Transcript VIRAL ZOONOSES

Rhabdoviruses
G. Jamjoom
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VIRAL ZOONOSES
PART I I
VERTEBRATE VECTORS
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HUMAN RABIES
• >50,000 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
RHABDOVIRUSES
• Rhabdoviridae
family
• Lyssavirus genus
• helical, enveloped
• ss RNA, -VE sense
G glycoprotein
SPIKES
M protein
lipid bilayer membrane
helical nucleocapsid (RNA plus
N protein)
polymerase complex
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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
Middle East
Asia
Africa
N America
S America
fox, bats
wolf, dog
dog
dog, mongoose, antelope
foxes, skunks, raccoons,
insectivorous bats
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
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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
• >95% WORLDWIDE DEATHS ASSOCIATED
WITH CANINE RABIES
– CANINE RABIES PREVALENT IN LATIN
AMERICA, ASIA, AFRICA
• USA 1990-2004 ~75% BAT-ASSOCIATED
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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
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CDC silver-haired bat
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.
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