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

血吸虫病即将被消灭：残留传播热点地区新感染源的特征

• 批准号: 10508509
• 负责人: Elizabeth Carlton
• 金额: $ 63.36万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-11-23 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10508509
• 关键词: Affect; Africa South of the Sahara; Animals; Area; Big Data; Characteristics; China; Communicable Diseases; Communities; Community Health; Complex; Data; Disease; Ecology; Effectiveness; Focal Infection; Generations; Genomic approach; Genomics; Goals; Grant; Habitats; Human; Inbreeding; Individual; Infection; Interruption; Intervention; Malaria; Measures; Methods; Movement; Output; Parasites; Pathway interactions; Pattern; Persons; Population; Population Intervention; Research; Residual state; Resolution; Sampling; Schistosoma; Schistosoma japonicum; Schistosomiasis; Scientist; Snails; Source; Testing; Time; Work; World Health Organization; Zoonoses; disorder control; drug distribution; epidemiologic data; genomic tools; global health; improved; neglected tropical diseases; novel strategies; pathogen; pressure; prevent; programs; social; transmission process; waterborne; waterborne infection

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.

项目概要/摘要 血吸虫病是一种水传播疾病，影响约 2 亿人，在某些地区持续存在 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都有记录表明这种现象的持续存在和重新出现 非洲。这些热点有可能破坏消除血吸虫病的全球目标，并凸显了消除血吸虫病的必要性 了解这些地区新感染的起源，以改进控制策略。可能的感染 来源包括社区内的人类宿主、其他哺乳动物物种以及通过以下途径输入的感染： 例如，移动人类宿主。然而，这些来源对可持续发展的实际贡献 血吸虫病等复杂大型寄生虫在控制压力地区的传播情况较差 解决了。基因组工具提供了辨别详细传播途径的潜力，即使是高度近交的传播途径 寄生虫，如血吸虫。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跨代寄生虫祖先， 允许识别作为感染源的主机。超过十年的纵向数据 中国西南地区，以及对血吸虫病热点地区的持续访问将被用来描述宿主和血吸虫病的特征 预测不同宿主的贡献和寄生虫输入的贡献的村级特征 到传输。具体来说，这三个拟议目标将评估人类高传播率的证据 宿主（超级传播者）作为新感染源（目标 1），确定促进感染的条件 非人类宿主对感染的贡献（目标 2），并测试和确定是否存在关键途径 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 努力重点关注即将消除地区的主要感染源。

项目成果

A genomic can of worms for schistosome host-specificity.

• DOI: 10.1016/j.pt.2022.04.005
• 发表时间: 2022-07
• 期刊: TRENDS IN PARASITOLOGY
• 影响因子: 9.6
• 作者: Nikolakis, Zachary L.;Carlton, Elizabeth J.;Pollock, David D.;Castoe, Todd A.
• 通讯作者: Castoe, Todd A.

Viral CpG Deficiency Provides No Evidence That Dogs Were Intermediate Hosts for SARS-CoV-2

• DOI: 10.1093/molbev/msaa178
• 发表时间: 2020-09-01
• 期刊: MOLECULAR BIOLOGY AND EVOLUTION
• 影响因子: 10.7
• 作者: Pollock, David D.;Castoe, Todd A.;Goldstein, Richard A.
• 通讯作者: Goldstein, Richard A.

Population genomic analyses of schistosome parasites highlight critical challenges facing endgame elimination efforts.

• DOI: 10.1038/s41598-021-86287-y
• 发表时间: 2021-03-25
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Shortt JA;Timm LE;Hales NR;Nikolakis ZL;Schield DR;Perry BW;Liu Y;Zhong B;Castoe TA;Carlton EJ;Pollock DD
• 通讯作者: Pollock DD

Predictors of bovine Schistosoma japonicum infection in rural Sichuan, China.

• DOI: 10.1016/j.ijpara.2022.04.002
• 发表时间: 2022-07
• 期刊: INTERNATIONAL JOURNAL FOR PARASITOLOGY
• 影响因子: 4
• 作者: Grover, Elise;Paull, Sara;Kechris, Katerina;Buchwald, Andrea;James, Katherine;Liu, Yang;Carlton, Elizabeth J.
• 通讯作者: Carlton, Elizabeth J.

Patterns of relatedness and genetic diversity inferred from whole genome sequencing of archival blood fluke miracidia (Schistosoma japonicum).

• DOI: 10.1371/journal.pntd.0009020
• 发表时间: 2021-01
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Nikolakis ZL;Hales NR;Perry BW;Schield DR;Timm LE;Liu Y;Zhong B;Kechris KJ;Carlton EJ;Pollock DD;Castoe TA
• 通讯作者: Castoe TA