypanosoma cruzi ribosomal protein (P2β) and the evolution of Chagas disease and the effect of trypanocidal treatment on these variables. Seventy-eight patients with chronic Chagas disease who were followed-up for more than 20 years were divided into three groups: 30 asymptomatic persons undergoing specific treatment (group A), 37 asymptomatic persons not undergoing specific treatment (group B), and 11 patients with chronic chagasic cardiomyopathy (CCC) who were not treated. Five patients in group B showed evolution to myocardial abnormalities. Among persons with CCC, six showed no changes; the remaining persons showed progression of cardiac involvement. Levels of antibodies to P2β in persons in group A decreased from their initial values. This finding was not observed in persons in groups B and C. Comparisons at the end of the follow-up showed lower amounts of antibodies to P2β in groups A and C. These findings support the benefits of specific treatment during chronic infection.

Topics: Animals; Antibodies, Protozoan; Cardiomyopathies; Chagas Disease; Chronic Disease; Female; Humans; Immunity, Humoral; Male; Nifurtimox; Nitroimidazoles; Protozoan Proteins; Ribosomal Proteins; Trypanocidal Agents; Trypanosoma cruzi