Rhabdoviruses

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

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

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

5. Rabies Virus

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

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

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

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

13. 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

14. Rhabdo Virus Replication

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

16. 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%

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

18. 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.

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

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

21. 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

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

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

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

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

27. 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.

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

29. 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

30. 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

31. 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

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

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

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

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

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

37. 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

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

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

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

41. 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

42. 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.

43. 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

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

45. 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

46. 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.

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

48. 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%

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

50. 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