Abstract:
Lyssaviruses cause the disease rabies, which is a fatal encephalitic disease resulting in
approximately 59,000 human deaths annually. The prototype species, rabies lyssavirus, is
the most prevalent of all lyssaviruses and poses the greatest public health threat. In Africa,
six confirmed and one putative species of lyssavirus have been identified. Rabies
lyssavirus remains endemic throughout mainland Africa, where the domestic dog is the
primary reservoir – resulting in the highest per capita death rate from rabies globally.
Rabies is typically transmitted through the injection of virus-laden saliva through a bite or
scratch from an infected animal. Due to the inhibition of specific immune responses by
multifunctional viral proteins, the virus usually replicates at low levels in the muscle tissue
and subsequently enters the peripheral nervous system at the neuromuscular junction.
Pathogenic rabies lyssavirus strains inhibit innate immune signaling and induce cellular
apoptosis as the virus progresses to the central nervous system and brain using viral
protein facilitated retrograde axonal transport. Rabies manifests in two different forms - the
encephalitic and the paralytic form - with differing clinical manifestations and survival times.
Disease symptoms are thought to be due mitochondrial dysfunction, rather than neuronal
apoptosis. While much is known about rabies, there remain many gaps in knowledge
about the neuropathology of the disease. It should be emphasized however, that rabies is
vaccine preventable and dog-mediated human rabies has been eliminated in various
countries. The global elimination of dog-mediated human rabies in the foreseeable future
is therefore an entirely feasible goal.
