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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

• 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)

8Murray et al., Medical Microbiology

Note: no viremia

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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)

15CDC

rabies virus infected

uninfected

FLUORESCENT ANTI-RABIES NUCLEOPROTEIN ANTIBODY

16CDC

rabies virus infected(Negri body)

uninfected

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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– 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 infectedbut 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.