VZV Flashcards
Varicella (chickenpox/ shingles) infection is normally mild self-limiting disease. Caused by human herpesvirus-3 DNA virus
Which groups are at high risk of severe/ life-threatening disease?
Neonates
Pregnant women
Immunosuppressed
There are limited supplies of VZIG, so need to decide who requires VZIG, and who can have oral anti-virals.
What is recommendation for -
Pregnant patient - up to 20 weeks
exposed to varicella
If varicella antibody negative (no previous exposure)
Give VZIG up to 20 weeks as PEP
Limited evidence on effectiveness of oral antivirals at preventing congenital varicella
If antibody present (VZIG >100mIU/ml), re-assure patient, no PEP required
There are limited supplies of VZIG, so need to decide who requires VZIG, and who can have oral anti-virals.
What is recommendation for -
Pregnant patient - exposed after 20 weeks
VZIG
or
Oral aciclovir 800mg 5x from days 7-14 post-exposure
Valaciclovir 1000mg TDS from days 7-14 post-exposure
Recent guidelines showed no difference in VZIG/ aciclovir
Based on evidence of aciclovir being safe in second/ third trimester, and sub-optimal efficacy of VZIG as PEP in pregnancy
If pregnant/ neonate/ immunosuppressed exposed to chickenpox, what do you want to know in history, and what blood tests?
Ask about history of chickenpox - exposure has >97% probability of developing protective antibodies.
If no history, then test for varicella antibodies.
Ask about exposure - higher risk if contact has exposed shingles, or disseminated shingles
Varicella IgG <100mIU/ml denotes susceptible
There are limited supplies of VZIG, so need to decide who requires VZIG, and who can have oral anti-virals.
What is recommendation for -
neonate (up to 28 days)
VZIG
There are limited supplies of VZIG, so need to decide who requires VZIG, and who can have oral anti-virals.
What is recommendation for -
healthy patient
No treatment
Antiviral treatment starts on day 7 to day 14. If patient were to present on day 12, then still offer a 7 day course of antivirals
What is day of exposure?
Why is treatment started at day 7?
Day of exposure is first date patient met contact who had rash
Study showed starting aciclovir immediately associated with higher severity of illness (77%), compared to starting at day 7 (21%)
Chickenpox/ shingles usually develops 10-21 days after exposure
There are limited supplies of VZIG, so need to decide who requires VZIG, and who can have oral anti-virals
What is recommended for -
immunosuppressed child
First assess does not need VZIG - not neonate
Children <2
- aciclovir 10mg/kg QDS daily, 7-14 days after exposure
Children 2-17
- aciclovir 10mg/kg QDS daily, 7-14 days after exposure
- valaciclovir 20mg/kg TDS daily, 7-14 days after exspoure
There are limited supplies of VZIG, so need to decide who requires VZIG, and who can have oral anti-virals.
What is recommendation for -
immunosuppressed adult
Oral aciclovir 800mg QDS from days 7-14 post-exposure
Valaciclovir 1000mg TDS from days 7-14 post-exposure
If severe - may need IV aciclovir.
Malabsorption - may need IV aciclovir
Renal toxicity - may need VZIG
If on long term aciclovir prophylaxis, may require dose to be increased temporarily, from day of onset of rash.
Aciclovir/ valacilovir are not licensed for PEP in chickenpox, but their use as treatment is well established.
How does off-label prescribing work?
Clinicians able to prescribe medicines outside terms of license, when it is in best interest of the patient on basis of available evidence
What to do if patient has second exposure to varicella?
Investigate as if it was first exposure
Perform further risk assessment
Check VZ IgG
Chickenpox in pregnancy can lead to fetal varicella syndrome (FVS)
What are the symptoms?
IUGR Microcephaly Cataract Limb hypoplasia Skin scarring
Does not appear to increase risk of miscarriage
What are side effects of aciclovir/ valaciclovir?
Headache Dizziness Vomiting Diarrhoea Photosensitivity Fatigue
Pregnant women present with chickenpox symptoms, what is treatment?
Oral aciclovir for 7 days, from day of onset of rash. Any stage of gestation, although caution using aciclovir before 20 weeks
If severe symptoms - IV aciclovir
Secondary treatment of bacterial skin infection
Advise to avoid contact with other people until lesions crusted over - usually 5 days. Infectious for 2 days prior to symptoms developing
VZIG has no benefit once infection established
Women planning pregnancy, who are varicella antibody negative, what advice to give?
Avoid chickenpox/ shingles
In some cases, vaccine for VZV can be given, but not routinely on NHS. If given vaccine, avoid pregnancy for 4 weeks
When we talk of “exposure” to varicella, what situations constitute exposure - home/ hospital
Household contact
Contacts in the same small room (e.g. in a house or classroom or a 2 to 4 bed hospital bay) for a
significant period of time (15 minutes or more)
Face to face contact, for example while having a conversation
Immune-suppressed contacts on large open wards, where air-borne transmission at a distance has
occasionally been reported, particularly in paediatric wards where the degree of contact may be difficult
to define
If patient has varicella antibodies, why do we not give VZIG
The administration of VZIG is unlikely to confer any additional benefit for patients who already have
varicella antibody (VZV IgG) and therefore VZIG is not recommended for individuals with adequate levels
of VZV IgG. Assessment of susceptibility will depend on the history of previous infection or vaccination
What is dosage of VZIG for PEP?
0 – 5 Years 250mg
6 – 10 Years 500mg
11 – 14 Years 750mg
15 years and older 1000mg
Given IM
Must be given within 10 days
Does not stop getting infection, but reduces severity of symptoms
If VZIG contraindicated, for example cannot give IM injection due to bleeding risk, then what is alternative treatment?
intravenous human normal immunoglobulin (IVIG) at a dose of 0.2g per kg body weight (i.e. 4ml/kg for a 5%
solution) instead.
This will produce serum VZV antibody levels equivalent to those achieved with VZIG.
Active chickenpox in
healthy adults
pregnancy
neonates
immunosuppressed
What is the treatment?
Do not treat healthy children
Aciclovir 800mg 5x for 7 days, from day of onset of rash
If severe symptoms - IV aciclovir
If pregnant <20 weeks, can give aciclovir if benefits outweigh risks
There is no evidence that VZIG is effective in the treatment of disease.
How is varicella infection diagnosed?
Clinical history - rash 10-21 days after exposure
Culture of vesicular fluid. Inoculate human kidney/ lung cells. Since cannot be asymptomatic, if virus present it indicates active infection
Viral PCR - swabs/ CSF
Serology IgG/ IgM. Detectable after a few days, and peaks at three weeks
Visualization of multinucleated giant cells or herpesvirus virions in tissues by histopathology or electron microscopy does not distinguish between VZV and herpes simplex virus (HSV)
What is mechanism of action of aciclovir?
Aciclovir phosphorylated by thymidine kinase
Is guanosine analogue, so incoroporated into viral DNA by viral DNA polymerase, causes chain termination
Viral DNA polymerase has a much higher affinity for acyclovir triphosphate than does cellular DNA polymerase, resulting in little incorporation of acyclovir triphosphate into cellular DNA.
What is aciclovir bioavailability?
15-30% bioavailability
Good penetration including CNS
What is aciclovir half life?
plasma half-life of acyclovir is 2–3 hours in adults and 3–4 hours in neonates with normal renal function
20 hours in anuric patients.
What are benefits of valaciclovir?
orally administered prodrug of acyclovir that overcomes the problem of poor oral bioavailability and exhibits improved pharmacokinetic properties
Valacyclovir, the L-valine ester of acyclovir, is well absorbed from the gastrointestinal tract via a stereospecific transporter and undergoes essentially complete first pass conversion in the gut and liver to yield acyclovir and L-valine.
Using this prodrug formulation, the bioavailability of acyclovir is increased to about 54%, yielding peak plasma acyclovir concentrations that are three- to fivefold higher than those achieved with oral administration of the parent compound.
What are serious complications of varicella in adults?
Pneumonitis
CNS infection - presenting as cerebellar ataxia, encephalitis, transverse myelitis, or stroke syndromes
Hepatitis
Decision to start treatment is based on clinical history/ past medical history/ pregnancy. Minimal benefit of anti-virals in healthy individuals
How is VZV transmitted?
transmitted by respiratory droplets and by direct personal contact with vesicle fluid or indirectly via fomites (e.g. skin cells, hair, clothing
and bedding)
What are initial VZV symptoms?
The primary infection is characterised by fever, malaise and a pruritic rash that develops into crops of maculopapules, which become vesicular and crust over before healing
How does shingles occur?
Following the primary infection, the virus remains dormant in sensory nerve root ganglia but can be
reactivated to cause a vesicular erythematous skin rash in a dermatomal distribution
Healthcare worker who has not previously had chickenpox. Exposed when changing dressing for shingles.
What needs to be done?
Exclude from patient contact from 8-21 days after exposure - may be incubating
If no symptoms, offer vaccination. Not often used
What are contra-indications to varicella vaccination?
Pregnant
Immunocompromised
Anaphylaxis to components of vaccine
Active VZV infection.
Who should be admitted to hospital for assessment?
Serious complications (such as meningitis, encephalitis, or myelitis) are suspected.
The person has shingles in the ophthalmic distribution of the trigeminal nerve, especially those with:
Hutchinson’s sign — a rash on the tip, side, or root of the nose, representing the dermatome of the nasociliary nerve, which is a prognostic factor for subsequent eye inflammation and permanent corneal denervation.
Visual symptoms.
An unexplained red eye.
Immunocompromised
Active VZV infection.
When is treatment indicated?
Should be commenced within 72 hours of rash starting
Neonate
Pregnant
Immunocompromised
Serious complications (such as meningitis, encephalitis, or myelitis) are suspected.
The person has shingles in the ophthalmic distribution of the trigeminal nerve, especially those with:
Hutchinson’s sign — a rash on the tip, side, or root of the nose, representing the dermatome of the nasociliary nerve, which is a prognostic factor for subsequent eye inflammation and permanent corneal denervation.
Visual symptoms.
An unexplained red eye.
Non-truncal involvement (such as shingles affecting the neck, limbs, or perineum).
Moderate or severe pain.
Moderate or severe rash
Anyone over 50 years old - as they are high risk for post-herpetic neuralgia
Steroids sometimes used in addition to anti-virals - but limited evidence for this
Not required -
- children who are well
- adults who are well
Active VZV infection.
What drugs are available to manage pain of shingles/ post-herpetic neuralgia?
NSAIDS
Amitryptiline
Duloxetine
Gabapentin
Pregabalin
Patient on prophlyactic aciclovir for recurrent shingles.
Turns 70, and is eligible for Zostavax vaccine.
Can patient have it?
Live vaccine - aciclovir interferes with vaccination response.
Stop aciclovir 48 hours before vaccination
Restart aciclovir 14 days after vaccination
Another option is varicella shingrix vaccine, which uses protein subunit. Do not need to stop aciclovir
Varicella exposure
What do we need to know about exposure event?
What was the contact -
Household contact
Face-face contact
15 min in same room
Where was rash?
Was rash covered? e.g shingles
Was rash crusted over?
What is Ramsay Hunt Syndrome?
VZV becomes reactivated in the geniculate ganglion of the VIIth cranial nerve (facial nerve) causing facial paralysis, loss of taste, vestibulocochlear dysfunction and pain
What are symptoms and signs of Ramsay Hunt?
Pain deep within ear
Tinnitus
Hearing loss - unilateral
Unilateral facial droop
Rash or blisters in ear canal
Rash or blisters on face/ tip of nose (Hutchinson’s sign)
What is management of Ramsay Hunt syndrome?
Ophthalmology review
Eye pad/ eye lubricants
Treatment within 72 hours improves outcome -
- Aciclovir 800 mg five times a day for seven days (continuing until two days after crusting of lesions in those who are immunocompromised). May need IV aciclovir if retinitis/ optic neuritis
- topical steroids - as advised by ophthalmology. Limited evidence of efficacy of oral steroids
Corneal transplant if does not heal
What is Zoster sine herpet?
VZV reactivation without a visible rash
e.g Ramsay Hunt Syndrome - patient can present with facial palsy, but it is actually VZV reactivation
Swab the areas where expect a rash e.g inner ear
What are the changes to the Shingles vaccine program in 2023?
From September 1st, more people will be eligible for the NHS shingles vaccine - shignrix
Previously the shingles vaccine programme was limited to those aged 70 – 79
from September 2023 eligibility will be extended to include those: -
- who turn 65
- who are aged 50 or over and have a severely weakened immune system
In USA they give Shingrix to all HIV patients regardless of CD4 count
