Abstract:
West Nile virus (WNV) is widely distributed in South Africa, but since a few cases of neurological disease have
been reported from this region, endemic lineage 2 strains were postulated to be of low virulence. Several cases
of nonfatal encephalitis in humans as well as fatal cases in a foal, dog, and ostrich chicks have, however, been
associated with lineage 2 WNV in South Africa. The pathogenesis of lineage 2 WNV strains was investigated
using mouse neuroinvasive experiments, gene expression experiments, and genome sequence comparisons
which indicated that lineage 2 strains that are highly pathogenic exist. To determine whether cases of WNV
were being missed in South Africa, horses with fever and neurological disease were investigated. Several cases
of WNV were identified, all associated with severe neurological disease, 85% of which had to be euthanized or
died. All cases positive by RT-PCR were shown to belong to lineage 2 WNV by DNA sequencing and phylogenetic
analysis. Two cases of occupational infection were investigated, including a case of zoonotic transmission
to a veterinarian who performed an autopsy on one of the horses as well as a laboratory infection after a
needle stick injury with a neuroinvasive lineage 2 strain. Both resulted in neurological disease. Cytokine
expression was investigated in the second case to assess the immunopathogenesis of WNV. Collectively, these
studies suggest that lineage 2 WNV may be significantly under estimated as a cause of neurological disease in
South Africa.
