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

项目摘要/摘要 东南亚仍然是新发人畜共患传染病的全球热点地区。最近的 猴疟疾寄生虫诺氏疟原虫传播增加，地方性 东南亚的这一案例说明了土地利用的变化如何会导致疾病蔓延到人类身上。在……里面 在马来西亚，诺氏疟原虫现在占疟疾病例的绝大多数，是 疟疾相关死亡的主要原因。最近的报道表明，诺氏拟青霉也是 印度尼西亚西部部分地区的优势物种，以及由于显微镜下的错误识别， 诊断不足的情况可能在整个地区都很普遍。分子监测对于 监测诺氏疟原虫的出现，为疟疾控制战略提供信息；以及 评估在消灭仅由人类传播的疟疾物种方面取得的进展。 在马来西亚沙巴州的这项研究中，我们首先计划进一步改善全州范围的疟疾分子 监测监测系统，以监测肺炎的流行病学和临床特征的变化 疾病，包括在怀孕期间，这可能会发生，因为诺氏疟原虫适应于 人际传播。我们将用有针对性的纵向健康来补充这些数据 方便对健康和发烧的参与者进行调查，以了解无症状或 除了筛查其他猿类疟疾物种外，诺氏疟原虫亚显微感染 如食蟹猴等。一个高通量的多重血清学疟疾监测平台将 也可用于整合最近开发的针对诺氏疟原虫的新型抗原。这个平台 将能够评估诺氏肺孢子虫暴露和传播的人口水平标志 其他人类疟疾的跨物种免疫力可能减弱的情况下的强度 并允许同时评估包括SARS-CoV-2在内的其他公共卫生优先事项。 其次，微单倍型多重深度定向测序的最新进展提供了 如果这些工具适用于诺氏疟原虫，则具有潜在的优势。我们之前的监视研究 收集了5500株诺氏肺孢子虫分离株，我们计划开发新的基于基因组的工具来评估 诺氏疟原虫种群结构具有足够的分辨率，以理解不断增加的传播和 沙巴州的疾病严重程度，并将这些发现与东南亚其他地区联系起来。最后，我们会 还使用全州范围内诺氏肺孢子虫病例的更新地理参考数据库 描述了精细空间尺度发病模式的变化特征，并生成了区域预测P. 包含环境遥感卫星数据和预测的诺列斯风险图 人类、猴子和蚊子种群分布，以提供信息和指导规划、监测 以及该区域其他有诺氏疟原虫传播风险的国家的预防活动。

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.