Exposure to Second-Hand Smoke and the Risk of Tuberculosis in Children and Adults: A Systematic Review and Meta-Analysis of 18 Observational Studies

<div><p>Background</p><p>According to WHO Global Health Estimates, tuberculosis (TB) is among the top ten causes of global mortality and ranks second after cardiovascular disease in most high-burden regions. In this systematic review and meta-analysis, we investigated the role of second-hand smoke (SHS) exposure as a risk factor for TB among children and adults.</p><p>Methods and Findings</p><p>We performed a systematic literature search of PubMed, Embase, Scopus, Web of Science, and Google Scholar up to August 31, 2014. Our a priori inclusion criteria encompassed only original studies where latent TB infection (LTBI) and active TB disease were diagnosed microbiologically, clinically, histologically, or radiologically. Effect estimates were pooled using fixed- and random-effects models. We identified 18 eligible studies, with 30,757 children and 44,432 adult non-smokers, containing SHS exposure and TB outcome data for inclusion in the meta-analysis. Twelve studies assessed children and eight studies assessed adult non-smokers; two studies assessed both populations. Summary relative risk (RR) of LTBI associated with SHS exposure in children was similar to the overall effect size, with high heterogeneity (pooled RR 1.64, 95% CI 1.00–2.83). Children showed a more than 3-fold increased risk of SHS-associated active TB (pooled RR 3.41, 95% CI 1.81–6.45), which was higher than the risk in adults exposed to SHS (summary RR 1.32, 95% CI 1.04–1.68). Positive and significant exposure–response relationships were observed among children under 5 y (RR 5.88, 95% CI 2.09–16.54), children exposed to SHS through any parent (RR 4.20, 95% CI 1.92–9.20), and children living under the most crowded household conditions (RR 5.53, 95% CI 2.36–12.98). Associations for LTBI and active TB disease remained significant after adjustment for age, biomass fuel (BMF) use, and presence of a TB patient in the household, although the meta-analysis was limited to a subset of studies that adjusted for these variables. There was a loss of association with increased risk of LTBI (but not active TB) after adjustment for socioeconomic status (SES) and study quality. The major limitation of this analysis is the high heterogeneity in outcomes among studies of pediatric cases of LTBI and TB disease.</p><p>Conclusions</p><p>We found that SHS exposure is associated with an increase in the relative risk of LTBI and active TB after controlling for age, BMF use, and contact with a TB patient, and there was no significant association of SHS exposure with LTBI after adjustment for SES and study quality. Given the high heterogeneity among the primary studies, our analysis may not show sufficient evidence to confirm an association. In addition, considering that the TB burden is highest in countries with increasing SHS exposure, it is important to confirm these results with higher quality studies. Research in this area may have important implications for TB and tobacco control programs, especially for children in settings with high SHS exposure and TB burden.</p></div

Study characteristics.

<p>AFB, acid-fast bacilli; BCG, Bacillus Calmette–Guérin; BMF, biomass fuel; BMI, biomass index; CXR, chest, X-ray; IAP, indoor air pollution; IU, international units; NHIS, National Health Interview Survey; OR, odds ratio; QFT-GIT, QuantiFERON TB Gold In-Tube test; RNTCP, Revised National Tuberculosis Control Programme; SES, socioeconomic status; TST, tuberculin skin test.</p><p>Study characteristics.</p

Funnel plot with pseudo 95% confidence limits.

<p>OR, odds ratio.</p

Risk of latent TB infection and active TB disease for second-hand smoke exposure compared to non-exposure in children and adults.

<p>(A) LTBI; (B) active TB disease. Singh et al. [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001835#pmed.1001835.ref024" target="_blank">24</a>] reported SHS risks for children with contacts with sputum-negative (95/281) and sputum-positive TB patients (45/100). The effect estimate (diamond) for US-born children in the study by Lindsay et al. [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001835#pmed.1001835.ref022" target="_blank">22</a>] is not displayed due to its smaller size and weight. Lin et al. [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001835#pmed.1001835.ref031" target="_blank">31</a>] did not report age-stratified TB cases. Weights are from random-effects analysis. *Patient with TB living in house. **No patient with TB living in house.</p

Flowchart of study identification and inclusion.

<p>RCT, randomized controlled trial.</p

Microbial Diversity of Source and Point-of-Use Water in Rural Haiti – A Pyrosequencing-Based Metagenomic Survey

<div><p>Haiti endures the poorest water and sanitation infrastructure in the Western Hemisphere, where waterborne diseases cause significant morbidity and mortality. Most of these diseases are reported to be caused by waterborne pathogens. In this study, we examined the overall bacterial diversity of selected source and point-of-use water from rural areas in Central Plateau, Haiti using pyrosequencing of 16s rRNA genes. Taxonomic composition of water samples revealed an abundance of Firmicutes phyla, followed by Proteobacteria and Bacteroidetes. A total of 38 bacterial families and 60 genera were identified. The presence of several <i>Klebsiella</i> spp. (tentatively, <i>K</i>. <i>pneumoniae</i>, <i>K</i>. <i>variicola</i> and other <i>Klebsiella</i> spp.) was detected in most water samples. Several other human pathogens such as <i>Aeromonas</i>, <i>Bacillus</i>, <i>Clostridium</i>, and <i>Yersinia</i> constituted significantly higher proportion of bacterial communities in the point-of-use water samples compared to source water. Bacterial genera traditionally associated with biofilm formation, such as <i>Chryseobacterium</i>, <i>Fusobacterium</i>, <i>Prevotella</i>, <i>Pseudomonas</i> were found in the point-of-use waters obtained from water filters or domestic water storage containers. Although the pyrosequencing method utilized in this study did not reveal the viability status of these pathogens, the abundance of genetic footprints of the pathogens in water samples indicate the probable risk of bacterial transmission to humans. Therefore, the importance of appropriate handling, purification, and treatment of the source water needed to be clearly communicated to the communities in rural Haiti to ensure the water is safe for their daily use and intake.</p></div

Genera listed are significantly different between the groups.

<p>Genera listed are significantly different between the groups.</p

Relative abundance of bacterial diversity in source and point-of-use water samples at phylum level as determined by bTEFAP^®.

<p>Relative abundance of bacterial diversity in source and point-of-use water samples at phylum level as determined by bTEFAP^®.</p

Dual Hierarchal dendrogram evaluation of the taxonomic classification of source and point-of-use water samples.

<p>Samples are clustered on the X-axis and labeled based upon the water source types. Samples with more similar microbial populations are mathematically clustered closer together. The genera (consortium) are used for clustering. Thus the samples with more similar consortium of bacterial genera cluster closer together with the length of connecting lines (top of heatmap) related to the similarity, shorter lines between two samples indicate closely matched bacterial consortium. The heatmap represents the relative percentages of each bacterial genus. The predominant genera are represented along the right Y-axis. The legend for the heatmap is provided in the upper left corner.</p

Relative abundance of bacterial families residing in source and point-of-use water samples as determined by bTEFAP^®.

<p>Multi-colored stack bar graphs represent the relative abundance of bacterial family in each sample.</p