Pneumokokkenimpfung: Konjugatimpfstoff induziert Herdenimmunität und reduziert Antibiotikaresistenz

 

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Zusammenfassung

Besonders Kleinkinder und ältere Menschen sind häufig von Infektionen mit Pneumokokken (Pneumonie, Otitis media, Sinusitis, Meningitis) betroffen. Derzeit sind zwei verschiedene Pneumokokkenimpfungen verfügbar, welche Antikörper gegen Kapselpolysaccharide der Bakterien induzieren. Der ältere Impfstoff ist ein reiner Polysaccharidimpfstoff, welcher eine begrenzte humorale Immunität gegen Pneumokokken induziert, da Polysaccharide wenig immunogen sind und primär B-Zellen stimulieren. Im Jahre 2000 wurde in den USA ein Impfprogramm für Kleinkinder mit einem neuen 7-valenten Pneumokokken-Konjugatimpfstoff initiiert. Hierbei induziert die Konjugation von Kapselpolysacchariden an hochimmunogenes Diphterietoxoid eine Effektor-T-Zell und B-Zellantwort mit konsekutiver Entwicklung einer humoralen und mukosalen Immunität. Daten aus den USA belegen, dass mit der Impfung von Kindern als dem Hauptreservoir für Pneumokokken gleichsam die durch den Konjugat-impfstoff abgedeckten Pneumokokken-Serotypen in der gesamten Bevölkerung eradiziert werden können. Diese ausgeprägte, sogenannte Herdenimmunität führt zu einer Reduktion invasiver Pneumokokkeninfektionen bei Nicht-Geimpften und zu einem Rückgang antibiotikaresistenter Pneumokokkenstämme. Allerdings häufen sich Hinweise, dass die von der Impfung nicht erfassten Serotypen ökologische Nischen besetzen und somit vermehrt auftreten können. Dieser Situation wird durch die Entwicklung eines 13-valenten Konjugatimpfstoffes bereits jetzt Rechnung getragen.

Summary

Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers and the elderly. Currently, two pneumococcal vaccines are in clinical use. The older vaccine consists of pure capsular polysaccharides from 23 pneumococcal serotypes and induces only a limited B-cell response because polysaccharides are poor antigens that stimulate mainly B-cells. In 2000, a vaccination program with a novel 7-valent pneumococcal conjugate vaccine was launched in the U.S. The conjugation of capsular polysaccharides with a highly immunogenic diphteria toxoid protein induces both a T cell and B cell response that results in specific humoral and mucosal immunity. Since children are the main reservoir of pneumococci, the 7-valent conjugate vaccine seems to eradicate the respective pneumococcal serotypes within the population, as demonstrated by recent US data. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates.

However, recent data suggest a replacement of vaccine-serotypes by non-vaccine serotypes, which conquer the ecological niche created by the vaccine. In order to encounter this problem a 13-valent conjugated vaccine is currently under development.

Literatur

• 1 Ada G. Vaccines and vaccination.  N Engl J Med. 2001;  345 1042-53
  Google Scholar
• 2 CDC . Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease.  Morb Mortal Wkly Rep. 2005;  54 893-7
  Google Scholar
• 3 Christenson B, Lundbergh P, Hedlund J, Ortqvist A. Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in adults aged 65 years or older.  Lancet. 2001;  357 1008-11
  Google Scholar
• 4 Colino J, Shen Y, Snapper C M. Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms.  J Exp Med. 2002;  195 1-13
  Google Scholar
• 5 Cowan M J, Ammann A J, Wara D W. et al . Pneumococcal polysaccharide immunization in infants and children.  Pediatrics. 1978;  62 721-7
  Google Scholar
• 6 Craig W A. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men.  Clin Infect Dis. 1998;  26 1-10
  Google Scholar
• 7 Daneman N, McGeer A, Green K, Low D E. Macrolide resistance in bacteremic pneumococcal disease.  Clin Infect Dis. 2006;  43 432-8
  Google Scholar
• 8 De Lencastre H, Kristinsson K G, Brito-Avo A. et al . Carriage of respiratory tract pathogens and molecular epidemiology of Streptococcus pneumoniae colonization in healthy children attending day care centers in Lisbon, Portugal.  Microb Drug Resist. 1999;  5 19-29
  Google Scholar
• 9 De Roux A, Schmidt N, Rose M, Zielen S, Pletz M, Lode H. Immunogenity of the pneumococcal polysaccharide vaccine in COPD patients.  Resp Med. 2004;  98 1187-1194
  Google Scholar
• 10 De Roux A, Schmöle-Thoma B, Siber G R, Hackell J G, Kuhnke A. et al . Comparison of pneumococcal conjugated polysaccharide vaccines in the elderly adults.  Clin Infect Dis. 2008, in press; 
  Google Scholar
• 11 Granoff D M, Gupta R K, Belshe R B, Anderson E L. Induction of immunologic refractoriness in adults by meningococcal C polysaccharide vaccination.  J Infect Dis. 1998;  178 870-4
  Google Scholar
• 12 Hendley J O, Wenzel J G, Ashe K M, Samuelson J S. Immunogenicity of Haemophilus influenzae type b capsular polysaccharide vaccines in 18-month-old infants.  Pediatrics. 1987;  80 351-4
  Google Scholar
• 13 Jackson L A, Neuzil K M, Nahm M H. et al . Immunogenicity of varying dosages of 7-valent pneumococcal polysaccharide-protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine.  Vaccine. 2007;  25 4029-37
  Google Scholar
• 14 Kupronis B A, Richards C L, Whitney C G. Invasive pneumococcal disease in older adults residing in long-term care facilities and in the community.  J Am Geriatr Soc. 2003;  51 1520-5
  Google Scholar
• 15 Kyaw M H, Lynfield R, Schaffner W. et al . Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae.  N Engl J Med. 2006;  354 1455-63
  Google Scholar
• 16 Mykietiuk A. et al . Effect of prior pneumococcal vaccination on clinical outcome of hospitalized adults with community-acquired pneumococcal pneumonia.  Eur J Clin Microbiol Infect Dis. 2006;  25 457-62
  Google Scholar
• 17 Pletz M W. Ambulant erworbene Pneumonie: Häufige Erreger und Antibiotikaresistenz.  Der Pneumologe. 2005;  2 17-27
  Google Scholar
• 18 Pletz M W, Fugit R V, McGee L, Glasheen J J, Keller D L, Welte T, Klugman K P. Fluoroquinolone-resistant Streptococcus pneumoniae.  Emerg Infect Dis. 2006;  12 1462-3
  Google Scholar
• 19 Pletz M W, McGee L, Burkhardt O, Lode H, Klugman K P. Ciprofloxacin treatment failure in a patient with resistant Streptococcus pneumoniae infection following prior ciprofloxacin therapy.  Eur J Clin Microbiol Infect Dis. 2005;  24 58-60
  Google Scholar
• 20 Pletz M W, McGee L, Jorgensen J, Beall B. et al . Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States.  Antimicrob Agents Chemother. 2004;  48 3491-7
  Google Scholar
• 21 Reinert R R, Haupts S. et al . Invasive pneumococcal disease in adults in North-Rhine Westphalia, Germany, 2001 - 2003.  Clin Microbiol Infect. 2005;  11 985-91
  Google Scholar
• 22 Reinert R R, Reinert S, van der Linden M. et al . Antimicrobial susceptibility of Streptococcus pneumoniae in eight European countries from 2001 to 2003.  Antimicrob Agents Chemother. 2005;  49 2903-13
  Google Scholar
• 23 Reinert R R, van der Linden M, Seegmuller I. et al . Molecular epidemiology of penicillin-non-susceptible Streptococcus pneumoniae isolates from children with invasive pneumococcal disease in Germany.  Clin Microbiol Infect. 2007;  13 363-8
  Google Scholar
• 24 Robert-Koch-Institut . Begründung der STIKO-Empfehlung zur Impfung gegen Pneumokokken und Menigokokken vom Juli 2006.  Epidemiol Bull. 2006;  50 255-260
  Google Scholar
• 25 Robinson K A, Baughman W, Rothrock G . et al . Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995 - 1998.  JAMA. 2001;  285 1729-35
  Google Scholar
• 26 Rubins J B. et al . Magnitude, duration, quality, and function of pneumococcal vaccine responses in elderly adults.  J Infect Dis. 1998;  178 431-40
  Google Scholar
• 27 Schnoor M, Klante T, Beckmann M, Robra B P, Welte T, Raspe H, Schäfer T. Risk factors for community-acquired pneumonia in German adults.  Epidemiol Infect. 2007;  135 1-9
  Google Scholar
• 28 Stein K E. Thymus-independent and thymus-dependent responses to polysaccharide antigens.  J Infect Dis. 1992;  165 Suppl 1 S49-52
  Google Scholar
• 29 Stephens D S, Zughaier S M, Whitney C G. et al . Incidence of macrolide resistance in Streptococcus pneumoniae after introduction of the pneumococcal conjugate vaccine.  Lancet. 2005;  365 855-63
  Google Scholar
• 30 van der Linden M, Al-Lahham A, Haupts S, Reinert R R. Clonal spread of mef-positive macrolide-resistant Streptococcus pneumoniae isolates causing invasive disease in adults in Germany.  Antimicrob Agents Chemother. 2007;  51 1830-4
  Google Scholar
• 31 Yu V L, Chiou C C. et al . An international prospective study of pneumococcal bacteremia.  Clin Infect Dis. 2003;  37 230-7
  Google Scholar

Dr. Mathias W. Pletz

Klinik für Pneumologie, Medizinische Hochschule Hannover

Carl-Neuberg-Str. 1

30625 Hannover

Phone: 0511/532-3661

Phone: 0511/532-3533

Email: Pletz.Mathias@mh-hannover.de