Long-term observational study on 6223 survivors of arsenic poisoning due to contaminated milk powder during infancy.

In 1955, an outbreak of arsenic poisoning caused by the ingestion of arsenic-contaminated Morinaga Dry Milk occurred in western Japan. This study aimed to assess the mortality and cancer incidence risk among Japanese individuals who were poisoned during this time as infants. In total, 6223 survivors (mean age at enrollment, 27.5 y) who had ingested contaminated milk when they were aged ≤ 2 y participated in this study. Follow-up was conducted from 1982 to 2018 (mean follow-up duration, 30.3 y). Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare mortality and cancer incidence rates of subjects with the respective Japanese population rates, and 95% confidence intervals (95% CIs) of the SMR and SIR were also calculated. In total, 561 deaths and 524 new cancer cases were observed. A statistically significant increase in mortality rate was observed for all causes (SMR, 1.15; 1.01-1.19), nervous system disease (2.83, 1.62-4.19), respiratory disease (2.02, 1.37-2.62), genitourinary system disease (2.25, 1.10-3.73), and traffic accident (2.03, 1.14-3.04). In contrast, a significant decrease in cancer incidence rate was observed for all cancers (SIR, 0.96; 0.84-0.99), stomach cancer (0.77, 0.57-0.92), colon cancer (0.63, 0.41-0.85), rectum cancer (0.69, 0.43-0.95), and breast cancer (0.72, 0.52-0.89). Liver cancer showed a high mortality rate (SMR, 1.68; 1.06-2.31). In this study, after the long-term follow-up we revealed overall and cause-specific mortality and cancer incidence risk among survivors who ingested arsenic-contaminated dry milk as infants.

Effects of health intervention programs and arsenic exposure on child mortality from acute lower respiratory infections in rural Bangladesh.

BACKGROUND: Respiratory infections continue to be a public health threat, particularly to young children in developing countries. Understanding the geographic patterns of diseases and the role of potential risk factors can help improve future mitigation efforts. Toward this goal, this paper applies a spatial scan statistic combined with a zero-inflated negative-binomial regression to re-examine the impacts of a community-based treatment program on the geographic patterns of acute lower respiratory infection (ALRI) mortality in an area of rural Bangladesh. Exposure to arsenic-contaminated drinking water is also a serious threat to the health of children in this area, and the variation in exposure to arsenic must be considered when evaluating the health interventions. METHODS: ALRI mortality data were obtained for children under 2 years old from 1989 to 1996 in the Matlab Health and Demographic Surveillance System. This study period covers the years immediately following the implementation of an ALRI control program. A zero-inflated negative binomial (ZINB) regression model was first used to simultaneously estimate mortality rates and the likelihood of no deaths in groups of related households while controlling for socioeconomic status, potential arsenic exposure, and access to care. Next a spatial scan statistic was used to assess the location and magnitude of clusters of ALRI mortality. The ZINB model was used to adjust the scan statistic for multiple social and environmental risk factors. RESULTS: The results of the ZINB models and spatial scan statistic suggest that the ALRI control program was successful in reducing child mortality in the study area. Exposure to arsenic-contaminated drinking water was not associated with increased mortality. Higher socioeconomic status also significantly reduced mortality rates, even among households who were in the treatment program area. CONCLUSION: Community-based ALRI interventions can be effective at reducing child mortality, though socioeconomic factors may continue to influence mortality patterns. The combination of spatial and non-spatial methods used in this paper has not been applied previously in the literature, and this study demonstrates the importance of such approaches for evaluating and improving public health intervention programs.

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.

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.

Homicide by poisoning.

By studying the number and method of homicidal poisoning in Miami-Dade County, Florida; New York City, NY; Oakland County, Michigan; and Sweden, we have confirmed that this is an infrequently established crime.Several difficulties come with the detection of homicidal poisonings. Presenting symptoms and signs are often misdiagnosed as natural disease, especially if the crime is committed in a hospital environment, suggesting that an unknown number of homicides go undetected.In the reported cases analyzed, the lethal agent of choice has changed over the years. In earlier years, traditional poisons such as arsenic, cyanide, and parathion were frequently used. Such poisonings are nowadays rare, and instead, narcotics are more commonly detected in victims of this crime.

Long-term impact of arsenic in drinking water on bladder cancer health care and mortality rates 20 years after end of exposure.

PURPOSE: In this study we assessed bladder cancer health care and mortality trends in recent decades in a well studied arsenic exposed area in Northern Chile. MATERIALS AND METHODS: Arsenic levels in the affected region were obtained for the last 60 years, and correlated with bladder cancer hospital discharge and mortality rates in recent decades. RESULTS: Bladder cancer hospital discharge rates were significantly higher in the affected region (peak RR 3.6, 95% CI 3.0-4.7). Mortality rates for bladder cancer showed a trend of increase during the period analyzed, reaching peak mortality rates of 28.4 per 100,000 for men and 18.7 per 100,000 for women in the last 10 years. Poisson regression models showed an increased mortality risk in the studied region compared to the rest of the country until the present for men (IRR 5.3, 95% CI 4.8-5.8) and women (IRR 7.8, 95% CI 7.0-8.7). Mean age at cancer specific death was significantly lower in the exposed region (69.6 years, 95% CI 68.4-70.7 vs 73.7 years, 95% CI 73.3-74.2, p <0.01). CONCLUSIONS: Exposure to arsenic is related to a significant need for bladder cancer health care and to high mortality rates even 20 years after having controlled arsenic levels in drinking water. Affected individuals should be aware of the significant impact of this ecological factor. Further research is required to identify strategies for the management of bladder cancer in arsenic exposed populations.

Arsenic in tube well water in Bangladesh: health and economic impacts and implications for arsenic mitigation.

A national drinking water quality survey conducted in 2009 furnished data that were used to make an updated estimate of chronic arsenic exposure in Bangladesh. About 20 million and 45 million people were found to be exposed to concentrations above the national standard of 50 µg/L and the World Health Organization's guideline value of 10 µg/L, respectively. From the updated exposure data and all-cause mortality hazard ratios based on local epidemiological studies, it was estimated that arsenic exposures to concentrations > 50 µg/L and 10-50 µg/L account for an annual 24,000 and perhaps as many as 19,000 adult deaths in the country, respectively. Exposure varies widely in the 64 districts; among adults, arsenic-related deaths account for 0-15% of all deaths. An arsenic-related mortality rate of 1 in every 16 adult deaths could represent an economic burden of 13 billion United States dollars (US$) in lost productivity alone over the next 20 years. Arsenic mitigation should follow a two-tiered approach: (i) prioritizing provision of safe water to an estimated 5 million people exposed to > 200 µg/L arsenic, and (ii) building local arsenic testing capacity. The effectiveness of such an approach was demonstrated during the United Nations Children's Fund 2006-2011 country programme, which provided safe water to arsenic-contaminated areas at a cost of US$ 11 per capita. National scale-up of such an approach would cost a few hundred million US dollars but would improve the health and productivity of the population, especially in future generations.

Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study.

BACKGROUND: Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. METHODS: In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. FINDINGS: 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. INTERPRETATION: Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure. FUNDING: US National Institutes of Health.

Cancer excess after arsenic exposure from contaminated milk powder.

OBJECTIVES: Long-term exposure to inorganic arsenic is related to increased risk of cancer in the lung, skin, bladder, and, possibly, other sites. However, little is known about the consequences of developmental exposures in regard to cancer risk. During early summer in 1955, mass arsenic poisoning of infants occurred in the western part of Japan because of contaminated milk powder. Okayama Prefecture was most severely affected. We examined whether the affected birth cohorts in this prefecture experienced increased cancer mortality. METHODS: We targeted subjects who were born from September 1950 to August 1960 and died in Okayama Prefecture between January 1969 and March 2008 due to malignant neoplasm (N = 3,141). We then compared cancer mortality (total, liver, pancreatic, lung, bladder/kidney, and hematopoietic cancers) between cohorts born before the milk poisoning (exposed group) and cohorts born after the poisoning (nonexposed group). We estimated mortality ratios and 95% confidence intervals. RESULTS: Total and liver cancers were elevated in the cohort up to 1 year of age at time of the poisoning. In addition, pancreatic and hematopoietic cancers were elevated in the cohorts up to 5 years of age, and mortality ratios were approximately twice those of the nonexposed group. Increased risk of lung and bladder/kidney cancers was not apparent. CONCLUSIONS: Although dilution is present in these cohort-based data, our study highlights the notion that developmental arsenic exposure may lead to a different pattern of cancer, including increases in pancreatic and hematopoietic cancer, as compared with adult or lifetime exposures to inorganic arsenic.

Arseniasis prevalence and mortality in a multiethnic, endemic township in Guizhou, China.

OBJECTIVE: Farmers in Southwest Guizhou Autonomous Prefecture, China, represent a unique case of arseniasis, which is related to indoor combustion of high arsenic-containing coal instead of to arsenic-contaminated drinking water. A significant difference in the prevalence of arseniasis was observed in two neighboring ethnic clans in one village. The question arose whether the ethnicity-dependent difference observed in this village was more widely spread throughout the whole township. An epidemiologic investigation was designed to explore arseniasis distribution and mortality among all four ethnic groups in a multiethnic township. METHODS: The cohort of arseniasis patients, diagnosed and registered in the overall field survey of 1991 as well as all the asymptomatic residents of the township, were enrolled in the present investigation. Indirect standardization was used for calculating the age-adjusted standardized incidence ratio (SIR) of arseniasis, the standardized mortality ratio (SMR) of various death causes (including some cancers), and their corresponding intervals of 95% confidence in both genders and in each local ethnic group. RESULTS: The descending rank of arseniasis SIRs among local ethnic groups was found as: Hui>Han>Bouyei>Hmong. The descending rank of SMRs of malignancies was displayed as: Han>Hui>Bouyei>Hmong in males and both genders together as well. Concerning deaths of non-malignant causes the rank was observed as: Hui>Han>Bouyei>Hmong in males. The arseniasis SIR for ethnic Hmong residents (both genders combined) was found to be significantly less profound than the overall level in the township. No death cases in diagnosed ethnic Hmong patients and no cases of death from malignant causes in asymptomatic Hmong residents were recorded. The significant increase of arseniasis prevalence was observed in all males, compared with the overall prevalence of all residents. However, a significantly lower prevalence was seen in all females. CONCLUSION: Significant ethnicity-dependent difference in arseniasis prevalence and mortality from all causes was found in a multiethnic rural township where farmers have been exposed to the indoor combustion of high arsenic coal for decades. The ethnic Hmong residents seemed to be the least susceptible to arseniasis among the four local ethnic groups.

Homicidal poisoning in India: A short review.

This review has analysed various studies and case reports on homicide by poison from different parts of India till date. This review shows that homicidal poisoning prevalence varies from 0.3% to 3.7% having varied prevalence from different regions with no homicidal cases too. The poisons used in homicide were mainly organophosphates, aluminium phosphide, paraquat, and arsenic. No age-group or gender was spared and the perpetrators were first degree relatives.

Clinical and epidemiological features of patients with genitourinary tract tumour in a blackfoot disease endemic area of Taiwan.

OBJECTIVES: To evaluate the clinical and epidemiological characteristics of patients with genitourinary (GU) tract transitional cell carcinoma (TCC) in an endemic area of blackfoot disease (BFD), the arsenic-exposed group, to compare them with characteristics among other non-BFD endemic areas (unexposed group). PATIENTS AND METHODS: In all, 474 patients with pathologically diagnosed GU-TCC were enrolled in the study. All follow-up data were prospectively collected and entered into a database throughout the study period. Statistical analysis was used to determine the association between clinical variables and prognosis, and multivariate regression models were used to assess the association between arseniasis and mortality from GU-TCC. RESULTS: There were no significant differences between the groups in age, sex, tumour stage and grade. However, the exposed group had a significantly higher proportion of females. The overall 5-year survival rate of patients with upper urinary tract (UUT) TCC was 49%, and the two groups had similar 5-year survival rates. The overall 5-year survival rate of patients with urinary bladder (UB) TCC was 68.3%, and there was a statistically significant difference in survival between the groups, with a 5-year survival rate of 58.7% for the exposed and 72.4% for the unexposed group. For patients with early-stage (pTa and pT1) UB cancers, the death rate was five times higher in exposed patients with tumour progression and recurrence after transurethral resection of bladder tumour than in the unexposed group. CONCLUSIONS: There was a significantly higher mortality rate for UB-TCC among exposed patients in the area endemic for arseniasis than in those from other non-endemic areas. The arsenic content of artesian-well water might contribute to the increased ratio of female patients with GU-TCC and the unusually high incidence of UUT-TCC in the BFD endemic area in Taiwan.

Lung, Bladder, and Kidney Cancer Mortality 40 Years After Arsenic Exposure Reduction.

Background: Region II in northern Chile (population 442 570) experienced a sudden major increase in arsenic water concentrations in 1958 in the main city of Antofagasta, followed by a major reduction in exposure when an arsenic removal plant was installed in 1970. It provides a unique opportunity to study latency effects of exposure to arsenic, and this is the first study with mortality data up to 40 years after exposure reduction. Methods: We previously identified high mortality rates in Region II up to the year 2000. Here we present rate ratios (RRs) for Region II compared with all the rest of Chile from 2001 to 2010, and with unexposed Region V (population 1 539 852) for all years from 1950 to 2010. All statistical tests were one-sided. Results: From 2001 to 2010, comparing Region II with the rest of Chile, lung and bladder mortality were still greatly elevated (RR = 3.38, 95% confidence interval [CI] = 3.19 to 3.58, P < .001 for lung cancer in men; RR = 2.41, 95% CI = 2.20 to 2.64, P < .001 for lung cancer in women; RR = 4.79, 95% CI = 4.20 to 5.46, P < .001 for bladder cancer in men; RR = 6.43, 95% CI = 5.49 to 7.54, P < .001 for bladder cancer in women). Kidney cancer mortality was also elevated (RR = 1.75, 95% CI = 1.49 to 2.05, P < .001 for men; RR = 2.09, 95% CI = 1.69 to 2.57, P < .001 for women). Earlier short latency acute myocardial infarction mortality increases had subsided. Conclusions: Lung, bladder, and kidney cancer mortality due to arsenic exposure have very long latencies, with increased risks manifesting 40 years after exposure reduction. Our findings suggest that arsenic in drinking water may involve one of the longest cancer latencies for a human carcinogen.

Acute myocardial infarction mortality in comparison with lung and bladder cancer mortality in arsenic-exposed region II of Chile from 1950 to 2000.

Arsenic in drinking water is known to be a cause of lung, bladder, and skin cancer, and some studies report cardiovascular disease effects. The authors investigated mortality from 1950 to 2000 in the arsenic-exposed region II of Chile (population: 477,000 in 2000) in comparison with the unexposed region V. Increased risks were found for acute myocardial infarction (AMI), with mortality rate ratios of 1.48 for men (95% confidence interval (CI): 1.37, 1.59; p < 0.001) and 1.26 for women (95% CI: 1.14, 1.40; p < 0.001) during the high-exposure period in region II from 1958 to 1970. The highest rate ratios were for young adult men aged 30-49 years who were born during the high-exposure period with probable exposure in utero and in early childhood (rate ratio = 3.23, 95% CI: 2.79, 3.75; p < 0.001). Compared with lung and bladder cancer, AMI mortality was the predominant cause of excess deaths during and immediately after the high-exposure period. Ten years after reduction of exposures, AMI mortality had decreased, and longer latency excess deaths from lung and bladder cancer predominated. With these three causes of death combined, increased mortality peaked in 1991-1995, with estimated excess deaths related to arsenic exposure constituting 10.9% of all deaths among men and 4.0% among women.

Primary intracerebral hemorrhage mortality reduction after installation of a tap-water supply system in an arseniasis-endemic area in southwestern Taiwan.

Mortality and morbidity of vascular diseases, including stroke, are known to be associated with chronic exposure to inorganic arsenic through drinking water. A tap-water supply system was implemented in the early 1960s in the blackfoot disease (BFD) endemic areas of Taiwan. The objective of this study was to examine whether mortality attributed to stroke decreased among residents living in the BFD-endemic areas after the curtailment of arsenic exposure. Further it was of interest to determine whether arsenic exposure was related to a specific type of stroke. Standardized mortality ratios (SMRs) for stroke were calculated for the BFD endemic area for the years 1971-2000. The study results show that mortality due to primary intracerebral hemorrhage (PIH) declined gradually after the improvement of drinking-water supply system by elimination of arsenic exposure through removal of artesian well water. Based on the reversibility and specificity criteria, the association between arsenic exposure and mortality due to PIH is likely to be causal.

A low-cost method to identify tubewells for longitudinal research on arsenic in groundwater.

Exposure to high concentrations of arsenic in tubewell groundwater from the shallow aquifers of Bangladesh could result in up to 300,000 arsenic-related cancer cases over the next four decades. Understanding the magnitude and temporal dynamics of this exposure, via longitudinal studies, is imperative for planning effective mitigation and management strategies. Appropriate methods are needed to identify tubewells for longitudinal sampling. A plastic band marked with a unique identification number was developed, and various methods for attaching the band to the tubewell were tested, resulting in the choice of a galvanized-iron split-rivet. Two follow-up surveys at two and 14 months post-banding assessed the durability and longevity under field conditions in the JiVitA Project area in rural, northwestern Bangladesh. After two months, approximately 96.0% of the original bands on 1,063 tubewells were functional, although the rivets were partially corroded. After 14 months, approximately 65% of a subsample of the bands were functional. With further improvements to the rivets, these bands offer an inexpensive, durable, enumeration technology for longitudinal studies on groundwater arsenic.

Fatalities following skin exposure to arsenic.

Arsenic is a toxic metal that can cause death following exposure. In an unusual event, seven patients unintentionally applied a 30% arsenic solution to their entire body instead of a benzyl benzoate solution to treat their scabies. Hours later they developed severe skin reactions, including bullae, and were admitted to the hospital with gastrointestinal and cardiovascular disorders. Despite therapeutic interventions, three patients died and the rest were discharged from hospital with neurological sequelae. Toxicological analysis confirmed the presence of arsenic in the solution used by patients.

[Excess mortality among 5,064 victims of arsenic poisoning from ingestion of arsenic-contaminated "Morinaga dry-milk" in 1955: a prospective study from 1982 to 2004].

OBJECTIVES: A prospective cohort study was conducted to assess the excess mortality among victims of arsenic poisoning who had ingested "Morinaga dry-milk" that was contaminated with arsenic compounds in 1955. METHODS: We identified and enrolled 5,064 individuals who had ingested contaminated Morinaga dry-milk when they were aged two years or younger, in 1982 (mean age: 27.4 years) and they were followed until 2004 (mean length of follow-up: 22.3 years). The death certificates of subjects who died between 1982 and 2004 were examined. The risk of death was assessed by the ratio of the observed number (O) to the expected number of deaths (E), calculated from the mortality rate among Osaka residents. RESULTS: The O/E ratio for all causes of death was 1.3 (O = 211, P < 0.01). Significant excess mortality was observed for diseases of the central nervous system (O/E = 5.4) or circulatory system (O/E = 1.4), external causes (O/E = 1.4) and traffic accidents (O/E = 2.0). Excess mortality from all causes appeared 0 to 4 years after study enrollment (O/E = 2.1, P < 0.01), and then the O/E ratio decreased to unity (O/E = 1.2) beyond 10 years after study enrollment. The 352 males who were unemployed at the time of enrollment in the study showed significantly elevated risk of death from all causes (O/E = 3.3), death from disease of the central nervous system (O/E = 36.7), circulatory system (O/E = 3.7) or respiratory system (O/E = 5.7), and death from external causes (O/E = 3.4). CONCLUSION: This prospective cohort study showed that excess mortality from all causes among the victims of arsenic poisoning from ingestion of arsenic-contaminated "Morinaga dry-milk" in 1955 decreased to unity when they reached middle age.