A study of Mycobacterium tuberculosis genotypic diversity & drug resistance mutations in Varanasi, north India.

BACKGROUND & OBJECTIVES: One-fifth of the world's new tuberculosis (TB) cases and two-thirds of cases in the South East Asian region occur in India. Molecular typing of Mycobacterium tuberculosis isolates has greatly facilitated to understand the transmission of TB. This study was aimed to investigate the molecular epidemiology of M. tuberculosis genotypes in Varanasi, north India, and their association with clinical presentation among patients with pulmonary TB.

METHODS

M. tuberculosis isolates from 104 TB patients attending a tertiary referral hospital of north India were screened for susceptibility to isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (STR) by proportion method and multiplex-allele-specific-polymerase chain reaction (MAS-PCR). These were genotyped by spoligotyping. The spoligotype patterns were compared with those in the international SITVIT2 spoligotyping database.

RESULTS

Eighty three of 104 isolates were distributed in 38 SITs, of which SIT3366 was newly created within the present study. The mass of ongoing transmission with MDR-TB isolates in Varanasi, northern India, was linked to Beijing genotype followed by the CAS1_Delhi lineage. HIV-seropositive patients had a significantly higher proportion of clustered isolates than HIV-seronegative patients and compared with the wild type(wt) isolates, the isolates with katG315Thr mutation were considerably more likely to be clustered.

INTERPRETATION & CONCLUSIONS: This study gives an insight into the M. tuberculosis genetic biodiversity in Varanasi, north India, the predominant spoligotypes and their impact on disease transmission. In this region of north India, TB is caused by a wide diversity of spoligotypes with predominance of four genotype lineages: Beijing, CAS, EAI and T. The Beijing genotype was the most frequent single spoligotype and strongly associated with multi drug resistant (MDR)-TB isolates. These findings may have important implications for control and prevention of TB in north India.