Viruses affecting the CNS Flashcards
Acute viral meningitis generally is? Bacterial meningitis is?
Mild and self-resolving
Life-threatening
Which type of meningitis is more common, viral or bacterial?
Viral
What are indicators of bacterial meningitis?
CSF glucose < 34
CSF protein > 220
CSF WBC count > 2000
CSF neutrophil count > 1100
How many of the indicators need to be positive to rule in bacterial meningitis?
One –> >99% certainty
Presentation of viral meningitis?
Pts don’t typically appear extremely ill. -Present with Fever & malaise, Headache, Neck stiffness, Low back pain (typically overshadowed by HA)
Duration of viral meningitis?
Typically self-limiting over 10-14 days
Can viral meningitis be recurrent? If so, how?
Yes, persistent or latent infections (e.g. HSV)
Most common causes of viral meningitis?
Enterovirus [80%]
What did MMR vaccine help prevent?
Meningitis caused by Mumps [10%]
- Ask about vaccination Hx
Recurrent aseptic viral meningitis can be caused by? How is it prevented? Other causes?
HSV - 2, continuous tx with Acyclovir
HIV and VZV
Viral encephalitis?
Inflammation of the brain by direct virus infection of brain tissue
Causes of viral encephalitis?
Arbovirus [30%]
Enterovirus [23%]
HSV - 1 [27%]
How are arboviruses transmitted? Time of year?
Mosquitos or ticks
Spring and Summer
Which viral encephalitis is the most dangerous?
HSV - 1
Clinical course of viral encephalitis?
Fever HA Lethargy Prodromal URI Confusion, seizures, coma, death
HSV Encephalitis can be caused by?
Acute infection or reactivation (more common)
Characteristic site of damage in HSV Encephalitis?
Temporal lobe
Genetic code of the flaviviruses?
Small, enveloped (+) strand RNA viruses
Examples of flaviviruses?
St. Louis and West Nile
Flavivirus replication cycle?
- Virus binds to membrane
- Enters by receptor-mediated endocytosis.
- Low pH dependent membrane fusion
- Uncoating from membrane
- (+) strand genome is translated into single
- Membrane-associated RNA replication (polyprotein cleaved)
- Virions morphogenesis in intracellular vesicles
- Virion transport glycoprotein maturation
- Vesicle fusion at plasma membrane –> virion release
Transmission of flavivirus?
By insect vectors
Where do flaviviruses initially replicate? What does it establish?
Site of inoculation
Transient primary viremia
Where do flaviviruses replicate post exposure as?
Macrophages, spleen, or lymph nodes
Note - it will most likely be cleared here as well
How does encephalitis occur in a flavivirus infection?
Infection is not controlled by immune system leading to a secondary viremia which results in severe systemic disease.
Where is St. Louis encephalitis virus epidemic?
North, Central, and South America
St. Louis Virus incubation period?
4 - 21 days
If pt dies from St. Louis virus, when is it most likely to occur?
W/n a week or two of presentation of CNS symptoms
Typical symptoms of St. Louis virus infection? Do most progress beyond these symptoms?
Generalized malaise, fever, chills, headache, sore throat, and/or cough
No
If secondary viremia occurs, how long before neurologic signs present?
1 - 4 days
Are there vaccines available for St. Louis Virus? Antivirals?
None
None
Where is the West Nile Virus enidemic?
Africa, West Asia, Europe, the Middle East, and the U.S.
Reservoir of West Nile virus?
Birds
For, West Nile virus are considered? How many of those infected will get severely iill?
Incidental host
1%
Symptoms of West Nile virus?
Febrile, HA, sore throat, backache, myalgia, arthralgia, fatigue, Rash, lymphadenopathy, Acute aseptic meningitis or encephalitis
Are there vaccines available for West Nile virus?
Nope
Where is the Japanese encephalitis virus epidemic?
SE Asia and the Far East
Is there a vaccine for Japanese encephalitis virus?
Yes - recommended for those traveling to rural areas of endemic areas
Structure of togaviridae genome?
Small, eveloped, nonsegmented (+) strand RNA viruses
Where is western equine encephalitis found? Eastern equine encephalitis? Venezuelan equine encephalitis?
West of the MS River
East of the MS River
Central and south America
What group are western equine encephalitis, eastern equine encephalitis, and venezuelan equine encephalitis a part of?
Alphaviruses – togaviridae
Typical disease progression of alphaviruses?
Fever for 7 to 11 days followed by resolution or abrupt onset of encephalitis –> Vomiting, dizziness, confusion, increasing loss of consciousness and w/n 2-3 days patients become comatose and die
Where does alphavirus transmission cycle occur?
Swampy areas
Structure of bunyaviruses genome?
Enveloped, segmented, single-stranded (-) sense RNA virus
How are bunyaviruses transmitted?
Mosquitoes
The most common cause of arboviral-induced pediatric encephalitis in the U.S.?
La Crosse Virus
What is special about the replication strategy of bunyaviruses?
Genes are found on 2 - 3 separate RNA segments
Structure of Rhabdoviridae genome?
Enveloped, nonsegmented (-) strand RNA virus
–> Characteristic bullet-shaped morphology
How do rhabdoviruses enter the cell?
pH-dependent manner following endocytosis
Glycoprotein found in rhabdoviruses? Function?
G
Attachment and fusion (pH-dependent)
Are rhabdoviruses syncytia forming?
No
What is the speed in which rabies virus reacts?
Slow, progressive disease
Rabies is uniformly fatal if what fails to occur?
Postexposure treatment is not administered
How does transmission of rabies virus typically occur? How else might it occur?
Animal bite; Nonbite exposure can occur (scratches, licks, aerosols)
Incubation period of rabies virus?
2 - 3 months
How long is the prodromal period in rabies?
2 - 10 days following exposure
Includes malaise, fever, headache
When does the acute neuologic phase occur in rabies?
Months to years after initial exposure
What happens during the acute neurologic phase of rabies?
Nervous system dysfunction
Types of nervous system dysfunction seen in rabies? Describe them
Furious rabies - anxiety, agitation - Encephalitis predominates - common symptom is hydrophobia Dumb rabies - paralysis
What follows the acute neurologic phase in rabies infections?
Coma and death
- 2 - 7 days after acute neurologic phase
- can last 3 day - ~1 month
Is there a vaccine for rabies?
Yes - three and all are inactivated
How do you treat rabies?
Post-exposure prophylaxis
Inject the vaccine in wound site after thorough cleaning
Structure of lymphocytic choriomeningitis virus (LCMV) [an arenavirus]?
Enveloped, segmented, ambisense RNA virus
LCMV virions contain how many RNA segments? They encode for how many proteins?
2
4
How does LCMV enter the cell?
pH-dependent endocytosis
How does replication occur in an arenavirus? Describe it
ambisense strategy
- The genome is first used as a template for transcription and the NP and L mRNAs are produced from either the L (long) or S (short) RNA segment
- The polymerase then produces a full-length antigenome for each of the segments
- The “(+)”-sense antigenome is then used as a template for transcription of the glycoprotein mRNA
- Virus particles are then assembled and released from the cell surface by budding
How is arenavirus transmitted?
Inhalation of aerosolized rodent excreta and saliva
How is LCMV disease characterized?
Two phases
- Prodrome of fever, HA, nausea, and vomiting
- Aseptic meningitis ~ 10 days later
