Abstract:
Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis
worldwide. Hepatitis A virus is classified in the genus Hepatovirus of the family
Picornaviridae. The virion has a 7.5 kb positive-sense single-stranded RNA
genome and only one serotype of the virus has been identified so far. There
are six genotypes of HAV distinguished by nucleotide sequence analysis of the
VP1 region. Genotypes I, II and III, each with their subdivisions A and B, infect
humans. Genotypes IV, V and VI infect non-human primates. These
genotypes have a distinct geographical distribution. In 1997, it was established
that genotype IA and IB prevail in South Africa (SA) with IB being predominant.
However, no recent data have been published on the types of HAV circulating in
SA even though the virus was detected in surface water sources and on fresh
produce at the point of retail. There is an effective vaccine for the prevention of
hepatitis A, but recent publications have reported the possible emergence of
antigenic escape mutants of HAV. The aim of the study was therefore to establish which genotypes and possibly variants thereof of HAV are circulating
the community compared to the genotypes present in water and food sources.
To identify the different strains of HAV circulating in SA, detection and
characterisation of HAV strains was performed on clinical and environmental
sources. A total of 117 clinical specimens and 80 water samples (irrigation,
surface and wastewater) and 20 fresh produce (tomatoes, lettuce, cabbage)
samples were analysed. Samples were collected in SA and neighbouring
countries. Hepatitis A virus was detected in 78% of the clinical specimens and
in only 46% of the water samples. None of the fresh produce analysed in the
study tested positive for HAV even though some of the produce were irrigated
with HAV contaminated water. Molecular characterisation of the detected
strains revealed the presence of genotype IB in SA. The SA strains have a
unique nucleic acid sequence, namely a R298K mutation within the VP1 region
and R71S substitution within the VP1/P2B junction, which distinguishes them
from strains detected in the rest of the world and even in neighbouring
countries. The characterised strains were also analysed for the presence of
previously isolated antigenic escape mutants and/or novel ones. One possible
vaccine escape mutant, with a I179T substitution next to the neutralisation
residue Y181 in the VP1 region, was identified. A variety of strains with
mutation(s) at or around the neutralisation sites were also identified as well as
circulation of quasispecies among clinical HAV strains. The study revealed the
circulation of a potential new HAV genotype among the SA simian population.
The data provided by the study stresses the need to implement a proper
surveillance system of the circulation of HAV strains in SA.