Epidemiology and Population Genetics of Malaria Parasites in Kenya

项目摘要 媒介干预的扩大、改进的诊断和有效的治疗共同促进了 在过去15年中，全球疟疾死亡率和发病率大幅下降。然而，疟疾 撒哈拉以南非洲的负担仍然很重，2019年报告了2.15亿例病例和38万人死亡。 疟疾减负参差不齐，一些国家或地区持续呈现高发态势 而其他国家则表现出大幅减少。因此，许多非洲国家提出了国家以下一级 疟疾风险分层，并制定了相应的监测和干预计划，以 疟疾负担的异质性。随着临床疟疾病例流行率的下降，传播变得 更多的局部和无症状的疟疾感染比例增加。无症状病例 通常不会被发现和治疗。它们构成了一个隐秘的寄生虫储藏库，默默地维持 传播和威胁疟疾控制和消除的努力。功能性和应答性疟疾 监测系统对于量化疾病的真实负担、确定残留传播是必要的。 有针对性的控制重点，并评估干预措施的有效性。改进的监测方法和 需要更灵敏的疟疾诊断方法来检测有症状和无症状的感染 低传输设置。此F31应用程序的中心目标是检查空间和 快速流行背景下肯尼亚低传播地区疟疾寄生虫的遗传流行病学 随着强化控制计划的实施，传播减弱。我会研究一下 以医院为基础的临床疟疾病例和反应性病例检测方法在传播中的效果 热点检测(目标1)，调查疟疾感染的遗传连通性和多样性 在使用扩增子深度测序和微卫星分型的疟疾病例群中(目标2)。鉴定 对传播热点的了解将为最适合当地流行病学情况的疟疾干预战略提供信息。 寄生虫分离株之间的遗传连接模式将揭示地理传播和传播 疟疾感染网络。这些数据将提高我们对疟疾流行病学的理解。 在传播迅速下降的地方，从而指导决策者量身定做最佳战略，以实现 地方疟疾控制和消除目标。这项拟议的研究将对疟疾产生广泛的影响。 正在经历疟疾传播显著减少的非洲其他地区的监测。在……下面 在一个多学科团队的指导下，我将获得传染病流行病学、空间学方面的技能 流行病学、分子群体遗传学和生物信息学，同时培养领导力和专业知识 为我的职业生涯做准备所必需的技能，成为一名独立的全球卫生研究人员，并具有传染性 疾病流行病学家。

Project Summary Scale-up of vector interventions, improved diagnosis, and effective treatment have collectively contributed to significant global reductions in malaria mortality and morbidity over the last 15 years. Nevertheless, malaria burden remains high in sub-Saharan Africa, which reported 215 million cases and 380,000 deaths in 2019. Malaria burden reduction is not uniform, with some countries or regions continuously exhibiting high incidence whereas others show drastic reductions. Consequently, many African countries have proposed sub-national stratification of malaria risk and have developed corresponding surveillance and intervention plans to target heterogeneous malaria burden. As the prevalence of clinical malaria cases decreases, transmission becomes more focal and the proportion of malaria infections that are asymptomatic increases. Asymptomatic cases typically go undetected and untreated. They constitute an obscure parasite reservoir, silently sustaining transmission and threatening malaria control and elimination efforts. Functional and responsive malaria surveillance systems are necessary for quantifying the true burden of disease, identifying residual transmission foci for targeted control, and evaluating the effectiveness of interventions. Enhanced surveillance methods and more sensitive malaria diagnostic methods are needed to detect symptomatic and asymptomatic infections in low-transmission settings. The central objective of this F31 application is to examine the spatial and genetic epidemiology of malaria parasites in low-transmission regions in Kenya in the context of rapidly declining transmission following the implementation of intensive control programs. I will examine the effectiveness of hospital-based clinical malaria cases and reactive case detection methods in transmission hotspot detection (Aim 1), and investigate the genetic connectivity and diversity of malaria infections within and among clusters of malaria cases using amplicon deep sequencing and microsatellite typing (Aim 2). Identification of transmission hotspots will inform malaria intervention strategies best suited to local epidemiological contexts. Patterns of genetic connectivity among parasite isolates will reveal the geographical spread and transmission network of malaria infections. These data will improve our understanding of malaria epidemiology in settings where transmission is rapidly declining, thus guiding decision-makers in tailoring optimal strategies to achieve local malaria control and elimination goals. This proposed research will have broad implications for malaria surveillance in other areas of Africa that are experiencing significant reductions in malaria transmission. Under the mentorship of a multidisciplinary team, I will gain skills in infectious disease epidemiology, spatial epidemiology, molecular population genetics, and bioinformatics while developing leadership and professional skills that are necessary to prepare me for a career as an independent global health researcher and infectious disease epidemiologist.