Viral Cns Disease

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Nationally reportable viral encephalitis/menigitis are (2)

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Poliomyelitis
Arbovirus

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Arboviruses (6)

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St Louis
West Nile
Powassan
Eastern equine
Western equine
California serogroup - includes La Crosse

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Picornavirus family includes (4)

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Enterovirus
Hepatovirus (Hep A)
Rhinovirus
Parechovirus

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Picornavirus family - Enertovirus genus - 5 species

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Poliovirus
Coxsackievirus (group A and B)
Echovirus
Enterovirus

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Enteroviruses spread through (2)

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Fecal-oral
Respiratory secretions

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Enteroviruses are most prevalent in _____

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Summer and fall

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Most enterovirus infections are asx but can have sxs that are _____ or ______

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flu-like
rash

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Most common cause of aseptic meningitis - esp in children

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Enteroviruses

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Sx of aseptic meningitis (7)

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Fever
Severe headache
Stiff neck
Photophobia
Drowsiness
Confusion
N/V

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Duration of aseptic meningitis (rarely fatal)

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7-10 days

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Most common serotypes of coxsackievirus based on National Enterovirus Surveillance System (NESS)

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B1 and A19

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Most common serotypes of Echovirus based on National Enterovirus Surveillance System (NESS)

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6, 9, 18

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Associated with myocarditis, aseptic meningitis, neonatal systemic illness (encephalomyocarditis syndrome)

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Coxsackie B virus

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Crowding, poor hygiene and poor sanitation causes polio infection in ______

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Young children and infants

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Good hygiene and sanitation associated with polio infection in

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Older age groups

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In 2010, there were 4 polio-endemic countries

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Nigeria
Afghanistan
India
Pakistan

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In ___ WHO declared polio eradicated from Western Hemisphere

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1994

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Polio - replication at site of entry (2)

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Oropharynx
GIT

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Dissemination of polio (2)

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- Crosses BBB
- Infects via axons of peripheral nerves --> infects mns, anterior horn of spinal cord, medulla and occassionally cerebellum and motor cortex

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Poliomyelitis clinical dz with no dissemination to CNS

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Abortive poliomyelitis

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Abortive poliomyelitis (no CNS dissemination) has _____ day incubation pd and will get mild sx's

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7-14 days

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Polio clinical dz of aseptic meningitis

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Nonparalytic poliomyelitis

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Nonparalytic poliomyelitis has sx's of abortive poliomyelitis +

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Stiffness and pain in back and neck

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Nonparalytic poliomyelitis is ____ duration and has complete recovery

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2-10 days

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Paralytic poliomyelitis has all the symptoms of less severe diseases + _____

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Flaccid paralysis

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Temporary paralysis of polio lasts less than _____

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6 months

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Permanent paralysis of polio lasts more than _______

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6 months

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Vast majority of polio infections are _______ in the spectrum of clinical disease

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Asx

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Post polio syndrome happens in former polio survivors from pre-vaccine ear - most are ____ yrs+

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60

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Symptoms of post-polio syndrome (4)

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Progressive muscle weakness
Fatigue
Pain
Trouble breathing/swallowing

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Most widely accepted theory of post-polio syndrome cause

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-Surviving nerves rebel against lifetime of being overworked (no longer able to make new sprouts)
- Muscles give out from overuse

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Post-polio syndrome can not be reversed but can be stablized by giving muscles _____

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rest

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Inactivated Polio Vaccine (IPV)

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Salk vaccine

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Polio vaccine that contains all 3 serotypes
Safe for immunodeficient pts
No risk of polio (to pt or contact)
Can combine with routine vaccines (DPT)

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Salk (IPV)

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Oral Polio Vaccine (OPV)

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Sabin

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Polio vaccine - live attenuated
Replicates in gut and she in stool
Causes "herd immunity"
Easily administered
Induces sIgA in gut
Higher level of seroconversion after single dose

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Sabin

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VDPV = ________

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vaccine derived polio virus

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Vaccine derived polio virus is from _______ in the vaccine so that it resembles wild type polio

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Mutations

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VDPV viruses arise from the _____ vaccine

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Oral polio vaccine = Sabin

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VDPV comes from continuous replication and mutations in the ______ individual

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Immunodeficient = iVDPV

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VDPV can come from circulation in populations with low polio vaccine coverage --> can recombo with other ________

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enteroviruses

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VDPV that come from people with no known immunodeficiency or sewage isolates from an unknown source are ____-

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ambiguous (aVDPVs)

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Case of 44 yr old immunodeficient F who died of iVDPV - found iVDPV in ______

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stool

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VDPV isolated whose RNA sequences differ from OPV strain by greater than __% have replicated for at least 1yr+ after admin of OPV dose

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1%

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Polio outbreak in 2005 in ____ community - 4 kids id'ed

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Amish

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iVDPV is associated with ____ cell deficiencies (not _____)

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Associated with B cell deficiencies (not T)

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Unvaccinated college student who traveled to ____ developed polio from child in host family who had OPV --> she got paralytic polio but recovered

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South America

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Current ACIP recommendations for Polio vaccine

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4 doses of IPV at
2 mos
4 mos
12-18 mos
4-6 yrs

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ACIP recommends the IPV vaccine in 4 doses but also recommends using OPV vaccine for: (3)

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-Mass vaccinations
- Unvaccinated kids traveling to endemic area in less than 4 wks
- For 3rd and 4th dose when parents object to injection

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Leading cause of sporadic viral encephalitis

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Herpes simplex 1

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Outbreaks of viral encephalitis are usually associated with (2)

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Enterovirus
Arbovirus

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Arboviruses are ______ viruses

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ARthropod BOrne

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3 families of arboviruses

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Togavirus
Flavivirus
Bunyavirus

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Tick borne Arbovirus

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Powassan

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Arboviruses - Togaviruses (3)

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Eastern equine encephalitis
WEE
Venezuelean EE

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Arboviruses - Flaviviruses in US (3)

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St Louis
West Nile
Powassan

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Arboviruses - Bunyaviruses seen in US (2)

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California
La Crosse

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Arbovirus sub-category
+ RNA
Icosohedral
Enveloped

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Togavirus

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Arbovirus sub category
+RNA
enveloped

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Flavivirus

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Arbovirus sub category
-RNA
3 segments
Helical
Enveloped

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Bunyavirus

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Arboviruses enter human via a ____ or _____

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Mosquito or tick

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Replication of arbovirus occurs in _____ and ______ --> may be asx and clear

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Vascular endothelial cells
Lymphatic cells

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Dissemination of Arbovirus to CNS and other organs can cause (3)

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Coma
Seizure
Paralysis

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Dissemination of arbovirus can cause brain damage and is fatal in ___%

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5%

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Dissemination of _____ is more severe than other arboviruses - causes death in 1/3

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EEE

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Arboviruses: animal host is the reservoir - humans are a ____ host

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dead-end

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Outbreak of equine encephalitis may forewarn of ______

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human epidemic

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_____ are monitored in WNV

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Birds

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Most imp arbovirus in US (Used to be St Loius)

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west nile virus

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Most prevalent arbovirus worldwide

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Japanese encephalitis

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- Arbovirus present in Asia and Pacific
- Death in 25%, Neuro probs in 40%
- In mosquitos --> pigs and wading birds (domestiv pigs especially)

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Japanese encephalitis

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Flavivirus that cause milder sx's than St Louis and Japanese encephalitis
Also, usually not virulent for birds

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West Nile virus

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Outbreak of this arbovirus in NYC in 1999 - 54 cases, 6 deaths

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west nile virus

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Outbreak of WNV in 1999 originally thought to be from _____
Sprayed city with pesticides and educated on how to prevent mosquito bites

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St Louis

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Transmission of WNV (3)

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- Mosquitos
- Blood transfusions
- Breastfeeding

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A donor may be ____ negative for WNV but ____ positive and transmit it in blood transfusions

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antibody negative
antigen positive

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Prevention of arboviruses (4)

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- Surveillance
- Decrease mosquito population
- Decrease exposure to mosquitos
- Vaccines

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Rabies is a _______ virus

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Rhabdovirus

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-s RNA, helical, enveloped

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Rabies

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Associated with highest case fatality rate of any infectious dz's

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Rabies

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There is no medical tx that is effective once there are clinical signs of this (documented survival of 6 pts - 5 previously had vaccine)

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Rabies

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Most US cases of Rabies are associated with transmission from _____

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bats

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Rabies reservoir in mid-US

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Skunks

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Rabies reservoir in mid-Atlantic (and moving north)

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Raccoons

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Rabies reservoir in NE

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Foxes

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Rabies reservoir that is widspread but is especially in southwest

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Bats

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Rabies reservoir in southern Texas

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Coyotes

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In US, rabies accounts for 1-2 deaths/yr b/c of vaccine for cats and dogs developed in ____

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1940s

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In _____ rabies accounts for 25,000+ deaths/yr - 96% transmitted by dogs

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India

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The closer the animal bite is to the ____, the greater than chance of rabies

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Face

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Rabies has possible transmission via _____ --> in lab workers, spelunkers, exposure through breaks in skin or at mucosal surfaces

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Aerosols

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Once rabies virus ____, it loses its infectivity

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Dries out

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Rabies replicates in _____ and _____ with a 3-8 wk incubation period

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Muscle and CT

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Rabies replicates in muscle and CT and enteres peripheral nerves at ________

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NM jx

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Rabies travels with ______ to CNS --> 90%+ fatality at this point

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nerve axons

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Rabies disseminates from CNS to ______ and other tissues (does not appear to be spread via viremia)

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Salivary glands

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Intial rabies sx = general sickness + _______

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abnormal sensation near wound

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Rabies sx = painful, spasmodic ctx's of muscles involved in swallowing (can't even swallow water)--> drool to avoid swallowing

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Hydrophobia

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CNS sx's of rabies = agitation, depression, etc + these imp ones (5)

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Dilated pupils
Hallucinations
Convulsions
Seizures
Coma

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Death from rabies is usually the results of _________

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respiratory paralysis

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Extensive CNS damage in rabies to cerebral cortex, cerebellum, hippocampus, DRG and __________

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demyelinization

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Dx of Rabies (5)

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- Negri bodies
- IF staining for viral antigens
- Isolate virus
- Serology
- RT-PCR

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Cytoplasmic inclusion bodies of Rabies
- aggregates of viral nucleocapsids
- absence does not r/o rabies

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Negri bodies

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_____ staining to dx rabies --> do of brain, cornea, skin, nape of neck

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Immunofluoresence

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Can isolate rabies virus from ___ or ____ --> cell culture or inoculate infant mice

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brain or saliva

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2 vaccines available for rabies in US --> both are ________ virus and considered equally sage and efficacious
-Given to at risk people - vets, spelunkers, travelers, etc

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Inactivated

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PEP prophylaxis of rabies (3 steps)

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- Wound tx
- Local admin of immune globulin (RIG)
- Vaccination

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PEP rabies prophylaxis given to confine virus to site of entry - given to bite be all ______ and _____ animals are observed for 10 days and ______ are killed and examined immediately

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Wild
Domestic
Bats

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Rabies _____ protocol = after sx start = coma induction and administration of amantadine

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Milwaukee

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JC virus = in _____ family

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Polyomavirus

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Naked icosahedral virus
dsDNA

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JC virus

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Virus that causes T antigens to bind and inactivate p53 and Rb

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JC virus

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JC virus binds and inactivates ____ and ____ --> sends cells through cell cycle, facilitates productive viral replication

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p53, Rb

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JC virus thoguht to enter via _______ and then disseminates via viremia to the kidney

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respiratory tract

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JC viruses has latent infection in the _____ --> B cell and monocyte lineage cells

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Kidney

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Reactivation of ____ virus can occur in immunocompromised individuals --> secondary viremia and dissemination into CNS

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JC virus

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Productive, lytic infection in oligodendrocytes of this virus leads to ___________

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Demyelinization

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JC virus may produce transformation in ______ cells

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Glial

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Demyelinating disease occuring in immunocompromised people with JC

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Progressive Multifocal Leukoencephalopathy (PML)

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Viral dz that impairs speech, vision, coordination, cognition
--> paralysis of arms and legs progresses to death
AIDS defining

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Progressive Multifocal Leukoencephalopathy

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Dx of PML based on (2)

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- Viral JC DNA in CSF (PCR)
- MRI or CT showing lesions in white matter

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JC associated with CNS tumors (5)

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Medulloblastoma
Oligodendroglioma
Astrocytoma
Glioblastoma
Ependymoma