Importation and transmission of malaria in Zanzibar: a case study for elimination

桑给巴尔疟疾的输入和传播：消除疟疾的案例研究

• 批准号: 10296505
• 负责人: Jonathan J Juliano
• 金额: $ 72.55万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10296505
• 关键词: Address; Africa; Annual Reports; Antimalarials; Area; Case Study; Clinical; Collaborations; Communities; Country; Culicidae; Data; Detection; Diagnostic tests; Disease Outbreaks; Ecology; Face; Future; Genetic; Genomics; Genotype; Goals; Health Priorities; Health care facility; High-Throughput Nucleotide Sequencing; Household; Human; Individual; Infection; Institution; International; Interruption; Intervention; Island; Legal patent; Link; Malaria; Maps; Measures; Methods; Modeling; Molecular; Parasites; Pattern; Plasmodium falciparum; Policies; Rapid diagnostics; Recording of previous events; Reporting; Research; Research Priority; Residual state; Resolution; Risk; Risk Factors; Route; Sampling; Shapes; Site; Source; Spatial Distribution; Tanzania; Time; Transcend; Travel; Vulnerable Populations; Zanzibar; design; disease transmission; evidence base; genome sequencing; genome-wide; genomic data; global health; identity by descent; indexing; malaria transmission; migration; novel; predictive modeling; prevent; programs; response; screening; targeted sequencing; therapy design; tool; transmission process; vector; vector control; whole genome

ABSTRACT Over the past decade, malaria elimination has re-emerged atop the global health agenda, with most countries setting goals to be malaria-free within two decades. However, major obstacles remain, including “getting to zero” in regions that have achieved pre-elimination status but remain surrounded by areas of ongoing transmission. As these regions near elimination, they are often “vulnerable” to re-introduction of malaria from nearby areas and “receptive” as they have the right ecology to support transmission. The Zanzibar Archipelago is one of these regions. Despite robust vector control and access to efficacious antimalarial treatment, its proximity to mainland Tanzania has made elimination difficult. Specifically, eliminating malaria on the archipelago requires a better understanding of why and where importation is occurring and understanding the factors that promote local transmission. This proposal will overlay genomic studies onto ongoing Zanzibar Malaria Elimination Program (ZAMEP) passive surveillance and reactive case detection (RCD) activities to identify foci of imported cases on the islands (Aim 1A), model the relationship between human travel, parasite genetics and importation (Aim 1B), determine the extent of secondary transmission from index cases (Aim 2A), and show the limits of RCD in detecting index cases and capturing parasite outbreaks (Aim 2B). Samples will be collected from every reported case on the archipelago and 10 sites on mainland Tanzania. Additionally, enhanced RCD - screening households surrounding a reported index case, both 1 and 4 weeks later - will be carried out in order to capture secondary asymptomatic cases, including those infected but with prepatent infection, as well as those yet to be inoculated by infected mosquitoes at the time of first RCD. We will deploy novel efficient high throughput sequencing methods that enable genotyping of thousands of samples on a genome-wide basis. This strategy is much cheaper than whole genome sequencing but still provides the resolution needed to use identity-by-descent analyses to infer relationships between highly related parasites. These methods will allow us to define individual and community risk factors for importation, as well as intervenable risk factors that impact the extent of local transmission arising from importation. Combined with geospatial data on human mobility patterns, we will achieve a deeper understanding of the drivers of importation and secondary transmission that will allow ZAMEP to tailor interventions at a local level. This study leverages an existing productive collaboration between leading academic institutions (UNC, Brown, Imperial, MUHAS) and ZAMEP to tackle questions cited amongst the highest research priorities for the WHO and other bodies that guide malaria research. As all malaria endemic countries will face the last mile of malaria elimination, whether now or in the future, we expect completion of the aims in this proposal to have a direct impact on global malaria policies.

抽象的 在过去的十年中，消除疟疾已经重新出现在全球卫生议程之上，大多数国家 将目标设定为二十年之内无疟疾。但是，仍然存在主要障碍，包括“去 零”在已经达到淘气前状态但仍在持续的地区的地区 传播。由于这些地区几乎被淘汰，它们通常“脆弱”以重新引入疟疾 附近的地区和“接受”，因为它们具有支持传播的正确生态。桑给巴尔群岛 是这些地区之一。尽管有强大的载体控制并获得有效的抗疟疾治疗，但 坦桑尼亚大陆的距离使消除变得困难。特别是消除疟疾 群岛需要更好地理解出口以及在哪里发生和理解 促进本地传播的因素。该提案将覆盖基因组研究到正在进行的桑给巴尔 疟疾消除计划（ZAMEP）被动监视和反应性病例检测（RCD）活动 确定进口案件的焦点（AIM 1A），建模人类旅行，寄生虫之间的关系 遗传学和进口（AIM 1B），确定索引病例的次级传播程度（AIM 2A）， 并显示RCD在检测索引病例和捕获寄生虫暴发（AIM 2B）时的极限。样品会 可以从群岛上的每个案件和坦桑尼亚大陆的10个地点收集。此外， 增强的RCD-在1周和4周后，围绕报告指数案例的筛查家庭 - 为了捕获次级不对称病例，包括感染但有预先处理的情况 感染，以及尚未在第一次RCD时被感染的蚊子接种的感染。我们将部署 新型有效的高通量测序方法，可以在A上进行基因分型 全基因组基础。该策略比整个基因组测序便宜得多，但仍然提供 分辨率需要使用逐渐分析来推断高度相关的寄生虫之间的关系。 这些方法将使我们能够定义进口的个人和社区风险因素，以及 会影响进口局部传播程度的可理用风险因素。与 关于人类流动性模式的地理空间数据，我们将对驱动因素的驱动力进行更深入的了解 导入和次要传输将使ZameP能够在本地级别量身定制干预措施。这项研究 利用领先学术机构（UNC，Brown，Imperial，， Muhas）和Zamep解决WHO和他人的最高研究优先事项中引用的问题 指导疟疾研究的身体。随着所有疟疾的内在国家将面临疟疾的最后一英里 消除，无论是现在还是将来，我们都希望在此提案中完成目标 对全球疟疾政策的影响。