Prevalence of clinical forms of Chagas disease: a systematic review and meta-analysis - data from the RAISE study

Background There is a lack of up-to-date estimates about the prevalence of Chagas disease (ChD) clinical presentations and, therefore, we aimed to assess the prevalence of clinical forms of ChD among seropositive adults, pooling available data. Methods A systematic review was conducted in Medline, Embase, Biblioteca Virtual em Sa & uacute;de and Cochrane databases looking for studies published from 1990 to August 2023, which investigated the prevalence of ChD clinical forms among seropositive adults, including: (i) indeterminate phase, (ii) chronic Chagas cardiomyopathy (CCM), (iii) digestive and (iv) mixed (CCM + digestive) forms. Pooled estimates and 95% confidence intervals (CI) were calculated using random-effects models. Studies quality and risk of bias was assessed with the Leboeuf-Yde and Lauritsen tool. Heterogeneity was assessed with the I-2 statistic. The study was registered in the PROSPERO database (CRD42022354237). Findings 1246 articles were selected for screening and 73 studies were included in the final analysis (17,132 patients, 44% men). Most studies were conducted with outpatients (n = 50), followed by population-based studies (n = 15). The pooled prevalence of the ChD clinical forms was: indeterminate 42.6% (95% CI: 36.9-48.6), CCM 42.7% (95% CI: 37.3-48.3), digestive 17.7% (95% CI: 14.9-20.9), and mixed 10.2% (95% CI: 7.9-13.2). In population-based studies, prevalence was lower for CCM (31.2%, 95% CI: 24.4-38.9) and higher for indeterminate (47.2%, 95% CI: 39.0-55.5) form. In meta-regression, age was inversely associated with the prevalence of indeterminate (beta = -0.05, P < 0.001) form, and directly associated with CCM (beta = 0.06, P < 0.001) and digestive (beta = 0.02, P < 0.001) forms. Heterogeneity was overall high. Interpretation Compared to previous publications, our pooled estimates show a higher prevalence of CCM among ChD seropositive patients, but similar rates of the digestive form.