Grant: Project Grant

Despite important gains over the last decades, infectious diseases continue to account for almost half of the global burden of disease in sub-Saharan Africa. Factors such as inadequate sanitation, difficult access to clean water, deficient health care systems and incomplete vaccine coverage are important determinants of infectious disease occurrence, accumulating evidence suggests that exposure to environmental immunotoxicants may play a role. DDT and pyrethroid insecticides are commonly used as part of Indoor Residual Spraying (IRS) programs, resulting in high exposure to children. Residents of IRS areas often use solid fuels such as wood and other biomass, which causes high exposure to household air pollution (HAP). Experimental in vitro and in vivo studies suggest that postnatal exposure to DDT, pyrethroids and HAP may inhibit immune response to vaccines and trigger allergic airway diseases. However, few human studies have investigated the question and no study has evaluated the combined effect of insecticides and HAP. The objective of this proposal is to characterize postnatal exposure to DDT, pyrethroid insecticides and PM2.5, and to determine whether exposure to these contaminants impact the immune system among highly-exposed South African children. Specifically, we aim to: 1. Characterize the levels, sources and determinants of exposure to DDT/E, pyrethroid insecticides and PM2.5 in rural South African children. 2. Determine whether exposure to DDT/E, pyrethroid insecticides and/or PM2.5 is associated with altered immunity between ages 6.5 and 8 years. We will determine whether 3. Determine whether exposure to DDT/E, pyrethroid insecticides and/or PM2.5 is associated with evidence of allergic airway disease between ages 6.5 and 8 years. For Aims 2 and 3, we will evaluate whether poverty, malnutrition and exposure to HIV enhance toxicity and whether insecticides and PM2.5 have supra-additive (synergistic) effects.