# Long-term outcomes of benznidazole treatment in chronic Chagas disease: A 27-year cohort study of parasitological cure and death in the Jequitinhonha Valley, Brazil

## TL;DR

A 27-year study in Brazil found that benznidazole treatment for chronic Chagas disease significantly improved cure rates and survival compared to no treatment.

## Contribution

This study provides long-term evidence of the effectiveness of benznidazole in chronic Chagas disease using multiple diagnostic criteria.

## Key findings

- Benznidazole-treated patients had 75-90% parasitological cure rates compared to no cure in the untreated group.
- Treated patients had a 95% survival rate versus 40% in the untreated group over 27 years.
- The Chagas-Flow ATE serology showed higher accuracy in monitoring treatment response.

## Abstract

Chagas disease (CD) is a neglected tropical infection prevalent in rural areas of Latin America. The etiological treatment is indicated for patients with both acute and chronic phases of CD, except in the most advanced clinical stage of the disease. However, there are still several divergences regarding the benefits of etiological treatment in chronic CD as far as the parasitological cure and survival/mortality outcomes. The present study aimed at verifying the impact of benznidazole (BZ) treatment on parasitological cure and death of patients with chronic CD at 9, 13, and 27 years post-treatment.

This study aimed to verify the impact of BZ-treatment on parasitological cure and death of patients with chronic CD at 9, 13, and 27-year follow-up.

A historical and prospective cohort of 42 patients with chronic CD, categorized as BZ-treated (BZ-T, n = 21) and Not-treated (NT, n = 21), were evaluated after 9, 13, and 27 years of follow-up, using parasitological tests (Hemoculture-HC, polymerase chain reaction-PCR, and quantitative real-time PCR-qPCR), conventional-CS (ELISA), and non-conventional-NCS (Chagas-Flow ATE) serology, employing three distinct cure criteria, one classical and two alternative. Survival analysis for death was determined by the Kaplan-Meier method.

Parasitological data (HC, PCR and qPCR) were negative in all patients (BZ-T and NT) at 27-year follow-up. The CS was negative in 75% and 23.1% of patients from BZ-T and NT, respectively. NCS had a higher negative rate (95%) than CS (23.1%) in BZ-T. The classic cure criterion demonstrated that 75% of BZ-T achieved a successful therapeutic outcome. Moreover, the use of the second and third alternative cure criteria revealed a higher proportion of cure in BZ-T (90%). The overall mortality over 27-year follow-up was 4.8% in BZ-T and 38.1% in NT. Kaplan-Meier survival curves for survival estimated 95% and 40% for BZ-T and NT patient groups.

The overall analysis demonstrated that BZ-T chronic CD patients yielded higher parasitological cure rates as well as increased survival over a 27-year follow-up. The Chagas-Flow ATE proved to be a valuable tool for monitoring therapeutic response and, together with parasitological and molecular parasitological methods, provided a more accurate cure criterion.

Chagas disease is a common parasitic disease that occurs mainly in poor regions of countries with low development rates of Latin America, including Brazil. According to the World Health Organization, it is estimated that between 6 and 7 million people are infected worldwide, with 10,000 deaths per year in historically endemic regions, such as Mexico, Central, and South America. Due to the human migratory process, CD has spread to other previously unaffected regions, such as Europe, Japan, Australia, Canada, and the United States. Specific treatment with the antiparasitic drug benznidazole is prescribed for patients infected in the acute and chronic phases. However, the studies demonstrating benefits, cure, and survival post-treatment are discordant. We periodically monitored 42 patients with CD, including: BZ-treated (n = 21) and Not-treated (n = 21) for 27-year follow-up. We analyzed the presence of the infection with three parasitological and two serological examinations. The global analysis, considering the average amongst the different cure criteria (1st = 75%; 2nd = 90%; 3rd = 90%), revealed parasitological cure in more than 85% of patients in BZ-T and no cure in the NT group. Furthermore, the overall survival was superior in BZ-T (95.0%) as compared to NT (40.0%). The mortality was 4.8% in treated and 38.1% in Not-treated patients. Thus, our study demonstrated that long-term follow-up of BZ-treatment brought about several benefits regarding cure rates and survival, highlighting the relevance of treating patients at chronic phase of CD.