Varicella Flashcards
How many serotypes of VZV are there? How many clades?
1 serotype, 5 clades
Where is VZV latent?
Ganglionic neurons (cranial and dorsal root ganglia)
What is the pathogenesis of primary VZV?
After contact, the virus spreads to regional lymph nodes, resulting in a primary viraemic phase. On days 4-6, the infection spreads to the liver, the spleen, and other cells within the reticuloendothelial system.
A secondary viraemic phase occurs at about day 9, with mononuclear cells transporting the virus to the skin and mucous membranes, causing the classic vesicular rash.
What is the incubation period of VZV?
7-21 days
What is the secondary attack rate of VZV in household contacts?
90%
How does a chickenpox rash present?
Lesions start on face, scalp and trunk and spread centripetally
When is chickenpox infectious (as per UKHSA) for a) immunocompetent b) immunocompromised
24 h prior to rash until 5 days after rash in immunocompetent
24 h prior to rash until all lesions have crusted in immunocompromised
When can VZV DNA be detected in blood in chickenpox infection?
10 days before to 1 week after rash
What are complications of chickenpox infection?
Bacterial sepsis
Pneumonia
Encephalitis
Haemorrhagic complications
Group A strep
What are complications of shingles infection?
Paresis
Cranial nerve palsies
Meningoencephalitis
Myelitis
Hepatitis
Vasculopathy
Herpes zozter opthalmicus
Post herpatic neuralgia (>90 days pain after rash onset)
What are CNS complications of VZV infection?
How are these diagnosed?
Meningitis
Meningoencephalitis
Meningoradiculitis
Cerebellitis
Myelopathy
Vasculopathy
Spinal cord infarction
Giant cell arteritis
Confirmed by DNA detection in CSF or evidence of intrathecal Ab production
a) treatment b) complication of VZV meningitis
a) None, supportive
b) Post infectious cerebellitis, esp in young children
Is VZV encephalitis caused by primary infection or reactivation?
Both
How is VZV encephalitis diagnosed?
DNA detection in CSF (variable sensitivity) or intrathecal Ab
Treatment for VZV encephalitis?
10-15 mg/kg aciclovir TDS for 14 days with rpt PCR at EOT - continue if still positive
Corticosteroids can be added (60-80 mg prednisolone for 3-5 d), more evidence for their use if there is a vasculitis component
True VZV encephalitis is rare, more likely to be vasculopathy
Does VZV vasculopathy most common occur during primary VZV or reactivation?
When does it occur post primary infection in children?
What is the highest risk in terms of rash?
Mostly with reactivation
Can occur after primary chickenpox, on average at 3 months post chickepox, ischemic stroke is most common in children
Hihgest risk post opthalmic zoster
What is the pathogenesis of VZV vasculopathy?
Pathogenesis thought to be reactivation from cranial nerve ganglia followed by transaxonal spread to the cerebral arteries
What histological feature is seen in VZV vasculopathy?
Type A Cowdry bodies in multinucleated giant cells
How is VZV vasculopathy diagnosed?
DNA detection in CSF - only positive in 1/3 of patients.
Intrathecal Ab positive in 90%
What is the treatment for VZV keratitis?
Oral aciclovir +/- topical ganciclovir
What is Hutchinson’s sign? And what is the significance?
Rash on the tip, side, or root of the nose, representing the dermatome of the nasociliary nerve, is associated with a high complication rate
Treatment for PORN/acute retinal necrosis?
5-10 days IV aciclovir followed by up to 12 weeks oral tx (intravitreal ganciclovir or foscarnet is also popular)
Who is at risk of VZV pneumonitis?
What is the treatment?
Chickenpox in adults, esp immunosuppressed and pregnant
10 mg/kg IV aciclovir TDS for 5-10 d
What is Rayes syndrome?
Associated with use of salicylates in VZV infection
Vomiting, encephalopathy, metabolic disturbances
30% fatality rate
What is Ramsay Hunt syndrome?
What are the symptoms?
What is the treatment?
Most common cause of unilateral facial paralysis due to reactivation of VZV in cranial nerves
Ulceration of the ear, tongue and soft palette. Tinnitus, hearing loss, nausea, vertigo. Rarely brainstem encephalitis
Treat with aciclovir (oral as effective as IV) and prednisolone within 3 days prevents degeneration of nerves and improves recovery
Treatment of uncomplicated chickenpox?
In 14+ years if present within 24 h of rash - 800 mg 5x day for 7 days (or valaciclovir 1 g TDS)
IV 5 mg/kg TDS for 5 days
Treatment of shingles?
Treat if > 50 and present within 72 h of rash - 800 mg 5x day for 7 days (or valaciclovir 1 g TDS)
Consider if <50 years
Treatment of severe VZV infection? Or chickenpox in immunocompromised?
10 mg/kg IV aciclovir TDS for 5 days
Treatment dose for neonates with varicella?
20 mg/kg IV aciclovir TDS for at least 7 days
Risk of VZV in pregnancy to mother?
Severe disease in mum - hepatitis, pneumonitis, encephalitis
Risk of fulmunating pneumonitis due to gravid uterus. Highest risk 18-20 weeks (5%)
Role of amniocentesis in VZV infection
VZV DNA in the amniotic fluid not routinely advised
NPV is good but PPV unknown
Only do in special circumstances and with serial ultrasound
Only consider termination if sonographic evidence of FVS
What investigations should be performed in neonate after confirmed VZV in pregnancy? And when?
Ultrasound/MRI can detect limb deformity, microcephaly, hydrocephalus, soft tissue calcification and fetal growth restriction. Wait 5 weeks from maternal infection.
What should you advise after birth for neonate whose mum has chickenpox during pregnancy?
Follow up of neonate at birth
What would you advise if neonate due to go home but sibling has chickenpox?
If chickenpox history (or mum IgG positive) can go home.
If susceptible then ideally delay contact until 7 days of age
Can a mother with chickenpox breastfeed?
Yes as breastmilk not a transmission route
If lesions around nipple then express milk which can be given to baby only if they are covered with aciclovir
Why is VZV IgG not tested for routinely in pregnancy screening?
National Screening Committee (NSC) review in 2019 and do not advise due to:
1) There is very little data on susceptibility to chickenpox in the UK or on the number of susceptible women who come into contact with the virus during pregnancy
2) Current tests have not been evaluated for use in the general pregnant population
3) There is no evidence looking at whether a screening programme improves the delivery of VZIG, so there is uncertainty on the benefit of a screening programme
Actions for pregnant women presenting with chickenpox?
Urgent clinical review
If uncomplicated - aciclovir 800 mg 5x day for 7d if within 24 h - low threshold for representing
If pneumonitis/deterioration/fever or rash >6 days - IV ACV 10 mg/kg TDS
Avoid contact with at risk people
Follow up of neonate at birth
Risk of foetal infection and foetal varicella syndrome by date of infection
Risk of infection:
<28 weeks - 5-10%
28-35 - 25%
>36 weeks - 50%
Risk of FVS:
0-13 weeks - 0.4%
13-20 weeks - 2%
20-28 weeks - case reports only
Mortality rate of foetal varicella syndrome? How many babies have developmental delay?
30% in first month
12% infants will have developmental delay
What diseases occur in neonate if infected at:
0-20 weeks
20-37 weeks
7-20 pre delivery
7 d before to 7 d post delivery
FVS
Shingles of infancy
Neonatal chickenpox
Severe disseminated haemorrhagic chickenpox
Symptoms of foetal varicella syndrome?
Think SKIN-EYES-LIMBS-CNS
Skin lesions
Neurological symptoms (microcephaly, limb paresis, seizures, encephalitis)
Eye disease (microphthalmia, chorioretinitis, cataract)
Limb hypoplasia
IUGR
Defects of organs (cardiovascular, GU etc)
What is the pathophysiology of foetal varicella syndrome?
Pathogenesis due to recurrent in-utero VZ reactivation, as immunologically immature foetus can’t produce Ab to get on top of virus.
Neurotropic nature of VZ stops development of central, peripheral and autonomic nervous system hence symptoms. i.e microcephaly/encephalitis, denervation of limb bud, optic tract infection.
Skin scarring is in dermatomal distribution, mimicking herpes zoster.
Mortality rate of :
Neonatal chickenpox (7-20 d pre delivery)
Severe disseminated neonatal cpox (7 d pre/post delivery)
0% - transplacental antibodies partially protect
Up to 20% mortality - highest risk 4 d before to 2 days post delivery
What type of vaccine is the chickenpox vaccine? What are the names of the vaccines? What strain is in it and how is this differentiated from wild type virus?
Live attenuated
Varilrix and Varivax (interchangeable)
Oka strain (mix of different genotypes)
Differentiated from wild type as it has 42 SNPs different. Advise is to look at 4 regions in ORF62 for differentiation
When is the chickenpox vaccine licensed from?
How is it used in the UK?
From 9 months
No universal vaccination but used in HCW, lab staff, contacts of immunosuppressed
However in Nov 2023 JCVI recommended including VZV in the routine immunisation programme - as MMRV at 12 m and 18 m
Reasons why VZV should be included in the routine childhood immunisation schedule
Reduces time off work/school
Reduces mild disease but also rare severe complications
US data shows childhood vaccine does not increase risk of zoster in older adults (thought due to exogenous boosting throughout life)
Recommended by JCVI in Nov 2023
Advise for those receiving VZV vaccine
Transmission from post vaccine rash to immunocompromised rare but possible
Avoid salicylates for six weeks and pregnancy for one month
OCH approach to assessing VZV susceptibility in HCW
History of chickenpox or shingles - consider immune (unless from oversease when history is less reliable)
Test and if IgG negative then vaccinate
Management of HCW with rash after chickenpox vaccine?
If generalised post vaccine rash = exclude from work
If local rash = cover and do not exclude unless working with high risk patients
Send sample to Colindale for typing
Management of susceptible HCW after chickenpox contact?
If unvaccinated, exposed and working with high risk patients, offer vaccine and either exclude from D8-21 post exposure or advise high vigilance for symptoms
Which patients are eligible for shingles vaccination?
Catch up programme startedin 2013.
Offered to 60-79 years olds - 2 doses 8-12 weeks apart
Severely immunosuppressed aged 50+ and adult HSCT - 2 doses 8w - 6 m apart
What are the three criteria for offering VZV PEP?
Significant exposure
At risk group
No previous VZV infection/vaccination
What is considered the infectious period for chickenpox in immunocompetent and immunosuppressed index?
Immunocompetent 24 hours before rash to 5 days after rash onset
Immunosuppressed 24 hours before rash until all lesions crusted over
What is considered the significant risk if exposed to shingles in immunocompetent and immunosuppresed index?
From day of rash until all lesions crusted over
Disseminated shingles
Immunosuppressed patient with localised shingles
Immunocompetent patient with uncovered shingles
What contact is considered significant in VZV exposure?
Face to face contact
In the same small room for 15+ minutes
Immunosuppressed contacts on a large open ward (particularly paeds)
What situations are Immunocompetent patients considered immune to VZV? What is the caveat?
What advise is given?
Previous history of chickenpox or shingles (caveat history unreliable in people from tropical climates, so test these patients)
Two doses of chickenpox vaccine
Reassure but advise to represent if rash develops
What action is taken If testing for VZV exposure in a pregnant women and a qualitative assay gives:
Negative
Equivocal
Both require confirmation on quantitative assay
If no time then PEP if negative, and no PEP if equivocal
What action is taken if you inadvertently test VZV IgG in a pregnant women with a reliable history of chickenpox on and a qualitative assay gives:
Negative
Equivocal
Both require confirmation on quantitative assay
If no time then PEP if negative, and no PEP if equivocal
What action is taken If testing for VZV exposure in an immunosuppressed patient and a qualitative assay gives:
Negative
Equivocal
Give PEP
Define Group 1 neonates as per VZV PEP guidance.
What prophylaxis?
Neonates whose mothers develop chickenpox 7 days before to 7 days after delivery
No Ab testing needed
Prophylax with IV aciclovir immediately � 20 mg/kg TDS (IVOS after 48 h if required) PLUS IVIG or varitect . Treat until 21 d post delivery
Define Group 2a and 2b neonates as per VZV PEP guidance.
What testing?
What prophylaxis?
Group 2a = Infants <1 y, who have never left hospital and were either born <28 weeks or weigh less than 1000 g OR
Infants <1 y, who have severe congenital or other condition which required prolonged specialist or ICU care in first year of life
Test for Ab, if <150 mIU/ml > PEP
Group 2b = Neonates exposed in first 7 days of life to someone other than mother
If no history of chickenpox, shingles or vaccine in mum > test for Ab (in either mum or baby) if <150 mIU/ml > PEP
PEP for both is oral acyclovir from day 7 post-exposure and continued for 14 days
When should varitect be issued in Group 1 infants? What if this is not available?
As soon as possible, if not obtained within 96 h then offer IVIG immediately
Dose of aciclovir and valaciclovir for PEP VZV?
In adults:
Aciclovir 800 mg QDS from d 7-14 post exposure
Valaciclovir 1000 mg TDS from d 7-14 post exposure
In children:
Aciclovir 10 mg/kg QDS from d 7-14 post exposure
Valaciclovir >2 y 20 mg/kg TDS from d 7-14 post exposure
What is Varitect?
When should it be given in relation to exposure?
Is it licensed and how is it procured?
VZV IgG for slow IV infusion
Dose is 50 IU/kg
Given preferably wihtin 96 hours and no longer than 10 days post exposure
Not licensed in UK (licensed in Germany) available from UKHSA RIGS
What PEP would be given to exposed individuals who are unable to take aciclovir? Why might they be unable?
Unable due to malabsorption or renal toxicity
Bolus dose of 0.2 g/kg IVIG which will produce serum Ab level equivalent to VZIG - this should be given within 7 days ideally but up to 10 days post contact
What would be your action if a pregnant woman was inadvertently vaccinated with
a) chickenpox vaccine
b) Zostavax
a) No PEP but report to UKHSA vaccine in pregnancy surveillance team
b) Treat like natural exposure and risk assess for PRP - also report to UKHSA vaccine in pregnancy surveillance team
What would be your action if an immunosuppressed patient was inadvertently vaccinated with
a) chickenpox vaccine
b) Zostavax
Consider both significant exposures, urgently assess level of immunosuppression.
Either monitor and treat if chickenpox occurs or risk assess and offer PEP if susceptible
What infection control should be provided for immunocompetent and immuncompriised patients with
a) localised shingles
b) disseminated shingles
Immunocompetent:
a) Cover lesions and follow SICPs until all lesions have scabbed over
b) Airborne and SICPs until all lesions have scabbed over
Immunocompromised:
a) Airborne and SICPs until all lesions have scabbed over until disseminated infection ruled out
b) Airborne and SICPs until all lesions have scabbed over
