Factors driving adolescent tuberculosis incidence by age and sex in 30 high-tuberculosis burden countries: a mathematical modelling study.

Introduction: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

Methods: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO's 30 high-tuberculosis burden countries (HBCs), which represent 86%-90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10-14 years vs 15-19 years old). We adjusted age subgroup-specific risks of disease progression by age- and sex-specific risks of low body mass index (BMI), pregnancy and postpartum period (PPP) and HIV coinfection. We calculated population attributable fractions (PAFs) to these factors.

Results: In 2019, 91.2 million (95% uncertainty interval (UI) 83.9 to 99.3 million) adolescents in the 30 HBCs had been infected with M. tuberculosis, and an estimated 1.0 million (95% UI 0.8 to 1.2 million) developed tuberculosis disease. The median PAF of tuberculosis disease to HIV, modified by antiretroviral therapy, was 1% and highest in Southern Africa. The median PAF for PPP among older adolescents of both sexes was 2.6%. The median PAF to low BMI was 16% and highest in South Asia. The MF risk ratio of tuberculosis disease was 1.2-fold higher among older adolescents, relative to young adolescents. The widening MF risk ratio was attributable mostly to low BMI, with a smaller contribution from sex-assortative social mixing.

Conclusion: Globally, large numbers of adolescents have been infected by M. tuberculosis and develop tuberculosis disease. Low BMI is the most important contributor to the overall incidence of tuberculosis disease, as well as to the sex difference that widens with age.