Characterization of hepatitis delta virus in sub-Saharan Africa.

Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV), and infection with this virus aggravates acute and chronic liver disease. While HBV seroprevalence is very high across sub-Saharan Africa, much less is known about HDV in the region. In this study, almost 2,300 blood serum samples from Burkina Faso (n=1,131), Nigeria (n=974), Chad (n=50), and the Central African Republic (n = 118) were screened for HBV and HDV. Among 743 HBsAg-positive serum samples, 74 were positive for HDV antibodies and/or HDV RNA, with considerable differences in prevalence, ranging from <2% (pregnant women from Burkina Faso) to 50% (liver patients from Central African Republic). HDV seems to be much more common in chronic liver disease patients in the Central African Republic (CAR) than in similar cohorts in Nigeria. In a large nested mother-child cohort in Burkina Faso, the prevalence of HDV antibodies was 10 times higher in the children than in their mothers, despite similar HBsAg prevalences, excluding vertical transmission as an important route of infection. The genotyping of 16 full-length and 8 partial HDV strains revealed clade 1 (17/24) in three of the four countries, while clades 5 (5/24) and 6 (2/24) were, at least in this study, confined to Central Nigeria. On the amino acid level, almost all our clade 1 strains exhibited a serine at position 202 in the hepatitis D antigen, supporting the hypothesis of an ancient African HDV-1 subgroup. Further studies are required to understand the public health significance of the highly varied HDV prevalences in different cohorts and countries in sub-Saharan Africa.

Bayesian inference of the evolution of HBV/E.

Despite its wide spread and high prevalence in sub-Saharan Africa, hepatitis B virus genotype E (HBV/E) has a surprisingly low genetic diversity, indicating an only recent emergence of this genotype in the general African population. Here, we performed extensive phylogeographic analyses, including Bayesian MCMC modeling. Our results indicate a mutation rate of 1.9 × 10(-4) substitutions per site and year (s/s/y) and confirm a recent emergence of HBV/E, most likely within the last 130 years, and only after the transatlantic slave-trade had come to an end. Our analyses suggest that HBV/E originated from the area of Nigeria, before rapidly spreading throughout sub-Saharan Africa. Interestingly, viral strains found in Haiti seem to be the result of multiple introductions only in the second half of the 20th century, corroborating an absence of a significant number of HBV/E strains in West Africa several centuries ago. Our results confirm that the hyperendemicity of HBV(E) in today's Africa is a recent phenomenon and likely the result of dramatic changes in the routes of viral transmission in a relatively recent past.

A high variability of mixed infections and recent recombinations of hepatitis B virus in Laos.

In Lao PDR, where more than 8% of the population are chronic carriers of HBsAg, multiple genotypes and subgenotypes co-circulate and are prone to generate recombinant viruses. Phylogenetic analyses of multiple clones per donor revealed mixed infections of subgenotypes B1, B2, B4, C1, C5, I1 and I2 in almost 6% of HBsAg positive rejected blood donors. Recombination analyses and distance calculations furthermore showed that about 65% (17/26) of the mixed infected donors showed recombinations in the S-gene alone, involving the predominant genotypes B and C. These results suggest that, at least in Laos, hepatitis B virus (HBV) mixed infections lead to frequent recombinations. In many donors with recombinant strains, the recombinant fragment and a non-recombinant strain of the same genotype co-existed (127/185 analysed recombinant fragments). For a large proportion of these (60/127), the most closely related known virus was found, although not always exclusively, in the same donor. Recombinant virus strains are largely distinct. This is reflected in an unexpected diversity in recombination breakpoints and the relatively rare recombinations with identical recombination patterns of the same genotypes in different donors. Recent recombination events would explain the limited spread of each of the recombinants. Using a published mutation rate of 4.2 × 10(-5) mutations per site and year, the observed minimum genetic distances of 0-0.60% between parent strain and recombinant fragment would correspond to 0-71 years of evolution from a most recent common ancestor (MRCA). Thus several lines of evidence are suggestive of recent independent recombination events, a proportion of these even occurring within the same donors. In conclusion, our analyses revealed a high variability of mixed infections as a very probable breeding ground of multiple variable recombination events in Laos that so far have not led to new dominant strains.

Slave trade and hepatitis B virus genotypes and subgenotypes in Haiti and Africa.

In Haiti, >90% of the population descended from African slaves. Of 7,147 Haitian pregnant women sampled, 44% of hepatitis B virus (HBV) infections were caused by genotype A1, which today is found mainly in eastern Africa. Twenty percent belong to a rare subgenotype, A5, which has been found only in the former Bight of Benin, a former primary slave trading post. Haitian A subgenotypes appear to have separated early from the African subgenotypes; the most prevalent genotype and subgenotype in West Africa today (E and A3, respectively) are rare in Haiti. This difference indicates that the dominant subgenotypes in Africa emerged in the general population only after the slave trade and explains the low genetic diversity of genotype E. The high prevalence of HBV genotype E in much of Africa further suggests that HBV hyperendemicity is a recent phenomenon, probably resulting from extensive use of unsafe needles.

Hepatitis B virus: the genotype E puzzle.

Hepatitis B virus (HBV) is highly endemic throughout sub-Saharan Africa. One of the two genotypes A and E dominates in most countries. With several subgenotypes and variants, genotype A is more diverse in Africa (4.00%) than in the rest of the world (2.96%), suggesting an African origin and a long history on the continent. Despite the African slave trade, genotype E has only sporadically been found within the Americas, indicating that this genotype was introduced only during the past 200 years into the general African population. A short history for this genotype in Africa is also supported by its conspicuously low genetic diversity (1.75%), which contrasts, however, with its excessively high HBsAg prevalence and its extensive spread throughout the vast West-African genotype E crescent. We discuss the spread and routes of transmission of genotype E and suggest that the distribution and current high prevalence levels of HBV (genotype E) in Africa are the result of the extensive use of unsafe needles, potentially solving the current African genotype E puzzle and shedding new light on the high HBV prevalence in Africa.

Hepatitis B virus genotype E variability in Africa.

BACKGROUND: In sub-Saharan Africa, genotype E is the predominant genotype throughout a vast region spanning from Senegal to Namibia and extending to the Central African Republic in the East. Despite its wide geographic distribution and the high prevalence throughout this genotype E crescent, this genotype has a very low genetic diversity. OBJECTIVES: Here we review our current understanding of genotype E reanalysing all currently available sequences of the S gene and the complete genome. RESULTS: Phylogenetic analysis of the complete genome sequences confirmed a previously suggested South-West/Central African cluster and several lineages of West African sequences. The overall mean genetic distance was 1.71%, with the more Southern countries of the genotype E crescent exhibiting lower distances than the Northern countries. CONCLUSIONS: Genotype E seems to have a longer natural history in the Northern part of the genotype E crescent than in the Southern countries. As genotype E is essentially absent from the Americas despite the Afro-American slave trade until at least the beginning of the 19th century, genotype E strains may have been introduced into the general African population only within the past 200 years. How the virus may have spread throughout the genotype E crescent warrants further investigation.