First evidence for continuous circulation of hepatitis A virus subgenotype IIA in Central Africa

Abstract

Although a high seroprevalence of antibodies against hepatitis A virus (HAV) has been estimated in Central Africa, the current status of both HAV infections and seroprevalence of anti-HAV antibodies remains unclear due to a paucity of surveillance data available. We conducted a serological survey during 2015-2017 in Gabon, Central Africa, and confirmed a high seroprevalence of anti-HAV antibodies in all age groups. To identify the currently circulating HAV strains and to reveal the epidemiological and genetic characteristics of the virus, we conducted molecular surveillance in a total of 1007 patients presenting febrile illness. Through HAV detection and sequencing, we identified subgenotype IIA (HAV-IIA) infections in the country throughout the year. A significant prevalence trend emerged in the young child population, presenting several infection peaks which appeared to be unrelated to dry or rainy seasons. Whole-genome sequencing and phylogenetic analyses revealed local HAV-IIA evolutionary events in Central Africa, indicating the circulation of HAV-IIA strains of a region-specific lineage. Recombination analysis of complete genome sequences revealed potential recombination events in Gabonese HAV strains. Interestingly, Gabonese HAV-IIA possibly acquired the 5'-untranslated region (5'-UTR) of the rare subgenotype HAV-IIB in recent years, suggesting the present existence of HAV-IIB in Central Africa. These findings indicate a currently stable HAV-IIA circulation in Gabon, with a high risk of infections in children aged under 5 years. Our findings will enhance the understanding of the current status of HAV infections in Central Africa and provide new insight into the molecular epidemiology and evolution of HAV genotype II.

Keywords: Africa; Gabon; Hepatitis A virus; subgenotype IIA.

FIGURE 1

Phylogenetic analysis of the VP1‐P2B sequence of HAV. A maximum‐likelihood tree was inferred with 5000 bootstrap replicates. For better visualization of sequence positions, several clusters were collapsed and shown as triangles. Virus lineages are shown on the right. Bootstrap values of ≥70% are shown at the nodes. Scale bar indicates nucleotide substitutions per site. An entire illustration of the phylogeny is provided in Figure S3

FIGURE 2

Phylogenetic analysis of the short VP1‐P2B sequence of HAV‐IIA using a time‐scaled Bayesian maximum clade credibility tree. Virus lineages are shown on the right. An entire illustration of the phylogeny, including 95% CI bars at each node, is provided in Figure S4

FIGURE 3

Detection of potential recombination events in Gabonese HAV strains. Bootscan evidence for the recombination event of (A) the representative of Gabonese HAV‐IIA strains (SYMAV‐D01) with the reference strains of HAV‐IIA and HAV‐IIB, and (B) Gabonese HAV‐IB (SYMAV‐D12) with the reference strains of HAV‐IA and HAV‐IB. Orange areas depict potential recombination events