VZV

Question 1

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?

Answer 1

Neonates
Pregnant women
Immunosuppressed

Question 2

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

Answer 2

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

Question 3

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

Answer 3

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

Question 4

If pregnant/ neonate/ immunosuppressed exposed to chickenpox, what do you want to know in history, and what blood tests?

Answer 4

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

Question 5

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)

Answer 5

VZIG

Question 6

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

Answer 6

No treatment

Question 7

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?

Answer 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

Question 8

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

Answer 8

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

Question 9

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

Answer 9

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.

Question 10

Aciclovir/ valacilovir are not licensed for PEP in chickenpox, but their use as treatment is well established.

How does off-label prescribing work?

Answer 10

Clinicians able to prescribe medicines outside terms of license, when it is in best interest of the patient on basis of available evidence

Question 11

What to do if patient has second exposure to varicella?

Answer 11

Investigate as if it was first exposure

Perform further risk assessment
Check VZ IgG

Question 12

Chickenpox in pregnancy can lead to fetal varicella syndrome (FVS)

What are the symptoms?

Answer 12

IUGR
Microcephaly
Cataract
Limb hypoplasia
Skin scarring

Does not appear to increase risk of miscarriage

Question 13

What are side effects of aciclovir/ valaciclovir?

Answer 13

Headache
Dizziness
Vomiting
Diarrhoea
Photosensitivity
Fatigue

Question 14

Pregnant women present with chickenpox symptoms, what is treatment?

Answer 14

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

Question 15

Women planning pregnancy, who are varicella antibody negative, what advice to give?

Answer 15

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

Question 16

When we talk of “exposure” to varicella, what situations constitute exposure - home/ hospital

Answer 16

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

Question 17

If patient has varicella antibodies, why do we not give VZIG

Answer 17

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

Question 18

What is dosage of VZIG for PEP?

Answer 18

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

Question 19

If VZIG contraindicated, for example cannot give IM injection due to bleeding risk, then what is alternative treatment?

Answer 19

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.

Question 20

Active chickenpox in

healthy adults
pregnancy
neonates
immunosuppressed

What is the treatment?

Do not treat healthy children

Answer 20

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.

Question 21

How is varicella infection diagnosed?

Answer 21

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)

Question 22

What is mechanism of action of aciclovir?

Answer 22

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.

Question 23

What is aciclovir bioavailability?

Answer 23

15-30% bioavailability

Good penetration including CNS

Question 24

What is aciclovir half life?

Answer 24

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.

Question 25

What are benefits of valaciclovir?

Answer 25

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.

Question 26

What are serious complications of varicella in adults?

Answer 26

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

Question 27

How is VZV transmitted?

Answer 27

transmitted by respiratory droplets and by direct personal contact with vesicle fluid or indirectly via fomites (e.g. skin cells, hair, clothing and bedding)

Question 28

What are initial VZV symptoms?

Answer 28

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

Question 29

How does shingles occur?

Answer 29

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

Question 30

Healthcare worker who has not previously had chickenpox. Exposed when changing dressing for shingles. What needs to be done?

Answer 30

Exclude from patient contact from 8-21 days after exposure - may be incubating If no symptoms, offer vaccination. Not often used

Question 31

What are contra-indications to varicella vaccination?

Answer 31

Pregnant Immunocompromised Anaphylaxis to components of vaccine

Question 32

Active VZV infection. Who should be admitted to hospital for assessment?

Answer 32

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

Question 33

Active VZV infection. When is treatment indicated? Should be commenced within 72 hours of rash starting

Answer 33

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

Question 34

Active VZV infection. What drugs are available to manage pain of shingles/ post-herpetic neuralgia?

Answer 34

NSAIDS Amitryptiline Duloxetine Gabapentin Pregabalin

Question 35

Patient on prophlyactic aciclovir for recurrent shingles. Turns 70, and is eligible for Zostavax vaccine. Can patient have it?

Answer 35

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

Question 36

Varicella exposure What do we need to know about exposure event?

Answer 36

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?

Question 37

What is Ramsay Hunt Syndrome?

Answer 37

VZV becomes reactivated in the geniculate ganglion of the VIIth cranial nerve (facial nerve) causing facial paralysis, loss of taste, vestibulocochlear dysfunction and pain

Question 38

What are symptoms and signs of Ramsay Hunt?

Answer 38

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)

Question 39

What is management of Ramsay Hunt syndrome?

Answer 39

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

Question 40

What is Zoster sine herpet?

Answer 40

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

Question 41

What are the changes to the Shingles vaccine program in 2023?

Answer 41

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