Yukiko Wagatsuma

Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh.

Chronic exposure to arsenic, a potent carcinogen and toxicant, via drinking water is a worldwide public health problem. Because little is known about early-life effects of arsenic on immunity, we evaluated the impact of in utero exposure on infant immune parameters and morbidity in a pilot study. Pregnant women were enrolled at 6-10 weeks of gestation in Matlab, a rural area of Bangladesh, extensively affected by arsenic contamination of tubewell water. Women (n=140) delivering at local clinics were included in the study. Anthropometry and morbidity data of the pregnant women and their children, as well as infant thymic size by sonography were collected. Maternal urine and breast milk were collected for immune marker and arsenic assessment. Maternal urinary arsenic during pregnancy showed significant negative correlation with interleukin-7 (IL-7) and lactoferrin (Ltf) in breast milk and child thymic index (TI). Urinary arsenic was also positively associated with fever and diarrhea during pregnancy and acute respiratory infections (ARI) in the infants. The effect of arsenic exposure on ARI was only evident in male children. The findings suggest that in utero arsenic exposure impaired child thymic development and enhanced morbidity, probably via immunosuppression. The effect seemed to be partially gender dependent. Arsenic exposure also affected breast milk content of trophic factors and maternal morbidity.

The effect of rainfall on the incidence of cholera in Bangladesh.

Background: The incidence of cholera in Bangladesh shows clear seasonality, suggesting that weather factors could play a role in its epidemiology. We estimated the effects of rainfall on the incidence of cholera in Dhaka, Bangladesh. Methods: We examined time-series patterns of the weekly number of hospital visits due to cholera in relation to weekly rainfall from 1996 to 2002. We used Poisson regression models, adjusted for seasonal variation, between-year variation, public holidays, and temperature. The role of river level on the rainfall-cholera relationship was also examined by incorporating river-level terms into the models. Results: The weekly number of cholera cases increased by 14% (95% confidence interval = 10.1%–18.9%) for each 10-mm increase above the threshold of 45 mm for the average rainfall, over lags 0 to 8 weeks. Conversely, the number of cholera cases increased by 24% (10.7%–38.6%) for a 10-mm decrease below the same threshold of average rainfall, over lags 0 to 16 weeks. River level partly explained the association between high rainfall and the number of cholera cases. Conclusions: The number of cholera cases increased with both high and low rainfall in the weeks preceding hospital visits. These results suggest that factors associated with river level are on the causal pathway between high rainfall and incidence of cholera.

Rotavirus infections and climate variability in Dhaka, Bangladesh: a time-series analysis.

Attempts to explain the clear seasonality of rotavirus infections have been made by relating disease incidence to climate factors; however, few studies have disentangled the effects of weather from other factors that might cause seasonality. We investigated the relationships between hospital visits for rotavirus diarrhoea and temperature, humidity and river level, in Dhaka, Bangladesh, using time-series analysis adjusting for other confounding seasonal factors. There was strong evidence for an increase in rotavirus diarrhoea at high temperatures, by 40.2% for each 1 degrees C increase above a threshold (29 degrees C). Relative humidity had a linear inverse relationship with the number of cases of rotavirus diarrhoea. River level, above a threshold (4.8 m), was associated with an increase in cases of rotavirus diarrhoea, by 5.5% per 10-cm river-level rise. Our findings provide evidence that factors associated with high temperature, low humidity and high river-level increase the incidence of rotavirus diarrhoea in Dhaka.

Early-life nutritional and environmental determinants of thymic size in infants born in rural Bangladesh

Aim:  The aim was to assess the impact of nutritional status and environmental exposures on infant thymic development in the rural Matlab region of Bangladesh.

Environmental exposure to arsenic and cadmium during pregnancy and fetal size: a longitudinal study in rural Bangladesh.

Prenatal exposures to arsenic (As) and cadmium (Cd) have been associated with decreased size at birth. We here studied associations of prenatal As and Cd exposures with multiple fetal size parameters measured by ultrasound in gestational week (GW) 14 and 30 in a population-based mother-child cohort in rural Bangladesh. We measured As (n=1929) and Cd (n=1616) in urine during pregnancy. In the longitudinal evaluation of combined exposure, urinary Cd (UCd) showed an inverted U-shaped association (turning-point 1.5 μg Cd/L) with all fetal size parameters, while UAs showed no significant association. Cross-sectional analyses indicated that associations with UCd were somewhat stronger in early gestation. Stratification indicated stronger associations between UCd and fetal size in girls than in boys, and in poorer than in richer families, while UAs was weakly associated with fetal size in boys. In conclusion, particularly Cd, but also As, appeared to influence fetal development in a sex-dependent manner.

The effect of temperature on mortality in rural Bangladesh—a population-based time-series study

BACKGROUND Studies in urban cities have consistently shown evidence of increased mortality in association with hot and cold weather. However, few studies have examined temperature-mortality relationship in the rural areas of developing countries. In this study we therefore aimed to characterize the daily temperature-mortality relationships in rural Bangladesh. METHODS A generalized linear Poisson regression model was used to regress a time-series of daily mortality for all-cause and selected causes against temperature, controlling for seasonal and interannual variations, day of week and public holidays. A total of 13 270 all-cause deaths excluding external causes for residents under demographic surveillance in Matlab, Bangladesh were available between January 1994 and December 2002. RESULTS There was a marked increase in all-cause deaths and deaths due to cardiovascular, respiratory and perinatal causes at low temperatures over a lag of 0-13 days. Every 1 degrees C decrease in mean temperature was associated with a 3.2% (95% CI 0.9-5.5) increase in all-cause mortality. However, there was no clear heat effect on all-cause mortality for any of the lags examined. CONCLUSIONS This study found that daily mortality increased with low temperatures in the preceding weeks, while there was no association found between high temperatures and daily mortality in rural Bangladesh. Preventive measures during low temperatures should be considered especially for young infants.

Arsenic exposure and cell-mediated immunity in pre-school children in rural Bangladesh.

Prenatal arsenic exposure has been associated with reduced thymic index and increased morbidity in infants, indicating arsenic-related impaired immune function. We aimed at elucidating potential effects of pre- and postnatal arsenic exposure on cell-mediated immune function in pre-school aged children. Children born in a prospective mother-child cohort in rural Bangladesh were followed up at 4.5 years of age (n = 577). Arsenic exposure was assessed by concentrations of arsenic metabolites (U-As) in child urine and maternal urine during pregnancy, using high-performance liquid chromatography online with inductively coupled plasma mass spectrometry. For assessment of delayed type hypersensitivity response, an intradermal injection of purified protein derivative (PPD) was given to Bacillus Calmette-Guerin vaccinated children. The diameter (mm) of induration was measured after 48-72 h. Plasma concentrations of 27 cytokines were analyzed by a multiplex cytokine assay. Childrens concurrent, but not prenatal, arsenic exposure was associated with a weaker response to the injected PPD. The risk ratio (RR) of not responding to PPD (induration <5 mm) was 1.37 (95% confidence interval (CI): 1.07, 1.74) in children in the highest quartile of U-As (range 126-1228 μg/l), compared with the lowest (range 12-34 μg/l). The p for trend across the quartiles was 0.003. The association was stronger in undernourished children. Childrens U-As in tertiles was inversely associated with two out of 27 cytokines only, i.e., IL-2 and TNF-α, both Th1 cytokines (in the highest tertile, regression coefficients (95% CI): -1.57 (-2.56, -0.57) and -4.53 (-8.62, -0.42), respectively), but not with Th2 cytokines. These associations were particularly strong in children with recent infections. In conclusion, elevated childhood arsenic exposure appeared to reduce cell-mediated immunity, possibly linked to reduced concentrations of Th1 cytokines.

Geographical distribution for malignant neoplasm of the pancreas in relation to selected climatic factors in Japan

BackgroundMalignant neoplasm of the pancreas has become one of the leading causes of death from malignant neoplasm in Japan (the 5th in 2003). Although smoking is believed to be a risk factor, other risk factors remain unclear. Mortality from malignant neoplasm of the pancreas tends to be higher in northern Japan and in northern European countries. A recent study reported that standardized mortality ratios (SMRs) for malignant neoplasm of the pancreas were negatively correlated to global solar radiation level. People residing in regions with lower solar radiation and lower temperatures may be at higher risk of development of malignant neoplasm of the pancreas. Therefore, this study aimed to examine the relationship between SMRs for malignant neoplasm of the pancreas and climatic factors, such as the amount of global solar radiation and the daily maximum temperature in Japan.ResultsThe study used multiple linear regression models. Number of deaths and demographic data from 1998 to 2002 were used for the calculation of SMR. We employed mesh climatic data for Japan published in 2006 by the Japan Meteorological Agency. Regression coefficients for the amount of global solar radiation and the daily maximum temperature in males were -4.35 (p = 0.00034) and -2.81 (p < 0.0001) respectively, and those in females were -5.02 (p < 0.0001) and -1.87 (p < 0.0001) respectively. Increased amount of global solar radiation or daily maximum temperature was significantly related to the decreased SMRs for malignant neoplasm of the pancreas in both males and females.ConclusionThis study suggested that low solar radiation and low temperature might relate to the increasing risk of malignant neoplasm of the pancreas. Use of group data has a limitation in the case of evaluating environmental factors affecting health, since the impact of climatic factors on the human body varies according to individual lifestyles and occupations. Use of geographical mesh climatic data, however, proved useful as an index of risk or beneficial factors in a small study area. Further research using individual data is necessary to elucidate the relationship between climatic factors and the development of malignant neoplasm of the pancreas.

Early exposure to toxic metals has a limited effect on blood pressure or kidney function in later childhood, rural Bangladesh

Background Chronic exposure to toxic metals such as arsenic and cadmium has been implicated in the development of kidney and cardiovascular diseases but few studies have directly measured exposure during inutero and early child development. Methods We investigated the impact of exposure to arsenic (mainly in drinking water) and cadmium (mainly in rice) during pregnancy on blood pressure and kidney function at 4.5 years of age in rural Bangladesh. The effect of arsenic exposure in infancy was also assessed. Results Within a cohort of 1887 children recruited into the MINIMat study, exposure to arsenic (maternal urinary arsenic, U-As), but not cadmium, during in utero development was associated with a minimal increase in blood pressure at 4.5 years. Each 1 mg/l increase in pregnancy U-As was associated with 3.69 mmHg (95% CI: 0.74, 6.63; P: 0.01) increase in child systolic and a 2.91 mmHg (95% CI: 0.41, 5.42; P: 0.02) increase in child diastolic blood pressure. Similarly, a 1 mg/l increase in child U-As at 18 months of age was associated with a 8.25 mmHg (95% CI: 1.37, 15.1; P: 0.02) increase in systolic blood pressure at 4.5 years. There was also a marginal inverse association between infancy U-As and glomerular filtration rate at 4.5 years (−33.4 ml/min/1.72 m2; 95% CI: −70.2, 3.34; P: 0.08). No association was observed between early arsenic or cadmium exposure and kidney volume at 4.5 years assessed by ultrasound. Conclusions These modest effect sizes provide some evidence that arsenic exposure in early life has long-term consequences for blood pressure and maybe kidney function.

Cholera in Bangladesh: climatic components of seasonal variation.

Background: The mechanisms underlying the seasonality of cholera are still not fully understood, despite long-standing recognition of clear bimodal seasonality in Bangladesh. We aimed to quantify the contribution of climatic factors to seasonal variations in cholera incidence. Methods: We investigated the association of seasonal and weather factors with the weekly number of cholera patients in Dhaka, Bangladesh, using Poisson regression models. The contribution of each weather factor (temperature and high and low rainfall) to seasonal variation was estimated as the mean over the study period (1983–2008) for each week of the year of each weather term. Fractions of the number of cholera patients attributed to each weather factor, assuming all values were constant at their minimum risk levels throughout the year, were estimated for spring and monsoon seasons separately. Results: Lower temperature predicted a lower incidence of cholera in the first 15 weeks of the year. Low rainfall predicted a peak in spring, and high rainfall predicted a peak at the end of the monsoon. The risk predicted from all the weather factors combined showed a broadly bi-modal pattern, as observed in the raw data. Low rainfall explained 18% of the spring peak, and high rainfall explained 25% of the peak at the end of the monsoon. Conclusions: Seasonal variation in temperature and rainfall contribute to cholera incidence in complex ways, presumably in interaction with unmeasured environmental or behavioral factors.