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Mutations in the 81-bp rifampin resistance-determining region (RRDR) of the rpoB gene were analyzed by DNA sequencing of 50 Mycobacterium tuberculosis clinical isolates (44 resistant and 6 sensitive) from various parts of India. Fifty-three mutations of 18 different kinds, 17 point mutations and one deletion, were observed in 43 of 44 resistant isolates. Three novel mutations and three new alleles within the RRDR, along with two novel mutations outside the RRDR, are reported in this study.Tuberculosis (TB), though curable, still remains a major killer disease worldwide. The magnitude of the problem is reflected in estimates of new cases, which are predicted to number around 10 million in the year 2000 and 12 million by 2005 (7). Global prevalence of infection due to Mycobacterium tuberculosis is 32%. Eighty percent of all new TB cases are found in around 22 countries, with more than half the cases occurring in 5 Southeast Asian countries (6). Thirty percent of the world's TB-infected population is in India. The enormity of the problem has increased with the emergence of multidrugresistant (MDR) strains of M. tuberculosis. Dual infection with human immunodeficiency virus and MDR TB is a virtual death sentence in this era.Rifampin (RIF) resistance serves as a surrogate marker for the detection of MDR TB, as 90% of Rif r isolates are also isoniazid resistant (5). RIF interferes with transcription and elongation of RNA by binding to the DNA-dependent RNA polymerase. It was observed that resistance to RIF follows a single-step, high-level resistance pattern in which mutations occur spontaneously at a frequency of 10 Ϫ9 . The genetic basis for RIF resistance in approximately 95% of the cases is due to mutations in an 81-bp RIF resistance-determining region (RRDR) of the rpoB gene, corresponding to codons 507 to 533 (Escherichia coli numbering system), which codes for the beta subunit of the RNA polymerase of M. tuberculosis.Different groups of workers from diverse regions of the world (4, 8-12, 14, 16, 19, 20, 21, 23, 24) have thus far reported around 65 substitutions, 12 deletions, and 4 insertions in the RRDR of the rpoB gene. Only one of these earlier reports is concerned with Indian isolates, and in that study rpoB mutations were observed in three Rif r isolates (8). Determination of the mutation patterns among large numbers of isolates from different parts of India is essential, since this would help not only in the design of a suitable diagnostic method for rapid detection of MDR TB but also in the identification of any hot-spot regions in the country for proper implementation of TB control programs. It would also help in understanding whether mutated alleles arise independently or due to the spread of a particular genotype. Moreover, it is well known that clinical isolates from southern India are very different from isolates from other parts of the world. The former have lower virulence in guinea pigs (2), higher susceptibility to hydrogen peroxide (13, 18) and thiophene-2-carboxylic acid hydrazide (TCH), lowe...

BackgroundShortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.MethodsNewly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.ResultsOf 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.Conclusions4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.Trial RegistrationClinical Trials Registry of India CTRI/2012/10/003060

The findings suggest that TB disease remains a major public health problem in the Saharia 'primitive' tribal community of Madhya Pradesh, Central India.

BackgroundThe present study provides an estimate of the prevalence of bacteriologially positive pulmonary tuberculosis in Jabalpur, a district in central India.Methodology/Principal FindingsA community based cross-sectional survey was undertaken in Jabalpur District of the central Indian state of Madhya Pradesh. A stratified cluster sampling design was adopted to select the sample. All eligible individuals were questioned for pulmonary symptoms suggestive of TB disease. Two sputum samples were collected from all eligible individuals and were examined by Ziehl-Neelsen smear microscopy and solid media culture methods. Of the 99,918 individuals eligible for screening, 95,071 (95.1%) individuals were screened. Of these, 7,916 (8.3%) were found to have symptoms and sputum was collected from 7,533 (95.2%) individuals. Overall prevalence of bacteriologically positive PTB was found to be 255.3 per 100,000 population (95% C.I: 195.3–315.4). Prevalence was significantly higher (p<0.001) amongst males (355.8; 95% C.I: 304.4–413.4) compared with females (109.0; 95% C.I: 81.2–143.3). Prevalence was also significantly higher in rural areas (348.9; 95% C.I: 292.6–412.8) as compared to the urban (153.9; 95% C.I: 123.2–190.1).Conclusions/SignificanceThe TB situation in Jabalpur district, central India, is observed to be comparable to the TB situation at the national level (255.3 versus 249). There is however, a need to maintain and further strengthen TB control measures on a sustained and long term basis in the area to have a significant impact on the disease prevalence in the community.