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Serological response to nifurtimox in adult patients with chronic Chagas disease: An observational comparative study in Argentina.

ABSTRACT: 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.

SUBMITTER: Vizcaya D

PROVIDER: S-EPMC8489720 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEvaluation of therapeutic response in chronic Chagas disease is a major challenge, due to prolonged persistence of Trypanosoma cruzi-specific antibodies, lack of sensitivity of parasitological tests, and need for long-term follow-up to observe negative seroconversion of conventional serological tests (CS). The objective of this study was to evaluate F2/3-ELISA serology, a promising early biomarker of therapeutic response, and T.cruzi Polymerase chain reaction (PCR) for T. cruzi Deoxyribonucleic acid (DNA), for neonatal diagnosis and evaluation of parasitemia after treatment.MethodsProspective cohort study, with three-year clinical, serological and parasitological follow-up of pediatric Chagas disease patients treated with benznidazole. Serology was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA), Indirect hemagglutination (IHA) and F2/3-ELISA; Parasitemia by microhematocrit (MH) and PCR.ResultsA cohort of 107 pediatric patients treated with benznidazole was enrolled in the study. ELISA and IHA were initially reactive in 100% of patients, F2/3-ELISA serology was reactive in 80% (86/107) and 91% (97/107) had detectable parasitemia. Seventy-six (71%) patients completed at least 36 months of serological follow up after treatment. Although a similar decreasing linear trend was observed for all serological tests, F2/3-ELISA presented earlier, age dependent, negative seroconversion compared to CS. All patients reaching undetectable CS titers had previously seroreverted by F2/3-ELISA. All patients with persistently decreasing antibody titers had negative PCRs throughout the follow up period. No new cardiological lesions were observed during the 3 years follow-up period.ConclusionsThe data reported here, using CS, F2/3 ELISA and PCR provide support for the efficacy of benznidazole in congenital Chagas diseases. These results provide support for scaling up of screening, diagnosis and access to benznidazole treatment.Trial registrationClinicalTrials.gov 0028/04 in the Research Council, Secretary of Health Buenos Aires city Goberment.

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Serological response to nifurtimox in adult patients with chronic Chagas disease: An observational comparative study in Argentina.

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