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
- 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 acyclovir ± prednisone
High-Risk Populations
- Certain populations are at higher risk for severe complications
- Pregnancy
- Spontaneous abortion, 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
- 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
- Indicated only for susceptible individuals with significant exposure who are at high risk of poor outcome and have a contraindication to vaccination
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