Introductory Chapter: Rabies in the 21st Century

1. Introduction

Rabies is known as a fatal viral infection that is most commonly spread to humans and pets through the bites, scratches, or contamination of mucous membranes with the infected saliva of an infected animal. In an infected organism, an acute progressive encephalomyelitis/encephalitis develops ultimately resulting in death.

The infection is caused by a neurotropic zoonotic virus belonging to the Lyssavirus genus (named after Lyssa, an ancient Greek goddess, the personification of rabies) of the Rhabdoviridae family (from the Latin rhabdos, meaning “rod”, because the members of this family have rod-shaped virions). Currently, the Lyssavirus genus contains 18 virus species (https://talk.ictvonline.org/), and between them, the rabies virus is the most important one concerning its impact on public health.

2. Molecular biology of rabies virus

The rabies virus (RABV) is enveloped, bullet-shaped viruses, 180 nm in length and 75 nm wide (Figure 1). Virions are composed of two structural units: an internal helical nucleocapsid (consisting of nucleoprotein N and viral genome RNA), and a lipid envelope derived from the host cytoplasmic membrane during virus budding.

Figure 1.

The structure of the rabies virus (https://viralzone.expasy.org/22).

RABV contains a negative-sense ssRNA genome 11.9–12.3 kb in length, encoding five protein-coding genes: N, P, M, G, and L, which are separated by intergenic regions of variable length (Figure 2) [1]. P gene has alternative initiation points that lead to translation of P protein and at least four additional shorter gene products [2]. At 3′- and 5′- ends of RABV genome 58 nt leader sequence, and 57–70 nt trailer is located, subsequently [3].

Figure 2.

Genome structure of the rabies virus (https://viralzone.expasy.org/22).

3. Genetic diversity of rabies virus

Currently, phylogenetic analysis of RABV is commonly based on the N gene [4]. Previously, it was demonstrated that RABV genetic diversity has a strong geographic pattern throughout the world, which possibly results from the recent virus spread [5, 6]. Based on data received, all currently known RABV genetic variants can be divided globally into seven major groups [6]. Within these major groups, smaller genetic groups could be distinguished; thus, within the Cosmopolitan, and the Arctic/Arctic-like major groups, circulating in the Russian Federation six smaller groups were described in Russia: Arctic rabies (northern parts of Siberia), Arctic-like rabies (Khabarovsk Krai, Transbaikal region), Steppe rabies (Eurasian Steppe), Central European Russian rabies, Northeast European Rabies, and Caucasian rabies [6, 7, 8].

4. Rabies distribution

Currently, RABV is distributed globally and rabies infection is registered on all continents except Antarctica and, possibly, Australia. According to CDC data (https://www.cdc.gov/rabies/), the most (more than 90%) of all animal cases of rabies reported occur in wild animals; before 1960, most were in domestic animals. According to current data, the principal rabies hosts are wild carnivores and bats. Despite significant progress in the prevention and prophylaxis of rabies worldwide [9], rabies remains an important public health concern, especially in developing countries within Africa and Asia where rabies virus causes approximately 50,000 lethal cases per year [10]. Also, the official statistical data could be greatly underestimated due to the lack of systematic surveillance in some countries.

5. Rabies pathogenesis, prevention, and prophylaxis

Delivered into a wound through the bite or wound contamination with virus-containing biological liquids, the virus can replicate at the inoculation site [11]. After that, RABV reaches the sensory or motor neurons and then propagates up to the central nervous system by following neuronal connections. Such pathways through nervous tissue shield the virus from the host immune system, resulting in absence of early antibody response [12]. Being delivered to the central nervous system, the virus disseminates rapidly, and nearly all regions of the central nervous system may be affected. Nevertheless, the duration of the asymptomatic incubation period can be long-standing (two months on average), while the symptomatic period with clinical signs is rapid and severe (about one week).

Although rabies has the highest case fatality rate (100%), fortunately, it is a preventable disease. Postexposure prophylaxis consisting of rabies immune globulin or/and rabies vaccine is very effective in preventing the disease development when administered promptly after virus exposure has occurred. Also, very important measures to reduce the risk of RABV transmission to humans are vaccination of domestic animals against rabies and stray animal control programs.