Epidemiological and molecular studies on chronic HBV infection in Gambian families

Dumpis, Uga (2001). Epidemiological and molecular studies on chronic HBV infection in Gambian families. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f98d

Abstract

Over 600 chronic hepatitis B virus (HBV) carriers were identified in The Gambia. 142 families with multiple affected siblings were recruited for this study. The prevalence of HBsAg carriage in siblings of the carriers was significantly higher than in normal population with the same exposure rate to the HBV infection, which could be considered as the sign of the family clustering of the disease. Significant correlation between birth order of a sibling and the risk of becoming a carrier was found. Relatively low prevalence in mothers of HBV carriers in these families was suggestive that mother to child HBV transmission did not play a major role. The index cases have been assumed to come from within a family unit or from sources outside an immediate family, such as other families or inhabitants of the same compound or village. I have attempted to define these routes of HBV transmission by phylogenetic analysis of sequences from the entire HBV pre core/core and surface gene regions. Pre core/core gene sequences were found to be more informative for this purpose. Despite the overall conserved nature of the pre- core/core sequences, distinct clusters with high bootstrap support were easily defined at the family and village level, but not on the wider geographical distribution level. Over one third of the families studied had a strong evidence of intrafamilial HBV transmission. Therefore clustering of HBV infection in the Gambian families was confirmed with epidemiological data and the hypothesis on horizontal HBV transmission between West African children for the first time was supported by sequencing data and phylogenetic analysis. A large number of unique Gambian HBV core promoter/pre-core/ core and surface gene sequences were obtained and their molecular characteristics described. The analysis also revealed for the first time that HBV genotypes A and E circulate in The Gambia, with the clear predominance of the latter.