Prevalence of Chronic Aflatoxin Exposure and the Resultant Clinical-immunological Effects in Children in Makueni County, Kenya

Abstract

Globally, approximately three million children die each year from vaccine preventable infectious diseases mainly in developing countries. Despite the success of the expanded immunization program, not all infants and children around the world develop the same protective immune response to the same vaccine. An ideal vaccine must be able to induce a response over the basal immune response that may be largely driven by environmental and other population specific and socio-economic factors. Mycotoxins such as aflatoxins and fumonisins are immune suppressants and are confirmed to interfere with both cell-mediated and acquired immunity. The mechanism of aflatoxin toxicity of aflatoxin is linked to the binding of the bio- activated AFB1-8, 9-epoxide to cellular macromolecules. Methods: We studied Hepatitis B surface antibodies [anti-HBs] levels to explore the immune modulation effects of dietary exposure to aflatoxins in children aged between one and fourteen years in Kenya. Hepatitis B vaccine was introduced for routine administration for Kenyan infants in November 2001. To assess the effects of Aflatoxin on immunogenicity of childhood vaccines Aflatoxin B1-lysine in blood serum samples were determined using High Performance Liquid Chromatography with Fluorescence detection while anti- HBs were measured using Bio-ELISA anti-HBs kit. Main Objective: To determine prevalence and clinical-immunologic effects of chronic exposure to aflatoxin in 410 asymptomatic children aged 1-14 years in Makueni County, Kenya. Methodology: This was a Cross sectional study. Serum aflatoxin-B1 lysine adduct (AFB1) was the measure of exposure and High Performance Liquid Chromatography with Fluorescent detection was used for this. Hepatitis Bs antibody levels (anti-HBs)- measured using Bio-Elisa anti-HBs kit-was the outcome measure. Wealth index and dietary diversity scores, anthropometry, liver function tests, blood counts, 8 cytokine markers, grain aflatoxin levels and fumonisin levels in urine were recorded. xix xix xix Results: AFB1 was detected in 100% of the children; geometric mean 20.4, median 19.98 (range of 0.74- 901.15) all in pg/mg albumin. Only 98/205 (47.8%) of the study population had protective antibodies for Hepatitis B surface antibodies. High AFB1 was associated with 73% increased odds of low anti-HBs. For every unit rise in AFB1, anti-HBs dropped by .91mIU/ml (OR 0.35; 95% CI 0.15-0.81, p<0.01). Females had 65% reduced odds of having low antibodies (OR 0.35; 95%CI 0.15-0.81 p<0.01). Malnourished children had a 35-fold increased risk of having high AFB1. 7 out of 8 cytokines showed a down-regulated trend that was not statistically significant. Socio-economic status was significantly associated with AFB1 exposure (p< 0.01) and dietary diversity scores (p< 0.003). There was high co-occurrence of fumonisin and AFB1 in the study population. Conclusions Aflatoxin was found in the serum of 100% of the studied population of children of Makueni County. More than half of the studied population (52%) did not have protective anti-HBs antibodies possibly associated with aflatoxin exposure. Despite the decline in the rate of stunting of children in Makueni County, the malnourished children were more at risk of having high aflatoxin. This study showed not only a high exposure to aflatoxin in asymptomatic children in the study area but also a direct relationship between poverty, dietary diversity and aflatoxin exposure. Co-occurrence of fumonisins with aflatoxin was high in this community. Fumonisins independently depressed immune response in this study. There is a compelling need to investigate if the other routinely administered vaccines behave similarly in the children highly exposed to aflatoxin.