INTRODUCTION: The aim of this study is to analyse the impact of vaccination of infants with pneumococcal conjugate vaccine (PCV) on the incidence of invasive pneumococcal disease (IPD) in children under 5 years of age in the Czech Republic. MATERIAL AND METHODS: The present study includes all IPD cases reported in children aged 0-4 years within the surveillance program in 2007-2017. The impact of PCV is analysed for five categories of IPD: cases caused by all serotypes, cases caused by PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), cases caused by three additional PCV10 serotypes (1, 5, and 7F), cases caused by three additional PCV13 serotypes (3, 6A, and 19A), and cases caused by non-PCV serotypes. To assess the impact of PCV, the study period was divided into the pre-vaccination period 2007-2008 and post-vaccination period 2009-2017, which was divided into three three-year parts: 2009-2011, 2012-2014, and 2015-2017. Analysis of differences between periods was based on the Poisson regression model where the population numbers were handled as an offset. RESULTS: The annual incidence of IPD in children under 5 years of age caused by all serotypes has had a downward trend since 2007: it dropped from 8.52/100 000 in 2007 to 2.67/100 000 in 2017, with slight increases in 2010 and 2013. All three post-vaccination periods show significantly lower (p<0.001) incidences in comparison to the pre-vaccination period, but they do not statistically significantly differ from each other. CONCLUSIONS: IPD surveillance data in the Czech Republic show that after the introduction of PCV vaccination of infants, there has been a significant decrease in the IPD incidence of children under 5 years of age. Continued IPD surveillance is essential to monitor for possible post-vaccination serotype replacement.

Department of Air Borne Bacterial Infections Centre for Epidemiology and Microbiology National Institute of Public Health Prague Czech Republic

Department of Air Borne Bacterial Infections National Reference Laboratory for Streptococcal Infections Centre for Epidemiology and Microbiology National Institute of Public Health Prague Czech Republic

Unit for Biostatistics National Institute of Public Health Prague Czech Republic

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WHO. Pneumococcal vaccines WHO position paper– 2012. Wkly Epidemiol Rec. 2012; 87:129–44. PubMed

Hanquet G, Perrocheau A, Kissling E, Bruhl DL, Tarragó D, Stuart J, et al.. Surveillance of invasive pneumococcal disease in 30 EU countries: Towards a European system? Vaccine. 2010; 28(23):3920–8. 10.1016/j.vaccine.2010.03.069 PubMed DOI

Siira L, Kaijalainen T, Lambertsen L, Nahm MH, Toropainen M, Virolainen A. From Quellung to multiplex PCR, and back when needed, in pneumococcal serotyping. J Clin Microbiol. 2012;50(8):2727–31. 10.1128/JCM.00689-12 PubMed DOI PMC

Vackova Z, Klimova M, Kozakova J. A novel typing method and scheme for Streptococcus pneumoniae. Epidemiol Mikrobiol Imunol. 2013;62(2):50–8. PubMed

Hilbe J.M. Modeling count data. Cambridge University Press, New York, 2014.

Waight PA, Andrews NJ, Ladhani SN, Sheppard CL, Slack MP, Miller E. Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study. Lancet Infect Dis. 2015;15(5):535–43. 10.1016/S1473-3099(15)70044-7 PubMed DOI

D’Ancona F, Caporali MG, Del Manso M, Giambi C, Camilli R, D’Ambrosio F, et al.. Invasive pneumococcal disease in children and adults in seven Italian regions after the introduction of the conjugate vaccine, 2008–2014. Epidemiol Prev. 2015;39(4 Suppl 1):134–8. PubMed

De Wals P, Lefebvre B, Markowski F, Deceuninck G, Defay F, Douville-Fradet M, et al.. Impact of 2+1 pneumococcal conjugate vaccine program in the province of Quebec, Canada. Vaccine. 2014;32(13):1501–6. 10.1016/j.vaccine.2013.11.028 PubMed DOI

Slotved HC, Dalby T, Hoffmann S. The effect of pneumococcal conjugate vaccines on the incidence of invasive pneumococcal disease caused by ten non-vaccine serotypes in Denmark. Vaccine. 2016;34(6):769–74. 10.1016/j.vaccine.2015.12.056 PubMed DOI

Andrews N, Kent A, Amin-Chowdhury Z, Sheppard C, Fry N, Ramsay M, et al.. Effectiveness of the seven-valent and thirteen-valent pneumococcal conjugate vaccines in England: The indirect cohort design, 2006–2018. Vaccine. 2019;37(32):4491–8. 10.1016/j.vaccine.2019.06.071 PubMed DOI

Harboe ZB, Dalby T, Weinberger DM, Benfield T, Mølbak K, Slotved HC, et al.. Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality. Clin Infect Dis. 2014;59(8):1066–73. 10.1093/cid/ciu524 PubMed DOI

Moore MR, Link-Gelles R, Schaffner W, Lynfield R, Lexau C, Bennett NM, et al.. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis. 2015;15(3):301–9. 10.1016/S1473-3099(14)71081-3 PubMed DOI PMC

Lepoutre A, Varon E, Georges S, Dorléans F, Janoir C, Gutmann L, et al.. Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001–2012. Vaccine. 2015;33(2):359–66. 10.1016/j.vaccine.2014.11.011 PubMed DOI

Picazo JJ, Ruiz-Contreras J, Casado-Flores J, Negreira S, Baquero-Artigao F, Hernández-Sampelayo T, et al.. Impact of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children under 15 years old in Madrid, Spain, 2007 to 2016: The HERACLES clinical surveillance study. Vaccine. 2019;37(16):2200–7. 10.1016/j.vaccine.2019.03.015 PubMed DOI

Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA, Cherian T, et al.. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med. 2013;10(9):e1001517. 10.1371/journal.pmed.1001517 PubMed DOI PMC

Savulescu C, Krizova P, Lepoutre A, Mereckiene J, Vestrheim DF, Ciruela P, et al.. Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study. Lancet Respir Med. 2017;5(8):648–656. 10.1016/S2213-2600(17)30110-8 PubMed DOI

Levy C, Ouldali N, Caeymaex L, Angoulvant F, Varon E, Cohen R. Diversity of Serotype Replacement After Pneumococcal Conjugate Vaccine Implementation in Europe J Pediatr. 2019;213:252–253.e3. 10.1016/j.jpeds.2019.07.057 PubMed DOI

Ladhani SN, Collins S, Djennad A, Sheppard CL, Borrow R, Fry NK, et al.. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study. Lancet Infect Dis. 2018;18(4):441–451. 10.1016/S1473-3099(18)30052-5 PubMed DOI

van der Linden M, Falkenhorst G, Perniciaro S, Imöhl M. Effects of Infant Pneumococcal Conjugate Vaccination on Serotype Distribution in Invasive Pneumococcal Disease among Children and Adults in Germany. PLoS One. 2015;10(7):e0131494. 10.1371/journal.pone.0131494 PubMed DOI PMC

Balsells E, Guillot L, Nair H, Kyaw MH. Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: A systematic review and meta-analysis. PLoS One. 2017;12(5):e0177113. 10.1371/journal.pone.0177113 PubMed DOI PMC

Stock NK, Maly M, Sebestova H, Orlikova H, Kozakova J, Krizova P. The Czech Surveillance System for Invasive Pneumococcal Disease, 2008–2013: A Follow-Up Assessment and Sensitivity Estimation. PLoS One. 2015;10(6):e0131117. 10.1371/journal.pone.0131117 PubMed DOI PMC

Slotved HC, Dalby T, Harboe ZB, Valentiner-Branth P, Casadevante VF, Espenhain L, et al.. The incidence of invasive pneumococcal serotype 3 disease in the Danish population is not reduced by PCV-13 vaccination. Heliyon. 2016. November 29;2(11):e00198. 10.1016/j.heliyon.2016.e00198 PubMed DOI PMC

De Wals P, Lefebvre B, Deceuninck G, Longtin J. Incidence of invasive pneumococcal disease before and during an era of use of three different pneumococcal conjugate vaccines in Quebec. Vaccine. 2018. January 8;36(3):421–426. 10.1016/j.vaccine.2017.11.054 PubMed DOI

Principi N, Di Cara G, Bizzarri I, Isidori C, Borgia P, Mignini C, et al.. Prevention of Invasive Pneumococcal Disease: Problems Emerged After Some Years of the 13-Valent Pneumococcal Conjugate Vaccine Use. Curr Infect Dis Rep. 2018. January 24;20(1):1. 10.1007/s11908-018-0607-z PubMed DOI

Silva-Costa C, Brito MJ, Aguiar SI, Lopes JP, Ramirez M, Melo-Cristino J; et al.. Dominance of vaccine serotypes in pediatric invasive pneumococcal infections in Portugal (2012–2015). Sci Rep. 2019. January 9;9(1):6. 10.1038/s41598-018-36799-x PubMed DOI PMC