Sex differences in the risk of Mycobacterium tuberculosis infection: a systematic review and meta-analysis of population-based immunoreactivity surveys

Background Tuberculosis killed 1·25 million people globally in 2023. Men have a 1·7 times higher tuberculosis incidence than women, but it is not known to what extent this discrepancy is driven by greater exposure to Mycobacterium tuberculosis. We aimed to analyse the effect of age and sex on M tuberculosis immunoreactivity. Methods In this systematic review and meta-analysis, we reviewed Embase, Global Health databases, Science Citation Index Expanded, and Global Index Medicus for population-based M tuberculosis immunoreactivity (with interferon-γ release assay or skin test) surveys done in high tuberculosis incidence settings from Jan 1, 1993, to Dec 31, 2022, with a sample size of at least 150 people. We included cross-sectional surveys, baseline surveys for interventional or cohort studies, and control groups of case–control studies with population-representative groups. We extracted data on M tuberculosis immunoreactivity prevalence, disaggregated by sex and age group. We constructed Bayesian hierarchical models, first of immunoreactivity prevalence by age and sex and second of the male-to-female (M:F) prevalence ratio by age. We analysed the effect of covariables including region, tuberculosis incidence, and study year. This study was registered on PROSPERO (CRD42022360483). Findings We screened 26 517 studies, of which 167 met our inclusion criteria. Sex-disaggregated results were available from 80 studies (81 surveys), from 38 different countries, comprising data from 478 968 participants. We found little sex difference in M tuberculosis immunoreactivity in childhood (M:F prevalence ratio for children younger than 10 years was 0·95; 95% credible interval 0·90–1·01). However, from adolescence onwards, men experienced higher immunoreactivity conversion than women (1·4 times higher by age 30 years). This higher conversion rate cumulatively drove a higher immunoreactivity prevalence in men, with a prevalence ratio of 1·07 (95% credible interval 1·01–1·13) in those aged 10–19 years, 1·13 (1·06–1·20) in those ...