Commentary Commentary
Human Vaccines & Immunotherapeutics 10:5, 1334–1336; May 2014; © 2014 Landes Bioscience
Pneumococcal conjugate vaccines for adults Daniel M Weinberger1 and Eugene D Shapiro1,2 Department of Epidemiology of Microbial Diseases; Yale School of Public Health; New Haven, CT USA; 2Department of Pediatrics; Yale University School of Medicine and Department of Investigative Medicine; Yale Graduate School of Arts and Sciences; New Haven, CT USA
1
Keywords: pneumococcus, vaccines, conjugate vaccines, pneumonia, prevention Correspondence to: Eugene D Shapiro; Email: [email protected] Submitted: 04/11/2014 Accepted: 04/22/2014
Pneumococcal polysaccharide vaccines have been recommended for routine use in adults in the US since 1977. The currently approved polysaccharide vaccine (PPV23) contains antigens from 23 of the more than 90 different serotypes of pneumococci. There are conflicting data on its efficacy against invasive infections, but its efficacy against non-bacteremic pneumonia, the most common manifestation of pneumococcal disease in adults, is poor.1–3 Moreover, efficacy of PPV23 declines markedly in persons over the age of 75,2 so older adults, who have both the highest incidence of and the most severe morbidity and mortality from pneumococcal infections, receive the smallest benefit. Therefore, a vaccine that is effective against non-bacteremic pneumonia and is also efficacious in the elderly would be an important advance. Conjugate vaccines might fill this role. Compared with PPV23, the 13-valent pneumococcal conjugate vaccine (PCV13) has superior immunogenicity against some serotypes.3 PCV13 has been approved by the FDA for use in adults. However, the Advisory Committee on Immunization Practices has not yet recommended that PCV13 replace PPV23 for routine use in adults, in part because the incremental benefit of recommending the more expensive PCV13 is unclear. Establishing the efficacy of PCV13 against pneumonia in adults and determining its efficacy in different age and risk groups would help policy makers formulate sound recommendations for use of PCV13.
Published Online: 04/24/2014 http://dx.doi.org/10.4161/hv.28962
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Human Vaccines & Immunotherapeutics
CAPiTA: A Randomized Controlled Trial of PCV13 in Adults To address the question of the efficacy of PCV13 against communityacquired pneumonia (CAP), CAPiTA (Community-Acquired Pneumonia immunization Trial in Adults), a placebo-controlled randomized clinical trial with nearly 85 000 subjects was conducted among persons ≥65 y of age in Holland. The preliminary results from this study were presented at the International Symposium on Pneumococci and Pneumococcal Diseases 9 in Hyderabad, India.4 Outcomes for which the vaccine’s efficacy was reported included CAP due to serotypes in PCV13 (both non-bacteremic CAP and CAP associated with invasive infections) and invasive pneumococcal infections due to vaccine serotypes. The study excluded residents of nursing homes/long-term care facilities, those with immune deficiencies, and those who had previously received a pneumococcal vaccine, among others.4
Some Encouraging Preliminary Results from CAPiTA Preliminary results of the study suggest that PCV13 is efficacious against both invasive pneumococcal infections caused by PCV13 serotypes (75% efficacy) and non-bacteremic pneumonia caused by PCV13 serotypes (45% efficacy).4 Given the large burden of nonbacteremic pneumonia among adults and the poor efficacy of PPV23 against non-bacteremic
Volume 10 Issue 5
©2014 Landes Bioscience. Do not distribute.
Reasons for optimism and for caution
But with Important Caveats The potential benefit of vaccinating adults with PCV13 will depend, in part, on the proportion of CAP in adults that is due to PCV13 serotypes; if these serotypes cause a small fraction of disease, the marginal benefit of vaccinating adults will be small. Because children are a major source of exposure to pneumococci for adults,7 the use of conjugate vaccines (which affect colonization as well as disease) in children has a large impact on the incidence of pneumococcal infections in adults.8 Following introduction of PCV7 for children in the United States, the 7 vaccine serotypes soon were nearly eliminated as a cause of invasive infections among both adults and children.8-10 If vaccination of children with PCV13 has a similar impact on infections in adults, the additional fraction of infections preventable by direct immunization of adults could be small.11 Given the large impact of vaccination of children on the incidence of infections in adults, additional information from the CAPiTA trial is needed before the potential impact of immunizing adults with PCV13 can be fully assessed. In the trial, PCV13 was efficacious against CAP caused by vaccine serotypes.4 The CAPiTA study was conducted when PCV7 and then PCV10 (starting in March 2011) were in widespread use among Dutch children. Therefore, to assess the potential impact of the vaccine using data from the CAPiTA trial, it will be critical to compare rates of all-cause pneumonia between the recipients of PCV13 and the controls and to
www.landesbioscience.com
determine whether there were changes after PCV10 was introduced. The CAPiTA trial assessed the efficacy of PCV13 compared with a placebo control, but did not assess its efficacy relative to the currently available PPV23. While PPV23 has limited efficacy against pneumonia, it does contain 10 additional serotypes not included in PCV13, potentially providing broader protection at a lower cost. As the proportion of disease due to serotypes not in PCV13 increases, the relative benefit of PPV23 also might increase. To determine the best vaccine to use in a particular setting, additional costeffectiveness analyses are needed. These analyses should account for the effectiveness of PCV13 and of PPV23 in adults, patterns of serotype replacement, and the indirect impact of vaccination of children on rates of disease in adults. The CAPiTA results will help to improve the accuracy of currently-available models.12 The CAPiTA trial excluded some individuals who are at a particularly high risk of disease (those with immunodeficiencies and nursing home residents). In addition, results of how age affected efficacy have not yet been reported. Because the risk of pneumococcal disease increases with age and with these underlying conditions, results from efficacy trials might overestimate the potential impact of the vaccine on populations in a real-world setting. Although the CAPiTA trial might not be sufficiently powered to enable detailed subgroup analyses, estimation of the vaccine’s efficacy in some subgroups might help in the formulation of recommendations. Finally, although the urinary antigen assay used to diagnose non-bacteremic pneumococcal pneumonia in the trial has been validated,13 to our knowledge this assay has not been validated in vaccinated individuals. It is possible that vaccineinduced antibodies could prevent polysaccharide antigens from reaching the urine in patients with non-bacteremic CAP. This could lead to misclassification of cases and could potentially lead to inflated estimates of the vaccine’s efficacy. Further validation of the cutoff values for the assay
in vaccinated individuals could help to clarify this issue.
Impact of Results of the CAPiTA Trial The currently-available results might aid decision-making about the use of PCV13 in adults in some settings. In particular, in countries in which PCVs are not widely used in children, many adults will still be exposed to the vaccine serotypes and could benefit from the protection provided by PCV13. In settings in which uptake of PCV is high, additional information will be required from the CAPiTA trial and from other studies before informed decisions can be made about the use of PCV13 in adults. In particular, estimates of the efficacy of PCV against all-cause pneumonia will be particularly informative, since the incremental benefit of the vaccine likely will be driven by its effect on this outcome. Likewise, secondary analyses of the effects of age and of underlying medical conditions on the efficacy of the vaccine could help to determine its potential impact in various target groups. Finally, information about the serotypes that are causing pneumococcal pneumonia in adults in the post-PCV13 era will help to determine its potential impact on disease and on the cost-effectiveness of immunization programs for adults.
Need for Alternative Vaccines The CAPiTA study has demonstrated that conjugate vaccines can prevent pneumococcal pneumonia in adults. However, when children are vaccinated against pneumococcus, the transmission of nonvaccine serotypes increases (serotype replacement).14 These replacing serotypes can then become important causes of disease in adults. As a result, there should be renewed efforts to develop adult-specific conjugate vaccines that include different serotypes than those included in vaccines administered to children. Such vaccines
Human Vaccines & Immunotherapeutics 1335
©2014 Landes Bioscience. Do not distribute.
pneumonia, this could be an important finding. In addition, results suggest that PCV13 protects against infections caused by serotype 3 in adults. Early results from other studies suggest that immunization of children with PCV13 might not affect rates of infections caused by serotype 3 in adults.5,6 Therefore, immunization of adults with PCV13 might provide a mechanism for preventing disease caused by serotype 3 in adults.
Conclusions The preliminary results from the CAPiTA trial provide evidence that conjugate vaccines can effectively prevent pneumococcal pneumonia in adults. Whether this means that PCV13 should replace PPV23 as the preferred vaccine against pneumococcal infections in adults remains uncertain. Additional questions about the potential impact of direct immunization of adults on the risk of pneumococcal infections in populations that already have robust vaccination programs for children remain to be answered. Disclosure of Potential Conflicts of Interest
D.M.W. has received consulting fees from Merck (the manufacturer of PPV23) and receives salary support from an investigator-initiated research grant from Pfizer (the manufacturer of PCV13) to Yale University. E.D.S. has nothing to disclose. Acknowledgments
This publication was made possible, in part, by support from CTSA Grants Number UL1 TR000142 and KL2 TR000140 from the National
1336
Center for Research Resources (NCRR) and the National Center for Advancing Translational Science (NCATS), components of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. References 1. Jackson LA, Neuzil KM, Yu O, Benson P, Barlow WE, Adams AL, Hanson CA, Mahoney LD, Shay DK, Thompson WW; Vaccine Safety Datalink. Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med 2003; 348:174755; PMID:12724480; http://dx.doi.org/10.1056/ NEJMoa022678 2. Shapiro ED, Berg AT, Austrian R, Schroeder D, Parcells V, Margolis A, Adair RK, Clemens JD. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991; 325:145360; PMID:1944423; http://dx.doi.org/10.1056/ NEJM199111213252101 3. Scott DA, Komjathy SF, Hu BT, Baker S, Supan LA, Monahan CA, Gruber W, Siber GR, Lockhart SP. Phase 1 trial of a 13-valent pneumococcal conjugate vaccine in healthy adults. Vaccine 2007; 25:61646; PMID:17629361; http://dx.doi.org/10.1016/j. vaccine.2007.06.004 4. Bonten M, Bolkenbaas M, Huijts S, Webber C, Gault S, Gruber W, et al. Community-acquired pneumonia immunization trial in aduilta-CAPiTA. International Symposium on Pneumococci and Pneumococccal Diseases 9. Hyderabad, India, 2014. 5. Steens A, Bergsaker MAR, Aaberge IS, Rønning K, Vestrheim DF. Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway. Vaccine 2013; 31:62328; PMID:24176490; http://dx.doi.org/10.1016/j. vaccine.2013.10.032 6. Lee GM, Kleinman K, Pelton SI, Hanage W, Huang SS, Lakoma M, Dutta-Linn M, Croucher NJ, Stevenson A, Finkelstein JA. Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts. J Pediatric Infect Dis Soc 2014; 3:23-32; PMID:24567842; http://dx.doi. org/10.1093/jpids/pit057
Human Vaccines & Immunotherapeutics
7. Walter ND, Taylor TH Jr., Dowell SF, Mathis S, Moore MR; Active Bacterial Core Surveillance System Team. Holiday spikes in pneumococcal disease among older adults. N Engl J Med 2009; 361:2584-5; PMID:20032333; http://dx.doi. org/10.1056/NEJMc0904844 8. Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, Reingold A, Thomas A, Schaffner W, Craig AS, 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; 201:32-41; PMID:19947881; http://dx.doi. org/10.1086/648593 9. Halasa NB, Grijalva CG, Arbogast PG, Talbot TR, Craig AS, Griffin MR, Schaffner W. Nearly complete elimination of the 7-valent pneumococcal conjugate vaccine serotypes in Tennessee. Pediatr Infect Dis J 2013; 32:604-9; PMID:23348816; http://dx.doi. org/10.1097/INF.0b013e318287fe0d 10. Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA, Cherian T, Levine OS, Whitney CG, O’Brien KL, Moore MR; Serotype Replacement Study Group. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med 2013; 10:e1001517; PMID:24086113; http://dx.doi.org/10.1371/journal. pmed.1001517 11. Fedson DS. Pneumococcal conjugate vaccination for older adults: Reply letter to Hollingsworth et al. Hum Vaccin Immunother 2013; 10:24-8; PMID:24030320 12. Smith KJ, Wateska AR, Nowalk MP, Raymund M, Nuorti JP, Zimmerman RK. Cost-effectiveness of adult vaccination strategies using pneumococcal conjugate vaccine compared with pneumococcal polysaccharide vaccine. JAMA 2012; 307:804-12; PMID:22357831; http://dx.doi. org/10.1001/jama.2012.169 13. Pride MW, Huijts SM, Wu K, Souza V, Passador S, Tinder C, Song E, Elfassy A, McNeil L, Menton R, et al. Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotypespecific polysaccharides in human urine. Clin Vaccine Immunol 2012; 19:1131-41; PMID:22675155; http://dx.doi.org/10.1128/CVI.00064-12 14. Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet 2011; 378:1962-73; PMID:21492929; http://dx.doi.org/10.1016/S0140-6736(10)62225-8
Volume 10 Issue 5
©2014 Landes Bioscience. Do not distribute.
would protect adults against the serotypes causing the largest fraction of residual disease. Because adults are not a significant reservoir for transmission of pneumococci, such an adult-centered strategy likely would minimize further serotype replacement while providing maximum protection against the dominant serotypes.
Human Vaccines & Immunotherapeutics 10:5, 1334–1336; May 2014; © 2014 Landes Bioscience
Pneumococcal conjugate vaccines for adults Daniel M Weinberger1 and Eugene D Shapiro1,2 Department of Epidemiology of Microbial Diseases; Yale School of Public Health; New Haven, CT USA; 2Department of Pediatrics; Yale University School of Medicine and Department of Investigative Medicine; Yale Graduate School of Arts and Sciences; New Haven, CT USA
1
Keywords: pneumococcus, vaccines, conjugate vaccines, pneumonia, prevention Correspondence to: Eugene D Shapiro; Email: [email protected] Submitted: 04/11/2014 Accepted: 04/22/2014
Pneumococcal polysaccharide vaccines have been recommended for routine use in adults in the US since 1977. The currently approved polysaccharide vaccine (PPV23) contains antigens from 23 of the more than 90 different serotypes of pneumococci. There are conflicting data on its efficacy against invasive infections, but its efficacy against non-bacteremic pneumonia, the most common manifestation of pneumococcal disease in adults, is poor.1–3 Moreover, efficacy of PPV23 declines markedly in persons over the age of 75,2 so older adults, who have both the highest incidence of and the most severe morbidity and mortality from pneumococcal infections, receive the smallest benefit. Therefore, a vaccine that is effective against non-bacteremic pneumonia and is also efficacious in the elderly would be an important advance. Conjugate vaccines might fill this role. Compared with PPV23, the 13-valent pneumococcal conjugate vaccine (PCV13) has superior immunogenicity against some serotypes.3 PCV13 has been approved by the FDA for use in adults. However, the Advisory Committee on Immunization Practices has not yet recommended that PCV13 replace PPV23 for routine use in adults, in part because the incremental benefit of recommending the more expensive PCV13 is unclear. Establishing the efficacy of PCV13 against pneumonia in adults and determining its efficacy in different age and risk groups would help policy makers formulate sound recommendations for use of PCV13.
Published Online: 04/24/2014 http://dx.doi.org/10.4161/hv.28962
1334
Human Vaccines & Immunotherapeutics
CAPiTA: A Randomized Controlled Trial of PCV13 in Adults To address the question of the efficacy of PCV13 against communityacquired pneumonia (CAP), CAPiTA (Community-Acquired Pneumonia immunization Trial in Adults), a placebo-controlled randomized clinical trial with nearly 85 000 subjects was conducted among persons ≥65 y of age in Holland. The preliminary results from this study were presented at the International Symposium on Pneumococci and Pneumococcal Diseases 9 in Hyderabad, India.4 Outcomes for which the vaccine’s efficacy was reported included CAP due to serotypes in PCV13 (both non-bacteremic CAP and CAP associated with invasive infections) and invasive pneumococcal infections due to vaccine serotypes. The study excluded residents of nursing homes/long-term care facilities, those with immune deficiencies, and those who had previously received a pneumococcal vaccine, among others.4
Some Encouraging Preliminary Results from CAPiTA Preliminary results of the study suggest that PCV13 is efficacious against both invasive pneumococcal infections caused by PCV13 serotypes (75% efficacy) and non-bacteremic pneumonia caused by PCV13 serotypes (45% efficacy).4 Given the large burden of nonbacteremic pneumonia among adults and the poor efficacy of PPV23 against non-bacteremic
Volume 10 Issue 5
©2014 Landes Bioscience. Do not distribute.
Reasons for optimism and for caution
But with Important Caveats The potential benefit of vaccinating adults with PCV13 will depend, in part, on the proportion of CAP in adults that is due to PCV13 serotypes; if these serotypes cause a small fraction of disease, the marginal benefit of vaccinating adults will be small. Because children are a major source of exposure to pneumococci for adults,7 the use of conjugate vaccines (which affect colonization as well as disease) in children has a large impact on the incidence of pneumococcal infections in adults.8 Following introduction of PCV7 for children in the United States, the 7 vaccine serotypes soon were nearly eliminated as a cause of invasive infections among both adults and children.8-10 If vaccination of children with PCV13 has a similar impact on infections in adults, the additional fraction of infections preventable by direct immunization of adults could be small.11 Given the large impact of vaccination of children on the incidence of infections in adults, additional information from the CAPiTA trial is needed before the potential impact of immunizing adults with PCV13 can be fully assessed. In the trial, PCV13 was efficacious against CAP caused by vaccine serotypes.4 The CAPiTA study was conducted when PCV7 and then PCV10 (starting in March 2011) were in widespread use among Dutch children. Therefore, to assess the potential impact of the vaccine using data from the CAPiTA trial, it will be critical to compare rates of all-cause pneumonia between the recipients of PCV13 and the controls and to
www.landesbioscience.com
determine whether there were changes after PCV10 was introduced. The CAPiTA trial assessed the efficacy of PCV13 compared with a placebo control, but did not assess its efficacy relative to the currently available PPV23. While PPV23 has limited efficacy against pneumonia, it does contain 10 additional serotypes not included in PCV13, potentially providing broader protection at a lower cost. As the proportion of disease due to serotypes not in PCV13 increases, the relative benefit of PPV23 also might increase. To determine the best vaccine to use in a particular setting, additional costeffectiveness analyses are needed. These analyses should account for the effectiveness of PCV13 and of PPV23 in adults, patterns of serotype replacement, and the indirect impact of vaccination of children on rates of disease in adults. The CAPiTA results will help to improve the accuracy of currently-available models.12 The CAPiTA trial excluded some individuals who are at a particularly high risk of disease (those with immunodeficiencies and nursing home residents). In addition, results of how age affected efficacy have not yet been reported. Because the risk of pneumococcal disease increases with age and with these underlying conditions, results from efficacy trials might overestimate the potential impact of the vaccine on populations in a real-world setting. Although the CAPiTA trial might not be sufficiently powered to enable detailed subgroup analyses, estimation of the vaccine’s efficacy in some subgroups might help in the formulation of recommendations. Finally, although the urinary antigen assay used to diagnose non-bacteremic pneumococcal pneumonia in the trial has been validated,13 to our knowledge this assay has not been validated in vaccinated individuals. It is possible that vaccineinduced antibodies could prevent polysaccharide antigens from reaching the urine in patients with non-bacteremic CAP. This could lead to misclassification of cases and could potentially lead to inflated estimates of the vaccine’s efficacy. Further validation of the cutoff values for the assay
in vaccinated individuals could help to clarify this issue.
Impact of Results of the CAPiTA Trial The currently-available results might aid decision-making about the use of PCV13 in adults in some settings. In particular, in countries in which PCVs are not widely used in children, many adults will still be exposed to the vaccine serotypes and could benefit from the protection provided by PCV13. In settings in which uptake of PCV is high, additional information will be required from the CAPiTA trial and from other studies before informed decisions can be made about the use of PCV13 in adults. In particular, estimates of the efficacy of PCV against all-cause pneumonia will be particularly informative, since the incremental benefit of the vaccine likely will be driven by its effect on this outcome. Likewise, secondary analyses of the effects of age and of underlying medical conditions on the efficacy of the vaccine could help to determine its potential impact in various target groups. Finally, information about the serotypes that are causing pneumococcal pneumonia in adults in the post-PCV13 era will help to determine its potential impact on disease and on the cost-effectiveness of immunization programs for adults.
Need for Alternative Vaccines The CAPiTA study has demonstrated that conjugate vaccines can prevent pneumococcal pneumonia in adults. However, when children are vaccinated against pneumococcus, the transmission of nonvaccine serotypes increases (serotype replacement).14 These replacing serotypes can then become important causes of disease in adults. As a result, there should be renewed efforts to develop adult-specific conjugate vaccines that include different serotypes than those included in vaccines administered to children. Such vaccines
Human Vaccines & Immunotherapeutics 1335
©2014 Landes Bioscience. Do not distribute.
pneumonia, this could be an important finding. In addition, results suggest that PCV13 protects against infections caused by serotype 3 in adults. Early results from other studies suggest that immunization of children with PCV13 might not affect rates of infections caused by serotype 3 in adults.5,6 Therefore, immunization of adults with PCV13 might provide a mechanism for preventing disease caused by serotype 3 in adults.
Conclusions The preliminary results from the CAPiTA trial provide evidence that conjugate vaccines can effectively prevent pneumococcal pneumonia in adults. Whether this means that PCV13 should replace PPV23 as the preferred vaccine against pneumococcal infections in adults remains uncertain. Additional questions about the potential impact of direct immunization of adults on the risk of pneumococcal infections in populations that already have robust vaccination programs for children remain to be answered. Disclosure of Potential Conflicts of Interest
D.M.W. has received consulting fees from Merck (the manufacturer of PPV23) and receives salary support from an investigator-initiated research grant from Pfizer (the manufacturer of PCV13) to Yale University. E.D.S. has nothing to disclose. Acknowledgments
This publication was made possible, in part, by support from CTSA Grants Number UL1 TR000142 and KL2 TR000140 from the National
1336
Center for Research Resources (NCRR) and the National Center for Advancing Translational Science (NCATS), components of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. References 1. Jackson LA, Neuzil KM, Yu O, Benson P, Barlow WE, Adams AL, Hanson CA, Mahoney LD, Shay DK, Thompson WW; Vaccine Safety Datalink. Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med 2003; 348:174755; PMID:12724480; http://dx.doi.org/10.1056/ NEJMoa022678 2. Shapiro ED, Berg AT, Austrian R, Schroeder D, Parcells V, Margolis A, Adair RK, Clemens JD. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991; 325:145360; PMID:1944423; http://dx.doi.org/10.1056/ NEJM199111213252101 3. Scott DA, Komjathy SF, Hu BT, Baker S, Supan LA, Monahan CA, Gruber W, Siber GR, Lockhart SP. Phase 1 trial of a 13-valent pneumococcal conjugate vaccine in healthy adults. Vaccine 2007; 25:61646; PMID:17629361; http://dx.doi.org/10.1016/j. vaccine.2007.06.004 4. Bonten M, Bolkenbaas M, Huijts S, Webber C, Gault S, Gruber W, et al. Community-acquired pneumonia immunization trial in aduilta-CAPiTA. International Symposium on Pneumococci and Pneumococccal Diseases 9. Hyderabad, India, 2014. 5. Steens A, Bergsaker MAR, Aaberge IS, Rønning K, Vestrheim DF. Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway. Vaccine 2013; 31:62328; PMID:24176490; http://dx.doi.org/10.1016/j. vaccine.2013.10.032 6. Lee GM, Kleinman K, Pelton SI, Hanage W, Huang SS, Lakoma M, Dutta-Linn M, Croucher NJ, Stevenson A, Finkelstein JA. Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts. J Pediatric Infect Dis Soc 2014; 3:23-32; PMID:24567842; http://dx.doi. org/10.1093/jpids/pit057
Human Vaccines & Immunotherapeutics
7. Walter ND, Taylor TH Jr., Dowell SF, Mathis S, Moore MR; Active Bacterial Core Surveillance System Team. Holiday spikes in pneumococcal disease among older adults. N Engl J Med 2009; 361:2584-5; PMID:20032333; http://dx.doi. org/10.1056/NEJMc0904844 8. Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, Reingold A, Thomas A, Schaffner W, Craig AS, 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; 201:32-41; PMID:19947881; http://dx.doi. org/10.1086/648593 9. Halasa NB, Grijalva CG, Arbogast PG, Talbot TR, Craig AS, Griffin MR, Schaffner W. Nearly complete elimination of the 7-valent pneumococcal conjugate vaccine serotypes in Tennessee. Pediatr Infect Dis J 2013; 32:604-9; PMID:23348816; http://dx.doi. org/10.1097/INF.0b013e318287fe0d 10. Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA, Cherian T, Levine OS, Whitney CG, O’Brien KL, Moore MR; Serotype Replacement Study Group. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med 2013; 10:e1001517; PMID:24086113; http://dx.doi.org/10.1371/journal. pmed.1001517 11. Fedson DS. Pneumococcal conjugate vaccination for older adults: Reply letter to Hollingsworth et al. Hum Vaccin Immunother 2013; 10:24-8; PMID:24030320 12. Smith KJ, Wateska AR, Nowalk MP, Raymund M, Nuorti JP, Zimmerman RK. Cost-effectiveness of adult vaccination strategies using pneumococcal conjugate vaccine compared with pneumococcal polysaccharide vaccine. JAMA 2012; 307:804-12; PMID:22357831; http://dx.doi. org/10.1001/jama.2012.169 13. Pride MW, Huijts SM, Wu K, Souza V, Passador S, Tinder C, Song E, Elfassy A, McNeil L, Menton R, et al. Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotypespecific polysaccharides in human urine. Clin Vaccine Immunol 2012; 19:1131-41; PMID:22675155; http://dx.doi.org/10.1128/CVI.00064-12 14. Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet 2011; 378:1962-73; PMID:21492929; http://dx.doi.org/10.1016/S0140-6736(10)62225-8
Volume 10 Issue 5
©2014 Landes Bioscience. Do not distribute.
would protect adults against the serotypes causing the largest fraction of residual disease. Because adults are not a significant reservoir for transmission of pneumococci, such an adult-centered strategy likely would minimize further serotype replacement while providing maximum protection against the dominant serotypes.
