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Articles  |   October 2011
Time for Changes in Pneumococcal Vaccination of Adults?
Author Notes
  •    Melissa C. Overman, DO, MPH, is the medical director with the South Carolina Department of Health and Environmental Control, Public Health Region 2, in Greenville.
     
  • Address correspondence to Melissa C. Overman, DO, South Carolina Department of Health and Environmental Control, 200 University Ridge, Greenville, SC 29601-3635. E-mail: mcoverman.do.mph@gmail.com  
Article Information
Preventive Medicine
Articles   |   October 2011
Time for Changes in Pneumococcal Vaccination of Adults?
The Journal of the American Osteopathic Association, October 2011, Vol. 111, S19-S22. doi:
The Journal of the American Osteopathic Association, October 2011, Vol. 111, S19-S22. doi:
Abstract

Because Streptococcus pneumoniae continues to be an important cause of morbidity and mortality, especially among young children and elderly adults, Healthy People 2020 includes several objectives for decreasing invasive pneumococcal disease and increasing pneumococcal vaccine uptake. Current recommendations of the Advisory Committee on Immunization Practices regarding pneumococcal vaccination for adults have not changed appreciatively in several years. However, it is possible that ongoing research may lead to changes in these recommendations within the next few years. Since the licensure of the 7-valent pneumococcal conjugate vaccine for children in 2000, impressive decreases in pneumonia-related diseases caused by strains in the vaccine have been noted among all age groups receiving vaccination. Coupled with continued concerns about the efficacy of the 23-valent pneumococcal polysaccharide vaccine for adults, particularly in regard to nonbacteremic pneumonia, questions are raised about the potential efficacy and viability of conjugate vaccines for adults.

Since 2000, an impressive amount of research has been dedicated to understanding the changing epidemiologic characteristics of pneumococcal infections, to analyzing the efficacy of both the polysaccharide and conjugate pneumococcal vaccines in terms of disease prevention in all age groups, and to evaluating methods of increasing adult immunization uptake. Substantial impacts of vaccination on rates of invasive pneumococcal disease (IPD) have been documented,1,2 fostering conversation about the efficacy and viability of a conjugate vaccine program for adults. In the present article, I investigate these aspects of pneumococcal vaccination. 
Epidemiologic Characteristics
Streptococcus pneumoniae is a gram-positive bacterium responsible for a variety of disease processes, most commonly bacteremia, pneumonia, and meningitis. The incidence of pneumococcal bacteremia in the United States is more than 50,000 cases annually, with an overall case fatality rate ranging from 20% (in young adults) to 60% (in the elderly population).3 Pneumococcal pneumonia causes as many as 175,000 hospitalizations in the United States annually, with a case fatality rate of 5% to 7% in young adults (and higher in older adults).3 Pneumococcal meningitis represents approximately 13% to 19% of all cases of bacterial meningitis in the United States, or approximately 3000 to 6000 cases annually.3 The case fatality rate of pneumococcal meningitis may be as high as 80% in the elderly population.3 
Invasive pneumococcal disease—defined as bacteremia, meningitis, or infection of other normally sterile sites—is an annually monitored indicator for S pneumoniae infection.4 In 2009, the overall case rate of IPD in the United States was 14.3 per 100,000, with the highest case rates noted in 2 age groups—individuals younger than 1 year and those aged 65 years or older.4 In these groups, the case rates in 2009 were 37.1 per 100,000 and 38.7 per 100,000, respectively. The death rate from IPD was also highest in those aged 65 years or older, at 6.56 per 100,000 persons.4 
While case rates and death rates secondary to S pneumoniae infection continue to be important causes of morbidity and mortality, the overall incidence rate of IPD across all ages decreased by 45% between 1998 (when the preconjugate vaccine was used) and 2007.1,2 The reductions in disease burden and deaths have been attributed to the development of new pneumococcal vaccines and to the implementation of vaccination programs.1,2,5,6 
Healthy People 2020—a collaborative program involving the US Department of Health and Human Services and other federal agencies—acknowledges the ongoing concern over IPD-related morbidity and mortality, particularly among young children and elderly adults.7 Their objectives include reducing invasive pneumococcal infections among children younger than 5 years and adults aged 65 years or older and increasing the percentage of adults who are vaccinated against pneumococcal disease (Figure 1).7 
Figure 1.
The Healthy People 2020 immunization and infectious disease (IID) objectives for reducing invasive pneumococcal infections among children and adults and for increasing the percentage of adults who are vaccinated against pneumococcal disease.7
Figure 1.
The Healthy People 2020 immunization and infectious disease (IID) objectives for reducing invasive pneumococcal infections among children and adults and for increasing the percentage of adults who are vaccinated against pneumococcal disease.7
Polysaccharide Vaccine
The 23-valent pneumococcal polysaccharide vaccine (PPV23) was licensed in 1983, replacing the 14-valent vaccine that had been licensed since 1977.3 These vaccines were originally licensed for adults aged 65 years or older, as well as adults aged 19 to 64 years with underlying medical conditions that increase the risk for pneumococcal disease. In 2008, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention added 2 indications for pneumococcal vaccination for adults aged 19 to 64 years: asthma and cigarette smoking.3 
Current recommendations for PPV23 support the Healthy People 2020 objectives. All individuals aged 65 years or older should receive a single dose of PPV23.1 The only recommendation for revaccination in adults is if the PPV23 dose was administered before age 65 and if 1 of the following conditions applies: (1) it has been more than 5 years since the first dose or (2) the patient has an immunocompromising condition (eg, congenital or acquired immunodeficiency, abnormal innate immune response, human immunodeficiency virus [HIV] infection, or functional or anatomic asplenia).1 Although no recommendation indicates ongoing revaccination for S pneumoniae, vaccination with PPV23 should not be skipped in any adult who has missing or incomplete vaccination records.1 
In 1991, Shapiro et al8 concluded that PPV23 was effective in preventing IPD among immunocompetent individuals, and that the vaccine should continue to be administered among those with appropriate indications. Subsequently, multiple studies have investigated the efficacy and effectiveness of PPV23. These studies have reported some conflicting results, particularly in regard to protection against nonbacteremic pneumococcal pneumonia in elderly patients.1,9 Also of note is the observation that vaccine efficacy decreases in elderly individuals with advancing age and in those with concomitant medical conditions. This decreased efficacy is of concern because the same populations are at increased risk for pneumococcal disease.10 
Antibody response to PPV23 appears to be transitory in older persons. Adults younger than 50 years demonstrated sufficient antibodies to the vaccine for more than 5 years, but antibody amounts declined with increasing age starting at age 65 years, to the extent that no demonstrable effect was noted more than 3 years after vaccination.8,10 To further muddy the waters, the level of antibody that is protective against pneumococcal disease is unknown.8,10 
The 23-valent pneumococcal polysaccharide vaccine continues to be a reliable and safe vaccine for adults, providing protection against IPD and related pneumococcal diseases.1 However, is there a better option for physicians to offer their adult patients who are at increased risk for IPD? 
Conjugate Vaccine
In 2000, the first pediatric pneumococcal vaccine—the 7-valent pneumococcal conjugate vaccine (PCV7)—was licensed for prevention of pneumococcal disease in children younger than 5 years.11 This population, like the elderly population, is at increased risk of IPD and poor outcomes. Uptake of PCV7 by the pediatric population was found to be rapid, and multiple direct and indirect impacts of the vaccine were noted in subsequent research.11 
The rate of IPD among all age groups declined from 24.3 cases per 100,000 individuals in 1998 and 1999 (before PCV7) to 17.3 per 100,000 individuals in 2001 (after PCV7).10 The greatest decline in the rate of pneumococcal disease (69%) was observed among children younger than 2 years.12 Pneumococcal disease rates for adults also declined between 1998 and 2001—by 32% in those aged 20 to 39 years, by 8% in those aged 40 to 64 years, and by 18% in those aged 65 years or older.12 In addition, the rate of penicillin-resistant disease decreased 35% during this period.12 
Comparisons of the causative strains of IPD in several studies demonstrated improved protective coverage and prevention for the strains included in PCV7 as opposed to PPV23.13,14 A comparison of the S pneumoniae strain composition of currently licensed vaccines (ie, PPV23, PCV7, 13-valent pneumococcal conjugate vaccine [PCV13]) is shown in Figure 2.15 Studies have also noted an increase in the incidence of IPD secondary to pneumococcal strains that were not included in the licensed vaccines.13,14 These strains, termed replacement strains, were 19A, 6C, and 22F.13,14 Of particular note was the increase in disease secondary to 19A isolates, a strain that was subsequently included in PPV23 and is known for multidrug resistance in both South Africa and the United States.13,16 To put this increase of replacement-strain disease in perspective, the increase in disease resulting from strains not in vaccines is not comparable to the decrease in overall disease secondary to the introduction of conjugate vaccine.5 
Figure 2.
Comparison of Streptococcus pneumoniae strain composition of currently licensed vaccines: 7-valent pneumococcal conjugate vaccine (PCV7), 13-valent pneumococcal conjugate vaccine (PCV13), and 23-valent pneumococcal polysaccharide vaccine (PPV23). An “X” indicates presence of that strain in the vaccine, and a blank space indicates absence of the strain.13,15,17
Figure 2.
Comparison of Streptococcus pneumoniae strain composition of currently licensed vaccines: 7-valent pneumococcal conjugate vaccine (PCV7), 13-valent pneumococcal conjugate vaccine (PCV13), and 23-valent pneumococcal polysaccharide vaccine (PPV23). An “X” indicates presence of that strain in the vaccine, and a blank space indicates absence of the strain.13,15,17
The rate of antibiotic-resistant IPD caused by vaccine-specific serotypes decreased in both children and older adults after PCV7 administration.12,16 This result demonstrates a break in the transmission of bacteria from children to adults, likely caused by decreased nasopharyngeal carriage that provides “herd immunity.”12,14,16 
In 2010, PCV13 was licensed for prevention of IPD and otitis media in children aged 6 weeks to 71 months (Figure 2).17 Based on multiple studies demonstrating the direct and indirect effects of PCV7 in both children and adults, research has shifted toward the utilization of the PCV vaccines in the adult population.9,18 The Community Acquired Pneumonia Immunization Trial in Adults (CAPITA)9 in Norway is a randomized, placebo-controlled trial that is expected to publish results within the next few years. The primary objective of CAPITA9 is to determine the effectiveness of a single dose of PCV13 in preventing community-acquired pneumonia in vaccinenaïve adults. Studies have observed that a previous dose of PPV23 severely inhibits the immune response to subsequent conjugate vaccine.10,19 This observation will have to be considered if the ACIP recommendations are changed to include the conjugate vaccine for adults. 
A trial of PCV7 in adults infected with HIV noted a 74% vaccine efficacy for vaccine-specific and 6A serotypes—even in patients with low CD4+ counts.20 This finding raises additional questions of immune response to the conjugate vaccine with potential impact on vaccine development.20 Musher et al21 reported that individuals who have a genetic basis for nonresponse to PPV may respond with IgG development after vaccination with PCV. These studies demonstrate great potential for vaccine prevention of IPD and other conditions related to S pneumoniae infection in adults. 
Issues With Adult Vaccine Uptake
Regardless of the ACIP adult immunization recommendations for S pneumoniae infection in adults, there remains the long-standing issue of how to engage both physicians and the general public in vaccination programs. Participating in vaccination programs can be expensive, and many insurance plans have poor coverage for preventive services, particularly adult immunizations.22 Physicians sporadically see recommendations for adult vaccinations as part of continuing medical education or professional conferences.22 In clinical settings, extended periods may pass before physicians see a case of IPD or community-acquired pneumonia caused by S pneumoniae. As a result, clinical suspicion wavers, as does the perceived need to protect patients from potential risk.22 
Clinical practices are typically busy taking care of mandated patient loads, which prevents vaccinations from being at the top of the list of issues to address with patients. Nevertheless, immunizations are an excellent example of primary prevention and provide substantial benefits in reduction of disease burden and healthcare costs. 
Many adults, even those who are opposed to immunizations, may agree to be vaccinated if their physicians or other healthcare providers offer the vaccines to them.22 Simplifying the screening and administration process for pneumococcal vaccination by changing the vaccine schedule (eg, PCV13 for all adults aged 50 years or older) or implementing standing orders for nurses to administer vaccinations may help facilitate vaccine use among providers.22 Improved vaccine coverage of patients in hospitals and nursing homes who have had recent episodes of IPD or community-acquired pneumonia would assist in decreasing repeat infections.3 
Many options and opportunities exist to improve uptake of pneumococcal vaccine by adults, but efforts must be tailored to fit the particular practice so as not to increase the burden on the practice. 
Conclusion
Several authors have noted that cost-benefit ratio may inhibit the availability of a pneumococcal conjugate vaccine for high-risk individuals worldwide, with 1 writer commenting that it is “premature to state whether a comprehensive immunization strategy may be based on a larger number of conjugates, combinations of polysaccharide conjugates and proteins, proteins alone, or a whole cell vaccine approach.”14 Currently, as a result of advances in vaccine development and coverage, the epidemiologic characteristics of IPD are changing, and the incidence of this disease is decreasing. Opportunities exist for continued improvement in both vaccine efficacy and uptake. 
   Financial Disclosures: None reported.
 
References
Centers for Disease Control and Prevention, Advisory Committee on Immunization Practices. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). MMWR Morb Mortal Wkly Rep. 2010;59(34):1102-1106. [PubMed]
Pilishvili T, Lexau C, Farley MM, et al.  Active Bacterial Core Surveillance/Emerging Infections Program Network. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 2010;201(1):32-41. [CrossRef] [PubMed]
Centers for Disease Control and Prevention, Atkinson W, Wolfe S, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Washington, DC: Public Health Foundation; 2011.
Active bacterial core surveillance report, Emerging Infections Program Network, Streptococcus pneumonia, 2009. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/abcs/reports-findings/survreports/spneu09.pdf. Accessed September 19, 2011.
Hicks LA, Harrison LH, Flannery Bet al. Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004. J Infect Dis. 2007;196(9):1346-1354. [CrossRef] [PubMed]
Centers for Disease Control and Prevention. Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease—United States, 1998-2003. MMWR Morb Mortal Wkly Rep. 2005;54(36):893-897. [PubMed]
Immunization and infectious diseases. Healthy People 2020 Web site. http://www.healthy-people.gov/2020/topicsobjectives2020/objectiveslist.aspx?topicId=23. Accessed September 19, 2011.
Shapiro ED, Berg AT, Austrian Ret al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med. 1991;325(21):1453-1460. [CrossRef] [PubMed]
Hak E, Grobbee DE, Sanders EAet al. Rationale and design of CAPITA: a RCT of 13-valent conjugated pneumococcal vaccine efficacy among older adults. Neth J Med. 2008;66(9):378-383. [PubMed]
Musher DM, Sampath R, Rodriguez-Barradas MC. The potential role for protein-conjugate pneumococcal vaccine in adults: what is the supporting evidence? Clin Infect Dis. 2011;52(5):633-640. [CrossRef] [PubMed]
Advisory Committee on Immunization Practices. Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2000;49(RR-9):1-35.
Whitney CG, Farley MM, Hadler J, et al.  Active Bacterial Core Surveillance of the Emerging Infections Program Network. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003;348(18):1737-1746. [CrossRef] [PubMed]
Jacobs MR, Good CE, Bajaksouzian S, Windau AR. Emergence of Streptococcus pneumonia serotypes 19A, 6C, and 22F and serogroup 15 in Cleveland, Ohio, in relation to introduction of the protein-conjugated pneumococcal vaccine. Clin Infect Dis. 2008;47(11):1388-1395. [CrossRef] [PubMed]
Moffitt KL, Malley R. Next generation pneumococcal vaccines [published online ahead of print April 21, 2011]. Curr Opin Immunol. 2011;23(3):407-413. [CrossRef] [PubMed]
Nuorti JP, Whitney CG, Centers for Disease Control and Prevention. Prevention of pneumococcal disease among infants and children—use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine-recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2010;59(RR-11):1-18. [PubMed]
Kyah MH, Lynfield R, Schaffner W, et al.  Active Bacterial Core Surveillance of the Emerging Infections Program Network. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumonia [published correction appears in N Engl J Med. 2006;355(6):638]. N Engl J Med. 2006;354(14):1455-1463. [CrossRef] [PubMed]
Centers for Disease Control and Prevention. Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children—Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. 2010;59(09):258-261. [PubMed]
Scott DA, Komjathy SF, Hu BTet al. Phase 1 trial of a 13-valent pneumococcal conjugate vaccine in healthy adults. Vaccine. 2007;25(33):6164-6166. [CrossRef] [PubMed]
O'Brien KL, Hochman M, Goldblatt D. Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue? Lancet Infect Dis. 2007;7(9):597-606. [CrossRef] [PubMed]
French N, Gordon SB, Mwalukomo Tet al. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J. Med. 2010;362(9):812-822. [CrossRef] [PubMed]
Musher DM, Groover JE, Watson DA, Rodriguez-Barradas MC, Baughn RE. IgG responses to protein-conjugated pneumococcal capsular polysaccharides in persons who are genetically incapable of responding to unconjugated polysaccharides. Clin Infect Dis. 1998;27(6):1487-1490. [CrossRef] [PubMed]
Whitney CG, Schaffner W, Butler JC. Rethinking recommendations for use of pneumococcal vaccines in adults [published online ahead of print July 30, 2001]. Clin Infect Dis. 2001;33(5):662-675. [CrossRef] [PubMed]
Figure 1.
The Healthy People 2020 immunization and infectious disease (IID) objectives for reducing invasive pneumococcal infections among children and adults and for increasing the percentage of adults who are vaccinated against pneumococcal disease.7
Figure 1.
The Healthy People 2020 immunization and infectious disease (IID) objectives for reducing invasive pneumococcal infections among children and adults and for increasing the percentage of adults who are vaccinated against pneumococcal disease.7
Figure 2.
Comparison of Streptococcus pneumoniae strain composition of currently licensed vaccines: 7-valent pneumococcal conjugate vaccine (PCV7), 13-valent pneumococcal conjugate vaccine (PCV13), and 23-valent pneumococcal polysaccharide vaccine (PPV23). An “X” indicates presence of that strain in the vaccine, and a blank space indicates absence of the strain.13,15,17
Figure 2.
Comparison of Streptococcus pneumoniae strain composition of currently licensed vaccines: 7-valent pneumococcal conjugate vaccine (PCV7), 13-valent pneumococcal conjugate vaccine (PCV13), and 23-valent pneumococcal polysaccharide vaccine (PPV23). An “X” indicates presence of that strain in the vaccine, and a blank space indicates absence of the strain.13,15,17