1. Hugh B. Fackrell Fackrel@Uwindsor.ca Rhabdo.ppt
Rhabdoviruses
Hugh B. Fackrell
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 ( 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 Negri Body
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. Rhabdo virus Replication
RNA polymerase
- ss RNA
+ mRNA
+ ssRNA
Cytoplasm
Rhabdo virus Replication

16. Transmission Bite of infected animal
Eating infected meat ( wild animals)
Airborne transmission-
bat caves 2 cases in USA ( )
lab workers - 2 cases in USA( )
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 days

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

39. Control Domestic Animal Wild animals Humans Vaccinations
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

51. 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.