Outbreak of seafood-related food poisoning from undetectable Vibrio parahaemolyticus-like pathogen, Chiang Mai Province, Thailand, December 2020.

OBJECTIVE: On 1 December 2020, the Department of Disease Control of Thailand was notified of a cluster of food poisoning cases among participants at a church festival in Mae Ai district, Chiang Mai province. We conducted an outbreak investigation to confirm diagnosis, describe the epidemiological characteristics of the outbreak, identify possible sources of the outbreak and provide appropriate control measures. METHODS: We reviewed medical records of the food poisoning cases from the health care centres. Active case finding was conducted among participants who had consumed food and water at the festival. An environmental survey was done in the village where the festival was held. A case-control study was conducted to identify the source of the outbreak. Samples for laboratory analysis included rectal swabs and fresh stool specimens from the cases and food handlers, surface swabs of cooking equipment, food, water and ice samples. RESULTS: Among 436 participants surveyed, 368 (84.4%) cases of food poisoning were identified. The most common clinical manifestation was abdominal pain (89.7%), followed by watery diarrhoea (45.7%), nausea (43.5%), vomiting (38.9%), fever (18.5%) and bloody diarrhoea (4.6%). None died in this outbreak. The case-control study showed that mixed spicy seafood salad served in the festival was significantly associated with the disease by both univariable and multivariable analyses. However, the causative agent could not be identified. The environmental investigation suggested this seafood might have been undercooked. CONCLUSION: Clinical manifestations of the cases, incubation period and the suspected seafood salad suggested seafood-related food poisoning. Grimontia hollisae, the organism causing illness similar to Vibrio parahaemolyticus and commonly undetectable in the laboratory with routine testing, might be the pathogen that caused this outbreak. G. hollisae should be in differential diagnosis and identified in seafood-associated outbreaks.

Etiologic features of diarrheagenic microbes in stool specimens from patients with acute diarrhea in Thailand.

Many microbial species have been recognized as enteropathogens for humans. Here, we predicted the causative agents of acute diarrhea using data from multiplex quantitative PCR (qPCR) assays targeting 19 enteropathogens. For this, a case-control study was conducted at eight hospitals in Thailand. Stool samples and clinical data were collected from 370 hospitalized patients with acute diarrhea and 370 non-diarrheal controls. Multiple enteropathogens were detected in 75.7% and 13.0% of diarrheal stool samples using multiplex qPCR and bacterial culture methods, respectively. Asymptomatic carriers of enteropathogens were found among 87.8% and 45.7% of individuals by qPCR and culture methods, respectively. These results suggested the complexity of identifying causative agents of diarrhea. An analysis using the quantification cut-off values for clinical relevance drastically reduced pathogen-positive stool samples in control subjects from 87.8% to 0.5%, whereas 48.9% of the diarrheal stool samples were positive for any of the 11 pathogens. Among others, rotavirus, norovirus GII, Shigella/EIEC, and Campylobacter were strongly associated with acute diarrhea (P-value < 0.001). Characteristic clinical symptoms, epidemic periods, and age-related susceptibility to infection were observed for some enteropathogens. Investigations based on qPCR approaches covering a broad array of enteropathogens might thus improve our understanding of diarrheal disease etiology and epidemiological trends.

Evaluation of Immunization Services for Children of Migrant Workers Along Thailand-Myanmar Border: Compliance with Global Vaccine Action Plan (2011-2020).

Immunization is a core component of the human right to health. However, accessibility to the Expanded Program on Immunization (EPI) might be difficult among migrant children. This study aims to assess the vaccination coverage of migrant children under a mobile immunization program, initiated by the Thai government in 2014. A cross-sectional, mixed-methods study was conducted in five districts along the Thailand-Myanmar border during July-December 2018. The immunization history during their first year of life was obtained. Focus group discussions were conducted among stakeholders to explore their satisfaction toward the immunization service. Mothers/guardians of 1707 migrant children participated in the survey, with a 71% response rate. The vaccination coverage increased during 2014-2017. The highest vaccination coverage was observed for Bacillus CalmetteGuérin vaccine, with 83.2% coverage in 2017. The vaccination coverage of three doses of diphtheriatetanuspertussis vaccine and Hepatitis B vaccine and oral polio vaccine increased from 34.8% in 2014 to 56.3% in 2017. For measles-containing vaccine, the vaccination coverage increased from 32.4% in 2014 to 54.6% in 2017. Overall, all stakeholders were satisfied with the immunization service. Increased workload and communication barriers were the main factors that influenced the satisfaction toward the immunization program.

Bone Fracture Risk and Renal Dysfunction in a Highly Cadmium Exposed Thai Population.

BACKGROUND: Paddy fields in the Mae Sot, Tak Province of Thailand are polluted with unsafe levels of cadmium (Cd). Elderly populations have a high Cd body burden, putting them at elevated risk of renal dysfunction and bone fractures. We aimed to compare bone fracture risk between glomerular dysfunction, proximal tubular dysfunction, and calcium (Ca) handling abnormalities. STUDY DESIGN: A cross-sectional study. METHODS: Serum osteocalcin and cross-linked N-telopeptide of type I collagen were used to detect bone metabolism abnormalities, whereas glomerular filtration rate, serum cystatin C, urinary ß2-microglobulin (ß2-MG) and fractional excretion of calcium (FECa) were used to indicate renal dysfunction. Urinary Cd was used as an exposure marker. RESULTS: FECa >2% was associated with high bone fracture risk in both genders. The adjusted odds of bone fracture risk were 6.029 and 3.288 in men and women, respectively with FECa >2% relative to the FECa < 2% group. Proximal tubular dysfunction and glomerular dysfunction did not significantly relate to the risk of bone fracture. CONCLUSIONS: Abnormal Ca handling is a key risk factor for bone fracture in Cd-exposed people. Men and women were at risk of bone fracture risk at a similar rate. FECa was a specific indicator of Ca wasting and was more cost-effective compared to ß2-MG and serum cystatin C. We recommend using FECa to monitor abnormal Ca metabolism in individuals with FECa>2%. Reduced renal toxicant exposure and Ca supplementation are recommended for Cd-exposed populations to reduce bone fracture risk.

Gender-Specific Impact of Cadmium Exposure on Bone Metabolism in Older People Living in a Cadmium-Polluted Area in Thailand.

To elucidate the influence of cadmium exposure on bone metabolism, associations between urinary/blood cadmium and bone resorption/formation markers were investigated in older cadmium exposed men and women. Increased urinary cross-linked N-telopeptide of type I collagen (NTx), a bone resorption marker, was found to be associated with increased levels of parathyroid hormone, fractional excretion of calcium, and urinary/blood cadmium after adjusting for confounding factors in men. In women, urinary NTx was significantly associated with only urinary cadmium and a strong relationship with increased fractional excretion of calcium. Risk for bone metabolic disorders, indicated by high urinary NTx, significantly increased in men with blood cadmium ≥ 10 µg/L or urinary cadmium ≥ 10 µg/g creatinine. Increased osteocalcin level was significantly associated with increased blood cadmium in men. In conclusion, cadmium exposure appeared to have an influence on bone remodeling both bone resorption and formation in this population of older Thai men, and blood cadmium was more closely associated with bone metabolism than urinary cadmium.

Cadmium exposure and age-associated DNA methylation changes in non-smoking women from northern Thailand.

DNA methylation changes with age, and may serve as a biomarker of aging. Cadmium (Cd) modifies cellular processes that promote aging and disrupts methylation globally. Whether Cd modifies aging processes by influencing establishment of age-associated methylation marks is currently unknown. In this pilot study, we characterized methylation profiles in > 450 000 CpG sites in 40 non-smoking women (age 40-80) differentially exposed to environmental Cd from Thailand. Based on specific gravity adjusted urinary Cd, we classified them as high (HE) and low (LE) exposed and age-matched within 5 years. Urinary Cd was defined as below 2 µg/l in the LE group. We predicted epigenetic age (DNAm-age) using two published methods by Horvath and Hannum and examined the difference between epigenetic age and chronologic age (Δage). We assessed differences by Cd exposure using linear mixed models adjusted for estimated white blood cell proportions, BMI, and urinary creatinine. We identified 213 age-associated CpG sites in our population (P < 10-4). Counterintuitively, the mean Δage was smaller in HE vs. LE (Hannum: 3.6 vs. 7.6 years, P = 0.0093; Horvath: 2.4 vs. 4.5 years, P = 0.1308). The Cd exposed group was associated with changes in methylation (P < 0.05) at 12, 8, and 20 age-associated sites identified in our population, Hannum, and Horvath. From the results of this pilot study, elevated Cd exposure is associated with methylation changes at age-associated sites and smaller differences between DNAm-age and chronologic age, in contrast to expected age-accelerating effects. Cd may modify epigenetic aging, and biomarkers of aging warrant further investigation when examining Cd and its relationship with chronic disease and mortality.

DNA methylation is differentially associated with environmental cadmium exposure based on sex and smoking status.

The adverse health effects of cadmium (Cd) are well known in human populations; however, much of what is known about biological mechanisms of Cd comes from in vitro and animal studies. The adverse health outcomes due to high levels of Cd exposure in the population of Mae Sot, Thailand have been extensively characterized. Here, for the first time, this population is being studied in an epigenetic context. The objective of this study was to characterize the association between DNA methylation markers and Cd exposure, taking into account sex and smoking differences, in an adult population at an increased risk of experiencing adverse health outcomes from high body burden of Cd. One hundred and sixty-nine residents from known exposure areas of Mae Sot, Thailand and one hundred residents from non-exposed areas nearby were surveyed in 2012. Urine and blood samples were collected for measurement of urinary Cd (UCd) and DNA methylation of Cd-related markers (DNMT3B, MGMT, LINE-1, MT2A). UCd levels were 7 times higher in the exposed compared to the unexposed populations (exposed median: 7.4 µg/L, unexposed median: 1.0 µg/L, p < 0.001). MGMT hypomethylation was associated with increasing levels of UCd in the total population. Sex-specific associations included MT2A and DNMT3B hypomethylation in women and LINE-1 hypermethylation in men with increasing UCd. Upon subanalysis, these associations separated by smoking status. In summary, environmental Cd exposure is associated with gene-specific DNA methylation in a sex and smoking dependent manner.

Increased platelet activation in subjects chronically exposed to cadmium: A pilot study.

Cadmium exposure has been reported to be associated with the risk of vascular disorders. Here, we investigated platelet activity in subjects with chronic cadmium exposure. Eighteen and 15 women participated in this study as chronically cadmium-exposed and control non-exposed subjects, respectively. Plasma P-selectin and CD40 ligand (CD40L), soluble markers of platelet activation, were measured. Platelet aggregation in whole blood, P-selectin and activated glycoprotein (aGP) IIb/IIIa expression on platelets and platelet-leukocyte aggregates were determined. The levels of plasma P-selectin and CD40L increased in subjects with chronic cadmium exposure compared with control subjects. Platelet aggregation induced by adenosine diphosphate (ADP) was higher in cadmium-exposed subjects than control subjects. Cadmium-exposed subjects had higher baseline and ADP-induced aGPIIb/IIIa expression on platelets than control subjects. Platelet-neutrophil aggregates also increased in cadmium-exposed subjects. Blood cadmium correlated with ADP-induced aggregation, aGPIIb/IIIa expression and platelet-neutrophil aggregates, while urinary cadmium correlated with soluble P-selectin. However, cadmium only at high concentration (15 µM) could potentiate ADP-induced platelet activation in vitro. In conclusion, our pilot data show that cadmium-exposed subjects have increased baseline platelet activation and reactivity.

HUMAN HEALTH EFFECTS FROM CADMIUM EXPOSURE: COMPARISON BETWEEN PERSONS LIVING IN CADMIUM-CONTAMINATED AND NON-CONTAMINATED AREAS IN NORTHWESTERN THAILAND.

Environmental cadmium contamination is present in some rural villages of Mae Sot District, Tak Province, northwestern Thailand. We compared the health of 751 persons aged ≥ 35 years living in 3 contaminated villages with 682 people from 3 non-contaminated villages with similar socio-demographic and lifestyle characteristics in the same district. All the subjects were screened for urinary cadmium (a biomarker for long-term cadmium exposure), renal function, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, urinary tract stone disease and bone mineral density in 2012. The study renal functions included urinary excretion of ß2-microglobulin (early tubular effect), total urine protein and glomerular filtration rate (glomerular effects). The geometric mean of urinary cadmium level was significantly higher among persons living in the contaminated areas (2.96 µg/g creatinine) than those in the non-contaminated areas (0.60 µg/g creatinine). Persons living in contaminated areas had a significantly higher prevalence of renal dysfunction, bone mineral loss, hypertension and urinary stones than those living in non-contaminated areas. There were no significant differences between the 2 groups in the prevalence of diabetes, hypercholesterolemia and hypertriglyceridemia. This study shows health effects due to environmental cadmium exposure. The prevalences of diabetes, hypercholesterolemia, and hypertriglyceridemia were not associated with cadmium exposure.

Endothelial dysfunction in subjects with chronic cadmium exposure.

Vascular endothelium is a target of cadmium (Cd) toxicity. Cd exposure has been reported to be associated with vascular disorders. In this study, we aimed to investigate the effects of Cd exposure on markers of endothelial function in human subjects chronically exposed to Cd. Based on blood Cd levels, seventy-five women were categorized into non-exposed, Cd-exposed and severely Cd-exposed groups. Nitrite, L-arginine, asymmetric dimethylarginine (ADMA), and soluble thrombomodulin levels in blood were measured. Nitrite levels were lower in Cd-exposed subjects than non-exposed subjects. Plasma L-arginine decreased while ADMA, an endogenous endothelial nitric oxide synthase (eNOS) inhibitor, increased in Cd-exposed subjects. Soluble thrombomodulin also increased in Cd-exposed subjects. In Cd-exposed subjects, plasma malondialdehyde and protein carbonyl groups increased while the erythrocytic glutathione decreased. Multiple linear regression analysis revealed a negative association between urinary Cd and nitrite levels in erythrocytes. Our research suggests that subjects with chronic Cd exposure have endothelial dysfunction.

Additional Burden of Diseases Associated with Cadmium Exposure: A Case Study of Cadmium Contaminated Rice Fields in Mae Sot District, Tak Province, Thailand.

The cadmium (Cd) contaminated rice fields in Mae Sot District, Tak Province, Thailand has been one of the major environmental problems in Thailand for the last 10 years. We used disability adjusted life years (DALYs) to estimate the burden of disease attributable to Cd in terms of additional DALYs of Mae Sot residents. Cd exposure data included Cd and ß2-microglobulin (ß2-MG) in urine (as an internal exposure dose) and estimated cadmium daily intake (as an external exposure dose). Compared to the general Thai population, Mae Sot residents gained 10%-86% DALYs from nephrosis/nephritis, heart diseases, osteoporosis and cancer depending on their Cd exposure type and exposure level. The results for urinary Cd and dietary Cd intake varied according to the studies used for risk estimation. The ceiling effect was observed in results using dietary Cd intake because of the high Cd content in rice grown in the Mae Sot area. The results from ß2-MG were more robust with additional DALYs ranging from 36%-86% for heart failure, cerebral infraction, and nephrosis/nephritis. Additional DALYs is a useful approach for assessing the magnitude of environmental Cd exposure. The Mae Sot population lost more healthy life compared to populations living in a non- or less Cd polluted area. This method should be applicable to various types of environmental contamination problems if exposure assessment information is available.

Renal and blood pressure effects from environmental cadmium exposure in Thai children.

Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of ß2-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥ 1 µg/g creatinine. The prevalence of urinary cadmium ≥ 1 µg/g creatinine was significantly higher in girls and in those consuming rice grown in cadmium-contaminated areas. The geometric mean levels of urinary ß2-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary ß2-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children.

Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand.

BACKGROUND: The aim of the present study was to estimate the benchmark doses (BMD) for renal effects for health risk assessment of residents living in Cd-polluted and non-polluted areas in a Thai population. METHODS: The study participants consisted of inhabitants aged 40 years or older who lived in a non-polluted area (40 men and 41 women) and in the environmentally polluted Mae Sot District (230 men and 370 women) located in northwestern Thailand. We measured urinary and blood cadmium (Cd) as markers of long-term exposure and urinary ß2-microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) as renal tubular effect markers. An updated hybrid approach was applied to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of urinary and blood Cd for Cd-induced renal effects in these subjects. BMD and BMDL corresponding to an additional risk (BMR) of 5% were calculated with the background risk at zero exposure set to 5% after adjusting for age and smoking status. RESULTS: The estimated BMDLs of urinary Cd for renal effect markers were 6.9 for urinary ß2-MG and 4.4 for NAG in men and 8.1 for ß2-MG and 6.1 for NAG µg/g creatinine (Creat) in women. These BMDLs of urinary Cd (µg/g Creat) for NAG were less than the geometric mean urinary Cd in the polluted area (6.5 in men and 7.1 in women). The estimated BMDLs of blood Cd (µg/L) were 6.2 for urinary ß2-MG and 5.0 for NAG in men and 5.9 for ß2-MG and 5.8 for NAG in women. The calculated BMDLs were similar or less compared with the geometric mean blood Cd (µg/L) in the polluted Thai area (6.9 in men and 5.2 in women). CONCLUSION: The BMDLs of urinary and blood Cd for renal effects were estimated to be 4.4-8.1 µg/g Creat and 4.4-6.2 µg/L in the Thai population aged ≥ 40 years old, suggesting that more than 40% of the residents were at risk of adverse renal effects induced by Cd exposure in Thailand.

A biomarker found in cadmium exposed residents of Thailand by metabolome analysis.

First, the urinary metabolic profiling by gas chromatography-mass spectrometry (GC-MS), was performed to compare ten cadmium (Cd) toxicosis cases from a Cd-polluted area in Mae Sot (Thailand) with gender-matched healthy controls. Orthogonal partial list square-discrimination analysis was used to identify new biomarker candidates in highly Cd exposed toxicosis cases with remarkable renal tubular dysfunction. The results of the first step of this study showed that urinary citrate was a negative marker and myo-inositol was a positive marker for Cd toxicosis in Thailand. In the second step, we measured urinary citrate in the residents (168 Cd-exposed subjects and 100 controls) and found significantly lower levels of urinary citrate and higher ratios of calcium/citrate and magnesium/citrate, which are risk factors for nephrolithiasis, in highly Cd-exposed residents. Additionally, this inverse association of urinary citrate with urinary Cd was observed after adjustment for age, smoking and renal tubular dysfunction, suggesting a direct effect of Cd on citrate metabolism. These results indicate that urinary citrate is a useful biomarker for the adverse health effects of Cd exposure in a Thai population with a high prevalence of nephrolithiasis.

PERSONAL AND ENVIRONMENTAL RISK FACTORS SIGNIFICANTLY ASSOCIATED WITH ELEVATED BLOOD LEAD LEVELS IN RURAL THAI CHILDREN.

A community-based study was conducted to determine personal risk factors and environmental sources of lead exposure for elevated blood lead levels (≥ 10 µg/dl, EBLLs) among rural children living at the Thailand-Myanmar border in Tak Province, northwestern Thailand. Six hundred ninety-five children aged 1-14 years old were screened for BLLs. Environmental specimens for lead measurements included samples of water from the streams, taps, and household containers, house floor dust, and foods. Possible lead release from the cooking ware was determined using the leaching method with acetic acid. The overall prevalence of EBLLs was 47.1% and the geometric mean level of blood lead was 9.16 µg/dl. Personal risk factors significantly associated with EBLLs included being male, younger age, anemia, and low weight-for-age. Significant environmental risk factors were exposure to a lead-acid battery of solar energy system and use of a non-certified metal cooking pot. Some families whose children had high BLLs reported production of lead bullets from the used batteries at home. About one-third of the house dust samples taken near batteries contained lead content above the recommended value, compared with none of those taken from other areas and from the houses with no batteries. The metal pots were safe for cooking rice but might be unsafe for acidic food preparation. Both nutritional intervention and lead exposure prevention programs are essential to reduce EBLLs in this population.

Increasing of syncytial knot and fibrinoid deposit in high-Cd accumulated human placentas / Aumento del nodo sincicial y depósitos de fibrinoide en placenta humanas con alta acumulación de cadmio

A toxic metal, cadmium (Cd), can accumulate in human organs. Placenta is usually used as indicator organ for Cd exposure. Therefore, we aim to investigate the different of placental morphology between the low- and high-Cd accumulated placentas. The samples were collected from 14 pregnant women who resided in low-Cd contaminated (L-Cd group) and high-Cd contaminated (H-Cd group) areas. The concentrations of Cd in blood (B-Cd), urine (U-Cd) and placentas (P-Cd) were measured by ICP-MS and AAS. The morphological appearance of placentas was examined by using routine paraffin section and H & E staining. The results showed that levels of B-Cd, U-Cd and P-Cd were significantly higher in H-Cd group than in L-Cd group (p= 0.001). Moreover, the B-Cd was positively correlated with U-Cd (rs= 0.823, p= 0.000) and P-Cd concentrations (rs= 0.854, p= 0.000). The appearances of syncytial knot (STK) and fibrinoid deposit (Fd) were obviously greater in H-Cd group than in L-Cd group (p= 0.007, p= 0.026). The STK was positively correlated with both Fd (rs= 0.572, p= 0.032) and P-Cd concentration (rs= 0.766, p= 0.001). Although the chorioamnitis and decidual inflammation features were found in both groups but the appearance in H-Cd group seems to be more severe than in L-Cd group. From these results, we suggested that high Cd level in placenta may be involved in morphological changes, especially STK and Fd increasing and probably disturb the connection between maternal and fetal circulation.

Un metal tóxico, el cadmio (Cd), se puede acumular en órganos humanos. La placenta se utiliza, por lo general, como órgano indicador de la exposición a Cd. Nuestro objetivo fue investigar la diferente morfología placentaria entre las placentas con baja y alta acumulación de Cd. Las muestras fueron recolectadas de 14 mujeres embarazadas que residían áreas con alta (grupo H-Cd) y baja contaminación por Cd (grupo L-Cd). Las concentraciones de Cd en la sangre (B- Cd), orina (U-Cd) y placentas (P-Cd) se midieron por ICP-MS y AAS. La apariencia morfológica de las placentas fue examinada usando cortes histológicos teñidos con H-E. Los resultados mostraron que los niveles de B-Cd, U-Cd y P-Cd fueron significativamente mayores en el grupo H-Cd (p= 0,001). Por otra parte, el B-Cd se correlacionó positivamente con las concentraciones de U-Cd (rs= 0,854, p = 0,000 ) y P-Cd (rs= 0,823, p = 0,000). Las apariciones de nodos sinciciales (NS) y depósitos fibrinoides (Fd) fueron mayores en el grupo H-Cd (rs= 0,007, p= 0,026). Los ND se correlacionaron positivamente con los Fd (rs= 0,572, p= 0,032) y la concentración de P-Cd (rs= 0,766, p = 0,001). Aunque características de corioamnitis e inflamación de la decidua se encontraron en ambos grupos, su aparición en el grupo H-Cd pareció ser más grave que en el grupo L-Cd. A partir de estos resultados, sugerimos que el nivel alto de Cd en la placenta puede estar involucrado en los cambios morfológicos, especialmente el aumento de NS y Fd, los que probablemente alteran la relación entre la circulación materna y fetal.

Use of the kidney injury molecule-1 as a biomarker for early detection of renal tubular dysfunction in a population chronically exposed to cadmium in the environment.

Cadmium (Cd) has been found as an environmental pollutant in Mae Sot district, Tak province, Thailand. Prolong exposure to high levels of Cd of the resident increases high risk of Cd toxicity especially to kidney which is the primary target of Cd. In order to investigate the early effect of Cd induced renal dysfunction, a kidney injury molecule-1 (KIM-1), a novel biomarker of renal tubular dysfunction, was measured using an enzyme linked immunosorbent assay (ELISA). The method was validated and used to quantify the KIM-1 concentrations in the urine of 700 subjects (260 men, 440 women) who lived in the Cd contaminated area. The KIM-1 concentrations were compared to the concentrations of two conventional renal tubular dysfunction biomarkers, N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG). Urinary KIM-1 was correlated with urinary and blood Cd as well as NAG. After adjustment of age and smoking, urinary KIM-1 was correlated with blood Cd more than urinary NAG did. Clear dose response relationships of urinary KIM-1 with urinary Cd were shown in both men and women. These results indicate that the urinary KIM-1 might be more sensitive biomarker than urinary NAG and ß2-MG for an early detection of renal tubular dysfunction. It is useful as a tool to detect renal effect of toxicity due to chronic Cd exposure at high level.

Modeling cadmium exposures in low- and high-exposure areas in Thailand.

BACKGROUND: Previous U.S. population modeling studies have reported that urinary cadmium (Cd) excretion patterns differ with age, sex, and dietary exposure; associations between Cd exposures and health outcomes also have differed by age and sex. Therefore, it is important to test models used to estimate Cd exposures across an expanded Cd-exposure range. OBJECTIVES: We estimated relative Cd exposures from both diet and smoking in low- and high-exposure scenarios to provide data for improving risk assessment calculations. METHODS: We used a Cd toxicokinetic-based model to estimate Cd exposures based on urinary Cd levels measured for 399 persons in a low-exposure area (Bangkok) and 6,747 persons in a high-exposure area (Mae Sot) in Thailand. RESULTS: In Bangkok, we estimated dietary Cd exposures of 50-56 µg/day for males and 21-27 µg/day for females 20-59 years of age who never smoked. In Mae Sot, we estimated dietary Cd exposures of 188-224 µg/day for males and 99-113 µg/day for females 20-59 years of age who never smoked. In Bangkok, we estimated Cd exposures from smoking to be 5.5-20.4 µg/day for male smokers 20-59 years of age. In Mae Sot, we estimated Cd exposures from smoking to be 9.8-26 µg/day for male heavy smokers and 26 µg/day for female heavy smokers. CONCLUSION: This study provides estimates of Cd exposures from diet and smoking in low- and high-exposure scenarios. Our findings suggest a relatively small safety margin between the established tolerable Cd reference exposure of 62 µg/day and exposure levels previously associated with evidence of kidney and bone effects in Mae Sot residents, where dietary Cd exposures among women were only 1.6-2.1 times the reference value.

Blood lead levels among rural Thai children exposed to lead-acid batteries from solar energy conversion systems.

We evaluate blood lead levels among Thai children to determine if exposure to lead-acid batteries is associated with elevated blood lead levels (EBLL). We screened 254 children aged 1-14 years old from 2 rural Thai villages for blood lead levels. We also screened 18 of 92 houses in these 2 villages for the presence of environmental lead. The overall prevalence of EBLL (> or = 10 microg/dl) was 43.3% and the mean lead level among study subjects was 9.8 +/- 5.1 microg/dl. The blood lead levels significantly decreased with increasing age. Fifty point eight percent of children who lived in a house with vented lead-acid batteries had EBLL while 23.3% of children who lived in a house without vented lead-acid batteries had EBLL. Multiple logistic regression analysis revealed a significant positive association between the presence of vented lead-acid batteries and EBLL, after adjusting for other variables. Forty-two point nine percent of house floor dust samples collected near the batteries had elevated lead levels, 7.1% of house floor dust samples collected from other areas in the house had elevated lead levels and 0% of the house floor dust samples collected in houses without vented lead-acid batteries had elevated lead levels. In the sampled houses with vented lead-acid batteries, lead contamination was found in the drinking-water kept in household containers, but not in the tap water or other village sources of water. Improper care and placement of vented lead-acid batteries can result in lead contamination in the home environment causing EBLL in exposed children.