Rabies is a fatal viral infection of the central nervous system that is transmitted through the bites of infected animals. The rabies virus causes either an encephalitic or paralytic form of disease in humans. Prodromal symptoms are non-specific but may include pain or tingling near the site of exposure. The encephalitic form leads to symptoms like hydrophobia and aerophobia, while the paralytic form causes muscle weakness. Diagnosis involves detecting viral antibodies, RNA, or inclusions in brain tissue. There is no cure once symptoms begin, but rabies can be prevented through prompt post-exposure prophylaxis including wound cleaning and vaccination.

1. RABIES
ROD PRASAD

2. INTRODUCTION
 Rabies is a rapidly progressive, acute infectious disease of the central nervous system
in humans and animals that is caused by infection with rabies virus.
 The infection is normally transmitted from animal vectors.
 Rabies has encephalitic and paralytic forms that progress to death.
 Rabies virus is the most significant pathogen of the rhabdoviruses.
 Until Louis Pasteur developed the killed-rabies vaccine, a bite from a “mad” dog always
led to the characteristic symptoms of hydrophobia and certain death.

3. ETIOLOGIC AGENT
 Rabies virus is a member of the family Rhabdoviridae.
 Two genera in this family, Lyssavirus and Vesiculovirus, contain species that cause human disease.
 Rabies virus is a lyssavirus that infects a broad range of animals and causes serious neurologic disease
when transmitted to humans.
 This single-strand RNA virus has a nonsegmented, antisense genome that consists of 11,932 nucleotides
and encodes 5 proteins:
 nucleocapsid protein
 phosphoprotein
 matrix protein
 glycoprotein
 and a large polymerase protein.

4. EPIDEMIOLOGY
 Rabies is a zoonotic infection that occurs in a variety of mammals
throughout the world except in Antarctica and on some islands.
 Rabies virus is usually transmitted to humans by the bite of an infected
animal.
 Most of these deaths occur in Asia and Africa, with rural populations and
children most frequently affected.
 Thus, in many resource-poor and resource-limited countries, canine rabies
continues to be a threat to humans.

5. EPIDEMIOLOGY

6. PATHOGENESIS
 The incubation period of rabies is usually 20–90 days but in rare cases is as short as a few days or >1
year.
 During most of the incubation period, rabies virus is thought to be present at or close to the site of
inoculation.
 In muscles, the virus is known to bind to nicotinic acetylcholine receptors on postsynaptic membranes at
neuromuscular junctions.
 Rabies virus spreads centripetally along peripheral nerves toward the CNS at a rate of up to ~250 mm/d
via retrograde fast axonal transport to the spinal cord or brainstem.
 Once the virus enters the CNS, it rapidly disseminates to other regions of the CNS via fast axonal
transport along neuroanatomic connections.

8. PATHOGENESIS
 After CNS infection becomes established, there is centrifugal spread along sensory and
autonomic nerves to other tissues, including the salivary glands, heart, adrenal glands, and skin.
 Rabies virus replicates in acinar cells of the salivary glands and is secreted in the saliva of rabid
animals that serve as vectors of the disease.
 The length of the incubation period is determined by
 the concentration of the virus in the inoculum
 the proximity of the wound to the brain
 the severity of the wound
 the host’s age
 the host’s immune status

9. CLINICAL MANIFESTATIONS
 Rabies should usually be suspected on the basis of the clinical presentation.
 The disease usually presents as atypical encephalitis with relative preservation of consciousness.
 Rabies may be difficult to recognize late in the clinical course when progression to coma has occurred.
 A minority of patients present with acute flaccid paralysis.
 There are prodromal, acute neurologic, and comatose phases that usually progress to death despite
aggressive therapy.
 Two acute neurologic forms of rabies are seen in humans: encephalitic (furious) in 80% and paralytic in 20%.

10. PRODROMAL FEATURES
 The clinical features of rabies begin with nonspecific prodromal manifestations, including
fever, malaise, headache, nausea, and vomiting.
 Anxiety or agitation may also occur.
 The earliest specific neurologic symptoms of rabies include paresthesias, pain, or pruritus
near the site of the exposure, one or more of which occur in 50–80% of patients and
strongly suggest rabies.
 The wound has usually healed by this point, and these symptoms probably reflect infection
with associated inflammatory changes in local dorsal root or cranial sensory ganglia.

11. ENCEPHALITIC FORM
 Manifestations of encephalitic rabies, including fever, confusion, hallucinations, combativeness,
and seizures.
 Autonomic dysfunction is common and may result in hypersalivation, gooseflesh, cardiac
arrhythmia, and priapism.
 Rabies encephalitis is distinguished by early brainstem involvement, which results in the classic
features of:
 hydrophobia (involuntary, painful contraction of the diaphragm and accessory respiratory, laryngeal,
and pharyngeal muscles in response to swallowing liquids)
 and aerophobia (the same features caused by stimulation from a draft of air).
 The combination of hypersalivation and pharyngeal dysfunction is also responsible for the
classic appearance of “foaming at the mouth”

12. RABIES MANIFESTATIONS

13. PARALYTIC FORM
 Patients of paralytic rabies in which muscle weakness predominates and cardinal features
of encephalitic rabies (hyperexcitability, hydrophobia, and aerophobia) are lacking.
 There is early and prominent flaccid muscle weakness, often beginning in the bitten
extremity and spreading to produce quadriparesis and facial weakness.
 Sphincter involvement is common, sensory involvement is usually mild.
 Patients with paralytic rabies generally survive a few days longer than those with
encephalitic rabies, but multiple-organ failure nevertheless ensues.

14. DIAGNOSIS
 Complete blood counts are usually normal.
 Examination of CSF often reveals mild mononuclear cell pleocytosis with a mildly elevated protein level.
Severe pleocytosis (>1000 white cells/μL) is unusual and should prompt a search for an alternative diagnosis.
 Rabies Virus–Specific Antibodies - In a previously unimmunized patient, serum neutralizing antibodies to
rabies virus are diagnostic.
 Detection of rabies virus RNA by RT-PCR is highly sensitive and specific.
 Direct fluorescent antibody (DFA) testing with rabies virus antibodies conjugated to fluorescent dyes is highly
sensitive and specific and can be performed quickly and applied to skin biopsies and brain tissue.
 The hallmark diagnostic finding has been the detection of intracytoplasmic inclusions consisting of
aggregates of viral nucleocapsids (Negri bodies) in affected neurons.

15. TREATMENT AND PROGNOSIS
 There is no established treatment for rabies. There have been many recent treatment
failures with the combination of antiviral drugs, ketamine, and therapeutic (induced)
coma.
 Measures that were used in a healthy survivor in whom antibodies to rabies virus were
detected at presentation.
 Mainstay is still palliative care.
 Rabies is an almost uniformly fatal disease but is nearly always preventable with
appropriate postexposure therapy during the early incubation period.

16. POSTEXPOSURE PROPHYLAXIS
 On the basis of the history of the exposure and local epidemiologic
information, the physician must decide whether initiation of PEP is warranted.
 PEP includes local wound care and both active and passive immunization.
 Immunization with vaccine in combination with administration of one dose of
human rabies immunoglobulin (HRIG) or equine antirabies serum is
recommended.

17. POSTEXPOSURE PROPHYLAXIS
 A series of five vaccinations is then administered over the course of a
month. The slow course of rabies disease allows active immunity to be
generated in time to afford protection.
 If anatomically feasible, the entire dose of RIG (20 IU/kg) should be
infiltrated at the site of the bite.
 Otherwise, any RIG remaining after infiltration of the bite site should be
administered IM at a distant site

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