부산대학교 도서관

Nifurtimox is indicated in Chagas disease but determining its effectiveness in chronic disease is hindered by the length of time needed to demonstrate negative serological conversion. We manually reviewed long-term follow-up data from hospital records of patients with chronic Chagas disease (N = 1,497) in Argentina diagnosed during 1967–1980. All patients were aged ≥18 years at diagnosis and were either treated with nifurtimox (n = 968) or received no antitrypanosomal treatment (n = 529). The primary endpoint was negative seroconversion (the "event"), defined as a change from positive to negative in the serological or parasitological laboratory test used at diagnosis. Time to event was from baseline visit to date of endpoint event or censoring. The effectiveness of nifurtimox versus no treatment was estimated with Cox proportional hazard regression using propensity scores with overlap weights to calculate the hazard ratio and 95% confidence interval. The nifurtimox group was younger than the untreated group (mean, 32.4 vs. 40.3 years), with proportionally fewer females (47.9% vs. 60.1%), and proportionally more of the nifurtimox group than the untreated group had clinical signs and symptoms of Chagas disease at diagnosis (28.9% vs. 14.0%). Median maximum daily dose of nifurtimox was 8.0 mg/kg/day (interquartile range [IQR]: 8.0–9.0) and median treatment duration was 44 days (IQR: 1–90). Median time to event was 2.1 years (IQR: 1.0–4.5) for nifurtimox-treated and 2.4 years (IQR: 1.0–4.2) for untreated patients. Accounting for potential confounders, the estimated hazard ratio (95% confidence interval) for negative seroconversion was 2.22 (1.61–3.07) favoring nifurtimox. Variable treatment regimens and follow-up duration, and an uncommonly high rate of spontaneous negative seroconversion, complicate interpretation of this epidemiological study, but with the longest follow-up and largest cohort analyzed to date it lends weight to the benefit of nifurtimox in adults with chronic Chagas disease. Trial registration: The study protocol was registered at ClinicalTrials.gov: NCT03784391. Author summary: Nifurtimox has been a treatment for Chagas disease since the 1970s, is a World Health Organization Essential Medicine, and was recently approved to treat pediatric patients in the USA. Chagas disease is typically transmitted to humans via insect bites and is endemic in parts of Latin America. Symptoms may be mild or absent in the early acute phase of disease and about two-thirds of individuals remain largely asymptomatic in the subsequent chronic phase. However, some chronic patients experience severe cardiac or gastrointestinal effects up to 30 years after infection. Chronic Chagas disease is treatable, but positive serology can persist long after the parasite has been cleared. Studies of the effectiveness of nifurtimox in the chronic phase of the disease have historically been limited by small size or short follow-up duration. From 3,633 patients with Chagas disease identified during review of hospital records in Argentina, we analyzed data retrospectively from 1,497 adults diagnosed with chronic Chagas disease over a 14-year period (1967–1980), looking for negative seroconversion among individuals who received nifurtimox or were untreated. The study had limitations that impact interpretation of the findings: treatment regimens and the amount of time patients were followed both varied, and many untreated patients unexpectedly underwent spontaneous negative seroconversion. However, patients treated with nifurtimox were at least twice as likely to be seronegative as untreated patients, providing supporting evidence for the effectiveness of nifurtimox in adults with chronic Chagas disease. [ABSTRACT FROM AUTHOR]