VZV Flashcards
Acyclovir vs VZIG in VZV prophylaxis
antivirals are now recommended for post-exposure prophylaxis for all at risk groups apart from susceptible neonates exposed within one week of delivery (either in utero or post-delivery). VZIG is recommended for those for whom oral antivirals are contraindicated.
Indications for PEP in VZV
significant exposure to chickenpox (varicella) or shingles (zoster) during the infectious period
at increased risk of severe chickenpox such as immunosuppressed individuals, neonates and pregnant women
no antibodies to varicella-zoster virus (VZV) – urgent VZV antibody testing can be performed within 24 hours
VZV infectious period
In immunocompetent individuals, as a general rule the infectious period the time should be taken as being from 24 hours prior to rash onset to 5 days after rash. For immunosuppressed individuals, it is harder to generalise and therefore the infectious period should be taken from 24 hours prior to rash onset until all lesions have crusted over.
Shingles infection is primarily transmitted by direct contact with vesicle fluid in immunocompetent individuals but may be transmitted via infected respiratory secretions from immunosuppressed patients. The infectious period for localised and disseminated shingles is considered as the time from onset of rash until all of the lesions have crusted over.
VZV structure & classification
Family: Orthoherpesviridae
Genus: Varicellovirus
Species: Human alphaherpesvirus 3
dsDNA
Baltimore: I
The VZV virion consists of a nucleocapsid surrounding a core that contains the linear, double-stranded DNA genome; a protein tegument separates the capsid from the lipid envelope, which incorporates the major viral glycoproteins.
VZV PEP
Same for immunocompromised & pregnant women - only cut off different: 100 for pregnancy & 150 for immunocompromised
Oral aciclovir (or valaciclovir) is now the first choice of PEP for susceptible immunosuppressed individuals, all susceptible pregnant women at any stage of pregnancy and infants at high risk
Individuals in these groups who are exposed to chickenpox or shingles should be assessed and for those identified as susceptible antivirals (oral aciclovir or valaciclovir) should be given from day 7 to day 14 after exposure. The day of exposure is defined as the date of onset of the rash if the index is a household contact and date of first or only contact if the exposure is on multiple or single occasions respectively.
If the patient presents after day 7 of exposure, a 7-day course of antivirals can be started up to day 14 after exposure, if necessary
In a study evaluating the comparative effectiveness of a 7-day course of aciclovir given either immediately after exposure or starting at day 7 after exposure to healthy children, the incidence and severity of varicella infection was significantly higher in those given aciclovir immediately after exposure (10 of 13; 77%) who received aciclovir immediately developed clinical varicella compared with 3 of 14 (21%) who started aciclovir at day 7
Acyclovir: 800mg 4 times daily, from days 7 to 14 after exposure
Valaciclovir: 1,000mg 3 times daily, from days 7 to 14 after exposure
VZIG: if acyclovir contraindicated & in infants < 7 days old
VZIG is issued by the: Rabies and Immunoglobulin Service UK Health Security Agency Colindale
Dosing: 0-5 years 250mg (100IU) slow IM
Adults: 1000mg slow IM
VZIG should ideally be administered within 10 days (preferably 7 days for neonates and immunosuppressed contacts) of the day of exposure.
If a second contact is reported beyond 10 days (7 days for immunosuppressed) of the first exposure, then repeat assessment based on the date of the second exposure should be made to determine the need for, and benefit from, additional PEP.
Individuals receiving regular IVIG replacement therapy do not require VZIG if the most recent dose was administered <= 3 weeks before exposure.
Individuals who have previously received VZIG or IVIG as VZV post-exposure prophylaxis require a new risk assessment if a second exposure occurs.
If the second exposure occurs:
• within 3 weeks of administration of VZIG or IVIG, further PEP is not required
• between 3 and 6 weeks following administration of VZIG or IVIG, further PEP (dose of VZIG) should be administered without further testing
• more than 6 weeks following administration of VZIG or IVIG, retesting of a new sample is required
VZV treatment
If a pregnant woman presents with a chickenpox rash, they should be changed to a therapeutic dose (aciclovir 800mg 5 times a day or 1,000mg valaciclovir 3 times a day for 7 days, starting from the day of onset of the rash). If severe chickenpox develops, the woman should be hospitalised and given IV aciclovir.
Same dosing for all adults
Treatment of neonates with varicella If chickenpox develops despite VZIG, high dose intravenous aciclovir treatment of 20mg/kg every 8 hours for at least 7 days should be started as soon as possible
Inadvertent VZV live vaccination
Both of the currently available chickenpox vaccines (Varilrix® and Varivax®) and the live shingles vaccine (Zostavax®) contain the same live attenuated strain (Oka) of varicella zoster virus. However, the live attenuated shingles vaccine has significantly higher antigen content than the chickenpox vaccine and therefore a risk assessment is required if a pregnant woman is inadvertently vaccinated. There is limited data on women who have been inadvertently vaccinated with the live attenuated shingles vaccine during pregnancy. Therefore, as a precautionary measure, health professionals should undertake a risk assessment, including assessment of immune status similar to that for a natural exposure.
No treatment is needed if the woman inadvertently receives Shingrix (recombinant zoster vaccine) as it is a non-replicating vaccine.
Neonatal VZV PEP
PEP is recommended for 3 groups:
- Neonates whose mothers develop chickenpox (but not shingles) in the period 7 days before to 7 days after delivery: VZIG can be given without VZV IgG antibody testing of the neonate or mother; in addition, prophylactic IV aciclovir (10 mg/kg every 8 hours for 10 days) should also be considered in addition to the VZIG for infants whose mothers develop chickenpox 4 days before to 2 days after delivery as they are at the highest risk of fatal outcome despite VZIG prophylaxis.
- VZV antibody-negative infants under 1 year who have remained in hospital since birth who are born before 28 weeks gestation or weighed < 1,000g at birth or
VZV antibody-negative infants who have a severe congenital or other underlying condition that requires prolonged intensive or special care during the first year of life.
- VZV susceptible neonates exposed to chickenpox or shingles (other than in the mother) in the first 7 days of life
In infants > 4 weeks (regardless of gestation at birth) oral aciclovir is the recommended PEP, unless contraindicated (renal toxicity or malabsorption). If contraindicated, VZIG should be given
Determination of immune status for neonates or infants
For infants in Group 2, maternal antibody may not be present despite a positive maternal history of chickenpox due to immaturity of the immune system at birth, or because birth occurred before maternal antibody transfer is likely to have occurred, or due to waning maternal antibodies. In addition, for those infants in Group 2 who have had repeated blood sampling with replacement by packed red cell infusion, maternal history cannot be relied upon. It is therefore recommended that such infants are tested to determine their VZV antibody status in the event of a contact.
For infants in Group 3, VZV antibody testing is not required for mothers or their infants, if the mother has a positive history of chickenpox or shingles. As antibody levels following vaccination are lower, for infants in Group 3, whose mothers have received varicella vaccine, antibody testing of the mothers (preferred) or infant is recommended. In addition, for infants in Group 3 whose mothers have a negative or uncertain history of chickenpox or shingles, testing is also recommended. A higher cut off (150mIU/ml) is used to determine need for VZIG for neonates (when testing either mother or infant’s bloods) compared to pregnant women. This is because the aim is to try to prevent infection as opposed to attenuating disease complications.
PEP is recommended for VZV antibody-negative neonates or infants, as defined as:
• infants whose mothers are VZV antibody-negative by a qualitative assay or <150 mIU/ml by a quantitative assay
• infants who are themselves tested and found to be VZV antibody-negative by a qualitative assay or <150 mIU/ml by a quantitative assay
Congenital VZV/VZV infection pregnancy risk
in the first 20 weeks of pregnancy – congenital (fetal) varicella syndrome, which includes limb hypoplasia, microcephaly, cataracts, growth retardation and skin scarring. The mortality rate is high. From the largest available prospective study, the incidence has been estimated to be less than 1% in the first 12 weeks and around 2% between 13 and 20 weeks of pregnancy (Enders et al., 1994). In this study, no cases of congenital varicella syndrome occurred among the 477 pregnancies in which maternal varicella occurred after 20 weeks’ gestation.
VZV vaccines
Two vaccines are currently available: Varilrix® (Oka-RIT) and Varivax® (Oka/Merck). BOTH LIVE.
The two-dose vaccination schedule provides about 98% protection in children (Shapiro et al., 2011) and about 75% protection in adolescents and adults.
Schedule : children 2 doses 12 and 18 months SUBCUTANEOUS
Varicella vaccine can, and ideally should (see below), be given at the same time as other live vaccines such as MMR.
After a live vaccine is given, natural interferon is produced in response to that vaccine. If a second live vaccine is given during this response, the interferon may prevent replication of the second vaccine virus. This may attenuate the response to the second vaccine.
Zoster vaccines
From September 2023, Shingrix replaced Zostavax in the routine immunisation programme.
Shingrix® is a recombinant vaccine and contains varicella zoster virus glycoprotein E antigen produced by recombinant DNA technology, adjuvanted with AS01B.
Adults should receive two doses of 0.5ml of Shingrix® a minimum of 8 weeks apart. However, a longer dose interval of between 6-12 months in England, Wales and Northern Ireland and 2-6 months in Scotland is being used.
INTRAMUSCULAR
The JCVI recommended that Shingrix should replace Zostavax® in the routine programme and that the programme should be offered at 60 years of age.
Severely immunosuppressed individuals represent the highest priority for vaccination given their risk of severe disease, and therefore the programme aims to catch up all eligible individuals aged 50 years
