A comparative study of the socio-economic risk factors for pulmonary tuberculosis in the Saharia tribe of Madhya Pradesh, India.

Background: To determine the socio-economic risk factors for pulmonary tuberculosis (PTB) in the Saharia tribal community in Madhya Pradesh, Central India. Methods: PTB cases detected during the year 2013-14 through a community active TB prevalence survey in the Shivpuri district, Madhya Pradesh were included in the study. For each case, three controls were selected randomly among the non-cases from the same village and the data on socio-economic risk factors were collected. Using logistic regression analysis, the risk factors for PTB disease were identified. Results: A total of 220 cases and 660 controls participated in the study. Of the 13 risk factors studied, on multivariate analysis the risk of PTB was found to be significantly associated with malnutrition (adjusted odds ratio [AOR] 2.02 [95% confidence interval {CI} 1.46 to 2.79]), living in a kaccha (built of naturally occurring materials) house (AOR 2.72 [95% CI 1.44 to 5.11]) and tobacco smoking (mostly beedis; AOR 1.59 [95% CI 1.12 to 2.18]). Conclusions: The findings highlight that malnutrition, poor living conditions in a Kaccha house (built of naturally occurring materials) and tobacco smoking are the major risk factors for PTB among Saharias, which need to be studied among other tribal populations in the country. There is a need to strengthen health and nutrition programmes in this community.

Assessment of Mycobacterium tuberculosis pantothenate kinase vulnerability through target knockdown and mechanistically diverse inhibitors.

Pantothenate kinase (PanK) catalyzes the phosphorylation of pantothenate, the first committed and rate-limiting step toward coenzyme A (CoA) biosynthesis. In our earlier reports, we had established that the type I isoform encoded by the coaA gene is an essential pantothenate kinase in Mycobacterium tuberculosis, and this vital information was then exploited to screen large libraries for identification of mechanistically different classes of PanK inhibitors. The present report summarizes the synthesis and expansion efforts to understand the structure-activity relationships leading to the optimization of enzyme inhibition along with antimycobacterial activity. Additionally, we report the progression of two distinct classes of inhibitors, the triazoles, which are ATP competitors, and the biaryl acetic acids, with a mixed mode of inhibition. Cocrystallization studies provided evidence of these inhibitors binding to the enzyme. This was further substantiated with the biaryl acids having MIC against the wild-type M. tuberculosis strain and the subsequent establishment of a target link with an upshift in MIC in a strain overexpressing PanK. On the other hand, the ATP competitors had cellular activity only in a M. tuberculosis knockdown strain with reduced PanK expression levels. Additionally, in vitro and in vivo survival kinetic studies performed with a M. tuberculosis PanK (MtPanK) knockdown strain indicated that the target levels have to be significantly reduced to bring in growth inhibition. The dual approaches employed here thus established the poor vulnerability of PanK in M. tuberculosis.

Prevalence of pulmonary tuberculosis--a baseline survey in central India.

BACKGROUND: The present study provides an estimate of the prevalence of bacteriologially positive pulmonary tuberculosis in Jabalpur, a district in central India. METHODOLOGY/PRINCIPAL FINDINGS: A 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/SIGNIFICANCE: The 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.