Varicella-zoster virus

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(Redirected from Herpes zoster)

Background

Microbiology

  • dsDNA virus in the Alphaherpesvirinae subfamily within the Herpesviridae family, related to HSV
  • Key glycoproteins
    • gB II target of neutralizing antibodies like VZIg
    • gC gp IV not essential
    • gE gp I binds Fc IgG
    • gH gp III fusion function
    • gL glycosylation

Epidemiology

  • Varicella is more late winter or spring in temperate climates, often corresponds to school year
  • Acquired by 5-10 years old in temperate climates
    • In tropical climates, more susceptibility in adults
  • Incubation period is 10 to 21 days
  • Infectiousness lasts from 24h before rash (around time of fever) to the final crusting
  • Transmitted airborne, respiratory secretions; not transmitted on fomites

Pathophysiology

  • Transmitted by respiratory route
  • Primary viremia infects liver and RES (~14 days)
  • Secondary viremia causes dissemination to skin

Clinical Manifestations

Primary Infection (Varicella)

  • Primary infection usually benign in childhood
  • Primary infection can be severe in adolescents, adults, and immunocompromised hosts
  • New vesicle formation stops within 4 days
  • Presentation modified by prior vaccination
    • Less severe, fewer vesicles, less classic rash
  • Vaccine-associated: can also get infected by the vaccine strain itself

Differential Diagnosis

Breakthrough

  • 20% of vaccinated children still acquire varicella
  • Milder, fewer sequelae

Sequelae

High-Risk Populations

  • Certain populations are at higher risk for severe complications
  • Pregnancy
  • Immune-compromised hosts
    • Can have progressive disease with prolonged lesions and multiorgan infection

Herpes Zoster (Shingles)

  • Varicella reactivation from dorsal root ganglia
  • Typically a dermatomal distribution
  • Herpes ophthalmaticus (CN V1)
  • Ramsay-Hunt syndrome
  • Post-herpetic neuralgia

Risk Factors

  • Rising age predict zoster as well as postherpetic neuralgia
    • 50% by age 85 years
  • Post-surgery
  • HIV (even with normal CD4)
  • Transplant (HSCT > SOT)

Disseminated Zoster

  • May become disseminated in immunocompromised patients, typically after transplantation
    • Involvement of visceral organs, or
    • Multidermatomal involving 3 or more dermatomes
  • Can become chronic with episodic viremia
  • Prophylaxis
    • HSCT: prophylax with valacyclovir for 1+ year following transplant (longer if GVHD)
    • SOT: 3-6 mo after transplant and for duration of lymphodepletion

Diagnosis

  • PCR most common, sensitive and specific, can be tissue, serum, CSF, saliva, etc
  • Multinucleated giant cells on histology
  • Cell culture
  • Serology

Management

  • Valacyclovir preferred to acyclovir
    • Main side effect of valacylovir is headache
    • Ideally started early, within 72 hours of symptom onset

Normal host

  • Primary varicella
    • Simple VZV infection, start ASAP (<72 hours) after onset of rash if going to treat; or, don't treat
    • If higher risk or severe sequelae, more likely to treat
    • 5 days in normal host
  • Zoster
    • Start treatment within 72 hours to reduce new lesions (doesn't affect PHN)

Immunocompromised host

  • Primary varicella: start with IV acyclovir, then step down to oral valacyclovir
  • Zoster: start with IV acyclovir, then PO with close followup, until no new lesions for 2 days (minimum 7 days)
  • Pregnancy: treat zoster if more than 50 lesions
  • Ophthalmic zoster should be treated (involve Ophtho)
  • Acute retinal necrosis: IV acyclovir for 10 to 14 days, with steroids (involve Ophtho)
  • Ramsay Hunt syndrome: PO antiviral with prednisone

Prevention

Infection Prevention and Control

  • Airborne isolation required for primary varicella and disseminated zoster

Post-Exposure Management

  • Identify contacts: very long list, includes anyone with 5 minutes of face-to-face time, adjacent rooms or beds, ...
    • Infectious 1-2 days before onset of rash
  • Isolation of contacts
    • Exposed patients without evidence of immunity should be discharge as soon as possible
    • If not discharged, isolate them starting 8 days from first exposure (in airborne)
    • Duration of isolation 21 days; if VZIg (or IVIg), extend duration of isolation to 28 days
    • i.e. day 8 to 21 if no VZIg, day 8 to 28 if VZIg
  • Post-exposure vaccination
    • Recommended for all susceptible exposed individuals, assuming that there is no documented immunity and there is no contraindication
    • Within 3-5 days post-exposure to prevent disease (or any time because they need vaccination anyway)
  • VZIg (or IVIg, if VZIg not available)
    • Indicated only for susceptible individuals with significant exposure who are at high risk of poor outcome and have a contraindication to vaccination
      • That is, anyone who is already fully vaccinated or is eligible for vaccination is ineligible for VZIg
      • If their serostatus is unknown and can be checked within 96 hours, then do that first (except for patients with HSCT, who get immunized regardless)
    • High risk groups include:
      • Neonates exposed to mother who had onset of varicella 5 days before to 2 days after delivery
      • Infant in NICU who is preterm <28 weeks or weighs <1000 g, regardless of maternal immunity
      • Pregnancy (again, only if susceptible)
      • Immunocompromised individuals, including HIV with CD4 <200 or <15%
      • HSCT who have not completed their vaccines post-transplant, regardless of prior immunity
    • Significant contact includes:
      • Continuous household contact
      • Indoors for more than 1 hour, including same hospital room
      • 15 minutes face-to-face contact
      • Touch lesions, clothes, or bedsheets
    • Start within 4 days of exposure to prevent disease, or within 10 days of exposure to attenuate it

Vaccination

Varicella

  • Live attenuated varicella vaccine at 12 months then again at 4 to 6 years
  • Can use for PEP if within 3 days of exposure to reduce severity and duration
  • Live vaccine, so must be at least 12 months
  • Two doses 90% effective, though can wane over time
  • Adverse effects
    • Injection site reaction 20%
    • Rash with 2-5 lesions (1-3%) or generalized within 1 month (3-5%); it is infectious
    • Febrile seizures: MMR + VZV at 12 months has higher risk of febrile seizures
    • Disseminated, including meningitis
  • See the Canadian Immunization Guide

Zoster

  • Vaccination prevents episodes of herpes zoster (HZ) as well as decreasing post-herpetic neuralgia (PHN)
  • Indicated in all people ≥50 years old to reduce risk of zoster and PHN
    • History of VZV or vaccination doesn't matter, everyone should get it
  • In Canada, preferentially use Shingrix, as it is more effective than the live vaccine
    • If received Zostavax, wait at least 1 year before giving a booster with Shingrix
    • If recent episode of HZ, wait at least 1 year before vaccinating
  • See the Canadian Immunization Guide
Recombinant Live Attenuated
Brand Name Shingrix Zostavax II
Schedule 2 doses, 2-6 months apart 1 dose
Effectiveness >90% for HZ and PHN, and persists over time 50-70% for HZ and 70% for PHL, but decreases significantly by 5 years