Genotypes of Helicobacter pylori isolates in Gambian children and adults

Helicobacter pylori is a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Earlier reports indicated high prevalence of H. pylori colonization, but a low frequency of H. pylori-associated diseases in Africa but recent reviews have shown that gastroduodenal disease is actually common in Africa. Most detailed analyses of H. pylori have used strains from non-African countries, despite the high importance of Africa in the emergence and evolution of humans and their pathogens. There have been far fewer critical studies such as genotypes in association with gastric disease, population genetics and antimicrobial resistance and susceptibility of H. pylori strains from Africa. It is with this background that the genotypes of H. pylori in association with gastroduodenal diseases, antibiotic susceptibility to commonly used drugs and population genetics from ethnic African adults and children in The Gambia were investigated. In this study, it was found that the prevalence of H. pylori is high in dyspeptic patients in The Gambia and that many strains were of the putatively more virulent cagA+, vacAs1 and vacAm1 genotypes. There was a high prevalence of cagA positive strains in patients with overt gastric diseases than those with non-ulcerative dyspepsia; conversely, the co-existence of both cagA+ and cagA- was found to be protective against the development of gastroduodenal disease. Analyses of the sequenced data with the STRUCTURE software indicated that Gambian H. pylori strains were closely related to hspWAfrica than to strains from more distant African regions (hspSAfrica and hpNEAfrica) indicating common ancestral origin. Essentially no traces of European or North African ancestry were found despite Gambia's history of invasion and colonisation by peoples from these regions during the last millennium. Antibiotic susceptibility tests have shown that Gambian strains were found to be highly sensitive to clarithromycin, erythromycin, tetracycline and amoxicillin but found that more than two-thirds of Gambian H. pylori strains were metronidazole resistant. These data indicate caution in use of metronidazole-based therapies in The Gambia. This thesis provides a detailed initial description of a set of H. pylori isolates directly related to a geographically defined West African population. The data presented has answered some relevant questions on H. pylori virulent genes in association with gastro-duodenal diseases and antibiotic susceptibility providing a comprehensive basis for future studies