Reactivation of Trypanosoma cruzi infection in immunosuppressed patients: a systematic review and meta-analysis

Background: The risk of Trypanosoma cruzi reactivation is poorly understood. Previous studies evaluating the risk of reactivation report imprecise findings, and recommendations for monitoring and management from clinical guidelines rely on consensus opinion. Objectives: We conducted a systematic review and meta-analysis to estimate the cumulative T. cruzi reactivation incidence in immunosuppressed adults, summarize the available evidence on prognostic factors for reactivation, and examine its prognostic effect on mortality. Data sources: MEDLINE, Embase, LILACS, Clinical Trials, and CENTRAL from inception to 4 July 2022. Study eligibility criteria: Studies reporting the incidence of T. cruzi reactivation. Participants: Immunosuppressed adults chronically infected by T. cruzi. Methods: Two authors independently extracted data (including, but not limited to, incidence data, reactivation de finition, follow-up, treatment, monitoring schedule, examined prognostic factors) and evaluated the risk of bias. We pooled cumulative incidence using a random-effects model. Results: Twenty-two studies (806 participants) were included. The overall pooled incidence of T. cruzi reactivation was 27% (95% CI, 19-36), with the highest pooled proportion in the sub-group of transplant recipients (36%; 95% CI, 25-48). The highest risk period was in the first 6 months after transplant (32%; 95% CI, 17-58), decreasing drastically the number of new cases later. People living with HIV and patients with autoimmune diseases experienced significantly lower cumulative reactivation incidences (17%; 95% CI, 8-29 and 18%; 95% CI, 9-29, respectively). A single study explored the independent effect of benznidazole and found bene fits for preventing reactivations. No studies evaluated the independent association between reactivation and mortality, while sensitivity analysis results using unadjusted estimates were inconclusive. The heterogeneity of diagnostic algorithms was substantial. Conclusions: Reactivation occurs in three out of ten T. cruzi-seropositive immunosuppressed adults. These findings can assist clinicians and panel guidelines in tailoring monitoring schedules. There is a great need for an accurate de finition of reactivation and targeted monitoring. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).