Post-TPT Risk of Tuberculosis Among Household Contacts: A Multistate Observational Cohort Study from India

Background : India carries the highest TB burden globally, with 31% of the population estimated to be infected with Mycobacterium tuberculosis, albeit in a dormant form . Household contacts (HHCs) represent a particularly vulnerable group due to intense exposure, with TB prevalence several-fold higher than the general population. To mitigate progression from TB infection to active TB disease, the government expanded TB preventive therapy eligibility to all HHCs in 2021. While evidence exists on TB prevalence among HHCs, limited evidence exists about post-TPT outcomes or risk factors for disease progression. This study evaluates symptoms, care-seeking behaviours, and TB occurrence among HHCs who completed TPT under programmatic conditions across nine Indian states. Methods : A total of 4,012 household contacts of pulmonary drug-sensitive TB patients who successfully completed TB preventive therapy between October 2022 and March 2023, were sampled from nine Indian states, using a stratified sampling approach. Of these, 78% received 6H and 22% received 3HP. Contacts were followed twice post-TPT completion, within 12 months and again within 18 months, to capture symptomatic incidence, care-seeking behaviour, diagnostic pathways, and TB outcomes. Descriptive statistics, logistic regression, and survival analysis were used to identify predictors of symptom development, care-seeking, and TB diagnosis, and to evaluate symptom-based algorithms for triage in resource-limited settings. Results : Marked state-level variation was observed in CXR screening uptake, TPT initiation timeliness, and access to diagnostic services, influencing symptomatic prevalence and TB detection rates. Symptom burden was the strongest predictor of TB diagnosis, with specific combinations, particularly recurrent cough with weight loss, showing high diagnostic accuracy. All TB diagnoses (n=22) occurred among symptomatic individuals, and majority were detected within six months of TPT completion. However, only 17% of symptomatic contacts had gone for a medical consultation by the time of follow ups, and only 18% were assessed with NAAT. Suggestive pre-TPT CXR findings and delays in TPT initiation were associated with higher post-TPT symptom incidence. Individuals on 3HP reported fewer post-TPT symptoms than those on 6H. Conclusion: Health-system disparities across states shape TPT outcomes and the timely identification of post-TPT TB. Strengthening routine CXR screening, reducing delays in TPT initiation, improving adherence support, especially for longer 6H regimens, and implementing earlier, risk-stratified follow-up could enhance early TB detection among high-risk HHCs. Integrating symptom-based triage tools and ensuring equitable access to diagnostic evaluation are critical for optimizing the preventive impact of TPT in resource-constrained settings.