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Viral Encephalitis
- Inflammation caused by viral growth in the CNS
- Virus gets there hematogenously - usually
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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
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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
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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
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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)
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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
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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
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Varicella Zoster Virus (VZV)
- Primary infection: chickenpox/varicella
- Secondary (recurrent infection): shingles/zoster
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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
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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
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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
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Picornaviruses
- family has several genera
- Enteroviruses: associated with meningitis/encephalitis, poliomyelitis, postpolio syndrome (neuronal loss)
- Rhinoviruses: common cold
- Hepatitis A: virus
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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
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the only vaccine available for enerovirus infection
- is for poliovirus
- 1955 (killed)
- 1962 (live attenuated) - with dramatic effect
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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
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Countries with highest current incidence of polio
- Oct 10, 2010 - Tajikistan
- Pakistan
- India
- Afghanistan
- Democratic Republic of Congo
- Angola
- Senegal
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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
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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
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Vaccination programs:
- for pets
- for "infected" or at-risk personell - prophylaxis and treatment
- For wild animals
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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!
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Flaviviruses
- yellow fever
- Japanese encephalitis
- Russian spring-summer encephalitis: now called tick-bourne encephalitis
- West Nile encephalitis
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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
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Arboviruses
- several virus families (toga/alpha; flavi, bunya)
- Several members are select agents
- WNV has been the most recent pressing problem NY
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Toga(alpha) viruses problems include
- Eastern equine virus: EEE
- Chickungunya in India: usually fever, polyarthralgia and rash, but some neurological/sensory issues reported
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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
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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
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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
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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
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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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