Herpes Zoster Vaccine and the Incidence of Recurrent Herpes Zoster in the Elderly
By Richard R. Watkins, MD, MS, FACP, Division of Infectious Diseases, Akron General Medical Center, Akron, OH; Associate Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH, is Associate Editor for Infectious Disease Alert.
Dr. Watkins reports no financial relationships in this field of study.
Synopsis: In a matched cohort study involving immunocompetent individuals ≥ 60 years of age, the incidence of herpes zoster recurrence following a recent initial episode was low in both herpes zoster vaccine recipients and the unvaccinated. This low risk questions the need for vaccinating immunocompetent adults with recent herpes zoster infections.
Source: Tseng HF, et al. Herpes zoster vaccine and the incidence of recurrent herpes zoster in an immunocompetent elderly population. J Infect Dis 2012;206:190-196.
A common question in clinical practice about the shingles vaccine is whether it is effective in preventing recurrent episodes in patients who have had herpes zoster (HZ). Currently the Advisory Committee on Immunization Practices (ACIP) recommends it for patients ≥ 60 years of age, including those with prior HZ.1 The actual risk of recurrence has not been elucidated, although it is thought to be higher in patients with more severe disease.2 Since it was first licensed in 2006, the shingles vaccine has been hampered by production difficulties and shortfalls in availability. Although the Food and Drug Administration approved the shingles vaccine for adults aged 50 through 59 years in March 2011, the ACIP declined to follow suit, citing available evidence and the supply issues.3 Healthcare policy-makers and providers therefore need guidance in determining shingles vaccination priorities.
To clarify these issues, Tseng and colleagues conducted a matched cohort study in the Kaiser Permanente system in Southern California. Members aged ≥ 60 years who received the shingles vaccine between 1/1/07 and 12/31/10 served as the vaccinated cohort. The unvaccinated cohort included randomly selected members who were matched 5:1 to the vaccinated group based on birth date (±1 year) and were assigned an index date that corresponded with the vaccination date of the matched vaccinated member. Both groups had the same selection criteria: (1) no diagnosis of HZ during 180 days prior to the date of vaccination; (2) they had a visit for a diagnosis of HZ that included a prescription of antiviral medication on the same day 180 to 730 days prior to vaccination; (3) they had not received a diagnosis of HZ ≤1 year prior to the index HZ case, defined as the first HZ case diagnosed in the reference period. Immunocompromised patients were excluded from both cohorts, including those with HIV, leukemia, lymphoma, or having been prescribed immunosuppressive agents during the period from ≤1 year before the index date until the end of follow-up. A propensity score was used to account for potential confounders and was created using a logistic regression model that predicted the probability of receiving the zoster vaccine. The study included 1036 vaccinated and 5180 unvaccinated subjects.
Compared with the unvaccinated cohort, the vaccinated cohort had more female, white, and Asian members and a lower prevalence of chronic diseases. The incidence of recurrent HZ per 1000 person-years in those aged <70 years was similar in the vaccinated and unvaccinated cohorts, 0.99 (95% confidence interval (CI) 0.02-5.5) and 2.20 (95% CI 1.10-3.93), respectively. The unadjusted incidence rate ratio was 0.45 (95% CI 0.06-3.51; p = 0.45). There was a trend toward the incidence being lower in the vaccinated group, but the scarcity of events precluded the ability to detect a meaningful difference between the two cohorts.
There were a few limitations to the study. The authors did not confirm the initial HZ episode or the recurrence by laboratory testing. The cases were detected using electronic medical records, which could introduce bias from misclassification. Moreover, the incidence rate was calculated from the period from the index date (the first day of follow-up set by the vaccinated cohort) instead of the period starting from the previous episode. Thus, comparing the incident rate from this study to other studies is difficult and may be open to different interpretations.
Commentary
As the authors describe, the occurrence of HZ is believed to result from a decline in a threshold level of varicella zoster virus (VZV) specific cell-mediated immunity. Ongoing exposures to VZV, both through endogenous and exogenous sources, may propagate effective VZV memory immunity. The shingles vaccine likely restores VZV-specific T cells to a level above the threshold. HZ and the shingles vaccine both generate a comparable VZV cell-mediated immunity that is protective against further episodes.4 This study is important because it suggests that the risk of recurrent HZ following a recent initial episode is low among immunocompetent adults. Therefore, vaccination immediately following a recent HZ episode may not be necessary. But before this becomes routine clinical practice, larger studies with longer follow-up and laboratory confirmation of cases need to be completed. Also, whether certain immunocompromised patients should be vaccinated following an episode of HZ remains an open question. Given the high cost of the vaccine and its frequent shortages, this study and future ones will hopefully aid policy makers and payers in prioritizing which patients should undergo vaccination.
References
- Harpaz R, et al. Prevention of herpes zoster: recommendations of the advisory committee on immunization practices. MMWR 2008;57:1-30.
- Yawn BP, et al. Herpes zoster recurrences more frequent than previously reported. Mayo Clin Proc 2011;86:88-93.
- Harpaz R, et al. Update on Herpes Zoster Vaccine: Licensure for Persons Aged 50 Through 59 Years. MMWR 2011;60:1528.
- Weinberg A, et al. Varicella-zoster virus-specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine. J Infect Dis 2009;200: 1068-1077.
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