Viral Encephalitis .txt

  1. Viral Encephalitis
    • Inflammation caused by viral growth in the CNS
    • Virus gets there hematogenously - usually
  2. Pathogenesis of viral encephalitis
    • caused by neural cell death may be directly attributable to viral growth
    • activation of the innate immune response
    • activation of cytotoxic T-cell responses
    • apoptosis
  3. What you might see in clinic in NY as causes of viral encephalitis (meningitis)
    • HSV: herpes symplex, enteroviruses,
    • RV: rabies virus, HIV
    • West Nile virus, CNVL cytomegalovirus, TBE
    • Human T-cell Leukemia
    • Other areas in the U.S. EEE: eastern equine, CE:
    • California SLE: St. Lous, HTLV-1: human T-cell leukemia (tropical spastic paraparesis)
    • Prion disease: found everywhere
  4. Herpesviruses
    • HSV-1 and HSV-2 (1 in 200,000 frequency; encephalitis, from both primary and recurrent infections)
    • VZV (recurrent infection only - zoster - shingles) meningoencephalitis, transient neurological signs; pain
    • vaccine now available for zoster
  5. Herpes simplex viruses
    • Primary HSV infection: gingivostomatitis; latency established
    • Secondary (recurrent) HSV infection: cold sore, result of reactivation from latency (same virus as the primary infection)
  6. Disease mechanisms for HSV
    • Infection by direct contact; local infection
    • Establishes latency in neurons (trigeminal HSV1; and sacral HSV2 usually)
    • Reactivated by stress, immune suppression, etc. can be frequent
    • cell-mediated immunity needed for resolution of infection
    • immune response contributes to symptoms
  7. HSV Encephalitis Diagnosis
    • Clinical signs
    • Rule out space-filling lesion
    • Spinal tap: CSF for PCR analysis
    • Speed is important; start therapy ASAP
    • Tx: Antiviral agents
  8. Varicella Zoster Virus (VZV)
    • Primary infection: chickenpox/varicella
    • Secondary (recurrent infection): shingles/zoster
  9. Disease mechanisms for VZV
    • Primary and recurrent
    • transmitted by respiratory droplets or direct contact; systemic infection
    • Virus establishes latent infection in a variety of spinal ganglia; reactivates following depressed immune response
    • Usually recurs only once, usually in older people
  10. Txs for herpesvirus infections
    • Excellent antivirals are available to treat both HSV 1&2, and VZV infections
    • Acyclovir (ACV) and its derivatives (e.g. Valtrex) stop synthesis of viral DNA specifically: acts as a stop codon in transcription
    • Foscarnet: for ACV-resistant strains (act on the viral DNA polymerase)
    • vaccines for varicella and zoster
  11. VZV Vaccines
    • the zoster vaccine (Zostavax, Merck) is available for those >60
    • Live attenuated
    • one shot
    • gives reasonable protection (2/3 will not have PHN)
    • Zoster - *** one of main causes of viral blindness
  12. Picornaviruses
    • family has several genera
    • Enteroviruses: associated with meningitis/encephalitis, poliomyelitis, postpolio syndrome (neuronal loss)
    • Rhinoviruses: common cold
    • Hepatitis A: virus
  13. Enteroviruses
    • feco-oral spread
    • Inside the enterovirus genus
    • Echoviruses (ECHO)
    • Coxackie viruses (NY)
    • Enteroviruses
    • Polioviruses - this is the most studied virus in this group
    • lab dx: using real-time PCR of spinal fluid
  14. the only vaccine available for enerovirus infection
    • is for poliovirus
    • 1955 (killed)
    • 1962 (live attenuated) - with dramatic effect
  15. Polio vaccine recommendations
    • polio vaccine now IPV (killed): 4,6,15mo, 4-6 yers
    • can use OPV for last two (not in U.S.)
    • Polio gone from most of the world
  16. Countries with highest current incidence of polio
    • Oct 10, 2010 - Tajikistan
    • Pakistan
    • India
    • Afghanistan
    • Democratic Republic of Congo
    • Angola
    • Senegal
  17. Rabies
    • reemerged in NE U.S.
    • cryptic rabies from bats
    • virus member of the rhabdovirus family: bullet-shaped
    • don't need a bite for infection - can also just get a lick of a wound
    • A uniformly fatal disease: once clinical symptoms begin
  18. Rabies epidemiology
    • a zoonosis with along incubation period
    • reservoir: wild animals
    • Vektor: wild animals and unvaccinated dogs and cats
    • Source of infection: saliva and bat aerosols
  19. Vaccination programs:
    • for pets
    • for "infected" or at-risk personell - prophylaxis and treatment
    • For wild animals
  20. Rabie Vaccine
    • safe but expensive
    • can be given POST EXPOSURE!
    • Whe to vaccinate depends on exposure situation
    • pre-exposure: 3 shots (0,7,21/28 days)
    • Post-exposure: 5 shots (-,3,7,14,28 days) 2 shots if vaccinated (0,3d)
    • default is to vaccinate!
  21. Flaviviruses
    • yellow fever
    • Japanese encephalitis
    • Russian spring-summer encephalitis: now called tick-bourne encephalitis
    • West Nile encephalitis
  22. West Nile virus
    • Fever: 90%
    • Fatigue: 63%
    • Altered mental status: 58
    • Headache 58%
    • Birds - surveillance animals!! - major reservoir hosts: 2 weeks to spread from birds to humans
  23. Arboviruses
    • several virus families (toga/alpha; flavi, bunya)
    • Several members are select agents
    • WNV has been the most recent pressing problem NY
  24. Toga(alpha) viruses problems include
    • Eastern equine virus: EEE
    • Chickungunya in India: usually fever, polyarthralgia and rash, but some neurological/sensory issues reported
  25. Other Flaviviruses of importance
    • St. Louis Encephalitis (SLE): occurs in sporadic outbreaks; can be confused with WN encephalitis/esp. in Rochester - recently
    • Japanese encephalitis: is an emerging infection in the far east, including Australia
    • Tick-borne encephalitis is widespread across central Asia/Europe; Powassan virus in the US?
    • Vaccines for JE and TBE
  26. Bunyaviruses
    • RNA viruses - so will mutate easily and avoid Tx and vaccines very easily
    • California encephalitis/la Crosse virus: most of it is east of the Mississippi
  27. Additional causes of CNS disease: prions
    • "slow virus diseases"
    • Prions - modified protein products of a cellular gene PrPc (no nucleic acid in prions)
    • resistant to autoclaving - infection from surgical instruments
    • TSE (transmissible spongiform encephalopathy): caused by a pathogenic prion - PrPsc
  28. Prion diseases
    • Kuru: probe no longer exists - New Guinea
    • Creutzfeldt-Jakob disease (CJD)
    • Gerstmann-Straussler-Scheinker (GSS disease)
    • Fatal familial insomnia (FFI)
    • Animal: bovine spongiform encephalopathy - mad cow disease
  29. Infection by prions
    • Agents are impervious to standard disinfection procedures
    • long incubation period: 1-30 years
    • transmission is through infected tissue or genetically
    • Infection occurs through cuts in skin, transplantation, ingestion, and through blood
    • 85% of cases are sporadic and not genetic
    • no immune response, since prions are "self"
    • function of normal gene product unclear
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Viral Encephalitis .txt