The cagA gene and vacAs1 and m1 alleles are often linked to severe disease, and the vacAs2 and m2 alleles with more benign infections in other populations. The possible effects of bacterial or human genetic and physiologic differences, food, history of other infections and other environmental and lifestyle factors, on outcomes of chronic H. pylori infections in sub-Saharan Africa merit further more detailed analyses. Most important, was our finding that co-existence of cagA positive and cagA negative strains was significantly more common amongst patients with NUD than among those with overt disease, which suggests that mixed colonization is protective. In principle, protection against development of overt gastric disease might stem from simple competition �C whereby carriage of an avirulent strain diminishes the vigour of growth of a coexisting virulent strain, thereby reducing its impact on host tissues. It is also possible that factors in cag-negative strains that diminish the impact of virulence proteins such as CagA might predominate during cagA-positive and cagA-negative mixed infections. Or, more generally, an increased complexity of immune Diniconazole responses during chronic infection by multiple divergent H. pylori strains might effectively diminish the inflammatory action of an individual virulent strain, and thereby resultant pathology in host tissues, as noted with other infections. In accord with this idea, the risk of developing overt disease seemed higher in subjects apparently colonized only with cagA negative H. pylori, than in those with mixed cagA positive and negative strains. Conversely, however, the presence of mixed infections might also stem from increased intrinsic host susceptibility to H. pylori infection and equally the development of a more severe clinical outcome. This study has revealed frequent gastro-duodenal disease among Gambians with gastric complaints. Many strains carried cagA+ and s1, m1 alleles of vacA, which are disease associated in many European and North American populations. Although cagA status was associated with disease in The Gambia, alleles of vacA were not. Comparison of our data with those from Pantoprazole sodium southern Nigeria pointed to a potentially significant difference in linkage of signal sequence and middle region alleles, which control the potency and tissue specificity of toxin action respectively. The possibility that such differences reflect selection for optimal genotypes or random genetic drift in these well-separated West African nations merit further study. We suggest that our most interesting finding is the significantly lower disease burden in Gambians infected with a mixture of cag-positive and cag-negative strains, relative to those containing only cagpositive or only cag-negative strains.