Zoster Vaccination: A New Opportunity for Adult Immunization

Abstract

Zostavax (Merck Frosst Canada, Inc) was granted approval for use in Canada in the summer of 2008. However, due to initial production limitations, this vaccine has only become available in September 2009 for the prevention of herpes zoster (shingles) infection in Canadian adults. Zostavax is a live, injectable, attenuated herpes zoster vaccine based on the Oka/Merck strain that is similar to varicella vaccine with the exception that it contains an approximately 14-fold higher dose. The underlying rationale for the vaccine is to boost the normal waning of cell-mediated immunity to varicella zoster virus that occurs with aging to reduce the risk of zoster and associated complications (1). Although a rare cause of death, zoster is an important cause of human disease and suffering among Canadian adults. A number of studies have identified an overall incidence of zoster in adults of approximately four cases per 1000 population per year and a lifetime risk of 20% to 30% (2–4). While zoster may occur at any age, there is a significant increased risk for zoster with advancing age beginning at 50 to 60 years, with a steep rise in incidence thereafter. Acute zoster may occasionally be severe, as with infections involving the eye or central nervous system, or those complicated by secondary bacterial infection. Reported rates of hospital admission in older adults may be as high as 10% (3). However, the most common complication of zoster is postherpetic neuralgia (PHN). PHN is characterized by prolonged (often defined as greater than 90 days) and debilitating neurogenic pain that persists from or follows acute zoster. This complication occurs in approximately one-fifth of adults overall but in one-third or more of octogenarians (5). PHN frequently has a major adverse impact on quality of life and treatments are of limited effectiveness (6–10). Paradoxically, models have projected that the incidence of zoster could rise over time as a result of childhood vaccination against varicella (due to the lack of boosting of immunity in adults through exposure to children with chickenpox) (11), although empirical data to date have failed to document such an effect (12). One large phase III randomized clinical trial, The Shingles Prevention Study, evaluated the efficacy of zoster vaccination (13). In this trial, nearly 40,000 healthy adults aged 60 years or older with a prior history of chickenpox (or residence in the continental United States for greater than 30 years), were randomized to a single subcutaneous injection of either zoster vaccine or placebo (13). Subjects were followed for a mean of 3.1 years and assessed for the primary end point of herpes zoster burden of illness as determined using a previously validated scale for measurement of health-related quality of life (7). Herpes zoster burden of illness scores were significantly reduced in the zoster vaccine group as compared with placebo (2.21 versus 5.68; P<0.001), and both duration and severity of zoster were reduced in vaccine recipients. Overall vaccine efficacy was 51% for confirmed zoster and 67% for PHN; burden of illness scores were also reduced by 61% in vaccinees. Although mild injection site reactions were more common in vaccine recipients, the vaccine was safe and generally well-tolerated. All Canadian adults are currently recommended to have immunity (either by previous natural infection or by vaccination) to tetanus, diphtheria, measles, mumps, rubella, pertussis and varicella (14,15). While rates of immunity in Canadian adults are suboptimal, rates of these diseases are generally low and may reflect, at least in part, high rates of childhood immunization with a degree of resultant herd immunity. In addition to these routine vaccines, some vaccines are recommended in a subset of adults. Influenza vaccination is widely recommended for adults but a particular focus is in those with conditions associated with increased risk for complications (16). Pneumococcal polysaccharide vaccine is recommended for adults older than 65 years of age and those with health conditions associated with an increased risk of severe pneumococcal disease (17). There are also a number of travel-recommended vaccines, and more recently the use of human papilloma virus vaccine has been recommended for certain adults (18).