Rhabdoviruses

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Rhabdoviruses

• G. Jamjoom

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VIRAL ZOONOSES

• PART I I
• VERTEBRATE VECTORS

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HUMAN RABIES

• gt50,000 DEATHS PER YEAR WORLD WIDE

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Rabies Virus
Structure of rabies virus (Source CDC)
Rabies virus particles
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RABIES VIRUS

• Rhabdoviridae family
• Lyssavirus genus
• helical, enveloped
• ss RNA, -VE sense

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Rabies Virus

• member of the Lyssavirus genus of the
  Rhabdoviridae.
• ssRNA enveloped virus, characteristic
  bullet-shaped appearance with 6-7 nm spike
  projections.
• virion 130-240nm 80nm
• -ve stranded RNA codes for 5 proteins G, M, N,
  L, S
• Exceedingly wide range of hosts.
• There are 5 other members of Lyssavirus Mokola,
  Lagosbat, Duvenhage, EBL-1, and EBL-2.
• Duvenhage and EBL-2 have been associated with
  human rabies.

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TRANSMISSION

• BITE - USUAL ROUTE
• CORNEAL AND OTHER TRANSPLANTS
• MUCOSAL MEMBRANES, WOUND
• AEROSOL (RARE)

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Note no viremia
Murray et al., Medical Microbiology
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NERVE MAN
CDC
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Epidemiology

• Rabies is a zoonosis which is prevalent in
  wildlife. The main animals involved differs from
  continent to continent.
•  
• Europe fox, bats
• Middle East wolf, dog
• Asia dog
• Africa dog, mongoose, antelope
• N America foxes, skunks, raccoons,
  insectivorous bats
• S America vampire bats , dog

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INCUBATION PERIOD

• 2 weeks to 18 months
• average about two months
• post-exposure prophylaxis

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Pathogenesis

• The commonest mode of transmission in man is by
  the bite of a rabid animal, usually in Asia a
  dog. Rabies is an acute infection of the CNS
  which is almost invariably fatal.
• Following inoculation, the virus replicates in
  the striated or connective tissue at the site of
  inoculation and enters the peripheral nerves
  through the neuromuscular junction.
• It then spreads to the CNS in the endoneurium of
  the Schwann cells.
• Terminally, there is widespread CNS involvement
  but few neurons infected with the virus show
  structural abnormalities. The nature of the
  profound disorder is still not understood.

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SYMPTOMS

• Variable, often misdiagnosed
• Tingling, paresthesia at bite site
• Fever, headache, malaise, anorexia
• Nausea, vomiting, myalgia, hydrophobia
• Confusion, hallucinations, seizures, paralysis
• Coma, respiratory failure, death

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DIAGNOSIS

• neutralizing antibodies in serum or CSF
• direct fluorescence antibody
• corneal smear, nuchal biopsy, brain biopsy
• RT-PCR saliva
• post-mortem staining of brain slice
• Negri bodies
• direct flouresent Ab test ( more sensitive)

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FLUORESCENT ANTI-RABIES NUCLEOPROTEIN ANTIBODY
rabies virus infected
uninfected
CDC
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rabies virus infected (Negri body)
uninfected
CDC
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HUMAN RABIES

• SINGLE SEROTYPE
• gt95 WORLDWIDE DEATHS ASSOCIATED WITH CANINE
  RABIES
• CANINE RABIES PREVALENT IN LATIN AMERICA, ASIA,
  AFRICA
• USA 1990-2004 75 BAT-ASSOCIATED
• 39 cases
• 29 cases bat-associated strain
• 1 case raccoon-associated strain
• 9 cases dog/coyote (8 acquired outside US)

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RABIES AND RODENTS

• Small rodents - rarely infected
• but can occur - esp. woodchucks

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HUMAN RABIES

• IN U.S.A. MOST OF RECENT CASES ASSOCIATED WITH
  BAT RABIES

CDC silver-haired bat
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HUMAN RABIES

• HUMAN-TO-HUMAN
• surgically - via transplants
• no direct human-to-human ever documented

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POST-EXPOSURE PROPHYLAXIS

• CLEAN WOUND
• Include soap and water, alcohol or benzyl
  alkonium chloride etc.
• STATE HEALTH DEPARTMENT
• determine risk, examine animal (if available)
• VACCINATION
• Human Diploid Cell Vaccine
• fetal rhesus lung cell vaccine
• Purified Chicken Embryo Cell vaccine
• HUMAN RABIES IMMUNE GLOBULIN
• HRIG
• infiltrate up to half around wound, rest IM

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PRE-EXPOSURE PROPHYLAXIS

• VETERINARIANS AND STAFF
• WILDLIFE OFFICERS ETC LIKELY TO CONTACT RABID
  ANIMALS
• Cave Explorers
• TRAVELERS
• RABIES RESEARCH WORKERS

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TREATMENT

• ONCE SYMPTOMS DEVELOP, TREATMENT VIRTUALLY ALWAYS
  UNSUCCESSFUL
• INTENSIVE SUPPORTIVE CARE
• ONLY 3 CASES DOCUMENTED RECOVERY

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Control of Rabies

• Urban - canine rabies accounts for more than 99
  of all human rabies. Control measures against
  canine rabies include
• stray dog control.
• Vaccination of dogs
• quarantine of imported animals
• Wildlife - this is much more difficult to control
  than canine rabies. However, there are on-going
  trials in Europe where bait containing rabies
  vaccine is given to foxes. Success had been
  reported in Switzerland.