The 2023 South Sudanese outbreak of Hepatitis E emphasizes ongoing circulation of genotype 1 in North, Central, and East Africa

In April 2023, an outbreak of acute hepatitis was reported amongst internally displaced persons in the Nazareth community of South Sudan. IgM serology-based screening suggested the likely etiologic agent to be Hepatitis E virus (HEV). In this study, plasma specimens collected from anti-HEV IgM-positive cases were subjected to additional RT-qPCR testing and sequencing of extracted nucleic acids, resulting in the recovery of five full and eight partial HEV genomes. Maximum likelihood phylogenetic reconstruction confirmed the genomes belong to HEV genotype 1. Using distance-based methods, we show that genotype 1 is best split into three sub-genotypes instead of the previously proposed seven, and that these sub-genotypes are geographically restricted. The South Sudanese sequences confidently cluster within sub-genotype 1e, endemic to northeast, central, and east Africa. Bayesian Inference of phylogeny incorporating sampling dates shows that this new outbreak is not directly descended from other recent local outbreaks for which sequence data is available. However, the analysis suggests that sub-genotype 1e has been consistently and cryptically circulating locally for at least the past half century and that the known outbreaks are often not directly descended from one another. The ongoing presence of HEV, combined with poor sanitation and hygiene in the conflict-affected areas in the region, place vulnerable populations at risk for infection and its more serious effects, including progression to fulminant hepatitis. •In April 2023, an outbreak of acute hepatitis caused by Hepatitis E virus (HEV) was reported amongst internally displaced persons in South Sudan.•Next-generation sequencing of patient plasma yielded five full and eight partial HEV genomes which belong to genotype 1, sub-genotype 1e.•Phylogenetic analyses suggest that there are three true sub-genotypes within genotype 1, and that these sub-genotypes are geographically restricted.•Temporal analysis suggests that sub-genotype 1e has been cryptically circulating in North, Central, and East Africa for the past half century.•We stress the need for to acquire more full-length HEV genomes to enhance surveillance efforts and improve molecular epidemiology studies.