Graduation Year


Document Type




Degree Name

Doctor of Public Health (Dr.PH.)

Degree Granting Department

Public Health

Major Professor

Ellen M. Daley, Ph.D.

Committee Member

Steve Freedman, Ph.D.

Committee Member

Sean T. Gregory, Ph.D.

Committee Member

Cheryl A. Vamos, Ph.D.


Herpes Zoster, Stroke, Cost-effectiveness, Vaccine, Cardiovascular Disease


Background: Over the last twenty years the incidence of herpes zoster (HZ) infection, also known as shingles, has been increasing among adults for unknown reasons. The economic burden of HZ is currently estimated at over $1 billion per year in the United States (U.S.) and is expected to increase as the susceptible adult population ages. HZ is caused by a re-activation of the varicella zoster virus (VZV), chicken pox, and more than 95% of adults living today carry the virus with a lifetime risk of 1 in 3 for developing HZ. In 2006 the FDA approved a vaccine for the prevention of HZ in adults 60 years and older and in 2011 approval was expanded to include adults age 50-59 years. Since 2006 rates of adult immunization for HZ have been modest, as of 2015 approximately two-thirds of the US population ≥ 60 are still unvaccinated and more than 94% of those ages 50-59 have not been vaccinated. There is now accumulating evidence of a significantly elevated risk of ischemic stroke (IS) within the first 12 months following infection with HZ. Every 40 seconds someone in the U.S. suffers a stroke with an estimated 795,000 strokes per year. In the U.S. stroke is a significant cause of disability with costs estimated at $33 billion per year including cost of healthcare, medication, and lost productivity. As the population in the U.S ages, the risk of both HZ infection and stroke will increase significantly thus impacting mortality, morbidity, and healthcare costs. The CDC Advisory Committee for Immunization Practices (ACIP) currently recommends routine vaccination against HZ for adults ≥ 60 but does not recommend vaccination for adults age 50-59 years and does not provided any guidance or recommendations for adults who may be at increased risk of stroke associated with HZ infection. The current ACIP vaccination recommendations for HZ are predominately based on clinical trial efficacy data and cost-effectiveness analyses (CEAs) in adults ≥ 60. These prior analyses did not included costs associated with the recent evidence demonstrating increased risk of stroke up to one year following HZ infection.

Aims: The objectives of this study were as follows; 1) To assess the cost-effectiveness of a targeted HZ vaccination strategy for adults age 50-59 years at increased cardiovascular (CV) risk in whom vaccination is approved but not recommended; 2) To develop a white paper directed at payers, providers, and policy makers translating the findings from the analysis into appropriate population health dissemination, implementation, and adoption priority recommendations.

Methods: A decision analytic Markov Model (MM) was used to compare costs and outcomes between two vaccination strategies; usual-care (no current vaccine recommendation) and targeted vaccination in adults age 50-59 years with cardiovascular disease (CVD) in a hypothetical cohort of 100,000 adults age 50-59 years. The private payer perspective was used as it best represents this population of adults age 50-59 years who are predominately employed and covered under employer sponsored commercial insurance. The simulated cohort was assessed for incidence of IS within 12 months following HZ infection occurring within the fifth decade of life. Risk was assessed from the age at entry to the analysis, median age 55, up to age 60 using TreeAge Pro 2017 software. The cohort was then aged out to 100 years or death, whichever came first. Costs were calculated using 2016 U.S. dollars.

Findings: As it relates to aim one, compared to usual-care targeting HZ vaccination in adults age 50-59 years with prevalent CVD was cost-effective with an incremental cost-effectiveness ratio (ICER) of $55,517 per quality of life-year (QALY) gained which falls well below the standard willingness-to-pay (WTP) threshold of $100,000 utilized in previous HZ CEAs (Le & Rothberg, 2015, 2016; Pellissier, Brisson, & Levin, 2007). The incremental cost of vaccinating the target population using a benchmark vaccination rate of 60% was $30.59 per person compared to $12.98 in the usual-care group with ICERs of $55,517 and $55,470 respectively. Moreover, when comparing the cost of universal vaccination in the entire 50-59 year old cohort cost-effectiveness was maintained with an incremental cost of $176.51 per person and an ICER of $55,523. Adopting the targeted strategy resulted in 162 fewer cases of HZ and 14 fewer strokes per 100,000 persons. Regarding aim two, following safety and efficacy, cost-effectiveness analysis are considered an essential metric in vaccine policy making and a substantial driver of vaccine adoption by policymakers, payers, and providers. Translating these favorable cost-effectiveness findings to policymakers, payers, and providers is necessary to help close the adoption curve gap in order to facilitate and inform effective and timely implementation strategies for HZ vaccination in this targeted population.

Conclusions: This study demonstrated that targeted HZ vaccination in patients age 50-59 years at increased CV risk is cost-effective and thus updating ACIP policy recommendations regarding vaccination in this population for whom the vaccine is currently FDA approved but not recommended should be considered. Furthermore, this study showed that universal vaccination in the general 50-59 year old population is cost-effective. Given the very limited data on cost-effectiveness of HZ vaccination in adults age 50-59 years, which has resulted in a lack of recommendation for this population, and recent evidence of IS risk the results of this study demonstrating cost-effectiveness of a targeted HZ vaccination strategy directly support the National Adult Immunization Plan (NAIP) to improve adult immunization uptake by providing economic evaluations which can be used to inform policymakers, payers, and providers.