Changing Trends in Chickenpox –

Pregnant Women and Prevention

with Vaccine

Changing Trends in Chickenpox –

Pregnant Women and Prevention

with Vaccine

A A Gershon(USA)

© 2000 The International Herpes Management Forum, all rights reserved.

Varicella zoster virus:Varicella zoster virus:risks during pregnancyrisks during pregnancyVaricella zoster virus:Varicella zoster virus:risks during pregnancyrisks 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

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 8–20– 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

Infant with fatal varicellaInfant with fatal varicellaInfant with fatal varicellaInfant with fatal varicella

Infant with congential varicella Infant with congential varicella syndromesyndromeInfant with congential varicella Infant with congential varicella syndromesyndrome

Infant with early zosterInfant with early zosterInfant with early zosterInfant with early zoster

Varicella susceptibility by age,Varicella susceptibility by age,USA 1988–1994USA 1988–1994Varicella susceptibility by age,Varicella susceptibility by age,USA 1988–1994USA 1988–1994

Age (years) Susceptibility (%)

6–11 14

12–19 6.8

20–29 4.5

30–39 1.1

>40 1.3

Live attenuated varicella vaccineLive attenuated varicella vaccineLive attenuated varicella vaccineLive 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 >1 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

Risk to pregnant woman if susceptible Risk to pregnant woman if susceptible child in family is vaccinated/not child in family is vaccinated/not vaccinatedvaccinated

Risk to pregnant woman if susceptible Risk to pregnant woman if susceptible child in family is vaccinated/not child in family is vaccinated/not vaccinatedvaccinated

Wild VZV (%) Vaccine (%)

Virus 7 100

Rash 100 5

Transmission 80 <1

Risk to mother <0.5 6

Risk to infant if susceptible child Risk to infant if susceptible child in family is vaccinatedin family is vaccinatedRisk to infant if susceptible child Risk to infant if susceptible child in family is vaccinatedin 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

Safety and efficacy of varicella Safety and efficacy of varicella vaccine in adults and childrenvaccine in adults and childrenSafety and efficacy of varicella Safety and efficacy of varicella vaccine in adults and childrenvaccine in adults and children

Adults require 2 doses to achieve >90% seroconversion

Vaccine extremely safe in children and adults:– rash in first 2 weeks may be wild type VZV– 5–10% mild rash 1–6 weeks (mean 4) after immunization– rare temporal association with severe adverse events

(e.g. pneumonia, anaphylaxis, thrombocytopaenia) 75–85% protection after household exposure to

varicella Rare zoster in USA vaccinees:

– <30 cases, 2/3 Oka, 1/3 wild type VZV Waning immunity not a significant problem

Varicella vaccine:Varicella vaccine:case-control efficacy studycase-control efficacy studyVaricella vaccine:Varicella vaccine:case-control efficacy studycase-control efficacy study

4 private practices in New Haven, CT, USA

83 case-control groupsVaricella group: 14% vaccinatedControl group: 48% vaccinated85% efficacy after 2 years of 5-year

study

Leukaemic child with Leukaemic child with breakthrough varicellabreakthrough varicellaLeukaemic child with Leukaemic child with breakthrough varicellabreakthrough varicella

Vaccination of health care Vaccination of health care workersworkersagainst chickenpoxagainst chickenpox

Vaccination of health care Vaccination of health care workersworkersagainst chickenpoxagainst chickenpox

120 healthy adults, 19–45 years oldVaccinated in USA 1979–1997Most received 2 doses, 1–2 months apartAverage follow-up 5 years (range 1–20

years)12 cases break-through varicella (10%):

– average 40 vesicles (<10 times expected)

– 0.5–7 years after vaccination

– Disease occurred in vaccinees who lost detectable antibodies to VZV

Zoster in immunocompromised Zoster in immunocompromised vaccinees vaccinees after immunizationafter immunizationZoster in immunocompromised Zoster in immunocompromised vaccinees vaccinees after immunizationafter immunization

Years after Vaccinees (%) Controls (%)immunization

Leukaemia (Takahashi) 6 6 19

Leukaemia (Brunell) 6 0 21

Leukaemia (Hardy) 10 2 16

Renal transplant (Broyer) 10 7 13

Varicella vaccine in USAVaricella vaccine in USACDC Draft: healthy people, 2010 CDC Draft: healthy people, 2010 goalsgoals

Varicella vaccine in USAVaricella vaccine in USACDC Draft: healthy people, 2010 CDC Draft: healthy people, 2010 goalsgoals Reduce indigenous varicella in USA by 90% Vaccine coverage >90% among children

(19–35 months):– national level and all 50 states

Vaccine coverage >95% 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

Varicella vaccine: persistence of Varicella vaccine: persistence of immunityimmunityVaricella vaccine: persistence of Varicella vaccine: persistence of immunityimmunity

Duration of immunity never known with new vaccine

In USA, 5–10 year follow-up of >500 immunized healthy children:

– over 90% remain seropositive

20-year follow-up of 26 Japanese vaccinees:

– 2 developed mild break-through infections, 100% seropositive

Varicella vaccine: persistence of Varicella vaccine: persistence of immunityimmunityVaricella vaccine: persistence of Varicella vaccine: persistence of immunityimmunity

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

VZV: practical aspects for VZV: practical aspects for pregnant womenpregnant womenVZV: practical aspects for VZV: practical aspects for pregnant womenpregnant women

Identification of varicella susceptibles

History of disease >95% reliable

ELISA tests approximately 75% accurate:– false negatives > false positives

– testing costs vary from US$1–40 per assay

– other antibody tests limited availability (LA, FAMA)

VZV: practical aspects for VZV: practical aspects for pregnant womenpregnant womenVZV: practical aspects for VZV: practical aspects for pregnant womenpregnant 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 <5 days before delivery

– or within 48 hours post-delivery

VZV: practical aspects for VZV: practical aspects for pregnant womenpregnant womenVZV: practical aspects for VZV: practical aspects for pregnant womenpregnant women

Immunization of healthy, non-pregnant

varicella susceptibles in household

Pre-exposure (preferable) or post-exposure vaccination