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Rabies Pathogenesis
• A major public health problem (widespread • Rabies usually results from the bite of a rabid
among animal reservoir) animal
• An acute infection of CNS (almost always fatal) • It causes secretion of the virus in its saliva and
• Usually transmitted to humans from the bite of a promotes aggressive behavior (mad dog) that
rabid animal promotes its transmission
• Other routes of infection that have been
Properties of the Virus documented?
• STRUCTURE – Inhalation of aerosolized virus
– Rod or bullet-shaped particles surrounded – Transplantation of infected tissue (e.g.
by a membranous envelope with cornea)
protruding spikes – Inoculation through intact mucous
– Inside the envelope is a ribonucleocapsid membrane
(genome is single-stranded RNA) • Rabies virus multiplies in muscle (striated) or
connective tissue at the site of inoculation à
• CLASSIFICATION enters peripheral nerves at neuromuscular
– Belong to Family Rhabdoviridae and to
junction, CNS à multiplies à progressive
the genus Lyssavirus
encephalitis à spread through peripheral nerves
– Rhaboviruses are widely distributed in
nature but rabies is the only medically to highly innervated areas à of skin of the head
important rhabdovirus and neck, salivary glands, retina, cornea, nasal
mucosa, adrenal medulla, renal prenchyma, and
• REACTIONS TO PHYSICAL AND CHEMICAL pancreatic acinar cells
AGENTS • Submaxillary salivary gland is the organ with the
highest titer of the virus
– Survives storage at 4ºC for weeks and at • Virus has not been isolated from the blood of
-70ºC for years infected persons
– Inactivated by CO2 • Invasion of the virus into the brain and spinal cord
– Rapidly killed by exposure to UV causes an encephalitis and neuronal degeneration
radiation, sunlight, heat (1 hour at 50ºC) • Few gross or histopathologic lesions are seen in
by lipid solvents like ether and 0.1% patients with rabies despite extensive CNS
sodium deoxycholate) by trypsin, involvement
detergents, and extremes of pH • With rare exception, rabies is fatal once clinical
disase is apparent
• ANIMAL SUSCEPTIBILITY
– Rabies has a wide host range Factors affecting susceptibility and incubation
– All warm-blooded animals including period
humans can be infected • Host age
– Virus widely distributed in infected • Genetic background
animals especially in the nervous system, • Immune status
saliva, urine, lymph, milk and blood • Viral strain
– Recovery from infection is rare except in • Amount of inoculum
certain bats, where the virus has become • Severity of lacerations
peculiarly adapted to the salivary glands. • Distance the virus has to travel from its point
(vampire bats may transmit the virus for of entry to the CNS
months without themselves ever showing
any signs of disease)
• GROWTH OF VIRUS
– When freshly isolated in the laboratory,
the strains are referred to as street virus
(this strains show long and variable
incubation period of 21-60 days in dogs
and regularly produce intracytoplasmic
inclusion bodies)
– Serial brain to brain passage in rabbits
yields a “fixed” virus (mutant) that no
longer multiplies in extraneural tissues.
This strain multiplies rapidly (incubation
period is shortened to 4-6 days) and
inclusion bodies are found only with
difficulty) Pathology
• Virus produces a
• ANTIGENIC PROPERTIES specific eosinophilic cytoplasmic inclusion, the Negri
– There is a single serotype of rabies virus body in infected cells
but there are strain differences among
• Presence of Negri encephalitis or unusual behavior, they should be
body is pathognomonic of rabies but is not observed sacrificed and the tissues examined in the
in 20% of cases laboratory
C. Convulsion, coma and death Human Slow Virus and Prion Diseases
• Subacute Sclerosing Panencephalitis
Laboratory Diagnosis • Progressive multifocal leukoencephalopathy
• Rabies antigen or Nucleic Acids Detection • Creutzfeldt-Jakob disease
• Viral isolation • Kuru
• Serology
• Animal observation Subacute Sclerosing Panencephalitis
• Caused by persistent measles virus infections
Rabies Antigen or Nucleic Acids Detection with slowly progressive demyelination in the CNS
• Immunofluorescence or immunoperoxidase ending in death
staining using antirabies monoclonal antibodies • Measles infection below 18 months of age
on infected tissues (biopsy specimen taken from increases risk
skin of the neck at the hairline or impression • Manifest as progressive behavioral and
preparation of brain or corneal tissue intellectual deterioration with seizures, most often
• Negri bodies in the brain and spinal cord. They myoclonic jerks, motor incoordination, visual and
contain rabies virus antigen and can be speech impairment
demonstrated by immunofluorescence • High titers of measles antibody in serum and CSF
• PCR testing to amplify rabies virus genome from
fixed or unfixed tissue Progressive Multifocal Leukoencephalopathy
• Caused by JC virus (Family Polyomaviridae)
Viral Isolation • Occurs in some immunosuppressed individuals
• Intracerebral inoculation of suckling mice of • Causes demyelination in the CNS
infected tissue resulting to encephalitis and death
à examination of CNS of inoculated animal for Kuru
Negri bodies and rabies antigen • Occurred in Eastern highbands of New Guinea
• Isolated virus is identified by fluorescent antibody • Spread by customs surrounding ritual cannibalism
test with specific antiserum of dead relatives
Serology CJD
• Rabies antibodies can be detected by • Develops gradually
immunofluorescence or Nt test • Progressive dementia
• In infected animals or humans, these antibodies • Ataxia
develop slowly during progression of the disease • Myoclonus
but promptly after vaccination with cell-derived • Death in 5 – 12 months
vaccines
• Antibodies in CSF are produced in infected Iatrogenic CJD
individuals but not after vaccination • Transmitted accidentally by contaminated growth
hormone preparation
Animal Observation • By corneal transplant
• All animals considered rabid or suspected rabid • By contaminated surgical instrument
should be sacrificed immediately for laboratory • By cadaveric human dura matter graft for surgical
examination of neural tissues repair of head injury
• Other animals should be held for observation for
10 days. If the observed animal develop
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