Molecular insights into MDR-TB transmission: a prospective household contact cohort study in Delhi, India

Multidrug-resistant tuberculosis (MDR-TB) remains a major public health challenge, particularly in high-burden countries such as India. Household contacts of MDR-TB patients are at increased risk of acquiring infection. This study investigated the microbiological and molecular epidemiology of MDR-TB transmission among previously treated pulmonary TB patients and their household contacts in Delhi, India. This prospective household contact cohort study enrolled 134 culture-confirmed rifampicin-resistant/ MDR-TB index cases and 305 household contacts between July 2016 and February 2018. Phenotypic drug susceptibility (DST) for rifampicin, isoniazid (INH), ofloxacin (OFX), and kanamycin (KAN) was performed. Spoligotyping was used to assess strain relatedness. Among 134 index cases, all were rifampicin-resistant and 90.3% were additionally resistant to isoniazid. Pre-XDR-TB was identified in 41% of cases according to the 2016–2018 WHO definition. Nineteen of 305 household contacts (6.2%) were culture-positive. DST concordance was observed in 18/19 index-contact pairs (94.7%; exact 95% CI: 74.0–99.9%), and spoligotype concordance was also observed in 18/19 pairs (94.7%; exact 95% CI: 74.0–99.9%), with Cohen’s κ = 0.89. Fourteen spoligotype patterns representing six major lineages were identified, with CAS1_DELHI and Beijing predominating. Polyclonal infection was detected in 39/134 (29.1%) index cases. The high concordance of phenotypic DST and spoligotype patterns between index cases and household contacts is compatible with possible household transmission of drug-resistant M. tuberculosis . However, because spoligotyping has limited discriminatory power, definitive transmission links cannot be established. These findings support systematic household contact investigation and highlight the potential value of higher-resolution molecular surveillance approaches.