Changing Trends in Chickenpox Pregnant Women and Prevention with Vaccine

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Changing Trends in Chickenpox Pregnant Women
and Prevention with Vaccine
A A Gershon (USA)
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Varicella zoster virusrisks during pregnancy

• Varicella zoster virus (VZV) is 25 times more
  serious in adults than in children
• 50 annual deaths in adults in the USA
• No apparent risk of spontaneous abortion
• Maternal risk probably highest in 3rd trimester
• reports of pneumonia requiring antiviral therapy
• reports of fatalities
• Risk to fetus and newborn due to maternal
  viraemia
• Zoster not a problem (secondary infection)
• Many susceptible adults in countries with
  tropical climate

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• Congenital varicella syndrome
• involvement of skin, limbs, eyes, brain, growth
• pathogenesis unclear possibly VZV reactivation
  in utero
• 2 of offspring affected when maternal varicella
  occurs at Weeks 820
• diagnosis difficult PCR, ultrasound
• no therapy, counselling difficult
• Severe disseminated infection of the newborn
• babies born 4 days or less after onset of
  maternal varicella
• can be modified with VZIG given at birth
• Asymptomatic at birth but early development of
  zoster

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Infant with fatal varicella
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Infant with congential varicella syndrome
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Infant with early zoster
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Varicella susceptibility by age,USA 19881994

• Age (years) Susceptibility ()
• 611 14
• 1219 6.8
• 2029 4.5
• 3039 1.1
• gt40 1.3

Source NHANES III, CDC, Unpublished data.
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Live attenuated varicella vaccine

• Developed by Takahashi over 25 years ago
• Oka strain produced by attenuation during cell
  passage
• Licensed for use in Japan and Korea 1989
• Licensed in USA in 1995 for healthy susceptibles
  aged gt1 year
• Over 15 million doses distributed in USA
• 3 instances of transmission (mild contact cases)
• Contraindicated during pregnancy
• 365 inadvertently vaccinated, no congenital
  varicella (CDC)
• recommended for susceptible children of pregnant
  women

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Risk to pregnant woman if susceptible child in
family is vaccinated/not vaccinated
Wild VZV () Vaccine () Virus 7 100 Rash
100 5 Transmission 80 lt1 Risk to mother lt0.5 6
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Risk to infant if susceptible child in family is
vaccinated

• Assumes mother is susceptible
• Assumes one child (double risk for two)
• Assumes 2 risk of congenital syndrome
• Assumes Oka causes congenital syndrome like wild
  type
• Assumes Oka crosses placenta like wild type
• no documented viraemia in healthy vaccinees
• Predict significantly lower risk to mother and
  fetus

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Safety and efficacy of varicella vaccine in
adults and children

• Adults require 2 doses to achieve gt90
  seroconversion
• Vaccine extremely safe in children and adults
• rash in first 2 weeks may be wild type VZV
• 510 mild rash 16 weeks (mean 4) after
  immunization
• rare temporal association with severe adverse
  events(e.g. pneumonia, anaphylaxis,
  thrombocytopaenia)
• 7585 protection after household exposure to
  varicella
• Rare zoster in USA vaccinees
• lt30 cases, 2/3 Oka, 1/3 wild type VZV
• Waning immunity not a significant problem

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Varicella vaccinecase-control efficacy study

• 4 private practices in New Haven, CT, USA
• 83 case-control groups
• Varicella group 14 vaccinated
• Control group 48 vaccinated
• 85 efficacy after 2 years of 5-year study

E. Shapiro et al, International Herpesvirus
Workshop, Boston, July 1999
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Leukaemic child with breakthrough varicella
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Vaccination of health care workersagainst
chickenpox

• 120 healthy adults, 1945 years old
• Vaccinated in USA 19791997
• Most received 2 doses, 12 months apart
• Average follow-up 5 years (range 120 years)
• 12 cases break-through varicella (10)
• average 40 vesicles (lt10 times expected)
• 0.57 years after vaccination
• Disease occurred in vaccinees who lost detectable
  antibodies to VZV

Saiman et al. IDSA, Philadelphia, 1999
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Zoster in immunocompromised vaccinees after
immunization
Years after Vaccinees () Controls
() immunization Leukaemia (Takahashi) 6 6 19 Leu
kaemia (Brunell) 6 0 21 Leukaemia
(Hardy) 10 2 16 Renal transplant (Broyer) 10 7 13
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Varicella vaccine in USACDC Draft healthy
people, 2010 goals

• Reduce indigenous varicella in USA by 90
• Vaccine coverage gt90 among children(1935
  months)
• national level and all 50 states
• Vaccine coverage gt95 for children at school
  entry
• Modelling indicates that fewer overall cases of
  varicella increased average age of onset
• however, as for measles in the USA, there will be
  fewer cases of adult varicella
• There are already changes in epidemiology of
  illness in children

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Impact of varicella vaccine in sentinal areas

• 3 counties in California, Pennsylvania and Texas
• Approximately 75 vaccine coverage in young
  children
• Over 60 reduction in number of cases of
  varicella in 1999
• reduction occurred at lower immunization level
  than was thought necessary for such a change

Source CDC, Unpublished data
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Varicella vaccine persistence of immunity

• Duration of immunity never known with new vaccine
• In USA, 510 year follow-up of gt500 immunized
  healthy children
• over 90 remain seropositive
• 20-year follow-up of 26 Japanese vaccinees
• 2 developed mild break-through infections, 100
  seropositive

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Varicella vaccine persistence of immunity

• No apparent increase in rate or severity of
  breakthrough disease with time
• children (Johnson et al)
• adults (Saiman et al)
• Effect on varicella and zoster in absence of
  boosting from natural disease will require
  further study

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VZV practical aspects for pregnant women

• Identification of varicella susceptibles
• History of disease gt95 reliable
• ELISA tests approximately 75 accurate
• false negatives gt false positives
• testing costs vary from US140 per assay
• other antibody tests limited availability (LA,
  FAMA)

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VZV practical aspects for pregnant women

• VZIG for pregnant susceptible women with
• close exposures and selected offspring
• To protect mother (impact on congenital
  syndrome?)
• At birth if mother has varicella onset lt5 days
  before delivery
• or within 48 hours post-delivery

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VZV practical aspects for pregnant women

• Immunization of healthy, non-pregnant
• varicella susceptibles in household
• Pre-exposure (preferable) or post-exposure
  vaccination