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

在人口一级，疟疾仍然是马拉维的一个棘手问题， 非洲东南部的一个国家。疟疾顽固不化的原因是神秘的，但新的发现 从我们目前的ICEMR调查中发现的一些线索： 学龄儿童的疟原虫感染率高于5奥尔兹以下儿童 学龄儿童也最有可能携带配子体，这是对按蚊媒介具有感染性的阶段。 分子（q-PCR）诊断测试显示，无症状的人感染水平较低，因此 未被治疗（“隐藏的水库”），因此可能是未被发现的传播源 在一个主要城市中心周围20公里半径范围内，按蚊媒介丰度各不相同， 与微观环境异质性有关，而不是简单的城乡划分 杀虫剂抗药性和使用驱虫蚊帐的模式可能导致预防失败。 在个人层面上，只有一小部分感染疟原虫的人会经历 疟疾疾病的症状;大多数与寄生虫无症状共存。甚至更小的比例 发展成严重和复杂的疟疾，但死亡率很高。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 处于感染极端的个体（持续无症状和危及生命的脑型疟疾）只有 最近变得可行。 马拉维ICEMR团队有能力在不同的环境中对人类群体进行长期观察。 传播环境，并收集广泛的生态学、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， 在不同环境中采取多种干预措施防止传播和感染的有效性， 感染频率/持续时间与疾病严重程度之间的关系， * 杀虫剂抗药性和驱虫蚊帐的质量和使用对疾病模式的影响， 寄生虫生长速率、克隆性、促炎和抗炎宿主反应的显著贡献 对变异表面抗原的免疫应答中的“洞”对疾病进展的重要性。 在为期七年的研究过程中，这将跨越马拉维的下一个大型国家驱虫蚊帐分布， 马拉维ICEMR项目将确定马拉维疟疾控制工作迄今为止无效的原因， 并将提供关于更可能有效的方法的数据驱动建议。研究将 在三个生态和流行病学上不同的地区开展， 强度对变化中的传播和疾病的分析将比较艾滋病毒/艾滋病之前、期间和之后的模式。 全国ITN分发方案。

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.