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ARTICLE |

Postlicensure Effectiveness of Varicella Vaccine During an Outbreak in a Child Care Center FREE

Hector S. Izurieta, MD, MPH; Peter M. Strebel, MBChB, MPH; Paul A. Blake, MD, MPH
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Use of the product trademark does not imply its endorsement by the US government.

Reprints: Peter M. Strebel, MBChB, MPH, Mailstop E-05, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, GA 30333 (email: PMS4@cdc.gov).


JAMA. 1997;278(18):1495-1499. doi:10.1001/jama.1997.03550180045035
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Published online

Context.  —Because lyophilized varicella vaccine must be stored frozen at -15°C or less (≤5°F) and administered within 30 minutes after reconstitution, the potential exists for decreased vaccine effectiveness when the vaccine is used under field conditions.

Objectives.  —To describe an outbreak of varicella in a child care center and to determine postlicensure effectiveness of varicella vaccine.

Design.  —Retrospective cohort study.

Setting.  —A child care center in DeKalb County, Georgia, in 1996.

Participants.  —Of the 184 children registered in the child care center, 148 were eligible for the study based on absence of history of varicella before January 1, 1996.

Main Outcome Measures.  —Data on disease status, severity and impact of disease, and risk factors for varicella and for vaccine failure were obtained from parents and their children's pediatricians. Varicella vaccine effectiveness was calculated among children aged 12 months or older (eligible for vaccination) using the cohort method.

Results.  —The outbreak started on January 17, 1996, and lasted 15 weeks. Of the 148 eligible children, 81 (55%) developed varicella. Cases among children younger than 12 months (n=7) were more severe than cases among older children. Varicella occurred in 9 (14%) of 66 vaccinated children and 72 (88%) of 82 unvaccinated children. Varicella was less severe and resulted in fewer days of absence from the child care center among vaccinated compared with unvaccinated cases. Varicella vaccine effectiveness against all forms of disease was 86% (95% confidence interval [CI], 73%-92%), and against moderate-to-severe varicella disease it was 100% (95% CI, 96%-100%). Vaccinated children with asthma or other reactive airway diseases were 7.1 times more likely to have varicella than were vaccinated children without reactive airway diseases (95% CI, 2.4-21.3).

Conclusions.  —Varicella vaccine administered under routine conditions in physicians' offices was highly effective in preventing varicella in an outbreak characterized by intense exposure. The role of asthma and other reactive airway diseases as risk factors for varicella disease and vaccine failure deserves to be investigated further.

REFERENCES

Centers for Disease Control and Prevention.  Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP) . MMWR Morb Mortal Wkly Rep . 1996;;45(No. (RR11) ):1-37.
Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T, Isomura S.  Live vaccine used to prevent the spread of varicella in children in hospital . Lancet . 1974;;2:1288-1290.
Krause PR, Klinman DM.  Efficacy, immunogenicity, safety, and use of live attenuated varicella vaccine . J Pediatr . 1995;;127:518-525.
Gershon A.  Human immune responses to live attenuated varicella vaccine . Rev Infect Dis . 1991;;13 ( (suppl 11) ):5957-5959.
Kutter B, Weibel RE, Guess HA, et al.  Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies . Vaccine . 1991;;9:643-647.
White CJ, Kuter BJ, Hildebrand CS, et al.  Varicella vaccine (VARIVAX) in healthy children and adolescents: results from clinical trials 1987-1989 . Pediatrics . 1991;;87:604-610.
Wharton M.  The epidemiology of varicella-zoster virus infections . Infect Dis Clin North Am . 1996;;10:571-581.
Jones SE, Armstrong CB, Bland C, Walter EB, Clements DA.  Varicella prevalence in day-care centers . Pediatr Infect Dis J . 1995;;14:404-405.
Finger R, Hughes J, Meade B, Pelletier AR, Palmer C.  Age-specific incidence of chickenpox . Public Health Rep . 1994;;109:750-755.
Comstock GW.  Vaccine evaluation by case-control or prospective studies . Am J Epidemiol . 1990;; 131:205-207.
Orenstein WA, Bernier RH, Hinman AR.  Assessing vaccine efficacy in the field . Epidemiol Rev . 1988;; 10:212-241.
Fleiss JL. Statistical Methods for Rates and Proportions . 2nd ed. New York, NY: John Wiley & Sons; 1981;.
Remington RD, Schork MA. Statistics With Applications to the Biological and Health Sciences . 2nd ed. Englewood Cliffs, NJ: Prentice-Hall Inc; 1985;:187-188,313-316.
Ipsen J.  The ubiquitous2X2 table, its parameters and their confidence limits . Scand J Soc Med . 1984;; 12:121-127.
Dean AG, Dean JA, Coulombier D, et al. A Word-Processing, Database, and Statistics Program for Public Health on IBM-Compatible Microcomputers . Atlanta, Ga: Centers for Disease Control and Prevention; 1994;.
Lee ET. Statistical Methods for Survival Data Analysis . 2nd ed. New York, NY: John Wiley & Sons Inc; 1992;.
Arbeter AM, Starr SE, Preblud SR, et al.  Varicella vaccine trials in healthy children: a summary of comparative and follow-up studies . AJDC . 1984;;138:434-438.
Asano Y, Suga S, Yoshikawa T, et al.  Experience and reason: twenty-year follow-up of protective immunity of the Oka strain live varicella vaccine . Pediatrics . 1994;;94:524-526.
Bernstein HH, Rothstein EP, Pennridge Pediatric Associates, et al.  Clinical survey of natural varicella compared with breakthrough varicella after immunization with live attenuated Oka/ Merck varicella vaccine . Pediatrics . 1993;;92:833-837.
White CJ, Kuter BJ, Ngai A, et al.  Modified cases of varicella after varicella vaccination: correlation of protection with antibody response . Pediatr Infect Dis J . 1992;;11:19-23.
Arbeter AM, Starr SE, Preblud SR, et al.  Varicella vaccine trials in healthy children: a summary of comparative and follow-up studies . AJDC . 1984;;138:434-438.
Just M, Berger R, Luescher D.  Live varicella vaccine in healthy individuals . Postgrad Med J . 1985;;61 ( (suppl 4) ):129-132.
Brunell PA, Novelli VM, Lipton S, Pollock B.  Combined vaccine against measles, mumps, rubella and varicella . Pediatrics . 1988;;81:779-784.
Preblud SR.  Age specific risks of varicella complications . Pediatrics . 1981;;68:14-17.
Asano Y, Hirose S, Iwayama S, Miyata T, Yazaki T, Takahashi M.  Protective effect of immediate inoculation of a live varicella vaccine in household contacts in relation to the viral dose and interval between exposure and vaccination . Biken J . 1982;;25:43-45.
Welch M.  Inhaled steroids and severe viral infections . J Asthma . 1994;;31:43-50.
Tinkelman DG.  FDA varicella warning . Pediatrics . 1992;;90:479-481.
Choong K, Zwaigenbaum L, Onyett H.  Severe varicella after low dose inhaled corticosteroids . Pediatr Infect Dis J . 1995;;14:809-811.
Azbug MJ, Cotton MF.  Severe varicella after intranasal use of corticosteroids . J Pediatr . 1993;;123:577-579.
Delclaux B, Derenne Jph.  Oesophagite herpétique chez un asthmatique traité par corticosteroids . Presse Med . 1992;;21:1432.
Cockcroft DW, Murdock KY.  Comparative effect of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine . J Allergy Clin Immunol . 1987;;79:734-740.
Bradding P.  Anti-inflammatory effects of longacting β-agonists in asthma . Clin Exp Allergy . 1995;; 25:912-914.

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Centers for Disease Control and Prevention.  Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP) . MMWR Morb Mortal Wkly Rep . 1996;;45(No. (RR11) ):1-37.
Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T, Isomura S.  Live vaccine used to prevent the spread of varicella in children in hospital . Lancet . 1974;;2:1288-1290.
Krause PR, Klinman DM.  Efficacy, immunogenicity, safety, and use of live attenuated varicella vaccine . J Pediatr . 1995;;127:518-525.
Gershon A.  Human immune responses to live attenuated varicella vaccine . Rev Infect Dis . 1991;;13 ( (suppl 11) ):5957-5959.
Kutter B, Weibel RE, Guess HA, et al.  Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies . Vaccine . 1991;;9:643-647.
White CJ, Kuter BJ, Hildebrand CS, et al.  Varicella vaccine (VARIVAX) in healthy children and adolescents: results from clinical trials 1987-1989 . Pediatrics . 1991;;87:604-610.
Wharton M.  The epidemiology of varicella-zoster virus infections . Infect Dis Clin North Am . 1996;;10:571-581.
Jones SE, Armstrong CB, Bland C, Walter EB, Clements DA.  Varicella prevalence in day-care centers . Pediatr Infect Dis J . 1995;;14:404-405.
Finger R, Hughes J, Meade B, Pelletier AR, Palmer C.  Age-specific incidence of chickenpox . Public Health Rep . 1994;;109:750-755.
Comstock GW.  Vaccine evaluation by case-control or prospective studies . Am J Epidemiol . 1990;; 131:205-207.
Orenstein WA, Bernier RH, Hinman AR.  Assessing vaccine efficacy in the field . Epidemiol Rev . 1988;; 10:212-241.
Fleiss JL. Statistical Methods for Rates and Proportions . 2nd ed. New York, NY: John Wiley & Sons; 1981;.
Remington RD, Schork MA. Statistics With Applications to the Biological and Health Sciences . 2nd ed. Englewood Cliffs, NJ: Prentice-Hall Inc; 1985;:187-188,313-316.
Ipsen J.  The ubiquitous2X2 table, its parameters and their confidence limits . Scand J Soc Med . 1984;; 12:121-127.
Dean AG, Dean JA, Coulombier D, et al. A Word-Processing, Database, and Statistics Program for Public Health on IBM-Compatible Microcomputers . Atlanta, Ga: Centers for Disease Control and Prevention; 1994;.
Lee ET. Statistical Methods for Survival Data Analysis . 2nd ed. New York, NY: John Wiley & Sons Inc; 1992;.
Arbeter AM, Starr SE, Preblud SR, et al.  Varicella vaccine trials in healthy children: a summary of comparative and follow-up studies . AJDC . 1984;;138:434-438.
Asano Y, Suga S, Yoshikawa T, et al.  Experience and reason: twenty-year follow-up of protective immunity of the Oka strain live varicella vaccine . Pediatrics . 1994;;94:524-526.
Bernstein HH, Rothstein EP, Pennridge Pediatric Associates, et al.  Clinical survey of natural varicella compared with breakthrough varicella after immunization with live attenuated Oka/ Merck varicella vaccine . Pediatrics . 1993;;92:833-837.
White CJ, Kuter BJ, Ngai A, et al.  Modified cases of varicella after varicella vaccination: correlation of protection with antibody response . Pediatr Infect Dis J . 1992;;11:19-23.
Arbeter AM, Starr SE, Preblud SR, et al.  Varicella vaccine trials in healthy children: a summary of comparative and follow-up studies . AJDC . 1984;;138:434-438.
Just M, Berger R, Luescher D.  Live varicella vaccine in healthy individuals . Postgrad Med J . 1985;;61 ( (suppl 4) ):129-132.
Brunell PA, Novelli VM, Lipton S, Pollock B.  Combined vaccine against measles, mumps, rubella and varicella . Pediatrics . 1988;;81:779-784.
Preblud SR.  Age specific risks of varicella complications . Pediatrics . 1981;;68:14-17.
Asano Y, Hirose S, Iwayama S, Miyata T, Yazaki T, Takahashi M.  Protective effect of immediate inoculation of a live varicella vaccine in household contacts in relation to the viral dose and interval between exposure and vaccination . Biken J . 1982;;25:43-45.
Welch M.  Inhaled steroids and severe viral infections . J Asthma . 1994;;31:43-50.
Tinkelman DG.  FDA varicella warning . Pediatrics . 1992;;90:479-481.
Choong K, Zwaigenbaum L, Onyett H.  Severe varicella after low dose inhaled corticosteroids . Pediatr Infect Dis J . 1995;;14:809-811.
Azbug MJ, Cotton MF.  Severe varicella after intranasal use of corticosteroids . J Pediatr . 1993;;123:577-579.
Delclaux B, Derenne Jph.  Oesophagite herpétique chez un asthmatique traité par corticosteroids . Presse Med . 1992;;21:1432.
Cockcroft DW, Murdock KY.  Comparative effect of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine . J Allergy Clin Immunol . 1987;;79:734-740.
Bradding P.  Anti-inflammatory effects of longacting β-agonists in asthma . Clin Exp Allergy . 1995;; 25:912-914.
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