Rabies is a vaccine-preventable, zoonotic, viral disease. Once clinical symptoms appear, rabies is virtually 100% fatal. In up to 99% of cases, domestic dogs are responsible for rabies virus transmission to humans. Yet, rabies can affect both domestic and wild animals. It is spread to people and animals through bites or scratches, usually via saliva.

Rabies is present on all continents, except Antarctica, with over 95% of human deaths occurring in the Asia and Africa regions. Rabies is one of the Neglected Tropical Diseases (NTD) that predominantly affects poor and vulnerable populations who live in remote rural locations. Approximately 80% of human cases occur in rural areas. Although effective human vaccines and immunoglobulins exist for rabies, they are not readily available or accessible to those in need. Globally, rabies deaths are rarely reported and children between the ages of 5–14 years are frequent victims. Managing a rabies exposure, where the average cost of rabies post-exposure prophylaxis (PEP) is currently estimated at an average of US$ 108 can be a catastrophic financial burden on affected families whose average daily income may be as low as US$ 1–2 per person[1].

Every year, more than 29 million people worldwide receive a post-bite vaccination. This is estimated to prevent hundreds of thousands of rabies deaths annually. Globally, the economic burden of dog-mediated rabies is estimated at US$ 8.6 billion per year.

Prevention

Eliminating rabies in dogs

Rabies is a vaccine-preventable disease. Vaccinating dogs is the most cost-effective strategy for preventing rabies in people. Dog vaccination reduces deaths attributable to dog-mediated rabies and the need for PEP as a part of dog bite patient care.

Awareness on rabies and preventing dog bites

Education on dog behaviour and bite prevention for both children and adults is an essential extension of a rabies vaccination programme and can decrease both the incidence of human rabies and the financial burden of treating dog bites. Increasing awareness of rabies prevention and control in communities includes education and information on responsible pet ownership, how to prevent dog bites, and immediate care measures after a bite. Engagement and ownership of the programme at the community level increases reach and uptake of key messages.

Immunization of people

The same vaccine is used to immunize people after an exposure (see PEP) or before exposure to rabies (less common). Pre-exposure immunization is recommended for people in certain high-risk occupations such as laboratory workers handling live rabies and rabies-related (lyssavirus) viruses; and people (such as animal disease control staff and wildlife rangers) whose professional or personal activities might bring them into direct contact with bats, carnivores, or other mammals that may be infected.

Pre-exposure immunization might be indicated also for outdoor travellers to and expatriates living in remote areas with a high rabies exposure risk and limited local access to rabies biologics. Finally, immunization should also be considered for children living in, or visiting such areas. As they play with animals, they may receive more severe bites, or may not report bites.

Symptoms

The incubation period for rabies is typically 2–3 months but may vary from 1 week to 1 year, dependent upon factors such as the location of virus entry and viral load. Initial symptoms of rabies include a fever with pain and unusual or unexplained tingling, pricking, or burning sensation (paraesthesia) at the wound site. As the virus spreads to the central nervous system, progressive and fatal inflammation of the brain and spinal cord develops.

There are two forms of the disease:

Furious rabies results in signs of hyperactivity, excitable behaviour, hydrophobia (fear of water) and sometimes aerophobia (fear of drafts or of fresh air). Death occurs after a few days due to cardio-respiratory arrest.

Paralytic rabies accounts for about 20% of the total number of human cases. This form of rabies runs a less dramatic and usually longer course than the furious form. Muscles gradually become paralyzed, starting at the site of the bite or scratch. A coma slowly develops, and eventually death occurs. The paralytic form of rabies is often misdiagnosed, contributing to the under-reporting of the disease.

Diagnosis

Current diagnostic tools are not suitable for detecting rabies infection before the onset of clinical disease, and unless the rabies-specific signs of hydrophobia or aerophobia are present, clinical diagnosis may be difficult. Human rabies can be confirmed intra-vitam and post mortem by various diagnostic techniques that detect whole viruses, viral antigens, or nucleic acids in infected tissues (brain, skin or saliva)[2].

Transmission



People are usually infected following a deep bite or scratch from an animal with rabies, and transmission to humans by rabid dogs accounts for 99% of cases.

In the Americas, bats are now the major source of human rabies deaths as dog-mediated transmission has mostly been broken in this region. Bat rabies is also an emerging public health threat in Australia and Western Europe. Human deaths following exposure to foxes, raccoons, skunks, jackals, mongooses and other wild carnivore host species are very rare, and bites from rodents are not known to transmit rabies.

Transmission can also occur if saliva of infected animals comes into direct contact with human mucosa or fresh skin wounds. Contraction of rabies through inhalation of virus-containing aerosols or through transplantation of infected organs is described, but extremely rare. Human-to-human transmission through bites or saliva is theoretically possible but has never been confirmed. The same applies for transmission to humans via consumption of raw meat or milk of infected animals.

Post-exposure prophylaxis (PEP)

Post-exposure prophylaxis (PEP) is the immediate treatment of a bite victim after rabies exposure. This prevents virus entry into the central nervous system, which results in imminent death. PEP consists of:

Extensive washing and local treatment of the bite wound or scratch as soon as possible after a suspected exposure;

a course of potent and effective rabies vaccine that meets WHO standards; and

the administration of rabies immunoglobulin (RIG), if indicated.

Starting the treatment soon after an exposure to rabies virus can effectively prevent the onset of symptoms and death.

Extensive wound washing

This first-aid measure includes immediate and thorough flushing and washing of the wound for a minimum of 15 minutes with soap and water, detergent, povidone iodine or other substances that remove and kill the rabies virus.

Exposure risk and indications for PEP

Depending on the severity of the contact with the suspected rabid animal, administration of a full PEP course is recommended as follows:

Table: Categories of contact and recommended post-exposure prophylaxis (PEP) Categories of contact with suspect rabid animal Post-exposure prophylaxis measures Category I - touching or feeding animals, animal licks on intact skin (no exposure) Washing of exposed skin surfaces, no PEP Category II - nibbling of uncovered skin, minor scratches or abrasions without bleeding (exposure) Wound washing and immediate vaccination Category III - single or multiple transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from animal licks, exposures due to direct contact with bats (severe exposure) Wound washing, immediate vaccination and administration of rabies immunoglobulin

All category II and III exposures assessed as carrying a risk of developing rabies require PEP.

This risk is increased if:

the biting mammal is a known rabies reservoir or vector species

the exposure occurs in a geographical area where rabies is still present

the animal looks sick or displays abnormal behaviour

a wound or mucous membrane was contaminated by the animal’s saliva

the bite was unprovoked

the animal has not been vaccinated.

The vaccination status of the suspect animal should not be the deciding factor when considering to initiate PEP or not when the vaccination status of the animal is questionable. This can be the case if dog vaccination programmes are not being sufficiently regulated or followed out of lack of resources or low priority.

WHO continues to promote human rabies prevention through the elimination of rabies in dogs, dog bite prevention strategies, and more widespread use of the intradermal route for PEP which reduces volume and therefore the cost of cell-cultured vaccine by 60% to 80%.

Integrated bite case management

If possible, the veterinary services should be alerted, the biting animal identified, removed from the community and either quarantined for observation (for healthy dogs and cats) or submitted for immediate laboratory examination (dead or euthanized animals showing clinical signs of rabies). PEP must be continued during the 10-day observation period or while awaiting laboratory results. Treatment may be discontinued if the animal is proven to be free of rabies. If a suspect animal cannot be captured and tested, then a full course of PEP should be completed. Joint contact tracing by veterinary and public health services is encouraged to identify additional suspected rabid animals and human bite victims, with the goal to apply preventive measures accordingly.

WHO response

Rabies is included in WHO’s new 2021-2030 road map. As a zoonotic disease, it requires close cross-sectoral coordination at the national, regional and global levels.

WHO, FAO (Food and Agriculture Organization) and OIE (World Organisation for Animal Health), have prioritized rabies under a One Health approach

WHO leads the ‘United Against Rabies’ (UAR) – a multi-stakeholder platform to advocate for, and prioritize investments in rabies control and coordinate the global rabies-elimination efforts to achieve zero human deaths from dog-mediated rabies by 2030

WHO works with partners to guide and support countries as they develop and implement their national rabies elimination plans

WHO regularly updates and disseminates technical guidance on rabies [4], for example on epidemiology, surveillance, diagnostics, vaccines, safe and cost-effective immunization[5], control and prevention strategies for human and animal rabies, operational programme implementation[6] and palliative care for human rabies patients

On the path towards rabies elimination countries can request WHO validation of achieving zero human deaths from dog-mediated rabies [4] and seek OIE endorsement of their dog rabies control programmes and self-declare freedom from dog rabies[7]



Mexico was the first country to have been validated by WHO in 2019 for eliminating human deaths from dog-mediated rabies



Inclusion of rabies biologics into countries list of essential medicines and advocating for increased access of poor and rural populations to PEP is a WHO priority and strengthens the global movement towards achieving Universal Health Coverage



In 2019 Gavi has included human rabies vaccines in its vaccine investment strategy 2021-2025 which will support scaling up rabies PEP in Gavi eligible countries, WHO will continue to advise on best strategies and practices for its roll out to countries requesting rabies vaccine.



Monitoring of rabies programmes and disease surveillance are needed to measure impact and for increasing awareness and advocacy.

The 2030 NTD Roadmap is a key guiding document for the global response to NTDs over the next decade and includes regional, progressive targets for rabies elimination[9]

The key towards sustaining and expanding the rabies programmes to adjacent geographies has been to start small, catalyse local rabies programmes through stimulus packages, demonstrate success and cost-effectiveness, and ensure the engagement of governments and affected communities.

Rabies elimination needs adequate and long-term investments. Showcasing local success and raising awareness on rabies have been proven effective to gain and maintain political will.

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