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Varicella zoster virus in pregnancy


ACIP no contraindication to breast feeding. Virus not present in breast milk and no transmission to babies. study at 6 weeks post partum ... – PowerPoint PPT presentation

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Title: Varicella zoster virus in pregnancy

Varicella zoster virus in pregnancy
  • Mike McKendrick
  • Department of Infection and Tropical Medicine
  • Royal Hallamshire Hospital
  • Sheffield, UK
  • Hon. Professor
  • Department of Genomic Medicine
  • University of Sheffield

VZV in pregnancy
  • Chickenpox
  • Consequences to mother
  • Consequences to child
  • Intervention post exposure
  • Prevention - Intervention pre exposure
  • Herpes zoster

VZV infection effects to mother
  • Primary infection
  • Typical chickenpox in adult
  • Complications
  • Usually none
  • Pneumonitis most common complication
  • secondary bacterial infection
  • (encephalitis)
  • Reactivation
  • Typical herpes zoster in adult

Is risk severe chickenpox increased in pregnancy?
  • Confidential enquiry into maternal deaths UK
  • 1985-1987 4 deaths
  • 1988-1990 3 deaths
  • All in second half pregnancy - ? immunotolerance
  • Nathwani et al J Infection 199836S59-71
  • No maternal deaths reported in last two reports
  • Maternal varicella five times more likely to be
    fatal than non pregnant women
    Drug and Therapeutic Bulletin 2005 4369-72
  • Review of adult deaths in VZV concluded no
    increase due to pregnancy
    Miller et al Reviews in Med Micro
  • 5 years in Sheffield 19 cases - no severe
  • McKendrick et al J Infection 20075564-67

VZV infection in pregnant woman
  • Conclusion
  • No definite evidence that varicella more likely
    to be fatal in pregnant women than in the non
    pregnant adult

Herpes zoster in pregnancy
  • No evidence to indicate increased severity in
  • Theoretical risk if uterine dermatomes D10 to L1
    are involved no reports.

Primary infection in pregnancy effects on
foetus (and baby)
  • No infection
  • Infection
  • Serological only
  • Clinical
  • minor varicella lesions
  • Major - Foetal varicella syndrome
  • Neonatal varicella (if delivery lt5 days after
    maternal rash)
  • Infant herpes zoster

Foetal varicella syndrome
  • Involves
  • Single organ eg eye or skin
  • Skin, neural system and GIT, GU tract, eyes,
    muscles and other organs
  • Multiple lesions and malformations may lead to
    fetal death
  • Due to reactivation of latent virus in neural or
    other tissue in utero
  • Identification of non productive latency like VZV
    in non neuronal cell types demonstrated in
    aborted 12 week foetus Nikkels et al JID

Transmission to foetus
  • Prospective study UK and Germany
  • 1739 cases up to 36 weeks gestation
  • 1373 varicella
  • 366 zoster
  • Detailed follow up of outcome
  • Enders et al Lancet 1994 343 1548-1551

Transmission to foetus
  • 9 cases fetopathy
  • 2 at lt13 weeks risk 0.4 (95 CI0.05-1.5)
  • 7 at 13-20 weeks risk 2 (95CI 0.8-4.1)
  • 0 at gt 20 weeks
  • 10 cases infant herpes zoster (probable
  • 13-24 weeks risk 0.8
  • 25-36 weeks risk 1.7
  • Enders et al Lancet 1994 343 1548-1551

Is FVS underdiagnosed? probably not.
  • 347 pregnancies with varicella
  • 140 first trimester
  • 1 case foetal death 9 wks after infection
  • 1 case foetal hydrops 12 weeks after infection
  • 122 second trimester
  • 100 third trimester
  • One case FVS (maternal infection at wk 24) with
    typical skin scars and left retinal macular
  • all babies actively followed up to 30 months to
    detect abnormalities of eyes, hearing and
    physical and developmental features
  • Harger et al Obstet Gynecol 2002100260-5

Gestational age and risk of FVS
  • Risk probably continues up to 28 weeks based on
    evidence from 9 cohort studies. Additionally 4
    further case reports of FVS after 20 weeks
    identified from 1979 to 2005.
  • Drug and Therapeutic Bulletin 20054394-5

Maternal management post exposure to chickenpox
  • Check VZV immunity
  • Consider
  • Prevention of chickenpox VZIG
  • However in Sheffield, 50/87 (60) women with
    chickenpox contact did not seek advice from GP or
    hospital in timeframe to facilitate intervention.
    McKendrick et al J Infection
  • Antiviral during incubation period not in any
  • Treatment of chickenpox with antiviral
  • Counselling of mother and close foetal monitoring

Maternal management non immune mother post
  • VZIG
  • Biological product
  • Must be given early
  • modest protection against infection and/or severe
  • Aim to protect mother from chickenpox
  • ? Reduce FVS no definite evidence
  • no cases in 97 women receiving VZIG but not
    sufficient power to reach significance.
  • Enders et al Lancet 1994 343 1548-1551
  • documented case of FVS despite VZIG
  • VZIG expensive
  • UK Health Protection Agency
  • Annual cost c. 1million (2 million)
  • 75-80 use in pregnant women
  • Miller E, Health Protection Agency personal

Management - antivirals
  • Aciclovir
  • Valaciclovir
  • Famciclovir

Antivirals - UK
  • British National Formulary
  • Aciclovir not known to be harmful
    manufacturers advise use only when potential
    benefit outweighs risk
  • Valaciclovir see aciclovir
  • Famciclovir see aciclovir

Antivirals second and third trimesters- IHMF
  • The use of oral aciclovir (800 mg five times
    daily) for pregnant women who contract varicella
    in their second or third trimester is
    recommended. It is important to note that this
    recommendation is based on anecdotal evidence,
    and that patients should be advised that
    antiviral drugs are not licensed for use during
  • The roles of valaciclovir and famciclovir for
    the treatment of varicella infection in the
    pregnant woman remain to be evaluated in clinical
  • IHMF - management of varicella in
    immunocompetent host

Antivirals - IHMF first trimester
  • It is recommended that further investigation be
    conducted to assess whether pregnant women who
    contract varicella during the first trimester of
    pregnancy should be administered intravenous
    aciclovir (10 mg/kg every 8 hours). There is
    currently no evidence that this treatment results
    in fetal malformations (Research need
  • IHMF - management of varicella in
    immunocompetent host

International aciclovir pregnancy registry
  • 1234 pregnancies with 1246 outcomes
  • Birth defects with first trimester exposure 19
    out of 256 (3.2 95CI, 2.0-5.0)
  • Conclusion
  • The observed rates and types of birth defects
    for pregnancies exposed to aciclovir did not
    differ significantly from those in the general
  • Stone et al. Birth Defects Research (Part A),
    Clinical and Molecular Teratology 2004
    70 201-207

Changing epidemiology
  • Increase adults at risk
  • Upward trend in adult chickenpox in last 20 years
    in UK (E Miller et al 1993) and USA (Gary GC et
    al 1990)
  • Adult seropositivity
  • Western countries c 90
  • London Tower Hamlets
  • British women 93
  • Bangladeshi women 86
  • Talukder et al Epidemiol Infect
    2007 april 10 1-10 Epub
  • 54 in Pakistan Akram et al SE Asian J Trop
    Med Pub Health 200031646-649
  • 56 in Sri Lanka Liyanage et al Indian J
    Med Sci 200761128-134
  • 81 in Italy Alfonsi et al
    Vaccine 2007 256086-8
  • Increased population movement will increase
    numbers at risk in Western countries

What is impact of childhood varicella
immunisation against chickenpox in pregnancy?
  • Less chickenpox in children should reduce cases
    in pregnancy
  • Majority had no identifiable exposure - European
    study Enders et al Lancet 1994 343
  • 58 (11/19) in Sheffield acquired infection from
    child at home McKendrick et al J
    Infection 20075564-67
  • CDC (USA) and Centre for Infection (UK) have no
    data available on epidemiology of varicella in

Cost effectiveness of antenatal screening and
post partum vaccination of susceptibles Pinot de
Moira A et al Vaccine 2006241298-1307
  • UK versus Bangladeshi women
  • Assumptions
  • VZIG 54 protection (100 v severe dis. or
  • Vaccine efficacy in adults (2 doses) 75
  • Cost of congenital varicella syndrome - 420K
  • Model
  • A) -Serological screening only if no history
  • B) -Serological screening all

Cost effectiveness of antenatal screening and
post partum vaccination of susceptibles Pinot de
Moira A et al Vaccine 2006241298-1307
  • A verbal and selective screening - savings
  • UK women - 149,000 per 100,000 screened
  • Bangladeshi - 257,000 per 100,000 screened
  • B universal screening cost to NHS
  • UK women gt1million per 100,000 screened
  • Bangladeshi 780,000 per 100,000 screened

Immunisation strategies post partum
  • Will fail to protect chickenpox in first
  • Five year retrospective review of chickenpox in
    pregnancy in Sheffield
  • Five of nineteen women (26) had chickenpox in
    first pregnancy
  • McKendrick et al J Infection 20075564-67

Immunisation strategies post partum
  • Can live vaccine be used post partum?
  • Immunisation not generally recommended by
    manufacturers ACIP post partum immunisation for
    non immune including breast feeding mothers
    second dose at 6-8 weeks
  • ACIP no contraindication to breast feeding
  • Virus not present in breast milk and no
    transmission to babies
  • study at gt6 weeks post partum
  • Bohlke K et al Obs and Gynae 2003102970-7
  • Manufacturers - avoid pregnancy for 3 months
    after dose ACIP avoid pregnancy for 1 month
    after dose

Vaccine strategies prepartum
  • Protective for the individual
  • Selective
  • Unreliable
  • Probably inequitable as a policy

Vaccine strategies - childhood
  • Universal immunisation in childhood as per USA
  • generation before immunised reach child bearing
  • Duration of immunity
  • ? Booster doses, ? Frequency
  • Effects of childhood immunisation on maternal

Vaccine strategies
  • Adolescent
  • Introduction of papilloma virus vaccine will
    facilitate health intervention at this age.
  • Selective immunisation only for those with no
    history of chickenpox would reduce costs though
    the wild virus will still circulate and pose risk
    to non immune adults.
  • ? Might be used in countries with no childhood
    immunisation and/or in conjunction with childhood

  • Chickenpox may be serious for pregnant woman and
  • Increasing numbers of seronegative women could
    result in increase in chickenpox in pregnancy in
    some countries
  • Strategies for immunisation to protect pregnant
    women from chickenpox needs careful
  • Vaccine strategy should aim to protect all non
    immune adults and not just women of child bearing
    age in view of severity of infection in adults.