Impact of Follow-Up Duration and Geographical Distribution of Whole-Genome Sequencing Studies on Estimates of Exogenous Reinfection in Recurrent Tuberculosis: A Systematic Review and Meta-Analysis

Truncated follow-up and low-resolution genotyping obscure the proportion of exogenous reinfection in recurrent tuberculosis. We aimed to quantify how extended follow-up (≥2 years) and whole-genome sequencing (WGS) affect the estimated proportion of reinfection. We did a systematic review and meta-analysis by searching PubMed, Embase, and Web of Science for English-language studies published between 1 January 2020 and 7 February 2026 that used genotyping techniques to distinguish relapse from reinfection in recurrent tuberculosis, and we integrated these with those from a 2021 meta-analysis that reported a 29% pooled reinfection proportion. Risk of bias was assessed using a modified Newcastle–Ottawa Scale, and random-effects model meta-analyses were conducted to estimate pooled proportions of reinfection. In studies with <2 years of follow-up, the pooled reinfection proportion was 22%. However, when follow-up was extended to ≥2 years, the proportion increased to 34% (95%CI 26–42%), with an adjusted OR of 1.94. Shorter follow-up was associated with a nearly 12% lower observed proportion of exogenous reinfection. Current WGS-related research is mainly concentrated in Asia (50%), especially China (36%), and lacks data from the Americas. The estimated proportion of exogenous tuberculosis reinfection is substantially influenced by follow-up duration and is constrained by the geographical distribution of current WGS data.