Determinants of TB Incidence in South Indian Population: Chengalpattu BCG Trial Revisited, South India

Background: Globally, tuberculosis (TB) continuous to be a major public health problem. New borne Bacillus Calmette Guerin (BCG) vaccination is known to provide some protection in children with very little or no protection in adults. Given the current interest in BCG revaccination and new TB vaccines for use in adolescents and adults. We aimed at studying TB incidence in BCG vaccinated individuals with prior sensitization to Mycobacterium tuberculosis (MTB) and non-tuberculosis mycobacteria (NTM). Methods: Secondary data analysis of a double-blind randomized controlled trial conducted at Chengalpattu, South India between 1968-1983. Individuals aged ≥1 year were tested with Purified Protein Derivative (PPD)-S (M. tuberculosis) and PPD-B (M. intracellulare); proxy for exposures to MTB and NTM respectively. Cut-off of induration to PPS-S (weakly reactive: ≤11 mm) and (strongly reactive: ≥ 12 mm), and PPD-B (≥10 mm as strongly reactive). Calculated incidence rates (IR)/100,000 person-years (PY) and Chi-square test with a p-value < 0.05 as significant. Findings: Total 261,756 people ≥ 10 years were included in BCG 0∙01 mg (n=86,827), BCG 0∙1 mg (n=87,040), and placebo (n=87,889) groups. At enrolment, 74% of children (5-14 year) had an induration of ≥ 10 mm to PPD-B; 26% ≥12 mm to PPD-S. Adults (≥ 25 year), 99% had an induration of ≥ 10 mm to PPD-B;74% ≥ 12 mm to PPD-S. Overall there was no difference in annual IR between placebo and BCG arms (p >0.5) over 15 years. IR ranged between 93-181/100,000 PY for individuals strongly reactive to PPD-B compared to PPD-S and 401-634/100,000 PY for individuals strongly reactive to PPD-S compared to PPD-B (p <0.001). Interpretation: In population with high exposure rates to NTMs and MTB, the incidence rates may be four-fold low in people exposed to NTM. Our findings indicate that children aged 5-14 years would make ideal candidates for BCG-revaccination studies. As majority of the population is exposed to MTB and NTMs at a very young age and may pose challenges during field trials of new TB vaccines for adults. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The institutional ethics committee of the ICMR-National Institute for Research in Tuberculosis, Indian Council of Medical Research, approved the project.