Understanding, tracking and eliminating malaria transmission in the Asia - Pacific Region

了解、追踪和消除亚太地区的疟疾传播

• 批准号: 10368193
• 负责人: Ivo J Mueller
• 金额: $ 34.58万
• 依托单位: WALTER AND ELIZA HALL INST MEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-28 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368193
• 关键词: Understanding; tracking; eliminating; malaria; transmission

Summary As the Asia-Pacific aim to eliminate malaria from the entire region by 2030, a number of key challenges related to increasing strong variations in malaria transmission, the presence of a large reservoir of infected but asymptomatic individual and the development of resistance to frontline antimalarial treatment need to be confronted. In addition, the predominance of P. vivax infections in the region results in the particular challenge of dealing with P. vivax hypnozoites and the relapsing infections the cause. The Asia-Pacific ICEMR project is proposing to conduct coordinated set of field and in-depth biological studies in 3 sites in Cambodia, Papua New Guinea and Thailand that span the range of transmission intensities currently found in the Asia-Pacific regions. In the Epidemiology Project spatio-temporal patterns of risk of malaria infection and disease will be investigate through a combination of large cross-sectional and longitudinal cohort studies that combine excellent epidemiological study designs with state-of-the-art molecular detection and genotyping of Plasmodium spp. infections and an assessment of host immune responses and their link to exposure and clinical protection. The information thus gained will be used to evaluate improved surveillance strategies through an innovative combination of computer simulations and field application. The Transmission Project will use direct membrane feeding assay as a xenodiagnostic tool to determine the infective reservoir as each site and investigate host, parasite and host factors that contribute to sustaining endemic transmission at each site. In addition, we will study patterns of human-vector contact in low transmission settings by investigating human antibodies to anopheline salivary protein as marker exposure to mosquito bites. A key question in both studies is how artemisinin and partner drug resistance affects parasite fitness both in chronic asymptomatic infections and transmissibility. Finally, the P. vivax Relapse Project will specifically address the role of relapsing infections from long-lasting liver stages in the increased resilience of P. vivax against control and elimination. The conduct of these studies will use spatially explicit malaria transmission models, next- generation sequencing (NGS)-based high-throughput genotyping methods and a range of high-throughput and functional assay of humoral immune responses that will be developed in 3 resource cores. These interconnected, multi-disciplinary studies thus aim to identify and characterize critical steps in malaria transmission cycle and thereby gain a better understanding of parasite, host and vector factors that contribute to continued transmission in the context of intensive national malaria control and elimination programs. This knowledge will assist in the development of novel approaches to target residual transmission pockets.

概括 亚太地区的目标是到 2030 年在整个地区消除疟疾，因此存在一些与疟疾相关的关键挑战 疟疾传播的变异性越来越大，存在大量受感染但 无症状个体以及对一线抗疟治疗产生耐药性的情况需要 面对。此外，该地区间日疟原虫感染占主导地位，导致了特殊的挑战 处理间日疟原虫休眠子及其病因的复发感染。亚太地区 ICEMR 项目 提议在柬埔寨、巴布亚的 3 个地点开展协调一致的实地和深入生物学研究 新几内亚和泰国的传播强度范围与亚太地区目前的传播强度相当 地区。在流行病学项目中，疟疾感染和疾病风险的时空模式将被 通过大型横断面和纵向队列研究的结合进行调查 出色的流行病学研究设计，采用最先进的分子检测和基因分型 疟原虫属感染和宿主免疫反应的评估及其与暴露和感染的联系 临床防护。由此获得的信息将用于评估改进的监测策略 通过计算机模拟和现场应用的创新结合。输电工程 将使用直接膜喂养测定作为异种诊断工具来确定每个病毒的感染储库 现场调查并调查有助于每个地区维持地方性传播的宿主、寄生虫和宿主因素 地点。此外，我们将通过调查研究低传播环境中人与媒介接触的模式 人类按蚊唾液蛋白抗体作为暴露于蚊虫叮咬的标记。两者中的一个关键问题 研究青蒿素及其伴侣耐药性如何影响慢性无症状寄生虫的适应性 感染性和传播性。最后，间日疟原虫复发项目将专门解决 间日疟原虫抵抗控制和抵抗力增强的持久肝脏阶段的复发性感染 消除。这些研究的进行将使用空间明确的疟疾传播模型，接下来- 基于世代测序（NGS）的高通量基因分型方法以及一系列高通量和 体液免疫反应的功能测定将在 3 个资源核心中开发。这些 因此，相互关联的多学科研究旨在确定和描述疟疾治疗的关键步骤 传播周期，从而更好地了解导致传播的寄生虫、宿主和媒介因素 在加强国家疟疾控制和消除计划的背景下继续传播。这 知识将有助于开发针对残留传播区域的新方法。