The Journal of infectious diseases · 2026
Risk Factors for Immunological Sensitization to Mycobacterium tuberculosis and Progression to Incident TB Disease Among HIV-uninfected Adults in a High Burden Setting.
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Mulenga Humphrey, Mendelsohn Simon C, Fiore-Gartland Andrew, Penn-Nicholson Adam, Musvosvi Munyaradzi, Tameris Michèle, Walzl Gerhard, Naidoo Kogieleum, Churchyard Gavin, Scriba Thomas J, Hatherill Mark
Аннотация
BACKGROUND: Identifying risk factors for Mycobacterium tuberculosis (Mtb) sensitization (defined as interferon-gamma release assays [IGRA]-positive) and progression to tuberculosis (TB) disease is critical to guide targeted prevention strategies.
METHODS: We analyzed data from a prospective cohort of adults (18-60 years) without HIV, enrolled at five high-incidence South African sites. Participants underwent testing for Mtb sensitization and microbiologically confirmed TB at baseline, and during 15 months follow-up. Multivariable logistic and Cox regression models were used to assess factors associated with Mtb sensitization and TB progression. Sampling weights were applied to reflect the screened population.
RESULTS: Among 2912 participants with valid IGRA results, 63.4% (n = 1895) were Mtb-sensitized. Prevalent TB was detected in 1.81% (62/1895) of Mtb-sensitized vs 0.62% (12/1017) of Mtb-unsensitized individuals (P = .01). During follow-up of participants without prevalent TB, 2.01% (48/1833) Mtb-sensitized and 0.53% (8/1005) Mtb-unsensitized individuals developed TB (P = .01). Factors associated with Mtb sensitization included increasing age (adjusted odds ratio [aOR] = 1.02, 95% CI 1.01-1.03), male sex (aOR = 1.34, 95% CI 1.08-1.67), smoking (aOR = 1.31, 95% CI 1.05-1.64), prior TB (aOR = 2.20, 95% CI 1.40-3.47), and TB contact history (aOR = 1.40, 95% CI 1.08-1.83). Risk factors for progression to TB were Mtb sensitization (adjusted hazard ratio [aHR] = 3.05, 95% CI 1.14-8.18), smoking history (aHR = 2.34, 95% CI 1.03-5.31), and lower body mass index (BMI) (aHR = 0.89, 95% CI .82-.97).
CONCLUSIONS: Mtb-sensitized individuals had a 3-fold higher risk of prevalent TB and progressing to TB compared to Mtb-unsensitized individuals. In high-prevalence settings, identifying individuals at greatest risk-such as those recently infected, with a history of smoking, or low BMI-could help refine TB prevention efforts and reduce community-level transmission.
METHODS: We analyzed data from a prospective cohort of adults (18-60 years) without HIV, enrolled at five high-incidence South African sites. Participants underwent testing for Mtb sensitization and microbiologically confirmed TB at baseline, and during 15 months follow-up. Multivariable logistic and Cox regression models were used to assess factors associated with Mtb sensitization and TB progression. Sampling weights were applied to reflect the screened population.
RESULTS: Among 2912 participants with valid IGRA results, 63.4% (n = 1895) were Mtb-sensitized. Prevalent TB was detected in 1.81% (62/1895) of Mtb-sensitized vs 0.62% (12/1017) of Mtb-unsensitized individuals (P = .01). During follow-up of participants without prevalent TB, 2.01% (48/1833) Mtb-sensitized and 0.53% (8/1005) Mtb-unsensitized individuals developed TB (P = .01). Factors associated with Mtb sensitization included increasing age (adjusted odds ratio [aOR] = 1.02, 95% CI 1.01-1.03), male sex (aOR = 1.34, 95% CI 1.08-1.67), smoking (aOR = 1.31, 95% CI 1.05-1.64), prior TB (aOR = 2.20, 95% CI 1.40-3.47), and TB contact history (aOR = 1.40, 95% CI 1.08-1.83). Risk factors for progression to TB were Mtb sensitization (adjusted hazard ratio [aHR] = 3.05, 95% CI 1.14-8.18), smoking history (aHR = 2.34, 95% CI 1.03-5.31), and lower body mass index (BMI) (aHR = 0.89, 95% CI .82-.97).
CONCLUSIONS: Mtb-sensitized individuals had a 3-fold higher risk of prevalent TB and progressing to TB compared to Mtb-unsensitized individuals. In high-prevalence settings, identifying individuals at greatest risk-such as those recently infected, with a history of smoking, or low BMI-could help refine TB prevention efforts and reduce community-level transmission.