Epidemiology and Ecology of Cholera in Africa

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.