The fundamental link between pneumococcal carriage and disease

References

• Skinner JM, Indrawati L, Cannon J et al. Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model. Vaccine 29(48), 8870–8876 (2011).
   PubMed Web of Science ®Google Scholar
• Moffitt KL, Malley R. Next generation pneumococcal vaccines. Curr. Opin. Immunol. 23(3), 407–413 (2011).
   PubMed Web of Science ®Google Scholar
• Linder TE, Daniels RL, Lim DJ, DeMaria TF. Effect of intranasal inoculation of Streptococcus pneumoniae on the structure of the surface carbohydrates of the chinchilla eustachian tube and middle ear mucosa. Microb. Pathog. 16(6), 435–441 (1994).
   PubMed Web of Science ®Google Scholar
• Peltola VT, Boyd KL, McAuley JL, Rehg JE, McCullers JA. Bacterial sinusitis and otitis media following influenza virus infection in ferrets. Infect. Immun. 74(5), 2562–2567 (2006).
   PubMed Web of Science ®Google Scholar
• van der Ven LT, van den Dobbelsteen GP, Nagarajah B et al. A new rat model of otitis media caused by Streptococcus pneumoniae: conditions and application in immunization protocols. Infect. Immun. 67(11), 6098–6103 (1999).
   PubMed Web of Science ®Google Scholar
• Kadioglu A, Gingles NA, Grattan K, Kerr A, Mitchell TJ, Andrew PW. Host cellular immune response to pneumococcal lung infection in mice. Infect. Immun. 68(2), 492–501 (2000).
   PubMed Web of Science ®Google Scholar
• Ogunniyi AD, LeMessurier KS, Graham RM et al. Contributions of pneumolysin, pneumococcal surface protein A (PspA), and PspC to pathogenicity of Streptococcus pneumoniae D39 in a mouse model. Infect. Immun. 75(4), 1843–1851 (2007).
   PubMed Web of Science ®Google Scholar
• Gray BM, Converse GM 3rd, Dillon HC Jr. Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J. Infect. Dis. 142(6), 923–933 (1980).
   PubMed Web of Science ®Google Scholar
• Syrjänen RK, Auranen KJ, Leino TM, Kilpi TM, Mäkelä PH. Pneumococcal acute otitis media in relation to pneumococcal nasopharyngeal carriage. Pediatr. Infect. Dis. J. 24(9), 801–806 (2005).
   PubMed Web of Science ®Google Scholar
• Syrjänen RK, Herva EE, Mäkelä PH et al. The value of nasopharyngeal culture in predicting the etiology of acute otitis media in children less than two years of age. Pediatr. Infect. Dis. J. 25(11), 1032–1036 (2006).
   PubMed Web of Science ®Google Scholar
• Sleeman KL, Daniels L, Gardiner M et al. Acquisition of Streptococcus pneumoniae and nonspecific morbidity in infants and their families: a cohort study. Pediatr. Infect. Dis. J. 24(2), 121–127 (2005).
   PubMed Web of Science ®Google Scholar
• Eldan M, Leibovitz E, Piglansky L et al. Predictive value of pneumococcal nasopharyngeal cultures for the assessment of nonresponsive acute otitis media in children. Pediatr. Infect. Dis. J. 19(4), 298–303 (2000).
   PubMed Web of Science ®Google Scholar
• Faden H, Stanievich J, Brodsky L, Bernstein J, Ogra PL. Changes in nasopharyngeal flora during otitis media of childhood. Pediatr. Infect. Dis. J. 9(9), 623–626 (1990).
   PubMed Web of Science ®Google Scholar
• Kamme C, Lundgren K, Märdh PA. The aetiology of acute otitis media in children. Occurrence of bacteria, L forms of bacteria and mycoplasma in the middle ear exudate. Relationship between bacterial findings in the middle ear exudate, nasopharynx and throat. Scand. J. Infect. Dis. 3(3), 217–223 (1971).
   PubMedGoogle Scholar
• Luotonen J. Streptococcus pneumoniae and Haemophilus influenzae in nasal cultures during acute otitis media. Acta Otolaryngol. 93(3–4), 295–299 (1982).
   PubMed Web of Science ®Google Scholar
• Austrian R, Howie VM, Ploussard JH. The bacteriology of pneumococcal otitis media. Johns Hopkins Med. J. 141(3), 104–111 (1977).
   PubMedGoogle Scholar
• Mastro TD, Nomani NK, Ishaq Z et al. Use of nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae from children in Pakistan for surveillance for antimicrobial resistance. Pediatr. Infect. Dis. J. 12(10), 824–830 (1993).
   PubMed Web of Science ®Google Scholar
• Lloyd-Evans N, O’Dempsey TJ, Baldeh I et al. Nasopharyngeal carriage of pneumococci in Gambian children and in their families. Pediatr. Infect. Dis. J. 15(10), 866–871 (1996).
   PubMed Web of Science ®Google Scholar
• Högberg L, Geli P, Ringberg H, Melander E, Lipsitch M, Ekdahl K. Age- and serogroup-related differences in observed durations of nasopharyngeal carriage of penicillin-resistant pneumococci. J. Clin. Microbiol. 45(3), 948–952 (2007).
   PubMed Web of Science ®Google Scholar
• Brueggemann AB, Peto TE, Crook DW, Butler JC, Kristinsson KG, Spratt BG. Temporal and geographic stability of the serogroup-specific invasive disease potential of Streptococcus pneumoniae in children. J. Infect. Dis. 190(7), 1203–1211 (2004).
   PubMed Web of Science ®Google Scholar
• Greenberg D, Givon-Lavi N, Newman N, Bar-Ziv J, Dagan R. Nasopharyngeal carriage of individual Streptococcus pneumoniae serotypes during pediatric pneumonia as a means to estimate serotype disease potential. Pediatr. Infect. Dis. J. 30(3), 227–233 (2011).
   PubMed Web of Science ®Google Scholar
• Gray BM, Turner ME, Dillon HC Jr. Epidemiologic studies of Streptococcus pneumoniae in infants. The effects of season and age on pneumococcal acquisition and carriage in the first 24 months of life. Am. J. Epidemiol. 116(4), 692–703 (1982).
   PubMed Web of Science ®Google Scholar
• Hodges RG, MacLeod CM. Epidemic pneumococcal pneumonia; final consideration of the factors underlying the epidemic. Am. J. Hyg. 44(2), 237–243 (1946).
   PubMedGoogle Scholar
• Ritchie ND, Mitchell TJ, Evans TJ. What is different about serotype 1 pneumococci? Future Microbiol. 7(1), 33–46 (2012).
   PubMed Web of Science ®Google Scholar
• Balicer RD, Zarka S, Levine H et al. Control of Streptococcus pneumoniae serotype 5 epidemic of severe pneumonia among young army recruits by mass antibiotic treatment and vaccination. Vaccine 28(34), 5591–5596 (2010).
   PubMed Web of Science ®Google Scholar
• Albrich WC, Madhi SA, Adrian PV et al. Use of a rapid test of pneumococcal colonization density to diagnose pneumococcal pneumonia. Clin. Infect. Dis. 54(5), 601–609 (2012).
   PubMed Web of Science ®Google Scholar
• Auranen K, Ranta J, Takala AK, Arjas E. A statistical model of transmission of Hib bacteria in a family. Stat. Med. 15(20), 2235–2252 (1996).
   PubMed Web of Science ®Google Scholar
• Irving TJ, Blyuss KB, Colijn C, Trotter CL. Modelling meningococcal meningitis in the African meningitis belt. Epidemiol. Infect. 140(5), 897–905 (2012).
   PubMed Web of Science ®Google Scholar
• Ranta J, Mäkelä PH, Arjas E. Predicting meningococcal disease outbreaks in structured populations. Stat. Med. 23(6), 927–945 (2004).
   PubMed Web of Science ®Google Scholar
• Loda FA, Collier AM, Glezen WP, Strangert K, Clyde WA Jr, Denny FW. Occurrence of Diplococcus pneumoniae in the upper respiratory tract of children. J. Pediatr. 87(6 Pt 2), 1087–1093 (1975).
   PubMed Web of Science ®Google Scholar
• Hendley JO, Sande MA, Stewart PM, Gwaltney JM Jr. Spread of Streptococcus pneumoniae in families. I. Carriage rates and distribution of types. J. Infect. Dis. 132(1), 55–61 (1975).
   PubMed Web of Science ®Google Scholar
• Ingvarsson L, Lundgren L, Ursing J. The bacterial flora in the nasopharynx in healthy children. Acta Otolaryngol (Stockh.) 386, 94–96 (1982).
   Google Scholar
• Syrjänen RK, Kilpi TM, Kaijalainen TH, Herva EE, Takala AK. Nasopharyngeal carriage of Streptococcus pneumoniae in Finnish children younger than 2 years old. J. Infect. Dis. 184(4), 451–459 (2001).
   PubMed Web of Science ®Google Scholar
• Roca A, Hill PC, Townend J et al. Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in The Gambia: a cluster-randomized trial. PLoS Med. 8(10), e1001107 (2011).
   PubMed Web of Science ®Google Scholar
• Scott JR, Millar EV, Lipsitch M et al. Impact of more than a decade of pneumococcal conjugate vaccine use on carriage and invasive potential in Native American communities. J. Infect. Dis. 205(2), 280–288 (2012).
   PubMed Web of Science ®Google Scholar
• Montgomery JM, Lehmann D, Smith T et al. Bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in Highland children of Papua New Guinea. Rev. Infect. Dis. 12(Suppl. 8), S1006–S1016 (1990).
   PubMedGoogle Scholar
• Faden H, Duffy L, Boeve M. Otitis media: back to basics. Pediatr. Infect. Dis. J. 17(12), 1105–1112; quiz 1112 (1998).
   PubMed Web of Science ®Google Scholar
• Gray BM, Converse GM 3rd, Dillon HC Jr. Serotypes of Streptococcus pneumoniae causing disease. J. Infect. Dis. 140(6), 979–983 (1979).
   PubMed Web of Science ®Google Scholar
• Eskola J, Takala AK, Kela E, Pekkanen E, Kalliokoski R, Leinonen M. Epidemiology of invasive pneumococcal infections in children in Finland. JAMA 268(23), 3323–3327 (1992).
   PubMed Web of Science ®Google Scholar
• Sniadack DH, Schwartz B, Lipman H et al. Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children – implications for vaccine strategies. Pediatr. Infect. Dis. J. 14(6), 503–510 (1995).
   PubMed Web of Science ®Google Scholar
• Kilpi T, Herva E, Kaijalainen T, Syrjänen R, Takala AK. Bacteriology of acute otitis media in a cohort of Finnish children followed for the first two years of life. Pediatr. Infect. Dis. J. 20(7), 654–662 (2001).
   PubMed Web of Science ®Google Scholar
• Hanage WP, Auranen K, Syrjänen R et al. Ability of pneumococcal serotypes and clones to cause acute otitis media: implications for the prevention of otitis media by conjugate vaccines. Infect. Immun. 72(1), 76–81 (2004).
   PubMed Web of Science ®Google Scholar
• Shouval DS, Greenberg D, Givon-Lavi N, Porat N, Dagan R. Site-specific disease potential of individual Streptococcus pneumoniae serotypes in pediatric invasive disease, acute otitis media and acute conjunctivitis. Pediatr. Infect. Dis. J. 25(7), 602–607 (2006).
   PubMed Web of Science ®Google Scholar
• Rodgers GL, Arguedas A, Cohen R, Dagan R. Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: potential implications for pneumococcal conjugate vaccines. Vaccine 27(29), 3802–3810 (2009).
   PubMed Web of Science ®Google Scholar
• Johnson HL, Deloria-Knoll M, Levine OS et al. Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project. PLoS Med. 7(10), pii: e1000348 (2010).
   PubMed Web of Science ®Google Scholar
• Turner P, Hinds J, Turner C et al. Improved detection of nasopharyngeal cocolonization by multiple pneumococcal serotypes by use of latex agglutination or molecular serotyping by microarray. J. Clin. Microbiol. 49(5), 1784–1789 (2011).
   PubMed Web of Science ®Google Scholar
• Brueggemann AB, Griffiths DT, Meats E, Peto T, Crook DW, Spratt BG. Clonal relationships between invasive and carriage Streptococcus pneumoniae and serotype- and clone-specific differences in invasive disease potential. J. Infect. Dis. 187(9), 1424–1432 (2003).
   PubMed Web of Science ®Google Scholar
• Hanage WP, Kaijalainen TH, Syrjänen RK et al. Invasiveness of serotypes and clones of Streptococcus pneumoniae among children in Finland. Infect. Immun. 73(1), 431–435 (2005).
   PubMed Web of Science ®Google Scholar
• Butler JC. Epidemiology of pneumococcal disease. In: The Pneumococcus. Tuomanen EI, Mitchell TJ, Morrison D Spratt BG (Eds.). American Society for Microbiology, Washington DC, USA 148–168 (2004).
   Google Scholar
• Burke JP, Klein JO, Gezon HM, Finland M. Pneumococcal bacteremia. Review of 111 cases, 1957–1969, with special reference to cases with undetermined focus. Am. J. Dis. Child. 121(4), 353–359 (1971).
   PubMedGoogle Scholar
• Gray BM, Dillon HC Jr. Clinical and epidemiologic studies of pneumococcal infection in children. Pediatr. Infect. Dis. 5(2), 201–207 (1986).
   PubMedGoogle Scholar
• Hansman D. Serotypes of pneumococci in pneumonia, meningitis and other pneumococcal infections. Aust. N. Z. J. Med. 7(3), 267–270 (1977).
   PubMedGoogle Scholar
• Riley ID, Lehmann D, Alpers MP. Pneumococcal vaccine trials in Papua New Guinea: relationships between epidemiology of pneumococcal infection and efficacy of vaccine. Rev. Infect. Dis. 13(Suppl. 6), S535–S541 (1991).
   Google Scholar
• Millar EV, O’Brien KL, Zell ER, Bronsdon MA, Reid R, Santosham M. Nasopharyngeal carriage of Streptococcus pneumoniae in Navajo and White Mountain Apache children before the introduction of pneumococcal conjugate vaccine. Pediatr. Infect. Dis. J. 28(8), 711–716 (2009).
   PubMed Web of Science ®Google Scholar
• O’Brien KL, Shaw J, Weatherholtz R et al. Epidemiology of invasive Streptococcus pneumoniae among Navajo children in the era before use of conjugate pneumococcal vaccines, 1989–1996. Am. J. Epidemiol. 160(3), 270–278 (2004).
   PubMed Web of Science ®Google Scholar
• Vernet G, Saha S, Satzke C et al. Laboratory-based diagnosis of pneumococcal pneumonia: state of the art and unmet needs. Clin. Microbiol. Infect. 17(Suppl. 3), 1–13 (2011).
   PubMed Web of Science ®Google Scholar
• O’Brien KL, Wolfson LJ, Watt JP et al.; Hib and Pneumococcal Global Burden of Disease Study Team. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374(9693), 893–902 (2009).
   PubMed Web of Science ®Google Scholar
• Weiser JN. The pneumococcus: why a commensal misbehaves. J. Mol. Med. 88(2), 97–102 (2010).
   PubMed Web of Science ®Google Scholar
• Henrichsen J. Six newly recognized types of Streptococcus pneumoniae. J. Clin. Microbiol. 33(10), 2759–2762 (1995).
   PubMed Web of Science ®Google Scholar
• Kamerling JP. Pneumococcal polysaccharides: a chemical view. In: Streptococcus pneumoniae: Molecular Biology and Mechanisms of Disease. Tomasz A (Ed.). Mary Ann Liebert, Inc. NY, USA, 81–114 (2000).
   Google Scholar
• Nelson AL, Roche AM, Gould JM, Chim K, Ratner AJ, Weiser JN. Capsule enhances pneumococcal colonization by limiting mucus-mediated clearance. Infect. Immun. 75(1), 83–90 (2007).
   PubMed Web of Science ®Google Scholar
• Gorter AD, Hiemstra PS, de Bentzmann S, van Wetering S, Dankert J, van Alphen L. Stimulation of bacterial adherence by neutrophil defensins varies among bacterial species but not among host cell types. FEMS Immunol. Med. Microbiol. 28(2), 105–111 (2000).
   PubMedGoogle Scholar
• Weiser JN, Bae D, Fasching C, Scamurra RW, Ratner AJ, Janoff EN. Antibody-enhanced pneumococcal adherence requires IgA1 protease. Proc. Natl Acad. Sci. USA 100(7), 4215–4220 (2003).
   PubMed Web of Science ®Google Scholar
• Bruyn GA, Zegers BJ, van Furth R. Mechanisms of host defense against infection with Streptococcus pneumoniae. Clin. Infect. Dis. 14(1), 251–262 (1992).
   PubMed Web of Science ®Google Scholar
• Watson DA, Musher DM, Verhoef J. Pneumococcal virulence factors and host immune responses to them. Eur. J. Clin. Microbiol. Infect. Dis. 14(6), 479–490 (1995).
   PubMed Web of Science ®Google Scholar
• Brown EJ, Hosea SW, Hammer CH, Burch CG, Frank MM. A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia. J. Clin. Invest. 69(1), 85–98 (1982).
   PubMed Web of Science ®Google Scholar
• Winkelstein JA. Complement and the host’s defense against the pneumococcus. Crit. Rev. Microbiol. 11(3), 187–208 (1984).
   PubMed Web of Science ®Google Scholar
• Andersson B, Dahmén J, Frejd T et al. Identification of an active disaccharide unit of a glycoconjugate receptor for pneumococci attaching to human pharyngeal epithelial cells. J. Exp. Med. 158(2), 559–570 (1983).
   PubMed Web of Science ®Google Scholar
• Andersson B, Beachey EH, Tomasz A, Tuomanen E, Svanborg-Edén C. A sandwich adhesion on Streptococcus pneumoniae attaching to human oropharyngeal epithelial cells in vitro. Microb. Pathog. 4(4), 267–278 (1988).
   PubMed Web of Science ®Google Scholar
• Krivan HC, Roberts DD, Ginsburg V. Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc beta 1-4Gal found in some glycolipids. Proc. Natl Acad. Sci. USA 85(16), 6157–6161 (1988).
   PubMed Web of Science ®Google Scholar
• Andersson B, Eriksson B, Falsen E et al. Adhesion of Streptococcus pneumoniae to human pharyngeal epithelial cells in vitro: differences in adhesive capacity among strains isolated from subjects with otitis media, septicemia, or meningitis or from healthy carriers. Infect. Immun. 32(1), 311–317 (1981).
   PubMed Web of Science ®Google Scholar
• Idänpään-Heikkilä I, Simon PM, Zopf D et al. Oligosaccharides interfere with the establishment and progression of experimental pneumococcal pneumonia. J. Infect. Dis. 176(3), 704–712 (1997).
   PubMed Web of Science ®Google Scholar
• King SJ. Pneumococcal modification of host sugars: a major contributor to colonization of the human airway? Mol. Oral Microbiol. 25(1), 15–24 (2010).
   PubMed Web of Science ®Google Scholar
• King SJ, Hippe KR, Weiser JN. Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae. Mol. Microbiol. 59(3), 961–974 (2006).
   PubMed Web of Science ®Google Scholar
• Marion C, Limoli DH, Bobulsky GS, Abraham JL, Burnaugh AM, King SJ. Identification of a pneumococcal glycosidase that modifies O-linked glycans. Infect. Immun. 77(4), 1389–1396 (2009).
   PubMed Web of Science ®Google Scholar
• Rosenow C, Ryan P, Weiser JN et al. Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol. Microbiol. 25(5), 819–829 (1997).
   PubMed Web of Science ®Google Scholar
• Brooks-Walter A, Briles DE, Hollingshead SK. The pspC gene of Streptococcus pneumoniae encodes a polymorphic protein, PspC, which elicits cross-reactive antibodies to PspA and provides immunity to pneumococcal bacteremia. Infect. Immun. 67(12), 6533–6542 (1999).
   PubMed Web of Science ®Google Scholar
• Hammerschmidt S, Talay SR, Brandtzaeg P, Chhatwal GS. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol. Microbiol. 25(6), 1113–1124 (1997).
   PubMed Web of Science ®Google Scholar
• Hostetter MK, Cheng Q, Finkel DA. C3-binding protein (pbcA) in Streptococcus pneumoniae. Presented at: 97th General Meeting of the American Society for Microbiology. Miami, FL, USA, 4–8 May 1997.
   Google Scholar
• Janulczyk R, Iannelli F, Sjoholm AG, Pozzi G, Bjorck L. Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function. J. Biol. Chem. 275(47), 37257–37263 (2000).
   PubMed Web of Science ®Google Scholar
• Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377(6548), 435–438 (1995).
   PubMed Web of Science ®Google Scholar
• Fischer W, Behr T, Hartmann R, Peter-Katalinic J, Egge H. Teichoic acid and lipoteichoic acid of Streptococcus pneumoniae possess identical chain structures. A reinvestigation of teichoid acid (C polysaccharide). Eur. J. Biochem. 215(3), 851–857 (1993).
   PubMedGoogle Scholar
• Bagnoli F, Moschioni M, Donati C et al. A second pilus type in Streptococcus pneumoniae is prevalent in emerging serotypes and mediates adhesion to host cells. J. Bacteriol. 190(15), 5480–5492 (2008).
   PubMed Web of Science ®Google Scholar
• Barocchi MA, Ries J, Zogaj X et al. A pneumococcal pilus influences virulence and host inflammatory responses. Proc. Natl Acad. Sci. USA 103(8), 2857–2862 (2006).
   PubMed Web of Science ®Google Scholar
• Hava DL, Camilli A. Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol. Microbiol. 45(5), 1389–1406 (2002).
   PubMed Web of Science ®Google Scholar
• Bergmann S, Rohde M, Chhatwal GS, Hammerschmidt S. Alpha-enolase of Streptococcus pneumoniae is a plasmin(ogen)-binding protein displayed on the bacterial cell surface. Mol. Microbiol. 40(6), 1273–1287 (2001).
   PubMed Web of Science ®Google Scholar
• Holmes AR, McNab R, Millsap KW et al. The pavA gene of Streptococcus pneumoniae encodes a fibronectin-binding protein that is essential for virulence. Mol. Microbiol. 41(6), 1395–1408 (2001).
   PubMed Web of Science ®Google Scholar
• van der Flier M, Chhun N, Wizemann TM, Min J, McCarthy JB, Tuomanen EI. Adherence of Streptococcus pneumoniae to immobilized fibronectin. Infect. Immun. 63(11), 4317–4322 (1995).
   PubMed Web of Science ®Google Scholar
• Kostyukova NN, Volkova MO, Ivanova VV, Kvetnaya AS. A study of pathogenic factors of Streptococcus pneumoniae strains causing meningitis. FEMS Immunol. Med. Microbiol. 10(2), 133–137 (1995).
   PubMedGoogle Scholar
• Weiser JN, Austrian R, Sreenivasan PK, Masure HR. Phase variation in pneumococcal opacity: relationship between colonial morphology and nasopharyngeal colonization. Infect. Immun. 62(6), 2582–2589 (1994).
   PubMed Web of Science ®Google Scholar
• Tuomanen EI. The biology of pneumococcal infection. Pediatr. Res. 42(3), 253–258 (1997).
   PubMed Web of Science ®Google Scholar
• Kim JO, Weiser JN. Association of intrastrain phase variation in quantity of capsular polysaccharide and teichoic acid with the virulence of Streptococcus pneumoniae. J. Infect. Dis. 177(2), 368–377 (1998).
   PubMed Web of Science ®Google Scholar
• Hoa M, Syamal M, Sachdeva L, Berk R, Coticchia J. Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media. Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
   PubMed Web of Science ®Google Scholar
• Sanderson AR, Leid JG, Hunsaker D. Bacterial biofilms on the sinus mucosa of human subjects with chronic rhinosinusitis. Laryngoscope 116(7), 1121–1126 (2006).
   PubMed Web of Science ®Google Scholar
• Sanchez CJ, Kumar N, Lizcano A et al. Streptococcus pneumoniae in biofilms are unable to cause invasive disease due to altered virulence determinant production. PLoS ONE 6(12), e28738 (2011).
   PubMedGoogle Scholar
• Dawid S, Roche AM, Weiser JN. The blp bacteriocins of Streptococcus pneumoniae mediate intraspecies competition both in vitro and in vivo. Infect. Immun. 75(1), 443–451 (2007).
   PubMed Web of Science ®Google Scholar
• Cope EK, Goldstein-Daruech N, Kofonow JM et al. Regulation of virulence gene expression resulting from Streptococcus pneumoniae and nontypeable Haemophilus influenzae interactions in chronic disease. PLoS ONE 6(12), e28523 (2011).
   PubMed Web of Science ®Google Scholar
• Bogaert D, De Groot R, Hermans PW. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect. Dis. 4(3), 144–154 (2004).
   PubMed Web of Science ®Google Scholar
• Regev-Yochay G, Raz M, Dagan R et al. Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings. Clin. Infect. Dis. 38(5), 632–639 (2004).
   PubMed Web of Science ®Google Scholar
• Ofek I, Goldhar J, Keisari Y, Sharon N. Nonopsonic phagocytosis of microorganisms. Annu. Rev. Microbiol. 49, 239–276 (1995).
   PubMed Web of Science ®Google Scholar
• Tino MJ, Wright JR. Surfactant protein A stimulates phagocytosis of specific pulmonary pathogens by alveolar macrophages. Am. J. Physiol. 270(4 Pt 1), L677–L688 (1996).
   PubMed Web of Science ®Google Scholar
• Goldblatt D, Hussain M, Andrews N et al. Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study. J. Infect. Dis. 192(3), 387–393 (2005).
   PubMed Web of Science ®Google Scholar
• Malley R. Antibody and cell-mediated immunity to Streptococcus pneumoniae: implications for vaccine development. J. Mol. Med. 88(2), 135–142 (2010).
   PubMed Web of Science ®Google Scholar
• McCool TL, Weiser JN. Limited role of antibody in clearance of Streptococcus pneumoniae in a murine model of colonization. Infect. Immun. 72(10), 5807–5813 (2004).
   PubMed Web of Science ®Google Scholar
• Trzcinski K, Thompson C, Malley R, Lipsitch M. Antibodies to conserved pneumococcal antigens correlate with, but are not required for, protection against pneumococcal colonization induced by prior exposure in a mouse model. Infect. Immun. 73(10), 7043–7046 (2005).
   PubMed Web of Science ®Google Scholar
• Malley R, Lipsitch M, Stack A et al. Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci. Infect. Immun. 69(8), 4870–4873 (2001).
   PubMed Web of Science ®Google Scholar
• Malley R, Trzcinski K, Srivastava A, Thompson CM, Anderson PW, Lipsitch M. CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization. Proc. Natl Acad. Sci. USA 102(13), 4848–4853 (2005).
   PubMed Web of Science ®Google Scholar
• Klugman KP, Smith SH, Koornhof H. Evidence that prevention of carriage by pneumococcal capsular vaccines may be the mechanism of protection from pneumococcal pneumonia. South Afr. J. Epidemiol. Infect. 26, 221–224 (2011).
   Google Scholar
• Dagan R, Melamed R, Muallem M et al. Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine. J. Infect. Dis. 174(6), 1271–1278 (1996).
   PubMed Web of Science ®Google Scholar
• Douglas RM, Hansman D, Miles HB, Paton JC. Pneumococcal carriage and type-specific antibody. Failure of a 14-valent vaccine to reduce carriage in healthy children. Am. J. Dis. Child. 140(11), 1183–1185 (1986).
   PubMedGoogle Scholar
• Herva E, Luotonen J, Timonen M, Sibakov M, Karma P, Mäkelä PH. The effect of polyvalent pneumococcal polysaccharide vaccine on nasopharyngeal and nasal carriage of Streptococcus pneumoniae. Scand. J. Infect. Dis. 12(2), 97–100 (1980).
   PubMed Web of Science ®Google Scholar
• Givon-Lavi N, Fraser D, Dagan R. Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings. Pediatr. Infect. Dis. J. 22(6), 524–532 (2003).
   PubMed Web of Science ®Google Scholar
• Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce N; Vaccine Trialists Group. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N. Engl. J. Med. 349(14), 1341–1348 (2003).
   PubMed Web of Science ®Google Scholar
• Mbelle N, Huebner RE, Wasas AD, Kimura A, Chang I, Klugman KP. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J. Infect. Dis. 180(4), 1171–1176 (1999).
   PubMed Web of Science ®Google Scholar
• Cutts FT, Zaman SM, Enwere G et al.; Gambian Pneumococcal Vaccine Trial Group. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet 365(9465), 1139–1146 (2005).
   PubMed Web of Science ®Google Scholar
• Cheung YB, Zaman SM, Nsekpong ED et al. Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian children who participated in a 9-valent pneumococcal conjugate vaccine trial and in their younger siblings. Pediatr. Infect. Dis. J. 28(11), 990–995 (2009).
   PubMed Web of Science ®Google Scholar
• O’Brien KL, Moulton LH, Reid R et al. Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial. Lancet 362(9381), 355–361 (2003).
   PubMed Web of Science ®Google Scholar
• O’Brien KL, David AB, Chandran A et al. Randomized, controlled trial efficacy of pneumococcal conjugate vaccine against otitis media among Navajo and White Mountain Apache infants. Pediatr. Infect. Dis. J. 27(1), 71–73 (2008).
   PubMed Web of Science ®Google Scholar
• O’Brien KL, Millar EV, Zell ER et al. Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial. J. Infect. Dis. 196(8), 1211–1220 (2007).
   PubMed Web of Science ®Google Scholar
• Lucero MG, Nohynek H, Williams G et al. Efficacy of an 11-valent pneumococcal conjugate vaccine against radiologically confirmed pneumonia among children less than 2 years of age in the Philippines: a randomized, double-blind, placebo-controlled trial. Pediatr. Infect. Dis. J. 28(6), 455–462 (2009).
   PubMed Web of Science ®Google Scholar
• Nohynek H, Mäkelä PH, Lucero MG et al. The impact of 11-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae in Philippine children. Presented at: 6th International Symposium on Pneumococci and Pneumococcal Diseases. Reykjavik, Iceland, 8–12 June 2008.
   Google Scholar
• Tregnaghi MW, Saez-Llorens X, Lopez P et al. Evaluating the efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PhiD-CV) against community-acquired pneumonia in Latin America. Presented at: 29th Annual Meeting of the European Society for the Pediatric Infectious Diseases (ESPID). The Hague, The Netherlands, 7–11 June 2011.
   Google Scholar
• Saez-Llorens X, Wong D, Rodriques M et al. Impact of 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PhiD-CV) on nasopharyngeal bacterial carriage in Panamian Children. Presented at: 7th World Society for Pediatric Infectious Diseases (WSPID). Melbourne, VIC, Australia, 16–19 November 2011.
   Google Scholar
• Eskola J, Kilpi T, Palmu A et al.;Finnish Otitis Media Study Group. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N. Engl. J. Med. 344(6), 403–409 (2001).
   PubMed Web of Science ®Google Scholar
• Kilpi TM, Syrjänen R, Palmu A et al. Parallel evaluation of the effect of a 7-valent pneumococcal conjugate vaccine (pncCRM) on pneumococcal carriage and acute otitis media. Presented at: 19th Annual Meeting of the European Society for the Pediatric Infectious Diseases (ESPID). Istanbul, Turkey, 26–28 March 2001.
   Google Scholar
• Prymula R, Peeters P, Chrobok V et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet 367(9512), 740–748 (2006).
   PubMed Web of Science ®Google Scholar
• Prymula R, Kriz P, Kaliskova E, Pascal T, Poolman J, Schuerman L. Effect of vaccination with pneumococcal capsular polysaccharides conjugated to Haemophilus influenzae-derived protein D on nasopharyngeal carriage of Streptococcus pneumoniae and H. influenzae in children under 2 years of age. Vaccine 28(1), 71–78 (2009).
   PubMed Web of Science ®Google Scholar
• Dagan R, Givon-Lavi N, Zamir O et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine to toddlers attending day care centers. J. Infect. Dis. 185(7), 927–936 (2002).
   PubMed Web of Science ®Google Scholar
• Dagan R, Sikuler-Cohen M, Zamir O, Janco J, Givon-Lavi N, Fraser D. Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care center attendees. Pediatr. Infect. Dis. J. 20(10), 951–958 (2001).
   PubMed Web of Science ®Google Scholar
• Palmu A, Kaijalainen TH, Syrjanen R et al. Effect of the seven-valent vaccine on quantitative bacterial load of pneumococcal nasopharyngeal carriage. Presented at: 8th International Symposium on Pneumococci and Pneumococcal Diseases. Iguaçu Falls, Brazil, 11–15 March 2012.
   Google Scholar
• Nurhonen M, Cheng A, Auranen K. Pneumococcal transmission and disease in silico: a microsimulation model of the indirect effects of vaccination. PloS ONE (2012) (In Press).
   Google Scholar
• Rinta-Kokko H, Dagan R, Givon-Lavi N, Auranen K. Estimation of vaccine efficacy against acquisition of pneumococcal carriage. Vaccine 27(29), 3831–3837 (2009).
   PubMed Web of Science ®Google Scholar
• Gilbert PB, Qin L, Self SG. Evaluating a surrogate endpoint at three levels, with application to vaccine development. Stat. Med. 27(23), 4758–4778 (2008).
   PubMed Web of Science ®Google Scholar