Correspondence

Varicella Vaccine

N Engl J Med 2007; 356:2648-2649June 21, 2007

Article

To the Editor:

Chaves et al. (March 15 issue)1 use complex statistical models, based on nonvalidated estimates and uncertain diagnoses, to conclude from epidemiologic data that vaccine-induced immunity to varicella–zoster virus (VZV) wanes. Our data based on serologic testing indicate that primary vaccine failure is the main reason for breakthrough varicella infection in 15 to 20% of vaccinees; in 20 of 84 children (24%) who were given one dose of vaccine, VZV antibodies failed to develop.2

Chaves and colleagues used an estimate of primary vaccine failure and cannot distinguish failure to elicit immunity from waning immunity. When directly tested in a case–control study, the vaccine's effectiveness did not diminish significantly over time3,4; although effectiveness decreased 1 year after vaccination, no further decrease occurred 8 years thereafter, a finding that is consistent with primary vaccine failure. The inference that immunity wanes might therefore be incorrect and discourage vaccination, enlarging the number of persons who may be susceptible to varicella. Varicella vaccine is highly effective3-5; a two-dose regimen is expected to address primary vaccine failure.

Anne A. Gershon, M.D.
Columbia University College of Physicians and Surgeons, New York, NY 10032
aag1@columbia.edu

Ann M. Arvin, M.D.
Stanford University School of Medicine, Stanford, CA 94305-2061

Eugene Shapiro, M.D.
Yale University School of Medicine, New Haven, CT 06520-8064

Drs. Gershon and Arvin report receiving consulting and lecture fees from Merck and GlaxoSmithKline, and Dr. Shapiro reports receiving lecture fees from Merck. No other potential conflict of interest relevant to this letter was reported.

5 References

1. 1

   Chaves SS, Gargiullo P, Zhang JX, et al. Loss of vaccine-induced immunity to varicella over time. N Engl J Med 2007;356:1121-1129
   Full Text | Web of Science | Medline

2. 2

   Michalik D, LaRussa P, Steinberg S, Wright P, Edwards KM, Gershon A. Primary immune failure after 1 dose of varicella vaccine may be the main cause of breakthrough infections in healthy vaccinated children. In: Proceedings of the 44th annual meeting of the Infectious Diseases Society of America, Toronto, October 12–15, 2006.
   

3. 3

   Vazquez M, LaRussa PS, Gershon AA, Steinberg SP, Freudigman K, Shapiro ED. The effectiveness of the varicella vaccine in clinical practice. N Engl J Med 2001;344:955-960
   Full Text | Web of Science | Medline

4. 4

   Vazquez M, LaRussa PS, Gershon AA, et al. Effectiveness over time of varicella vaccine. JAMA 2004;291:851-855
   CrossRef | Web of Science | Medline

5. 5

   Seward JF, Watson BM, Peterson CL, et al. Varicella disease after introduction of varicella vaccine in the United States, 1995-2000. JAMA 2002;287:606-611
   CrossRef | Web of Science | Medline

To the Editor:

Chaves and colleagues found that VZV vaccine–induced immunity waned over time, and they recommend a second dose of vaccine. The major concern of the VZV vaccination program has been that it might transfer the burden of disease to adults, who are 23 to 29 times as likely as children to die from primary infection.1 Will the loss of immunity from natural varicella infection in childhood (especially in the developed world) be at the expense of higher rates of severe primary varicella among adults in the future?

Sanjaya N. Senanayake, F.R.A.C.P., M.B., B.S.
Canberra Hospital, Woden, ACT 2606, Australia
sanjaya.senanayake@act.gov.au

1 References

1. 1

   Heininger U, Seward J. Varicella. Lancet 2006;368:1365-1376[Erratum, Lancet 2007;369:558.]
   CrossRef | Web of Science | Medline

Author/Editor Response

Gershon et al. correctly point out that primary vaccine failure may account for some of the cases of varicella disease among vaccinated children in our study. However, as we discuss in our article, this form of failure cannot fully explain our findings. If primary vaccine failure had been the predominant effect, we would have expected constant rates of breakthrough disease. We found the opposite — an increase in the rate and severity of breakthrough disease with time since vaccination. These findings can be better explained by the waning of immunity.

Moreover, a complete failure of immune response, (i.e., primary vaccine failure) is likely to present clinically as a typical case of disease. The modified presentation of breakthrough disease is consistent with partial protection afforded by vaccination, an immune response that is elicited after vaccination but that is insufficient to fully protect the person from the development of clinical disease. The immunity from this partial protection may be more likely to wane over time, as we discuss in our article.

We agree that it may be challenging to diagnose cases of breakthrough varicella clinically. However, if there were, for example, improvements in the diagnosis of breakthrough disease over time, these improvements would have an effect by the calendar year, not by the time since vaccination. The varicella cases that occurred in the most recent calendar years involved children who had been vaccinated at various intervals in the past, ranging from within 1 year to 8 years earlier. Thus, we do not believe that possible ascertainment bias has implications for the reliability of our findings.

With regard to the comments by Senanayake, the one-dose varicella vaccination program has been very successful in reducing the varicella disease burden in the United States.1-3 We acknowledge that our findings contrast with those of Vazquez et al., who found no decline in varicella vaccine effectiveness from 2 to 8 years after vaccination.4 Therefore, other studies of waning immunity should be undertaken to corroborate or refute our findings. The two-dose regimen in children is expected to decrease primary vaccine failure, improve vaccine effectiveness, and decrease the risk of breakthrough disease. Continued monitoring of the varicella vaccination program will be needed to assess the impact of the new policy recommendations regarding the two-dose vaccine schedule, including the duration of the immunity that it confers.

Sandra S. Chaves, M.D., M.Sc.
Jane F. Seward, M.B., B.S., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 30333
bev8@cdc.gov

4 References

1. 1

   Seward JF, Watson BM, Peterson CL, et al. Varicella disease after introduction of varicella vaccine in the United States, 1995-2000. JAMA 2002;287:606-611
   CrossRef | Web of Science | Medline

2. 2

   Nguyen HQ, Jumaan AO, Seward JF. Decline in mortality due to varicella after implementation of varicella vaccination in the United States. N Engl J Med 2005;352:450-458
   Full Text | Web of Science | Medline

3. 3

   Zhou F, Harpaz R, Jumaan AO, Winston CA, Shefer A. Impact of varicella vaccination on health care utilization. JAMA 2005;294:797-802
   CrossRef | Web of Science | Medline

4. 4

   Vazquez M, LaRussa PS, Gershon AA, et al. Effectiveness over time of varicella vaccine. JAMA 2004;291:851-855
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   E. D. Shapiro, M. Vazquez, D. Esposito, N. Holabird, S. P. Steinberg, J. Dziura, P. S. LaRussa, A. A. Gershon. (2011) Effectiveness of 2 Doses of Varicella Vaccine in Children. Journal of Infectious Diseases 203:3, 312-315
   CrossRef

2. 2

   Eugene D. Shapiro. (2008) Second Dose of Varicella Vaccine for Children: Are We Giving It Too Late?. The Journal of Infectious Diseases 197:7, 935-937
   CrossRef