Skip to main content
Top
Published in: BMC Infectious Diseases 1/2015

Open Access 01-12-2015 | Research article

Pneumococcal meningitis and vaccine effects in the era of conjugate vaccination: results of 20 years of nationwide surveillance in Germany

Authors: Matthias Imöhl, Jens Möller, Ralf René Reinert, Stephanie Perniciaro, Mark van der Linden, Orhan Aktas

Published in: BMC Infectious Diseases | Issue 1/2015

Login to get access

Abstract

Background

Long-term complications and a case mortality rate of 7.5% make meningitis caused by Streptococcus pneumoniae a serious clinical threat. In 2006, a general pneumococcal conjugate vaccination (PCV) recommendation was issued for all children under 2 years in Germany. Here, we investigate serotype changes in meningitis cases after this vaccine recommendation.

Methods

The German National Reference Center for Streptococci (NRCS) has conducted surveillance for invasive pneumococcal disease (IPD) in Germany since 1992. Pneumococcal isolates were serotyped by the Neufeld’s Quellung reaction and antibiotic susceptibility was tested using the broth microdilution method.

Results

Of 22,204 IPD isolates sent to the NRCS from July 1992 to June 2013, 3,086 were meningitis cases. Microbiological and statistical investigations were performed to characterize and quantify all meningitis cases, focusing on changes reflecting implementation of the national PCV recommendation. 1,766 isolates (57.2% of meningitis cases) were from adults (≥16 years) and 1,320 isolates (42.8%) originated from children (<16 years). Overall, the leading serotypes were 14 (9.7%), 7F (7.8%), 3 (6.9%), 19F (5.7%) and 23F (5.0%). Among children, serotypes 14 (16.2%), 7F (8.9%) and 19F (7.1%) were most common, whereas among adults, serotypes 3 (9.6%), 7F (6.9%), 22F (5.0%), 23F (4.9%) and 14 (4.8%) were most prevalent. After the introduction of general PCV7/10/13 vaccination a significant decrease for most vaccine serotypes was observed. Generally, the differences in antibiotic nonsusceptibility between children <16 years and adults ≥16 were low. For macrolides in the pre-PCV7 period, a significantly higher proportion of resistant isolates was found in children (25.1%), compared to the post-vaccination period (9.7%; p<0.0001).

Conclusions

Implementation of the pneumococcal conjugate vaccines broadly reduced vaccine-type meningitis cases. Changes in serotype prevalence must be continuously monitored to observe future trends concerning pneumococcal meningitis.
Literature
2.
go back to reference Levy C, Varon E, Bingen E, Picard C, de La Rocque F, Aujard Y, et al. [Pneumococcal meningitis in children in France: 832 cases from 2001 to 2007]. Arch Pediatr. 2008;15 Suppl 3:S111–8.CrossRefPubMed Levy C, Varon E, Bingen E, Picard C, de La Rocque F, Aujard Y, et al. [Pneumococcal meningitis in children in France: 832 cases from 2001 to 2007]. Arch Pediatr. 2008;15 Suppl 3:S111–8.CrossRefPubMed
3.
go back to reference von Kries R, Hermann M, Hachmeister A, Siedler A, Schmitt HJ, Al-Lahham A, et al. Prediction of the potential benefit of different pneumococcal conjugate vaccines on invasive pneumococcal disease in German children. Pediatr Infect Dis J. 2002;21(11):1017–23.CrossRef von Kries R, Hermann M, Hachmeister A, Siedler A, Schmitt HJ, Al-Lahham A, et al. Prediction of the potential benefit of different pneumococcal conjugate vaccines on invasive pneumococcal disease in German children. Pediatr Infect Dis J. 2002;21(11):1017–23.CrossRef
4.
go back to reference Casado Flores J, Fenoll A, Aristegui Fernandez J, Rodrigo De Liria C, Martinon Sanchez JM, Berron S, et al. [Pneumococcal meningitis in Spanish children: incidence, serotypes and antibiotic resistance. Prospective and multicentre study]. An Esp Pediatr. 2002;57(4):295–300.CrossRefPubMed Casado Flores J, Fenoll A, Aristegui Fernandez J, Rodrigo De Liria C, Martinon Sanchez JM, Berron S, et al. [Pneumococcal meningitis in Spanish children: incidence, serotypes and antibiotic resistance. Prospective and multicentre study]. An Esp Pediatr. 2002;57(4):295–300.CrossRefPubMed
5.
go back to reference Johnson AP, Waight P, Andrews N, Pebody R, George RC, Miller E. Morbidity and mortality of pneumococcal meningitis and serotypes of causative strains prior to introduction of the 7-valent conjugant pneumococcal vaccine in England. J Infect. 2007;55(5):394–9.CrossRefPubMed Johnson AP, Waight P, Andrews N, Pebody R, George RC, Miller E. Morbidity and mortality of pneumococcal meningitis and serotypes of causative strains prior to introduction of the 7-valent conjugant pneumococcal vaccine in England. J Infect. 2007;55(5):394–9.CrossRefPubMed
6.
go back to reference Stanek RJ, Mufson MA. A 20-year epidemiological study of pneumococcal meningitis. Clin Infect Dis. 1999;28(6):1265–72.CrossRefPubMed Stanek RJ, Mufson MA. A 20-year epidemiological study of pneumococcal meningitis. Clin Infect Dis. 1999;28(6):1265–72.CrossRefPubMed
7.
go back to reference Reinert RR. Pneumococcal conjugate vaccines–a European perspective. Int J Med Microbiol. 2004;294(5):277–94.CrossRefPubMed Reinert RR. Pneumococcal conjugate vaccines–a European perspective. Int J Med Microbiol. 2004;294(5):277–94.CrossRefPubMed
8.
go back to reference Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med. 1992;327(12):864–72.CrossRefPubMed Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med. 1992;327(12):864–72.CrossRefPubMed
9.
go back to reference Hammerschmidt S, Wolff S, Hocke A, Rosseau S, Muller E, Rohde M. Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect Immun. 2005;73(8):4653–67.CrossRefPubMedPubMedCentral Hammerschmidt S, Wolff S, Hocke A, Rosseau S, Muller E, Rohde M. Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect Immun. 2005;73(8):4653–67.CrossRefPubMedPubMedCentral
10.
go back to reference Braun JS, Sublett JE, Freyer D, Mitchell TJ, Cleveland JL, Tuomanen EI, et al. Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. J Clin Invest. 2002;109(1):19–27.CrossRefPubMedPubMedCentral Braun JS, Sublett JE, Freyer D, Mitchell TJ, Cleveland JL, Tuomanen EI, et al. Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. J Clin Invest. 2002;109(1):19–27.CrossRefPubMedPubMedCentral
11.
go back to reference Hoffmann O, Priller J, Prozorovski T, Schulze-Topphoff U, Baeva N, Lunemann JD, et al. TRAIL limits excessive host immune responses in bacterial meningitis. J Clin Invest. 2007;117(7):2004–13.CrossRefPubMedPubMedCentral Hoffmann O, Priller J, Prozorovski T, Schulze-Topphoff U, Baeva N, Lunemann JD, et al. TRAIL limits excessive host immune responses in bacterial meningitis. J Clin Invest. 2007;117(7):2004–13.CrossRefPubMedPubMedCentral
12.
go back to reference de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549–56.CrossRefPubMed de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549–56.CrossRefPubMed
13.
14.
go back to reference de Sevilla MF, Garcia-Garcia JJ, Esteva C, Moraga F, Hernandez S, Selva L, et al. Clinical presentation of invasive pneumococcal disease in Spain in the era of heptavalent conjugate vaccine. Pediatr Infect Dis J. 2012;31(2):124–8.CrossRefPubMed de Sevilla MF, Garcia-Garcia JJ, Esteva C, Moraga F, Hernandez S, Selva L, et al. Clinical presentation of invasive pneumococcal disease in Spain in the era of heptavalent conjugate vaccine. Pediatr Infect Dis J. 2012;31(2):124–8.CrossRefPubMed
15.
go back to reference Ladhani SN, Slack MP, Andrews NJ, Waight PA, Borrow R, Miller E. Invasive pneumococcal disease after routine pneumococcal conjugate vaccination in children, England and Wales. Emerg Infect Dis. 2013;19(1):61–8.CrossRefPubMedPubMedCentral Ladhani SN, Slack MP, Andrews NJ, Waight PA, Borrow R, Miller E. Invasive pneumococcal disease after routine pneumococcal conjugate vaccination in children, England and Wales. Emerg Infect Dis. 2013;19(1):61–8.CrossRefPubMedPubMedCentral
16.
go back to reference Pichon B, Ladhani SN, Slack MP, Segonds-Pichon A, Andrews NJ, Waight PA, et al. Changes in molecular epidemiology of Streptococcus pneumoniae causing meningitis following introduction of pneumococcal conjugate vaccination in England and Wales. J Clin Microbiol. 2013;51(3):820–7.CrossRefPubMedPubMedCentral Pichon B, Ladhani SN, Slack MP, Segonds-Pichon A, Andrews NJ, Waight PA, et al. Changes in molecular epidemiology of Streptococcus pneumoniae causing meningitis following introduction of pneumococcal conjugate vaccination in England and Wales. J Clin Microbiol. 2013;51(3):820–7.CrossRefPubMedPubMedCentral
17.
go back to reference Elberse KE, van der Heide HG, Witteveen S, van de Pol I, Schot CS, van der Ende A, et al. Changes in the composition of the pneumococcal population and in IPD incidence in The Netherlands after the implementation of the 7-valent pneumococcal conjugate vaccine. Vaccine. 2012;30(52):7644–51.CrossRefPubMed Elberse KE, van der Heide HG, Witteveen S, van de Pol I, Schot CS, van der Ende A, et al. Changes in the composition of the pneumococcal population and in IPD incidence in The Netherlands after the implementation of the 7-valent pneumococcal conjugate vaccine. Vaccine. 2012;30(52):7644–51.CrossRefPubMed
18.
go back to reference Myint TT, Madhava H, Balmer P, Christopoulou D, Attal S, Menegas D, et al. The impact of 7-valent pneumococcal conjugate vaccine on invasive pneumococcal disease: a literature review. Adv Ther. 2013;30(2):127–51.CrossRefPubMed Myint TT, Madhava H, Balmer P, Christopoulou D, Attal S, Menegas D, et al. The impact of 7-valent pneumococcal conjugate vaccine on invasive pneumococcal disease: a literature review. Adv Ther. 2013;30(2):127–51.CrossRefPubMed
19.
go back to reference Imöhl M, Reinert RR, Ocklenburg C, van der Linden M. Association of serotypes of Streptococcus pneumoniae with age in invasive pneumococcal disease. J Clin Microbiol. 2010;48(4):1291–6.CrossRefPubMedPubMedCentral Imöhl M, Reinert RR, Ocklenburg C, van der Linden M. Association of serotypes of Streptococcus pneumoniae with age in invasive pneumococcal disease. J Clin Microbiol. 2010;48(4):1291–6.CrossRefPubMedPubMedCentral
20.
go back to reference Clinical Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. Wayne, PA;2014. Clinical Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. Wayne, PA;2014.
21.
go back to reference Ständige Impfkommission (STIKO). Empfehlungen der Ständigen Impfkommission (STIKO) am Robert Koch-Institut (Stand Juli 2006):Begründungen zur allgemeinen Empfehlung der Impfungen gegen Pneumokokken- und Meningokokken im Säuglings- und Kindesalter. Epidemiolgisches Bulletin. 2006;(31):255–260. Ständige Impfkommission (STIKO). Empfehlungen der Ständigen Impfkommission (STIKO) am Robert Koch-Institut (Stand Juli 2006):Begründungen zur allgemeinen Empfehlung der Impfungen gegen Pneumokokken- und Meningokokken im Säuglings- und Kindesalter. Epidemiolgisches Bulletin. 2006;(31):255–260.
22.
go back to reference McIntyre PB, O’Brien KL, Greenwood B, van de Beek D. Effect of vaccines on bacterial meningitis worldwide. Lancet. 2012;380(9854):1703–11.CrossRefPubMed McIntyre PB, O’Brien KL, Greenwood B, van de Beek D. Effect of vaccines on bacterial meningitis worldwide. Lancet. 2012;380(9854):1703–11.CrossRefPubMed
23.
go back to reference van der Linden M, Weiss S, Falkenhorst G, Siedler A, Imöhl M, von Kries R. Four years of universal pneumococcal conjugate infant vaccination in Germany: Impact on incidence of invasive pneumococcal disease and serotype distribution in children. Vaccine. 2012;30(40):5880–5.CrossRefPubMed van der Linden M, Weiss S, Falkenhorst G, Siedler A, Imöhl M, von Kries R. Four years of universal pneumococcal conjugate infant vaccination in Germany: Impact on incidence of invasive pneumococcal disease and serotype distribution in children. Vaccine. 2012;30(40):5880–5.CrossRefPubMed
24.
go back to reference Hsu HE, Shutt KA, Moore MR, Beall BW, Bennett NM, Craig AS, et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med. 2009;360(3):244–56.CrossRefPubMedPubMedCentral Hsu HE, Shutt KA, Moore MR, Beall BW, Bennett NM, Craig AS, et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med. 2009;360(3):244–56.CrossRefPubMedPubMedCentral
25.
go back to reference Casado-Flores J, Rodrigo C, Aristegui J, Martinon JM, Fenoll A, Mendez C. Decline in pneumococcal meningitis in Spain after introduction of the heptavalent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2008;27(11):1020–2.CrossRefPubMed Casado-Flores J, Rodrigo C, Aristegui J, Martinon JM, Fenoll A, Mendez C. Decline in pneumococcal meningitis in Spain after introduction of the heptavalent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2008;27(11):1020–2.CrossRefPubMed
26.
go back to reference Stephens DS. Protecting the herd: the remarkable effectiveness of the bacterial meningitis polysaccharide-protein conjugate vaccines in altering transmission dynamics. Trans Am Clin Climatol Assoc. 2011;122:115–23.PubMedPubMedCentral Stephens DS. Protecting the herd: the remarkable effectiveness of the bacterial meningitis polysaccharide-protein conjugate vaccines in altering transmission dynamics. Trans Am Clin Climatol Assoc. 2011;122:115–23.PubMedPubMedCentral
27.
go back to reference Pantosti A, D’Ambrosio F, Tarasi A, Recchia S, Orefici G, Mastrantonio P. Antibiotic susceptibility and serotype distribution of Streptococcus pneumoniae causing meningitis in Italy, 1997–1999. Clin Infect Dis. 2000;31(6):1373–9.CrossRefPubMed Pantosti A, D’Ambrosio F, Tarasi A, Recchia S, Orefici G, Mastrantonio P. Antibiotic susceptibility and serotype distribution of Streptococcus pneumoniae causing meningitis in Italy, 1997–1999. Clin Infect Dis. 2000;31(6):1373–9.CrossRefPubMed
28.
go back to reference Verhaegen J, Vandecasteele SJ, Vandeven J, Verbiest N, Lagrou K, Peetermans WE. Antibiotic susceptibility and serotype distribution of 240 Streptococcus pneumoniae causing meningitis in Belgium 1997–2000. Acta Clin Belg. 2003;58(1):19–26.CrossRefPubMed Verhaegen J, Vandecasteele SJ, Vandeven J, Verbiest N, Lagrou K, Peetermans WE. Antibiotic susceptibility and serotype distribution of 240 Streptococcus pneumoniae causing meningitis in Belgium 1997–2000. Acta Clin Belg. 2003;58(1):19–26.CrossRefPubMed
29.
go back to reference Vieira AC, Gomes MC, Rolo Filho M, Eudes Filho J, Bello EJ, de Figueiredo RB. Streptococcus pneumoniae: a study of strains isolated from cerebrospinal fluid. J Pediatr (Rio J). 2007;83(1):71–8. Vieira AC, Gomes MC, Rolo Filho M, Eudes Filho J, Bello EJ, de Figueiredo RB. Streptococcus pneumoniae: a study of strains isolated from cerebrospinal fluid. J Pediatr (Rio J). 2007;83(1):71–8.
30.
go back to reference Imöhl M, Reinert RR, van der Linden M. Regional differences in serotype distribution, pneumococcal vaccine coverage, and antimicrobial resistance of invasive pneumococcal disease among German federal states. Int J Med Microbiol. 2009;300(4):237–47.CrossRefPubMed Imöhl M, Reinert RR, van der Linden M. Regional differences in serotype distribution, pneumococcal vaccine coverage, and antimicrobial resistance of invasive pneumococcal disease among German federal states. Int J Med Microbiol. 2009;300(4):237–47.CrossRefPubMed
31.
go back to reference Imöhl M, Reinert RR, van der Linden M. Adult invasive pneumococcal disease between 2003 and 2006 in North-Rhine Westphalia, Germany: serotype distribution before recommendation for general pneumococcal conjugate vaccination for children <2 years of age. Clin Microbiol Infect. 2009;15(11):1008–12.CrossRefPubMed Imöhl M, Reinert RR, van der Linden M. Adult invasive pneumococcal disease between 2003 and 2006 in North-Rhine Westphalia, Germany: serotype distribution before recommendation for general pneumococcal conjugate vaccination for children <2 years of age. Clin Microbiol Infect. 2009;15(11):1008–12.CrossRefPubMed
32.
go back to reference Feikin DR, Klugman KP, Facklam RR, Zell ER, Schuchat A, Whitney CG. Increased prevalence of pediatric pneumococcal serotypes in elderly adults. Clin Infect Dis. 2005;41(4):481–7.CrossRefPubMed Feikin DR, Klugman KP, Facklam RR, Zell ER, Schuchat A, Whitney CG. Increased prevalence of pediatric pneumococcal serotypes in elderly adults. Clin Infect Dis. 2005;41(4):481–7.CrossRefPubMed
33.
go back to reference Harboe ZB, Thomsen RW, Riis A, Valentiner-Branth P, Christensen JJ, Lambertsen L, et al. Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study. PLoS Med. 2009;6(5):e1000081.CrossRefPubMedPubMedCentral Harboe ZB, Thomsen RW, Riis A, Valentiner-Branth P, Christensen JJ, Lambertsen L, et al. Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study. PLoS Med. 2009;6(5):e1000081.CrossRefPubMedPubMedCentral
34.
go back to reference Alexandre C, Dubos F, Courouble C, Pruvost I, Varon E, Martinot A. Rebound in the incidence of pneumococcal meningitis in northern France: effect of serotype replacement. Acta Paediatr. 2010;99(11):1686–90.CrossRefPubMed Alexandre C, Dubos F, Courouble C, Pruvost I, Varon E, Martinot A. Rebound in the incidence of pneumococcal meningitis in northern France: effect of serotype replacement. Acta Paediatr. 2010;99(11):1686–90.CrossRefPubMed
35.
go back to reference Rajasingham CR, Bonsu BK, Chapman JI, Cohen DM, Barson WJ. Serious neurologic sequelae in cases of meningitis arising from infection by conjugate vaccine-related and nonvaccine-related serogroups of Streptococcus pneumoniae. Pediatr Infect Dis J. 2008;27(9):771–5.CrossRefPubMed Rajasingham CR, Bonsu BK, Chapman JI, Cohen DM, Barson WJ. Serious neurologic sequelae in cases of meningitis arising from infection by conjugate vaccine-related and nonvaccine-related serogroups of Streptococcus pneumoniae. Pediatr Infect Dis J. 2008;27(9):771–5.CrossRefPubMed
36.
go back to reference Nigrovic LE, Kuppermann N, Malley R. Children with bacterial meningitis presenting to the emergency department during the pneumococcal conjugate vaccine era. Acad Emerg Med. 2008;15(6):522–8.CrossRefPubMed Nigrovic LE, Kuppermann N, Malley R. Children with bacterial meningitis presenting to the emergency department during the pneumococcal conjugate vaccine era. Acad Emerg Med. 2008;15(6):522–8.CrossRefPubMed
37.
go back to reference Livermore DM. Bacterial resistance: origins, epidemiology, and impact. Clin Infect Dis. 2003;36 Suppl 1:S11–23.CrossRefPubMed Livermore DM. Bacterial resistance: origins, epidemiology, and impact. Clin Infect Dis. 2003;36 Suppl 1:S11–23.CrossRefPubMed
38.
go back to reference Jacobs MR, Good CE, Beall B, Bajaksouzian S, Windau AR, Whitney CG. Changes in serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae strains in Cleveland: a quarter century of experience. J Clin Microbiol. 2008;46(3):982–90.CrossRefPubMedPubMedCentral Jacobs MR, Good CE, Beall B, Bajaksouzian S, Windau AR, Whitney CG. Changes in serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae strains in Cleveland: a quarter century of experience. J Clin Microbiol. 2008;46(3):982–90.CrossRefPubMedPubMedCentral
39.
go back to reference Adam D. Global antibiotic resistance in Streptococcus pneumoniae. J Antimicrob Chemother. 2002;50(Suppl):1–5.CrossRefPubMed Adam D. Global antibiotic resistance in Streptococcus pneumoniae. J Antimicrob Chemother. 2002;50(Suppl):1–5.CrossRefPubMed
40.
go back to reference Felmingham D, Reinert RR, Hirakata Y, Rodloff A. Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin. J Antimicrob Chemother. 2002;50(Suppl S1):25–37.CrossRefPubMed Felmingham D, Reinert RR, Hirakata Y, Rodloff A. Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin. J Antimicrob Chemother. 2002;50(Suppl S1):25–37.CrossRefPubMed
41.
go back to reference Imöhl M, Reinert RR, van der Linden M. New penicillin susceptibility breakpoints for Streptococcus pneumoniae and their effects on susceptibility categorisation in Germany (1992–2008). Int J Antimicrob Agents. 2009;34(3):271–3.CrossRefPubMed Imöhl M, Reinert RR, van der Linden M. New penicillin susceptibility breakpoints for Streptococcus pneumoniae and their effects on susceptibility categorisation in Germany (1992–2008). Int J Antimicrob Agents. 2009;34(3):271–3.CrossRefPubMed
42.
go back to reference Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae--United States, 2006–2007. MMWR Morb Mortal Wkly Rep. 2008;57(50):1353–5. Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae--United States, 2006–2007. MMWR Morb Mortal Wkly Rep. 2008;57(50):1353–5.
43.
go back to reference Imöhl M, Reinert RR, Mutscher C, van der Linden M. Macrolide susceptibility and serotype specific macrolide resistance of invasive isolates of Streptococcus pneumoniae in Germany from 1992 to 2008. BMC Microbiol. 2010;10:299.CrossRefPubMedPubMedCentral Imöhl M, Reinert RR, Mutscher C, van der Linden M. Macrolide susceptibility and serotype specific macrolide resistance of invasive isolates of Streptococcus pneumoniae in Germany from 1992 to 2008. BMC Microbiol. 2010;10:299.CrossRefPubMedPubMedCentral
44.
go back to reference Skoczynska A, Hryniewicz W. Genetic relatedness, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae responsible for meningitis in Poland, 1997–2001. Microb Drug Resist. 2003;9(2):175–82.CrossRefPubMed Skoczynska A, Hryniewicz W. Genetic relatedness, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae responsible for meningitis in Poland, 1997–2001. Microb Drug Resist. 2003;9(2):175–82.CrossRefPubMed
45.
go back to reference Sjostrom K, Spindler C, Ortqvist A, Kalin M, Sandgren A, Kuhlmann-Berenzon S, et al. Clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen. Clin Infect Dis. 2006;42(4):451–9.CrossRefPubMed Sjostrom K, Spindler C, Ortqvist A, Kalin M, Sandgren A, Kuhlmann-Berenzon S, et al. Clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen. Clin Infect Dis. 2006;42(4):451–9.CrossRefPubMed
Metadata
Title
Pneumococcal meningitis and vaccine effects in the era of conjugate vaccination: results of 20 years of nationwide surveillance in Germany
Authors
Matthias Imöhl
Jens Möller
Ralf René Reinert
Stephanie Perniciaro
Mark van der Linden
Orhan Aktas
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2015
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-015-0787-1

Other articles of this Issue 1/2015

BMC Infectious Diseases 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.