Rabies

17 May 2021

Key facts
 Rabies is a vaccine-preventable viral disease which occurs in more than
150 countries and territories.
 Dogs are the main source of human rabies deaths, contributing up to 99%
of all rabies transmissions to humans.
 Interrupting transmission is feasible through vaccination of dogs and
prevention of dog bites.
 Infection causes tens of thousands of deaths every year, mainly in Asia
and Africa.
 Globally rabies causes an estimated cost of US$ 8.6 billion per year
 40% of people bitten by suspect rabid animals are children under 15 years
of age.
 Immediate, thorough wound washing with soap and water after contact
with a suspect rabid animal is crucial and can save lives.
 Engagement of multiple sectors and One Health collaboration including
community education, awareness programmes and vaccination campaigns
are critical.
 WHO leads the collective “United Against Rabies” to drive progress
towards "Zero human deaths from dog-mediated rabies by 2030".

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 paralysed, 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 up to 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)     

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

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 and have
launched he ‘United Against Rabies Forum’ (UAR), a multi-stakeholder platform.
 UAR advocates and prioritizes investments in rabies control and coordinates the
global rabies-elimination efforts to achieve zero human deaths from dog-mediated
rabies by 2030Progress in rabies elimination provides an indicator of One Health
operationalization and strengthened human and animal health systems.
 Rabies can significantly contribute to building of capacity outside of the health
structures and of a siloed notion of health, and demonstrate that One Health can
truly provide a framework in which cross-cutting benefits can be realised and
shared.
 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 3, for
example on epidemiology, surveillance, diagnostics, vaccines, safe and cost-
effective immunization4, control and prevention strategies for human and animal
rabies, operational programme implementation 5 ;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 3; and seek OIE
endorsement of their dog rabies control programmes and self-declare freedom from
dog rabies  6;
 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 included human rabies vaccines in its vaccine investment strategy
2021-2025 which will support scaling up rabies PEP in Gavi eligible countries. Its
roll out has been disrupted due to Covid-19 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 guiding document for the global response to NTDs over
the next decade and includes regional, progressive targets for rabies elimination 7

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. 

Rabies is a viral zoonotic disease that causes progressive and fatal inflammation of the
brain and spinal cord. Clinically, it has two forms: 

1. Furious rabies – characterized by hyperactivity and hallucinations.

2. Paralytic rabies – characterized by paralysis and coma.

Although fatal once clinical signs appear, rabies is entirely avoidable; vaccines,
medicines and technologies have long been available to prevent death from rabies.
Nevertheless, rabies still kills tens of thousands of people each year. Of these cases,
approximately 99% are acquired from the bite of an infected dog. 

Dog-mediated human rabies can be eliminated by tackling the disease at its source:
infected dogs. Making people aware of how to avoid the bites of rabid dogs, to seek
treatment when bitten and to vaccinate animals can successfully disrupt the rabies
transmission cycle. 
Rabies is estimated to cause 59 000 human deaths annually in over 150 countries, with
95% of cases occurring 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. 

Vaccinating against
rabies to save lives
 

Human rabies is a 100% vaccine-preventable disease, yet it continues to kill.

Rabies vaccinations are highly effective, safe and well tolerated.

The WHO recommends 2 main immunization strategies for the prevention of human
rabies:

 Post exposure prophylaxis (PEP) which includes extensive and thorough wound washing
at the rabies-exposure site, together with rabies immunoglobulin (RIG) administration if
indicated, and the administration of a course of several doses of rabies vaccine;
 Pre-exposure prophylaxis (PrEP) which is the administration of several doses of rabies
vaccine to high risk populations before exposure to rabies.

For both PEP and PrEP, vaccines can be administered by either intra-dermal (ID) or
intra-muscular (IM) routes. Previously WHO-recommended rabies vaccine schedules for
IM administration remain acceptable, but the new ID administration schedules
recommended by the WHO Strategic Advisory Group of Experts (SAGE) offer
advantages through savings in costs, doses and time. Rabies vaccines: WHO position
paper – April 2018
While deaths can be averted by human vaccination, this intervention alone will never eliminate
the disease, and costs will only escalate over time. Investment in eliminating the risk of rabies at
its source – dogs –  is the most cost-effective measure. Vaccination of at least 70% of dogs in
areas at risk is now accepted as the most effective way of preventing human rabies deaths. 

WHO recommends the intradermal route for rabies post-exposure

prophylaxis

Rabies

Rabies continues to kill 59 000 people a year, with a vast majority of these occurring in
Africa and Asia. The disease is preventable with rapid administration of post-exposure
prophylaxis (PEP) after exposure, however many of those persons affected by rabies
are faced with vaccine shortages or cost prohibitive prices for treatment. Many countries
still use intramuscular vaccine PEP schedules, which require 4-5 vials of vaccine to
complete a full course. This can cost up to US$100 in rabies-endemic countries. When
the average daily income per person in these communities is US$1-2, this can place a
huge financial burden on patients.

WHO promotes the use of intradermal administration of modern cell culture rabies
vaccines (with a potency of >2.5IU per intramuscular dose) for PEP. Intradermal
administration offers an equally safe and efficacious alternative to intramuscular
vaccination. Intradermal vaccination reduces the volume of vaccine used by 60-80%, is
less costly and has potential to mitigate vaccine shortages. It requires only 1–2 vials of
vaccine to complete a full course of PEP. Cost effectiveness modelling shows that when
compared with intramuscular vaccination schedules, intradermal schedules are cost
effective and dose sparing in all settings, even if the number of new bite patients is as
low as 5 per month.

Multiple studies have been performed demonstrating the efficacy of intradermal

administration and intradermal PEP schedules have been successfully introduced to
many countries throughout Asia and Africa ( The Immunological Basis for Immunization
Series, Module 17: Rabies (2017, update)). These include India, Pakistan, Nepal,
Bangladesh, Philippines, Sri Lanka, Madagascar and the United Republic of Tanzania.
In countries where intradermal administration is an approved route for PEP, vaccine
manufacturers should be requested to state that their vaccine can be used
intradermally. Proper delivery of the vaccine requires sufficient staff training to ensure
correct storage, reconstitution and injection.

WHO in the recently published WHO position paper on rabies vaccines (Weekly

Epidemiological Record, 2018, 93:201-220) recommends a one week, 2 site intradermal
PEP schedule with 0.1mL of vaccine injected on days 0, 3 and 7. If the patient has
already been immunized against rabies, then this can be reduced to a 1-site intradermal
injection of 0.1mL on days 0 and 3 (WHO Expert Consultation on Rabies, third report,
TRS 1012, WHO 2018). This additional revision, the reduction of the PEP intradermal
schedule to one week, further improves cost effectiveness, reduces the number of
required clinic visits by patients and improves patient compliance.

Any WHO-recommended PEP regimen can be used for people with category II and
category III exposures. In category III exposures rabies immunoglobulin should be
administered in addition to vaccine and thorough washing with soap and water of all bite
wounds and scratches should be done immediately. (See Summary of Key Points;
WHO Position Paper on Rabies Vaccine, February 2018). A change in route of
administration or in vaccine product during a PEP course is acceptable if such a change
is unavoidable to complete the course.

In adopting intradermal vaccine schedules, countries can mitigate vaccine shortages,

improve treatment affordability and provide more equitable access to rabies PEP. With
efforts already underway to reduce the global burden of rabies and eliminate dog
mediated rabies deaths worldwide by 2030, the adoption of intradermal vaccine
schedules can help make this goal a reality.

Vaccinations and immunization

Rabies

Rabies is a zoonotic viral disease which infects domestic and wild animals. It is

transmitted to other animals and humans through close contact with saliva from infected
animals (i.e. bites, scratches, licks on broken skin and mucous membranes). Once
symptoms of the disease develop, rabies is fatal to both animals and humans. Rabies
differs from many other infections in that the development of clinical disease can be
prevented through timely immunization even after exposure to the infecting agent.
Two types of vaccines to protect against rabies in humans exist - nerve tissue and cell
culture vaccines. WHO recommends replacement of nerve tissue vaccines with the
more efficacious, safer vaccines developed through cell culture as soon as possible.
Cell culture vaccines which are more affordable and require less vaccine have been
developed in recent years.

Intradermal immunization using cell-culture-based rabies vaccines is an acceptable

alternative to standard intramuscular administration. Intradermal vaccination has been
shown to be as safe and immunogenic as intramuscular vaccination, yet requires less
vaccine, for both pre- and post-exposure prophylaxis, leading to lower direct costs. This
alternative should thus be considered in settings constrained by cost and/or supply
issues.

Pre-exposure prophylaxis is recommended for anyone at continual, frequent or

increased risk of exposure to rabies virus, either by nature of their residence or
occupation.

Periodic booster injections are recommended as an extra precaution only for people
whose occupation puts them at continual or frequent risk of exposure. If available,
antibody monitoring of personnel at risk is preferred to the administration of routine
boosters.

Rabies vaccines
WHO prequalified vaccines
Veterinary vaccines

Recommendations for post-exposure

All cases of suspected rabies exposure should be treated immediately to prevent the
onset of clinical symptoms and death. Post-exposure prophylaxis (PEP) consists of
wound treatment, the administration of rabies vaccines based on WHO
recommendations, and if indicated, the administration of rabies immunoglobulin.

Local treatment of wounds

Elimination of rabies virus at the site of the infection by chemical or physical means is
an effective mechanism of protection. Local treatment of wounds involving possible
exposure to rabies is recommended in all exposures.

Recommended first-aid procedures include 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 of proven lethal effect on rabies virus.

If soap or an antiviral agent is not available, the wound should be thoroughly and
extensively washed with water. If suturing after wound cleansing cannot be avoided, the
wound should first be infiltrated with passive rabies immunization products and suturing
delayed for several hours.

Other treatments, such as the administration of antibiotics and tetanus prophylaxis,

should be applied as appropriate for other bite wounds.

The recommendations given here are intended as a general guide. It is recognized

that, in certain situations, modifications of the procedures laid down may be warranted.
Such situations include exposure of infants or mentally disabled persons and other
circumstances where a reliable history cannot be obtained, particularly in areas where
rabies is enzootic, even though the animal is considered to be healthy at the time of
exposure. Such cases may be treated as category II or III (see recommendations
below).

Rabies vaccine and rabies immunoglobulin

 ©

Recommendations for post-exposure depend on the type of contact with the suspected
rabid animal.

 For category I exposure (touching or feeding animals, licks on intact skin), no

prophylaxis is required;
 For category II (nibbling of uncovered skin, minor scratches or abrasions without
bleeding), immediate vaccination; and
 For category III (single or multiple transdermal bites or scratches, contamination
of mucous membrane with saliva from licks, licks on broken skin, exposures to bats),
immediate vaccination and administration of rabies immunoglobulin are recommended.

WHO strongly recommends the discontinuation of production and use of nerve tissue
vaccine and their replacement by modern cell culture vaccines. Intradermal vaccination
is recommended as an alternative to intramuscular vaccination as it is safe,
immunogenic and dose and cost sparing.

There are no contraindications to PEP; it can be safely given to infants, pregnant

women and immunocompromised individuals. Life-saving PEP should not be withheld
from these individuals.
Where possible, animals that conform to the definition of a suspected or probable rabies
case should be euthanized humanely and sent for laboratory diagnosis. Animals that
are deemed healthy by a trained professional, should be observed closely for 10 days.
However, in rabies endemic areas the availability of the animal for observation should
not delay the victim in seeking PEP.

Prompt administration of rabies vaccine after exposure, combined with proper wound
management and administration of rabies immunoglobulins where indicated, is almost
invariably effective in preventing rabies, even after high-risk exposure.

WHO recommends the intradermal route for rabies post-exposure

prophylaxis

Rabies

Rabies continues to kill 59 000 people a year, with a vast majority of these occurring in
Africa and Asia. The disease is preventable with rapid administration of post-exposure
prophylaxis (PEP) after exposure, however many of those persons affected by rabies
are faced with vaccine shortages or cost prohibitive prices for treatment. Many countries
still use intramuscular vaccine PEP schedules, which require 4-5 vials of vaccine to
complete a full course. This can cost up to US$100 in rabies-endemic countries. When
the average daily income per person in these communities is US$1-2, this can place a
huge financial burden on patients.

WHO promotes the use of intradermal administration of modern cell culture rabies
vaccines (with a potency of >2.5IU per intramuscular dose) for PEP. Intradermal
administration offers an equally safe and efficacious alternative to intramuscular
vaccination. Intradermal vaccination reduces the volume of vaccine used by 60-80%, is
less costly and has potential to mitigate vaccine shortages. It requires only 1–2 vials of
vaccine to complete a full course of PEP. Cost effectiveness modelling shows that when
compared with intramuscular vaccination schedules, intradermal schedules are cost
effective and dose sparing in all settings, even if the number of new bite patients is as
low as 5 per month.

Multiple studies have been performed demonstrating the efficacy of intradermal

administration and intradermal PEP schedules have been successfully introduced to
many countries throughout Asia and Africa ( The Immunological Basis for Immunization
Series, Module 17: Rabies (2017, update)). These include India, Pakistan, Nepal,
Bangladesh, Philippines, Sri Lanka, Madagascar and the United Republic of Tanzania.
In countries where intradermal administration is an approved route for PEP, vaccine
manufacturers should be requested to state that their vaccine can be used
intradermally. Proper delivery of the vaccine requires sufficient staff training to ensure
correct storage, reconstitution and injection.

WHO in the recently published WHO position paper on rabies vaccines (Weekly

Epidemiological Record, 2018, 93:201-220) recommends a one week, 2 site intradermal
PEP schedule with 0.1mL of vaccine injected on days 0, 3 and 7. If the patient has
already been immunized against rabies, then this can be reduced to a 1-site intradermal
injection of 0.1mL on days 0 and 3 (WHO Expert Consultation on Rabies, third report,
TRS 1012, WHO 2018). This additional revision, the reduction of the PEP intradermal
schedule to one week, further improves cost effectiveness, reduces the number of
required clinic visits by patients and improves patient compliance.

Any WHO-recommended PEP regimen can be used for people with category II and
category III exposures. In category III exposures rabies immunoglobulin should be
administered in addition to vaccine and thorough washing with soap and water of all bite
wounds and scratches should be done immediately. (See Summary of Key Points;
WHO Position Paper on Rabies Vaccine, February 2018). A change in route of
administration or in vaccine product during a PEP course is acceptable if such a change
is unavoidable to complete the course.

In adopting intradermal vaccine schedules, countries can mitigate vaccine shortages,

improve treatment affordability and provide more equitable access to rabies PEP. With
efforts already underway to reduce the global burden of rabies and eliminate dog
mediated rabies deaths worldwide by 2030, the adoption of intradermal vaccine
schedules can help make this goal a reality.