Epidemic History and Evolutionary Dynamics of Hepatitis B Virus Infection in Two Remote Communities in Rural Nigeria

Abstract

BackgroundIn Nigeria, hepatitis B virus (HBV) infection has reached hyperendemic levels and its nature and origin have been described as a puzzle. In this study, we investigated the molecular epidemiology and epidemic history of HBV infection in two semi-isolated rural communities in North/Central Nigeria. It was expected that only a few, if any, HBV strains could have been introduced and effectively transmitted among these residents, reflecting limited contacts of these communities with the general population in the country.Methods and FindingsDespite remoteness and isolation, ∼11% of the entire population in these communities was HBV-DNA seropositive. Analyses of the S-gene sequences obtained from 55 HBV-seropositive individuals showed the circulation of 37 distinct HBV variants. These HBV isolates belong predominantly to genotype E (HBV/E) (n = 53, 96.4%), with only 2 classified as sub-genotype A3 (HBV/A3). Phylogenetic analysis showed extensive intermixing between HBV/E variants identified in these communities and different countries in Africa. Quasispecies analysis of 22 HBV/E strains using end-point limiting-dilution real-time PCR, sequencing and median joining networks showed extensive intra-host heterogeneity and inter-host variant sharing. To investigate events that resulted in such remarkable HBV/E diversity, HBV full-size genome sequences were obtained from 47 HBV/E infected persons and P gene was subjected to Bayesian coalescent analysis. The time to the most recent common ancestor (tMRCA) for these HBV/E variants was estimated to be year 1952 (95% highest posterior density (95% HPD): 1927–1970). Using additional HBV/E sequences from other African countries, the tMRCA was estimated to be year 1948 (95% HPD: 1924–1966), indicating that HBV/E in these remote communities has a similar time of origin with multiple HBV/E variants broadly circulating in West/Central Africa. Phylogenetic analysis and statistical neutrality tests suggested rapid HBV/E population expansion. Additionally, skyline plot analysis showed an increase in the size of the HBV/E-infected population over the last ∼30–40 years.ConclusionsOur data suggest a massive introduction and relatively recent HBV/E expansion in the human population in Africa. Collectively, these data show a significant shift in the HBV/E epidemic dynamics in Africa over the last century.

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…This would support HBV/B1 being closely associated to HBV/B5, phylogenetically and with clinical outcomes, and suggests HBV/B1and HBV/B5 share a common ancestor predating estimated migration waves associated with present day Inuit [146]. The long-term relationship between host and pathogen may have led to the evolution of a 'pathogen attenuation' towards the host [147].…”

Evaluation of Some Immunological and Haematological Indices of Hepatitis B Infected Subjects in Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

“…Blood samples were collected from confirmed 150 HBV positive subjects that have tested HIV and HCV negative that consists of (65 males), (85 females) and same blood sample from 102 apparently healthy subjects (as control) consisted of (58 males ) and (44 females) [22].…”

Hepatitis B Virus Genotypes, Epidemiological Characteristics, and Clinical Presentation of HBV Chronic Infection in Immigrant Populations Living in Southern Italy

“…HBV genotype E shows a low degree of genetic diversity in blood samples collected from Senegal to Angola, supporting the segregation of this genotype into monophyletic groups (30), its relatively recent introduction to Central/Western Africa, and its explosive spread in these geographical areas through unsafe re-using of glass syringes and needles during mass-vaccination campaigns against yaws, sleeping sickness, smallpox, and measles (32,33). The data of the current paper confirmed this spread; out of the 109 HBsAg-positive immigrants with a detectable HBV genotype, 84 were from sub-Saharan areas and of these, 70 (83.3%) carried HBV genotype E. Another 5 patients showed HBV genotype E in the current study, 3 from Eastern Europe, 1 from the India-Pakistan subcontinent, and 1 from South America.…”