1. M. RASOOLINEJAD,MD DEPATMENT OF INFECTIOUS DISEASE TEHRAN UNIVERCITY OF MEDICAL SCIENCE

2. RABIES Acute viral disease of CNS All mammals RNA virus  Lassavirus  Rhabdovirus

5. EPIDEMIOLOGY  Worldwide distribution ( Australia,Antarcitica )  Urban rabies: dogs,cats  Sylvatic rabies: foxes, wolves, bats,…  Transmission: Bite Aerosol Aerosol Ingestion Ingestion Transplantation Transplantation  EPIDEMIOLOGY IN IRAN

8. Raccoon

9. fox

11. Bats

19. PATHOGENESIS Live virus  Epidermis, Mucus membrane Peripheral nerve CNS ( gray matter ) Other tissue (salivary glands,…) centripettally centrifugally

22. CLINICAL MANIFESTATIONS Non specific prodrome 1 – Non specific prodrome 2 – Acute neurologic encephalitis Acute encephalitis Acute encephalitis Profound dysfunction of brainstem Profound dysfunction of brainstem 3 – Coma 4 - Death ( Rare cases  recovery )

23. CLINICAL MANIFESTATIONS Non specific prodrome 1 – Non specific prodrome 1 - 2 days  1 week  Fever, headache, sore throat  Anorexia, nausea, vomiting,  Agitation, depression  Paresthesia or fasciculations at or Around the site of inoculation of virus. Around the site of inoculation of virus.

24. CLINICAL MANIFESTATIONS 2 – Acute Neurologic Encephalitis Phase Furious Rabies Dumb ( Rage tranquille ) (Landry/Guillain-Barre Syndrome) (Landry/Guillain-Barre Syndrome)

25. CLINICAL MANIFESTATIONS 2 – Acute Neurologic Encephalitis 1 – 2 days to < 1 week  Excessive motor activity, Excitation, Agitation  Confusion, Hallucinations, Delirium,  Bizarre aberrations of thought, Seizures,  Muscle spasms, Meningismus,  Opisthotonic posturing  Mental aberration ( Lucid period  coma )  Hypersalivation, Aphasia, Pharyngeal spasms  Incordination, Hyperactivity,

26. CLINICAL MANIFESTATIONS 2 – Acute Neurologic Encephalitis Phase  Fever T > 40.6  Dilated irregular pupils  Lacrimation, Salivation & Perspiration  Upper motor neuron paralysis  D eep tendon reflexes  Extensor plantar responses ( as a rule )  Hydrophobia or Aerophobia (50 -70% )

30. DIAGNOSIS Laboratory finding: ( CBC, CSF )Laboratory finding: ( CBC, CSF ) Exclusion of other etiologiesExclusion of other etiologies Pathology:Pathology: Formation of cytoplasmic inclusions: Formation of cytoplasmic inclusions: ( Negri bodies ) ( Negri bodies ) ( Ammon’s horn, Cerebral cortex, ( Ammon’s horn, Cerebral cortex, Brainstem, Hypothalamus, Brainstem, Hypothalamus, The Purkinje cells of cerebellum, The Purkinje cells of cerebellum, Dorsal spinal ganglia ) Dorsal spinal ganglia )

32. DIAGNOSIS Isolation of virus (saliva,CSF, brain )Isolation of virus (saliva,CSF, brain ) SerologySerology Viral Ag detection ( infected tissue )Viral Ag detection ( infected tissue ) Viral DNA detection ( PCR )Viral DNA detection ( PCR )

33. DIFFERENTIAL DIAGNOSIS  Other viral encephalitis  Hysteria reaction to animal bite  Landry/Guillan-barre syndrome  Poliomyelitis  Allergic encephalomyelitis ( rabies vaccine )

34. PREVENTION  Preexposure Prophylaxis  Postexposure Prophylaxis

35. HUMAN RABIES BIOLOGICS PRODUCT  Rabies immune globulin:

36. HUMAN RABIES BIOLOGICS PRODUCT  Vaccine: Human diploid cell vaccine (HDCV) Human diploid cell vaccine (HDCV) Purified chick embryo cell vaccine (PCEC) Purified chick embryo cell vaccine (PCEC) Purified Vero cell vaccine (PVRV) Purified Vero cell vaccine (PVRV) Purified duck embryo vaccine (PDEV) Purified duck embryo vaccine (PDEV)

38. PREEXPOSURE PROPHYLAXIS Veterinarian, Cave explorers, Lab workers, Animal handlers  Active immunization (Vaccine) On days: 0, 7, 21 (28) On days: 0, 7, 21 (28)  Booster doses (Neutralizing Ab <1:5 )

39. POSTEXPOSURE PROPHYLAXIS Wound cleaning & treatment 1 – Wound cleaning & treatment ( Tetanus & Antibiotics ) ( Tetanus & Antibiotics ) 2 – Passive immunization 3 – Active immunization

42. POSTEXPOSURE PROPHYLAXIS Wound cleaning & treatment 1 – Wound cleaning & treatment

45. POSTEXPOSURE PROPHYLAXIS 2 – Passive immunization HRIG 20IU/Kg IM on day 0 HRIG 20IU/Kg IM on day 0

46. POSTEXPOSURE PROPHYLAXIS 3 – Active immunization 3 – Active immunization

47. PREVENTION IN ANIMALS