Five-year serological and clinical evolution of chronic Chagas disease patients in Cochabamba, Bolivia.

Background: Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected infectious disease that exerts the highest public health burden in the Americas. There are two anti-parasitic drugs approved for its treatment–benznidazole and nifurtimox—but the absence of biomarkers to early assess treatment efficacy hinders patients´ follow-up. Methodology/Principal findings: We conducted a longitudinal, observational study among a cohort of 106 chronically T. cruzi-infected patients in Cochabamba (Bolivia) who completed the recommended treatment of benznidazole. Participants were followed-up for five years, in which we collected clinical and serological data, including yearly electrocardiograms and optical density readouts from two ELISAs (total and recombinant antigens). Descriptive and statistical analyses were performed to understand trends in data, as well as the relationship between clinical symptoms and serological evolution after treatment. Our results showed that both ELISAs documented average declines up to year three and slight inclines for the following two years. The recorded clinical parameters indicated that most patients did not have any significant changes to their cardiac or digestive symptoms after treatment, at least in the timeframe under investigation, while a small percentage demonstrated either a regression or progression in symptoms. Only one participant met the "cure criterion" of a negative serological readout for both ELISAs by the final year. Conclusions/Significance: The study confirms that follow-up of benznidazole-treated T. cruzi-infected patients should be longer than five years to determine, with current tools, if they are cured. In terms of serological evolution, the single use of a total antigen ELISA might be a more reliable measure and suffice to address infection status, at least in the region of Bolivia where the study was done. Additional work is needed to develop a test-of-cure for an early assessment of drugs´ efficacy with the aim of improving case management protocols. Author summary: Chagas disease is a neglected parasitic disease prevalent throughout the Americas, with approximately seven million people infected. The highest infection rates have been identified in Bolivia. There, we followed for five years a cohort of chronically T. cruzi-infected patients attending the Platform for Integral Care of Chagas disease Patients in Cochabamba. With the aim to understand clinical and serological responses after completing treatment with benznidazole, we recorded clinical symptomatology and collected serum samples to run two ELISAs based on total and recombinant antigens in each yearly follow-up visit. Upon analyzing clinical and serological data, we found there were no major changes in the patients´ clinical status while serological reactivity generally declined until the third year of follow-up, particularly with the total antigen test. Remarkably, only one participant met the cure criterion of negative serological reversion for both ELISAs at the final visit. Our findings confirm that, using currently available tools, the appropriate time to address treatment efficacy is longer than five years. Additional studies are needed to find biomarkers for the early assessment of treatment efficacy. [ABSTRACT FROM AUTHOR]