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: 9263459
• 负责人: Ivo J Mueller
• 金额: $ 69.02万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263459
• 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; 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; innovation; malaria infection; malaria transmission; mathematical model; molecular marker; multidisciplinary; next generation sequencing; novel strategies; programs; public health emergency; resilience; 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.

概括 作为到2030年，亚太地区的目标是消除整个地区的疟疾，许多关键挑战与 为了增加疟疾传播的强烈变化，存在大量感染的储层，但 无症状的个体以及对前线抗疟疾治疗的抗性的发展需要 面对。另外，该区域中疟原虫感染的优势导致了特定的挑战 与Vivax P. hypnozoite和复发感染的原因有关。亚太ICEMR项目是 提议在柬埔寨的3个地点进行协调的现场和深入的生物学研究 新几内亚和泰国跨越了亚太目前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时空模式将是 通过大型横截面和纵向队列研究的结合进行调查，该研究结合了 具有最先进的分子检测和基因分型的优秀流行病学研究设计 疟原虫属。感染和评估宿主免疫反应及其与暴露的联系 临床保护。因此获得的信息将用于评估改进的监视策略 通过计算机模拟和现场应用的创新组合。传输项目 将使用直接膜喂养测定作为Xenodiagnostic工具，以确定感染性储层 站点并调查宿主，寄生虫和宿主因素，导致每种持续的地方性传播 地点。此外，我们将通过研究低传输设置中人类矢量接触的模式 人类垂直唾液蛋白的人类抗体是暴露于蚊子叮咬的标志物。两者的关键问题 研究是青蒿素和伴侣耐药性如何影响慢性无症状的寄生虫健康 感染和传播性。最后，维瓦克斯复发项目将专门解决 在维瓦克斯对照和对照组的弹性增加中，来自持久肝脏阶段的感染感染和 消除。这些研究的进行将使用空间明确的疟疾传播模型，其次 基于生成测序（NGS）的高通量基因分型方法以及一系列高通量和 将在3个资源核心中开发的体液免疫反应的功能测定。这些 因此，相互联系的多学科研究旨在识别和表征疟疾的关键步骤 传输周期，从而更好地了解寄生虫，宿主和向量因素 在强化国家疟疾控制和消除计划的背景下继续传播。这 知识将有助于开发新的方法，以靶向剩余的传输袋。