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1 Rhabdoviruses Hugh B. Fackrell Fackrel@Uwindsor.ca Rhabdo.ppt 4/13/2015 2 Rhabdoviruses Structure Classification Multiplication Clinical manifestations Epidemiology Diagnosis Control Baron’s Web Site 4/13/2015 3 Structure Anti-sense ssRNA genome codes for five proteins bullet shaped capsid (60-180 nm) lipid envelope glycoprotein peplomers 4/13/2015 4 4/13/2015 5 Rabies Virus 4/13/2015 6 4/13/2015 7 4/13/2015 8 4/13/2015 9 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 4/13/2015 1 0 Rhabdovirus G protein Glycoprotein in peplomer 64-68,000 MW Induces protective virus neutralizing antibody 4/13/2015 1 1 Rabies virus genome ssRNA 12 kbase antisense leader at 3’ end intergenic region between each gene 4/13/2015 1 2 Multiplication 1903. Adelchi Negri, an Italian physician found negri bodies. in cytoplasm of CNS 4/13/2015 1 3 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 4/13/2015 1 4 Rhabdo Virus Replication 4/13/2015 RNA polymerase 1 5 - ss RNA + mRNA + ssRNA Cytoplasm Rhabdo virus Replication 4/13/2015 1 6 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% 4/13/2015 1 7 Infections from Trauma Bites Zoonosis: Reservoir in wild animals Skunks, Bats, Racoons, Foxes Transmissible to man and domestic animals by bites 4/13/2015 1 8 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. 4/13/2015 1 9 Epidemiology Described 5 century B.C. and 4 century B.C. by ancient Greeks Rabid dogs th th 4/13/2015 2 0 Pasteur evidence of infections agent in saliva, CNS, peripheral nerves. He attenuated the agent used it to protect against rabies Joesph Meister. 4/13/2015 2 1 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 4/13/2015 2 2 4/13/2015 2 3 Clinical Manifestations Fever, Malaise, Headache, Sensory disturbances, Respiratory muscle spasms , Swallowing muscle spasms 4/13/2015 2 4 Paralytic Rabies ‘Dumb’ rabies Flaccid paralysis including respiratory muscles Coma and Death 4/13/2015 2 5 ‘Furious’ rabies excitability- CNS disturbances recurrent spasms of muscles involed in swallowing 17-50% ‘Hydrophobia” choking panic delerium, convulsions 4/13/2015 2 6 Incubation Period usually 4-6 weeks severe head or neck bites -2 weeks range 5 days- 2 years 4/13/2015 2 7 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. 4/13/2015 2 8 Wild life rabies ONTARIO - Foxes, Racoons, Skunks - 59% Bats/cave dust 14% 4/13/2015 2 9 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 4/13/2015 3 0 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 4/13/2015 3 1 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 4/13/2015 Tetanus antiserum & antibiotics 3 2 Vaccine Duck embryo vaccine has side effects Human diploid cell vaccine Merieux Institute 4/13/2015 3 3 Human Diploid Cell Vaccine HDCV =Merieux vaccine 1% allergic encephalitis 4/13/2015 3 4 Pre-exposure vaccine Merieux vaccine (HDCV) lyophilized dose in syringe intradermal injection 0.1 ml 0,7,21,28 days Booster every 2 years 4/13/2015 3 5 High risk Populations Rabies research lab workers Rabies diagnostic labs Spelunkers Veterinarians Animal control workers International travelers 4/13/2015 3 6 Postexposure Prophylaxis Intramuscular Deltoid in adults Thigh in children Days 0,3,7 Booster day30,90 4/13/2015 3 7 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 4/13/2015 3 8 Single verified case of transient neuroparalytic illness after HDCV Bernard et al 1982, JAMA 248:3136-3138 4/13/2015 3 9 Control Domestic Animal intradermal vaccination Wild animals oral vaccines meatballs Humans Vaccinations high risk populations 4/13/2015 4 0 Rabies free countries England, Australia, Japan,Sweden, Spain. Due to vaccination strict import regulations. 6 months quarantine. 4/13/2015 4 1 Infections from Trauma bites RABIESRhabdovirus ssRNA zoonosis: Reservoir in wild animals e.g. Skunks, Bats, Raccoons, Foxes Transmissible to man and domestic animals 4/13/2015 4 2 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. 4/13/2015 4 3 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 4/13/2015 4 4 Rabies Clinical Course: Fever, Malaise, Headache, Sensory disturbances, Respiratory muscle spasms , Swallowing muscle spasms Choking panic “ Hydrophobia” CNS disturbances - excitability Delirium, Convulsions 4/13/2015 4 5 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 4/13/2015 bodies - Brain cells 4 6 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. 4/13/2015 4 7 Rabies cont’d 1958 - Fluorescent antibodies used to detect rabies. Can be detected without symptoms. 4/13/2015 4 8 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% 4/13/2015 4 9 Rabies Control: Pets vaccinated Cats, Dogs, Horses, Cattle Humans at risk: Veterinarians, Vaccinations originally 14 injections - agonising. Now intramuscular. 4/13/2015 5 0 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 4/13/2015 5 1 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. 4/13/2015
