Hildegund C. J. Ertl - Rabies and Rabies Vaccines

Rabies has shaped humanity for centuries and continues to be one of the few pathogens that have a near 100% case fatality rate following the onset of clinical disease. Rabies virus, as with all related viruses within the Lyssavirus genus, is spread via the mechanistic action of the bite of an infected animal. Lyssaviruses are strongly neurotropic and as such most often require the dermal barrier to be breached to enable access to and infection of the nervous system. The domestic dog represents the principal reservoir of rabies virus globally and 99% of human cases involve the bite of an infected dog. Lyssaviruses are predominantly shed through saliva and so although a bite appears to be the most efficient mechanism of transmission rare alternative routes, including organ transplantation, have been reported. Despite the near 100% case fatality rate, post-exposure intervention can prevent the development of clinical disease and resulting fatality. Vaccines against rabies have been available, in various forms, for over 100 years and alongside the observation that passive immunisation with rabies immunoglobulin can completely prevent disease when administered pre-clinically the disease is entirely preventable. However, in endemic regions the cost and availability of post-exposure vaccines and immunoglobulins often precludes their use and rabies develops with the concomitant high fatality reported in endemic countries. The need for efficacious and yet cheaper pan-lyssavirus vaccines and biologicals to both prevent and treat rabies remains an important issue for future development. Furthermore, a lack of adequate reporting systems means that rabies is grossly underreported and that the burden of disease may be considerably higher. This chapter considers the basis of rabies classification, epidemiology and pathogenesis is reviewed highlighting areas for potential improvement in our understanding of this important group of viruses.

Introduction

Rabies is an ancient zoonotic disease caused by viruses of the order Mononegavirales, family Rhabdoviridae, and genus Lyssavirus [].

Classification and Epidemiology of the Lyssaviruses

The prototype virus of the Lyssavirus genus is RABV. However, although RABV is the most notable cause of human fatalities from rabies, other lyssaviruses have been described that are capable of causing rabies and that have contributed to the human and animal death toll from these viruses. In total, there are 16 proposed members of the Lyssavirus genus with the majority of the lyssavirus species having been detected in bats [.