‘Biomarkers to predict advance of TB in household contacts of patients an important find’: Dr S Subash Babu, Scientific Director of NIAID–ICER

According to Dr S Subash Babu, the Scientific Director and first Indian scientist to be honoured with the prestigious Bailey K Ashford Medal last year for exemplary research, “these findings carry important implications for early intervention and preventive strategies in TB-endemic regions.”

On the specific set of plasma biomarkers and their affordability

Traditional TB diagnosis methods involve techniques like sputum smear microscopy, culture, and chest X-rays. Researchers have been exploring the potential of biomarkers for TB diagnosis and monitoring. Plasma biomarkers are substances in the blood that can signal the presence of TB progression.

The team has defined two distinct sets of biomarkers using Quantiferon whole blood supernatant or plasma. Their recent study, with findings presented at the annual meeting of RePORT India, suggests that a specific set of plasma biomarkers—namely GM-CSF, CXCL10, and IL-1Ra—can effectively identify household contacts at significant risk of developing TB disease.

These markers boast an impressive sensitivity of 100%, specificity of 93%, and an area under the curve of 98%, thereby meeting the WHO’s recommended Target Product Profile as predictive biomarkers for active TB development.

The aim now is to translate these tests into point-of-care solutions, making them more accessible. It is important to note that these plasma biomarkers hold great promise for TB diagnosis and monitoring but are typically used in conjunction with other diagnostic methods.

Study findings carry substantial implications for TB prevention strategies

A cohort of household contacts (HHCs) comprising 1,051 individuals, newly diagnosed with pulmonary tuberculosis (PTB), were recruited from two study sites: the Indian Council of Medical Research- National Institute of Research in TB (ICMR-NIRT), Chennai, and BJ Government Medical College (BJGMC), Pune.

This collaborative effort was a part of the Cohort for Tuberculosis Research by the Indo-US Medical Partnership (C-TRIUMPH) study. These participants were closely monitored between August 2014 and December 2017. Among them, 20 individuals (1.9%) were classified as ‘progressors’ as they developed active TB over a two-year period. The time between enrollment and the diagnosis of active TB ranged from 3 to 21 months.

Equally, a matched number of HHCs, referred to as ‘non-pProgressors’, were selected based on age and sex. However, these non-progressors did not develop active TB throughout the study duration.

The plasma biomarkers discovered in this study demonstrated exceptional accuracy in distinguishing between progressors and non-progressors, several months before the onset of active TB.

On the TB burden, and significance of identifying household contacts

The National TB Elimination Programme (NTEP) is actively working to eliminate TB by 2025. Despite the decline in TB notifications seen in 2020 and 2021 due to the COVID-19 pandemic, TB surveillance efforts have regained momentum in India in 2022. According to the India TB report for 2023, a total of 24.2 lakh cases were reported last year. According to the Global TB report for 2022, India accounts for 28 percent of all TB cases worldwide.

However, currently, there is no reliable way to identify household contacts who will develop TB and distinguish them from those who will not. Presently, TB preventive treatment is primarily recommended for people living with HIV, household contacts of Pulmonary TB patients, and immuno-suppressed patients.