The Intransigence of Malaria in Malawi: Understanding Hidden Reservoirs, Successful Vectors and Prevention Failures

在人口层面，疟疾在马拉维仍然是一个棘手的问题，虽然规模不大，但在生态上是多样化的。 非洲东南部的一个国家。疟疾顽固不化的原因是谜，但新的发现 我们目前对ICEMR的调查提供了一些线索： 学龄儿童疟原虫感染率高于5岁以下儿童 学龄儿童也最有可能携带配子体，这是感染按蚊媒介的阶段 分子(Q-聚合酶链式反应)诊断测试显示，无症状的人感染水平较低，因此 未得到治疗(“隐蔽的水库”)，因此可能是未检测到的传播来源 按蚊的媒介丰度在一个主要城市中心周围半径20公里的范围内变化很大，有一些“热点” 与微环境异质性联系在一起，而不是简单的城乡划分 预防失败可能是由于杀虫剂耐药性和杀虫剂处理后的净使用模式造成的。 在个人层面上，只有一小部分感染疟原虫的人曾经历过 疟疾疾病的症状；大多数与寄生虫无症状共存。一个更小的比例 演变成严重和复杂的疟疾，但死亡率很高。潜在的机制 沿着感染到疾病谱的进展是未知的，部分原因是可靠地识别 处于感染极端的个人(持续无症状和危及生命的脑型疟疾)只有 最近变得可行了。 马拉维ICEMR团队有能力对不同地区的人类队列进行长期观察 并收集广泛的生态、昆虫学和寄生虫学数据，以评估： 病原体传播和人类宿主反应的模式， 在不同环境中预防传播和感染的多种干预措施的有效性， 感染频率/持续时间与疾病严重程度之间的关系 杀虫剂抗性和杀虫剂处理蚊帐的质量和使用对疾病模式的影响， 寄生虫生长速度、克隆性、促炎和抗炎宿主反应的贡献 对变异表面抗原的免疫反应中“洞”对疾病进展的重要性。 在七年的研究过程中，这将跨越马拉维的下一个大型国家ITN分布 马拉维ICEMR将查明马拉维疟疾控制努力迄今无效的原因， 并将就更有可能有效的方法提供数据驱动的建议。研究将会 在三个生态和流行病学不同的地区进行，这些地区跨越了一系列传播 强度。对传播和疾病变化的分析将比较之前、期间和之后的模式 全国范围内的ITN分配计划。

At the population level, malaria remains an intractable problem in Malawi, a small but ecologically diverse country in southeastern Africa. The reasons for malaria's intransigence are enigmatic, but new findings emerging from our current ICEMR investigations have provided some clues:  Plasmodium parasite infection prevalence is greater in school-age children than in under-five year olds  School-age children are also most likely to carry gametocytes, the stage infectious to Anopheles vectors  Molecular (q-PCR) diagnostic tests revealed low-level infection in people who were asymptomatic, hence not being treated ("hidden reservoirs"), hence a likely source of undetected transmission  Anopheles vector abundance varied across a 20-km radius around a major urban center, with "hot spots" being linked to micro-environmental heterogeneity, and not to a simple urban-rural designation  Prevention failures may result from insecticide resistance and patterns of insecticide treated net use. At the individual level, only a small proportion of people infected with Plasmodium parasites ever experience symptoms of malaria illness; most co-exist asymptomatically with the parasite. An even smaller proportion evolves into severe and complicated malaria, but the mortality rates are high. The mechanisms underlying progression along the infection-to-disease spectrum are not known, in part because reliably identifying individuals at the infection extremes (persistently asymptomatic and life-threatening cerebral malaria) has only recently become feasible. The Malawi ICEMR team has the capacity to sustain long-term observations of human cohorts in different transmission settings and to collect extensive ecological, entomological and parasitological data to evaluate:  patterns of pathogen transmission and human host responses,  effectiveness of multiple interventions against transmission and infection in different environments,  relationships between infection frequency/duration and disease severity,  impacts of insecticide resistance and insecticide treated net (ITN) quality and use on disease patterns,  contributions of parasite growth rate, clonality, pro- and anti-inflammatory host responses  importance of “holes” in the immune response to variant surface antigens to disease progression. Over the course of seven years of research, which will span Malawi's next large national ITN distribution program, the Malawi ICEMR will identify why malaria control efforts in Malawi have been ineffective thus far, and will provide data-driven suggestions regarding approaches that are more likely to be effective. Studies will be undertaken in three ecologically and epidemiologically different districts that span a range of transmission intensities. Analyses of changing transmission and disease will compare patterns before, during and after the nation-wide ITN distribution program.