Malarial Impact on Neurobehavioral Development (MIND)

疟疾对神经行为发育（MIND）的影响

• 批准号: 10405271
• 负责人: Paul Bangirana
• 金额: $ 8.24万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405271
• 关键词: 5 year old; Adolescence; Adult; Affect; Africa South of the Sahara; Age; Area; Cerebral Malaria; Child; Childhood; Chronic; Cognition; Cognitive; Data; Development; Early Intervention; Economics; Enrollment; Immune response; Immunologics; Impairment; Intervention; Lead; Malaria; Mental Health; Metabolic; Neurobehavioral Manifestations; Pathogenesis; Predictive Factor; Prospective Studies; Quality of life; Retrospective Studies; Risk Factors; Study Skills; Testing; cognitive skill; cohort; cost; economic cost; emerging adult; functional disability; improved; malarial anemia; neurobehavioral; prevent; prospective; public health relevance; research study; skills; social; societal costs; socioeconomics; young adult

ABSTRACT Cerebral malaria (CM) and severe malarial anemia (SMA) are estimated to affect >500,000 children and 1-5 million children, respectively, in sub-Saharan Africa annually. Our research studies in Ugandan children have demonstrated that CM and SMA are associated with significant neurobehavioral impairment (NBI). Our data suggest that: 1) the pathogenesis of CM and SMA-related NBI differs; 2) CM and SMA lead to greater NBI than other forms of severe malaria; 3) NBI persists for at least 2 years; and 4) several host immune response factors are associated with NBI in children ≥5 years of age but not in children <5 years of age. Retrospective studies suggest NBI is present up to 9 years after CM, but there are no prospective studies on the duration of NBI after CM beyond 2 years, or on chronic cognitive or mental health sequelae of other forms of severe malaria such as SMA. We prospectively enrolled >1,700 children in 3 studies that assessed NB sequelae of severe malaria. These studies provide a unique cohort in which to assess the effects of the 5 major forms of severe malaria on long-term cognition and mental health. We propose to study ~1,100 of these children 4-20 years after their severe malaria episode, to answer 3 key questions: 1) Do NB sequelae of severe malaria persist through childhood into adulthood, and do they differ by form of severe malaria? 2) What are the long- term functional and economic costs of these sequelae? 3) What are the risk factors for long-term NBI, and are some factors identifiable only as children grow older and acquire specific cognitive skills? The study’s central hypotheses are that: 1) NBI after severe malaria differs by type of severe malaria and age at episode; 2) these impairments have significant social, economic and quality of life costs; and 3) risk factors for impairment may become apparent only after 5 years of age. Our study has 3 Aims. Aim 1 is to establish the duration and age- specific manifestations of neurobehavioral sequelae of severe malaria from childhood to early adulthood. Aim 2 is to determine the functional and economic costs of neurobehavioral sequelae of severe malaria. Aim 3 is to identify the metabolic, immunologic and parasitic factors predictive of long-term neurobehavioral and functional impairment after severe malaria. We predict that severe malaria-related NBI will persist into adolescence and young adulthood, leading to substantial societal and economic costs, and that a number of risk factors for impairment will be detectable only as the child gets older and can be tested for higher level skills. Identification of risk factors present at a young age will allow for early intervention. We expect the study will constitute a major advance in the understanding of the neurobehavioral, functional and socioeconomic costs of severe malaria, and form the basis for focused interventions that can prevent or decrease neurobehavioral impairment in the millions of children who suffer from severe malaria.

抽象的 据估计，脑型疟疾 (CM) 和严重疟疾贫血 (SMA) 将影响超过 500,000 名儿童和 1-5 名儿童。 撒哈拉以南非洲地区每年分别有 100 万名儿童。我们对乌干达儿童的研究表明 证明 CM 和 SMA 与显着的神经行为损伤 (NBI) 相关。我们的数据 提示：1）CM和SMA相关NBI的发病机制不同； 2) CM 和 SMA 导致 NBI 大于 其他形式的严重疟疾； 3）NBI持续至少2年； 4）几种宿主免疫反应 这些因素与 5 岁以上儿童的 NBI 相关，但与 5 岁以下儿童的 NBI 无关。回顾性 研究表明 NBI 在 CM 后长达 9 年都存在，但没有关于持续时间的前瞻性研究 CM 超过 2 年后，或其他形式的严重慢性认知或心理健康后遗症的 NBI 疟疾，例如 SMA。我们前瞻性地招募了超过 1,700 名儿童参与 3 项评估 NB 后遗症的研究 严重的疟疾。这些研究提供了一个独特的队列来评估 5 种主要形式的影响 严重疟疾对长期认知和心理健康的影响。我们建议对这些 4-20 岁儿童中的约 1,100 名进行研究 严重疟疾发作多年后，回答 3 个关键问题：1) NB 严重疟疾后遗症吗 从童年一直持续到成年，它们的严重疟疾形式有何不同？ 2）什么是长- 这些后遗症的功能和经济成本是多少？ 3) 长期NBI的风险因素有哪些？ 有些因素只有当孩子长大并获得特定的认知技能时才能识别？该研究的中心 假设是： 1) 严重疟疾后的 NBI 因严重疟疾类型和发病年龄而异； 2）这些 损伤会造成巨大的社会、经济和生活质量成本； 3) 减值的风险因素可能 5岁以后才明显。我们的研究有 3 个目标。目标 1 是确定持续时间和年龄 儿童期至成年早期严重疟疾神经行为后遗症的具体表现。 目标 2 是确定严重疟疾神经行为后遗症的功能和经济成本。目标 3 是为了确定预测长期神经行为的代谢、免疫和寄生因素 严重疟疾后功能障碍。我们预测，与疟疾相关的严重 NBI 将持续到 青春期和青年期，导致巨大的社会和经济成本，并且许多 只有当孩子长大后才能检测到损伤的风险因素，并且可以进行更高水平的测试 技能。识别年轻时存在的危险因素将有助于早期干预。我们期待这项研究 将构成对神经行为、功能和社会经济理解的重大进步 严重疟疾的成本，并构成预防或减少重点干预措施的基础 数百万患有严重疟疾的儿童的神经行为受损。