Lec 30 Herpes and Varicella

Question 1

What are the common characteristics of herpes viruses – viral characteristics, transmission, who gets it?

Answer 1

• large enveloped double strand DNA
• ubiquitous [except HHV 8]
• chronic/latent infection follows acute
• reactivations common
• most transmitted during asymptomatic shedding by close contact [except varicella]
• important in immunocompromised especially with CMI [cell mediated immunity] deficiency

Question 2

Mech of injury of herpes viruses?

Answer 2

• direct cell damage [lytic phase]
• immune reaction
• malignant transformation
• suppress immune system

Question 3

What is life cycle of herpes virus?

Answer 3

• attachment by fusion, DNA to nucleus
• immediate early protein synthesis: proteins produced that regulate rest of viral replication, latent viruses remain in this stage
• early protein synthesis: genome replicated by viral DNA pol
• late prot synthesis: viral particles assemble
• release: exocytosis or lysis
• cell to cell spread [formation giant cells]

Question 4

What is acyclovir?

Answer 4

herpes DNA pol inhibitor
requires phosphorylation by viral thimydine kinase, results in chain termination
acyclovir needs to be activated by herpes thymidine kinase
- resistance if pt has herpes thymidine kinase doesn’t function

Question 5

What is pathogenesis of HSV 1 and 2?

Answer 5

• entry via break in skin, mucosa
• —- HSV 1 = mouth, HSV 2 = genital
• lesions form at site of entry from lytic phase in epithelial cell
• virus travels through sensory neurons and becomes latent in sensory ganglia
• — geniculate [HSV 1] or dorsal root [HSV 2]
• reactivation by triggers including: stress, immunosuppression, intercurrent illness

Question 6

What is the Tzanck test?

Answer 6

• diagnostic test for herpes
• scrape lesion at mouth/genitals and look under microscope
• look for multinucleated giant cells

Question 7

Where does HSV1 infection occur? In who?

Answer 7

more commonly oral

in children and adults

Question 8

Where does HSV2 infection occur? in who?

Answer 8

more commonly genital

mostly in adults

Question 9

How are HSV1/2 transmitted?

Answer 9

• by direct close contact

- often have have asymptomatic shedding

Question 10

What are symptoms of HSV1/2?

Answer 10

• most infections asymptomatic
• crops of painful, small blisters and ulcers in skin and mucous membranes
• can be oral, genital, in conjunctiva
• whitlow [in finger], other body sites
• eczema herpeticum
• encephalitis
• occassionally disseminates internally –> usually neonates or immunocompromised
• can cause bells palsy

Question 11

Can you get recurrences of HSV1/2?

Answer 11

yes but they are less severe

Question 12

Who gets HSV encephalitis? when?

Answer 12

• immunocompetent or immunocompromised

- year round [in contract to enterovirus mosquito-borne encephalitis]

Question 13

What are findings of skin, eye, mouth HSV in neonate?

Answer 13

• onset at 7-14 days

- have vesicles, conjunctivitis

Question 14

What are findings of CNS HSV in neonate?

Answer 14

• onset at 14-21 days

- seizures, lethargy, irritability, fever

Question 15

What are findings of disseminated HSV in neonate?

Answer 15

• onset at 5-10 days

- hepatitis, resp distress, shock, DIC

Question 16

How do you diagnose HSV?

Answer 16

• viral culture [not good for CSF]
• DFA of skin lesion
• PCR on CSF
• Tzanck smear [less sensitive/specific]

Question 17

What is treatment for herpes?

Answer 17

• oral acyclovir, valacyclovir

- for serious: IV acyclovir

Question 18

What is valcyclovir?

Answer 18

prodrug of acyclovir that is converted in body

better absorbed than acyclovir

Question 19

What are adverse events for acyclovir?

Answer 19

• kidney disfunction [prevent with hydration]

Question 20

What is mech of resistance to acyclovir?

Answer 20

mutation in viral TK [most common
mutation in DNA pol
very rare, usually in immunocompromised

Question 21

How do you treat acyclovir resistant HSV?

Answer 21

foscarnet

Question 22

What is mech of foscarnet action? administration? side effects?

Answer 22

mech: pyrophosphate that inhibits viral DNA pol
administration: IV
side effects: nephrotoxic, hypo/hypercalcemia, hypo/hyperphosphatemia

Question 23

When do you use prophylactic valacyclovir?

Answer 23

• in patients with frequent symptomatic recurrences [AIDS]
• in pregnant women with recurrent HSV –> decreases shedding in genital secretions, also do C section to prevent fetal transmission
• in transplant recipients at risk for severe disease

Question 24

What is pathogenesis of varicella?

Answer 24

1. infection of mucosa or URI
2. viral replication in regional lymph nodes
3. primary viremia/incubation period
4. viral replication in liver, spleen, other
5. secondary viremia
6. fever
7. infection of skin, get vesicular rash

Question 25

In what stages of disease is varicella contagious?

Answer 25

contagious during secondary viremia, fever stage that follows, and for early part of rash [days 11-17] == prior to onset of symptoms

Question 26

What is primary infection of varicella zoster? reactivation?

Answer 26

``` primary = chickenpox reactivation = zoster [shingles] ```

Question 27

Where is the latency site of varicella zoster?

Answer 27

sensory/dorsal root ganglia

Question 28

How is varicella zoster spread?

Answer 28

varicella highly contagious varicella: spread via respiratory droplets and aerosols and contact zoster: just spread via contact

Question 29

What are complications of varicella?

Answer 29

- bacterial superinfection - adults have worse disease than children - in immunocompromised/perinatal get: hepatitis, pneumotitis, prolonged rash, encephalitis

Question 30

What are complications of zoster?

Answer 30

- post herpetic neuralgia [most common] - keratitis - disseminated disease in immunocompromised pts

Question 31

What is treatment for VZV?

Answer 31

- acyclovir or valacyclovir [higher dose than HSV] | - forscarnet for resistant strains

Question 32

How do you prevent VZV?

Answer 32

- live attenuated vaccine | - varicella zoster Ig for higher risk hosts who are exposed