PATHOGENESIS, PATHOLOGY AND IMMUNITY

Animal rabies is characterized by encephalitis and myelitis, which cause a progressive alteration of the central nervous system (CNS) and a range of clinical features. Rabies virus was shown to be highly pathogenic in the red fox, with an incubation period varying from 11 days up to 15 months, depending on the dose and on the route of inoculation.

Rabies viruses have profound effects on the functions of infected and some uninfected neurons. Minor elec­troencephalographic changes during animal infection indicate neuronal dysfunction. However, a range of abnor­malities are seen in magnetic resonance imaging (MRI) as human encephalitis progresses. Several hypotheses have been raised to explain the effect of rabies virus on neuronal function: changes in neurotransmitter functions could lead to failure of brain networking and regulation of responses, and disruption of neuronal metabolism, ending in the exhaustion of metabolic pools; infections of neurons by rabies virus may result in modifications of the expres­sion of numerous genes involved in, for example, protein synthesis, neuron growth and interferon response.

The spread of the virus through the nerves does not promote the rapid onset of a strong immunological response. The serological response to rabies virus appears irregularly, and always late in the clinical course of the disease and is therefore of little value for diagnostic pur­poses or protection.

The neurotropism and clinical effects of bat lyssaviruses are known to be comparable to those of the RABV; when natural transmission to other mammals of these viruses occurs, clinical signs are similar to rabies. These ‘terrestrial mammals’ are dead-end hosts and unable to transmit an infectious, bat-derived virion to a new host. Nevertheless, RNA can be detected in salivary glands of infected animals(⁹). Experiments have shown that terrestrial mammal susceptibility to EBLV is low by the intramuscu­lar (IM) route; however, animals were sensitive to intrac­ranial (IC) inoculation. Foxes inoculated IC exhibited clinical signs of rabies and succumbed from 14—24 days post-infection (dpi). All clinically ill foxes developed neu­tralizing antibodies, and viral antigen, infectious particles and viral RNA occurred in the brain. Salivary glands were infected in half of the animals, but none of the oral swabs collected from these animals were positive for viral RNA or infectious particles⁽¹⁰⁾. These data suggest that the chance of an EBLV spillover from bat to fox is low, but with a greater probability for EBLV1 than for EBLV2.

There is no specific gross pathology in rabies- infected animals. Some external skin damage can be linked with disturbances in behaviour induced by rabid encephalitis. Self-mutilation, injuries resulting from muscular spasm or paresis can be suggestive of the disease, mostly in small ruminants such as the roe deer, where abrasion of the forehead skin is a frequent finding in animals that have died from rabies infection.

Histologically, rabies shows mild changes. Apoptosis has been demonstrated in cell culture and in inoculated mice together with non-specific encephalomyelitis, with perivas­cular cuffing with lymphocytes or polymorphonuclear cells. Intracytoplasmic inclusion bodies - Negri bodies - in the neurons are typical of certain forms of brain rabies infection.