RABIES

D r. p . n a t a r a j a n
 Introduction
1. Rabies virus is a bullet-shaped, negative-sense, single-stranded, enveloped RNA virus Family:
Rhabdoviridae, genus: Lyssavirus. 12 known genotypes . Type I is the major cause for rabies.

2. Rabies virus can infect any mammal & animal reservoirs are terrestrial carnivores (jackals,
mongooses, and raccoon dog and bats). Worldwide, transmission from dogs accounts for >90%
of human cases.

3. Rabies virus is found in the saliva of infected animals, and transmission occurs through a bite or
scratch from a rabid mammal. Infection rate is high in bites of innervated parts of the body such
as the face and the hands.

4. No case of nosocomial transmission to a healthcare worker has been documented to date, but
caregivers are advised to use full barrier precautions.
 Pathogenesis

1. After inoculation, rabies virus replicates slowly in muscle or skin. This slow initial step accounts for
the disease’s long incubation period. Virus then enters the peripheral motor nerve, utilizing the
nicotinic acetylcholine receptor and other receptors for entry. Once in the nerve, the virus travels by
fast axonal transport, crossing synapses roughly every 12 hr.
2. Rapid dissemination occurs throughout the brain and spinal cord before symptoms appear. Infection
of the dorsal root ganglia causes radiculitis. Infection concentrates in the brainstem, accounting for
autonomic dysfunction and relative sparing of cognition.
3. The hallmark of rabies, the Negri body, is composed of clumped viral nucleocapsids that create
cytoplasmic inclusions on routine histology.
4. Rabies may be a metabolic disorder of neurotransmission; tetrahydrobiopterin deficiency in human
rabies causes severe deficiencies in dopamine, norepinephrine, and serotonin metabolism.
 Clinical manifestations
1. The incubation period for rabies is 1-3 mo, but is variable. In severe wounds to the head, symptoms may occur within 5
days after exposure, and occasionally the incubation period can extend to longer than 6 mo.
2. Rabies has 2 principal clinical forms.
a. Encephalitic or “furious” rabies:
i. Fever, sore throat, malaise, headache, nausea and vomiting, and weakness. Soon the patient begins to
demonstrate symptoms of encephalitis, with agitation, depressed mentation, and, occasionally, seizures.
ii. periods of lucidity alternating with periods of profound encephalopathy.
iii. Hydrophobia and aerophobia are the cardinal signs of rabies; they are unique to humans and are not universal
or specific. Phobic spasms are manifested by agitation and fear created by being offered a drink or fanning of
air in the face, which in turn produce choking and aspiration through spasms of the pharynx, neck, and
diaphragm.
iv. Death almost always occurs within 1-2 days
b. Paralytic or “dumb” rabies is seen much less frequently and is characterized by fevers and ascending motor
weakness affecting both the limbs and the cranial nerves. Most patients with paralytic rabies also have some
element of encephalopathy as the disease progresses sub acutely.
 Differential diagnosis
1. Tetanus,

2. Some intoxications

3. Envenomation.

4. Autoimmune (anti–n-methyld- aspartate receptor) encephalitis,

5. Infectious encephalitis,

6. Psychiatric illness,

7. Drug abuse, and

8. Conversion disorders.

9. Paralytic: Guillain-Barre syndrome.

 Diagnosis

1. Reverse transcription polymerase chain reaction is the most sensitive available assay for the
diagnosis of rabies when done iteratively.

2. The virus can be grown both in cell culture and after animal injection, but identification of rabies
by these methods is slow.

3. Rabies antigen is detected through immunofluorescence of saliva or biopsies of hairy skin or

brain. Corneal impressions are not recommended.

4. Antibody in CSF is rarely detected after vaccination and is considered diagnostic of rabies
regardless of immunization status.

5. CSF abnormalities in cell count, glucose, and protein content are minimal and are not diagnostic.

6. MRI findings in the brain are late.

 Treatment and prognosis

1. Rabies is generally fatal. Conventional critical care yielded 1 survivor from

74 attempts since 1990. Five of 16 patients survived without use of critical
care (including 3 milder cases) and 7 with use of the Milwaukee Protocol.

2. Survival using the Milwaukee Protocol is estimated at 20%; neurologic

outcomes are poor in one third of patients.

3. Neither rabies immunoglobulin (RIG) nor rabies vaccine provides benefit

once symptoms have appeared.

4. Antiviral treatments have not been effective.

 Prevention

Primary prevention of rabies infection includes vaccination of domestic animals and

education to avoid wild animals, stray animals, and animals with unusual behavior.
 Postexposure Prophylaxis

1. No case of rabies has been documented in a person receiving the recommended schedule of PEP since introduction

of modern cellular vaccines in the 1970s.

2. Given the incubation period for rabies, PEP is a medical urgency, not emergency.

3. The first step in rabies PEP is to cleanse the wound thoroughly. Soapy water is sufficient to inactivate an enveloped

virus, and its effectiveness is supported by broad experience. Other commonly used disinfectants, such as iodine-

containing preparations, are virucidal and should be used in addition to soap when available.

4. No wound suturing

5. Human RIG is administered at a dose of 20 IU/kg. As much of the dose is infused around the wound as possible,

and the remainder is injected intramuscularly in a limb distant from the 1 injected with the killed vaccine.

6. Either a purified chick-embryo cell cultivated vaccine, or human diploid cell cultures vaccine is administered

intramuscularly in a 1 mL volume in the deltoid or anterolateral thigh on days 0, 3, 7, and 14 after presentation.

Injection into the gluteal area should not be used. The rabies vaccines can be safely administered during pregnancy.
 Preexposure Prophylaxis

1. The killed rabies vaccine can be given to prevent rabies in persons at high risk
for exposure to wild-type virus, including laboratory personnel working with
rabies virus, veterinarians, and others likely to be exposed to rabid animals as
part of their occupation.

2. The schedule for preexposure prophylaxis consists of 3 intramuscular

injections on days 0, 7, and 21 or 28.

3. PEP in the patient who has received preexposure prophylaxis or a prior full
schedule of PEP consists of 2 doses of vaccine (1 each on days 0 and 3) and
does not require RIG.
 Recommendations for post-exposure depending
on the type of contact with the suspected rabid
animal.
1. For category I exposure (touching or feeding animals, licks on intact skin), no
prophylaxis is required;

2. For category II (nibbling of uncovered skin, minor scratches or abrasions without

bleeding), immediate vaccination; and

3. 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.