Aflatoxin Exposure In Children Research Articles

A TGF-β-dominant chemoresistant phenotype of hepatoblastoma associated with aflatoxin exposure in children.

Hepatoblastoma (HB) is the most common liver cancer in children, posing a serious threat to children's health. Chemoresistance is the leading cause of mortality in patients with HB. A more explicit definition of the features of chemotherapy resistance in HB represents a fundamental urgent need. We performed an integrative analysis including single-cell RNA sequencing, whole-exome sequencing, and bulk RNA sequencing in 180 HB samples, to reveal genomic features, transcriptomic profiles, and the immune microenvironment of HB. Multicolor immunohistochemistry staining and in vitro experiments were performed for validation. Here, we reported four HB transcriptional subtypes primarily defined by differential expression of transcription factors. Among them, the S2A subtype, characterized by strong expression of progenitor ( MYCN , MIXL1 ) and mesenchymal transcription factors ( TWIST1 , TBX5 ), was defined as a new chemoresistant subtype. The S2A subtype showed increased TGF-β cancer-associated fibroblast and an immunosuppressive microenvironment induced by the upregulated TGF-β of HB. Interestingly, the S2A subtype enriched SBS24 signature and significantly higher serum aflatoxin B1-albumin (AFB1-ALB) level in comparison with other subtypes. Functional assays indicated that aflatoxin promotes HB to upregulate TGF-β. Furthermore, clinical prognostic analysis showed that serum AFB1-ALB is a potential indicator of HB chemoresistance and prognosis. Our studies offer new insights into the relationship between aflatoxin and HB chemoresistance and provide important implications for its diagnosis and treatment.

A mixed methods assessment of knowledge, attitudes and practices related to aflatoxin contamination and exposure among caregivers of children under 5 years in western Kenya.

Identifying factors that may influence aflatoxin exposure in children under 5 years of age living in farming households in western Kenya. We used a mixed methods design. The quantitative component entailed serial cross-sectional interviews in 250 farming households to examine crop processing and conservation practices, household food storage and consumption and local understandings of aflatoxins. Qualitative data collection included focus group discussions (N 7) and key informant interviews (N 13) to explore explanations of harvesting and post-harvesting techniques and perceptions of crop spoilage. The study was carried out in Asembo, a rural community where high rates of child stunting exist. A total of 250 female primary caregivers of children under 5 years of age and thirteen experts in farming and food management participated. Study results showed that from a young age, children routinely ate maize-based dishes. Economic constraints and changing environmental patterns guided the application of sub-optimal crop practices involving early harvest, poor drying, mixing spoiled with good cereals and storing cereals in polypropylene bags in confined quarters occupied by humans and livestock and raising risks of aflatoxin contamination. Most (80 %) smallholder farmers were unaware of aflatoxins and their harmful economic and health consequences. Young children living in subsistence farming households may be at risk of exposure to aflatoxins and consequent ill health and stunting. Sustained efforts to increase awareness of the risks of aflatoxins and control measures among subsistence farmers could help to mitigate practices that raise exposure.

Aflatoxin exposure among children of age 12–59 Months in Butajira District, South-Central Ethiopia: a community based cross-sectional study

BackgroundThe continued provision of safe food, free of aflatoxin remains a huge challenge in developing countries. Despite several favourable climatic conditions that facilitate aflatoxin contamination in Ethiopia, there is little information showing aflatoxin exposure in children. Therefore, this study assessed aflatoxin exposure among young children in Butajira district, South-Central Ethiopia.MethodsCommunity based cross-sectional study stratified by agro-ecology was employed in Health and Demographic Surveillance Site (HDSS) of Butajira. The study included 332 children aged 12–59 months and were selected by simple random sampling technique using the HDSS registration number as a sampling frame. We collected data on dietary practice and aflatoxin exposure. Aflatoxin M1 concentration in urine was measured by Enzyme-Linked Immunosorbent assay (ELISA). The data analysis was carried out using STATA.ResultsDetectable urinary Aflatoxin M1 was found in 62.4% (95% CI: 56.9 – 67.5%) of the children at a level ranging from 0.15 to 0.4 ng/ml. Children living in lowland agro-ecological zone had [AOR = 2.11 (95% CI; 1.15, 3.88] odds of being exposed to aflatoxin as compared to children living in highland agro-ecological zone. Children at lower socio-economic status [AOR = 0.27 (95% CI; 0.14, 0.50] and medium socio-economic status [AOR = 0.47 (95% CI; 0.25, 0.87] had 73% and 53% lower odds of being exposed to aflatoxin as compared to children in the higher socio-economic status, respectively.ConclusionsAflatoxin exposure among young children was very high in South-Central Ethiopia. This high aflatoxin exposure might emphasize the need for aflatoxin exposure mitigation strategies in Ethiopia. Especially, raising awareness of the community towards aflatoxin exposure is very crucial. In addition, further research is required to assess long-term aflatoxin exposure and its association with child growth and development.

Aflatoxin exposure in children living in Mirpur, Dhaka: data from MAL-ED companion study

Dietary exposure to aflatoxin is implicated in growth faltering of children. Despite the high burden of childhood stunting in urban Bangladesh, there are no data on long-term exposure to aflatoxin. This study aimed to explore aflatoxin exposure levels in a group of children followed longitudinally. The current study used data and biospecimens collected during 2010–2014 as part of the MAL-ED birth cohort study in an urban slum of Mirpur, Dhaka where children were followed from birth to 36 months. AFB1-lysine adduct concentrations were determined by isotope dilution mass spectrometry from plasma samples collected at 7, 15, 24, and 36 months of age. The limit of detection was 0.5 pg of AFB1-lys/mg albumin. In 744 plasma samples, the geometric mean of AFB1-lysine/mg albumin was 1.07 pg (range 0.04–123.5 pg/mg albumin). The proportion of children with detectable aflatoxin exposure was 10.1, 20.9, 17.9, and 61.7% for 7, 15, 24, and 36 months, respectively. Reduction in breastfeeding prevalence (80% at 24 months vs. 38% in 36 months) corresponded with the high-level detection of AFB1-lysine at the age of 36 months. AFB1-lysine concentrations were the highest at the end of monsoon. This study reveals that 62% of children in slum settlement were exposed to aflatoxin by the end of the third year of life. High aflatoxin exposure was detected at the end of rainy season and with the introduction of family food. These findings suggest interventions to ameliorate the problem of chronic aflatoxin exposure including childhood stunting.

Chronic aflatoxin exposure in children living in Bhaktapur, Nepal: Extension of the MAL-ED study.

Exposure to aflatoxin, a mycotoxin common in maize and groundnuts, has been associated with childhood stunting in sub-Saharan Africa. In an effort to further our understanding of growth impairment in relation to mycotoxins and other risk factors, biospecimens from a cohort of children enrolled in the Bhaktapur, Nepal MAL-ED study were assessed for aflatoxin exposure at 15, 24, and 36 months of age. Exposure was assessed through a well-established serum biomarker, the AFB1-lysine adduct. In this manuscript, the levels of aflatoxin exposure in the Nepal cohort were compared with those observed in aflatoxin studies, with child growth parameters as a health outcome. Results from this preliminary analysis demonstrated chronic aflatoxin exposure in children residing in Bhaktapur with a geometric mean of 3.62 pg AFB1-lysine/mg albumin. The range of exposure in this population is similar to those in African populations where associations with aflatoxin biomarkers and poor child growth have been observed. Future work will analyze the relationships between aflatoxin levels, growth, and other risk factors collected by the MAL-ED study.

Aflatoxin exposure may contribute to chronic hepatomegaly in Kenyan school children.

Background: Presentation with a firm type of chronic hepatomegaly of multifactorial etiology is common among school-age children in sub-Saharan Africa.Objective: Aflatoxin is a liver toxin and carcinogen contaminating staple maize food. In this study we examined its role in chronic hepatomegaly.Methods: Plasma samples collected in 2002 and again in 2004 from 218 children attending two schools in neighboring villages were assayed for aflatoxin exposure using the aflatoxin-albumin adduct (AF-alb) biomarker. Data were previously examined for associations among hepatomegaly, malaria, and schistosomiasis.Results: AF-alb levels were high in children from both schools, but the geometric mean (95% confidence interval) in year 2002 was significantly higher in Matangini [206.5 (175.5, 243.0) pg/mg albumin] than in Yumbuni [73.2 (61.6, 87.0) pg/mg; p < 0.001]. AF-alb levels also were higher in children with firm hepatomegaly [176.6 (129.6, 240.7) pg/mg] than in normal children [79.9 (49.6, 128.7) pg/mg; p = 0.029]. After adjusting for Schistosoma mansoni and Plasmodium infection, we estimated a significant 43% increase in the prevalence of hepatomegaly/hepatosplenomegaly for every natural-log-unit increase in AF-alb. In 2004, AF-alb levels were markedly higher than in 2002 [539.7 (463.3, 628.7) vs. 114.5 (99.7, 131.4) pg/mg; p < 0.001] but with no significant difference between the villages or between hepatomegaly and normal groups [539.7 (436.7, 666.9) vs. 512.6 (297.3, 883.8) pg/mg], possibly because acute exposures during an aflatoxicosis outbreak in 2004 may have masked any potential underlying relationship.Conclusions: Exposure to aflatoxin was associated with childhood chronic hepatomegaly in 2002. These preliminary data suggest an additional health risk that may be related to aflatoxin exposure in children, a hypothesis that merits further testing.

Aflatoxin B1 Level in Relation to Child’s Feeding and Growth

To study the influence of sociological factors, breast feeding and weaning on aflatoxin exposure in children as well as to determine the effect of aflatoxin exposure on child's growth. A questionnaire, administered to the mothers of forty-six children, obtained information on the child's age, sex, residence, feeding, weaning and general health status. Maternal parity, education and occupation were also collected. Height for age Z-score (HAZ) and weight for age Z-score (WAZ) of children were calculated at the time of recruitment. TLC analysis was performed for aflatoxin B1 level in studied children and their mothers. Aflatoxin B1 was detected in 17 out of 46 (36.96%) of children's serum at a median concentration of 51.61 (30.565-62.795) ppm and in 17 out of 46 (36.96%) of mother's serum at a median concentration of 50 (35.59-84.93) ppm. Aflatoxin B1 level was neither affected by child's age, sex, residence whether rural or urban, maternal age, parity, education nor occupation. Aflatoxin B1 in breastfed patients was significantly lower than in non-breastfed ones (p = 0.034). Weight for age Z-score (WAZ) showed no significant difference between aflatoxin B1 negative and positive cases (p = 0.422) while height for age Z-score (HAZ) was significantly lower in aflatoxin B1 positive compared to negative cases (p = 0.001). A significant positive correlation between aflatoxin B1 in the present cases and their mothers (r = 0.881, p = 0.0001) and a significant negative correlation between aflatoxin B1 in present cases and their height-z-score (HAZ) (r = -0.460, p = 0.001) was detected. Breast feeding results in lower aflatoxin exposure. Also, a strong association between aflatoxin exposure and impaired child's growth exists.

Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning.

Dietary exposure to high levels of the fungal toxin, aflatoxin, occurs in West Africa, where long-term crop storage facilitates fungal growth. We conducted a cross-sectional study in Benin and Togo to investigate aflatoxin exposure in children around the time of weaning and correlated these data with food consumption, socioeconomic status, agro-ecological zone of residence, and anthropometric measures. Blood samples from 479 children (age 9 months to 5 years) from 16 villages in four agro-ecological zones were assayed for aflatoxin-albumin adducts (AF-alb) as a measure of recent past (2-3 months) exposure. Aflatoxin-albumin adducts were detected in 475/479 (99%) children (geometric mean 32.8 pg/mg, 95% CI: 25.3-42.5). Adduct levels varied markedly across agro-ecological zones with mean levels being approximately four times higher in the central than in the northern region. The AF-alb level increased with age up to 3 years, and within the 1-3 year age group was significantly (P = 0.0001) related to weaning status; weaned children had approximately twofold higher mean AF-alb adduct levels (38 pg AF-lysine equivalents per mg of albumin [pg/mg]) than those receiving a mixture of breast milk and solid foods after adjustment for age, sex, agro-ecological zone, and socioeconomic status. A higher frequency of maize consumption, but not groundnut consumption, by the child in the preceding week was correlated with higher AF-alb adduct level. We previously reported that the prevalence of stunted growth (height for age Z-score HAZ) and being underweight (weight for age Z-score WAZ) were 33% and 29% respectively by World Health Organziation criteria. Children in these two categories had 30-40% higher mean AF-alb levels than the remainder of the children and strong dose- response relationships were observed between AF-alb levels and the extent of stunting and being underweight. Exposure to this common toxic contaminant of West African food increases markedly following weaning and exposure early in life is associated with reduced growth. These observations reinforce the need for aflatoxin exposure intervention strategies within high-risk countries, possibly targeted specifically at foods used in the post-weaning period.

Modification of immune function through exposure to dietary aflatoxin in Gambian children.

Aflatoxins are immunotoxins that frequently contaminate staple foods in The Gambia and other parts of sub-Saharan Africa, resulting in high exposure throughout life. Impaired infant immune system development may be a key predictor of mortality from infectious disease. In this study we aimed to determine the effect of dietary aflatoxin exposure on a number of immune parameters in Gambian children. A cohort of 472 Gambian children 6-9 years of age was recruited. Serum aflatoxin-albumin (AF-alb) adducts were analyzed to provide a measure of exposure. Immune parameters included secretory IgA (sIgA) in saliva, cell-mediated immunity (CMI), determined using the CMI multitest where test antigens are applied to the skin, and antibody responses to both rabies and pneumococcal polysaccharide vaccines. Birth weight, current anthropometry, and micronutrient status were also recorded. AF-alb adducts were detected in 93% of the children (geometric mean level 22.3 pg/mg; range 5-456 pg/mg). AF-alb level was strongly influenced by month of sampling. In a multivariable analysis, sIgA was markedly lower in children with detectable AF-alb compared with those with nondetectable levels [50.4 micro g/mg protein (95% confidence interval [CI] 48.0-52.8) and 70.2 micro g/mg protein (95% CI 61.1-79.2), respectively; p < 0.0001]. Antibody response to one of four pneumococcal serotypes, but not rabies vaccine, was weakly associated with higher levels of AF-alb. There was no association between CMI responses to test antigens and AF-alb. These data confirm that children in rural Gambia are frequently exposed to high levels of aflatoxin. The study provides evidence that sIgA in saliva may be reduced because of dietary levels of aflatoxin exposure. Given the high burden of infection-related mortality in West Africa, further investigation of the immune effects of aflatoxin exposure in children is merited.