Rabies

Additional scientific description

Human

Rabies is caused by the rabies virus in the family Rhabdoviridae and the genus Lyssavirus. It is a zoonotic disease, (an infectious disease which spreads from humans to animals) and probably the oldest known infectious disease of people. Rabies is a serious public health problem (WHO, 2024a).

Tens of thousands of people die from rabies each year. Rabies is a fatal but preventable infectious disease. Human rabies is preventable via thorough wound washing, administration of a course of human rabies vaccine and, when indicated, rabies immunoglobulins (RIG) (WHO, 2024a)

In up to 99% of human rabies cases, dogs are responsible for virus transmission. Children between the ages of 5 and 14 years are frequent victims (WHO, 2024a).

Rabies is transmitted through inoculation of infectious saliva via a bite (most common), scratch, or direct contact with mucosa (e.g. eyes, mouth, or open wound). This causes local muscle infection and then uptake by peripheral nerves where it spreads to the central nervous system and replicates in the brain prior to spreading to salivary glands and being excreted in saliva (WHO, 2024a).

Vaccinating people and dogs saves lives and stops transmission. Rabies in people can be prevented through dog bite prevention, wound washing, and post-exposure prophylaxis. Rabies in dogs can be prevented through responsible dog ownership and routine mass dog vaccination (WHO, 2024a).

Clinically rabies is characterized by an incubation phase, a prodromal phase and then a neurological phase which precedes death. In humans, following exposure, the incubation period is usually 4-12 weeks (but may range from < 1 week to > 12 months). Rabies is almost always fatal once clinical signs appear. This is followed by a prodromal phase of generic symptoms such as fever, malaise, fatigue, headaches, loss of appetite and tingling at the wound site. Their neurological phase consists of two distinct clinical forms, furious and paralytic. The furious form is characterized by hyperactivity, hallucinations, aerophobia, hydrophobia, excessive salivation, and aggression and usually lasts 5 days. The paralytic form is characterized by progressive paralysis and coma and usually lasts up to 14 days (WHO, 2018a).

An estimated 59,000 people die each year from rabies; however, this number is likely a gross underestimate due to underreporting and uncertain estimates. It can be misdiagnosed as another viral encephalitis or cerebral malaria, many deaths occur at home, surveillance is inadequate, and it commonly affects poor, rural communities which are commonly underserved.

Currently, there are no WHO-approved diagnostic tools for detecting rabies infection before the onset of clinical disease. Clinical diagnosis of rabies is difficult without a reliable history of contact with a rabid animal or specific symptoms of hydrophobia or aerophobia. Accurate risk assessment is crucial for deciding on PEP administration (WHO, 2024a). Once symptoms emerge, and death is inevitable, offering comprehensive and compassionate palliative care is recommended. Post-mortem confirmation of rabies infection is done by various diagnostic techniques that detect whole viruses, viral antigens, or nucleic acids in infected tissues (brain, skin or saliva) (WHO, 2024a). Where possible, the biting animal should be tested (WHO, 2024a).

Wound washing as soon as possible after exposure for 15 minutes with copious amounts of soap and water is the first life-saving measure following exposure. A detailed assessment should be conducted to determine PEP eligibility, including an assessment of the health status of the biting animal, wound category and if the patient has already received rabies vaccine. Pre-exposure prophylaxis shortens but does not replace post-exposure prophylaxis, WHO has produced a decision tree to aid this process (WHO, 2024b; WHO 2024a PEP should be started as soon as possible following exposure; it is never too late to administer PEP. Pre-exposure prophylaxis vaccine is recommended for high-risk individuals such as communities and travellers in remote, highly endemic settings and individuals at occupational risk. WHO prequalified vaccines are safe, effective, and well tolerated (WHO, 2024a). There are a number of approved vaccine schedules, however, intra-dermal vaccination is recommended as it saves costs, doses and time (WHO, 2018b). Rabies immunoglobulin (RIG) is recommended for severe exposure for those who have not previously received rabies vaccines.

Since rabies is widespread in most of the world and across many animal species, it is very difficult to eradicate but: domestic dogs play a crucial role in the transmission of rabies to other species.

Rabies elimination requires a One Health approach. Human and dog rabies are correlated. Addressing rabies at its source - dog rabies -is the most efficient and cost-effective way to break transmission. The World Health Organization (WHO), the World Organization for Animal Health (WOAH), the Food and Agricultural Organization of the United Nations (FAO) and the Global Alliance for Rabies Control have united to deliver Zero by 30: The Global Strategic Plan to Prevent Human Deaths from Dog-Transmitted Rabies by 2030. It provides a coordinated response using a three-pillar approach: increasing availability of human post-exposure prophylaxis, awareness and community engagement and mass dog vaccination. This aligns with the United Nations Sustainable Development Goals through strengthening human and veterinary health systems to reach the world's most underserved populations (WHO, FAO & OIE, 2018).

Community engagement is fundamental to the success of mass dog vaccination; local communities are key stakeholders. Rabies elimination happens at community level. Awareness activities must target vulnerable populations.

Animal

Rabies is a viral disease that affects the central nervous system of mammals (dogs, cats, foxes etc.) (WOAH, no date). Rabies is preventable through vaccination (Rupprecht & Gatewood, 2021). While 99% of human rabies cases are due to bites from infected dogs, rabies vaccines for dogs can efficiently eliminate the disease at its animal source (WOAH, no date). Most countries maintain a list of approved veterinary vaccines for use. For specific regulations, consult the country's veterinary authorities.

Rabid dogs are infective even when their clinical signs are still mild. Notably in dogs, the furious form is characterized by altered behaviour, aggression, incoordination, drooping jaw and altered tone of bark. There is an absence of aerophobia and hydrophobia in dogs (WOAH, 2024a; WOAH, 2024b)). Rabid cats can attack suddenly, biting and scratching viciously. As the disease progresses, seizures and lack of muscle coordination are common. Death is caused by progressive paralysis (MSD, 2024). In the Americas, bat species are also reservoirs for rabies virus (WHO, 2024).

Clinical signs in affected wildlife can be variable and subtle. A common and important feature is a change in behaviour including a loss of fear, ataxia, and subsequent aggression towards other animals and people. Wild animals will often lose their natural caution around humans. Animals may wander into urban areas and into buildings. Abnormal appetite (pica) and unusual vocalisation, which is often incessant. Excitation is often seen and may present as ceaseless running over long distances, with or without snapping at nearby objects, animals or people. A rabid fox may charge at and bite passing people, animals and even vehicles. Paralysis, paresis and, in the terminal stages, coma occur (Wildlife Health Australia, 2024).

There are many strains of the rabies virus maintained in particular reservoir hosts. These include Canidae (dogs, jackals, coyotes, wolves, foxes and raccoon dogs), Mustelidae (skunks, martens, weasels and stoats), Viverridae (mongooses and meerkats), Procyonidae (raccoons), and the order Chiroptera (bats). The important reservoir hosts vary with the area. Cat-adapted rabies variants have not been seen, although cats are often infected with rabies viruses from other hosts, and they can readily transmit the virus (CFSPH et al., 2009).

Metrics and numeric limits

An estimated 59,000 people die of rabies every year in over 150 countries, approximately 99% are acquired from the bite of an infected dog. 95% of human cases occur in Africa and Asia. Due to underreporting and uncertain estimates, this number is likely a gross underestimate. The burden of disease is disproportionally borne by rural poor populations, with approximately half of cases attributable to children under 15 years of age (WHO, 2024a).

The global cost of rabies is estimated to be around US$ 8.6 billion per year including lost lives and livelihoods, medical care and livestock losses, as well as uncalculated psychological trauma (WHO, 2024a).