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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...

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Neutrophils are innate immune cells implicated in the process of killing Mycobacterium tuberculosis early during infection. Once the mycobacteria enter the human system, neutrophils sense and engulf them. By secreting bactericidal enzymes and α-defensins like human neutrophil peptides loaded in their granule armory, neutrophils kill the pathogen. Peripheral blood neutrophils secrete a wide range of cytokines like IL-8, IL-1-β and IFN-γ in response to mycobacterial infection. Thus they signal and activate distant immune cells thereby informing them of prevailing infection. The activated monocytes, dendritic cells and T cells further continue the immune response. As a final call, neutrophils release neutrophil extracellular traps in circulation which can trap mycobacteria in patients with active pulmonary tuberculosis. Extensive neutrophilic response is associated with inflammation, pulmonary destruction, and pathology. For example, inappropriate phagocytosis of mycobacteria-infected neutrophils can damage host cells due to necrosis of neutrophils, leading to chronic inflammation and tissue damage. This dual nature of neutrophils makes them double-edged swords during tuberculosis, and hence data available on neutrophil functions against mycobacterium are controversial and non-uniform. This article reviews the role of neutrophils in tuberculosis infection and highlights research gaps that need to be addressed. We focus on our understanding of new research ideologies targeting neutrophils (a) in the early stages of infection for boosting specific immune functions or (b) in the later stages of infection to prevent inflammatory conditions mediated by activated neutrophils. This would plausibly lead to the development of better tuberculosis vaccines and therapeutics in the future.

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