Southeast Asia Malaria Research Center

总体总结 东南亚大湄公河次区域(GMS)的疟疾仍然是一个重要的公共卫生问题 有问题。疟疾分布存在巨大的空间异质性，其中缅甸的空间异质性最高 区域疟疾负担。跨越漏洞百出的国际边界的高流动性人口是一个主要的 寄生虫传入和持续传播的贡献者。最近出现了对经济衰退的抵抗 青蒿素(ART)家族药物及其伙伴药物引起了全球关注。向量系统 是高度多样化的，户外叮咬的增加和杀虫剂抗药性的发展使得 两项核心病媒控制干预措施--驱虫蚊帐和室内残留物喷洒效果较差。 此外，伪造和不符合标准的基于ART的联合疗法(ACTs)已经成为一场全球危机。 因此，这个项目的中心目标是提高我们对流动人口如何， 寄生虫耐药性和蚊子生物学有助于疟疾在国际上的持续传播 边界，以便制定创新的控制战略，以推动区域疟疾的进程 淘汰赛。为了实现这一总体目标，我们在国际边界选择了学习地点 三个大湄公河次区域国家，缅甸，中国和泰国，疟疾流行病学截然不同 在四个相互关联的项目中对人类、病媒和寄生虫进行综合研究。在项目中 1、在整个项目的基础上，我们将进行疟疾监测，监测人类迁徙及其 对寄生虫传入的影响，并评估目前治疗优势P。 间日疟。项目2将研究环境变化如何影响蚊子群落结构和 疟疾传播，确定主要媒介的行为变化是否由遗传决定，以及 确定疟疾病媒对杀虫剂抗药性的程度和机制。在项目3中，我们将解决 恶性疟原虫对ART家族药物和配对药物的耐药性问题 通过跟踪抗性在核不育系中的传播，对抗性机制进行了分子研究。最后，我们想要 开发基于单抗的免疫分析方法来检测ACT中的两种有效成分，并使用我们的 新开发的医疗点试纸分析用于大规模评估问题的程度 使用分层随机抽样方法对大湄公河次区域国家的造假和不合标准的行为进行调查。这 计划，建立在当前ICEMR计划的科学成果和强大的 国际合作者，旨在剖析移民人口之间的复杂互动， 不同的蚊子媒介、耐多药寄生虫以及造假和不合格的行为，这些都是 疟疾继续沿国际边界传播。这些科学问题不仅与 GMS国家，但也适用于其他疟疾地区。因此，这些研究的结果将 对全球消除疟疾产生深远影响。

OVERALL SUMMARY Malaria in the Greater Mekong Subregion (GMS) of Southeast Asia remains an important public health problem. There is immense spatial heterogeneity in malaria distribution, with Myanmar having the highest regional malaria burden. Highly mobile populations crossing porous international borders are a major contributor to parasite introduction and continued transmission. The recent emergence of resistance to the artemisinin (ART) family of drugs as well as to their partner drugs raised global concerns. The vectorial system is highly diverse, and increased outdoor biting and development of insecticide resistance have rendered the two core vector control interventions – insecticide-treated nets and indoor residue spray less effective. Furthermore, falsified and substandard ART-based combination therapies (ACTs) have become a global crisis. Therefore, the central goal of this program is to improve our understanding of how mobile human populations, parasite drug resistance, and mosquito biology contribute to continuous malaria transmission at international borders so that innovative control strategies can be developed to propel the course of regional malaria elimination. To achieve this overarching objective, we have selected study sites in the international border regions of three GMS countries, Myanmar, China, and Thailand, with drastically different malaria epidemiology to conduct comprehensive research on humans, vectors, and parasites in four interrelated projects. In Project 1, the foundation of the whole program, we will conduct malaria surveillance, monitor human migration and its impact on parasite introduction, and evaluate the effectiveness of the current treatment of the predominant P. vivax malaria. Project 2 will study how environmental changes affect mosquito community structures and malaria transmission, identify whether behavioral changes of major vectors are genetically determined, and determine the extent and mechanisms of insecticide resistance in malaria vectors. In Project 3, we will address the emerging problem of resistance of P. falciparum to both the ART family of drugs and partner drugs through molecular studies of resistance mechanisms and by tracking resistance spread in the GMS. Finally, we want to develop monoclonal antibody-based immunoassays to detect both active ingredients in an ACT, and use our newly developed point-of-care dipstick assays for large-scale assessment of the extent of problem of the falsified and substandard ACTs in the GMS countries using a stratified random sampling approach. This program, built on the scientific achievements of the current ICEMR program and the strong network of international collaborators, aims to dissect the complex interactions between migrant human populations, diverse mosquito vectors, MDR parasites, and falsified and substandard ACTs, which are responsible for continued malaria transmission along international borders. These scientific questions are not only pertinent to the GMS nations, but are also applicable to other malaria regions. Therefore, findings from these studies will bear far-reaching impacts on global malaria elimination.