Rabies is one of the most dreadful zoonotic diseases that affects the central nervous system of humans and warm-blooded animals. The disease is transmitted from animal to man and from animal to animal through saliva, as animal bites introduce the causative virus into the muscle and nerve ending-rich tissues.

After penetration into nerve cells, viral replication ensues and the virus progressively travels to the brain through the spinal cord. Depending on the distance from the site of the bite and the brain, the travelling can take weeks or even months. Nevertheless, once the symptoms appear (such as hydrophobia, aggressiveness, hallucinations and paralysis), rabies is practically always fatal.

This disease has been recognized for centuries, and has a long and interesting history. The word rabies is derived from the Latin word rabere, which comes from an old Sanskrit word rhabas, meaning “to do violence”. The ancient Greeks even had a special god in their mythology that counteracted the effect of rabies – his name was Aristaeus.

Etiological agent and its epidemiology

Taxonomically, rabies virus is a rhabdovirus that belongs to the genus Lyssavirus and family Rhabdoviridae. Virion particles have a bullet-shaped structure, with an average diameter of 25 nanometers and length of 180 nanometers. Each particle contains a helical nucleocapsid surrounded by a lipid bilayer, and the genome consists of nonsegmented, single-stranded RNA.

Rabies virus is currently endemic in at least 150 countries. Although certain countries (such as Australia, UK, Japan, Norway, Sweden, Singapore and some islands in Indonesia) have been free of the classical rabies virus for years, the size and number of rabies-free territories is small when compared to areas affected with this disease.

According to the estimates of the World Health Organization (WHO), there are more than 30 thousand human rabies deaths every year in Asia. India accounts for 36% of the global rabies death burden, whereas Nepal has one of the highest per capita rates of deaths in the world.

In Africa, rabies is responsible for at least 24 thousand deaths every year, most of them reported in children and poor rural communities. Although the virus is still found in Europe, the human form of the disease has disappeared from many European countries, probably as a result of animal vaccination policy.

Defining a susceptible host

A number of events are required for infection to be established, such as direct contact with a receptive host cell and subsequent entry, followed by uncoating of viral particles. Intracytoplasmic production of nucleic acid and viral proteins occurs afterwards, and virions have to be able to assemble and successfully exit the cells in order to perpetuate the infection cycle.

From the cellular, biochemical, and tissue levels of organization to an entire organism, such viral strategy of entrance, self-production and exit of progeny forms the innate capability of a human or animal host to become rabid and infectious to others. In theory, a single virion is sufficient to initiate the process.

Nevertheless, due to innate immunity, multiple infectious units are usually needed, thus a very susceptible species or host could be defined as the one in which only a small number of viral particles are required to result in rabies. Host susceptibility is also influenced by individual factors (such as age and immune status), as well as attributes unique to different species.

Reservoir host species are those that can successfully sustain intra-species maintenance of a rabies virus variant within a specific geographic area. The co-evolution of mammalian reservoirs and associated viral variants is still not completely clear, but we know that the genetic differences are the greatest between rabies viruses of terrestrial species and those found in bats.

Risk assessment of human exposure

As the nature of bite or contact differs in each event, and taking into account the varied epidemiology of rabies in different regions, the individual risk assessment of rabies transmission is pivotal for appropriate decision-making regarding the course of post exposure prophylaxis. Exhaustive and meticulous history is the crucial step in that regard.

WHO has introduced guidelines for potential rabies exposure into Category I, II and III, with appropriate prophylactic measures linked to different categories. Groups of people considered as high-risk for acquiring this disease (such as animal handlers, veterinarians or laboratory workers) necessitate pre-exposure prophylaxis.

Most of animal and human exposures to rabies can be successfully prevented by better awareness of transmission routes, appropriate veterinary care and limited contact with wildlife. Swift application of measures such as local wound cleaning, passive immunization, as well as vaccination with tissue-culture vaccines has shown consistent effectiveness.