M. RASOOLINEJAD,MDM. RASOOLINEJAD,MDDEPATMENT OF INFECTIOUS DISEASEDEPATMENT OF INFECTIOUS DISEASE

TEHRAN UNIVERCITY OF MEDICAL SCIENCETEHRAN UNIVERCITY OF MEDICAL SCIENCE

RABIES

Acute viral disease of CNS

All mammals

RNA virus Lassavirus Rhabdovirus

EPIDEMIOLOGYEPIDEMIOLOGYWorldwide distributionWorldwide distribution( ( Australia,AntarciticaAustralia,Antarcitica))

Urban rabies: dogs,catsUrban rabies: dogs,catsSylvatic rabies: foxes, wolves, batsSylvatic rabies: foxes, wolves, bats,…,…Transmission: BiteTransmission: Bite AerosolAerosol Ingestion Ingestion TransplantationTransplantationEPIDEMIOLOGY IN IRANEPIDEMIOLOGY IN IRAN

RaccoonRaccoon

foxfox

BatsBats

PATHOGENESISPATHOGENESISLive virusLive virus Epidermis, Mucus membrane Epidermis, Mucus membrane

Peripheral nervePeripheral nerve

CNS ( gray matter )CNS ( gray matter )

Other tissue (salivary glands,…)Other tissue (salivary glands,…)

centripettally

centrifugally

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

1 – Non specific prodromeNon specific prodrome

2 – Acute neurologic encephalitis2 – Acute neurologic encephalitis Acute encephalitisAcute encephalitis Profound dysfunction of brainstemProfound dysfunction of brainstem

3 – Coma3 – Coma

4 - Death ( Rare cases 4 - Death ( Rare cases recovery ) recovery )

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

1 – Non specific prodrome Non specific prodrome 1 - 2 days 1 - 2 days 1 week 1 weekFever, headache, sore throatFever, headache, sore throatAnorexia, nausea, vomiting, Anorexia, nausea, vomiting, Agitation, depressionAgitation, depressionParesthesia or fasciculations at orParesthesia or fasciculations at or Around the site of inoculation of virus. Around the site of inoculation of virus.

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS2 – Acute Neurologic Encephalitis Phase2 – Acute Neurologic Encephalitis Phase

Furious RabiesFurious Rabies

Dumb ( Rage tranquille )Dumb ( Rage tranquille ) (Landry/Guillain-Barre Syndrome)(Landry/Guillain-Barre Syndrome)

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS2 – Acute Neurologic Encephalitis 2 – Acute Neurologic Encephalitis 1 – 2 days to < 1 week1 – 2 days to < 1 weekExcessive motor activity, Excitation, AgitationExcessive motor activity, Excitation, AgitationConfusion, Hallucinations, Delirium, Confusion, Hallucinations, Delirium, Bizarre aberrations of thought, Seizures,Bizarre aberrations of thought, Seizures,Muscle spasms, Meningismus, Muscle spasms, Meningismus, Opisthotonic posturingOpisthotonic posturing Mental aberration ( Lucid period Mental aberration ( Lucid period coma ) coma ) Hypersalivation, Aphasia, Pharyngeal spasmsHypersalivation, Aphasia, Pharyngeal spasmsIncordination, Hyperactivity, Incordination, Hyperactivity,

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS2 – Acute Neurologic Encephalitis Phase2 – Acute Neurologic Encephalitis PhaseFever T > 40.6 Fever T > 40.6 Dilated irregular pupils Dilated irregular pupils Lacrimation, Salivation & PerspirationLacrimation, Salivation & PerspirationUpper motor neuron paralysisUpper motor neuron paralysis DDeep tendon reflexeseep tendon reflexesExtensor plantar responses ( as a rule )Extensor plantar responses ( as a rule )Hydrophobia or Aerophobia (50 -70% )Hydrophobia or Aerophobia (50 -70% )

DIAGNOSISDIAGNOSIS•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 )

DIAGNOSISDIAGNOSIS•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 )

DIFFERENTIAL DIAGNOSISOther viral encephalitisOther viral encephalitis

Hysteria reaction to animal bite

Landry/Guillan-barre syndrome

Poliomyelitis

Allergic encephalomyelitis ( rabies vaccine )

PREVENTIONPREVENTION

Preexposure ProphylaxisPreexposure Prophylaxis

Postexposure ProphylaxisPostexposure Prophylaxis

HUMAN RABIES BIOLOGICS PRODUCTHUMAN RABIES BIOLOGICS PRODUCT

Rabies immune globulin:Rabies immune globulin:

HUMAN RABIES BIOLOGICS PRODUCTHUMAN RABIES BIOLOGICS PRODUCT

Vaccine: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)

PREEXPOSURE PROPHYLAXISPREEXPOSURE PROPHYLAXIS

Veterinarian, Cave explorers, Veterinarian, Cave explorers, Lab workers, Animal Lab workers, Animal handlershandlersActive immunization (Vaccine) Active immunization (Vaccine)

On days: 0, 7, 21 (28)On days: 0, 7, 21 (28)

Booster doses (Neutralizing Ab <1:5 )Booster doses (Neutralizing Ab <1:5 )

POSTEXPOSURE PROPHYLAXISPOSTEXPOSURE PROPHYLAXIS

1 – Wound cleaning & treatmentWound cleaning & treatment ( Tetanus & Antibiotics )( Tetanus & Antibiotics )

2 – 2 – Passive immunizationPassive immunization

3 –3 – Active immunizationActive immunization

POSTEXPOSURE PROPHYLAXISPOSTEXPOSURE PROPHYLAXIS

1 – Wound cleaning & treatmentWound cleaning & treatment

POSTEXPOSURE PROPHYLAXISPOSTEXPOSURE PROPHYLAXIS

2 – 2 – Passive immunizationPassive immunization HRIG 20IU/Kg IM on day 0HRIG 20IU/Kg IM on day 0

POSTEXPOSURE PROPHYLAXISPOSTEXPOSURE PROPHYLAXIS 3 –3 – Active immunizationActive immunization

PREVENTION IN ANIMALSPREVENTION IN ANIMALS