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Molecular and conventional epidemiologic techniques were used to study the mechanisms and risk factors for tuberculosis transmission in a rural area with high prevalence in south India. Restriction fragment length polymorphism analysis with IS6110 and direct repeat probes was performed with 378 Mycobacterium tuberculosis isolates from patients. Forty-one percent of M. tuberculosis isolates harbored a single copy of IS6110. Of 378 patients, 236 had distinct strains; 142 (38%) shared a strain with other patients, indicating recent infection. Older patients, those detected by a house-to-house community survey, and those hospitalized in a sanatorium were more likely to have had a recent infection. These findings suggest that the majority of the tuberculosis cases in south India were due to reactivation; therefore, efforts to control tuberculosis should be sustained.Each year, nearly 3.5 million new cases of infectious tuberculosis (TB) occur worldwide (11). Molecular epidemiologic studies of Mycobacterium tuberculosis strains by using DNA fingerprinting have provided valuable information about the mechanisms of transmission of TB. Most of these studies, however, have been conducted in countries with a low incidence of tuberculosis and usually in urban settings with pockets of high transmission. In such settings, 35 to 50% of new TB cases are the result of recent person-to-person or exogenous transmission (1,12,25). Few molecular epidemiologic studies have been conducted in countries with a high incidence of TB (10,16).India has the highest number of incident TB cases in the world. The limited numbers of molecular epidemiologic studies conducted in India were laboratory based and comprised small numbers of patients (9, 24). Risk factors for exogenous transmission of TB have not been documented in the country. This study combined molecular and conventional epidemiologic techniques to investigate the mechanisms and risk factors for TB transmission in a rural area of high prevalence in south India.The study site was Tiruvallur District, where the world's largest Mycobacterium bovis BCG trial was conducted (28). The total population of the study area is 580,000. The incidence of smear-positive TB is 76 per 100,000 in the population (29). The study subjects were all TB patients undergoing treatment according to the Revised National Tuberculosis Control Program guidelines (21) at one of the 17 primary health centers in the study area from July 1999 to June 2000. Within a week of commencing treatment, two sputum samples were collected from each patient for mycobacterial culture on Lowenstein-Jensen (LJ) medium. The samples that yielded positive cultures were further confirmed to be typical M. tuberculosis strains (2) and tested for drug susceptibility. The DNA extraction and restriction fragment length polymorphism (RFLP) analysis were performed by standard protocols (9,18,24,30). Two investigators independently analyzed the patterns by visual inspection. For quality control, RFLP was repeated with an additional specimen fo...

Mycobacterium tuberculosis is a very important global pathogen. One quarter of the world's TB cases occur in India. The tuberculosis strains isolated from south Indian patients exhibit certain phenotypic characteristics like low virulence in guinea-pigs, resistance to isoniazid, thiophene-2-carboxylic acid hydrazide (TCH) and para-amino salicylic acid (PAS) enhanced susceptibility to H 2 O 2 . Besides this, a large percentage of the isolates harbor only a single copy of IS 6110 which makes these strains distinct. Hence we have studied the genotypic characteristics of these strains by using advanced techniques like Deletion Micro array, deletion PCR, allelic discrimination RT-PCR using several lineage specific markers and KatG G13887 (non synonymous) polymorphism along with spoligotyping. The analysis of 1,215 tuberculosis patient isolates from South India revealed that 85.2% belonged to the ancestral lineage of Mycobacterium tuberculosis.Comparative whole-genome hybridization identified six new genomic regions within this lineage that were variably deleted.

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