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: 9893782
• 负责人: Ivo J Mueller
• 金额: $ 31.83万
• 依托单位: INSTITUT PASTEUR
• 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 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893782
• 关键词: 4-aminoquinoline; Address; Affect; Antibodies; Antimalarials; Archives; Area; Artemisinins; Asia; Biological; Biological Assay; Biology; Biometry; Bite; Cambodia; Chronic; Clinical; Cohort Studies; Computer Simulation; Country; Cross-Sectional Studies; Culicidae; Data; Detection; Development; Disease; Drops; Drug resistance; Effectiveness; Epidemiology; Exposure to; Far East; Genomics; Genotype; Goals; Head; Health care facility; Hot Spot; Human; Immune response; Immunologics; Immunology; Individual; Infection; Integration Host Factors; Knowledge; Link; Liver; Longitudinal Studies; Longitudinal cohort study; Malaria; Membrane; Methods; Microscopic; Modeling; Molecular; Molecular Diagnosis; Movement; Papua New Guinea; Parasite resistance; Parasites; Pattern; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Play; Politics; Population; Population Group; Primary Infection; Relapse; Research Design; Residual state; Resistance; Resistance development; Resources; Risk; Risk Factors; Role; Salivary Proteins; Sampling; Series; Site; Systems Biology; Testing; Thailand; Variant; base; clinical effect; cohort; cost; density; design; disease transmission; epidemiologic data; epidemiology study; feeding; fitness; high risk; high risk population; high throughput screening; improved; in silico; infection risk; innovation; malaria infection; malaria transmission; mathematical model; molecular marker; multidisciplinary; next generation sequencing; novel strategies; programs; public health emergency; resilience; resistant Plasmodium falciparum; spatiotemporal; surveillance strategy; symposium; tool; transmission process; vector; vector mosquito

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.

摘要 由于亚太地区的目标是到2030年在整个区域消除疟疾，与此相关的一些关键挑战 由于疟疾传播的强烈变异，存在大量受感染的但 无症状个体和对一线抗疟疾治疗的抗药性的发展需要 对峙。此外，该地区间日疟原虫感染的优势导致了这一特殊挑战。 应对间日疟原虫催眠虫和复发感染的原因。亚太ICEMR项目是 提议在柬埔寨、巴布亚的3个地点进行一套协调一致的实地和深入生物学研究 新几内亚和泰国跨越了目前在亚太地区发现的传播强度范围 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是 通过结合大型横断面和纵向队列研究进行研究 优秀的流行病学研究设计，拥有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 临床防护。由此获得的信息将被用于评估改进的监视战略 通过计算机模拟和现场应用的创新组合。输电工程 将使用直接膜喂养试验作为异种诊断工具来确定感染性宿主 地点和调查宿主、寄生虫和宿主因素，这些因素有助于维持每个地方的地方性传播 地点。此外，我们将通过调查研究低传播环境下人与媒介接触的模式 人类抗按蚊唾液蛋白抗体作为蚊虫叮咬暴露的标志。这两个问题中的一个关键问题 研究表明青蒿素和伴侣耐药性如何影响慢性无症状寄生虫的适合性 感染性和传播性。最后，间日疟原虫复发项目将具体解决 间日疟原虫对对照组和对照组的抵抗力增强的长期肝脏阶段的复发感染 淘汰赛。这些研究的进行将使用空间上明确的疟疾传播模型，下一步- 基于世代测序(NGS)的高通量基因分型方法和一系列高通量和 将在3个资源核心中开发的体液免疫反应的功能分析。这些 因此，相互关联的多学科研究旨在确定和描述疟疾的关键步骤。 传播循环，从而更好地了解寄生虫、宿主和媒介因素 在密集的国家疟疾控制和消除方案的背景下继续传播。这 知识将有助于开发针对残存变速箱的新方法。