Epidemiology and Ecology of Cholera in Africa

长期目标是通过确定传播模式来消除非洲的霍乱 使流行的非洲国家能够减少霍乱流行地区的数量，方法是在 以及不同地区之间。这一目标与全球霍乱控制工作队的目标一致 到2030年，从20个国家“消灭”霍乱。使用创新的监视、分子和地理信息系统方法， 这项研究将在尼日利亚和乌干达进行详细的分子流行病学研究，以检测传播情况 霍乱弧菌(VC)基因谱系和噬菌体的研究，并将监测干预措施的影响 旨在防止霍乱的传播。通过阻止霍乱在一个国家内传播，这个国家将 减少霍乱病区的数量；从而创建一张“消除霍乱记分卡”，以便 监测全国消灭的进展情况。 这个应用程序建立在我们最初的非洲霍乱RO1研究的证据上，表明霍乱 血统“蔓延”到流行地区，而不是“走出”流行地区，控制霍乱的战略需要调整 对这一新的理解。许多撒哈拉以南非洲国家是“地方病”，因为它们定期报告 霍乱病例；然而，大多数暴发时间很短(几周)，仅限于少数几个区或分区，以及 是由穿过一个地区然后灭绝的遗传谱系造成的。因为水、卫生设施和 卫生(WASH)很差，当引入新的基因谱系时，这些地区仍然容易受到影响。 为了提高消除战略的有效性，需要改进监测以发现 迅速爆发以进行干预和防止向外传播。快速的分子监测现在是可能的 快速诊断测试(RDT)能够立即识别病例，同时还为 利用MLVA进行了PCR验证和分子鉴定。粪便也将被培养，以创造一个 VC菌株和粪便的储存库将在滤纸上留下斑点并烘干。干粪便样本(DFS)可以 无需冷藏即可无限期储存，运输方便，对生物无害，可用于 检测VC和噬菌体。收集污水样本以检测Vc和噬菌体。 暴发，以进一步表征遗传谱系和噬菌体的传播。通过将密集的 监测、分子流行病学和快速评估病例地理信息系统坐标，快速识别模式 预防霍乱传播应改进有针对性的干预措施(疫苗和洗涤)。 该项目使用在初始RO1赠款期间开发的创新新技术，适用于 发展中国家的情况。这包括对RDT的评估，使RDT的结果得以声明 一次暴发以及用于分子研究，使用一种新的简化LAMP方法快速检测VC (称为RLDT)，DFS和RDT的基因分型(MLVA)，d)分离株的全基因组测序(WGS) 以及DFS，以及d)来自DFS的噬菌体检测。

The long-term goal is the elimination of cholera in Africa by identifying patterns of transmission that will enable endemic African countries reduce the number of districts with cholera by stopping transmission within and between districts. This goal is consistent with the goal of the Global Task Force for Cholera Control to “eliminate” cholera from > 20 countries by 2030. Using innovative surveillance, molecular and GIS methods, the study will conduct detailed molecular epidemiological studies in Nigeria, and Uganda to detect the spread of specific V. cholerae (Vc) genetic lineages and vibriophage and will monitor the impact of interventions intended to prevent cholera’s spread. By stopping cholera’s transmission within a country, the country will reduce the number of districts with cholera; thereby, creating a “cholera elimination scorecard” with which to monitor progress toward national elimination. This application builds on evidence from our initial RO1 study of cholera in Africa showing that cholera lineages “spread to” rather than “emerge from” endemic areas, and strategies to control cholera need to adapt to this new understanding. Many Sub-Saharan African countries are “endemic” since they regularly report cholera cases; however, most outbreaks are short (few weeks), are limited to a few districts or subdistricts and are caused by genetic lineages that move through an area and then die out. Because water, sanitation and hygiene (WASH) is poor, these areas remain susceptible when a new genetic lineage is introduced. To improve the effectiveness of an elimination strategy, improved surveillance is needed to detect outbreaks quickly to intervene and prevent outward transmission. Rapid molecular surveillance is now possible with rapid diagnostic tests (RDTs) able to immediately identify cases while also providing DNA samples for PCR confirmation and molecular characterization using MLVA. Stools will also be cultured to create a repository of Vc strains, and feces will be spotted on filter paper and dried. The dried fecal samples (DFS) can be stored indefinitely without refrigeration, are easily transported, are not biohazardous, and can be used to detect Vc and vibriophage. Sewage samples will be collected to detect Vc and phage during and between outbreaks to further characterize transmission of genetic lineages and phage. By combining intensive surveillance, molecular epidemiology, and rapid evaluation of case GIS coordinates, quickly identified patterns of cholera transmission should improve targeted interventions (vaccine and WASH). The project uses innovative new technologies developed during the initial RO1 grant applicable to conditions in developing countries. These include evaluation of RDTs that allow results from RDTs to declare an outbreak as well as be used for molecular studies, rapid detection of Vc using a new simplified LAMP assay (termed RLDT), genotyping (MLVA) from DFS and RDTs, d) whole genome sequencing (WGS) from isolates as well as DFS, and d) phage detection from DFS.