Epidemiology and Population Genetics of Malaria Parasites in Kenya

肯尼亚疟疾寄生虫的流行病学和群体遗传学

• 批准号: 10642702
• 负责人: Brook Jeang
• 金额: $ 4.32万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-11 至 2025-04-10
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642702
• 关键词: Africa; Africa South of the Sahara; African; Area; Bioinformatics; Blood; Cessation of life; Clinical; Communicable Diseases; Communities; Country; County; Data; Detection; Development; Diagnosis; Diagnostic Procedure; Disease; Disease Outbreaks; Dryness; Effectiveness of Interventions; Epidemiologic Monitoring; Epidemiologist; Epidemiology; Exhibits; Faculty; Genetic; Genotype; Geography; Goals; Health care facility; Hospitals; Household; Incidence; Infection; Infectious Disease Epidemiology; Infrastructure; Intervention; Kenya; Leadership; Malaria; Malaria Diagnostic; Maps; Measures; Mentorship; Microsatellite Repeats; Molecular; Molecular Epidemiology; Morbidity - disease rate; Nosocomial Infections; Outcome; Parasites; Pattern; Plasmodium; Population Genetics; Prevalence; Program Reviews; Public Health; Reporting; Research; Research Personnel; Residual state; Resolution; Risk; Sampling; Spatial Distribution; Spottings; Stratification; Surveillance Methods; System; Testing; Training; burden of illness; career; deep sequencing; design; detection method; effective therapy; effectiveness evaluation; epidemiologic data; experience; genetic epidemiology; genetic variant; global health; improved; indexing; international center; malaria infection; malaria transmission; member; mortality; multidisciplinary; novel strategies; programs; scale up; screening; skills; spatial epidemiology; stem; tool; transmission process; vector

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.

项目摘要 载体干预措施的扩展，改进的诊断和有效治疗已共同促成 在过去的15年中，全球疟疾死亡率和发病率的大幅降低。然而，疟疾 撒哈拉以南非洲的负担仍然很高，2019年报告了2.15亿例病例和380,000例死亡。 减轻疟疾的负担并不统一，某些国家或地区不断表现出很高的发病率 而其他人则显示急剧减少。因此，许多非洲国家提出了次国家 疟疾风险的分层，并制定了相应的监视和干预计划以针对目标 异质性疟疾负担。随着临床疟疾病例的患病率降低，传播变成 无症状增加的局灶性和疟疾感染的比例。无症状的情况 通常没有发现且未治疗。它们构成一个晦涩的寄生虫水库，默默维持 传播和威胁疟疾控制和消除工作。功能性和反应型疟疾 监视系统对于量化疾病的真正负担是必要的，确定了残留的传播 焦点进行靶向控制，并评估干预措施的有效性。增强的监视方法和 需要采用更敏感的疟疾诊断方法来检测有症状和无症状感染 低转移设置。该F31应用的核心目的是检查空间和 肯尼亚低转移地区疟疾寄生虫的遗传流行病学在迅速的背景下 实施密集控制计划后，传输下降。我将检查 传播中基于医院的临床疟疾病例和反应性病例检测方法的有效性 热点检测（AIM 1），并研究内部疟疾感染的遗传连通性和多样性 在使用Amplicon Deep测序和微卫星分类的疟疾病例簇中（AIM 2）。鉴别 传输热点的态度将为最适合当地流行病学环境的疟疾干预策略提供信息。 寄生虫分离株之间遗传连通性的模式将揭示地理传播和传播 疟疾感染网络。这些数据将改善我们对疟疾流行病学的理解 传输迅速下降的地方，从而指导决策者量身定制最佳策略以实现 当地的疟疾控制和消除目标。这项拟议的研究将对疟疾具有广泛的影响 非洲其他地区的监视正在经历大幅降低疟疾的传播。在下面 多学科团队的指导，我将获得传染病流行病学的技能 在发展领导力和专业的同时，流行病学，分子种群遗传学和生物信息学 为我做好准备的技能，使我成为独立的全球健康研究员和感染力的职业 疾病流行病学家。