Background: The prevalence of tuberculosis in adult men in India is 2-4 times higher than in women. Tobacco smoking is prevalent almost exclusively among men, so it is possible that tobacco smoking may be a risk factor for developing pulmonary tuberculosis. A nested case control study was carried out to study the association between tobacco smoking and pulmonary tuberculosis. Methods: A tuberculosis disease survey was carried out in two Panchayat unions in the Tiruvallur district of Tamil Nadu in India. Eighty five men aged 20-50 years with bacteriological tuberculosis (smear and/or culture positive) were selected as cases and 459 age matched men without tuberculosis were selected randomly as controls. Information on smoking status, type of tobacco smoked, quantity of tobacco smoked, and duration of tobacco smoking was collected from cases and controls using a questionnaire. Results: The estimated crude odds ratio (OR) of the association between tobacco smoking and bacillary tuberculosis was 2.48 (95% confidence interval (CI) 1.42 to 4.37), p<0.001.The age adjusted OR (Mantel-Hanszel estimate) was 2.24.(95% CI 1.27 to 3.94), p<0.05. The ORs for mild (1-10 cigarettes/day), moderate (11-20/day), and heavy (>20/day) smokers were 1.75, 3.17, and 3.68, respectively (p<0.0001 test for linear trend). The ORs for smokers with <10 years, 11-20 years, and >20 years of smoking were 1.72, 2.45, and 3.23, respectively (p<0.0001 test for linear trend). Conclusion: There is a positive association between tobacco smoking and pulmonary (bacillary) tuberculosis (OR 2.5). The association also shows a strong dose-response relationship.
Mycobacterium tuberculosis and filarial coinfection is highly prevalent, and the presence of a tissue-invasive helminth may modulate the predominant type 1 T helper (Th1; interferon [IFN]–γ–mediated) response needed to control M. tuberculosis infection. By analyzing the cellular responses to mycobacterial antigens in patients who had latent tuberculosis with or without filarial infection, we were able to demonstrate that filarial infection coincident with M. tuberculosis infection significantly diminishes M. tuberculosis–specific Th1 (interleukin [IL]–12 and IFN-γ) and type 17 T helper (Th17; IL-23 and IL-17) responses related to increased expression of cytotoxic T lymphocyte antigen (CTLA)–4 and programmed death (PD)–1. Blockade of CTLA-4 restored production of both IFN-γ and IL-17, whereas PD-1 blockade restored IFN-γ production only. Thus, coincident filarial infection exerted a profound inhibitory effect on protective mycobacteria-specific Th1 and Th17 responses in latent tuberculosis, suggesting a mechanism by which concomitant filarial (and other systemic helminth) infections predispose to the development of active tuberculosis in humans.
The findings suggest that TB disease remains a major public health problem in the Saharia 'primitive' tribal community of Madhya Pradesh, Central India.
The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination; 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin.
Mycobacterium tuberculosis (Mtb) and filarial coinfection is highly prevalent, and the presence of filarial infections may regulate the Toll-like receptor (TLR)-dependent immune response needed to control Mtb infection. By analyzing the baseline and mycobacterial antigen–stimulated expression of TLR1, 2, 4, and 9 (in individuals with latent tuberculosis [TB] with or without filarial infection), we were able to demonstrate that filarial infection, coincident with Mtb, significantly diminishes both baseline and Mtb antigen-specific TLR2 and TLR9 expression. In addition, pro-inflammatory cytokine responses to TLR2 and 9 ligands are significantly diminished in filaria/TB-coinfected individuals. Definitive treatment of lymphatic filariasis significantly restores the pro-inflammatory cytokine responses in individuals with latent TB. Coincident filarial infection exerted a profound inhibitory effect on protective mycobacteria-specific TLR-mediated immune responses in latent tuberculosis and suggests a novel mechanism by which concomitant filarial infections predispose to the development of active tuberculosis in humans.
BackgroundFilarial (and other helminth) infections are known to modulate mycobacteria-specific pro-inflammatory cytokine responses necessary for maintaining latency in tuberculosis (TB). We sought to address whether helminth co-infection alters progression to active pulmonary TB in a co-endemic area of South India.Methods/Principal FindingsIncidence of active pulmonary TB was assessed in 5096 subjects from five villages among helminth-infected (hel+) and –uninfected (hel−) groups. Baseline stool examinations, circulating filarial antigen, and tuberculin skin testing (PPD) were performed along with chest radiographs, sputum microscopy, and culture. During three follow-up visits each 2.5 years, patients were assessed using PPD tests and questionnaires and—for those with potential symptoms of TB—sputum microscopy and culture. Of the 5096 subjects, 1923 were found to be hel+ and 3173 were hel−. Follow up interval stool examination could not be performed. In each group, 21 developed active TB over the course of the study. After adjusting for sex, age, BCG vaccination status, and PPD positivity, no difference was seen in active TB incidence between hel+ and hel− groups either at baseline (relative risk (RR) 1.60; 95% confidence interval (CI): 0.69, 3.71, P = 0·27), or when followed prospectively (RR 1.24; 95% CI: 0.48, 3.18, P = 0·66).Conclusions/SignificanceOur findings suggest that, despite the immunomodulatory effects of helminth infection, baseline co-morbid infection with these parasites had little effect on the clinical progression from latent to active pulmonary TB.
The findings suggest that the TB situation amongst the tribal population is not that different from the situation among the non-tribal population in the country. However, TB remains a major public health problem amongst the tribal population and there is a need to maintain and further strengthen TB control measures on a sustained and long-term basis.
Tuberculosis (TB) is a major public health problem among the Saharia, a marginalized tribal group in Madhya Pradesh state, central India. However, there is no information on the risk factors associated with the development of TB disease in this community. A cross-sectional TB prevalence survey was conducted among the Saharia residing in Sheopur district of Madhya Pradesh. Information on tobacco smoking and alcohol consumption was collected from all the individuals. Persons aged ≥45 years, males, smokers and alcohol consumers had higher risks of developing TB disease. There is an urgent need to develop and implement culturally appropriate awareness raising activities to target smoking and alcohol consumption to support the efforts to control TB in this community.
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