Emerging zoonotic malaria in Malaysia: strengthening surveillance and evaluating population genetic structure to improve regional risk prediction tools

马来西亚新出现的人畜共患疟疾：加强监测和评估人群遗传结构以改进区域风险预测工具

• 批准号: 10217295
• 负责人: Giri Rajahram
• 金额: $ 13.55万
• 依托单位: INFECTIOUS DISEASE SOCIETY KOTA KINABALU
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10217295
• 关键词: 2019-nCoV; Address; Antigen Targeting; Biological; Borneo; Case Study; Cessation of life; Clinical; Communicable Diseases; Country; Culicidae; Data; Data Set; Databases; Detection; Diagnosis; Disease; Epidemiological trend; Epidemiology; Evaluation; Fever; Genetic; Genome; Genomics; Genotype; Goals; Government; Health; Health care facility; Hospitals; Human; Immunity; Incidence; Indonesia; Infection; Malaria; Malaysia; Malaysian; Maps; Methods; Microscopy; Molecular; Monitor; Monkeys; Outcome Study; Parasites; Pattern; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium vivax; Population; Population Distributions; Pregnancy; Prevalence; Prevention; Public Health; Reporting; Resolution; Risk; Sabah; Sampling; Serology; Seroprevalences; Severity of illness; Southeastern Asia; Spatial Distribution; Structure; Surveys; Time; Training; Update; Zoonoses; anthropogenesis; authority; base; burden of illness; clinical diagnostics; clinical phenotype; data tools; detection method; detection platform; disease transmission; forest; improved; land use; novel; pathogen; population genetic structure; programs; public health priorities; remote sensing; risk prediction; screening; spatiotemporal; surveillance strategy; surveillance study; targeted sequencing; tool; transmission process; trend

Project Summary/Abstract Southeast Asia remains a global hotspot for emerging zoonotic infectious diseases. The recent increase in transmission of the monkey malaria parasite Plasmodium knowlesi, endemic to Southeast Asia, exemplifies how land-use change can drive disease spill-over to humans. In Malaysia, P. knowlesi now accounts for the vast majority of malaria cases and is the predominant cause of malaria-related deaths. Recent reports suggest that P. knowlesi is also the predominant species in parts of western Indonesia, and that due to misidentification by microscopy, under-diagnosis is likely widespread across the region. Molecular surveillance is essential for monitoring the emergence of zoonotic P. knowlesi, informing malaria control strategies, and assessing progress towards elimination of the human-only malaria species. In this study in Sabah, Malaysia, we firstly plan to further improve molecular state-wide malaria surveillance detection systems to monitor for changing epidemiological and clinical features of disease, including in pregnancy, which potentially could occur with adaption of P. knowlesi to human-human transmission. We will supplement these data with targeted longitudinal health facility surveys of healthy and febrile attendees to understand the true burden of asymptomatic or submicroscopic P. knowlesi infections, in addition to screening for other simian malaria species such as P. cynomolgi. A high-throughput multiplex serological malaria surveillance platform will also be used to integrate recently developed novel antigens targeting P. knowlesi. This platform will enable evaluation of population-level markers of P. knowlesi exposure and transmission intensity in the context of potential waning cross-species immunity from other human malaria species, and allow concurrent assessment of other public health priorities including SARS-CoV-2. Secondly, recent advances in multiplexed deep targeted sequencing of microhaplotypes offer potential advantages if these tools are adapted for P. knowlesi. Our previous surveillance study collected >5500 P. knowlesi isolates, and we plan to develop novel genome-based tools to evaluate P. knowlesi population structure at sufficient resolution to understand increasing transmission and disease severity in Sabah, and relate these findings to elsewhere in Southeast Asia. Finally, we will also use an updated georeferenced database of state-wide P. knowlesi cases over time to characterise changing fine spatial scale incidence patterns, and to generate regional predictive P. knowlesi risk mapping incorporating environmental remote-sensing satellite data and predicted human, monkey and mosquito population distributions to inform and guide planning, surveillance and prevention activities in other countries in the region at risk of P. knowlesi transmission.

项目摘要/摘要 东南亚仍然是新兴的人畜共患感染疾病的全球热点。最近 猴子疟疾寄生虫疟原虫的传播增加了 东南亚，体现了土地利用变化如何将疾病溢出到人类中。在 马来西亚，P。Knowlesi现在占绝大多数疟疾病例，是 与疟疾相关死亡的主要原因。最近的报告表明，P。Knowlesi也是 印度尼西亚部分地区的主要物种，并且由于显微镜错误识别， 整个地区可能会广泛诊断。分子监视对于 监视人畜共患病的出现，告知疟疾控制策略，并 评估消除只有人类疟疾物种的进展。 在马来西亚沙巴的这项研究中，我们首先计划进一步改善全州分子疟疾 监视检测系统，以监测改变流行病学和临床特征 疾病，包括怀孕，可能会随着P. knowlesi的适应而发生的疾病 人类传播。我们将通过有针对性的纵向健康补充这些数据 对健康和高温参与者的设施调查，以了解无症状或 除筛查其他猿猴种类外 例如cynomolgi。高通量多重血清学疟疾监测平台将 还用于整合最近开发的新型抗原，靶向P. Knowlesi。这个平台 将能够评估P. knowlesi暴露和传播的人口水平标记 在潜在减弱的跨物种免疫力的背景下，强度是其他人类疟疾的 物种，并允许对包括SARS-COV-2在内的其他公共卫生重点进行评估。 其次，多重深度靶向测序的最新进展提供了 如果这些工具适用于P. Knowlesi，那么潜在的优势。我们以前的监视研究 收集> 5500 P.诺尔斯分离株，我们计划开发基于基因组的新工具来评估 P. Knowlesi人口结构以足够的分辨率了解增加的传播和 沙巴的疾病严重程度，并将这些发现与东南亚其他地方联系起来。最后，我们会的 还使用更新的全州范围的地理专用数据库P. Knowlesi案例随着时间的推移 表征更改良好的空间尺度发生率模式并产生区域预测P。 Knowlesi风险映射包含环境遥感卫星数据并预测 人类，猴子和蚊子人口分布，以告知和指导计划，监视 以及该地区其他国家的预防活动，有诺尔斯氏菌的传播风险。