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 亿人感染疟疾，导致 88 万人死亡，其中主要是五岁以下的非洲儿童。许多疟疾流行国家使用室内滞留喷洒（IRS），即在房屋内墙上喷洒二氯二苯三氯乙烷（DDT）或拟除虫菊酯杀虫剂来控制疟疾。对长期、高浓度滴滴涕接触所造成的意外后果的担忧引起了广泛的国际争论。例如，《关于持久性有机污染物的斯德哥尔摩公约》旨在禁止滴滴涕，而世界卫生组织和美国国际开发署则促进和/或资助国税局，包括使用滴滴涕。 DDT 和拟除虫菊酯是昆虫和动物的神经毒物。主要在低至中等接触水平的西方人群中进行的人体研究表明，产前接触滴滴涕及其分解产物 DDE 可能会对儿童的神经发育产生不利影响。 DDT/E 暴露还与甲状腺功能、妊娠持续时间和出生体重的不利影响以及整体 DNA 甲基化的变化有关，这可能是神经发育受损的途径。尽管几乎没有针对拟除虫菊酯对人类健康影响的研究，但对啮齿类动物的研究表明，滴滴涕单独或协同作用都会对神经发育产生有害影响。没有研究评估人类接触 DDT 和/或拟除虫菊酯对 IRS 背景下神经发育的影响。我们建议通过检查接触 IRS 杀虫剂和神经发育之间的关系以及出生队列研究中可能的介质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，并对她们的孩子进行为期 24 个月的跟踪，前瞻性评估暴露情况和神经发育情况。我们利用了一项自然实验，其中海拔的梯度会影响蚊子的生存，进而影响 IRS 的使用，但喷过药和未喷过药的村庄在其他方面是相似的，例如人口统计。我们提出的研究将是第一个：1）评估 IRS 处理的家庭中孕妇和婴儿接触 IRS 杀虫剂的水平和决定因素； 2）研究非常高的DDT/E和拟除虫菊酯暴露对人类神经发育的影响； 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加剧这些暴露对健康的影响。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 模型来量化婴儿子宫内、母乳和其他产后环境暴露的相对贡献，以及使用最先进的表观遗传学确定环境暴露是否会改变胎儿组织中 DNA 甲基化的方法。 本研究旨在提供数据来评估不同疟疾控制方法的风险/效益，并制定适当的干预措施以减少孕妇和儿童的接触。