Live, attenuated varicella vaccine was licensed in March, 1995 for use in healthy individuals in the United States. There has been controversy about both its short-term and its long-term efficacy (in part because licensure was based on limited data, much of which was from studies with a vaccine that contained a higher concentration of virus). Consequently, many physicians have been reluctant to use the vaccine, although routine immunization of all susceptible, immunocompetent children (beginning at 12 months of age) has been recommended by the U.S. Public Health Service Advisory Committee on Immunization Practices and by other advisory committees. The primary purpose of the proposed study is to assess the protective efficacy of this varicella vaccine, as it is used in actual practice, and to assess the effects of both age at the time of vaccination and of the time since vaccination on vaccine efficacy. This will be a case-control study in which the cases will be immunocompetent children from 15 months-16 years of age who develop varicella. The cases will be identified through active surveillance conducted at both private practices and health maintenance organizations in greater New Haven, Connecticut, and in Westchester County, New York. A research assistant will visit the home of each potential case subject on the third day of the rash to assess the severity of the illness by use of a scale based on pre-defined criteria (e.g., number of vesicles, elevation of fever, etc.). In addition, material from the lesions will be tested with both a direct fluorescent antibody test and polymerase chain reaction (to confirm the presence of varicella-zoster virus and to determine whether it is wild-type or vaccine-type virus). The controls will be immunocompetent children without a history of chickenpox who are matched (2:1) to the cases by both age and the source of primary care. The medical records of both the cases and the controls will be reviewed to determine whether they had received varicella vaccine. The protective efficacy of the vaccine (and the associated 95% confidence interval) will be estimated from the matched odds ratios. The estimates will be adjusted for possible confounders with the use of conditional logistic regression. The effects on the efficacy of the vaccine of both age at the time of vaccination and the time since vaccination will be assessed by stratification and by multivariate analysis. Additionally, differences in the clinical severity of varicella (as determined by the clinical scale) among vaccinated and unvaccinated cases will be assessed. This study will provide important information about the efficacy of varicella vaccine in actual practice. Such information is critical for assessing the cost-effectiveness of the vaccine and will be useful both for educating physicians and for counselling parents who may be concerned about having their children vaccinated.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Beisel, Christopher E
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Yale University
Schools of Medicine
New Haven
United States
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Shapiro, Eugene D; Vazquez, Marietta; Esposito, Daina et al. (2011) Effectiveness of 2 doses of varicella vaccine in children. J Infect Dis 203:312-5
Niccolai, Linda M; Ogden, Lorraine G; Muehlenbein, Catherine E et al. (2007) Methodological issues in design and analysis of a matched case-control study of a vaccine's effectiveness. J Clin Epidemiol 60:1127-31
Vazquez, Marietta; LaRussa, Philip S; Gershon, Anne A et al. (2004) Effectiveness over time of varicella vaccine. JAMA 291:851-5
Shapiro, Eugene D (2004) Case-control studies of the effectiveness of vaccines: validity and assessment of potential bias. Pediatr Infect Dis J 23:127-31
Vazquez, M; LaRussa, P S; Gershon, A A et al. (2001) The effectiveness of the varicella vaccine in clinical practice. N Engl J Med 344:955-60
Shapiro, E D; LaRussa, P S (1997) Vaccination for varicella--just do it! JAMA 278:1529-30