Across the globe, men develop tuberculosis (TB) at substantially higher rates than women. New research suggests that this disparity may have more to do with men's greater risk of becoming infected in the first place than with a greater likelihood of the infection progressing to disease.
An estimated 10.7 million people worldwide developed TB in 2024—5.8 million men and 3.7 million women. Researchers have long wondered about the precise mechanisms behind the higher prevalence in men: Does the disparity reflect differences in exposure to Mycobacterium tuberculosis, biological differences in susceptibility to disease after infection, or a combination of the two?
The findings, published last week in eClinicalMedicine, are drawn from 11 prospective cohort studies conducted in sub-Saharan Africa, Europe, Asia, and South America. Together, the studies tracked more than 22,000 participants for 12 years.
No sex difference in disease progression
For the analysis, an international research team led by scientists at the Institute for Global Health at University College London analyzed data from 22,424 participants in studies conducted between 2005 and 2017. The researchers followed participants for an average of 2.8 years, during which 411 people, or 1.8%, developed TB. Two-thirds of participants were adults.
At baseline, 38.1% of males and 35.0% of females were infected with TB. After adjusting for age, males had a 12% higher likelihood of TB infection than females. But once the researchers took infection status into account, they found no significant difference in the risk of developing TB disease.
Among those who tested positive for infection at baseline, the incidence of TB disease was 15.6 cases per 1,000 person-years in males and 16.3 per 1,000 person-years in females—a difference that was not statistically significant. Similarly, among participants who initially tested negative for TB infection, future TB risk did not differ significantly between males and females.
“These findings suggest that the well-documented excess burden of TB among males appears more consistent with differences in TB infection risk than with a large sex difference in progression from infection to disease,” write the researchers.
Findings can’t rule out biological differences
The researchers note that they did not measure other determinants of infection risk, such as social interactions, occupational exposures, and behavioral risks, which may explain men’s greater likelihood of being infected with TB. They also note that healthcare-related and clinical factors may partly explain the observed differences in infection incidence. In a separate Italian cohort study published earlier this year, for example, men were more likely to be lost to follow-up.
In addition, the findings can’t rule out biological differences in TB susceptibility, write the researchers, noting that a recent review highlights the possible roles sex hormones, sex chromosomes, and sex-specific innate and adaptive immune responses may play in TB progression and outcomes.
The higher burden of TB among males is likely to reflect multiple mechanisms rather than a single pathway.
“The higher burden of TB among males is likely to reflect multiple mechanisms rather than a single pathway,” they say.
Still, the results highlight the potential value of prevention and screening strategies that address sex-specific patterns of TB exposure.
“Our findings improve our understanding of why TB disproportionately affects men and suggest that reducing inequalities in TB exposure among men may have a greater impact on narrowing the sex gap in TB burden than interventions focused solely on progression from infection to disease,” co-lead author and senior research fellow at the Institute for Global Health, Yohhei Hamada, PhD, said in a University College London news release.
