Impact of aflatoxin on health in Sub-Saharan Africa

Aflatoxins (AFs) are one of the major types of mycotoxins and are common contaminants of crops such as maize and groundnuts, especially in tropical and sub- tropical areas. Suitable climate for fungal growth, subsistence farming practices and dietary reliance on staple crops contribute to the chronic and high exposure to AFs in populations in sub-Saharan Africa. AFs have been identified as carcinogens. However, the impact on growth and immune functions have been less investigated in humans. In this work, aflatoxin exposure of populations from Gambia, Malawi and Tanzania was assessed using the aflatoxin-albumin (AF-alb) biomarker, in relation to various health outcomes. Very high levels of AF-alb were measured in blood samples from cases from the aflatoxicosis outbreak in Tanzania in 2016, which caused 20 deaths. Cases were also found to have abnormal level in liver and kidney function indicators. The Gambia study provided a novel evidence of aflatoxin effect on both innate and adaptive immune function in children through examining the association between aflatoxin exposure and thymus growth and antibody response to vaccination. A significant inverse association was determined in AF-alb level and thymus growth, especially during the first eight weeks of infancy. A potential synergistic effect of aflatoxin on antibody response to diphtheria vaccine was also found in these children. Aflatoxin may also cause damage to the gastro-intestinal tract. In the Malawi study, an association between aflatoxin exposure and environmental enteropathy has been identified. High levels of AF-alb were associated with increase in the expression of immune related genes. The potential molecular mechanism of AFs effect on immune function was examined in vitro using three cellular models. Significant stimulation of IL-6/STAT3 pathway by AFs have been determined in peripheral blood lymphocytes, Jurkat T cells and a human hepatocyte line HHL-16 at both mRNA and protein level. Overall, this study provides evidence that exposure to AFs in children could retard thymus growth, modulate antibody response to vaccination and immune related genes expression. The IL-6/STAT3 pathway also identified as a potential signalling pathway that AFs can modulate immune system through regulate this pathway and further investigation in vivo will be needed