By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

Changing Herpes Zoster Risk in Adults

SOURCE: Harpaz R, Leung JW. The epidemiology of herpes zoster in the United States during the era of varicella and herpes zoster vaccines: Changing patterns among older adults. Clin Infect Dis 2018; Nov 29. doi: 10.1093/cid/ciy953. [Epub ahead of print].

There are approximately 1 million adult cases of herpes zoster (HZ) every year in the United States. The epidemiology of HZ in adults appears to be changing, with younger adults at increasing risk. This study examined the age-specific risk of HZ in adults > 35 years of age throughout the United States from 1993 to 2015. The HZ incidence was based on ICD-9/10 coding for varicella zoster and for post-herpetic complications. The prospective population at risk was an estimated 27 million individuals, with a median follow-up of 49 months. From population tables, there was an estimated number of 934,000 HZ cases in individuals 35 years of age or older, whereas insurance enrollment tables identified 804,000 HZ cases in a similar age group. Approximately 62% of HZ cases were in women, and the median ages from 1993 to 2003 and from 2004 to 2016 were similar (59.4 years and 59.3 years, respectively).

Vaccination time lines are important considerations when evaluating population data for varicella and shingles. Following the introduction of the varicella vaccine in 1996, the reported incidence of acute primary varicella continued to decline by 97% by 2014. However, mild varicella infections continued to occur in those receiving one dose of varicella vaccine, leading to modified recommendations in 2006 for two doses of vaccine in children. In addition, once the first commercially available shingles vaccine (Zostavax) was licensed in 2008, adults > 60 years of age began, slowly, to receive this vaccine (up from 2% in 2007 to 14% in 2010 to 33% by 2016). At the same time, the age for vaccination was extended to those > 50 years of age in 2011. It is important to remember that vaccine immunogenicity from this vaccine probably wanes within 10 years, so vaccine received in 2006 may no longer provide protection in 2016. (The newest HZ vaccine approved in 2017 would not affect these data.)

Despite the introduction of these two vaccines, the age-related incidence of HZ in adults > 35 years of age has been increasing steadily. In adults > 35 years of age, HZ incidence in 1993 was as low as 2.5 cases per 1,000 population. By 2006, this figure had increased to 6.1/1,000, and by 2016 had increased further to 7.2/1,000. This increase is largely due to a steady increase in HZ cases in individuals aged 35 to 50-55 years. Earlier analysis indicated that adults 50-55 years and older also were at increased risk for HZ, but since 2006-2016, the risk seems to be declining. In fact, the data have starkly diverged, with a steady increase in younger adults and a decline in HZ risk among older adults.

The authors were unable to provide an explanation for this finding. Obviously, comorbidity, diabetes, and immunosuppression, which would be more frequent in older adults, does not provide an explanation. Although it is conceivable that the broader use of varicella vaccine in children has reduced any possible VZV immunological boosting effect in adults, it is not at all clear why that effect would be differentially expressed in younger vs. older adults. Perhaps the present-day stressors on younger adults are just that much greater than for older adults. Or, perhaps older adults had repeated exposure and priming in their earlier years — resulting in somewhat more durable immunity — whereas younger adults are dependent on what limited exposure has existed the past 10 to 20 years with effectively no “communal vaccination.”

Trends in Herpes Zoster Risk Among Children

SOURCE: Harpaz R, Leung JW. The epidemiology of herpes zoster in the United States during the era of varicella and herpes zoster vaccines: Changing patterns among children. Clin Infect Dis 2018. doi: 10.1093/cid/ciy954. [Epub ahead of print].

Although the epidemiology of herpes zoster (HZ) in adults continues to evolve, the risk of HZ in children < 18 years of age has declined steadily. These authors examined the risk of HZ in approximately 13 million children from 1998 to 2016, representing approximately 51 million person-years of follow-up. The number of children enrolled in successful years of the study remained fairly stable. In contrast to adults, with nearly 1 million HZ cases per year, there were 35,405 cases of HZ in children during the entire time period.

Trends in HZ in children from 1998 to 2016, based on all age cohorts, showed steady increases during the first years of observation, through about 2006-2007. However, since then, the risk of HZ has declined steadily. This likely is related to the different risks of reactivation in younger cohorts vs. more modern cohorts. It is largely believed that the risk of reactivation from vaccine strain VZV (vs-VZV) is substantially less than from wild type VZV (wt-VZV). Thus, children born prior to 2010, who may have received only one dose of VZV vaccine, were at greatest risk for developing wild type infection; some may have had mixtures of vaccine strain and WT virus. However, by 2010, more than 90% of children had received at least one dose, if not two doses, of VZV vaccine, and were infected almost exclusively with vs-VZV. Thus, the risk of reactivation HZ has declined steadily since 2008-2010.

The current risk of HZ among children in the two youngest age cohorts is approximately 0.22/1,000. This suggests that, although the risk of HZ may never reach zero, the risk of HZ may continue to decline as these cohorts age and become adults.