Epidemiology of Malaria Risk in Malawi: Vector Resistance, ITNS, and Human Behavior

尽管在马拉维全国广泛采取了抗疟疾干预措施，包括在全国范围内分发 尽管有驱虫蚊帐和免费治疗，但疟疾的负担仍然极高， 在过去十年中，感染或疾病的发生率显著下降。许多因素已经 这一假设解释了疟疾在马拉维和撒哈拉以南非洲许多地区的顽固性， 如无法获得治疗、耐药性、诊断不当、“沉默”的感染库和失败 的预防措施。该项目与马拉维ICEMR中的另外两个项目相结合， 从使用驱虫蚊帐影响的人与病媒相互作用的角度来看疾病风险的流行病学， 有效性和杀虫剂抗性（IR）。我们设计了系统的研究来了解为什么 尽管为减少感染和疾病作出了如此大的努力，但马拉维的疟疾负担仍然很重。我们 先前在马拉维的工作表明，在主要病媒，如不死按蚊中，感染率很高， 这些蚊子在通常的睡眠时间前后叮咬，这时驱虫蚊帐可能有用。我们假设 经杀虫剂处理过的蚊帐的有效性将根据传播强度、红外线以及人类和蚊子的行为而有所不同。 因此，这项拟议研究的目标是： 1)了解人类感染和疾病风险如何随着ITN的使用和有效性而变化， 不同的环境背景和病媒-人类接触情景， 2)确定媒介和人类的疟原虫感染如何随拟除虫菊酯IR和媒介而变化 在三个级别的传输强度上的行为，以及 3)评估人类行为和按蚊种的叮咬行为如何改变昆虫学 接种率（EIR）和人类疾病风险。 为了实现这些目标，我们将对人类和病媒群体进行以群体为基础的实地研究， 测量2018年马拉维驱虫蚊帐大规模分发之前、期间和之后的感染和疾病发生率 运动中这一努力使我们能够通过监测来评估大规模“实验性”干预的影响。 干预措施的有效性和疾病风险的任何变化。将围绕一个 政府卫生中心在三个生态和流行病学不同的研究地点。的 感染队列将允许测量恶性疟原虫感染的发生率，并且疾病队列将被 用于评估疟疾发病率。通过了解这些因素及其在整个环境中的相互作用， 在一系列地方性传播环境中，可以确定关键的干预失败，并制定新的战略， 预防疟疾的设计。我们的研究结果应该有助于提高马拉维的干预效果， 在撒哈拉以南非洲，尽管作出了协调一致的努力，但疟疾负担仍然很高。

Despite widespread anti-malaria interventions throughout Malawi, including country-wide distribution of insecticide treated nets (ITNs) and free treatment, the burden of malaria remains extremely high, with no measurable decrease in incidence of infection or disease over the past decade. Many factors have been hypothesized to explain such intransigence of malaria in Malawi, and in many parts of sub-Saharan Africa, such as unavailable treatment, drug resistance, improper diagnosis, "silent" reservoirs of infection, and failure of prevention measures. This project, which is integrated with two others in the Malawi ICEMR, addresses the epidemiology of disease risk from the perspective of human-vector interactions as influenced by ITN use and effectiveness and insecticide resistance (IR). We have designed systematic studies to understand why the burden of malaria remains high in Malawi, despite such intense efforts to reduce infection and disease. Our previous work in Malawi has shown that IR is high among major vectors such as Anopheles funestus, and that these mosquitoes are biting before and after usual sleeping time when ITNs could be useful. We hypothesize that ITN effectiveness will vary based on the intensity of transmission, IR, and human and mosquito behaviors. Hence, the goals of this proposed research are: 1) Understand how human infection and disease risk changes with ITN use and effectiveness across diverse environmental contexts and vector-human contact scenarios, 2) Determine how Plasmodium infection in vectors and humans varies with pyrethroid IR and vector behavior across three levels transmission intensity, and 3) Evaluate how human behaviors and biting behavior of Anopheles species alter the entomological inoculation rate (EIR) and human disease risk. To broach these objectives, we will undertake cohort-based, field studies of human and vector populations, measuring infection and disease incidence before, during and after the 2018 Malawi ITN mass distribution campaign. This effort allows us to evaluate the impacts of a massive "experimental" intervention by monitoring effectiveness of interventions and any changes in disease risk. Two cohorts will be established around a government health center in each of the three ecologically and epidemiologically different study sites. The infection cohort will allow measurement of incidence of P. falciparum infection and the disease cohort will be used to assess the incidence of malaria illness. By understanding these factors and their interactions across a range of endemic transmission settings, critical intervention failures can be identified and new strategies to prevent malaria designed. Our results should help improve intervention effectiveness in Malawi, and many other settings in sub-Saharan Africa where malaria burden remains high despite concerted efforts.