Varicella-zoster virus
From IDWiki
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 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 Presentation
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: 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 acyclovir ± prednisone
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
- Valacyclovir preferred to 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 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
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
- Indications
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
- Shingrix (non-live recombinant; 2 doses, 6 months apart; more effective) and Zostavax (live attenuated, 1 dose)
- If Zostavax, give Shingrix after 7 years as a booster
- 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 Canadian Immunization Guide