Childhood diarrhoea and bacterial bloodstream infections account for a considerable proportion of illnesses and deaths among children under five years of age worldwide. The under-five mortality produced by these infections is disproportionately high in Nigeria and other parts of Africa. This study proposes to examine two causes of these infections, enteroaggregative Escherichia coli and Salmonella, and to identify bacterial lineages that account for a significant proportion of childhood diarrhoeas and invasive infections among Nigerian children. Stool specimens will be obtained from children with diarrhoea and from healthy children attending clinics in Ibadan, Nigeria. E. coli and Salmonella will be isolated from the specimens and characterized at the molecular level to identify disease-causing strains and the disease-causing genes these subtypes carry. Enteroaggregative Escherichia coli and Salmonella isolates will be subjected to further analysis, involving sequencing parts of their genomes. The resulting DNA sequences will be compared to determine inter-relationships among different genetic lineages of bacteria isolated in this study and between these isolates from Nigeria and strains other parts of the world. These analyses will reveal how disease-causing lineages change over time and are transmitted locally and globally. This research will improve our understanding of the epidemiology and evolution of two important but under-addressed bacterial pathogens. The study will determine which subgroups of enteroaggregative Escherichia coli and Salmonella are more likely to cause disease and whether there are subtypes that are associated with life-threatening disease. This is important for the study location, Nigeria, because very little is known about locally-prevalent subtypes within the country or in neighbouring countries. Identification and characterization of predominant subgroups serve as the basis for devising diagnostics to better their detection and surveillance. The findings from this study will also inform vaccine development and vaccine use policy because the most harmful subtypes can be targetted. This research will also determine whether healthy individuals carry these organisms, and if so, to what extent. Understanding healthy carriage is key to determining how these organisms are maintained and transmitted in communities. The study will use molecular methods to characterize the strains in a laboratory to be set up at the University of Ibadan and lead by the African Research Leader Candidate who is co-investigator on this grant. The African Research Leader will additionally build on collaborative links with other regional laboratories and extend some of the expertise built at Ibadan to those labs. The research will therefore build capacity in the area of molecular bacteriology and provide a collaborative link between West African scientists and the Wellcome Trust Sanger Institute, where the principal investigator is located.