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

Lewis F Buss,Erika R Manuli,Flavia C Sales,Cesar De Almeida-Neto,Clara Di Germanio,Antonio L Ribeiro,Léa Campos De Oliveira- Da Silva,Paul Constable,Ingra Morales,Ester C Sabino,Sonia Bakkour,Carlos H V Moreira,Marcelo M Pinto-Filho,Michael Busch,Ricardo E Gürtler

doi:10.1371/journal.pntd.0008787

Abstract

BackgroundAlthough 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 findingsThis 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/SignificanceLow and falling antibody levels define a phenotype of possible spontaneous parasite clearance.

Highlights

Chagas disease (CD)–due to infection by Trypanosoma cruzi–is a neglected tropical 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
We report a retrospective cohort of T. cruzi seropositive blood donors with longitudinal measurement of antibody levels over a median of 12 years follow-up

Summary

Introduction

Chagas disease (CD)–due to infection by Trypanosoma cruzi–is a neglected tropical disease. It affects 6–8 million people worldwide [1] and is responsible for 50,000 deaths annually [2,3]. Acute infection is characterized by a mild illness in which the parasite is readily detected in the blood This gives way to chronic tissue sequestration, affecting the myocardium. The development of clinically apparent cardiomyopathy is variable, with most individuals remaining asymptomatic for life [5]. The mechanisms underlying this process remain poorly understood. We test the association between a downwards antibody trajectory, PCR positivity and ECG alterations in untreated individuals with Chagas disease

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Results

Discussion

Conclusion