Varicella-zoster virus: Difference between revisions

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== Background ==
==Background==


=== Microbiology ===
===Microbiology===
* dsDNA virus in the Alphaherpesvirus 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


*dsDNA virus in the Alphaherpesvirus family, related to HSV
=== Epidemiology ===
*Key glycoproteins
* Varicella is more late winter or spring in temperate climates, often corresponds to school year
**gB II target of neutralizing antibodies like VZIg
* Acquired by 5-10 years old in temperate climates
**gC gp IV not essential
** In tropical climates, more susceptibility in adults
**gE gp I binds Fc IgG
* Incubation period is [[Usual incubation period::10 to 21 days]]
**gH gp III fusion function
* Infectiousness lasts from 24h before rash (around time of fever) to the final crusting
**gL glycosylation
* Transmitted airborne, respiratory secretions; ''not'' transmitted on fomites


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


*Varicella is more late winter or spring in temperate climates, often corresponds to school year
== Clinical Manifestations ==
*Acquired by 5-10 years old in temperate climates
**In tropical climates, more susceptibility in adults
*Incubation period is [[Usual incubation period::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===
=== 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


*Transmitted by respiratory route
==== Differential Diagnosis ====
*Primary viremia infects liver and RES (~14 days)
* [[Enterovirus]]
*Secondary viremia causes dissemination to skin
* [[Staphylococcus aureus]]
* Drug reactions
* Contact dermatitits
* Eczema herpeticum
* Insect bites


==Clinical Manifestations==
==== Breakthrough ====
* 20% of vaccinated children still acquire varicella
* Milder, fewer sequelae


==== Sequelae ====
===Primary infection (varicella)===
* SSTI: invasive GAS including nec fasc
* Hepatitis, especially in immunocompromised, transplant, and AIDS (can be severe)
* Diarrhea, pharyngitis, otitis, nephritis, transient arthritis, myocarditis, ...
* Neurologic
** Acute cerebellar ataxia
** Diffuse encephalitis
** Aseptic meningitis, transverse myelitis, strokes
* Reye syndrome: vomiting, excitability, delirium, and coma
** Secondary to varicella and concomitant aspirin
* Respiratory: pneumonitis can be severe
** Typically develops days after rash
** Consider [[Is treated by::acyclovir]] ± [[prednisone]]


*Primary infection usually benign in childhood
==== High-risk populations ====
*Primary infection can be severe in adolescents, adults, and immunocompromised hosts
* Pregnancy
*New vesicle formation stops within 4 days
** Spontaneous abortions, IUFD, prematurity
*Presentation modified by prior vaccination
** Congenital varicella syndrome
**Less severe, fewer vesicles, less classic rash
*** Highest risk <20 weeks
*Vaccine-associated: can also get infected by the vaccine strain itself
*** Cutaneous defects, cicatral scarring and limb atrophy
*** Microcephaly, autonomic dysfunction
** If primary varicella 5 days before to 2 days after delivery, high risk of mortality
* Immune-compromised hosts
** Can have progressive disease with prolonged lesions and multiorgan infection


====Differential Diagnosis====
=== Herpes zoster (shingles) ===


*[[Enterovirus]]
* Varicella reactivation from dorsal root ganglia
*[[Staphylococcus aureus]]
* Dermatomal
*Drug reactions
* Herpes ophthalmaticus (CN V1)
*Contact dermatitits
* Ramsay-Hunt syndrome
*Eczema herpeticum
* Post-herpetic neuralgia
*Insect bites


==== Risk factors ====
====Breakthrough====


*20% of vaccinated children still acquire varicella
* Rising age predict zoster as well as postherpetic neuralgia
*Milder, fewer sequelae
** 50% by age 85 years
* Post-surgery
* [[HIV]] (even with normal CD4)
* Transplant (HSCT > SOT)


==== Immunocompromized ====
====Sequelae====


*SSTI: invasive GAS including nec fasc
* May become disseminated
*Hepatitis, especially in immunocompromised, transplant, and AIDS (can be severe)
* Can become chronic with episodic viremia
*Diarrhea, pharyngitis, otitis, nephritis, transient arthritis, myocarditis, ...
* Prophylaxis
*Neurologic
** HSCT: prophylax with valacyclovir for 1+ year following transplant (longer if GVHD)
**Acute cerebellar ataxia
** SOT: 3-6 mo after transplant and for duration of lymphodepletion
**Diffuse encephalitis
**Aseptic meningitis, transverse myelitis, strokes
*Reye syndrome: vomiting, excitability, delirium, and coma
**Secondary to varicella and concomitant aspirin
*Respiratory: pneumonitis can be severe
**Typically develops days after rash
**Consider [[Is treated by::acyclovir]] ± [[prednisone]]


====High-risk populations====
== Diagnosis ==


*Pregnancy
* PCR most common, sensitive and specific, can be tissue, serum, CSF, saliva, etc
**Spontaneous abortions, IUFD, prematurity
* Multinucleated giant cells on histology
**Congenital varicella syndrome
* Cell culture
***Highest risk <20 weeks
* Serology
***Cutaneous defects, cicatral scarring and limb atrophy
***Microcephaly, autonomic dysfunction
**If primary varicella 5 days before to 2 days after delivery, high risk of mortality
*Immune-compromised hosts
**Can have progressive disease with prolonged lesions and multiorgan infection


===Herpes zoster (shingles)===
== Management ==
* [[Is treated by::Valacyclovir]] preferred to [[Is treated by::acyclovir]]
** Main side effect of valacylovir is headache


*Varicella reactivation from dorsal root ganglia
=== Normal host ===
*Dermatomal
* '''Primary varicella'''
*Herpes ophthalmaticus (CN V1)
** Simple VZV infection, start ASAP (<72 hours) after onset of rash if going to treat; or, don't treat
*Ramsay-Hunt syndrome
** If higher risk or severe sequelae, more likely to treat
*Post-herpetic neuralgia
** 5 days in normal host
* '''Zoster'''
** Start treatment within 72 hours to reduce new lesions (doesn't affect PHN)


====Risk factors====
=== Immunocompromised host ===
* '''Primary varicella''': start with IV [[Is treaed by::acyclovir]], then step down to oral [[Is treaed by::valacyclovir]]
* '''Zoster''': start with IV [[Is treated by::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 [[Is treaed by::acyclovir]] for 10 to 14 days, with steroids (involve Ophtho)
* '''Ramsay Hunt syndrome''': PO antiviral with prednisone


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


====Immunocompromized====
=== 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 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 everyone, assuming that there is no documented immunity and there is no contraindication
** Within 3-5 days post-exposure
* '''VZIg''' (or IVIg, if VZIg not available)
** Indications
*** Immune-compromised without evidence of immunity
*** Pregnant woman without evidence of immunity
*** Child of mother she had primary chicken pox 5 days before to 2 days after delivery
*** Preterm >28 days without evidence of immunity
*** Preterm <28 weeks gestation
*** HSCT who have not had their vaccine post-transplant
** Start within 10 days after exposure


*May become disseminated
=== Vaccination ===
*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


==== Varicella ====
==Diagnosis==
* 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 [https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-24-varicella-chickenpox-vaccine.html Canadian Immunization Guide]


*PCR most common, sensitive and specific, can be tissue, serum, CSF, saliva, etc
==== Zoster ====
*Multinucleated giant cells on histology
* '''Shingrix''' (non-live recombinant; 2 doses, 6 months apart; '''more effective''') and '''Zostavax''' (live attenuated, 1 dose)
*Cell culture
** If Zostavax, give Shingrix after 7 years as a booster
*Serology
** If recent zoster, wait three years after an episode
** Zostavax-induced immunity wanes fairly quickly while Shingrix-induced immunity appears to be much more durable
* Indicated in all people ≥50 years old to reduce risk of zoster and PHN
** History of VZV or vaccination doesn't matter, everyone can get it
* See the [https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html Canadian Immunization Guide]


==Management==

*[[Is treated by::Valacyclovir]] preferred to [[Is treated by::acyclovir]]
**Main side effect of valacylovir is headache

===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 [[Is treaed by::acyclovir]], then step down to oral [[Is treaed by::valacyclovir]]
*'''Zoster''': start with IV [[Is treated by::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 [[Is treaed by::acyclovir]] for 10 to 14 days, with steroids (involve Ophtho)
*'''Ramsay Hunt syndrome''': PO antiviral with prednisone

==Prevention==

===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 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 everyone, assuming that there is no documented immunity and there is no contraindication
**Within 3-5 days post-exposure
*'''VZIg''' (or IVIg, if VZIg not available)
**Indications
***Immune-compromised without evidence of immunity
***Pregnant woman without evidence of immunity
***Child of mother she had primary chicken pox 5 days before to 2 days after delivery
***Preterm >28 days without evidence of immunity
***Preterm <28 weeks gestation
***HSCT who have not had their vaccine post-transplant
**Start within 10 days after exposure

===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 [https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-24-varicella-chickenpox-vaccine.html 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 [https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html Canadian Immunization Guide]

{| class="wikitable"
!
!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
|}
[[Category:Herpesviridae]]
[[Category:Herpesviridae]]

Revision as of 17:46, 16 August 2020

Background

Microbiology

  • dsDNA virus in the Alphaherpesvirus 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

  • SSTI: invasive GAS including nec fasc
  • Hepatitis, especially in immunocompromised, transplant, and AIDS (can be severe)
  • Diarrhea, pharyngitis, otitis, nephritis, transient arthritis, myocarditis, ...
  • Neurologic
    • Acute cerebellar ataxia
    • Diffuse encephalitis
    • Aseptic meningitis, transverse myelitis, strokes
  • Reye syndrome: vomiting, excitability, delirium, and coma
    • Secondary to varicella and concomitant aspirin
  • Respiratory: pneumonitis can be severe

High-risk populations

  • Pregnancy
    • Spontaneous abortions, IUFD, prematurity
    • Congenital varicella syndrome
      • Highest risk <20 weeks
      • Cutaneous defects, cicatral scarring and limb atrophy
      • Microcephaly, autonomic dysfunction
    • If primary varicella 5 days before to 2 days after delivery, high risk of mortality
  • Immune-compromised hosts
    • Can have progressive disease with prolonged lesions and multiorgan infection

Herpes zoster (shingles)

  • Varicella reactivation from dorsal root ganglia
  • Dermatomal
  • 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)

Immunocompromized

  • May become disseminated
  • 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

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

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 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 everyone, assuming that there is no documented immunity and there is no contraindication
    • Within 3-5 days post-exposure
  • VZIg (or IVIg, if VZIg not available)
    • Indications
      • Immune-compromised without evidence of immunity
      • Pregnant woman without evidence of immunity
      • Child of mother she had primary chicken pox 5 days before to 2 days after delivery
      • Preterm >28 days without evidence of immunity
      • Preterm <28 weeks gestation
      • HSCT who have not had their vaccine post-transplant
    • Start within 10 days after exposure

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

References

  1. ^  Burke A. Cunha, Jeffrey Baron. The pharmacokinetic basis of oral valacyclovir treatment of herpes simplex virus (HSV) or varicella zoster virus (VZV) meningitis, meningoencephalitis or encephalitis in adults. Journal of Chemotherapy. 2016;29(2):122-125. doi:10.1179/1973947815y.0000000065.

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