Declining antibody levels to Trypanosoma cruzi correlate with polymerase chain reaction positivity and electrocardiographic changes in a retrospective cohort of untreated Brazilian blood donors

Author summary Infection with the single-celled parasite Trypanosoma cruzi (Chagas disease) is thought to be lifelong. However, only a third of infected people develop Chagas cardiomyopathy-the main disease manifestation. This may reflect the different extent to which individuals control the parasite, with some potentially clearing it entirely. In chronically infected immunocompetent patients, a marker of parasite burden is the quantity of antibody against T. cruzi in the blood: more parasite, more immune stimulation, more antibody. In this study we show how antibody levels change over many years in a cohort of untreated patients with Chagas disease. We find that among individuals with falling or low/borderline antibody levels there was a lower rate of parasite detection in the blood and a lower rate of cardiomyopathy. 60% of subjects with falling antibody levels had no evidence of active disease, twice as many as among patients with other antibody trajectories (stable or rising). Our findings support an account of the natural history of Chagas disease in which a proportion of those infected achieve a greater control of the parasite, with some individuals potentially clearing it completely. Background Although infection with Trypanosoma cruzi is thought to be lifelong, less than half of those infected develop cardiomyopathy, suggesting greater parasite control or even clearance. Antibody levels appear to correlate with T. cruzi (antigen) load. We test the association between a downwards antibody trajectory, PCR positivity and ECG alterations in untreated individuals with Chagas disease. Methodology/Principal findings This is a retrospective cohort of T. cruzi seropositive blood donors. Paired blood samples (index donation and follow-up) were tested using the VITROS Immunodiagnostic Products Anti-T.cruzi (Chagas) assay (Ortho Clinical Diagnostics, Raritan NJ) and PCR performed on the follow-up sample. A 12-lead resting ECG was performed. Significant antibody decline was defined as a reduction of > 1 signal-to-cutoff (S/CO) unit on the VITROS assay. Follow-up S/CO of < 4 was defined as borderline/low. 276 untreated seropositive blood donors were included. The median (IQR) follow-up was 12.7 years (8.5-16.9). 56 (22.1%) subjects had a significant antibody decline and 35 (12.7%) had a low/borderline follow-up result. PCR positivity was lower in the falling (26.8% vs 52.8%, p = 0.001) and low/borderline (17.1% vs 51.9%, p < 0.001) antibody groups, as was the rate of ECG abnormalities. Falling and low/borderline antibody groups were predominantly composed of individuals with negative PCR and normal ECG findings: 64% and 71%, respectively. Conclusions/Significance Low and falling antibody levels define a phenotype of possible spontaneous parasite clearance.