Do varicella vaccination programs change the epidemiology of herpes zoster? A comprehensive review, with focus on the United States

ABSTRACT

Introduction: Policy-makers in many countries have been wary of introducing varicella vaccination programs because of concerns that reduced exposures to varicella-zoster virus could increase herpes zoster (HZ) incidence. The U.S. introduced varicella vaccination in 1996 and has empiric evidence regarding this concern.

Areas covered: This comprehensive review provides background emphasizing the epidemiology of varicella and of HZ in the U.S. before and after the introduction of their respective vaccines. The epidemiology is complex, and interpretation is complicated by methodologic challenges, by unexplained increases in age-specific HZ incidence that preceded varicella vaccination, and by introduction of vaccines for prevention of HZ. Nonetheless, observations from studies using different platforms and designs have yielded consistent findings, suggesting they are robust.

Expert opinion: There has been no evidence that the U.S. varicella vaccination program increased HZ incidence in the general adult population over baseline trends. Furthermore, HZ incidence in children is declining. The U.S. experience can inform the development of new generations of models to predict HZ trends. More importantly, it provides reassurance for countries considering varicella vaccination that an effective program can reduce varicella morbidity and mortality while reducing the likelihood of HZ among children, and potentially, over time, across the entire population.

KEYWORDS:

• Zoster
• varicella
• varicella vaccine
• varicella zoster virus
• zoster vaccine
• chicken pox
• herpes zoster
• shingles

Article Highlights

• VZV-specific immunity helps control VZV latency, preventing HZ. Varicella exposure plausibly helps maintain that immunity. If true, by reducing varicella incidence, varicella vaccination may cause increasing HZ incidence among VZV-infected individuals. This concern has made policy-makers in many countries wary of introducing varicella vaccine into their childhood schedules.

• The U.S. introduced varicella vaccination in 1996. The program reduced varicella incidence measurably within a few years, and by >95% within 10–15 years. Empiric evidence from the U.S. regarding HZ incidence can thus help settle this concern.

• Major knowledge gaps remain regarding HZ epidemiology. In particular, HZ incidence has increased for decades, preceding the varicella vaccination program, making it challenging to resolve superimposed program effects. This review also emphasizes methodological challenges posed by HZ ascertainment: not all patients experiencing HZ seek healthcare; those that do not are necessarily missed.

• Adequate observation time is needed to assess varicella vaccination-impact on HZ incidence among older adults. Several U.S. studies meet such criteria. None provide evidence that HZ incidence has accelerated among adults; indeed, there is evidence of deceleration among adults aged ≥60 years.

• Considerations underlying HZ risk are fundamentally different for persons born since the introduction of varicella vaccination since they more likely harbor latent v-VZV rather than wt-VZV. HZ incidence is declining in recent birth cohorts. Early data suggest that over time, declines may extend to the entire population, but the magnitude of the decline will depend on age-specific risks of v-VZV-attributable HZ as vaccinated cohorts age.

• The U.S. experience provides reassurance for countries considering adoption of varicella vaccination that an effective program can accomplish a reduction in varicella morbidity and mortality while reducing the likelihood of HZ among children, and potentially, over time, across the entire population.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Reviewer disclosures

A reviewer on this manuscript has disclosed an NIH Research grant (DK 093094) and a contract for laboratory identification of VZV; and conducted a safety study for Merck, although no salary support was directly given. Another reviewer has disclosed that they are a company employee of Merck, which is a vaccine manufacturer. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Disclaimer

The findings and conclusions in this report are those of the author and do not necessarily represent the official position of CDC.

Additional information

Funding

This paper was not funded.