Download RABIES OVERVIEW: This is primarily a viral infection of non

RABIES
OVERVIEW:
This is primarily a viral infection of non-human carnivores. Transmission to man is rare and is usually
effected through a bite. Clinical evidence of involvement of the CNS appears after an extremely variable
period of incubation. A deep-seated fear of rabies is almost instinctual despite the actual rarity of the
infection in man, perhaps reflecting a primordial knowledge of the virtual certainty of death once disease is
overt.
ETIOLOGICAL AGENT:
Rabies virus (a rhabdovirus)
PATHOLOGY:
 The rabies virus is usually transmitted to man by a bite that implants saliva containing an infective dose
of virus in muscle and near nerve tissue.
 The virus may undergo a limited amount of reproduction in the muscle cells at the site of inoculation.
 The virus travels along the nerves from the point of inoculation to the CNS.
 The dense concentration of sensory nerve endings in the head, face, neck and fingers accounts for the
higher fatality rate observed when these areas are exposed.
 Similarly, the more extensive or severe the bite wounds, the higher the mortality, because more nerve
tissue is exposed to an infective dose of rabies virus.
 After entering the CNS, the virus replicates in the neurons of the gray matter before traveling
centrifugally along nerves from the CNS to invade a variety of organs and tissues.
 Humans and animals dying of rabies commonly exhibit characteristic cytoplasmic inclusion bodies in
neurons of the brain; these are called Negri bodies.
 The presence of Negri bodies is pathognomonic of rabies infection, but their absence does not preclude
the disease.
 In humans who have died from rabies, Negri bodies are prominent in ganglion cells, particularly in the
hippocampus and cerebellum.
 Other changes also present in the CNS include edema, hemorrhage, congestion, chromatolysis and
perivascular cuffing in all parts, but most severe in the pons and medulla.
 In the cranial, spinal, and sympathetic ganglia, there are actual foci of necrosis with neuronophagia and
infiltration with lymphocytes.
 The severity of the histopathologic changes in the spinal cord often corresponds to the site of bite - for
example, the lumbar cord is most extensively affected when the bite is on the foot. Gross changes are
inconspicuous.
DIAGNOSIS:
Where there is a history of bite by a known rabid animal and the bitten person shows typical symptoms, the
clinical diagnosis of rabies is usually evident. In many instances, a history of exposure is lacking, and the
diagnosis of rabies may be missed unless revealed by postmortem laboratory tests.
The manifestations of rabies begins in man anywhere from 10-240 days after exposure. However, the
incubation period is usually 30-90 days. The length of this incubation period is a function of:
1. The number of sensory nerves ending in the bitten area
2. The dose of virus
3. The severity of the bite wounds
4. The distance from the bite wound from the CNS
There are three clinical phases of the disease:
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1. Prodromal phase - the onset of clinical rabies includes 2-4 days of prodromal manifestations, most of
which are
 low fever, malaise, headache, anorexia, nausea and sore throat
 increasing nervousness, anxiety, irritability and depression and melancholia, with or without a
sense of impending death.
 Hyperesthesia, an increased sensitivity to bright light and loud noise,
 excessive salivation, lacrimation and perspiration
 general muscle tone may be increased, and facial expression can be overactive.
 Dilated pupils, an increased pulse rate and shallow respirations are seen.
 most significant symptoms are abnormal sensations referred to the site of inoculation; noted by
80% of patients, these include:
o pain (local or radiating),
o a sensation of cold, pruritus (itching) and tingling.
2. Excitation phase - the excitation phase begins gradually and may persist to death. It may be punctuated at
any time by depression and paralysis.
 the tone of the somatic musculature is increased, there may be weakness of the muscle groups around
the location of the bite.
 Cranial nerve malfunctions result in ocular palsies with:
o Strabismus - failure of the eyes to follow one another in any movement. This is due to
incoordination of the extra-ocular muscles.
o Dilation or constriction of the pupils that may be asymmetric and associated with:
o Hippus (abnormal exaggeration of the rhythmic contraction and dilation of the pupil,
independent of changes in illumination or in fixation of the eyes).
o Nystagmus (continuous rolling of eyeball)
o Diplopia
o Absence of corneal reflexes
o Weakness of facial muscles
o Hoarseness
o Babinski and Chaddock signs
o Papilledema
 There may be:
o tachycardia or bradycardia (slow heart beat),
o cyclic respiration,
o urinary retention
o constipation.
 Hydrophobia, the classical diagnostic manifestation of rabies, is an affliction of the excitatory phase
of the disease. When the patient attempts to swallow liquids, forceful, painful expulsion occurs as a
consequence of spasmodic contraction of the muscles of swallowing and respiration. Once
experienced, the sight, sound or smell of liquids may provoke the syndrome. The ensuing choking
may cause severe apnea (temporary cessation of breathing) and cyanosis. Death frequently occurs
during the course of such a convulsive attack. Dehydration is a common consequence.
3. Paralytic phase - hydrophobia, if present, disappears and swallowing becomes possible, although
difficult, as the paralytic phase sets in.
o A progressive, general, flaccid paralysis develops.
o Apathy shades into stupor, progressing to coma.
o There is urinary incontinence.
o Peripheral vascular collapse ensues and death follows.
Definitive diagnosis of rabies depends on laboratory procedures:
1. Isolation of the virus from saliva, CSF, urine, nerve tissue
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2. Fluorescent rabies antibody (FRA) test on brain tissue
3. Presence of Negri bodies
PROGNOSIS:
Only 3 (6?) people have ever recovered from rabies. CNS sequelae are common.
Medical Care:
 Administer human rabies immunoglobulin (HRIG) to any person not previously vaccinated against
rabies in a dose of 20 IU/kg (for adults and children). Apply as much of the dose as possible at the
injury site and the remainder as a deep intramuscular injection in the gluteal area. HRIG may be
administered up to the seventh day after the first dose of vaccine if it is not immediately available
when the patient presents for evaluation.
 Equine rabies immunoglobulin may be available in other countries. Minimal adverse effects occur
if it is in the purified form, but if unpurified, it may cause serum sickness and anaphylaxis.
 Three different inactivated rabies vaccines are licensed in the United States as follows:
o Human diploid cell vaccine (HDCV, Imovax) - Comes as an intradermal (ID) preparation for
use only as preexposure prophylaxis and as regular dosing to be administered as intramuscular
(IM) injection
o Rabies vaccine adsorbed (RVA) - Made and distributed in Michigan for IM use only
o Purified chick embryo cell vaccine (PCEC, RabAvert) - Licensed in the United States in 1997
for IM use only
 Doses of all the vaccines for postexposure prophylaxis are 1.0 mL IM in deltoid or upper outer thigh
in infants.
 The 5-dose schedule is the same for all 3 vaccine products, as follows: day 0, day 3, day 7, day 14,
and day 28 postexposure.
 Postexposure antibody testing is not necessary in healthy individuals.
 Mild local and systemic adverse reactions to these vaccines and immunoglobulin may occur but are
usually treatable with supportive care, antihistamines, and anti-inflammatory medications. Local pain,
erythema, headache, nausea, and abdominal pain may occur. If prophylaxis is warranted, do not
postpone or discontinue treatment because of mild adverse effects.
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Postexposure rabies prophylaxis for patients not previously vaccinated is as follows:
o Local wound cleansing: Begin all postexposure treatment with immediate thorough cleansing
for 10 minutes with soap and water.
o HRIG: Administer 20 IU/kg with the full dose infiltrated at the wound and any remaining
volume administered IM gluteally or at another other anatomic site distant from the site of
vaccine administration.
o Vaccine: Administer HDCV, RVA, or RabAvert 1.0 mL IM (deltoid or thigh) on days 0, 3, 7,
14, and 28.
Bite wound management involves the following:
o Cleanse the wound with soap and water or preferably povidone/iodine solution for at least 10
minutes, with debridement of devitalized tissue as necessary. Failure of adequate cleansing
has caused failure of passive and active immunoprophylaxis in human rabies cases.
o Check tetanus status and update immunization and antibiotics as necessary.
o Determine rabies immune status of the biting animal. In many instances, determination of the
nature of the interaction may be critical; determine whether the attack was provoked.
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o
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If the domestic animal (cat, dog, ferret) is known and can be observed for 10 days,
prophylaxis can be postponed. Similarly, prophylaxis can be postponed if a wild animal is
caught and is tested for rabies in a timely fashion. If the animal was not captured, proceed
with prophylactic immunization.
o Recommendations for postexposure prophylaxis have changed regarding bat exposure. If
rabies cannot be ruled out by testing the bat, consider prophylaxis for any person who had
direct contact with a bat, any person who was sleeping who awakened to find a bat near, or
any person who may be unaware of contact with a bat.
Preexposure prophylaxis involves the following:
o Certain occupations or travel destinations pose a risk for possible rabies exposure. Administer
preexposure rabies vaccine to all rabies laboratory workers, animal control officers,
veterinarians, spelunkers, and travelers to areas where rabies is enzootic and where immediate
access to medical care may not be available.
o All 3 IM preparations can be administered as a 1.0-mL dose in the deltoid on days 0, 7, and 21
or 28.
o The ID preparation of HDCV is administered as a 0.1-mL dose ID over the lateral deltoid on
days 0, 7, and 21 or 28.
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