Anti-Ascaris IgE as a Risk Factor for Asthma Symptoms among 5-Year-Old Children in Rural Bangladesh with Even Decreased Ascaris Infection Prevalence.

BACKGROUND: Epidemiological studies have indicated that anti-Ascaris IgE enhances asthma and allergies under specific conditions although the association between them is still controversial. The association of anti-Ascaris IgE with increased asthma symptoms among children from a general population with a mild to moderate Ascaris infection prevalence was investigated. METHODS: A total of 126 children aged 5 years with wheezing during the previous year and 110 children who did not have wheezing were selected randomly from the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Serum levels of total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anti-cockroach IgEs were tested, and their risks for wheezing were analyzed. The wheezing children were then classified by hierarchical cluster analysis to investigate the contribution of anti-Ascaris IgE to wheezing. RESULTS: The anti-Ascaris IgE levels in wheezing and never-wheezing children were 1.07 and 0.65 UA/mL, and it contributed to 11% of wheezing in children. Anti-Ascaris IgE was significantly associated with wheezing (odds ratio [OR] per loge increment: 1.37 [95% CI: 1.01-1.87], p = 0.046). The ORs, which were adjusted for sex, parental asthma, pneumonia history, helminth infections, Haemophilus influenzae type B combination vaccination, antibiotic use during infancy, and total and specific IgE levels, increased even when only children with more specific symptoms of asthma were included in the analysis. Namely, the ORs for wheezing with sleep disturbance, four or more attacks, and wheezing with speech difficulties during the previous 1 year were OR = 1.44/loge increment [95% CI: 1.01-2.07], OR = 1.90/loge increment [95% CI: 1.11-3.25], and OR = 1.78/loge increment [95% CI: 1.01-3.14], respectively. CONCLUSIONS: The anti-Ascaris IgE levels in wheezing and never-wheezing children in the current study significantly decreased concurrently with Ascaris infection prevalence compared with their corresponding values in 2001. The contribution of anti-Ascaris IgE to wheezing also dropped from 26% in 2001 to 11% in the current study. Despite significant decreases in the levels and the seroprevalence and its contribution to wheezing, anti-Ascaris IgE remained significantly associated with increased risk of wheezing. Anti-Ascaris IgE significantly increased the risk of wheezing in a general population with a mild to moderate Ascaris infection prevalence, suggesting robustness as a risk factor and a possible dose-response relationship.

Impact of Haemophilus influenzae type b combination vaccination on asthma symptoms and pneumonia in 5-year-old children in rural Bangladesh: a longitudinal study and comparison with a previous cross-sectional study.

BACKGROUND: Although the prevalence of bronchial asthma has been increasing worldwide since the 1970's, the prevalence among 5-year-old children was significantly lower in 2016 than in 2001 in rural Bangladesh. We aimed to determine whether the Haemophilus influenzae type b (Hib) combination vaccination (without booster) started in 2009 contributed to this decrease. METHODS: A case-control study was conducted among 1658 randomly selected 5-year-old children from Matlab, Bangladesh. Data on wheezing were collected using the International Study of Asthma and Allergies in Childhood questionnaire. The vaccination data were collected from the records of the Matlab Health and Demographic Surveillance System, while data on pneumonia were obtained from the clinical records of Matlab Hospital. Adjusted odds ratios (aORs) were calculated for the risk for wheezing. The reduction rate was calculated to determine the impact of the vaccination on pneumonia history between the present study and our previous study conducted in 2001 by using the following formula: (percentage of pneumonia cases in 2001 - percentage of pneumonia cases in 2016)/(percentage of pneumonia cases in 2001) times 100 (%). RESULTS: Hib combination vaccination was a protecting factor against wheezing (aOR: 0.50; p = 0.010), while pneumonia at 1, 2, 3-4 years of age were risk factors for wheezing (aOR: 2.86, 3.19, 2.86; p = 0.046, 0.030, 0.030, respectively). The history of pneumonia was significantly lower in the 2016 study participants than those in 2001 both in the overall cohort and the wheezing group (paired t-test: p = 0.012, p < 0.001, respectively). Whereas the history of pneumonia decreased when the children grew older in the 2001 overall cohort, it peaked at the age of 2 years in 2016 wheezing group. The reduction rate decreased when children grew older in both the overall cohort and the wheezing group, however, it decreased faster in the wheezing group. CONCLUSIONS: Hib combination vaccination was a protective factor against wheezing in 0-year-old children. However, the effects of vaccination might have attenuated at the ages of 1-4 years, because no booster dose was administered. The addition of a booster dose might further decrease the prevalence of asthma and wheezing.

Weather factors, PCV intervention and childhood pneumonia in rural Bangladesh.

Available evidence is limited on the association between weather factors and childhood pneumonia, especially in developing countries. This study examined the effects of weather variability on childhood pneumonia after the introduction of pneumococcal conjugate vaccines (PCV) intervention in rural Bangladesh. Data on pneumonia cases and weather variables (temperature and relative humidity) between the 1st January 2012 and the 31st December 2016 were collected from Matlab Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, and Bangladesh Meteorological Department, respectively. Time series cross-correlation functions were applied to identify the time lags of the effect of each weather factor on pneumonia. Generalized linear regression model with Poisson link was used to quantify the association between weather factors and childhood pneumonia after adjustment of PCV intervention. The annual incidence rate of pneumonia reduced from 5691/100,000 to 2000/100,000 after PCV intervention. Generalized linear regression model suggested that temperature had a negative association with childhood pneumonia (relative risk, 0.985; 95% confidence interval (CI), 0.974-0.997), and PCV intervention was a protective factor with the relative risk estimate of 0.489 (95% CI, 0.435-0.551). However, no substantial association was found with relative humidity. PCV intervention appeared protective against childhood pneumonia, and temperature might be associated with this disease in children. Our findings may help inform public health policy, including the potential of development of early warning systems based on weather factors and PCV for the control and prevention of pneumonia in lower middle-income country like Bangladesh.

Food as medicine: Selenium enriched lentils offer relief against chronic arsenic poisoning in Bangladesh.

Chronic arsenic (As) exposure is a major environmental threat to human health affecting >100 million people worldwide. Low blood selenium (Se) increases the risk of As-induced health problems. Our aim was to reduce As toxicity through a naturally Se-rich lentil diet. In a randomized, double-blind, placebo-control trial in Bangladesh, 405 participants chronically exposed to As were enrolled. The intervention arm (Se-group) consumed Se-rich lentils (55 µg Se/day); the control arm received lentils of similar nutrient profile except with low Se (1.5 µg Se/day). Anthropometric measurements, blood, urine and stool samples, were taken at baseline, 3 and 6 months; hair at baseline and 6 months after intervention. Morbidity data were collected fortnightly. Measurements included total As in all biological samples, As metabolites in urine, and total Se in blood and urine. Intervention with Se-rich lentils resulted in higher urinary As excretion (p = 0.001); increased body mass index (p ≤ 0.01), and lower incidence of asthma (p = 0.05) and allergy (p = 0.02) compared to the control group. The Se-group demonstrated increased excretion of urinary As metabolite, dimethylarsinic acid (DMA) at 6 months compared to control group (p = 0.008). Consuming Se-rich lentils can increase As excretion and improve the health indicators in the presence of continued As exposure.

Sociodemographic, climatic variability and lower respiratory tract infections: a systematic literature review.

Pneumonia is the leading cause of mortality and morbidity in developing countries, particularly for children and elderly. The main objective of this review paper is to review the epidemiological evidence about the effects of sociodemographic and climatic variability on pneumonia and other lower respiratory tract infections. A detailed literature search was conducted in PubMed and Scopus following PRISMA guidelines. The articles, which considered the effect of only climatic or both climatic and sociodemographic factors on pneumonia and other lower respiratory tract infections, included in this review. A total thirty-four relevant articles were reviewed. Of 34 studies, only 14 articles (41%) examined the joint effects of sociodemographic and climate factors on pneumonia and other lower respiratory infections while most of them (59%) assessed climate factors separately. Among these fourteen, only three articles (8.8%) considered detailed sociodemographic factors. All of the reviewed articles suggested different degrees of positive or negative relationship of temperature with pneumonia or other lower respiratory tract infections. Fifteen (44%) articles suggested an association with relative humidity and 13 (38%) with rainfall. Only 3 articles (8.8%) found a relationship with wind speed. Three articles (8.8%) considered other risk factors such as particulate matter 2.5 (PM2.5) and particulate matter 10 (PM10). One study among the reviewed articles used spatial analysis methods but this study did not examine the joint effects. Among the reviewed articles, 18 (53%) articles used different time series models, one article (3%) used spatiotemporal time series model, 8 (23%) studies used other models and rest 7 (21%) studies used simple descriptive analysis. A total of 18 studies (53%) were conducted in Asia, most of them in China. There were 6 studies (17%) in Europe and 8 studies (23%) in America (South, North and Central). In Africa and Oceania, only one study was found for each region. The joint effect of climate and sociodemographic factors on pneumonia and other lower respiratory tract infections remain to be determined and further research is highly recommended for future prevention of this important and common disease.

Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.

BACKGROUND: Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. OBJECTIVES: We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. METHODS: Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. RESULTS: We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. CONCLUSIONS: Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age.

Arsenic and lung disease mortality in Bangladeshi adults.

BACKGROUND: Chronic arsenic exposure through drinking water is a public health problem affecting millions of people worldwide, including at least 30 million in Bangladesh. We prospectively investigated the associations of arsenic exposure and arsenical skin lesion status with lung disease mortality in Bangladeshi adults. METHODS: Data were collected from a population-based sample of 26,043 adults, with an average of 8.5 years of follow-up (220,157 total person-years). There were 156 nonmalignant lung disease deaths and 90 lung cancer deaths ascertained through October 2013. We used Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals (CIs) for lung disease mortality. RESULTS: Creatinine-adjusted urinary total arsenic was associated with nonmalignant lung disease mortality, with persons in the highest tertile of exposure having a 75% increased risk for mortality (95% CI = 1.15-2.66) compared with those in the lowest tertile of exposure. Persons with arsenical skin lesions were at increased risk of lung cancer mortality (hazard ratio = 4.53 [95% CI = 2.82-7.29]) compared with those without skin lesions. CONCLUSIONS: This prospective investigation of lung disease mortality, using individual-level arsenic measures and skin lesion status, confirms a deleterious effect of ingested arsenic on mortality from lung disease. Further investigations should evaluate effects on the incidence of specific lung diseases, more fully characterize dose-response, and evaluate screening and biomedical interventions to prevent premature death among arsenic-exposed populations, particularly among those who may be most susceptible to arsenic toxicity.

Relationship between arsenic skin lesions and the age of natural menopause.

BACKGROUND: Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women's reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. METHODS: We compared menopausal age in two groups of women--with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies--participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. RESULTS: Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups' age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. CONCLUSIONS: The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure.

A prospective cohort study of stroke mortality and arsenic in drinking water in Bangladeshi adults.

BACKGROUND: Arsenic in drinking water causes increased coronary artery disease (CAD) and death from CAD, but its association with stroke is not known. METHODS: Prospective cohort study with arsenic exposure measured in well water at baseline. 61074 men and women aged 18 years or older on January 2003 were enrolled in 2003. The cohort was actively followed for an average of 7 years (421,754 person-years) through December 2010. Based on arsenic concentration the population was categorized in three groups and stroke mortality HR was compared to the referent. The risk of stroke mortality Hazard Ratio (HR) and 95% Confidence Interval was calculated in relation to arsenic exposure was estimated by Cox proportional hazard models with adjustment for potential confounders. RESULTS: A total of 1033 people died from stroke during the follow-up period, accounting for 23% of the total deaths. Multivariable adjusted HRs (95% confidence interval) for stroke for well water arsenic concentrations <10, 10-49, and ≥50 µg/L were 1.0 (reference), 1.20 (0.92 to 1.57), and 1.35 (1.04 to 1.75) respectively (Ptrend=0.00058). For men, multivariable adjusted HRs (95%) for well water arsenic concentrations <10, 10-49, and ≥50 µg/L were 1.0 (reference), 1.12 (0.78 to 1.60), and 1.07 (0.75 to 1.51) respectively (Ptrend=0.45) and for women 1.0 (reference),1.31 (0.87 to 1.98), and 1.72 (1.15 to 2.57) respectively (Ptrend=0.00004). CONCLUSION: The result suggests that arsenic exposure was associated with increased stroke mortality risk in this population, and was more significant in women compared to men.

Arsenic and cadmium in food-chain in Bangladesh--an exploratory study.

Arsenic contamination of tubewell water is a major public-health problem in Bangladesh. In the recent years, the use of shallow and deep tubewell water for irrigation and the use of excess amount of cheap fertilizers and pesticides containing cadmium pose a serious threat of contamination of arsenic and cadmium in food. In an exploratory study, arsenic and cadmium were measured in foods from Matlab, a rural area in Bangladesh, that is extensively affected by arsenic and the economy is agriculture-based. Raw and cooked food samples were collected from village homes (households, n=13) and analyzed to quantify concentrations of arsenic and cadmium using atomic absorption spectrophotometry. Washing rice with water before cooking reduced the concentration of arsenic in raw rice by 13-15%. Rice, when cooked with excess water discarded, showed a significant decrease in arsenic concentration compared to that cooked without discarding the water (p<0.001). In contrast, concentration of cadmium did not decrease in cooked rice after discarding water. Cooked rice with discarded water had significantly lower concentration of arsenic compared to raw rice (p=0.002). Raw rice had higher concentration of arsenic compared to raw vegetables (p<0.001); however, no such difference was found for cadmium. Compared to raw vegetables (e.g. arum), concentration of arsenic increased significantly (p=0.024) when cooked with arsenic-contaminated water. Thus, the practice of discarding excess water while cooking rice reduces the concentration of arsenic but not of cadmium in cooked rice. However, water generally not discarded when cooking vegetables to avoid loss of micronutrients consequently retains arsenic. The results suggest that arsenic and cadmium have entered the food-chain of Bangladesh, and the cooking practices influence the concentration of arsenic but not of cadmium in cooked food.

Concurrent decreases in the prevalence of wheezing and Ascaris infection among 5-year-old children in rural Bangladesh and their regulatory T cell immunity after the implementation of a national deworming program.

INTRODUCTION: Epidemiological research on the prevalence of asthma and helminthic infections in various countries has led to the hypothesis that helminthic infections protect against asthma by suppressing the host's immune response. This study was conducted to elucidate whether decreased Ascaris infection following a national deworming program was associated with increased recurrent wheezing among rural Bangladeshi children and to test their anti-inflammatory immunity. METHODS: This nested case-control study was conducted from December 2015 to October 2016 in the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Of the 1800 5-year old children randomly selected for the study, informed consent was obtained from the guardians of 1658 children. Data were collected using a semistructured questionnaire adopted from the International Study of Asthma and Allergies in Childhood and blood samples for the analysis of regulatory T (Treg) cell immune responses and the balance between Th1 and Th2 immunity in Ascaris infections. RESULTS: A total of 145 children were found to have wheezing, yielding a prevalence rate of 8.7%, which was significantly lower than the rate found in 2001 (16.2%, P < .001); Ascaris infection also decreased from 2001 to 2016. The 127 wheezing children who agreed to participate further were compared to 114 randomly selected never-wheezing children. Wheezing had a significant positive association with antibiotic use, history of pneumonia, parents' history of asthma, and Ascaris infection; children with Ascaris infection were twice as likely to have wheezing (adjusted odds ratio = 2.31, P = .053). Flow cytometry found no significant differences in the rates of Th1, Th2, and CD4 + CD25 + CD127low cells by the wheezing group. CONCLUSIONS: Ascaris infection had a positive rather than a negative association with wheezing and the rates of wheezing and Ascaris infections both decreased from 2001 to 2016. These findings undermines the hypothesis that such infections provide protection against asthma.

Magnitude and determinants of inadequate third-trimester weight gain in rural Bangladesh.

OBJECTIVES: The objective of this study was to estimate the magnitude and determinants of inadequate weight gain in the third-trimester among rural women in Matlab, Bangladesh. METHODS: The study analyzed data on weight gain in the third trimester in 1,883 pregnant women in Matlab, Bangladesh. All these women were admitted to Matlab hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) for childbirth during 2012-2014, and they had singleton live births at term. Data were retrieved from the electronic databases of Matlab Health and Demographic Surveillance System and Matlab hospital. A multivariable logistic regression for inadequate weight gain in the third trimester (≤4 kg) was built with sociodemographic, environmental and maternal factors as predictors. RESULTS: One thousand and twenty-six (54%) pregnant women had inadequate weight gain in the third trimester. In the multivariable model, short stature turned out to be the most robust risk factor for inadequate weight gain in the third trimester (OR = 2.5; 95% CI 1.8, 3.5 for short compared to tall women). Pre-third-trimester BMI was inversely associated with insufficient weight gain (OR = 0.96; 95% CI 0.93, 0.99 for 1 unit increase in BMI). Other risk factors for inadequate weight gain in the third trimester were advanced age (OR = 1.9; 95% CI 1.2, 3.1 for ≥35 years compared to ≤19 years), parity (OR = 1.5; 95% CI 1.2, 1.9 for multipara compared to nulliparous women), low socioeconomic status (OR = 1.7; 95% CI 1.2, 2.3 for women in the lowest compared to women in the highest wealth quintile), low level of education (OR = 1.6; 95% CI 1.2, 2.1 for ≤5 years compared to ≥10 years of education), belonging to the Hindu religious community (OR = 1.8; 95% CI 1.3, 2.5), consuming arsenic-contaminated water (OR = 1.4; 95% CI 1.1, 1.9), and conceiving during monsoon or dry season compared to summer (OR = 1.4; 95% CI 1.1, 1.8). CONCLUSIONS: Among rural Bangladeshi women in Matlab, third-trimester weight gain was in general poor. Maternal characteristics such as short stature, low BMI, advanced age, parity, low level of education and socioeconomic status, being Hindu, intake of arsenic contaminated water, and conceiving during monsoon or dry season were the risk factors for inadequate weight gain in the third trimester. Special attention should be given during prenatal care to women with the risk factors identified in this study.

Screening of arsenic in tubewell water with field test kits: evaluation of the method from public health perspective.

There is an urgent need for Bangladesh to identify the arsenic (As) contaminated tubewells (TWs) in order to assess the health risks and initiate appropriate mitigation measures. This will involve testing water in millions of TWs and raising community awareness about the health problems related to chronic As exposure from drinking water. Field test kits offer the only practical tool within the time frame and financial resources available for screening and assessment of the As contaminated TWs as well as their monitoring than that of the laboratory measurement. A comparison of field test kit and laboratory measurements by AAS as "gold standard" for As in water of 12,532 TWs in Matlab Upazila in Bangladesh, indicates that the field kit correctly determined the status of 91% of the As levels compared to the Bangladesh Drinking Water Standard (BDWS) of 50 microg/L, and 87% of the WHO guideline value of 10 microg/L. Nevertheless, due to analytical and human errors during the determination of As by the field test kits, some misclassification of wells is inevitable. Cross-checking of the field test kit results, both by Field Supervisor and by the laboratory analyses reveal considerable discrepancies in the correct screening mainly at As concentration ranges of 10-24.9 microg/L and 50-99.9 microg/L, critical from a public health point of view. The uncertainties of misclassification of these two groups of TWs have severe public health implications due to As exposure from drinking water sources. This can be reduced through proper training of the field personnel, cross verification of the field test kit results with laboratory analyses and further development of the field test kits to determine As at low concentrations.

Prenatal arsenic exposure and drowning among children in Bangladesh.

There is increasing concern regarding adverse effects of prenatal arsenic exposure on the neurodevelopment of children. We analyzed mortality data for children, who were born to 11,414 pregnant women between 2002 and 2004, with an average age of 5 years of follow-up. Individual drinking-water arsenic exposure during pregnancy was calculated using tubewell water arsenic concentration between last menstrual period and date of birth. There were 84 drowning deaths registered, with cause of death ascertained using verbal autopsy (International Classification of Diseases, 10th revision, codes X65-X70). The prenatal water arsenic exposure distribution was tertiled, and the risk of drowning mortality was estimated by Cox proportional hazard models, adjusted for potential confounders. We observed a significant association between prenatal arsenic exposure and drowning in children aged 1-5 years in the highest exposure tertile (HR=1.74, 95% CI: 1.03-2.94). This study showed that in utero arsenic exposure might be associated with excess mortality among children aged 1-5 years due to drowning.

Increased childhood mortality and arsenic in drinking water in Matlab, Bangladesh: a population-based cohort study.

BACKGROUND: Arsenic in drinking water was associated with increased risk of all-cause, cancer, and cardiovascular death in adults. However, the extent to which exposure is related to all-cause and deaths from cancer and cardiovascular condition in young age is unknown. Therefore, we prospectively assessed whether long-term and recent arsenic exposures are associated with all-cause and cancer and cardiovascular mortalities in Bangladeshi childhood population. METHODS AND FINDINGS: We assembled a cohort of 58406 children aged 5-18 years from the Health and Demographic Surveillance System of icddrb in Bangladesh and followed during 2003-2010. There were 185 non-accidental deaths registered in-about 0.4 million person-years of observation. We calculated hazard ratios for cause-specific death in relation to exposure at baseline (µg/L), time-weighted lifetime average (µg/L) and cumulative concentration (µg-years/L). After adjusting covariates, hazard ratios (HRs) for all-cause childhood deaths comparing lifetime average exposure 10-50.0, 50.1-150.0, 150.1-300.0 and ≥300.1µg/L were 1.37 (95% confidence interval [CI], 0.74-2.57), 1.44 (95% CI, 0.88-2.38), 1.22 (95% CI, 0.75-1.98) and 1.88 (95% CI, 1.14-3.10) respectively. Significant increased risk was also observed for baseline (P for trend = 0.023) and cumulative exposure categories (P for trend = 0.036). Girls had higher mortality risk compared to boys (HR for girls 1.79, 1.21, 1.64, 2.31; HR for boys 0.52, 0.53, 1.14, 0.99) in relation to baseline exposure. For all cancers and cardiovascular deaths combined, multivariable adjusted HRs amounted to 1.53 (95% CI 0.51-4.57); 1.29 (95% CI 0.43-3.87); 2.18 (95%CI 1.15-4.16) for 10.0-50.0, 50.1-150.0, and ≥150.1, comparing lowest exposure as reference (P for trend = 0.009). Adolescents had higher mortality risk compared to children (HRs = 1.53, 95% CI 1.03-2.28 vs. HRs = 1.30, 95% CI 0.78-2.17). CONCLUSIONS: Arsenic exposure was associated with substantial increased risk of deaths at young age from all-cause, and cancers and cardiovascular conditions. Girls and adolescents (12-18 years) had higher risk compared to boys and child.

Vaccine specific immune response to an inactivated oral cholera vaccine and EPI vaccines in a high and low arsenic area in Bangladeshi children.

BACKGROUND: Immune responses to the inactivated oral whole cell cholera toxin B (CTB) subunit cholera vaccine, Dukoral(®), as well as three childhood vaccines in the national immunization system were compared in children living in high and low arsenic contaminated areas in Bangladesh. In addition, serum complement factors C3 and C4 levels were evaluated among children in the two areas. VACCINATIONS: Toddlers (2-5 years) were orally immunized with two doses of Dukoral 14 days apart. Study participants had also received diphtheria, tetanus and measles vaccines according to the Expanded Program on Immunization (EPI) in Bangladesh. RESULTS: The mean level of arsenic in the urine specimens in the children of the high arsenic area (HAA, Shahrasti, Chandpur) was 291.8µg/L while the level was 6.60µg/L in the low arsenic area (LAA, Mirpur, Dhaka). Cholera specific vibriocidal antibody responses were significantly increased in the HAA (87%, P<0.001) and the LAA (75%, P<0.001) children after vaccination with Dukoral, but no differences were found between the two groups. Levels of CTB specific IgA and IgG antibodies were comparable between the two groups, whereas LPS specific IgA and IgG were higher in the LAA group, although response rates were comparable. Diphtheria and tetanus vaccine specific IgG responses were significantly higher in the HAA compared to the LAA group (P<0.001, P=0.048 respectively), whereas there were no differences in the measles specific IgG responses between the groups. Complement C3 and C4 levels in sera were higher in participants from the HAA than the LAA groups (P<0.001, P=0.049 respectively). CONCLUSIONS: The study demonstrates that the oral cholera vaccine as well as the EPI vaccines studied are immunogenic in children in high and low arsenic areas in Bangladesh. The results are encouraging for the potential use of cholera vaccines as well as the EPI vaccines in arsenic endemic areas.

Bangladesh arsenic mitigation programs: lessons from the past.

Ensuring access to safe drinking water by 2015 is a global commitment by the Millennium Development Goals (MDGs). In Bangladesh, significant achievements in providing safe water were made earlier by nationwide tubewell-installation programme. This achievement was overshadowed in 1993 by the presence of arsenic in underground water. A total of 6 million tubewells have been tested for arsenic since then, the results of which warranted immediate mitigation. Mitigation measures included tubewell testing and replacing; usage of deeper wells; surface water preservation and treatment; use of sanitary dug wells, river sand and pond sand filters; rainwater collection and storage; household-scale and large-scale arsenic filtrations; and rural pipeline water supply installation. Shallow tubewell installation was discouraged. Efforts have been made to increase people's awareness. This paper describes the lessons learned about mitigation efforts by the authors from experience of arsenic-related work. In spite of national mitigation plans and efforts, a few challenges still persist: inadequate coordination between stakeholders, differences in inter-sectoral attitudes, inadequate research to identify region-specific, suitable safe water options, poor quality of works by various implementing agencies, and inadequate dissemination of the knowledge and experiences to the people by those organizations. Issues such as long-time adaptation using ground water, poor surface water quality including bad smell and turbidity, and refusal to using neighbor's water have delayed mitigation measures so far. Region-specific mitigation water supply policy led by the health sector could be adopted with multisectoral involvement and responsibility. Large-scale piped water supply could be arranged through Public Private Partnerships (PPP) in new national approach.

Arsenic exposure and adverse health effects: a review of recent findings from arsenic and health studies in Matlab, Bangladesh.

The recent discovery of large-scale arsenic (As) contamination of groundwater has raised much concern in Bangladesh. Reliable estimates of the magnitude of As exposure and related health problems have not been comprehensively investigated in Bangladesh. A large population-based study on As and health consequences in Matlab (AsMat) was done in Matlab field site where International Centre for Diarrhoeal Disease Research, Bangladesh has maintained a health and demographic surveillance system registering prospectively all vital events. Taking advantage of the health and demographic surveillance system and collecting data on detailed individual level As exposure using water and urine samples, AsMat investigated the morbidity and mortality associated with As exposure. Reviews of findings to date suggest the adverse effects of As exposure on the risk of skin lesions, high blood pressure, diabetes mellitus, chronic disease, and all-cause infant and adult disease mortality. Future studies of clinical endpoints will enhance our knowledge gaps and will give directions for disease prevention and mitigations.

Detecting arsenic-related skin lesions: experiences from a large community-based survey in Bangladesh.

A cross-sectional survey was conducted in Matlab, Bangladesh, to determine the prevalence of skin lesions (a three-step procedure) associated with arsenic exposure and discuss validity and feasibility in relation to recommended screening algorithms. Cases with skin lesions were identified by screening above 4 years of age (n = 166,934). Trained field teams conducted a careful house-to-house screening and identified 1682 individuals with skin lesions, who were referred to physicians for confirmation. Physicians diagnosed 579 cases as probable and documented all these with digital photographs. Two experts inspected all photographs for consensus agreement that was reached for 504 cases. Using the experts' opinions as reference, the positive predictive value of the physicians' diagnosis was 87% (male = 82% vs. female = 94%; p < 0.01). The physicians had difficulties in separating arsenic-induced keratosis from differential diagnoses, while probability for correct diagnosis was high for arsenic-related pigmentation changes. Including information on current arsenic concentration in drinking water (which was masked at time of skin examination) or urine in the diagnostic algorithm should have increased the number of false negative cases. In the present transition of drinking water sources these markers of current exposure levels provide no information on past exposure. A 2-3 step procedure with house-to-house screening and clinic-based confirmation of arsenic-induced skin lesions is a feasible approach. Information on arsenic concentration in current water sources or in urine should not have improved the precision in the diagnosis. These results may have policy implications for community screening of arsenic-related skin lesions in Bangladesh and elsewhere.