CNS Infections - Viral Flashcards

1
Q

HSV-1 -What infections?
Where does it act/attack?
What drug for treatment?

A
  • Keratoconjunctivitis (dedritic ulcers), Encephalitis (temporal lobe)
  • Trigeminal ganglia
  • Acyclovir!
  • Eye-Trifluridine
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2
Q

HSV-2 (herpes genitalis) - What infections?
Where does it act/attack?
What drug for treatment?

A
  • Aseptic meningitis, myelitis, neonatal herpes-meningitis, cerivial carcinogenesis
  • Sacral ganglia
  • Acyclovir!
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3
Q

VZV (chicken pox, zoster-shingles) - What infections?
Where does it act/attack?
What drug for treatment?

A
  • Meningoencephalitis, Keratitis
  • Trigeminal and dorsal root ganglia
  • Acyclovir, Varicella Vaccine
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4
Q

EBV (infectious mononucleosis) -What infections?
Where does it act/attack?
What drug for treatment?

A
  • Meningeoencephalitis
  • B lymphocytes
  • Self limited
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5
Q

CMV (cytomegalovirus) - What infections?
Where does it act/attack?
What drug for treatment?

A
  • Encephalitis, Chorioretinitis, Alzheimer’s Disease!
  • Mononuclear cells
  • Ganciclovir
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6
Q

What are the main causes of encephalitis?

A
  1. Alphaherpesviruses (HSV & VZV)
  2. Postinfectious immune responses (Measles, mumps, ruebella, VZV, influenza)
  3. Tuberculosis
  4. Autoimmune disorders
  5. Enteroviruses (poliovirus, coxackie A and B, Echoviru, Enterovirus 71, Parechovirus –> all except 71 cause fever and all are spread via fecal-to-oral route)
  6. Other minor/rare causes
    a. Arborviruses (WNV, Powassan virus, La Crosse Virus, etc.)
    b. Other herpesviruses (immunocompromised)
    c. JC virus (immunocompromised)
    d. Respiratory viruses
    e. Rabies
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7
Q

What viruses are common in the summer?

A

Enteroviruses

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8
Q

What are the polyomaviruses?

A

JC and BK viruses

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9
Q

Describe JC and BK viruses?

A

Small viruses with circular dsDNA genomes of around 5,000 bases.
They do early & late gene expression:
-Early: T (transformation) proteins. Large and small.
-Large T = cell growth promotion and transformation
-Small T = viral DNA replication
-Late = capsid (3) proteins

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10
Q

How are polymaviruses spread and how do they infect others?

A
  • Virus is probably acquired through the resp. or oral route
  • Infects tonsils & lymphocytes
  • Spreads by viremia to the kidneys in early life
  • Virus is ubiquitous and infections are typically asymptomatic (almost everyone has this)
  • Establishes persistent and latent infection in organs like kidneys and lungs
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11
Q

What happens with JC virus in immunocompromised people?

A

JC virus is reactivated and can spread to the brain. Here JC virus causes PML, a “slow virus” disease [ex: similar to subacute sclerosing pan encephalitis (SSPE) of measles]

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12
Q

What happens when someone is immunosuppressed and infected with JC virus?

A

Reactivated virus can:

  1. BK virus multiplies in urinary tract and causes viruria and possible hemorrhagic cystitis
  2. JC virus viremia goes to the CNS and causes possible PML
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13
Q

What happens in PML (progressive multifocal leukoencephalopathy)?

A

JC virus partially transforms astrocytes and kills oligodendrocytes. This causes lesion characteristic of JC viral infection as well as sites of demyelination.
–Demyelinated PML lesions (only in white matter) also contain unusual large astrocytes and oligodendroglial cells with very large nuclei –> look kind of like cancer

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14
Q

How can you diagnose JC Virus in the lab?

A
  • In situ immunofluorescence, DNA probe analysis, and PCR analysis of CSF, urine or biopsy material
  • –Urine cytologic tests can reveal the presence of JC or BK virus infection by revealing the existence of enlarged cell with dense, basophilic intranuclear inclusions resembling those induced by CMV
  • -Usually NOT cultured - too difficult to isolate
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15
Q

What is used to treat JC virus?

A

Cidofovir (used to treat polyomavirus infections)

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16
Q

How do you define encephalitis?

A
  1. Evidence of encephalopathy (altered level of consciousness persisting for more than 24 hours)
  2. AND at least two of the following:
    a. Fever or history of fever
    b. Seizures/focal neurological deficits
    c. CSF pleocytosis
    d. Electroencephalogram characteristics consistant with encephalitis
    e. Neuroimaging abnormalities consistent with encephalitis
17
Q

What is the timing and incidence of viral encephalitis?

A

Can happen year-round in any age group. Overall incidence of viral encephalitis is higher in children.

18
Q

What should you think about in diagnosis viral encephalitis?

A
  1. Vaccination history (MMR)
  2. Immune system function (EBV, HCMV, HHV-6, JC virus)
  3. Time of year
    - Later summer/early fall (Enteroviruses)
    - Mosquito or tick bites (WNV & other arboviruses, RMSF)
    - Winter (adenoviruses, influnza virus)
  4. Postinfectious (Measles, Mumps, Rubella, VZV, and Influenza)
  5. Animal bite (Rabies)
19
Q

What are common physical exam findings with viral encephalitis?

A
  • Low grade fever (under 102F)
  • Pulse rate, respiratory rate, and blood pressure typically normal
  • Signs of confusion/focal neurological deficitis
  • –Weakness on one side of the body
20
Q

What are laboratory findings with viral encephalitis?

A

ALL LABS NORMAL!!

  • Hematocrit should be normal
  • WBC should be normal (if taken from blood stream)
  • –Differential (cells) should be normal
  • Blood gases should be normal
  • Serum chemistries should be normal
21
Q

What does a head MRI show for viral encephalitis?

A
  • Can show irregular areas of hemorrhagic necrosis

- –Temporal lobe for HSV, etc.

22
Q

What does lumbar puncture/CSF show for viral encephalitis?

A

-Can show CSF pleocytosis (WBCs > 5 ul - primarily lymphocytes), RBCs present/high, normal glucose concentration, elevated protein concentration

23
Q

How can you do a definitive diagnosis of viral encephalitis?

A
  • Isolate virus from the CSF or brain (grow virus in tissue culture cells)
  • Serology of antibodies against virus
  • PCR detection of viral genome
24
Q

What’s the diagnosis?

  • Change in behavior
  • Fever & headache (2 days)
  • left-sided weakness
  • temporal lobe (irregular area of hemorrhagic necrosis)
A

HSV - viral encephalitis

25
How to treat HSV encephalitis?
Acyclovir | -If acyclovir isn't working, use cidofivir (can be used in alpha herpes viruses that don't respond well to acyclovir)
26
What's the diagnosis? - Healthy young woman, summer, complete vaccination history - CSF shows increased lymphocytes, normal glucose and elevated protein levels (viral encephalitis)
First: Give acyclovir as prophylactic Two most likely organisms = 1. Enteroviruses 2. Arboviruses (West Nile Virus) Why not adenovirus? Not winter Why not HSV? no MRI and not immunocompromised
27
What's the diagnosis? - AIDS patient with difficulty speaking, seeing, keeping balance, lesions in many sites - Paralysis & death - Demyelination with oligodendrocytes containing inclusion bodies only in white matter
JC Virus (causing PML - progressive multifocal leukoencephalopathy)
28
Tell me about Nucleoside Analogues (Antiviral drugs):
- Many antiviral drugs are nucleoside analogues - Modify the base, sugar or both - Viral DNA polymerases and reverse transcriptase are main targets - Prodrugs --> must be activated - Typically the viral polymerase has a much higher affinity for the activated analogue --> selective toxicity - Mode of action can be chain termination (acyclovir) or altered base pairing leading to inactivating genomic mutations (trifuridine)
29
What is the mechanism of acyclovir?
Chain termination
30
What is the mechanism of trifluridine?
Altered base pairing leading to inactivating genomic mutations
31
Why does acyclovir work on only lytic alpha herpes viruses?
Lytic alphaherpes viruses make thymidine kinase
32
What are the traits of Acyclovir?
- Used to treat HSV and VZV infections (alphaherpesviruses). Encephalitis, disseminated herpes, etc. - Requires viral thymidine kinase to be expressed in its wild type form - Chain terminator - Selective toxicity for cells infected with active viral infection and has a binding potential for the viral DNA 100X higher than the host cell DNA polymerase. - Resistance to the drug comes from mutations to the thymidine kinase and/or the viral DNA polymerase
33
What are the traits of Ganciclovir?
- Differs from acyclovir by the addition of one hydroxymethyl group in the acyclic side chain - Good activity against HCMV infections - HCMV is a betaherpesvirus --> no thymidine kinase. A different viral protein kinase phosphorylates ganciclovir - Once activated, it has activity against all herpesviruses DNA polymerases with a specificity for binding the viral DNA polymerase 30X higher than the cellular DNA polymerase - Effective against HCMV retinitis and other forms of HCMV infections
34
What are the traits of trifluridine?
- Analog of thymidine - Replaces thymidine and becomes incorporated into the viral DNA - Blocks further synthesis of the virus/causes extensive misreading of the viral genome leading to mutation and inactivation of the virus - Has cellular toxicity as well. Any cell undergoing a high rate of DNA replication seems to be targeted. - -It is a component of experimental anti-cancer drugs - -Modified base rather than sugar!!
35
What should you do if acyclovir doesn't work?
Switch to cidofovir