VZV Flashcards
What is the incubation period (IP) for varicella?
7-21 days
Can be prolonged if patient is on steroids, immunosuppressants, or has received VZIG.
What is the infectious period (InP) for varicella?
24 hours before onset of rash until all vesicles crust over
Who is at risk of severe chickenpox (CP)?
- Pregnant (susceptible)
- Neonates
- Immunosuppressed (IS)
Why is post exposure prophylaxis (PEP) recommended for varicella?
- Attenuate disease
- Reduce risk of complications
Prevent infection in neonates
What caused the recommendation change regarding VZIG for PEP?
Severe national shortage of VZIG and evidence on safety and efficacy of antivirals as PEP
When did VZIG production stop, and when does the last stock expire?
Production stopped in Summer 2023, last stock expired in September 2024
Hence new guidance»_space; Now Anti-virals are recommended for PEP for all at risk groups including neonates.
What is recommended for neonates exposed to varicella within 1 week of delivery?
They should receive IV varicella IG (Varitect CP) or normal IVIG
What should be considered for eligible groups for whom oral antivirals are contraindicated?
A bolus dose of IVIG may also be considered
For who is PEP required?
For those who fulfill ALL of the following:
*Significant exposure to CP/Shingles during the InP.
* At risk of severe chickenpox
* No antibodies to VZV (urgent VZV Ab test can be performed within 24H)
How is varicella primarily transmitted?
Person-to-person primarily by:
-Direct contact
-Inhalation of aerosols generated from vesicular fluid from CP/SH lesions
-Inhalation of aerosols from infected RT secretions
What is the secondary infection rate from HH contact with a case of chickenpox?
Can be as high as 90%
1 HH study found that the risk for VZV transmission from herpes zoster/SH was ~20% of the risk for transmission from varicella (limited data).
What is the infectious period for immunocompetent individuals?
24 hours before rash onset to 5 days after rash first appears
What is the infectious period for immunosuppressed individuals?
24 hours before rash onset until all lesions have crusted over
How is shingles primarily transmitted?
Direct contact with vesicle fluid , but may also be aerosolized from infected respiratory tract in immunocompromised patients
What factors are considered significant exposure to VZV during the InP?
- Type of VZV infection in index case:
-CP
-dShingles
-IC with exposed shingle lesions
-IS with localized shingles on any part of the body (viral shedding maybe greater) - Timing of exposure:
-Continuous exposure to CP/SH (HH/nursery/care worker)
-Single or >1 exposure during InP - Closeness and duration of contact:- In the -Same room for =/>15min (house/classroom/2-4 bed hospital bay)
- F2F contact (having conversation)
- IS contacts on large open wards (Air-borne transmission at a distance has occasionally been reported - esp Paeds).
What types of VZV infections in an index case are relevant?
- Chickenpox
- Disseminated shingles
- Immunocompromised with exposed shingles lesions
- Immunosuppressed with localized shingles
What is considered close and prolonged contact for varicella exposure?
- In the same room for 15 minutes or more
- Face-to-face contact
- Immunosuppressed contacts in large open wards
What factors affect the assessment of susceptibility?
- History of previous CH/vaccination
- Underlying clinical condition
- Persons current treatment
What is VZ PEP unlikely to confer?
Any additional benefit for patients who already have VZV IgG
What is sufficient evidence of immunity for pregnant individuals?
History of CP/SH or 2 doses of VZV vaccine
What should be done if there is no evidence of immunity in pregnant individuals?
Test for VZV IgG with a recent sample
What is the VZV Ab cut off used in pregnant woman? what action is recommended if VZV IgG is <cut-off?
The cut off for pregnant woman in 100mIU/ml
If VZV IgG is < 100mIU/ml —> Give PEP
Why can’t VZV IgG testing results be used to determine susceptibility in vaccinated patients?
Ab responses following vaccination may not be detectable
What is the reliability of VZV IgG testing for immunosuppressed individuals?
The above is not reliable; VZV IgG needs to be checked URGENTLY at time of exposure
What is the cut off for VZV IgG for immunosuppressed individuals?
They should be offered PEP if VZV IgG is <150 mIU/ml in a quantitative assay OR
if Negative/Equivocal in qualitative assay
When is quantitative Ab testing recommended?
When IVIG is considered, except for G1 neonates born to mothers with CP within 7 days of delivery
What are the 3 types of PEP?
*Anti-virals (ACV/VCV)
*Varicella Ig for (Varitect CP)
*Normal IVIG
What are the first choice antivirals for PEP?
ACV 800mg 4/day OR
VCV 1g TDS
***From day 7 - day 14 after exposure (can be started up to day 14 after exposure , if presented late)
Antivirals are the 1st choice PEP for susceptible IS patients, pregnant women, and high-risk infants.
Could be considered for neurodisabilities
What is the definition of “day of exposure”?
The date of onset of rash if the index is a HH contact and
The date of FIRST/only contact if the exposure is on multiple/single occasions.
When should antivirals be administered to G1 neonates?
As soon as the baby is born and on recognition of the onset in the mother
To mitigate potential in utero exposure.
Why is antiviral treatment recommended to start at day 7 after exposure?
In immediate ACV PEP group –> 77% developed CP compared to 21% in group starting on day 7
This indicates a significant difference in outcomes based on timing of starting PEP
What are the most common side effects of ACV?
- Dizziness
- Headache
- Nausea/Vomiting/Diarrhea
- Skin rashes/Pruritus
- Photosensitivity
- Urticaria
With IV: renal impairment
Monitoring for side effects is crucial during treatment.
What PEP for ppl on LT ACV/VCV (eg post HSCT)
Increase the dose of ACV/VCV
What should be done if ACV is contraindicated?
Administer IVIG
This provides an alternative treatment option.
What is the recommended dose of Varicella Ig (Varitect) for IV administration?
50IU/kg (2ml/kg) as a single dose
Administered as a slow IV infusion.
What is the indication of Varitect? and When should it be given to neonates?
For neonates whose mothers developed CP 7D b4 or 7D after delivery
As soon as possible after exposure/delivery,
Preferably within 96 hours
No longer than 10 days after exposure.
What are the side effect of Varicella Ig?
V RARE
Anaphylaxis in individuals with:
Hypogammaglobulinaemia who have IgA antibodies
OR
In those who hv had an atypical reaction to blood transfusion.
This highlights the importance of patient history before administration.
What is the alternative treatment for G1 neonates if there are delays (96H) in obtaining Varitect?
Normal IVIG at a dose of 0.2g/kg (4ml/kg for 5% solution)
This will produce serum VZV Ab levels equivalent to those achieved with VZIG.
When is normal IVIG can be given? What is the ideal time frame for administering after exposure?
Contact who CANNOT receive ACV/VCV.
-As Alternative for G1 neonate - if delays in getting Varitect
Within 10D
Preferably 7D for neonates and IS patients
BUT can be given later if necessary.
What is the dosage adjustment for patients with eGFR <10 when using ACV?
Reduce frequency
Adjustments are necessary to avoid toxicity.
What should be done if a second exposure occurs within the first 7 days of treatment?
Extend the course until 14 days after the first day of the second exposure
Continuous monitoring and adjustment of treatment duration is essential.
What should be done if a second exposure occurs =/>8D after the 1st exposure
Start a new course of anti-virals
Is VCV approved for use in children under 2 years?
No, VCV is NOT for children under 2 years
What was the % of IS children who developed chickenpox in the UK observational study PEPtalk3 after receiving:
1)ACV?
2)VZIG?
1) 6% (5 out of 84)
2)11.1% (2 out of18)
ACV was Not inferior to VZIG
What should be done if an immunosuppressed individual presents with chickenpox despite receiving IVIG/ACV?
Change to an oral therapeutic dose of ACV/VCV from the day of the rash onset for 7D
If severe, assess for admission +/- IV ACV.
What is the risk assessment step for immunosuppressed individuals with a second exposure to chickenpox?
Repeat VZV Ab test prior to ACV/VZV
As asymptomatic seroconversion with ACV may occur.
What should be done if LA chickenpox vaccines are inadvertently administered to IS individuals?
Urgently assess degree of immunosuppression
Treat with ACV/VCV from day 7 if needed,
OR
Observe and use therapeutic ACV/VCV if chickenpox develops.
What is the risk of IUI by gestational
age?
Under 28 weeks: 5 to 10%
28 to 36 weeks: 25%
Over 36 weeks: 50%
Fetal varicella syndrome risk:
Under 13 weeks: 0.4%
13 to 20 weeks: 2%
Neonatal chickenpox risk in 4
days prior to 2 days postdelivery: 20%
What are the risks associated with chickenpox during pregnancy?
During the 1st 20W: can lead to FVS
<13W 0.4%
13-20W 2%
During the 2nd and early 3rd trimester: greatest risk of severe maternal disease/Viral pneumonitis.
(Risk of fatal Varicella is 5X higher)
Late in pregnancy (20-37W): SH on infancy/early childhood (0.8-1.7% risk in first 2Y of life due reactivation of in utero infection)
7-20d b4 delivery: Neonatal CP (usually less severe as trans-placentally transmitted Ab partially protect fetus at this stage)
Within 7d b4-7d after delivery: Severe disseminated haemorrhagic neonatal CP/Purpurs fulminans/death may occur (Neonatal CP 20%).
What are the clinical signs of FVS?
- Low birth weight
- Severe multi-system involvement
- Microcephaly/Neuro complications
- Cataracts/Eye lesions
- Skeletal anomalies
- Skin scarring
- Limb hypoplasia
Why is post-exposure prophylaxis (PEP) recommended for pregnant contacts?
To reduce severity of maternal disease and
Theoretical reduction in the risk of fetal infection ( for women contracting CP in the 1st 20W)
Reduce the risk of neonatal infection (for women contracting CP in late pregnancy)
What are the risks associated with chickenpox during late pregnancy?
0.8-1.7% risk of severe complications in infancy/early childhood due to reactivation of in utero infection can occur.
What is the incidence of chickenpox in pregnancy?
5-6/10,000
This highlights the relative rarity of occurrence but significant implications.
What is the risk of developing chickenpox in seronegative pregnant women after exposure without PEP?
72%
13 of 18 seronegative pregnant women developed chickenpox after exposure.
What is the efficacy of ACV and VZIG? in preventing fetal varicella syndrome (FVS)?
Efficacy of ACV is as good as VZIG***
Limited data on ACV/VZIG on prevention of FVS and transplacental infection following potential exposure in the 1st 19W.
***Based on a recent PHE/UKHSA study of confirmed seronegative pregnant women exposed to CP:
36.6% (53 of 145) received VZIG to develop CP,
compared to
30.8% (8 of 26) individuals treated with ACV
With No SEe with ACV reported
When should VZIG be offered to pregnant women?
If unable to take ACV/VCV due to malabsorption or renal toxicity
This is a crucial risk management strategy.
What should be done if a pregnant woman inadvertently receives the live attenuated CP (Varilix & Varivax) and SH (Zostvax) vaccine?
If received Zostavax (significantly higher live virus content):
Conduct risk assessment —> +/- VZV IgG test if no history of CH/SH or 2 doses of CP vaccine.
If Ab negative»_space; Offer TTT BUT the value of this will be discussed with national experts.
TTT should be given ideally within 7D But can be given upto 10D after vaccination.
For Zostavax and all other vaccines:
Advised to seek prompt medical advice if they develop a vesicular rash post vaccination.
REPORT to the UK vaccine in Pregnancy surveillance programme.
What reassurance can be given to women who have inadvertently received the chickenpox vaccine?
No conditions consistent with congenital varicella syndrome have been reported
This provides comfort regarding potential risks.
What is the increased risk associated with infants under 1 year of age?
Increased risk of severe CP
Risk of life-threatening complications especially in neonates during their first week of life.
What factors are included in the risk assessment for neonates?
Factors include:
* Presence of maternal Ab
* Prematurity
* Timing of exposure
* Whether the infant is still hospitalized
When is PEP not recommended for neonates?
PEP NOT recommended for:
- Neonates born >7d after the onset of maternal CP
- Neonates of mothers who developed SH before/after delivery
(Those above will hv maternal Ab passed to them) - Neonates <7d old whose mothers hv been exposed during pregnancy and hv been found VZV IgG Negative unless the mother developed CP
Under what condition is PEP required for neonates? and for how long?
If they may have been exposed to IUI around the time of delivery manifesting as maternal infection within 1W of delivery
As the precise timing of neonatal exposure will be unknown and given that the requirement for antivirals should cover from day 7 to day 14 post exposure, as a precaution, infants in Group 1 should continue to receive acyclovir until day 21 post delivery.
Who are the neonates in Group 1 and Group 2?
Group 1 are neonates whose their MUM developed CP within 7D b4 to 7D after delivery.
Group 2 are neonates who got exposed to CH/SH in the1st 7D of life BUT not mother
What is the recommended PEP for Group 1 neonates?
Recommended PEP includes:
* No VZV IgG test needed
* Varitect or IVIG (asap and preferably within 7D of exposure)
* If Varitect not available within 96H of the onset —> IVIG immediately
* Prophylactic IV ACV 20mg/kg every 8H for a minimum of 48H
* Converted to PO AV until D21 post delivery
Which neonates are in group 2A?How do you manage an exposure?
Remained in hospital since birth,
Born <28W OR
Wt <1Kg at birth
OR
Have severe congenital/other underlying condition that require long ITU/special care during 1st y of L.
Test for VZV IgG in infants ONLY
If <150miu/ml (susceptible)
Give oral ACV should start from D7 post exposure and continue for 14 DAYS
Which neonates are in group 2B?How do you manage an exposure?
Neonates who are exposed to CP/SH (other than in mother) in the 1st 7d of L.
For infants whose mothers have a history of CH/SH or 2 doses of varicella vaccine, assume immune.
Otherwise, test either mother (preferred) or neonate
If <150mIU/ml (susciptible)
Give oral ACV should start from D7 post exposure and continue for 14 DAYS**
What is the determination process for immune status in neonates or infants?
Immune status determination includes:
* Testing premature infants for VZV Ab due to potential lack of maternal antibodies
* Testing term infants only if maternal history is uncertain, using a higher cutoff (150IU/ml) for testing
The goal is to prevent infection, not just to mitigate disease complications.
What is the incidence of chickenpox (CP) in pregnancy?
5-6/10,000 deliveries
What percentage of young adults in the UK have been infected with chickenpox (seropositive/immune)?
> 85%
What is the clinical diagnosis specificity of chickenpox in pregnancy?
Highly specific but not very sensitive as sub-clinical/mild cases
What is the risk to pregnant women who develop CP?
Pneumonitis 10-14% historically, now 2.5% with no death. Risk increased toward term (after 18-20W).
Encephalitis (rare-MR 5-10%)
Risk of adverse fetal
outcome in relation to GA?
Fetal varicella syndrome risk:
Under 13 weeks: 0.4%
13 to 20 weeks: 2%
Neonatal chickenpox risk in 7
days prior to 7 days postdelivery: 20%
What is the management protocol for confirmed chickenpox infection in a pregnant woman?
- See GP at first sign
- Avoid contact with at-risk individuals
- Urgent clinical assessment
-if evidence of severe disease at that stage/subsequently» refer immediately for urgent assessment in specialist unit (Obs/ID/peads) - If uncomplicated/not severe: Reassure and send home
*Offer ACV if appropriate + daily reviews and follow ups» seek help if unwell.
What are the indications for urgent hospital assessment?
If there is deterioration/fever persists/cropping of the rash continues after 6 days/develop respiratory symptoms
What are the Criteria for Hospitalization?
1) Absolute indications:
Respiratory symptoms
Neurological symptoms,
Haemorrhagic rash/bleeding,
Severe disease (dense rash/numerous mucosal lesions),
Significant immunosuppression.
2) Contributory factors include:
Approaching term,
Complex obs history,
Smoker,
CLD,
Poor social,
GP unable to monitor
What is the recommended treatment if a pregnant woman presents within 24 hours of rash onset?
Offer 7 days of treatment (ACV 800mg 5/day)
What is the recommended action if a pregnant woman presents more than 24 hours after rash onset without complications?
Not routinely advised
There is no evidence that antivirals alter the natural history of uncomplicated CP when given > 24H after rash onset; however, this is a clinical decision
What is the ttt fro complicated/Varicella pneumonitis?
ACV IV 10mg/kg TDS for 5-10d
*C/S may be considered
Can Varicella infection of the fetus be diagnosed prenatally?
Women who develop CP in pregnancy shud b referred to fetal medicine at 16-20W or 5W after infection, for discussion and detailed US exam
Given that Amniocentesis has a strong NPV but a poor PPV in detecting fetal damage that connot be detected by non invasive methods (advice risk vs benefits)
What should parents be offered if there is proven chickenpox exposure in utero?
Parents should be offered counseling in a specialist fetal unit and
The option of abortion care following an early sonographic diagnosis of FVS.
What do you do If a woman with a reliable history of CH/SH or full vaccination is inadvertently tested for VZV Ab, and:
1)VZV IgG positive
2)VZV IgG Equivocal/Negative (qualitative)
3)If <100 mIU/ml (quantitative)
1) VZV IgG positive – reassure as PEP is not indicated.
2) VZV IgG equivocal/negative with a qualitative assay *Retest using a quantitative assay.
*If time does not permit additional testing within 10D of contact and the individual is VZV IgG:
-Negative: recommend PEP (if necessary, antivirals starting after D7).
-Equivocal: PEP is not recommended.
3) If less than 100mIU/ml with a quantitative assay, recommend PEP.
What is the management for a pregnant woman who has had a second exposure to chickenpox?
Further risk assessment and potential second course of antivirals if necessary
What is the theoretical risk associated with localized maternal shingles post-delivery?
Postnatal transmission to the baby
True or False: Chickenpox re-infection in pregnant women is common.
False
What is the recommended action if a pregnant woman has previously received IVIG as VZV PEP and has a second exposure?
A new risk assessment is required
How do you manage a pregnant woman who previously received IVIG as VZV PEP and had a second exposure?
If the second exposure occurs:
* Within 3W: a further dose is not required
- Between 3-6W: further PEP should be administered without further testing
- > 6W: retesting of a new sample is required
How should a pregnant woman be managed after exposure to chickenpox with regards IPC?
Managed as possibly infectious 8-28 days after exposure
Advice to contact GP if developed rash
What is the % of pregnant woman who develop rash despite PEP?
Up to 50% may develop modified form of disease
Maternal pneumonitis associated with chickenpox infection has been reported in spite of timely PEP
