Revaccination of High-Risk Adults With Pneumococcal Polysaccharide Vaccine

Pneumococcal disease accounts for approximately 500,000 cases of pneumonia, 50,000 cases of bacteremia, and 40,000 deaths each year.¹ Vaccination of adults with the pneumococcal polysaccharide vaccine has not been convincingly demonstrated to reduce the risk for pneumonia among groups currently targeted for vaccination² but is associated with substantial reductions in invasive disease.¹ Among the elderly, vaccination is not only cost-effective but cost saving for the prevention of bacteremia.³ Few other diagnostic or therapeutic interventions can make such a claim.

Initial vaccination induces a serotype-specific antibody response that is not associated with significant T-cell activation or immune memory. Antibody levels may decline over 5 to 10 years to prevaccination levels among immunocompromised persons and the elderly, which suggests that protection may wane over time.¹ In a large case-control study, Shapiro et al⁴ found decreasing estimates of protection with increasing intervals after vaccination among the elderly. Following revaccination, antibody levels increase, although the magnitude of the increase may be less than after initial vaccination.¹ Taken together, these data suggest that revaccination may improve protection for certain groups. The Advisory Committee on Immunization Practices recommends revaccination 5 or more years after initial vaccination for adults who are younger than 65 years and are immunocompromised or asplenic, and for those who are 65 years or older and were younger than 65 years when first vaccinated.¹

With increasing pneumonia death rates among the elderly⁵ and the emergence of drug-resistant Streptococcus pneumoniae,^{6 - 7} there is a heightened sense of urgency to both treat and prevent pneumococcal disease. Despite long-standing recommendations for immunizing high-risk individuals, less than 50% of targeted adults have received even 1 dose of pneumococcal vaccine.^{8 - 9}

Concerns about adverse effects remain a barrier to successful vaccination efforts. After initial vaccination, up to one half of recipients will experience mild, local reactions that usually persist less than 48 hours.¹ Severe local reactions are rare. In a recent meta-analysis of trials assessing pneumococcal vaccine effectiveness, information on vaccine adverse effects was summarized for 3 trials that included 7531 vaccinated and 7661 control subjects.² There were no reports of severe febrile reactions or anaphylactic reactions in these studies. Early studies of revaccination with pneumococcal vaccine suggested that local reactions in adults were more severe than with initial vaccination if revaccination occurred within 13 months of the initial vaccination.¹⁰ Subsequent studies using longer intervals between vaccination suggested that revaccination after 4 or more years was associated with rates of local reactions that were similar to those after initial vaccination.^{10 - 13} However, several of these studies lacked sufficient statistical power or adequate comparison groups and most used the 14-valent vaccine, which was used in the United States from 1977 until the 23-valent vaccine was licensed in 1983. Thus, questions remain regarding the risks associated with revaccination.

The study by Jackson et al¹⁴ in this issue of THE JOURNAL provides welcome new information regarding the frequency of adverse effects following pneumococcal revaccination. This large, quasi-experimental study compared the rates of local and systemic reactions following initial (901 subjects) and repeat (514 subjects) vaccination in high-risk adults aged 50 to 74 years. In contrast to previous reports, in this study, subjects who received repeat vaccinations 5 or more years after their first vaccination were more likely to experience sizable local reactions than first-time vaccine recipients (11% vs 3%). However, most of these participants experienced only mild to moderate limitations in the use of the arm in which the injection was made and only for a short time. The risk for sizable local reactions was associated with higher prevaccination antibody titers, suggesting that these reactions represented localized, Arthus-type reactions. The rates of systemic symptoms, including fever, were low and did not differ between the study groups. However, this study could not determine whether the rates of systemic symptoms for either group were higher than background rates that might be observed in an unvaccinated control group. No serious or unexpected adverse events associated with vaccination occurred.

The study by Jackson et al¹⁴ confirms the safety and tolerability of pneumococcal revaccination of adults. While sizable local reactions were more frequent following revaccination, they were uncommon and not serious. The risk of a local reaction does not represent a contraindication to revaccination. This information should help practitioners and patients as they consider the risks and benefits of pneumococcal vaccination. Ultimately, these findings will be fully applied only when they are incorporated into organized programs to promote vaccine delivery. Knowledge of the facts must be translated into effective clinical practice strategies to achieve and sustain high vaccination rates.¹⁵ When this happens, true progress will have been made against this serious vaccine-preventable disease.