For treatment of Chagas disease, benznidazole can be taken for a shorter period of time and at lower doses with similar efficacy to the current standard regimen and is much more tolerable, a new study suggests. Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America, where an estimated 5.7 million people are infected. Benznidazole is a highly effective antiparasitic treatment for Chagas disease but side effects with the standard dose and long duration of treatment (300 mg daily for eight weeks) lead many patients to stop treatment. The current study found that a reduced dose and shorter course of benznidazole is effective in patients with chronic indeterminate Chagas disease, with clearance of parasitemia and decrease in lytic antibody titers, with superior safety. The BENDITA trial included 210 adults from Bolivia with chronic indeterminate Chagas disease, confirmed by serological testing and positive qualitative PCR results. They were randomly allocated to one of seven groups (30 patients per group): the current standard treatment (benznidazole 300 mg daily for eight weeks); shortened or reduced regimens of benznidazole (300 mg daily for two or four weeks, or 150 mg daily for four weeks); combination therapies (fosravuconazole plus benznidazole 150 mg daily for four weeks or 300 mg once per week for eight weeks); and placebo. Sustained parasitological clearance at six months of follow-up was achieved in 89% of patients in the standard-treatment group, and was similar (83% to 89%) in the shortened monotherapy and combination-therapy groups, all of which were significantly higher than in the placebo group (3%). The use of fosravuconazole in combination with benznidazole did not significantly affect efficacy. The incidence of adverse events was lower in the shortened monotherapy regimen groups than in the standard treatment group. There were no serious or severe adverse events, or adverse events leading to discontinuation of treatment, in patients treated with benznidazole 300 mg daily for two weeks. A two-week benznidazole treatment regimen appears "particularly promising because, in addition to being substantially shorter than the standard treatment regimen, no patients in this group had serious or severe adverse events, adverse events of special interest, or adverse events leading to treatment discontinuation," Dr. Faustino Torrico of Mayor San Simon University, in Cochabamba, Bolivia, and colleagues report in The Lancet Infectious Diseases. "Reducing the current eight-week standard treatment regimen of benznidazole to a shorter two-week regimen could greatly simplify the treatment of Chagas disease and facilitate better adherence for patients, improving access to treatment for patients with this long-neglected disease," they conclude "As the study had a small sample size and groups were only powered to be compared against placebo, these results should be interpreted cautiously and confirmatory studies evaluating the efficacy of reduced-exposure benznidazole regimens compared with the standard benznidazole regimen with larger patient numbers are required," they caution. The authors of a linked comment say the BENDITA trial "brings some hope to the field with direly needed high-quality evidence." "The main lessons derived from this study highlight that benznidazole remains the standard of care, and that reduced doses and shorter treatment periods (ie, two weeks) could remain effective in achieving parasitological clearance that is sustained for at least six months. This is welcomed news, as one of the greatest limitations of etiological treatment of Chagas disease has been the high incidence of side effects and treatment discontinuation. Furthermore, benznidazole is cheap and effective and should be implemented as a public health intervention," the Comment authors say. The BENDITA study, they add, "provides a strong light at the end of this long-neglected tunnel; with future developments, the noble aspiration of eradicating Chagas disease worldwide within the next 30 years could be an achievable goal." Funding for the study was provided by the Drugs for Neglected Diseases initiative (DNDi). The authors have no conflicts of interest. —Reuters Staff Source
