Estimating Catastrophic Costs due to Pulmonary Tuberculosis in Bangladesh.

To eliminate TB from the country by the year 2030, the Bangladesh National Tuberculosis (TB) Program is providing free treatment to the TB patients since 1993. However, the patients are still to make Out-of-their Pocket (OOP) payment, particularly before their enrollment Directly Observed Treatment Short-course (DOTS). This places a significant economic burden on poor-households. We, therefore, aimed to estimate the Catastrophic Health Expenditure (CHE) due to TB as well as understand associated difficulties faced by the families when a productive family member age (15-55) suffers from TB. The majority of the OOP expenditures occur before enrolling in. We conducted a cross-sectional study using multistage sampling in the areas of Bangladesh where Building Resources Across Communities (BRAC) provided TB treatment during June 2016. In total, 900 new TB patients, aged 15-55 years, were randomly selected from a list collected from BRAC program. CHE was defined as the OOP payments that exceeded 10% of total consumption expenditure of the family and 40% of total non-food expenditure/capacity-to-pay. Regular and Bayesian simulation techniques with 10,000 replications of re-sampling with replacement were used to examine robustness of the study findings. We also used linear regression and logit model to identify the drivers of OOP payments and CHE, respectively. The average total cost-of-illness per patient was 124 US$, of which 68% was indirect cost. The average CHE was 4.3% of the total consumption and 3.1% of non-food expenditure among the surveyed households. The poorest quintile of the households experienced higher CHE than their richest counterpart, 5% vs. 1%. Multiple regression model showed that the risk of CHE increased among male patients with smear-negative TB and delayed enrolling in the DOTS. Findings suggested that specific groups are more vulnerable to CHE who needs to be brought under innovative safety-net schemes.

Prevention of social exclusion and role of antenatal care by BRAC community health workers in improving safe motherhood and neonatal care in urban slums of Bangladesh.

The transformation of the BRAC MANOSHI programme from humanitarian to a social enterprise model, has made it increasingly urgent to enumerate the minimum number of door-to-door antenatal care (ANC) visits by community health workers (CHWs), for the purpose of effectively improving facility delivery. Thus prevent social exclusion of poor slum communities in Bangladesh with regard to safe motherhood and essential newborn care (ENC). This cross-sectional study was conducted, during March-July, 2015 in slums of Chittagong, Dhaka and Sylhet city corporations of Bangladesh. A census was conducted among 25,700 households covering 10 branch offices of MANOSHI to identify women with a delivery outcome in the preceding three years of the survey. A total of 1100 respondents were interviewed randomly through a structured questionnaire. These women were stratified into three categories-1, 2 & 3, consisting of 497, 205 and 398 women respectively. Women in category-1 did not receive any ANC checkup from the BRAC CHWs, while women in category-2 and category-3 received one to three and ≥four ANC checkups from BRAC CHWs respectively. Data was analysed using STATA Version 13 (Chicago Inc.). Findings revealed that women, who received ≥four ANC checkups from BRAC CHWs, are 25% more likely to avail facility delivery [adjusted Prevalence Ratio (aPR) 1.25; 95% confidence interval (CI) (1.01-1.54)] compared to the women who did not receive any ANC from BRAC CHWs. Women in category-2 [aPR3.64; 95% CI (1.76-7.54)] and in category-3 [aPR5.92; 95% CI (3.04-11.53)] respectively had four and six folds higher tendency to receive postnatal care (PNC) within 48 hours after delivery. Furthermore, facility delivery improved PNC assisted by medically trained providers (MTPs) within 48 hours after delivery and ENC in both categories 2 & 3. The evidence shows that at least four ANC visits of BRAC CHWs can increase institutional delivery, and which can further facilitate PNC and ENC visits. At present, the BRAC MANOSHI programme needs to implement feasible strategies to include pregnant women in the slums in receiving at least four ANC checkups by BRAC CHWs for ensuring safe motherhood and newborn care.

Assessing the impact of arsenic metabolism efficiency on DNA methylation using Mendelian randomization.

BACKGROUND: Arsenic exposure affects >100 million people globally and increases risk for chronic diseases. One possible toxicity mechanism is epigenetic modification. Previous epigenome-wide association studies (EWAS) have identified associations between arsenic exposure and CpG-specific DNA methylation. To provide additional evidence that observed associations represent causal relationships, we examine the association between genetic determinants of arsenic metabolism efficiency (percent dimethylarsinic acid, DMA%, in urine) and DNA methylation among individuals from the Health Effects of Arsenic Longitudinal Study (n = 379) and Bangladesh Vitamin E and Selenium Trial (n = 393). METHODS: We used multivariate linear models to assess the association of methylation at 221 arsenic-associated CpGs with DMA% and measures of genetically predicted DMA% derived from three SNPs (rs9527, rs11191527, and rs61735836). We also conducted two-sample Mendelian randomization analyses to estimate the association between arsenic metabolism efficiency and CpG methylation. RESULTS: Among the associations between DMA% and methylation at each of 221 CpGs, 64% were directionally consistent with associations observed between arsenic exposure and the 221 CpGs from a prior EWAS. Similarly, among the associations between genetically predicted DMA% and each CpG, 62% were directionally consistent with the prior EWAS results. Two-sample Mendelian randomization analyses produced similar conclusions. CONCLUSION: Our findings support the hypothesis that arsenic exposure effects DNA methylation at specific CpGs in whole blood. Our novel approach for assessing the impact of arsenic exposure on DNA methylation requires larger samples in order to draw more robust conclusions for specific CpG sites.

Prevalence of multimorbidity among Bangladeshi adult population: a nationwide cross-sectional study.

OBJECTIVE: This study aimed to report prevalence and evaluate the association between multimorbidity and associated risk factors in the adult population of Bangladesh. DESIGN: A cross-sectional study was conducted using a multistage clustered random sampling strategy. SETTING: The study was conducted among the general population of 58 districts in Bangladesh. PARTICIPANTS: A total of 12 338 male and female individuals aged ≥35 were included for analysis in this study. Identified through a household listing conducted prior to the study, from 15 297 individuals meeting the inclusion criteria, 12 338 participants were included based on availability during data collection, consent and health condition. OUTCOME MEASURES: Multimorbidity in terms of hypertension, diabetes, cancer, cardiovascular diseases, stroke and chronic obstructive pulmonary disease. RESULTS: Approximately 8.4% (95% CI 7.0 to 9.7) of individuals suffer from multimorbidity, of which hypertension accounted for (30.1%) followed by diabetes (10.6%). The mean age of the population was 58.6 (SD ±9.2) years. The prevalence of multimorbidity was lower among men (7.7%) compared with women (8.9%). The likelihood of having multimorbidity among obese individuals were more than double than people with normal body mass index (BMI). Physical activity protected individuals from developing multimorbidity: however, the physical activity adjusted OR was 0.5 (95% CI 0.2 to 1.2). After adjusting for all covariates, higher age, higher educational status, economic status, and higher BMI were found to be significantly associated with the odds of developing multimorbidity, with an overall adjusted OR of 0.02 (95% CI 0.01 to 0.02). CONCLUSION: This study reported a high prevalence of multimorbidity in Bangladesh, although it explored the burden and identified risk factors considering only six chronic diseases. Further detailed exploration through longitudinal studies considering a wider range of diseases is needed to document the actual burden, develop effective preventive measures and clinical guidelines to improve the quality of life of the population.

What Constitutes Health Care Seeking Pathway of TB Patients: A Qualitative Study in Rural Bangladesh.

Given the targeted 4-5% annual reduction of tuberculosis (TB) cure cases to reach the "End TB Strategy" by 2020 milestone globally set by WHO, exploration of TB health seeking behavior is warranted for insightful understanding. This qualitative study aims to provide an account of the social, cultural, and socioeconomic breadth of TB cases in Bangladesh. We carried out a total of 32 In-depth Interviews (IDIs) and 16 Key Informant Interviews (KIIs) in both rural and urban areas of Bangladesh. We covered both BRAC [a multinational Non-governmental Organization (NGO)] and non-BRAC (other NGOs) TB program coverage areas to get an insight. We used purposive sampling strategy and initially followed "snowball sampling technique" to identify TB patients. Neuman's three-phase coding system was adopted to analyze the qualitative data. Underestimation of TB knowledge and lack of awareness among the TB patients along with the opinions from their family members played key roles on their TB health seeking behavior. Quick decision on the treatment issue was observed once the diagnosis was confirmed; however, difficulties were in accepting the diseases. Nevertheless, individual beliefs, intrinsic ideologies, financial abilities, and cultural and social beliefs on TB were closely inter-connected with the "social perception" of TB that eventually influenced the care seeking pathways of TB patients in various ways. Individual and community level public health interventions could increase early diagnosis; therefore, reduce recurrent TB.

Prevalence and Risk Factors of Cardiovascular Diseases among Bangladeshi Adults: Findings from a Cross-sectional Study.

Ever rising prevalence of Cardiovascular Diseases (CVD) is a major challenge for the health sector in Bangladesh. This study aimed to explore the prevalence of CVD and sociodemographic and lifestyle factors associated with it in Bangladesh. The data were collected through a cross-sectional survey following a two-stage cluster random sampling procedure. The present analysis was performed among 12,338 respondents aged ≥35 years, selected from rural areas and urban slums. Information was gathered using a structured questionnaire, whereas measurements were taken using standardized procedures. Logistic regression with exchangeable correlation structure among clusters was executed to explore the association. About 30% of participants had hypertension, 5% diabetes, 20% obesity; 77% were either smokers or consumed smokeless tobacco, and 28% were physically inactive. The prevalence of CVD was 4.5% (stroke: 1.8% and heart diseases: 3.2%). After adjusting for potential confounders, hypertension, diabetes, body mass index, extra salt intake, daily sleep, tiredness, age, gender, occupation, administrative division, and wealth quintile were found to be significantly associated with CVD. The study highlighted that the prevalence of CVD is high in Bangladesh, and its associated risk factors such as hypertension and diabetes are on the rise, especially in the older population, women, and high-income groups. Therefore, immediate public health intervention is warranted to address the issue.

The effect of age on DNA methylation in whole blood among Bangladeshi men and women.

BACKGROUND: It is well-known that methylation changes occur as humans age, however, understanding how age-related changes in DNA methylation vary by sex is lacking. In this study, we characterize the effect of age on DNA methylation in a sex-specific manner and determine if these effects vary by genomic context. We used the Illumina HumanMethylation 450 K array and DNA derived from whole blood for 400 adult participants (189 males and 211 females) from Bangladesh to identify age-associated CpG sites and regions and characterize the location of these age-associated sites with respect to CpG islands (vs. shore, shelf, or open sea) and gene regions (vs. intergenic). We conducted a genome-wide search for age-associated CpG sites (among 423,604 sites) using a reference-free approach to adjust for cell type composition (the R package RefFreeEWAS) and performed an independent replication analysis of age-associated CpGs. RESULTS: The number of age-associated CpGs (p < 5 x 10- 8) were 986 among men and 3479 among women of which 2027(63.8%) and 572 (64.1%) replicated (using Bonferroni adjusted p < 1.2 × 10- 5). For both sexes, age-associated CpG sites were more likely to be hyper-methylated with increasing age (compared to hypo-methylated) and were enriched in CpG islands and promoter regions compared with other locations and all CpGs on the array. Although we observed strong correlation between chronological age and previously-developed epigenetic age models (r ≈ 0.8), among our top (based on lowest p-value) age-associated CpG sites only 12 for males and 44 for females are included in these prediction models, and the median chronological age compared to predicted age was 44 vs. 51.7 in males and 45 vs. 52.1 in females. CONCLUSIONS: Our results describe genome-wide features of age-related changes in DNA methylation. The observed associations between age and methylation were generally consistent for both sexes, although the associations tended to be stronger among women. Our population may have unique age-related methylation changes that are not captured in the established methylation-based age prediction model we used, which was developed to be non-tissue-specific.

Correction: A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

[This corrects the article DOI: 10.1371/journal.pgen.1007984.].

Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults.

BACKGROUND: Arsenic exposure affects [Formula: see text] people worldwide, including [Formula: see text] in Bangladesh. Arsenic exposure increases the risk of cancer and other chronic diseases, and one potential mechanism of arsenic toxicity is epigenetic dysregulation. OBJECTIVE: We assessed associations between arsenic exposure and genome-wide DNA methylation measured at baseline among 396 Bangladeshi adults participating in the Health Effects of Arsenic Longitudinal Study (HEALS) who were exposed by drinking naturally contaminated well water. METHODS: Methylation in whole blood DNA was measured at [Formula: see text] using the Illumina InfiniumMethylationEPIC (EPIC) array. To assess associations between arsenic exposure and CpG methylation, we used linear regression models adjusted for covariates and surrogate variables (SVs) (capturing unknown technical and biologic factors). We attempted replication and conducted a meta-analysis using an independent dataset of [Formula: see text] from 400 Bangladeshi individuals with arsenical skin lesions. RESULTS: We identified 34 CpGs associated with [Formula: see text] creatinine-adjusted urinary arsenic [[Formula: see text]]. Sixteen of these CpGs annotated to the [Formula: see text] array, and 10 associations were replicated ([Formula: see text]). The top two CpGs annotated upstream of the ABR gene (cg01912040, cg10003262 ). All urinary arsenic-associated CpGs were also associated with arsenic concentration measured in drinking water ([Formula: see text]). Meta-analysis ([Formula: see text] samples) identified 221 urinary arsenic-associated CpGs ([Formula: see text]). The arsenic-associated CpGs from the meta-analysis were enriched in non-CpG islands and shores ([Formula: see text]) and depleted in promoter regions ([Formula: see text]). Among the arsenic-associated CpGs ([Formula: see text]), we observed significant enrichment of genes annotating to the reactive oxygen species pathway, inflammatory response, and tumor necrosis factor [Formula: see text] ([Formula: see text]) signaling via nuclear factor kappa-B ([Formula: see text]) hallmarks ([Formula: see text]). CONCLUSIONS: The novel and replicable associations between arsenic exposure and DNA methylation at specific CpGs observed in this work suggest that epigenetic alterations should be further investigated as potential mediators in arsenic toxicity and as biomarkers of exposure and effect in exposed populations. https://doi.org/10.1289/EHP3849.

A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

Inorganic arsenic (iAs) is a carcinogen, and exposure to iAs via food and water is a global public health problem. iAs-contaminated drinking water alone affects >100 million people worldwide, including ~50 million in Bangladesh. Once absorbed into the blood stream, most iAs is converted to mono-methylated (MMA) and then di-methylated (DMA) forms, facilitating excretion in urine. Arsenic metabolism efficiency varies among individuals, in part due to genetic variation near AS3MT (arsenite methyltransferase; 10q24.32). To identify additional arsenic metabolism loci, we measured protein-coding variants across the human exome for 1,660 Bangladeshi individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS). Among the 19,992 coding variants analyzed exome-wide, the minor allele (A) of rs61735836 (p.Val101Met) in exon 3 of FTCD (formiminotransferase cyclodeaminase) was associated with increased urinary iAs% (P = 8x10-13), increased MMA% (P = 2x10-16) and decreased DMA% (P = 6x10-23). Among 2,401 individuals with arsenic-induced skin lesions (an indicator of arsenic toxicity and cancer risk) and 2,472 controls, carrying the low-efficiency A allele (frequency = 7%) was associated with increased skin lesion risk (odds ratio = 1.35; P = 1x10-5). rs61735836 is in weak linkage disequilibrium with all nearby variants. The high-efficiency/major allele (G/Valine) is human-specific and eliminates a start codon at the first 5´-proximal Kozak sequence in FTCD, suggesting selection against an alternative translation start site. FTCD is critical for catabolism of histidine, a process that generates one-carbon units that can enter the one-carbon/folate cycle, which provides methyl groups for arsenic metabolism. In our study population, FTCD and AS3MT SNPs together explain ~10% of the variation in DMA% and support a causal effect of arsenic metabolism efficiency on arsenic toxicity (i.e., skin lesions). In summary, this work identifies a coding variant in FTCD associated with arsenic metabolism efficiency, providing new evidence supporting the established link between one-carbon/folate metabolism and arsenic toxicity.

Individual-, maternal- and household-level factors associated with stunting among children aged 0-23 months in Bangladesh.

OBJECTIVE: Childhood stunting remains a major public health concern in Bangladesh. To accelerate the reduction rate of stunting, special focus is required during the first 23 months of a child's life when the bulk of growth takes place. Therefore the present study explored individual-, maternal- and household-level factors associated with stunting among children under 2 years of age in Bangladesh. DESIGN: Data were collected through a nationwide cross-sectional survey conducted between October 2015 and January 2016. A two-stage cluster random sampling procedure was applied to select 11 428 households. In the first stage, 210 enumerations areas (EA) were selected with probability proportional to EA size (180 EA from rural areas, thirty EA from urban slums). In the second stage, an average of fifty-four households were selected from each EA through systematic random sampling. SETTING: Rural areas and urban slums of Bangladesh.ParticipantsA total of 6539 children aged 0-23 months. RESULTS: Overall, 29·9 % of the children were stunted. After adjusting for all potential confounders in the modified Poisson regression model, child's gender, birth weight (individual level), maternal education, age at first pregnancy, nutrition (maternal level), administrative division, place of residence, socio-economic status, food security status, access to sanitary latrine and toilet hygiene condition (household level) were significantly associated with stunting. CONCLUSIONS: The study identified a number of potentially addressable multilevel risk factors for stunting among young children in Bangladesh that should be addressed through comprehensive multicomponent interventions.

The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans.

Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., "direct" inheritance). Prior studies of LTL h2 have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5069 Bangladeshi adults with substantial relatedness. For each of the 6318 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL ((ΔLTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness (ϕ). The association between Tshared and (ΔLTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs (ϕ > 0.05), the association between Tshared and (ΔLTL)2 (P = 0.01) was stronger than the association between ϕ and (ΔLTL)2 (P = 0.43). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere "reprogramming" during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direct transmission of telomeres.

Arsenic exposure and young adult's mortality risk: A 13-year follow-up study in Matlab, Bangladesh.

BACKGROUND: Widespread arsenic contamination in underground water is a well-documented public health concern that threatens millions of lives worldwide. We investigated the risk of young-adult mortality due to high chronic exposure to arsenic through years of drinking arsenic contaminated water. METHODS: A prospective cohort study of 58,406 individuals was enrolled who were 4-18 years at baseline. Since Matlab HDSS (Health and Demographic Surveillance System) has an active surveillance system, all individuals were included in the follow up. Each individual's arsenic exposure was calculated at (1) baseline As level as current exposure (2) time-weighted lifetime (average or lifetime average) and (3) cumulative arsenic exposure. Age, sex, educational attainment and SES were adjusted during the analysis. In this 13 years closed-cohort study (2003-2015), all young-adult deaths were captured through verbal autopsy (VA) using International Classification of Diseases (ICD-10) to define the causes. RESULTS: Although, girls had higher values of cumulative arsenic exposure via tube well water than boys (median: 1858.5 µg/year/L vs. 1798.8 µg/year/L) but higher mortality due to cancers and due to cerebro-vascular disease, cardio-vascular disease, and respiratory disease (7.0 vs. 5.7 per 100,000 person-years and 6.4 vs. 4.2 per 100,000 person-years respectively). Higher risk of deaths among young adults (Adjusted HR: 2.7, 1.3-5.8) due to all cancers among those who were exposed to As > 138.7 compared to As ≤ 1.1 µg/L. For cerebro-vascular disease, cardio-vascular disease, and respiratory disease deaths, average arsenic in well water (>223.1 µg/L vs. ≤90.9 µg/L) and cumulative arsenic in well water (>2711.0 µg/year/L vs. ≤1013.3 µg/year/L) had 4.8 (1.8-12.8) and 5.1 (1.7-15.1) times higher risks of mortality than to those lowest exposed. CONCLUSION: Higher concentration of, and chronic exposure to arsenic in drinking water, increases the mortality risk among the young adults, regardless of gender.

Exploring the gap between coverage, access, and utilization of long-lasting insecticide-treated nets (LLINs) among the households of malaria endemic districts in Bangladesh.

BACKGROUND: Malaria is still a major public health concern in Bangladesh in spite of mass distribution of long-lasting insecticide-treated nets (LLINs) as a key preventive strategy. There might be a considerable gap between coverage and actual use of nets by the population in endemic areas. This study intended to assess the gap between coverage, access to and use of LLINs among the households in malaria-endemic settings in Bangladesh. METHODS: This cross-sectional study collected data from 2640 households of 13 endemic districts of Bangladesh through three-stage cluster random sampling. The gap between coverage, access and use of LLINs were calculated using the procedure established by the Roll Back Malaria Monitoring and Evaluation Reference Group. To support the quantitative findings, qualitative data were also collected through in-depth interview, focus group discussion and key informant interview and analysed accordingly. RESULTS: Of 2640 total households, 77.4% (n = 2044) possessed at least two LLINs, 56.8% (n = 1499) had insufficient access, and 18.8% (n = 495) had excess LLINs. Members of 77.9% (n = 2056) households had used LLINs the previous night and 6.0% (n = 68) did not use LLINs despite having sufficient access. LLIN use was lower in non-hill track areas, in Bengali community, in richer households and households with more than four members. Moreover, qualitative findings revealed that the major reasons behind not using LLINs were insufficient access, sleeping outside the home, migration, perceived low efficacy of LLINs, or fear of physical side effects. CONCLUSION: Closing the access gap by providing enough nets through solid investment and well-designed behavioural change interventions are crucial for achieving and sustaining universal coverage.

The association between daily 500 mg calcium supplementation and lower pregnancy-induced hypertension risk in Bangladesh.

BACKGROUND: Evidence suggests that daily supplementation of 1500 to 2000 mg of calcium during pregnancy reduces pregnancy-induced hypertension (PIH). However, the evidence on the efficacy of low-dose calcium supplementation on PIH is limited. This paper assesses the longitudinal correlation between low-dose calcium intake (500 mg daily) and change in blood pressure during pregnancy among a homogeneous population in terms of hypertension and pre-eclampsia. METHODS: The study followed a retrospective cohort study design, and was carried out among 11,387 pregnant women from 10 rural upazilas (sub-districts) of Bangladesh where maternal nutrition initiative (MNI), implemented by Building Resources Across Communities (BRAC), was ongoing. The modified Poisson regression model was used to estimate the association (risk ratio) between consumption of calcium tablets and PIH. RESULTS: The present research found that women who consumed 500 mg/d calcium tablets for more than 6 months during their pregnancy had a 45% lower risk of developing hypertension compared to those who consumed less calcium (RR = 0.55, 95% CI = 0.33-0.93). CONCLUSIONS: Daily supplementation of 500 mg oral calcium during pregnancy for at least 180 tablets is associated with a considerably reduced risk of PIH, but this study is unable to confirm whether this association is causal. The causal relationship needs to be confirmed through a large scale randomized controlled trial.

Access to water and sanitation among people with disabilities: results from cross-sectional surveys in Bangladesh, Cameroon, India and Malawi.

OBJECTIVES: To assess access to adequate water, sanitation and hygiene (WASH) among people with disabilities at the household and individual level. DESIGN: Cross-sectional surveys. SETTING: Data were included from five district-level or regional-level surveys: two in Bangladesh (Bangladesh-1, Bangladesh-2), and one each in Cameroon, Malawi and India. PARTICIPANTS: 99 252 participants were sampled across the datasets (range: 3567-75 767), including 2494 with disabilities (93-1374). OUTCOME: Prevalence of access to WASH at household and individual level. DATA ANALYSIS: Age/sex disaggregated disability prevalence estimates were calculated accounting for survey design. The Unicef/WHO Joint Monitoring Programme definitions were used to classify facilities as improved/unimproved. Multivariable logistic regression was undertaken to compare between households with/without a person with a disability, and to identify predictors of access among people with disabilities. RESULTS: There were no differences in access to improved sanitation or water sources between households with/without members with disabilities across the datasets. In Bangladesh-2, households including a person with a disability were more likely to share facilities with other households (OR 1.3, 95% CI 1.1 to 1.5). Households with people with disabilities were more likely to spend >30 min (round-trip) collecting drinking water than households without in both Cameroon (OR 1.8, 95% CI 1.0 to 3.4) and India (OR 2.3, 95% CI 1.2 to 4.7). Within households, people with disabilities reported difficulties collecting water themselves (23%-80% unable to) and accessing the same sanitation facilities as other household members, particularly without coming into contact with faeces (up to 47% in Bangladesh-2). These difficulties were most marked for people with more severe impairments. CONCLUSIONS: People with disabilities may not have poorer access to WASH at the household level, but may have poorer quality of access within their households. Further programmatic work is needed to ensure WASH facilities are inclusive of people with disabilities.

Co-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms.

Inherited genetic variation affects local gene expression and DNA methylation in humans. Most expression quantitative trait loci (cis-eQTLs) occur at the same genomic location as a methylation QTL (cis-meQTL), suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, here we use co-localization methods to identify eQTL-meQTL pairs likely to share a causal variant. We use partial correlation and mediation analyses to identify >400 of these pairs showing evidence of a causal relationship between expression and methylation (i.e., shared mechanism) with many additional pairs we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite associations with expression and methylation, although many SNPs affect multiple CpGs in opposite directions. This work demonstrates the pervasiveness of co-regulated expression and methylation in the human genome. Applying this approach to other types of molecular QTLs can enhance our understanding of regulatory mechanisms.

Screening for gene-environment (G×E) interaction using omics data from exposed individuals: an application to gene-arsenic interaction.

Identifying gene-environment interactions is a central challenge in the quest to understand susceptibility to complex, multi-factorial diseases. Developing an understanding of how inter-individual variability in inherited genetic variation alters the effects of environmental exposures will enhance our knowledge of disease mechanisms and improve our ability to predict disease and target interventions to high-risk sub-populations. Limited progress has been made identifying gene-environment interactions in the epidemiological setting using existing statistical approaches for genome-wide searches for interaction. In this paper, we describe a novel two-step approach using omics data to conduct genome-wide searches for gene-environment interactions. Using existing genome-wide SNP data from a large Bangladeshi cohort study specifically designed to assess the effect of arsenic exposure on health, we evaluated gene-arsenic interactions by first conducting genome-wide searches for SNPs that modify the effect of arsenic on molecular phenotypes (gene expression and DNA methylation features). Using this set of SNPs showing evidence of interaction with arsenic in relation to molecular phenotypes, we then tested SNP-arsenic interactions in relation to skin lesions, a hallmark characteristic of arsenic toxicity. With the emergence of additional omics data in the epidemiologic setting, our approach may have the potential to boost power for genome-wide interaction research, enabling the identification of interactions that will enhance our understanding of disease etiology and our ability to develop interventions targeted at susceptible sub-populations.

Relationship of sleep pattern and snoring with chronic disease: findings from a nationwide population-based survey.

OBJECTIVES: To investigate the association of total sleep time and presence or absence of snoring with chronic disease among the Bangladeshi adult population. DESIGN: Cross-sectional survey. SETTING: Urban and rural Bangladesh. PARTICIPANTS: A total of 12,338 men and women aged ≥35 years. MEASUREMENTS: Total sleep time was considered as the total hours of sleep in 24 hours. Furthermore, sleep time was categorized into <7, 7-9, and >9 hours according to National Sleep Foundation (2015) guidelines. Self-reported snoring history was captured and corroborated with their respective sleep partner/spouse in more than 80% cases. Registered physician-diagnosed current and/or previous cases of hypertension, diabetes, coronary heart disease, cancer, stroke, chronic obstructive pulmonary disease, and any other chronic conditions were counted. RESULTS: Overall prevalence of at least 1 chronic disease in our study population was around 18%: men (15.4%) and women (20.0%). Hypertension has the highest prevalence (overall: 12.7%, men: 12.2%, women: 15%) followed by diabetes (4.9%), coronary heart diseases (3.2%), stroke (1.8%), chronic obstructive pulmonary disease (0.9%), and cancer (any type: 0.1%). Sleep pattern and snoring are significantly associated with all individual chronic disease except cancer. Sociodemographic, behavioral, and lifestyle variables were adjusted, and inadequate total sleep time (<7 hours) and snoring (yes/no) showed significant association with chronic disease status (risk ratio = 1.11, 95% confidence interval 1.00-1.22 and risk ratio = 1.20, 95% confidence interval 1.11-1.29, respectively). CONCLUSION: Inadequate sleep and snoring are independently associated with chronic disease in Bangladeshi adult population and perhaps elsewhere.