Influenza and the risk of active tuberculosis occurrence among individuals with latent tuberculosis infection: A national cohort study in South Korea (2015–2020)

BACKGROUND: Influenza's potential impact on active tuberculosis (TB) development has been debated, with limited clinical evidence. To address this, we explored the association between influenza episodes and TB incidence in a national cohort of individuals with latent TB infection (LTBI). METHODS: We examined adults (≥20 years) diagnosed with LTBI between 2015 and 2020, using the Health Insurance Review and Assessment Service's national database in South Korea. We collected demographic data, comorbidities, and influenza episodes within 6 months before and after the initial LTBI diagnosis (prior vs. subsequent episode). We stratified the analysis into groups with and without TB preventive therapy (TPT). RESULTS: Among 220,483 LTBI subjects, 49% received TPT, while 51% did not. The average age was 48.4 years, with 52% having comorbidities. A prior and subsequent influenza episode was identified in 3221 and 4580 individuals, respectively. Of these, 1159 (0.53%) developed incident TB over an average follow-up of 1.86 years. The incidence rates of TB were comparable between individuals with and without prior and/or subsequent influenza episodes in the TPT group, but 1.4 times higher in the non-TPT group for those with such episodes. Cox proportional-hazards regression analysis indicated that influenza was not a risk factor for incident TB in the TPT group. However, a subsequent influenza episode significantly increased TB risk in the non-TPT group (hazard ratio: 1.648 [95% CI, 1.053-2.580]). CONCLUSIONS: In individuals with LTBI not receiving TPT, experiencing an influenza episode may elevate the risk of developing active TB.