GS Paper II

News Excerpt:

23 states have agreed to participate in a program implementation study to evaluate the effectiveness of the BCG vaccine in reducing TB disease incidence in adults.

About the study:

• The study aims to target high-risk groups such as those over 50, those with prior TB disease, underweight adults, diabetics, and those who smoke and consume alcohol.
• The focus is on closing gaps in the immunisation programme post-pandemic.
• Phase 1 will be conducted in Uttar Pradesh and Madhya Pradesh, with Tamil Nadu having 44 TB districts.
• Kerala, Bihar, Chhattisgarh, West Bengal, and Uttarakhand have not consented to participate in the study.
• The safety profile of BCG revaccination will be studied programmatically, while a sub-group of participants will be followed-up for two-three years by National Institute for Research in Tuberculosis (NIRT), Chennai for vaccine efficacy.
• Incidentally, while NIRT will be conducting a BCG booster dose clinical trial in children aged 6-18 years.
• The BCG revaccination study in adults is being undertaken mainly based on the retrospective data analysis of a small sub-group of the Chingleput BCG vaccination trial conducted in 1968.
• In the 1968 trial, 2,890 adults received a BCG revaccination and 1,546 did not, and the efficacy of the vaccine to reduce TB incidence was found to be 36%.
• But the protective efficacy was seen only at the end of 15 years of follow-up, and the protective effect of BCG revaccination was significant only in the 31-40 years age group.

• The government has decided to go ahead with the “programme implementation study mode”. Since it is felt that a trial would take too long to complete and wanted to implement BCG revaccination at scale.
• Accordingly, 50% of the districts in a State will be included in the intervention arm and the remaining 50% will act as control.

Issues with the revaccination strategy:

• The Chingleput BCG revaccination study has limitations due to its small sample size, unknown confounders like nutritional status, diabetes, smoking, alcohol consumption, TB exposure status, and the time interval between the first dose and BCG revaccination.
• BCG revaccination in adults has not been studied in India to prevent TB disease, and studies in other countries have yielded mixed results.
• St. John's Research Institute, Bengaluru in its 2019 and 2023 studies found it immunogenic.
• Most global studies have not found significant impacts on TB incidence.
• A recent phase-2 trial in South Africa suggested it may prevent TB infection.
• The World Health Organization (WHO) does not recommend programmatic or pilot BCG revaccination, even in high-burden countries like India.
• The 2018 BCG vaccine position paper states that studies show minimal or no evidence of additional benefits of repeat BCG vaccination against TB or leprosy.
• The protective effect of a single dose of the vaccine in India wanes within a short time, and a 15-year follow-up study found a lack of protective efficacy in children after 7.5 years.

Way forward:

• An expert committee constituted by Indian Council of Medical Research (ICMR) recommended that a robust trial be carried out in India and implementation at population-level be undertaken once evidence of efficacy was available.
• The committee suggested that some districts be used as an intervention arm and some as the control arm, and TB incidence be captured over a couple of years.
• Further trials are needed to assess the effectiveness of revaccination in different populations, age groups, timing, and types of TB.