Hopp til innhold

Get alerts of updates about «Efficacy and effectiveness of pneumococcal vaccination in adults – an update of the literature»

How often would you like to receive alerts from fhi.no? (This affects all your alerts)

The email address you register will only be used to send you these alerts. You can cancel your alerts and delete your email address at any time by following the link in the alerts you receive.
Read more about the privacy policy for fhi.no

You have subscribed to alerts about:

  • Efficacy and effectiveness of pneumococcal vaccination in adults – an update of the literature

Report

Efficacy and effectiveness of pneumococcal vaccination in adults – an update of the literature

Published

This work is a collaboration between colleagues at the Norwegian, Swedish and Danish Public Health Institutes based on a common need for an updated knowledgebase to inform national guidelines for pneumococcal vaccination in medical risk groups and adults.

This work is a collaboration between colleagues at the Norwegian, Swedish and Danish Public Health Institutes based on a common need for an updated knowledgebase to inform national guidelines for pneumococcal vaccination in medical risk groups and adults.


Can be downloaded as PDF

About this publication

  • Year: 12/2019
  • By: Folkehelseinstituttet
  • Authors Winje BA, Berild JD, Vestrheim DF, Denison E, Lepp T, Roth A, Valentiner-Branth P, Slotved HC, Storsæter J .
  • ISBN (digital): 978-82-8406-053-8

Summary

  • S. pneumonia is a major cause of morbidity and mortality, specifically at the extremes of age and in individuals with immunocompromising medical conditions. Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent pneumococcal conjugate vaccine (PCV13) are available to prevent pneumococcal disease in adults.
  • No studies compare vaccine effectiveness of PPV23 and PCV13 head-to-head.
  • Direct comparison between the two vaccines are difficult due to differences in populations, time since vaccination and study designs.
  • Whereas the evidence for PCV13 is dominated by one large trial with overall healthy elderly, the evidence for PPV23 VE is based on several trials of moderate quality and several observational studies.
  • Results obtained from RCTs and those obtained from various observational designs are inconsistent, making it difficult to summarize available evidence into single quantitative measures.
  • Higher vaccine effectiveness seen in clinical trials may reflect shorter follow-up time compared with observational studies, where waning immunity is likely to play a role.
  • Both PPV23 and PCV13 are comparably effective for the prevention of all-type invasive pneumococcal disease (IPD) in the broader adult population, across study designs and settings.
  • PCV13 seems to provide better protection than PPV23 against vaccine type IPD (for serotypes common to PCV13 and PPV23).
  • The overall body of evidence shows PPV23 VE at a level comparable to PCV13.
  • Both vaccines showed generally lower VE with increasing age, but data are limited for PCV13.
  • Both vaccines showed generally lower VE in groups with comorbidities compared with groups without known risk.
  • With one exception from a case-control study with overall high VE estimates, both vaccines failed to show significant VE in immunocompromised groups.

Introduction

Young children, elderly and persons with weakened immune systems are at high risk of acquiring invasive pneumococcal disease and pneumococcal pneumonia. Two different vaccines are available for the prevention of pneumococcal disease in adults; a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The updated review will serve as a bases to inform national recommendations for use of pneumococcal vaccines in elderly in Norway, Sweden and Denmark.

Methods

The report covers publications on PCV13 and PPV23 efficacy and effectiveness from 2000 until April 2019 from randomized controlled trials and observational studies. Outcomes include invasive pneumococcal disease and pneumococcal pneumonia.

Results

A total of 27 publications are included; 18 publications on PPV23 effectiveness and nine publications on PCV13 effectiveness. No study compared the effectiveness of PPV23 and PCV13 directly. One large trial with overall healthy elderly dominates the evidence for PCV13 efficacy and effectiveness. The evidence for PPV23 vaccine effectiveness, on the other hand, is based on trials of moderate quality and several observational studies. Differences in populations, study designs and time since vaccination makes it difficult to summarize available evidence into single quantitative measures.

The vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease was consistent with past systematic reviews and similar to the estimates that have been reported for PCV13 efficacy and effectiveness. Consistent effects were reported across observational studies and ecological studies of surveillance data for the general elderly population. PCV13 seems to provide better protection than PPV23 against vaccine-type invasive pneumococcal disease (for serotypes common to PCV13 and PPV23).

We found both PPV23 and PCV13 to be effective in preventing pneumococcal pneumonia in elderly at comparable levels. The PPV23 vaccine effectiveness was higher in clinical trials than observational studies, possibly reflecting a shorter follow-up time and a more limited impact of waning immunity.

Both PPV23 and PCV13 showed generally lower effectiveness with increasing age for all outcomes and in groups with immunocompromising conditions. Overall, significant VE was not shown for immunocompromised groups.

Conclusion

This report shows that both PCV13 and PPV23 provide prevention for invasive disease and pneumococcal pneumonia in the elderly. The overall body of evidence shows PPV23 effectiveness at a level comparable to PCV13. This finding is of paramount importance for public health due to the high pneumococcal pneumonia disease burden. The serotype distribution in carriage and disease is important to consider for the impact of vaccination. The currently low proportion of patients falling ill with serotypes included in PCV13 suggests limited potential for prevention from adult PCV13 vaccination. Well-designed and serotype specific randomized controlled trials are important to improve evidence.

1.       Djennad A, Ramsay ME, Pebody R, et al. Effectiveness of 23-Valent Polysaccharide Pneumococcal Vaccine and Changes in Invasive Pneumococcal Disease Incidence from 2000 to 2017 in Those Aged 65 and Over in England and Wales. EClinicalMedicine 2018;6:42-50. doi: 10.1016/j.eclinm.2018.12.007 [published Online First: 2019/06/14]

2.       Ardanuy C, Marimon JM, Calatayud L, et al. Epidemiology of invasive pneumococcal disease in older people in Spain (2007-2009): implications for future vaccination strategies. PLoS One 2012;7(8):e43619. doi: 10.1371/journal.pone.0043619

3.       Benfield T, Skovgaard M, Schønheyder HC, et al. Serotype Distribution in Non-Bacteremic Pneumococcal Pneumonia: Association with Disease Severity and Implications for Pneumococcal Conjugate Vaccines. PLoS ONE2013;8(8):e72743. doi: 10.1371/journal.pone.0072743

4.       Rozenbaum MH, Pechlivanoglou P, van der Werf TS, et al. The role of Streptococcus pneumoniae in community-acquired pneumonia among adults in Europe: a meta-analysis. Eur J Clin Microbiol Infect Dis 2013;32(3):305-16. doi: 10.1007/s10096-012-1778-4

5.       Said MA, Johnson HL, Nonyane BA, et al. Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques. PLoS One 2013;8(4):e60273. doi: 10.1371/journal.pone.0060273

6.       European Medicines Agency (EMA). European public assessment report (EPAR) for Prevenar 13. Summary of product characteristics. In: (EMA). EMa, ed. London, 2015.

7.       Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. Journal of the American Medical Association 2006;295(19):2275-85. doi: 295/19/2275 [pii];10.1001/jama.295.19.2275

8.       Lujan M, Burgos J, Gallego M, et al. Effects of immunocompromise and comorbidities on pneumococcal serotypes causing invasive respiratory infection in adults: implications for vaccine strategies. Clin Infect Dis 2013;57(12):1722-30. doi: 10.1093/cid/cit640

9.       Shigayeva A, Rudnick W, Green K, et al. Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs. Clin Infect Dis 2016;62(2):139-47. doi: 10.1093/cid/civ803

10.    Wotton CJ, Goldacre MJ. Risk of invasive pneumococcal disease in people admitted to hospital with selected immune-mediated diseases: record linkage cohort analyses. Journal of Epidemiology & Community Health 2012;66(12):1177-81. doi: jech-2011-200168 [pii];10.1136/jech-2011-200168

11.    Hanquet G, Krizova P, Valentiner-Branth P, et al. Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination. Thorax 2019;74(5):473-82. doi: 10.1136/thoraxjnl-2018-211767

12.    Berild JD, Storsæter J, Vestrheim DF, et al. A systematic review of the effectiveness of pneumococcal vaccines for the prevention of pneumococcal disease 2016-2019. under submission 2019

13.    Blommaert A, Hanquet G, Lander W, et al. Use of pneumococcal vaccines in the elderly: an economic evaluation. In: Centre BHCK, ed. Health Technology Assessment, KCE Report 274. Brussels: Belgian Health Care Knowledge Centre, 2016.

14.    Falkenhorst G, Remschmidt C, Harder T, et al. Effectiveness of the 23-valent pneumococcal polysaccharide vaccine (ppv23) against pneumococcal disease in the elderly: Systematic review and meta-analysis. PLoS ONE 2017;12 (1) (no pagination)(e0169368) doi: http://dx.doi.org/10.1371/journal.pone.0169368

15.    Htar MTT, Stuurman AL, Ferreira G, et al. Effectiveness of pneumococcal vaccines in preventing pneumonia in adults, a systematic review and meta-analyses of observational studies. PLoS ONE 2017;12 (5) (no pagination)(e0177985) doi: http://dx.doi.org/10.1371/journal.pone.0177985

16.    Kraicer-Melamed H, O'Donnell S, Quach C. The effectiveness of pneumococcal polysaccharide vaccine 23 (PPV23) in the general population of 50 years of age and older: A systematic review and meta-analysis. Vaccine2016;34(13):1540-50. doi: 10.1016/j.vaccine.2016.02.024 [published Online First: 2016/02/24]

17.    Moberley S, Holden J, Tatham DP, et al. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev 2013(1):CD000422. doi: 10.1002/14651858.CD000422.pub3

18.    Schiffner-Rohe J, Witt A, Hemmerling J, et al. Efficacy of PPV23 in preventing pneumococcal pneumonia in adults at increased risk - A systematic review and meta-analysis. PLoS ONE 2016;11 (1) (no pagination)(e0146338) doi: http://dx.doi.org/10.1371/journal.pone.0146338

19.    Huss A, Scott P, Stuck AE, et al. Efficacy of pneumococcal vaccination in adults: a meta-analysis. CMAJ 2009;180(1):48-58. doi: 10.1503/cmaj.080734

20.    Diao WQ, Shen N, Yu PX, et al. Efficacy of 23-valent pneumococcal polysaccharide vaccine in preventing community-acquired pneumonia among immunocompetent adults: A systematic review and meta-analysis of randomized trials. Vaccine 2016;34(13):1496-503. doi: http://dx.doi.org/10.1016/j.vaccine.2016.02.023

21.    Fedson DS, Liss C. Precise answers to the wrong question: prospective clinical trials and the meta-analyses of pneumococcal vaccine in elderly and high-risk adults. Vaccine 2004;22(8):927-46. doi: 10.1016/j.vaccine.2003.09.027

22.    Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. doi: 10.1136/bmj.d5928 [published Online First: 2011/10/20]

23.    Wells G, Shea, B., Higgins, J.P.T., Sterne, J., Tugwell, P., Reeves, B.C. Checklists of methodological issues for review authors to consider when including non-randomized studies in systematic reviews. Res Syn Meth 2013;4:63-77.

24.    Effective Health Care Program. Nitrous Oxide for the Management of Labor Pain, AHRQ Publication No. 12-EHC071-EF. Comparative Effectiveness Review. Maryland, USA: Agency for Healthcare Research and Quality, 2012.

25.    Sons JWa, ed. Comparison of Newcastle Ottawa scale (NOS) and Agency for Health Research and Quality (AHRQ) as risk of bias assessment tools for cohort studies. Filtering the information overload for better decisions. 23rd Cochrane Colloquium; 2015; Vienna, Austria.

26.    Hipwell AE, Kahn LG, Factor-Litvak P, et al. Exposure to non-persistent chemicals in consumer products and fecundability: a systematic review. Hum Reprod Update 2019;25(1):51-71. doi: 10.1093/humupd/dmy032

27.    Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol2011;64(4):401-6. doi: 10.1016/j.jclinepi.2010.07.015 [published Online First: 2011/01/07]

28.    Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011;64(4):383-94. doi: 10.1016/j.jclinepi.2010.04.026 [published Online First: 2011/01/05]

29.    Ahmed F. U.S. Advisory Committee on Immunization Practices Handbook for Developing Evidence-based  Recommendations Work Group. Centers for Disease Control and Prevention, Atlanta, 2013;Version 1.2.

30.    Dominguez A, Ciruela P, Hernandez S, et al. Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study. Plos One2017;12(8):15. doi: 10.1371/journal.pone.0183191

31.    Kolditz M, Schmitt J, Pletz MW, et al. Impact of pneumococcal polysaccharide vaccine on incidence and mortality after pneumonia in adults aged >=60 years-a population-based retrospective cohort study. Clinical Microbiology and Infection 2018;24(5):500-04. doi: http://dx.doi.org/10.1016/j.cmi.2017.08.010

32.    Kondo K, Suzuki K, Washio M, et al. Effectiveness of 23-valent pneumococcal polysaccharide vaccine and seasonal influenza vaccine for pneumonia among the elderly - Selection of controls in a case-control study. Vaccine2017;35(36):4806-10. doi: http://dx.doi.org/10.1016/j.vaccine.2017.07.005

33.    Kolditz M, Schmitt J, Pletz MW, et al. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on the Incidence of All-cause Pneumonia in Adults Aged >/=60 Years: A Population-based, Retrospective Cohort Study. Clin Infect Dis2019;68(12):2117-19. doi: 10.1093/cid/ciy993

34.    Martinelli D, Fortunato F, Cappelli M, et al. Effectiveness of PCV13 in the prevention of pneumococcal pneumonia among older adults: results from a test-negative design study in Italy, January 2013 - January 2015 - Conference Proceedings. ECCMID 2015 2015

35.    Prato R, Fortunato F, Cappelli MG, et al. Effectiveness of the 13-valent pneumococcal conjugate vaccine against adult pneumonia in Italy: a case-control study in a 2-year prospective cohort. BMJ Open 2018;8(3):e019034. doi: 10.1136/bmjopen-2017-019034 [published Online First: 2018/03/28]

36.    Honkanen PO, Keistinen T, Miettinen L, et al. Incremental effectiveness of pneumococcal vaccine on simultaneously administered influenza vaccine in preventing pneumonia and pneumococcal pneumonia among persons aged 65 years or older. Vaccine 1999;17(20-21):2493-500.

37.    Örtqvist A, Hedlund J, Burman LA, et al. Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish Pneumococcal Vaccination Study Group. Lancet 1998;351(9100):399-403.

38.    Jalonen E, Paton JC, Koskela M, et al. Measurement of antibody responses to pneumolysin--a promising method for the presumptive aetiological diagnosis of pneumococcal pneumonia. J Infect 1989;19(2):127-34.

39.    Leinonen M, Syrjälä H, Jalonen E, et al. Demonstration of pneumolysin antibodies in circulating immune complexes - a new diagnostic method for pneumococcal pneumonia. Serodiagnosis and Immunotherapy in Infectious Disease1990;4(6):451-8.

40.    Scott JA, Hall AJ, Leinonen M. Validation of immune-complex enzyme immunoassays for diagnosis of pneumococcal pneumonia among adults in Kenya. Clin Diagn Lab Immunol 2000;7(1):64-7. doi: 10.1128/cdli.7.1.64-67.2000

41.    Musher DM, Mediwala R, Phan HM, et al. Nonspecificity of assaying for IgG antibody to pneumolysin in circulating immune complexes as a means to diagnose pneumococcal pneumonia. Clin Infect Dis 2001;32(4):534-8. doi: 10.1086/318709

42.    Vila-Corcoles A, Ochoa-Gondar O, Hospital I, et al. Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study. Clin Infect Dis 2006;43(7):860-8. doi: 10.1086/507340

43.    Vila-Corcoles A, Salsench E, Rodriguez-Blanco T, et al. Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in middle-aged and older adults: a matched case-control study. Vaccine 2009;27(10):1504-10. doi: 10.1016/j.vaccine.2009.01.013

44.    Vila-Corcoles A, Ochoa-Gondar O, Guzman JA, et al. Effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal disease in people 60 years or older. BMC Infect Dis 2010;10:73. doi: 10.1186/1471-2334-10-73 [published Online First: 2010/03/20]

45.    Vila-Corcoles A, Ochoa-Gondar O, Rodriguez-Blanco T, et al. Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in patients with chronic pulmonary diseases: a matched case-control study. Hum Vaccin Immunother 2012;8(5):639-44. doi: 10.4161/hv.19466 [published Online First: 2012/05/29]

46.    Alfageme I, Vazquez R, Reyes N, et al. Clinical efficacy of anti-pneumococcal vaccination in patients with COPD. Thorax2006;61(3):189-95. doi: 10.1136/thx.2005.043323

47.    Maruyama T, Taguchi O, Niederman MS, et al. Efficacy of 23-valent pneumococcal vaccine in preventing pneumonia and improving survival in nursing home residents: double blind, randomised and placebo controlled trial. BMJ2010;340:c1004. doi: 10.1136/bmj.c1004

48.    Tsai YH, Hsieh MJ, Chang CJ, et al. The 23-valent pneumococcal polysaccharide vaccine is effective in elderly adults over 75 years old--Taiwan's PPV vaccination program. Vaccine 2015;33(25):2897-902. doi: 10.1016/j.vaccine.2015.04.068 [published Online First: 2015/05/06]

49.    Hechter RC, Chao C, Jacobsen SJ, et al. Clinical effectiveness of pneumococcal polysaccharide vaccine in men: California Men's Health Study. Vaccine 2012;30(38):5625-30. doi: 10.1016/j.vaccine.2012.06.085 [published Online First: 2012/07/14]

50.    Ochoa-Gondar O, Vila-Corcoles A, Rodriguez-Blanco T, et al. Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in the general population aged >/= 60 years: 3 years of follow-up in the CAPAMIS study. Clin Infect Dis 2014;58(7):909-17. doi: 10.1093/cid/ciu002

51.    Jackson LA, Neuzil KM, Yu O, et al. Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med2003;348(18):1747-55. doi: 10.1056/NEJMoa022678 [published Online First: 2003/05/02]

52.    Kim JH, Chun BC, Song JY, et al. Direct effectiveness of pneumococcal polysaccharide vaccine against invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia in elderly population in the era of pneumococcal conjugate vaccine: A case-control study. Vaccine 2019;37(21):2797-804. doi: 10.1016/j.vaccine.2019.04.017

53.    Leventer-Roberts M, Feldman BS, Brufman I, et al. Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive disease and hospital-treated pneumonia among people aged >/=65 years: a retrospective case-control study. Clin Infect Dis 2015;60(10):1472-80. doi: 10.1093/cid/civ096 [published Online First: 2015/02/12]

54.    Dominguez A, Salleras L, Fedson DS, et al. Effectiveness of pneumococcal vaccination for elderly people in Catalonia, Spain: a case-control study. Clin Infect Dis 2005;40(9):1250-7. doi: 10.1086/429236 [published Online First: 2005/04/13]

55.    Andrews NJ, Waight PA, George RC, et al. Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in the elderly in England and Wales. Vaccine 2012;30(48):6802-8. doi: 10.1016/j.vaccine.2012.09.019 [published Online First: 2012/09/25]

56.    Rudnick W, Liu Z, Shigayeva A, et al. Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995-2011. Vaccine 2013;31(49):5863-71. doi: 10.1016/j.vaccine.2013.09.049 [published Online First: 2013/10/09]

57.    Wright LB, Hughes GJ, Chapman KE, et al. Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in people aged 65 years and over in the North East of England, April 2006–July 2012. Trials in Vaccinology 2013;2:45-48. doi: https://doi.org/10.1016/j.trivac.2013.09.004

58.    Gutierrez Rodriguez MA, Ordobas Gavin MA, Garcia-Comas L, et al. Effectiveness of 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and over in the Region of Madrid, Spain, 2008-2011. Euro Surveill2014;19(40):20922. [published Online First: 2014/10/18]

59.    Wiemken TL, Carrico RM, Klein SL, et al. The effectiveness of the polysaccharide pneumococcal vaccine for the prevention of hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia in the elderly differs between the sexes: Results from the Community-Acquired Pneumonia Organization (CAPO) international cohort study. Vaccine 2014;32(19):2198-203. https://doi.org/10.1016/j.vaccine.2014.02.048

60.    Suzuki MD, B. G.: Ishifuji, T.: Yasunami, M.: Yaegashi, M.: Asoh, N.: Ishida, M.: Hamaguchi, S.: Aoshima, M.: Ariyoshi, K.: Morimoto, K.: Adult Pneumonia Study, Group-Japan. Serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study. Lancet Infect Dis 2017;17(3):313-21. doi: 10.1016/S1473-3099(17)30049-X [published Online First: 2017/01/28]

61.    de Serres G, Skowronski XW, Ambrose CS. The test-negative design: validity, accuracy and precision of vaccine efficacy estimates compared to the gold standard of randomised placebo-controlled clinical trials. Euro surveillance 2013;18(37):2165-68.

62.    Jackson ML, Nelson JC. The test-negative design for estimating influenza vaccine effectiveness. Vaccine2013;31(17):2165-8. doi: 10.1016/j.vaccine.2013.02.053

63.    Andrews N, Waight PA, Borrow R, et al. Using the indirect cohort design to estimate the effectiveness of the seven valent pneumococcal conjugate vaccine in England and Wales. PLoS One 2011;6(12):e28435. doi: 10.1371/journal.pone.0028435

64.    Broome CV, Facklam RR, Fraser DW. Pneumococcal disease after pneumococcal vaccination: an alternative method to estimate the efficacy of pneumococcal vaccine. N Engl J Med 1980;303(10):549-52. doi: 10.1056/NEJM198009043031003

65.    Ruckinger S, van der Linden M, Reinert RR, et al. Efficacy of 7-valent pneumococcal conjugate vaccination in Germany: An analysis using the indirect cohort method. Vaccine 2010;28(31):5012-6. doi: 10.1016/j.vaccine.2010.05.021

66.    Bonten MJ, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015;372(12):1114-25. doi: 10.1056/NEJMoa1408544

67.    Gessner BD, Jiang Q, Van Werkhoven CH, et al. A public health evaluation of 13-valent pneumococcal conjugate vaccine impact on adult disease outcomes from a randomized clinical trial in the Netherlands. Vaccine 2018 doi: http://dx.doi.org/10.1016/j.vaccine.2018.05.097

68.    Huijts SM, van Werkhoven CH, Bolkenbaas M, et al. Post-hoc analysis of a randomized controlled trial: Diabetes mellitus modifies the efficacy of the 13-valent pneumococcal conjugate vaccine in elderly. Vaccine 2017;35(34):4444-49. doi: http://dx.doi.org/10.1016/j.vaccine.2017.01.071

69.    Patterson S, Webber C, Patton M, et al. A post hoc assessment of duration of protection in CAPiTA (Community Acquired Pneumonia immunization Trial in Adults). Trials in Vaccinology 2016;5:92-96. doi:http://dx.doi.org/10.1016/j.trivac.2016.04.004

70.    Webber C, Patton M, Patterson S, et al. Exploratory efficacy endpoints in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Vaccine 2017;35(9):1266-72. doi: http://dx.doi.org/10.1016/j.vaccine.2017.01.032

71.    Suaya JA, Jiang Q, Scott DA, et al. Post hoc analysis of the efficacy of the 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia in at-risk older adults. Vaccine 2018;36(11):1477-83. doi: http://dx.doi.org/10.1016/j.vaccine.2018.01.049

72.    McLaughlin JMJ, Q.: Isturiz, R. E.: Sings, H. L.: Swerdlow, D. L.: Gessner, B. D.: Carrico, R. M.: Peyrani, P.: Wiemken, T. L.: Mattingly, W. A.: Ramirez, J. A.: Jodar, L. Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design. Clin Infect Dis 2018 doi: 10.1093/cid/ciy312 [published Online First: 2018/05/24]

73.    Vila-Corcoles AO-G, O.: de Diego, C.: Satue, E.: Aragon, M.: Vila-Rovira, A.: Gomez-Bertomeu, F.: Magarolas, R.: Figuerola-Massana, E.: Raga, X.: Perez, M. O.: Ballester, F. Evaluating clinical effectiveness of 13-valent pneumococcal conjugate vaccination against pneumonia among middle-aged and older adults in Catalonia: results from the EPIVAC cohort study. BMC Infect Dis 2018;18(1):196. doi: 10.1186/s12879-018-3096-7 [published Online First: 2018/04/28]

74.    van Werkhoven CH, Hollingsworth RC, Huijts SM, et al. Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly. Vaccine 2016;34(28):3275-82. doi: http://dx.doi.org/10.1016/j.vaccine.2016.05.002

75.    Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practice (ACIP). MMWR Morb Mortal Wkly Rep. Atlanta, 1997.

76.    Sinclair A, Xie X, Teltscher M, et al. Systematic review and meta-analysis of a urine-based pneumococcal antigen test for diagnosis of community-acquired pneumonia caused by Streptococcus pneumoniae. J Clin Microbiol2013;51(7):2303-10. doi: 10.1128/JCM.00137-13 [published Online First: 2013/05/17]

77.    Wunderink RG, Self WH, Anderson EJ, et al. Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary Antigen Detection Assays. Clin Infect Dis 2018;66(10):1504-10. doi: 10.1093/cid/cix1066 [published Online First: 2018/01/18]

78.    Pride MW, Jansen KU. Reevaluation of Positivity Cutoff Values for the Pneumococcal Urinary Antigen Detection Assay. Clin Vaccine Immunol 2017;24(11) doi: 10.1128/CVI.00239-17 [published Online First: 2017/11/08]

79.    Pride MW, Huijts SM, Wu K, et al. Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine. Clin Vaccine Immunol 2012;19(8):1131-41. doi: 10.1128/CVI.00064-12 [published Online First: 2012/06/08]

80.    Schwartz LM, Halloran ME, Rowhani-Rahbar A, et al. Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design. Vaccine 2017;35(1):184-90. doi: 10.1016/j.vaccine.2016.10.077 [published Online First: 2016/11/24]

81.    Dhoubhadel BG, Yasunami M, Yoshida LM, et al. A novel high-throughput method for molecular serotyping and serotype-specific quantification of Streptococcus pneumoniae using a nanofluidic real-time PCR system. J Med Microbiol 2014;63(Pt 4):528-39. doi: 10.1099/jmm.0.071464-0 [published Online First: 2014/01/28]