Sex differences in tuberculosis incidence: a pooled analysis of 11 prospective cohort studies.

Background: Tuberculosis (TB) incidence is consistently higher in men than women globally. Whether this disparity arises from differential infection risk or sex-specific rates of progression from infection to disease remains unclear. We evaluated sex differences in the development of TB disease while accounting for baseline infection status. Methods: We conducted a pooled individual participant data analysis of 11 prospective cohort studies (n = 22,424), conducted between 2005 and 2017 across Sub-Saharan Africa, Europe, Asia, and South America. TB infection was defined by a positive QuantiFERON-TB Gold In-Tube result, and incident TB was defined by bacteriologically confirmed or clinical diagnosis. We used mixed-effects logistic and Cox proportional hazards models, adjusted for age, to estimate odds ratios (OR) for infection and hazard ratios (HR) for incident TB by sex. Findings: Participants were followed for a median of 2.8 years, during which 411 individuals (1.8%) developed TB. Most participants were from Europe (52%) or South Africa/Zambia (34.4%). At baseline, males had a significantly higher likelihood of infection (OR 1.12; 95% CI 1.02-1.22). Among those with baseline infection, pooled incidence rates were 16.3 per 1000 person-years (95% CI 10.9-24.4) in females and 15.6 (95% CI 9.8-24.8) in males. The risk of developing TB did not differ by sex among those with baseline infection (HR 0.86; 95% CI 0.65-1.14) or without baseline infection (HR 1.02; 95% CI 0.71-1.47). Interpretation: In these cohorts, males had a higher prevalence of baseline TB infection, but no clear excess risk of subsequent TB disease after accounting for baseline infection status. These findings suggest that sex differences in TB infection risk may contribute more to higher TB incidence among males than differences in TB disease risk after infection. Funding: None.