Schistosomiasis at the edge of elimination: characterizing sources of new infections in residual transmission hotspots

项目概要/摘要 血吸虫病是一种水传播的传染病，影响约2亿人，在一些地区持续存在 尽管采取了积极的控制措施，但原因尚不清楚。血吸虫病热点地区 在中国部分地区，以及最近在撒哈拉以南地区， 非洲这些热点有可能破坏消除血吸虫病的全球目标，并突出表明需要 了解这些地区新感染病例的来源，以改进控制策略。疑似感染 来源包括社区内的人类宿主，其他哺乳动物物种，以及通过， 例如，移动的人类宿主。然而，这些来源对可持续发展的实际贡献 在有控制压力的地区，复杂的大型寄生虫（如血吸虫病）的传播很差 解决了基因组工具提供了辨别详细的传播途径的潜力，即使是高度近交的 寄生虫，如寄生虫。拟议的研究利用基因组方法和纵向 流行病学数据，以确定传播热点地区新感染的来源。高分辨率测序 日本血吸虫的分析方法将用于推断世代间的寄生虫祖先， 允许识别作为感染源的宿主。来自十多年的纵向数据 中国西南部，以及对血吸虫病热点地区的持续访问将用于表征宿主和 预测不同宿主贡献和寄生虫输入贡献的村级特征 传输。具体而言，这三个拟议目标将评估高传播人类 宿主（超级传播者）作为新感染源（目标1），确定促进 非人类宿主对感染的贡献（目标2），并测试和确定是否存在感染的关键途径。 寄生虫输入（目标3）。控制血吸虫病和其他被忽视的热带疾病的宏伟目标 尽管采取了控制措施，但疾病在传播热点地区的持续存在凸显了 需要新的方法来防止传播。通过确定新感染的程度， 来自人类宿主、动物宿主或村庄之间的移动，将有可能微调控制 在接近消除的地区，努力集中注意主要的感染源。

PROJECT SUMMARY/ABSTRACT Schistosomiasis, a waterborne infection that affects approximately 200 million people, persists in some areas despite aggressive control measures, for reasons that are not well understood. Hotspots of schistosomiasis persistence and reemergence have been documented in parts of China and, more recently, sub-Saharan Africa. These hotspots threaten to disrupt global targets for schistosomiasis elimination, and highlight the need to understand the origins of new infections in these areas to improve control strategies. Plausible infection sources include human hosts within a community, other mammalian species, and imported infections via, for example, mobile human hosts. However, the actual contributions of such sources to the sustained transmission of complex macroparasites such as schistosomiasis in areas under control pressure is poorly resolved. Genomic tools offer the potential to discern detailed transmission pathways, even for highly inbred parasites such as schistosomes. The proposed research leverages genomic approaches and longitudinal epidemiological data to identify origins of new infections in transmission hotspots. High-resolution sequencing and analysis methods for Schistosoma japonicum will be used to infer parasite ancestry across generations, allowing identification of hosts that serve as infection sources. Over ten years of longitudinal data from southwest China, and ongoing access to schistosomiasis hotspots will be used to characterize host and village-level characteristics that predict the contribution of distinct hosts and the contributions of parasite import to transmission. Specifically, the three proposed aims will evaluate evidence that high transmission human hosts (superspreaders) serve as sources of new infections (Aim 1), identify the conditions that facilitate the contributions of non-human hosts to infection (Aim 2), and test for and identify if present key pathways of parasite import (Aim 3). The ambitious goals for the control of schistosomiasis and other neglected tropical diseases and the persistence of the disease in transmission hotspots despite control measures highlights the need for new approaches to prevent transmission. By determining the extent to which new infections are coming from human hosts, animal hosts, or movement between villages, it will be possible to fine-tune control efforts to focus on key sources of infection in areas approaching elimination.