Effectiveness Over Time of Varicella Vaccine

Vázquez, Marietta MD
LaRussa, Philip S. MD
Gershon, Anne A. MD
Niccolai, Linda M. PhD
Muehlenbein, Catherine E. MPH
Steinberg, Sharon P.
Shapiro, Eugene D. MD

Departments of Pediatrics (Drs Vázquez and Shapiro and Ms Muehlenbein) and Epidemiology and Public Health (Drs Niccolai and Shapiro) and the Children's Clinical Research Center (Dr Shapiro), Yale University School of Medicine, New Haven, Conn; and Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY (Drs LaRussa and Gershon and Ms Steinberg).

Corresponding Author: Eugene D. Shapiro, MD, Department of Pediatrics, Yale School of Medicine, 333 Cedar St, PO Box 208064, New Haven, CT 06520-8064 ([email protected]).

Author Contributions: As principal investigator, Dr Shapiro had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Vázquez, LaRussa, Gershon, Shapiro.

Acquisition of data: Vázquez, LaRussa, Gershon, Steinberg.

Analysis and interpretation of data: Vázquez, LaRussa, Gershon, Niccolai, Muehlenbein, Shapiro.

Drafting of the manuscript: Vázquez, Shapiro.

Critical revision of the manuscript for important intellectual content: Vázquez, LaRussa, Gershon, Niccolai, Muehlenbein, Steinberg, Shapiro.

Statistical expertise: Vázquez, Niccolai, Muehlenbein, Shapiro.

Obtained funding: Gershon, Shapiro.

Administrative, technical, or material support: LaRussa.

Supervision: Vázquez, LaRussa, Gershon, Shapiro.

Funding/Support: This work was supported in part by grants R01-AI41608, R01-AI 24021, and K24-AI01703 from the National Institute of Allergy and Infectious Diseases and by the Yale Children's Clinical Research Center grant MO1-RR06022, General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health, Bethesda, Md. Dr Vázquez was supported in part by the Robert Wood Johnson Minority Medical Faculty Development Program.

Role of the Sponsor: The National Institute of Allergy and Infectious Diseases and the Yale Children's Clinical Research Center did not participate in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

Acknowledgment: We are grateful for the efforts of Valerie Parcells, RN, who visited the case subjects and collected much of the data.

Financial Disclosures: Dr LaRussa is the recipient of a contract from Merck & Co to perform a varicella-specific PCR assay on blinded samples from recipients of varicella vaccine who have had adverse events potentially related to vaccination. Dr Gershon has received research support for a basic science project from Merck & Co. Drs Shapiro and Gershon served as consultants at a 1-day meeting on vaccine cost-effectiveness sponsored by Merck & Co.

JAMA: The Journal of the American Medical Association 291(7):p 851-855, February 18, 2004.

Context

Reports of outbreaks of varicella in highly immunized groups have increased concern about the effectiveness of varicella vaccine.

Objective

To assess whether the effectiveness of varicella vaccine is affected either by time since vaccination or by age at the time of vaccination.

Design

Case-control study conducted from March 1997 through June 2003.

Setting

Twenty different group practices in southern Connecticut.

Participants

Case subjects, identified by active surveillance of all practices, consisted of 339 eligible children 13 months or older who were clinically diagnosed as having chickenpox and who also had a polymerase chain reaction (PCR) test result that was positive for varicella-zoster virus DNA. For each case subject, 2 controls were selected, matched by both age and pediatric practice.

Main Outcome Measures

The effectiveness of the vaccine, especially the effects of time since vaccination and age at the time of vaccination, adjusted for possible confounders.

Results

Although the adjusted overall effectiveness of the vaccine was 87% (95% confidence interval, 81%–91%; P<.001), there was a substantial difference in the vaccine's effectiveness in the first year after vaccination (97%) and in years 2 to 8 after vaccination (84%, P =.003). The vaccine's effectiveness in year 1 was substantially lower if the vaccine was administered at younger than 15 months (73%) than if it was administered at 15 months or older (99%, P = .01), although the difference in effectiveness overall for children immunized at younger than 15 months was not statistically significantly different than for those immunized at 15 months or older (81% vs 88%, P =.17). Most cases of chickenpox in vaccinees were mild.

Conclusions

Although varicella vaccine is effective, its effectiveness decreases significantly after 1 year, although most cases of breakthrough disease are mild. If administered at younger than 15 months, the vaccine's effectiveness was lower in the first year after vaccination, but the difference in effectiveness was not statistically significant for subsequent years.