View source for Varicella-zoster virus

==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 [[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===

*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====

*[[Enterovirus]]
*[[Staphylococcus aureus]]
*Drug reactions
*Contact dermatitits
*Eczema herpeticum
*Insect bites

====Breakthrough====

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

====Sequelae====

*[[SSTI]] caused by secondary bacterial infection with invasive [[GAS]], and can including [[necrotizing fasciitis]]
*[[Hepatitis]], especially in immunocompromised, transplant, and advanced HIV (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]]

====High-Risk Populations====

*Certain populations are at higher risk for severe complications
*Pregnancy
**[[Spontaneous abortion]], [[IUFD]], [[prematurity]]
**[[Congenital varicella syndrome]]
***Highest risk &lt;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
*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 &gt; 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==

*[[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

===Immunocompetent Host===

*'''Primary varicella'''
**For chickenpox treatment is not necessary but can be considered
**If higher risk or severe sequelae, more likely to treat
**If going to treat, start ASAP (&lt;72 hours) after onset of rash
**[[Valacyclovir]] 1 g p.o. three times daily for 5 to 7 days in normal host
*'''Zoster'''
**Start treatment within 72 hours to reduce new lesions (doesn't affect postherpetic neuralgia)
**Mild to moderate disease: [[valacyclovir]] 1 g p.o. three times daily for 7 days
**Severe disease including neurologic, ocular, or disseminated infections: [[acyclovir]] 10 mg/kg IV every 8 hours for 7 to 14 days

===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]]