Varicella-zoster virus: Difference between revisions

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== Background ==
==Background==


=== Microbiology ===
===Microbiology===
* dsDNA virus in the Alphaherpesvirus family, related to HSV
* Key glycoproteiins
** 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 ''Alphaherpesvirinae'' subfamily within the [[Herpesviridae]] family, related to HSV
=== Epidemiology ===
*Key glycoproteins
* Varicella is more late winter or spring in temperate climates
**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 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 Presentation ==
*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]] caused by secondary bacterial infection with invasive [[GAS]], and can including [[necrotizing fasciitis]]
* May become disseminated
*[[Hepatitis]], especially in immunocompromised, transplant, and advanced HIV (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 ==


*Certain populations are at higher risk for severe complications
* PCR most common, sensitive and specific, can be tissue, serum, CSF, saliva, etc
*Pregnancy
* Multinucleated giant cells on histology
**[[Spontaneous abortion]], [[IUFD]], [[prematurity]]
* Cell culture
**[[Congenital varicella syndrome]]
* Serology
***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)===
== Management ==
* [[Is treated by::Valacyclovir]] preferred to [[Is treaed by::acyclovir]]
** Main side effect of valacylovir is headache


*Varicella reactivation from dorsal root ganglia
=== Normal host ===
*Typically a dermatomal distribution
* '''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 treaed 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
=== Post-exposure management ===
**50% by age 85 years
* Identify contacts: very long list, includes anyone with 5 minutes of face-to-face time, adjacent rooms or beds, ...
*Post-surgery
** Infectious 1-2 days before onset of rash
*[[HIV]] (even with normal CD4)
* '''Isolation''' of contacts
*Transplant (HSCT > SOT)
** 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 ===
====Disseminated Zoster====


*May become disseminated in immunocompromised patients, typically after transplantation
=== Varicella ===
**Involvement of visceral organs, or
* Varicella vaccine at 12 months then again at 4 to 6 years
**Multidermatomal involving 3 or more dermatomes
* Can use for PEP if within 3 days of exposure to reduce severity and duration
*Can become chronic with episodic viremia
* Live vaccine, so must be at least 12 months
*Prophylaxis
* Two doses 90% effective, though can wane over time
**HSCT: prophylax with [[valacyclovir]] for 1+ year following transplant (longer if GVHD)
* Adverse effects
**SOT: 3-6 mo after transplant and for duration of lymphodepletion
** 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


=== Zoster ===
==Diagnosis==

* '''Shingrix''' (not live; 2 doses, 6 months apart; '''more effective''') and Zostavax (live attenuated, 1 dose)
*PCR most common, sensitive and specific, can be tissue, serum, CSF, saliva, etc
** If Zostavax, give Shingrix after 7 years as a booster
*Multinucleated giant cells on histology
** If recent zoster, wait three years after an episode
*Cell culture
* Vaccinate age >50 years to reduce risk of zoster and PHN
*Serology
* History of VZV or vaccination doesn't matter, everyone can get it

==Management==

*[[Is treated by::Valacyclovir]] preferred to [[Is treated by::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 [[Is treated by::acyclovir]], then step down to oral [[Is treaed by::valacyclovir]]
*'''Herpes 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 treated by::acyclovir]] for 10 to 14 days, with steroids (involve Ophtho)
*'''Ramsay Hunt syndrome''': PO [[Is treated by::acyclovir]] or [[Is treated by::valacyclovir]], with prednisone
*'''CNS disease''': IV [[Is treated by::acyclovir]] for 10 to 14 days

==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 [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
|}

=== Antiviral Prophylaxis ===

* [[Acyclovir]] 400 mg p.o. twice daily (though range is 200 mg once daily to 300 mg three ties daily)
* [[Valacyclovir]] 500 mg p.o. daily (or 250 mg daily)
* [[Famciclovir]] 500 mg p.o. daily


[[Category:Herpesviridae]]
[[Category:Herpesviridae]]

Latest revision as of 14:43, 16 September 2024

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
  • Herpes 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 acyclovir or valacyclovir, with prednisone
  • CNS disease: IV acyclovir for 10 to 14 days

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

Antiviral Prophylaxis

  • Acyclovir 400 mg p.o. twice daily (though range is 200 mg once daily to 300 mg three ties daily)
  • Valacyclovir 500 mg p.o. daily (or 250 mg daily)
  • Famciclovir 500 mg p.o. daily
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