IRS insecticides for malaria control and child neurodevelopment in South Africa

IRS 杀虫剂用于南非疟疾控制和儿童神经发育

• 批准号: 8323153
• 负责人: Brenda Eskenazi
• 金额: $ 63.71万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-25 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8323153
• 关键词: Address; Adverse effects; Affect; African; Age; Age-Months; Agency for International Development; Altitude; Animals; Anopheles Genus; Area; Benefits and Risks; Birth; Birth Weight; Blood; Body Weight Changes; Breast Feeding; Cessation of life; Chemical Exposure; Chemicals; Child; Chronic; Cognition; Cohort Studies; Communities; Country; Culicidae; DNA Methylation; Data; Development; Dichlorodiphenyl Dichloroethylene; Enrollment; Environment; Environmental Exposure; Environmental Health; Epigenetic Process; Europe; Exposure to; Fetal Growth; Fetal Growth Retardation; Fetal Tissues; Funding; Goals; Health; Home environment; Hospitals; Housing; Human; Human Milk; Infant; Insecta; Insecticides; International; Intervention; Knowledge; Location; Low Birth Weight Infant; Malaria; Malnutrition; Measures; Mediating; Mediator of activation protein; Memory; Methods; Modeling; Mothers; Natural experiment; Neonatal; Neurotoxins; Outcome; Pathway interactions; Perinatal Exposure; Population; Postpartum Period; Poverty; Pregnancy; Pregnant Women; Premature Birth; Recording of previous events; Relative (related person); Relative Risks; Research; Residual state; Risk; Rodent; Rural; Sampling; Serum; South Africa; Techniques; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Toxic effect; Trichloroethanes; Umbilical Cord Blood; Woman; World Health Organization; base; cohort; exposed human population; fetal blood; human data; human tissue; in utero; neonate; neurobehavioral; neurodevelopment; parity; pharmacokinetic model; pollutant; postnatal; prenatal exposure; pyrethroid

DESCRIPTION (provided by applicant): Every year, 250 million people are infected with malaria, resulting in 880,000 deaths, primarily to African children under age five. Many malaria-endemic countries use Indoor Residual Spraying (IRS), the application of dichlorodiphenyl trichloroethane (DDT) or pyrethroid insecticides to interior walls of homes, to control malaria. Concerns regarding the unintended consequences of chronic, high-level DDT exposure have resulted in considerable international debate. For example, the Stockholm Convention on Persistent Organic Pollutants aims to ban DDT, while the World Health Organization and the U.S. Agency for International Development promote and/or fund IRS, including with DDT. DDT and pyrethroids are neurotoxicants in insects and animals. Human studies, primarily conducted in Western populations with low to moderate levels of exposure, suggest that prenatal exposure to DDT and its breakdown product, DDE, may adversely affect children's neurodevelopment. DDT/E exposure has also been related to adverse effects on thyroid function, gestational duration and birth weight, and changes in global DNA methylation, which could serve as pathways for compromised neurodevelopment. Although there is virtually no research in humans on the health effects of pyrethroids, research in rodents has shown detrimental effects on neurodevelopment both independently and synergistically with DDT. No study has evaluated the impact of human exposure to DDT and/or pyrethroids on neurodevelopment in the context of IRS We propose to address these important knowledge gaps by examining relationships between exposure to IRS insecticides and neurodevelopment, and possible mediators in a birth cohort study. We aim to enroll 750 rural South African mothers and to follow their children for 24 months, assessing exposures and neurodevelopment prospectively. We take advantage of a natural experiment where gradations in altitude impact mosquito survival and, by extension, use of IRS, but sprayed and unsprayed villages are otherwise similar, e.g, demographically. Our proposed study will be the first to: 1) assess levels and determinants of IRS insecticide exposure to pregnant women and infants in IRS-treated homes; 2) study the effects of very high DDT/E and pyrethroid exposures on human neurodevelopment; 3) assess the relative and synergistic health impacts of alternative IRS insecticides; and 4) evaluate whether poverty, malnutrition and poor health potentiate the health effects of these exposures. We will introduce two techniques with wider implications for environmental health science: the use of PBPK models to quantify the relative contributions of in utero, breast milk, and other postnatal environmental exposures in infants, and the use of state-of-the-art epigenetic methods to determine whether environmental exposures can alter DNA methylation in fetal tissue. This study aims to provide data to evaluate the risk/benefit of different methods of malaria control and for the development of appropriate interventions to reduce exposure to pregnant women and children.

描述（由申请人提供）：每年，有2.5亿人感染了疟疾，导致880,000人死亡，主要是五岁以下的非洲儿童。许多疟疾流行国家使用室内残留喷涂（IRS），二氯二苯三氯乙烷（DDT）或拟除虫菊酯杀虫剂的应用到房屋内壁，以控制疟疾。对慢性高级滴滴涕暴露的意外后果的担忧导致了大量国际辩论。例如，斯德哥尔摩持续性有机污染物公约旨在禁止DDT，而世界卫生组织和美国国际发展机构促进和/或资金IR，包括与DDT在内的IRS。 DDT和拟除虫菊酯是昆虫和动物中的神经毒性。人类研究主要是在暴露水平低到中等水平的西方人群中进行的，这表明对DDT及其分解产物DDE的暴露可能会对儿童的神经发育产生不利影响。 DDT/E暴露也与对甲状腺功能，妊娠持续时间和出生体重的不利影响以及全球DNA甲基化的变化有关，这可能是神经发育受损的途径。尽管人类几乎没有关于拟除虫菊酯的健康影响的研究，但对啮齿动物的研究表明，对神经发育有害，与DDT独立和协同作用。在IRS的背景下，没有研究人类对DDT和/或拟除虫菊酯对神经发育的影响，我们建议通过检查对IRS杀虫剂与神经发育之间的关系，以及在出生队列研究中可能的介体之间的关系来解决这些重要的知识差距。我们的目标是招募750名南非农村母亲，并跟随他们的孩子24个月，对暴露和神经发育进行预期。我们利用自然实验的优势，在该实验中，高度的渐变会影响蚊子的生存，并扩展使用IRS，但是喷涂和无喷雾的村庄在其他人的人口统计学上是相似的。我们提出的研究将是第一个：1）评估IRS杀虫剂暴露于IRS治疗房屋中孕妇和婴儿的水平和决定因素； 2）研究非常高的DDT/E和拟除虫菊酯暴露对人神经发育的影响； 3）评估替代IRS杀虫剂的相对和协同健康影响； 4）评估贫困，营养不良和健康状况不佳是否会增强这些暴露的健康影响。我们将介绍两种对环境健康科学具有更广泛影响的技术：使用PBPK模型来量化婴儿，母乳和其他出生后环境暴露的相对贡献，以及使用最先进的表观遗传学方法来确定是否可以改变胎儿组织中DNA甲基化的DNA甲基化。 这项研究旨在提供数据，以评估不同疟疾控制方法的风险/益处，以及制定适当的干预措施以减少孕妇和儿童的接触。