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Introduction
The World Health Organization (WHO) reported that there were 214 million cases of malaria in 2015, resulting in about 438,000 deaths, with most deaths occurring in children under 5 y of age (WHO 2015). Increased prevention and control measures have led to a 60% reduction in global malaria mortality rate since 2000 (WHO 2015). Indoor residual spraying (IRS), or systematic insecticide application to the interior walls of homes to kill malaria-infected mosquitoes as they rest, is one of the main techniques for controlling the Anopheles mosquito vector. In malarial-endemic regions of South Africa, IRS with dichlorodiphenyltrichloroethane (DDT) has been ongoing since 1946 (Bouwman et al. 2006), even as DDT use was effectively banned in most Western countries due to its toxicity. DDT and its main breakdown product, dichlorodiphenyldichloroethylene (DDE), have long half-lives in the human body (6 y and up to 10 y, respectively) and in the environment (ATSDR 2002; Longnecker 2005; Wolff et al. 2000). In recent years, pyrethroids, such as alpha-cypermethrin or deltamethrin, have become South Africa’s IRS insecticides of choice (Hlongwana et al. 2013). Unlike DDT, pyrethroids are rapidly metabolized and have short half-lives in humans (hours to days) (Barlow et al. 2001), and are still widely used in global agriculture (van Balen et al. 2012). Both DDT and pyrethroids are neurotoxic in developing animals through a number of mechanisms, including effects on cholinergic muscarinic receptors and on the sodium channels of axons (Eriksson et al. 1992; Malik et al. 2017). In addition, both DDT (Patisaul and Adewale 2009) and some pyrethroids (Ben Slima et al. 2017) are endocrine disruptors. Without question, effective prevention of malaria is of critical importance to human health; nonetheless, there is growing concern about the potential health effects of IRS insecticides on developing children given their demonstrated neurotoxicity in animals (Mandhane and Chopde 1997; Nasuti et al. 2003) and suggested evidence of developmental neurotoxicity in humans.
The majority of studies investigating DDT exposure and children’s neurobehavioral development have focused on its main breakdown product, DDE, and have found null (Eskenazi et al. 2006; Gaspar et al. 2015; Gladen et al. 1988; Jusko et al. 2012; Lyall et al. 2017; Pan et al. 2009; Ribas-Fitó et al. 2006; Rogan and Gladen 1991; Torres-Sánchez et al. 2007) or...