World Rabies Day is September 28

RABIES ICD-9 071; ICD-10 A82

(Hydrophobia, Lyssa)

1. Identification—An almost invariably fatal acute viral encephalomyelitis;

onset generally heralded by a sense of apprehension, headache,

fever, malaise and indefinite sensory changes often referred to the site of

a preceding animal bite. Excitability and aerophobia are frequent symptoms.

The disease progresses to paresis or paralysis; spasms of swallowing

muscles leads to fear of water (hydrophobia); delirium and convulsions

follow. Without medical intervention, the usual duration is 2–6 days,

sometimes longer; death is often due to respiratory paralysis.

Diagnosis is made through specific FA staining of brain tissue or virus

isolation in mouse or cell cultures. Presumptive diagnosis by specific FA

staining of frozen skin sections taken from the back of the neck at the

hairline. Serological diagnosis based on neutralization tests in mice or cell

culture.

2. Infectious agent—Rabies virus, a rhabdovirus of the genus Lyssavirus.

All members of the genus are antigenically related, but use of

monoclonal antibodies and nucleotide sequencing shows differences

according to animal species or geographical location of origin. Rabiesrelated

viruses in Africa (Mokola and Duvenhage) have been associated,

rarely, with fatal rabies-like human illness. A new lyssavirus, first identified

in 1996 in several species of flying foxes and bats in Australia, has been

associated with 2 human deaths from rabies-like illnesses. This virus,

provisionally named Australian bat lyssavirus, is closely related to, but not

identical to classical rabies virus. Some of the illnesses due to rabies related

viruses may be diagnosed as rabies by the standard FA test.

3. Occurrence—Worldwide, with an estimated 65 000–87 000 deaths

a year, almost all in developing countries, particularly Asia (an estimated

38 000 to 60 000 deaths) and Africa (estimated 27 000 deaths). Most

human deaths follow dog bites for which adequate post-exposure prophylaxis

was not or could not be provided. In Latin America a regional dog

rabies control program coordinated by PAHO since 1981 has led to a

reduction by 84% in the number of human deaths with only 56 cases

reported in 2001. During the past 10 years drastic decrease of the numbers

of human deaths have also been reported by several Asian countries

particularly China, Thailand and Viet Nam. Western, central and eastern

Europe including the Russian Federation report less than 50 rabies deaths

annually. From 1958 through 2000, in the USA, 35 of 57 human deaths

from rabies were acquired domestically. Of those infected within the USA,

almost all were bat-associated rabies (strain analysis).

Rabies is a disease primarily of animals. The areas currently free of

autochthonous rabies in the animal population (excluding bats) include

most of Australasia and western Pacific, many countries in Western Europe

(insular and continental), part of Latin America including the Caribbean.

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Dogs transmit urban (or canine) rabies, whereas sylvatic rabies is a disease

of wild carnivores and bats, with sporadic spillover to dogs, cats and

livestock. In western Europe, fox rabies, once widespread, has decreased

considerably since oral rabies immunization of foxes began in the early

1990s. Since 1985 bat rabies cases have been reported in Denmark,

Finland, France, Germany, Luxembourg, the Netherlands, Spain, Switzerland

and the United Kingdom. In the USA and Canada, wildlife rabies most

commonly involves racoons, skunks, foxes, coyotes and bats. There has

been a progressive epizootic among racoons in the eastern USA and among

coyotes and dogs in south Texas.

4. Reservoir—Wild and domestic Canidae, including dogs, foxes,

coyotes, wolves and jackals; also skunks, racoons, mongooses and other

biting mammals. In developing countries, dogs remain the principal

reservoir. Infected populations of vampire, frugivorous and insectivorous

bats occur in Mexico, Central and South America; infected insectivorous

bats in Canada, the USA and Europe. Rabbits, opossums, squirrels,

chipmunks, rats and mice are rarely infected: their bites rarely call for

rabies prophylaxis.

5. Mode of transmission—Virus-laden saliva of rabid animal introduced

though a bite or scratch (very rarely into a fresh break in the skin

or through intact mucous membranes). Person-to-person transmission is

theoretically possible, but rare and not well documented. Organ (corneal)

transplants from persons dying of undiagnosed CNS disease have resulted

in rabies in the recipients. Airborne spread has been demonstrated in a

cave where bats were roosting and in laboratory settings, but this occurs

very rarely. Transmission from infected vampire bats to domestic animals

is common in Latin America. In the USA, rabid insectivorous bats rarely

transmit rabies to terrestrial animals, wild or domestic.

6. Incubation period—Usually 3–8 weeks, rarely as short as 9 days or

as long as 7 years; depends on wound severity, wound site in relation to

nerve supply and distance from the brain, amount and strain of virus,

protection provided by clothing and other factors.

7. Period of communicability—In dogs and cats, usually for 3–7 days

before onset of clinical signs (rarely over 4 days) and throughout the

course of the disease. Longer periods of excretion before onset of clinical

signs (14 days) have been observed with Ethiopian dog rabies strains. In

one study, bats shed virus for 12 days before evidence of illness; in

another, skunks shed virus for at least 8 days before onset of clinical signs.

Skunks may shed virus for up to 18 days before death.

8. Susceptibility—All mammals are susceptible to varying degrees,

which may be influenced by the virus strain. Humans are more resistant to

infection than several animal species; a study in the Islamic Republic of

Iran showed that, of those bitten by proven rabid animals and not treated,

about 40% developed the disease.

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9. Methods of control—

A. Preventive measures: Many preventive measures are possible

at the level of the main animal main host(s) and transmitter(s) of

rabies to humans. They are all part of a comprehensive rabies

control program.

1) Register, license and immunize all dogs in enzootic countries;

collect and sacrifice ownerless animals and strays.

Immunize all cats. Educate pet owners and the public on the

importance of restrictions for dogs and cats (e.g. pets must

be leashed in congested areas when not confined on owner’s

premises; strange-acting or sick animals of any species,

domestic or wild, should not be picked up/handled; reporting

of such animals and of animals that have bitten a person

or another animal to police/local health department; confinement

and observation of such animals as a preventive

measure; wild animals should not be kept as pets). Where

dog control is sociologically impractical, repetitive total dog

population immunization has been effective.

2) Maintain active surveillance for rabies in animals. Laboratory

capacity should be developed to perform FA testing on all

wild animals involved in human or domestic animal exposures

and all domestic animals clinically suspected of having

rabies. Get physicians, veterinarians and animal control

officials to obtain/sacrifice/test animals involved in human

and domestic animal exposures.

3) Detain and clinically observe for 10 days any healthy-appearing

dog or cat known to have bitten a person (unwanted

dogs and cats may be sacrificed immediately and examined

for rabies by fluorescent microscopy); dogs and cats showing

suspicious signs of rabies should be sacrificed and tested for

rabies. If the biting animal was infective at the time of bite,

signs of rabies will usually follow within 4–7 days, with a

change in behaviour and excitability or paralysis, followed

by death. All wild mammals that have bitten a person must

be sacrificed immediately and the brain examined for

evidence of rabies. In the case of bites by a normally

behaving valuable pet or zoo animal, it may be appropriate

to consider postexposure prophylaxis for the human

victim, and, instead of sacrificing the animal, hold it in

quarantine for 3–12 weeks.

4) Immediately submit to a laboratory the intact head of animals

that die of suspected rabies, packed in ice (not frozen), for

viral antigen testing by FA staining, or, if not available, by

microscopic examination for Negri bodies, followed by

mouse inoculation.

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5) Immediately sacrifice unimmunized dogs or cats bitten by

known rabid animals; if detention is elected, hold the animal

in a secure pound or kennel for at least 6 months under

veterinary supervision, and immunize against rabies 30 days

before release. If previously immunized, reimmunize and

detain (leashing and confinement) for at least 45 days.

6) Oral immunization of wildlife animal reservoirs, using airdrops

of bait containing attenuated or recombinant vector

vaccine, has eliminated fox rabies from parts of Europe and

Canada. The technique is being evaluated within the USA.

7) Cooperative programs with wildlife conservation authorities

to reduce fox, skunk, racoon and other terrestrial wildlife

hosts of sylvatic rabies may be used in circumscribed enzootic

areas near campsites and areas of human habitation. If

such focal depopulation is undertaken, it must be maintained

to prevent repopulation from the periphery.

8) Individuals at high risk (e.g. veterinarians, wildlife conservation

personnel and park rangers in enzootic or epizootic

areas, staff of quarantine kennels, laboratory and field

personnel working with rabies, long-term travellers to

rabies-endemic areas) should receive pre-exposure immunization,

using potent and safe cell-culture vaccines. Vaccine

can be given in 3 doses of 1.0 ml (IM) on days 0, 7 and

21 or 28: Post-immunization serological testing may be

advisable for groups at high risk of exposure or immunodeficient

persons. Results with ID immunization for Human

Diploid Cell rabies Vaccine (HDCV) have generally

been good, but the mean antibody response is somewhat

lower and may be of shorter duration than for the 1.0 ml

dose given IM. Antibody response to ID immunization has

been erratic in some groups on chloroquine for antimalarial

chemoprophylaxis. Although immune response has not

been evaluated for antimalarials structurally related to

chloroquine (e.g. mefloquine, hydroxychloroquine), similar

precautions for individuals receiving these drugs

should be followed. Other cell-culture vaccines fulfilling

WHO requirements for the ID route, such as vero cell

vaccine and chick embryo cell vaccine, are widely used in

rabies-endemic countries.

If risk of exposure continues, single booster doses are

given, or preferably serum is tested for neutralizing antibody

every 2 years, with booster doses given when indicated.

9) Prevention of rabies after animal bites (“postexposure prophylaxis”)

consists of the following (8th Report of WHO

Expert Committee on Rabies, 1992; Recommendations of

the Advisory Committee for Immunization Practices, MMWR

48(RR-1): 1–21, 1999):

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a) First aid: Clean and flush the wound immediately with

soap or detergent and water (or water alone) then apply

either 70% ethanol, tincture of aqueous solution of iodine

or povidone iodine. The wound should not be sutured

unless unavoidable. Sutures, if required, should be placed

after local infiltration of antiserum (see 9b); they should

be loose and not interfere with free bleeding and drainage.

b) Specific treatment (serum and vaccine): Specific immunological

protection in humans is provided by administration

of human (HRIG) or equine (ERIG) rabies immune

globulin at site of bite as soon as possible after exposure

to neutralize the virus, and then by giving vaccine at a

different site to elicit active immunity. Animal studies

suggest that human disease caused by the Australian bat

lyssavirus may be prevented by rabies vaccine and rabies

immune globulin, and such post-exposure prophylaxis is

recommended for persons bitten or scratched by any bat

in Australia. Although rabies vaccine may not always be

effective for the treatment of African bat lyssaviruses, it

should be administered.

Passive immunization: HRIG should be used in a single

dose of 20 IU/kg and ERIG in a single dose of 40 IU/kg. As

much as possible of this must be infiltrated into and

around the bite wound and the rest, if any, given IM. If

serum of animal origin is used, an intradermal or subcutaneous

test dose should precede its administration to

detect allergic sensitivity. Modern cell-culture vaccines

should be given in 5 IM doses of 0.5 or 1.0 ml (see

manufacturer’s instructions) in the deltoid region; to start

as soon as possible after exposure and the last dose

within 28 days for IM (0, 3, 7, 14, 28) and 90 days for ID

(0, 3, 7, 28, 90) vaccination.

Although the ID dose/route at multiple sites has not

been approved in the USA, it may be used for postexposure

prophylaxis when vaccine is in short supply or out

of reach for patients; WHO recommends 2 ID multisite

regimens with cell-culture vaccines known to be safe and

immunogenic when they are given ID: i) 2-site regimen

(2-2-20-1-1); ii) 8-site regimen (8-0-4-0-1-1)—see WHO

Recommendations on Rabies Post-Exposure Treatment

and the Correct Technique of Intradermal immunization

against Rabies (http://whqlibdoc.who.int/hq/1996/

WHO_EMC_ZOO_96.6.pdf).

In individuals with possible immunodeficiency, a serum

specimen should be collected at the time the last

dose of vaccine is administered and tested for rabies

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antibodies. If sensitization reactions appear in the course

of immunization, consult the health department or infectious

disease consultants for guidance. If the person has

had a previous full course of antirabies immunization

with an approved vaccine, or had developed neutralizing

antibodies after pre-exposure immunization (see 9A8) or

after a postexposure regimen, only 2 doses of vaccine

need to be given–one immediately and one 3 days later.

With severe exposure (e.g. head bites), a third dose may

be given on day 7. Neither HRIG nor ERIG is used with

this regimen.

c) The combination of local wound treatment, passive immunization

with HRIG or ERIG and vaccination is recommended

for all severe exposures (category III, see end of

this item), virtually guaranteeing complete protection. In

the US, passive immunization is standard for all postexposure

vaccination. Pregnancy and infancy are never

contraindications to post-exposure rabies vaccination.

Persons presenting even months after the bite must be

dealt with in the same way as recent exposures. Factors

to be considered in the initiation of post-exposure treatment

are: nature of the contact; rabies endemicity at site

of encounter or origin of animal; animal species involved;

vaccination/clinical status and availability of animal for

observation plus type of vaccine used; laboratory results

of animal for rabies if available.

d) Immunization with current rabies vaccines has occasionally

been followed by Guillain-Barre´ syndrome, but too

rarely to be certain of causal association. Local reactions,

such as pain, erythema, swelling or itching at the injection

site have been reported in 25% of those receiving 5

doses of 1.0 ml. Mild systemic reactions of headache,

nausea, muscle aches, abdominal pain and dizziness were

reported in about 20%. “Serum sickness-like” reactions,

including primarily urticaria with generalized itching and

wheezing, have been reported infrequently.

Among those receiving booster doses for pre-exposure

prophylaxis, hypersensitivity reactions occur in approximately

6% of recipients 2–21 days after HDCV, presenting

as a generalized pruritic rash, urticaria, possible arthralgia,

arthritis, angioedema, nausea, vomiting, fever and

malaise. These symptoms have responded to antihistamines;

a few have required corticosteroids or epinephrine.

Persons exposed to rabies who develop these

symptoms should complete the required number of injections

using a rabies vaccine prepared with another cell

type. This reaction has not been definitely associated with

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other rabies vaccines. Systemic allergic reactions in those

receiving booster doses have been rare. No significant

adverse reactions have been attributed to HRIG; however,

antiserum from a nonhuman source produces serum

sickness in 5%–40% of recipients. Newer commercially

produced purified animal globulins, in particular

equine globulin, have only a 1% risk of adverse reactions.

The risk of contracting fatal rabies usually outweighs the

risks of allergic reactions.

B. Control of patient, contacts and the immediate environment:

1) Report to local health authority: Obligatory case report

required in most countries, Class 2 (see Reporting).

2) Isolation: Contact isolation for respiratory secretions for

duration of the illness.

3) Concurrent disinfection: Of saliva and articles soiled therewith.

Although transmission from a patient to attending

personnel has not been documented, immediate attendants

should be warned of the potential hazard of infection from

saliva, and wear rubber gloves, protective gowns, and protection

to avoid exposure from a coughing patient.

4) Quarantine: Not applicable.

5) Immunization of contacts: Contacts who have an open

wound or mucous membrane exposure to the patient’s saliva

must receive specific antirabies treatment (see 9A9b).

6) Investigation of contacts and source of infection: Search for

rabid animal and for people and other animals bitten.

7) Specific treatment: For clinical rabies, intensive supportive

medical care.

C. Epidemic (epizootic) measures: Applicable only to animals;

a sporadic disease in humans.

1) Establish area control under authority of laws, regulations

and ordinances, in cooperation with appropriate wildlife

conservation and animal health authorities.

2) Immunize dogs and cats through officially sponsored, intensified

mass programs that provide immunizations at temporary

and emergency stations. For protection of other domestic

animals, use approved vaccines appropriate for each

animal species.

3) In urban areas of industrialized countries, strict enforcement

of regulations requiring collection, detention and killing of

ownerless and stray dogs, and of nonimmunized dogs found

off owners’ premises; control of the dog population by

castration, spaying or drugs have been effective in breaking

transmission cycles.

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4) Immunization of wildlife through baits containing vaccine

has successfully contained fox rabies in western Europe and

Canada and is investigated in the USA.

D. Disaster implications: A potential problem if the disease is

freshly introduced or enzootic in an area where there are many

stray dogs or wild reservoir animals.

E. International measures:

1) Strict compliance by common carriers and travellers with

national laws and regulations in rabies-free countries. Immunization

of animals, certificates of health and origin, or

microchip identification of animals may be required.

2) WHO Collaborating Centres. Further information on http://

www.oms2.b3e.jussieu.fr/rabnet

POSTEXPOSURE PROPHYLAXIS GUIDE

Consult local or state health officials if questions arise about the need for

rabies prophylaxis. In addition to treatment as described under A9a, b.

WHO recommendations for post-exposure rabies management follow:

Category of

exposure

Type of contact with a

suspect or confirmed rabid

domestic or wilda animal

or animal unavailable for

observation Recommended treatment

I Touching or feeding of animal

Licks on intact skin

None, if reliable case history available

II Nibbling of uncovered skin Administer vaccine immediatelyb

Minor scratches or abrasion

without bleeding

Licks on broken skin

Stop treatment if animal remains

healthy throughout observationc

(10 days) or is killed and found to

be negative for rabies by appropriate

laboratory techniques

III Single or multiple transdermal

bites or scratches

Administer vaccine immediatelyb

Contamination of mucous

membrane with saliva

(licks)

Stop treatment if animal remains

healthy throughout observationc

(10 days) or is killed and found to

be negative for rabies by appropriate

laboratory techniques

aExposure to rodents, rabbits and hares seldom if ever requires specific anti-rabies

treatment

bThe placing of an apparently healthy dog or cat in or from a low-risk area under

careful supervision may warrant delaying treatment

cApplicable only to dogs and cats. Except for threatened or endangered species,

other animals suspected of rabies must be killed and their tissues examined using

appropriate laboratory techniques

484 / RABIES

USA recommendations for post-exposure management follow (ACIP):

Human Rabies Prevention – United States, 1999: Recommendations of Advisory

Committee on Immunization Practices (ACIP). MMWR, 48:(RR) 1–21, 1999.

Vaccination

Status Treatment Regimen*

Not previously

vaccinated

Wound

cleansing

All postexposure treatment to begin with immediate

thorough cleansing of all wounds with soap and

water. If available, a virucidal agent such as a povidone-

iodine solution should be used to irrigate the

wounds.

HRIG Administer 20 IU/kg body weight. If anatomically

feasible, the full dose should be infiltrated around

the wound(s); any remaining volume should be administered

intramuscularly (IM) at an anatomic site

distant from that of vaccine administration. RIG

should not be administered in the same syringe as

the vaccine. Because HRIG may partially suppress

active production of antibody, no more than the

recommended dose should be given.

Vaccine HDCV, RVA, or PCECV, 1.0 ml, IM (deltoid area†),

one each on days 0**, 3, 7, 14, and 28.

Previously

vaccinated§

Wound

cleansing

All postexposure treatment to begin with immediate

thorough cleansing of all wounds with soap and

water. If available, a virucidal agent such as a povidone-

iodine solution should be used to irrigate

wounds.

RIG RIG should not be administered.

Vaccine HDCV, RVA (rabies vaccine, adsorbed), or PCEV, 1.0

mL, IM (deltoid area†), one each on days 0** and 3.

*Regimens are applicable for all age groups, including children.

†The deltoid area is the only acceptable site of vaccination for adults and older

children. For younger children, the outer aspect of the thigh may be used. Never

administer vaccine in the gluteal area.

**Day 0 is the day the 1st dose of vaccine is administered.

§History of pre-exposure vaccination with HDCV, RVA, or PCVEC; prior postexposure

prophylaxis with HDCV, RVA, or PCECV; or previous vaccination with any other

type of rabies vaccine and a documented history of antibody response to the prior

vaccination.

[F. Meslin]

❖

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