Hugh B. Fackrell Fackrel@Uwindsor.ca Rhabdo.ppt Rhabdoviruses Hugh B. Fackrell Fackrel@Uwindsor.ca Rhabdo.ppt

Rhabdoviruses Structure Classification Multiplication Clinical manifestations Epidemiology Diagnosis Control Baron’s Web Site

Structure Anti-sense ssRNA genome codes for five proteins bullet shaped capsid (60-180 nm) lipid envelope glycoprotein peplomers

Rabies Virus

Rhabdovirus proteins Protein L -RNA dependent RNA polymerase Protein G- surface antigen Protein N -RNA binding protein Protein NS- phosphoprotein Protein M-membrane/matrix protein

Rhabdovirus G protein Glycoprotein in peplomer 64-68,000 MW Induces protective virus neutralizing antibody

Rabies virus genome ssRNA 12 kbase antisense leader at 3’ end intergenic region between each gene

Multiplication Negri Body 1903. Adelchi Negri, an Italian physician found negri bodies. in cytoplasm of CNS Negri Body

Multiplication Attaches to host via G protein penetration uncoated in cytoplasm Protein synthesis 5 complementary mRNA developed RNA dependent RNA polymerase Positive strand of RNA template for antisense RNA

Rhabdo Virus Replication

Rhabdo virus Replication RNA polymerase - ss RNA + mRNA + ssRNA Cytoplasm Rhabdo virus Replication

Transmission Bite of infected animal Eating infected meat ( wild animals) Airborne transmission- bat caves 2 cases in USA (1950-88) lab workers - 2 cases in USA( 1950-1988) Corneal transplants - 6 cases no known exposure -22%

Infections from Trauma Bites Zoonosis: Reservoir in wild animals Skunks, Bats, Racoons, Foxes Transmissible to man and domestic animals by bites

Distribution Global all mammals Endemic in dogs in Asia, Africa, India 17,000 deaths/year, 3,000,000 vaccines Philppines canine rabies 25,000 /yr Mexico, Central and south America, Canada, U.S.A., western Europe Wildlife rabies -increasing canine rabies controlled.

Epidemiology Described 5th century B.C. and 4th century B.C. by ancient Greeks Rabid dogs

Pasteur evidence of infections agent in saliva, CNS, peripheral nerves. He attenuated the agent used it to protect against rabies Joesph Meister.

Pathology of Rabies Virus enters local tissue through bites Travels along sensory nerves to CNS Virus multiplies in CNS neurones Hippocampus and cerebellum viremia Infects other organs

Clinical Manifestations Fever, Malaise, Headache, Sensory disturbances, Respiratory muscle spasms , Swallowing muscle spasms

Paralytic Rabies ‘Dumb’ rabies Flaccid paralysis including respiratory muscles Coma and Death

‘Furious’ rabies excitability- CNS disturbances recurrent spasms of muscles involed in swallowing 17-50% ‘Hydrophobia” choking panic delerium, convulsions

Incubation Period usually 4-6 weeks severe head or neck bites -2 weeks range 5 days- 2 years

Canine Rabies Dog acts as if it had a sore throat or something caught in its throat. Paralysed - “Dumb” rabies agitated or aggressive furious rabies throat muscle spasms - drooling Dog has difficulty swallowing appears to be foaming at the mouth, eventually becomes staperous and dies.

Wild life rabies ONTARIO - Foxes, Racoons, Skunks - 59% Bats/cave dust 14%

Diagnosis Clinical symptoms Can be detected without symptoms. Fluorescent antibodies -developed 1958. Isolate animal observe 5 days if symptoms disappear - not rabies - autopsy animal - Negri bodies - Brain cells

Laboratory Diagnosis Antibodies in serial serum specimens virus cultured from saliva virus antigen skin biopsy detected by fluorescent antibody mouse test inject saliva into mouse isolate virus

Treatment of Suspected Rabies Wash bite - soap, water Disinfect quaternary ammonium 0.1% benzalkonium chloride Iodine or 70% ethanol. Rabies antiserum around skin of bite area Vaccinate with HDCV immediately Tetanus antiserum & antibiotics

Vaccine Duck embryo vaccine has side effects Human diploid cell vaccine Merieux Institute

Human Diploid Cell Vaccine HDCV =Merieux vaccine 1% allergic encephalitis

Pre-exposure vaccine Merieux vaccine (HDCV) lyophilized dose in syringe intradermal injection 0.1 ml 0,7,21,28 days Booster every 2 years

High risk Populations Rabies research lab workers Rabies diagnostic labs Spelunkers Veterinarians Animal control workers International travelers

Postexposure Prophylaxis Intramuscular Deltoid in adults Thigh in children Days 0,3,7 Booster day30,90

Reactions to HDCV Local <10% redness, induration, 24-48 hours General slight fever, malaise 1/10,000 type I hypersensitivity 1/1,000 type III 2-21 days

Single verified case of transient neuroparalytic illness after HDCV Bernard et al 1982, JAMA 248:3136-3138

Control Domestic Animal Wild animals Humans Vaccinations intradermal vaccination Wild animals oral vaccines meatballs Humans Vaccinations high risk populations

Rabies free countries England, Australia, Japan,Sweden, Spain. Due to vaccination strict import regulations. 6 months quarantine.

Infections from Trauma bites RABIES Rhabdovirus ssRNA zoonosis: Reservoir in wild animals e.g. Skunks, Bats, Raccoons, Foxes Transmissible to man and domestic animals to man by bites

Epidemiology Described 5th century B.C. and 4th century B.C. by ancient Greeks Pasteur - found evidence of infections agent in saliva, CNS, peripheral nerves. He attenuated the agent and used it to protect against rabies. 1903. Adelchi Negri, an Italian physician found negri bodies.

Pathology of Rabies Bites/ Virus enters local tissue. Travels along sensory nerves to CNS Virus multiplies in CNS neurons Hippocampus and cerebellum viremia Infects other organs

Rabies Clinical Course: Fever, Malaise, Headache, Sensory disturbances, Respiratory muscle spasms , Swallowing muscle spasms Choking panic “ Hydrophobia” CNS disturbances - excitability Delirium, Convulsions

Rabies: Terminal Symptoms Flaccid paralysis including respiratory muscles Coma and Death Incubation: 4-6 weeks if severe head or neck bites -2 weeks Isolate animal observe 5 days if symptoms disappear - not rabies - use fluorescent antibody If symptoms get worse, kill animal - Negri bodies - Brain cells

Treatment of Suspected Rabies 1.Wash bite - soap, water, alcohol, lavage with Iodine. 2. Inject hyper immune serum around skin of bite area 3. Vaccinate immediately - Human tissue culture Vaccine - Duck embryo vaccine has side effects 1% allergic encephalitis 4. If symptoms develop. Death very likely.

Rabies cont’d 1958 - Fluorescent antibodies used to detect rabies. Can be detected without symptoms.

Rabies: Incidence Rabies - World wide - all mammals Rabies endemic in dogs in Asia, Africa, Mexico, Central and south America, In Canada, U.S.A., western Europe - Rabies in dogs controlled. Wild life rabies ONTARIO - Foxes, Racoons, Skunks - 59% Bats/cave dust 14%

Rabies Control: Pets vaccinated Cats, Dogs, Horses, Cattle Humans at risk: Veterinarians, Vaccinations - originally 14 injections - agonising. Now intramuscular.

Rabies in dogs: Dog acts as if it had a sore throat or something caught in its throat. Paralyzed - “Dumb” rabies agitated or aggressive furious rabies throat muscle spasms - drooling

Rabies Dog has difficulty swallowing appears to be foaming at the mouth, eventually becomes staperous and dies. Rabies free countries include: England, Australia, Japan, Sweden, Spain. Due to vaccination and strict import regulations. 6 months quarantine.