Bimodal distributions of anti-Trypanosoma cruziantibody levels in blood donors are associated with parasite detection and antibody waning in peripheral blood

Background In our previous study of blood donors in the Argentinian Chaco Province, we documented bimodal distributions of anti- Trypanosoma cruzi antibody (Ab) levels, suggesting potential self-cure in donors with low-reactive samples. This study aimed to correlate “high” and “low” Ab level groups, defined by a mathematical model, with parasitemia and electrocardiogram findings. Ab decline over time was also assessed. Methodology / Principal Findings We invited T. cruzi Ab reactive blood donors to enroll in the study from October 2018 to November 2019 with a follow up visit two years later. Blood samples were tested for T cruzi Ab by: Chagatest ELISA Lisado and Chagatest ELISA Recombinante v.4.0 (Wiener Lab, Argentina); VITROS Immunodiagnostic Products Anti-T.cruzi (Chagas) (Ortho-Clinical Diagnostics Inc., UK), and Architect Chagas (Abbott Laboratories, Germany). Target capture PCR was performed on lysed whole blood samples from enrollment visits and electrocardiograms on second visits. Four hundred fifty donors were recruited, but 68 were excluded due to negative results on all study Ab assays. Ab level distributions were bimodal and classified as “high” or “low” at a calculated threshold for each of four assays. There were 160 donors with low and 179 with high Ab results on all assays. The remainder 43 were discordant reactive. Ninety-seven percentage of the PCR positive donors were among the concordant high Ab group. During the 2-4 year follow-up interval, relative Ab declines by three assays were significantly greater among those classified as low Ab and with negative PCR results. Conclusions / Significance Ab reactivity is associated with PCR-detectable parasitemia. Greater Ab declines were detected among donors with low and/or discordant Ab reactivity and negative PCR results, suggesting spontaneous parasite clearance in these donors.