Lec 30 Herpes and Varicella Flashcards
What are the common characteristics of herpes viruses – viral characteristics, transmission, who gets it?
- 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
Mech of injury of herpes viruses?
- direct cell damage [lytic phase]
- immune reaction
- malignant transformation
- suppress immune system
What is life cycle of herpes virus?
- 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]
What is acyclovir?
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
What is pathogenesis of HSV 1 and 2?
- 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
What is the Tzanck test?
- diagnostic test for herpes
- scrape lesion at mouth/genitals and look under microscope
- look for multinucleated giant cells
Where does HSV1 infection occur? In who?
more commonly oral
in children and adults
Where does HSV2 infection occur? in who?
more commonly genital
mostly in adults
How are HSV1/2 transmitted?
- by direct close contact
- often have have asymptomatic shedding
What are symptoms of HSV1/2?
- 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
Can you get recurrences of HSV1/2?
yes but they are less severe
Who gets HSV encephalitis? when?
- immunocompetent or immunocompromised
- year round [in contract to enterovirus mosquito-borne encephalitis]
What are findings of skin, eye, mouth HSV in neonate?
- onset at 7-14 days
- have vesicles, conjunctivitis
What are findings of CNS HSV in neonate?
- onset at 14-21 days
- seizures, lethargy, irritability, fever
What are findings of disseminated HSV in neonate?
- onset at 5-10 days
- hepatitis, resp distress, shock, DIC
How do you diagnose HSV?
- viral culture [not good for CSF]
- DFA of skin lesion
- PCR on CSF
- Tzanck smear [less sensitive/specific]
What is treatment for herpes?
- oral acyclovir, valacyclovir
- for serious: IV acyclovir
What is valcyclovir?
prodrug of acyclovir that is converted in body
better absorbed than acyclovir
What are adverse events for acyclovir?
- kidney disfunction [prevent with hydration]
What is mech of resistance to acyclovir?
mutation in viral TK [most common
mutation in DNA pol
very rare, usually in immunocompromised
How do you treat acyclovir resistant HSV?
foscarnet
What is mech of foscarnet action? administration? side effects?
mech: pyrophosphate that inhibits viral DNA pol
administration: IV
side effects: nephrotoxic, hypo/hypercalcemia, hypo/hyperphosphatemia
When do you use prophylactic valacyclovir?
- 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
What is pathogenesis of varicella?
- infection of mucosa or URI
- viral replication in regional lymph nodes
- primary viremia/incubation period
- viral replication in liver, spleen, other
- secondary viremia
- fever
- infection of skin, get vesicular rash
In what stages of disease is varicella contagious?
contagious during secondary viremia, fever stage that follows, and for early part of rash [days 11-17]
== prior to onset of symptoms
What is primary infection of varicella zoster? reactivation?
primary = chickenpox reactivation = zoster [shingles]
Where is the latency site of varicella zoster?
sensory/dorsal root ganglia
How is varicella zoster spread?
varicella highly contagious
varicella: spread via respiratory droplets and aerosols and contact
zoster: just spread via contact
What are complications of varicella?
- bacterial superinfection
- adults have worse disease than children
- in immunocompromised/perinatal get: hepatitis, pneumotitis, prolonged rash, encephalitis
What are complications of zoster?
- post herpetic neuralgia [most common]
- keratitis
- disseminated disease in immunocompromised pts
What is treatment for VZV?
- acyclovir or valacyclovir [higher dose than HSV]
- forscarnet for resistant strains
How do you prevent VZV?
- live attenuated vaccine
- varicella zoster Ig for higher risk hosts who are exposed
