Cost-effectiveness of Varicella Vaccination Programs: An Update of the Literature

Mark H. Rozenbaum; Albert Jan van Hoek; Stefan Vegter; Maarten J. Postma

Disclosures

Expert Rev Vaccines. 2008;7(6):753-782. 

In This Article

Abstract and Introduction

Abstract

Varicella is one of the most common infectious diseases in childhood, caused by the varicella zoster virus. Although vaccines are available, there are only a few countries with an early-childhood vaccination program. Most countries mainly focus on vaccination of high-risk groups, such as susceptible healthcare workers. One of the main concerns with a routine early-childhood vaccination program is a potential (temporal) increase of the incidence of herpes zoster among elderly adults. In this review, we focus on the cost-effectiveness of varicella vaccination and on the methodology used in the health-economic studies. In particular, we focus on the perspective adopted, type of model used, the modeled effect on herpes zoster, the vaccine efficacy and price, and on the value of time lost by infection. The vast majority of studies show vaccination of high-risk groups - including susceptible adolescents - to be cost saving. Routine early-childhood vaccination programs are always cost saving if indirect costs of production losses are included, or cost effective, as long as the potential negative effects on zoster are not taken into account. We note that most studies included in the review used old vaccine prices and a single dose of the varicella vaccine, whereas multiple doses are now becoming the standard. Despite that, those aspects limit the timeliness of our review and we believe that the current work does provide useful insights in the cost-effectiveness of varicella vaccination.

Introduction

Varicella, or chickenpox, is one of the most common infectious diseases in childhood caused by the varicella zoster virus (VZV). Although a vaccine is available, there are only a few countries with an early-childhood vaccination program, generally because varicella is considered a mild and self-limiting disease in young children. However, the perception of varicella as a mild disease is erroneous and relevant mortality and morbidity risks could contribute to significant burdens of disease. For example, mortality was estimated at 0.030-0.048 per 100,000 person-years in the USA (prior to widespread vaccination), England, Wales and Australia.[1,2,3] In addition, varicella infection can cause serious and costly complications, such as meningitis, encephalitis and bacterial superinfection.[4,5]

Furthermore, varicella inflicts considerable costs to society as parents may take days off to take care of their offspring. For example, in the German situation, the burden of varicella disease was recently monetarized at €188 million for 2003, with 82% of these costs attributed to work loss of parents.[6] For some countries (the USA, Germany and Australia), such figures have been the motivation to start immunizing infants against varicella.

Whereas infants represent the most considered target group for vaccination, other groups have been discussed. In Finland, for example, it is recommended to vaccinate all susceptible adolescents aged 13 years and older to reduce complications of the infection in early adulthood.[7] As the risk for complications increases with the age at which VZV is contracted, such vaccination programs may prevent serious disease, with case- fatality rates in nonelderly adults at 21-57 per 100,000 infections.[2,8] Increasing complication rates by age are also relevant in light of the possible effect that childhood vaccination causes an upward shift in the average age of infection incidence. Thus, it is argued that early-childhood vaccinations prevent noncomplicated young cases with low costs at the expense of older, more complicated cases with higher costs.[9]

After natural infection with varicella, VZV adopts a latent state in the body and can reactivate at later stages due to waning immunity or immunosuppression, causing rash and pain, known as shingles or herpes zoster (HZ). The full dynamics of the VZV cycle in humans - and the interaction with vaccination - is not fully understood. Two contradictory notions are currently voiced in literature[9,10,11]:

 

  • Exposure to wild-type VZV (usually through infectious children) boosts the specific immunity to VZV, which is prevented by vaccination, possibly leading to increased HZ incidence at a later age[12,13,14]

  • Even with a widespread vaccination program, subclinical reactivation of the VZV in unvaccinated cohorts is adequate to boost the immunity of nonvaccinated people to protect against HZ[11,15]

Adoption of either of the two arguments obviously leads to fundamentally different results in cost-effectiveness estimates of infant VZV vaccination.[16]

Herpes zoster is more severe compared with chickenpox, mainly due to the high incidence of the most common complication, known as postherpetic neuralgia (PHN).[17] For example, in the UK, the burden of disease was estimated to be up to €75 million annually for PHN.[18] In addition, the estimated case-fatality rate for HZ was estimated at 36 per 100,000 for individuals over 65 years of age.[8]

A live-attenuated varicella vaccine was developed in Japan in the early 1980s using the OKA strain of the virus.[19] Currently, there are three live-attenuated VZV vaccines available worldwide (Varivax®, Merck & Co. Inc.; Varilrix®, GlaxoSmithKline [GSK], and Oka/Biken, Biken, Osaka, Japan). These vaccines are highly efficacious and have a duration of protection that is probably beyond 10 years.[20,21,22,23,24] The vaccine is safe, although the vaccine does contain an attenuated virus transmission of the virus, and adverse events (including breakthrough and zoster infections) cannot be fully ruled out.[7,25,26,27] However, breakthrough infections are, in general, considered mild in nature[28,29] and severe adverse reactions are rare.[7,25]

The efficacy of a single dose of vaccine in clinical trials was shown to vary from 70 to over 95%, with efficacy decreasing with the age of the vaccinee.[20,21,22,23,24,30] A recent meta-analysis calculated lower effectiveness values in real-world settings, at 72.5% (95% confidence interval: 68.5-76.0%) among children.[31] Effectiveness against moderate-to-severe manifestations of varicella in children may be close to 100%.[26,30]

In summary, the VZV vaccine can be used to prevent infection by means of a widespread vaccination program among infants; however, this may (or may not) lead to an increase in incidence of HZ among elderly adults, due to a decrease in immunity boosting against VZV. Alternatively, the vaccine can be used to prevent older more severe cases by targeting subpopulations. The cost-effectiveness of both strategies will be discussed in detail in this review.

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