Chapter 19 : Nasopharyngeal Carriage

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The pneumococcus is one of the most common etiologies of respiratory tract infections like sinusitis, otitis media, and pneumonia, as well as nonrespiratory infections like meningitis, sepsis, and bacteremia. The authors presume the existence of special niches for pneumococcal attachment and the subsequent establishment of colonization, processes in which the newly arriving pneumococcus has to evade the local host defenses and compete with the resident polymicrobial flora, including other strains of pneumococci. Pneumococcal colonization induces a variety of immune responses in humans, including the production of antibodies directed at both surface proteins and the PS capsule. This chapter defines the direct effect of vaccine on carriage as those effects observed among the vaccinated individuals These effects include the impact on vaccine type (VT) carriage, vaccine-associated serotype carriage, nonvaccine type (NVT) carriage, and nonpneumococcal NP carriage. and are common constituents of the microflora of the human nasopharynx and, after pneumococci, are the most common causes of upper respiratory infection; therefore, they could be expected to be affected by changes in pneumococcal colonization. The experience accumulated from the large-scale use of pneumococcal conjugate vaccine (PCV) has also allowed an analysis of the immunization schedule. The direct effect of PCV on pneumococcal carriage is to reduce vaccine serotype and increase nonvaccine serotype colonization among vaccinated children. There are three phases of a nasopharyngeal colonization episode: acquisition, the period of colonization, and clearance of the organism.

Citation: O’Brien K, Dagan R, Mäkelä P. 2008. Nasopharyngeal Carriage, p 279-300. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch19

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1. Aniansson, G.,, B. Alm,, B. Andersson,, P. Larsson,, O. Nylen,, H. Peterson,, P. Rigner,, M. Svanborg, and, C. Svanborg. 1992. Nasopharyngeal colonization during the first year of life. J. Infect. Dis. 165(Suppl. 1):S38S42.
2. Auranen, K.,, E. Arjas,, T. Leino, and, A. Takala. 2000. Transmission of pneumococcal carriage in families: a latent Markov process model for binary longitudinal data. J. Am. Stat. Assoc. 95:10441053.
3. Barbour, M. L. 1996. Conjugate vaccines and the carriage of Haemophilus influenzae type b. Emerg. Infect. Dis. 2:176182.
4. Barocchi, M.,, J. Ries,, X. Zogaj,, C. Hemsley,, B. Albiger,, A. Kanth,, S. Dahlberg,, J. Fernebro,, M. Moschioni,, K. Masignani,, K. Hultenby,, A. Taddei,, K. Beiter,, F. Wartha,, A. von Euler,, A. Covacci,, D. Holden,, S. Normark,, R. Rappuoli, and, B. Henriques-Normark. 2006. A pneumococcal pilus influences virulence and host inflammatory responses. Proc. Natl. Acad. Sci. USA 103:28572862.
5. Bogaert, D.,, M. N. Engelen,, A. J. Timmers-Reker,, K. P. Elzenaar,, P. G. Peerbooms,, R. A. Coutinho,, R. de Groot, and, P. W. Hermans. 2001. Pneumococcal carriage in children in The Netherlands: a molecular epidemiological study. J. Clin. Microbiol. 39:33163320.
6. Bogaert, D.,, A. van Belkum,, M. Sluijter,, A. Luijendijk,, R. de Groot,, H. C. Rumke,, H. A. Verbrugh, and, P. W. Hermans. 2004. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet 363:18711872.
7. Brimblecombe, F.,, R. Cruickshank,, P. Masters,, D. Reid, and, G. Stewart. 1958. Family studies on respiratory infections. Br. Med. J. 1:119128.
8. Bronsdon, M. A.,, K. L. O'Brien,, R. R. Facklam,, C. G. Whitney,, B. Schwartz, and, G. M. Carlone. 2004. Immunoblot method to detect Streptococcus pneumoniae and identify multiple serotypes from nasopharyngeal secretions. J. Clin. Microbiol. 42:15961600.
9. Brueggemann, A. B.,, D. T. Griffiths,, E. Meats,, T. Peto,, D. W. Crook, and, B. G. Spratt. 2003. Clonal relationships between invasive and carriage Streptococcus pneumoniae and serotype- and clone-specific differences in invasive disease potential. J. Infect. Dis. 187:14241432.
10. Cauchemez, S.,, L. Temime,, V. Alain-Jacques,, E. Varon,, G. Thomas,, D. Guillemot, and, P.-Y. Boelle. 2006. S. pneumoniae transmission according to inclusion in conjugate vaccines: Bayesian analysis of a longitudinal follow-up in schools. BMC Infect. Dis. 6:110.
11. Christenson, B.,, S. Sylvan, and, B. Noreen. 1997. Carriage of multiresistant Streptococcus pneumoniae among children attending day-care centres in the Stockholm area. Scand. J. Infect. Dis. 29:555558.
12. Cohen, R.,, E. Bingen,, E. Varon,, F. de la Rocque,, N. Brahimi,, C. Levy,, M. Boucherat,, J. Langue, and, P. Geslin. 1997. Change in nasopharyngeal carriage of Streptococcus pneumoniae resulting from antibiotic therapy for acute otitis media in children. Pediatr. Infect. Dis. J. 16:555560.
13. Cohen, R.,, C. Levy,, F. De la Rocque,, N. Gelbert,, A. Wollner,, B. Fritzell,, E. Bonnet,, R. Tetelboum, and, E. Varon. 2006. Impact of pneumococcal conjugate vaccine and of reduction of antibiotic use on nasopharyngeal carriage of nonsusceptible pneumococci in children with acute otitis media. Pediatr. Infect. Dis. J. 25:10011007.
14. Cundell, D. R.,, N. P. Gerard,, C. Gerard,, I. Idanpaan-Heikkila, and, E. I. Tuomanen. 1995. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377:435438.
15. Dagan, R.,, N. Givon-Lavi,, D. Fraser,, M. Lipsitch,, G. R. Siber, and, R. Kohberger. 2005. Serum serotype-specific pneumococcal anticapsular immunoglobulin G concentrations after immunization with a 9-valent conjugate pneumococcal vaccine correlate with nasopharyngeal acquisition of pneumococcus. J. Infect. Dis. 192:367376.
16. Dagan, R.,, N. Givon-Lavi,, O. Zamir,, M. Sikuler-Cohen,, L. Guy,, J. Janco,, P. Yagupsky, and, D. Fraser. 2002. 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. 185:927936.
17. Dagan, R.,, S. Gradstein,, I. Belmaker,, N. Porat,, Y. Siton,, G. Weber,, J. Janco, and, P. Yagupsky. 2000. An outbreak of Streptococcus pneumoniae serotype 1 in a closed community in Southern Israel. Clin. Infect. Dis. 30:319321.
18. Dagan, R.,, R. Melamed,, M. Muallem,, L. Piglansky,, D. Greenberg,, O. Abramson,, P. M. Mendelman,, N. Bohidar, and, P. Yagupsky. 1996. Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine. J. Infect. Dis. 174:12711278.
19. Dagan, R.,, R. Melamed,, M. Muallem,, L. Piglansky, and, P. Yagupsky. 1996. Nasopharyngeal colonization in southern Israel with antibiotic-resistant pneumococci during the first 2 years of life: relation to serotypes likely to be included in pneumococcal conjugate vaccines. J. Infect. Dis. 174:13521355.
20. Dagan, R.,, M. Muallem,, R. Melamed,, O. Leroy, and, P. Yagupsky. 1997. Reduction of pneumococcal nasopharyngeal carriage in early infancy after immunization with tetravalent pneumococcal vaccines conjugated to either tetanus toxoid or diphtheria toxoid. Pediatr. Infect. Dis. J. 16:10601064.
21. Dagan, R.,, O. Zamir,, N. Tirosh,, I. Belmaker,, L. Guy,, D. Greenberg, and, D. Fraser. 2000. Nasopharyngeal carriage of Streptococcus pneumoniae in toddlers vaccinated during infancy with an 11-valent pneumococcal vaccine conjugated to diphtheria and tetanus toxoids, abstr. 47. 40th Annu. Intersci. Conf. on Antimicrob. Agents Chemother., Toronto, Canada, 17 to 20 September 2000.
22. de Wals, P., and, A. Bouckaert. 1985. Methods for estimating the duration of bacterial carriage. Int. J. Epidemiol. 14:628634.
23. Douglas, R.,, D. Hansman,, H. Miles, and, J. Paton. 1986. Pneumococcal carriage and type-specific antibody. Failure of a 14-valent vaccine to reduce carriage in healthy children. Am. J. Dis. Child. 140:11831185.
24. Edwards, K. M.,, G. Wandling,, P. Palmer, and, M. D. Decker. 1999. Carriage of pneumococci among infants immunized with a 9-valent pneumococcal (Pnc) vaccine at 2, 4, and 6 months of age, abstr. 34. Abstracts of the IDSA 37th annual meeting. Clin. Infect. Dis. 29:966.
25. Ekdahl, K.,, I. Ahlinder,, H. B. Hansson,, E. Melander,, S. Mölstad,, M. Söderström, and, K. Persson. 1997. Duration of nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae: experiences from the South Swedish Pneumococcal Intervention Project. Clin. Infect. Dis. 25:11131117.
26. Eskola, J.,, T. Kilpi,, A. Palmu,, J. Jokinen,, J. Haapakoski,, E. Herva,, A. Takala,, H. Kayhty,, P. Karma,, R. Kohberger,, G. Siber, and, P. H. Mäkelä. 2001. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N. Engl. J. Med. 344:403409.
27. Faden, H.,, M. J. Waz,, J. M. Bernstein,, L. Brodsky,, J. Stanievich, and, P. L. Ogra. 1991. Nasopharyngeal flora in the first three years of life in normal and otitis-prone children. Ann. Otol. Rhinol. Laryngol. 100:612615.
28. Finkelstein, J.,, S. Huang,, J. Daniel,, S. Rufas-Shiman,, K. Kleinman,, D. Goldmann,, S. Pelton,, A. DeMaria, and, R. Platt. 2003. Antibiotic-resistant Streptococcus pneumoniae in the heptavalent pneumococcal conjugate vaccine era: predictors of carriage in a multicommunity sample. Pediatrics 112:862869.
29. Fraser, C.,, W. P. Hanage, and, B. G. Spratt. 2005. Neutral microepidemic evolution of bacterial pathogens. Proc. Natl. Acad. Sci. USA 102:19681973.
30. Fraser, D.,, R. Dagan,, N. Givon-Lavi,, M. Sikuler-Cohen,, J. Janco,, I. Chang,, G. Siber, and, P. Yagupsky. 2000. Density of nasopharyngeal colonization (NP-col) of vaccine-type and non-vaccine type pneumococci after administration of 9-valent CRM pneumococcal conjugate vaccine, abstr. P97. Second Int. Symp. Pneumococci pneumococcal Dis., Sun City, South Africa, 19 to 23 March 2000.
31. Frazao, N.,, A. Brito-Avo,, C. Simas,, J. Saldanha,, R. Mato,, S. Nunes,, N. G. Sousa,, J. A. Carrico,, J. S. Almeida,, I. Santos-Sanches, and, H. de Lencastre. 2005. Effect of the seven-valent conjugate pneumococcal vaccine on carriage and drug resistance of Streptococcus pneumoniae in healthy children attending day-care centers in Lisbon. Pediatr. Infect. Dis. J. 24:243252.
32. Ghaffar, F.,, T. Barton,, J. Lozano,, L. S. Muniz,, P. Hicks,, V. Gan,, N. Ahmad, and, G. H. McCracken, Jr. 2004. Effect of the 7-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae in the first 2 years of life. Clin. Infect. Dis. 39:930938.
33. Givon-Lavi, N.,, D. Fraser, and, R. Dagan. 2003. Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings. Pediatr. Infect. Dis. J. 22:524532.
34. Goldblatt, D.,, M. Hussain,, N. Andrews,, L. Ashton,, C. Virta,, A. Melegaro,, R. Pebody,, R. George,, A. Soininen,, J. Edmunds,, N. Gay,, H. Käyhty, and, E. Miller. 2005. Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study. J. Infect. Dis. 192:387393.
35. Granat, S.,, J. Ollgren,, E. Herva,, M. Zakaria,, K. Auranen, and, P. Mäkelä. 2006. Previous pneumococcal carriage is associated with protection from reacquisition in Bangladeshi infants, abstr. SY7.05. Fifth Int. Symp. pneumococci Pneumococcal Dis., Alice Springs, Australia, 2 to 6 April 2006.
36. Granat, S. M.,, Z. Mia,, J. Ollgren,, E. Herva,, M. Das,, L. Piirainen,, K. Auranen, and, P. H. Mäkelä. 2007. Longitudinal study on pneumococcal carriage during the first year of life in Bangladesh. Pediatr. Infect. Dis. J. 26:319324.
37. Gratten, M.,, H. Gratten,, A. Poli,, E. Carrad,, M. Raymer, and, G. Koki. 1986. Colonisation of Haemophilus influenzae and Streptococcus pneumoniae in the upper respiratory tract of neonates in Papua New Guinea: primary acquisition, duration of carriage, and relationship to carriage in mothers. Biol. Neonate 50:114120.
38. Gratten, M.,, J. Montgomery,, G. Gerega,, H. Gratten,, H. Siwi,, A. Poli, and, G. Koki. 1989. Multiple colonization of the upper respiratory tract of Papua New Guinea children with Haemophilus influenzae and Streptococcus pneumoniae. Southeast Asian J. Trop. Med. Public Health 20:501509.
39. Gray, B. M.,, G. M. Converse III, and, H. C. Dillon, Jr. 1980. Epidemiologic studies on Streptococcus pneumoniae in infants; acquisition, carriage, and infection during the first 24 months of life. J. Infect. Dis. 142:923933.
40. Greenberg, D.,, N. Givon-Lavi,, A. Broides,, I. Blancovich,, N. Peled, and, R. Dagan. 2006. The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers. Clin. Infect. Dis. 42:897903.
41. Hammitt, L. L.,, D. L. Bruden,, J. C. Butler,, H. C. Baggett,, D. A. Hurlburt,, A. Reasonover, and, T. W. Hennessy. 2006. Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease. J. Infect. Dis. 193:14871494.
42. Hanage, W. P.,, T. H. Kaijalainen,, R. K. Syrjänen,, K. Auranen,, M. Leinonen,, P. H. Mäkelä, and, B. G. Spratt. 2005. Invasiveness of serotypes and clones of Streptococcus pneumoniae among children in Finland. Infect. Immun. 73:431435.
43. Hansman, D., and, S. Morris. 1988. Pneumococcal carriage amongst children in Adelaide, South Australia. Epidemiol. Infect. 101:411417.
44. Hansman, D.,, S. Morris, and, M. Gregory. 1985. Pneumococcal carriage amongst Australian aborigines in Alice Springs. J. Hyg. 95:677684.
45. Hava, D., and, A. Camilli. 2002. Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol. Microbiol. 45:13891405.
46. Hendley, J. O.,, M. A. Sande,, O. M. Stewart, and, J. M. J. Gwaltney. 1975. Spread of Streptococcus pneumoniae in families. I. Carriage rates and distribution of types. J. Infect. Dis. 132:5561.
47. Hennessy, T. W.,, R. J. Singleton,, L. R. Bulkow,, D. L. Bruden,, D. A. Hurlburt,, D. Parks,, M. Moore,, A. J. Parkinson,, A. Schuchat, and, J. C. Butler. 2005. Impact of heptavalent pneumococcal conjugate vaccine on invasive disease, antimicrobial resistance and colonization in Alaska Natives: progress towards elimination of a health disparity. Vaccine 23:54645473.
48. Herva, E.,, J. Luotonen,, M. Timonen,, M. Sibakov,, P. Karma, and, P. Mäkelä. 1980. The effect of polyvalent pneumococcal polysaccharide vaccine on nasopharyngeal and nasal carriage of Streptococcus pneumoniae. Scand. J. Infect. Dis. 12:97100.
49. Hill, P. C.,, A. Akisanya,, K. Sankareh,, Y. B. Cheung,, M. Saaka,, G. Lahai,, B. M. Greenwood, and, R. A. Adegbola. 2006. Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Clin. Infect. Dis. 43:673679.
50. Holmlund, E.,, B. Quiambao,, J. Ollgren,, H. Nohynek, and, H. Käyhty. 2006. Development of natural antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A and pneumolysin in Filipino pregnant women and their infants in relation to pneumococcal carriage. Vaccine 24:5765.
51. Huang, S. S.,, R. Platt,, S. L. Rifas-Shiman,, S. I. Pelton,, D. Goldmann, and, J. A. Finkelstein. 2005. Post-PCV7 changes in colonizing pneumococcal serotypes in 16 Massachusetts communities, 2001 and 2004. Pediatrics 116:e408e413.
52. Huebner, R. E.,, R. Dagan,, N. Porath,, A. D. Wasas, and, K. P. Klugman. 2000. Lack of utility of serotyping multiple colonies for detection of simultaneous nasopharyngeal carriage of different pneumococcal serotypes. Pediatr. Infect. Dis. J. 19:10171020.
53. Hussain, M.,, A. Melegaro,, R. G. Pebody,, R. George,, W. J. Edmunds,, R. Talukdar,, S. A. Martin,, A. Efstratiou, and, E. Miller. 2005. A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting. Epidemiol. Infect. 133:891898.
54. Jacoby, P.,, K. Watson,, J. Bowman,, A. Talor,, T. Riley,, D. Smith, and, D. Lehmann. 2006. Modelling interactions of Streptococcus pneumoniae with other bacterial and viral pathogens in the upper respiratory tract of Aboriginal and non-Aboriginal children in Western Australia, abstr. SY7.04. Fifth Int. Symp. Pneumococci Pneumococcal Dis., Alice Springs, Australia, 2 to 6 April 2006.
55. Jacoby, P.,, K. Watson,, J. Bowman,, A. Taylor,, T. V. Riley,, D. W. Smith,, D. Lehmann, and Kalgoorlie Otitis Media Research Project Team. 2007. Modelling the co-occurrence of Streptococcus pneumoniae with other bacterial and viral pathogens in the upper respiratory tract. Va c-cine 25:24582464.
56. Jones, V. F.,, C. Harrison,, G. G. Stout, and, J. Hopkins. 2005. Nasopharyngeal colonization with heptavalent pneumococcal conjugate vaccine serotypes of Streptococcus pneumoniae with prolonged vaccine dosing intervals. Pediatr. Infect. Dis. J. 24:969973.
57. Karma, P.,, J. Pukander,, M. Sipila,, M. Timonen,, S. Pontynen,, E. Herva,, P. Gronroos, and, H. Makela. 1985. Prevention of otitis media in children by pneumococcal vaccination. Am. J. Otolaryngol. 6:173184.
58. Kauppi-Korkeila, M.,, L. van Alphen,, D. Madore,, L. Saarinen, and, H. Kayhty. 1996. Mechanism of antibody-mediated reduction of nasopharyngeal colonization by Haemophilus influenzae type b studied in an infant rat model. J. Infect. Dis. 174:13371340.
59. Kayhty, H.,, H. Peltola,, V. Karanko, and, P. H. Makela. 1983. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J. Infect. Dis. 147:1100.
60. Kilpi, T.,, R. Syrjanen,, A. Palmu,, E. Herva,, J. Eskola,, P. H. Mäkelä, and the FinOM Study Group. 2001. Parallel evaluation of the effect of a 7-valent pneumococcal conjugate vaccine (PncCRM) on pneumococcal (Pnc) carriage and acute otitis media (AOM), p. 4. 19th Annu. Meet. Eur. Soc. Paediatr. Infect. Dis., Istanbul, Turkey, 26 to 27 March 2001.
61. Kim, J., and, J. Weiser. 1998. Association of intrastrain phase variation in quantity of capsular polysaccharide and teichoic acid with the virulence of Streptococcus pneumoniae. J. Infect. Dis. 177:368377.
62. Kristinsson, K.,, S. Sigurdardottir, and, T. Gudnason. 1997. Effect of vaccination with octavalent protein conjugated pneumococcal vaccines on pneumococcal carriage in infants, abstr. G5. 37th Annu. Intersci. Conf. Antimicrob. Agents Chemother., Toronto, Canada, 28 September to 1 October 1997.
63. Lakshman, R.,, C. Murdoch,, G. Race,, R. Burkinshaw,, L. Shaw, and, A. Finn. 2003. Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy. Arch. Dis. Child. 88:211214.
64. Leach, A.,, T. M. Shelby-James,, M. M. Gratten,, A. Laming,, B. Currie, and, J. Mathews. 1997. A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clin. Infect. Dis. 24:356362.
65. Leach, A. J.,, J. B. Boswell,, V. Asche,, T. Nienhuys, and, J. Mathews. 1994. Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian Aboriginal infants. Pediatr. Infect. Dis. J. 13:983989.
66. Leino, T.,, K. Auranen,, J. Jokinen,, M. Leinonen,, P. Tervonen, and, A. K. Takala. 2001. Pneumococcal carriage in children during their first two years: important role of family exposure. Pediatr. Infect. Dis. J. 20:10221027.
67. Lipsitch, M. 2001. Interpreting results from trials of pneumococcal conjugate vaccines: a statistical test for detecting vaccine-induced increases in carriage of nonvaccine serotpes. Am. J. Epidemiol. 154:8592.
68. Lipsitch, M.,, J. K. Dykes,, S. E. Johnson,, E. W. Ades,, J. King,, D. E. Briles, and, G. M. Carlone. 2000. Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model. Vaccine 18:28952901.
69. Lipsitch, M.,, K. O'Neill,, B. Bugalter,, K. Trzinski,, D. Cordy,, C. Thompson,, R. Goldstein,, S. Pelton,, H. Huot,, V. Bouchet,, R. Reid,, M. Santosham, and, K. O'Brien. 2007. Strain characteristics of Streptococcus pneumoniae isolated from carriage and invasive disease during a cluster-randomized clinical trial of the 7-valent pneumococal conjugate vaccine. J. Infect. Dis. 196:12211227.
70. Lloyd-Evans, N.,, T. J. O'Dempsey,, I. Baldeh,, O. Secka,, E. Demba,, J. E. Todd,, T. F. Mcardle,, W. S. Banya, and, B. M. Greenwood. 1996. Nasopharyngeal carriage of pneumococci in Gambian children and in their families. Pediatr. Infect. Dis.J. 15:866871.
71. Long, S. S.,, F. M. Henretig,, M. J. Teter, and, K. L. McGowan. 1983. Nasopharyngeal flora and acute otitis media. Infect. Immun. 41:987991.
72. Lysenko, E. S.,, A. J. Ratner,, A. L. Nelson, and, J. N. Weiser. 2005. The role of innate immune responses in the outcome of interspecies competition for colonization of mucosal surfaces. PLoS Pathog. l:e1.
73. MacLeod, M.,, R. G. Hodges,, M. Heidelberger, and, W. G. Bernhard. 1945. Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. J. Exp. Med. 82:445465.
74. Mäkelä, P. H.,, J. Eskola,, H. Peltola,, A. K. Takala, and, H. Käyhty. 1990. Clinical experience with Haemophilus influenzae type b conjugate vaccines. Pediatrics 85:651653.
75. Malley, R.,, A. M. Stack,, M. L. Ferretti,, C. M. Thompson, and, R. A. Saladino. 1998. Anticapsular polysaccharide antibodies and nasopharyngeal colonization with Streptococcus pneumoniae in infant rats. J. Infect. Dis. 178:878882.
76. Malley, R.,, K. Trzcinski,, A. Srivastava,, C. M. Thompson,, P. W. Anderson, and, M. Lipsitch. 2005. CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization. Proc. Natl. Acad. Sci. USA 102:48484853.
77. Mbelle, N.,, R. E. Huebner,, A. D. Wasas,, A. Kimura,, I. Chang, and, K. P. Klugman. 1999. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J. Infect. Dis. 180:11711176.
78. McCool, T. L.,, T. R. Cate,, E. I. Tuomanen,, P. Adrian,, T. J. Mitchell, and, J. N. Weiser. 2003. Serum immunoglobulin G response to candidate vaccine antigens during experimental human pneumococcal colonization. Infect. Immun. 71:57245732.
79. McCool, T. L., and, J. N. Weiser. 2004. Limited role of antibody in clearance of Streptococcus pneumoniae in a murine model of colonization. Infect. Immun. 72:58075813.
80. Melegaro, A.,, Y. Choi,, R. Pebody, and, N. Gay. 2007. Pneumococcal carriage in United Kingdom families: estimating serotype-specific transmission parameters from longitudinal data. Am.J. Epidemiol. 166:228235.
81. Melegaro, A.,, N. J. Gay, and, G. F. Medley. 2004. Estimating the transmission parameters of pneumococcal carriage in households. Epidemiol. Infect. 132:433441.
82. Millar, E. V.,, K. L. O'Brien,, J. P. Watt,, M. A. Bronsdon,, J. Dallas,, C. G. Whitney,, R. Reid, and, M. Santosham. 2006. Effect of community-wide conjugate pneumococcal vaccine use in infancy on nasopharyngeal carriage through 3 years of age: a cross-sectional study in a high-risk population. Clin. Infect. Dis. 43:815.
83. Millar, E. V.,, K. L. O'Brien,, M. A. Bronsdon,, D. Madore,, J. G. Hackell,, R. Reid, and, M. Santosham. 2007. Anticapsular serum antibody concentration and protection against pneumococcal colonization among children vaccinated with 7-valent pneumococal conjugate vaccine. Clin. Infect. Dis. 44:11731179.
84. Montgomery, J. M.,, L. Deborah,, T. Smith,, A. Michael,, B. Joseph,, T. Lupiwa,, C. Coakley,, V. Sopooner,, B. Best,, I. D. Riley, and, M. P. Alpers. 1990. Bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in highland children in Papua New Guinea. Rev. Infect. Dis. 12:S1006S1016.
85. Moore, M. R.,, T. B. Hyde,, T. W. Hennessy,, D. J. Parks,, A. L. Reasonover,, M. Harker-Jones,, J. Gove,, D. L. Bruden,, K. Rudolph,, A. Parkinson,, J. C. Butler, and, A. Schuchat. 2004. Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska. J. Infect. Dis. 190:20312038.
86. Musher, D.,, J. Groover,, M. Reichler,, F. Riedo,, B. Schwartz,, D. Watson,, R. Baughn, and, R. F. Breiman. 1997. Emergence of antibody to capsular polysaccharides of Streptococcus pneumoniae: association with nasopharyngeal colonization. Clin. Infect. Dis. 24:441446.
87. Nelson, A.,, A. Roche,, J. Gould,, K. Chim,, A. Ratner, and, J. Weiser. 2007. Capsule enhances pneumococcal colonization by limiting mucus-mediated clearance. Infect. Immun. 75:8390.
88. Nohynek, H.,, M. Lucero,, J. Ollgren,, L. Sombrero,, G. Esparar,, E. Herva,, J. Ugpo,, O. Leroy, and, P. Mäkelä. 2002. Effect of 11-valent pneumococcal (Pnc) conjugate vaccine (11PncTD) on nasopharyngeal (NP) carriage of Pnc in Filipino children, p. 53. Third Int. Symp. Pneumococci pneumococcal Dis., Anchorage, AK, 5 to 6 May 2002.
89. Obaro, S. K.,, R. A. Adegbola,, W. A. Banya, and, B. M. Greenwood. 1996. Carriage of pneumococci after pneumococcal vaccination. Lancet 348:271272.
90. Obaro, S. K.,, R. A. Adegbola,, I. Chang,, W. A. Banya,, S. Jaffar,, K. W. McAdam, and, B. M. Greenwood. 2000. Safety and immunogenicity of a nonavalent pneumococcal vaccine conjugated to CRM197 administered simultaneously but in a separate syringe with diphtheria, tetanus and pertussis vaccines in Gambian infants. Pediatr. Infect. Dis. J. 19:463469.
91. O'Brien, K. L.,, L. H. Moulton,, R. Reid,, R. Weatherholtz,, J. Oski,, L. Brown,, G. Kumar,, A. Parkinson,, D. Hu,, J. Hackell,, I. Chang,, R. Kohberger,, G. Siber, and, M. Santosham. 2003. Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial. Lancet 362:355361.
92. O'Brien, K. L., and, H. Nohynek. 2003. Report from a WHO working group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae. Pediatr. Infect. Dis. J. 22:e1e11.
93. O'Brien, K. L.,, E. Millar,, E. Zell,, M. Bronsdon,, R. Weatherholtz,, R. Reid,, J. Becenti,, S. Kvamme,, C. Whitney, and, M. Santosham. 2007. Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children. J. Infect. Dis. 196:12111220.
94. Orihule, C.,, G. Gao,, K. Francis,, J. Yu, and, E. I. Tuomanen. 2004. Tissue-specific contributions of pneumococcal virulence factors to pathogenesis. J. Infect. Dis. 190:16611669.
95. Pai, R.,, M. R. Moore,, T. Pilishvili,, R. E. Gertz,, C. G. Whitney, and, B. Beall. 2005. Postvaccine genetic structure of Streptococcus pneumoniae serotype 19A from children in the United States. J. Infect. Dis. 192:19881995.
96. Palmu, A.,, T. Kaijalainen,, E. Herva,, R. Syrjänen,, P. H. Mäkelä, and, T. Kilpi. 2003. Long-term effects of the seven-valent PncCRM vaccine on pneumococcal carriage in various subgroups. 21st Annu. Meet. Eur. Soc. Paediatr. Infect. Dis., Taormina, Italy, 9 to11 April 2003.
97. Pelton, S.,, A. Loughlin, and, C. Marchant. 2004. Seven-valent pneumococcal vaccine immunization in 2 Boston communities: changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr. Infect. Dis. J. 23:10151022.
98. Polissi, A.,, A. Pontiggia,, G. Feger,, M. Altieri,, H. Mottl,, L. Ferrari, and, D. Simon. 1998. Large-scale identification of virulence genes from Streptococcus pneumoniae. Infect. Immun. 66:56205629.
99. Porat, N.,, A. Arguedas,, B. G. Spratt,, R. Trefler,, E. Brilla,, C. Loaiza,, D. Godoy,, N. Bilek, and, R. Dagan. 2004. Emergence of penicillin-nonsusceptible Streptococcus pneumoniae clones expressing serotypes not present in the antipneumococcal conjugate vaccine. J. Infect. Dis. 190:21542161.
100. Prymula, R.,, P. Peeters,, V. Chrobok,, P. Kriz,, E. Novakova,, E. Kaliskova,, I. Kohl,, P. Lommel,, J. Poolman,, J. P. Prieels, and, L. Schuerman. 2006. 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 367:740748.
101. Regev-Yochay, G.,, R. Dagan,, M. Raz,, Y. Carmeli,, B. Shainberg,, E. Derazne,, G. Rahav, and, E. Rubinstein. 2004. Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in children. JAMA 292:716720.
102. Regev-Yochay, G.,, M. Raz,, R. Dagan,, N. Porat,, B. Shainberg,, E. Pinco,, N. Keller, and, E. Rubinstein. 2004. Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings. Clin. Infect. Dis. 38:632639.
103. Revai, K.,, D. McCormick,, J. Patel,, J. Grady,, K. Saeed, and, T. Chonmaitree. 2006. Effect of pneumococcal conjugate vaccine on nasopharyngeal bacterial colonization during acute otitis media. Pediatrics 117:18231829.
104. Sandgren, A.,, B. Albiger,, C. Orihuela,, E. Tuomanen,, S. Normark, and, B. Henriques-Normark. 2005. Virulence in mice of pneumococcal types with known invasive disease potential in humans. J. Infect. Dis. 192:791800.
105. Sell, S.,, P. Wright,, W. Vaughn,, J. Thompson, and, G. Schifman. 1981. Clinical studies of pneumococcal vaccines in infants. I. Reactogenicity and immunogenicity of two polyvalent polysaccharide vaccines. Rev. Infect. Dis. 3:S97S107.
106. Simell, B.,, T. M. Kilpi, and, H. Käyhty. 2002. Pneumococcal carriage and otitis media induce salivary antibodies to pneumococcal capsular polysaccharides in children. J. Infect. Dis. 186:11061114.
107. Simell, B.,, M. Korkeila,, H. Pursiainen,, T. M. Kilpi, and, H. Käyhty. 2001. Pneumococcal carriage and otitis media induce salivary antibodies to pneumococcal surface adhesin A, pneumolysin, and pneumococcal surface protein A in children. J. Infect. Dis. 183:887896.
108. Sleeman, K. L.,, L. Daniels,, M. Gardiner,, D. Griffiths,, J. J. Deeks,, R. Dagan,, S. Gupta,, E. R. Moxon,, T. E. Peto, and, D. W. Crook. 2005. Acquisition of Streptococcus pneumoniae and nonspecific morbidity in infants and their families: a cohort study. Pediatr. Infect. Dis. J. 24:121127.
109. Sleeman, K. L.,, D. Griffiths,, F. Shackley,, L. Diggle,, S. Gupte,, M. C. Maiden,, E. R. Moxon,, D. W. Crook, and, T. E. Peto. 2006. Capsular serotype-specific attack rates and duration of carriage of Streptococcus pneumoniae in a population of children. J. Infect. Dis. 194:682688.
110. Smith, T.,, D. Lehmann,, J. Montgomery,, M. Gratten,, I. D. Riley, and, M. P. Alpers. 1993. Acquisition and invasiveness of different serotypes of Streptococcus pneumoniae in young children. Epidemiol. Infect. 111:2739.
111. Soininen, A.,, H. Pursiainen,, T. Kilpi, and, H. Käyhty. 2001. Natural development of antibodies to pneumococcal capsular polysaccharides depends on the serotype: association with pneumococcal carriage and acute otitis media in young children. J. Infect. Dis. 184:569576.
112. Sundberg-Kovamees, M.,, T. Holme, and, A. Sjögren. 1994. Specific binding of Streptococcus pneumoniae to two receptor saccharide structures. Microb. Pathog. 17:6368.
113. Syrjänen, R. K.,, K. J. Auranen,, T. M. Leino,, T. M. Kilpi, and, P. H. Mäkelä. 2005. Pneumococcal acute otitis media in relation to pneumococcal nasopharyngeal carriage. Pediatr. Infect. Dis. J. 24:801806.
114. Syrjänen, R. K.,, T. M. Kilpi,, T. H. Kaijalainen,, E. E. Herva, and, A. K. Takala. 2001. Nasopharyngeal carriage of Streptococcus pneumoniae in Finnish children younger than 2 years old. J. Infect. Dis. 184:451459.
115. Takala, A. K.,, J. Eskola,, M. Leinonen,, H. Kayhty,, A. Nissinen,, E. Pekkanen, and, P. H. Makela. 1991. Reduction of oropharyngeal carriage of Haemophilus influenzae type b (Hib) in children immunized with an Hib conjugate vaccine. J. Infect. Dis. 164:982986.
116. Takala, A. K.,, J. Vuopio-Varkila,, E. Tarkka,, M. Leinonen, and, J. M. Musser. 1996. Subtyping of common pediatric pneumococcal serotypes from invasive disease and pharyngeal carriage in Finland. J. Infect. Dis. 173:128135.
117. Tomasson, G.,, T. Gudnason, and, K. G. Kristinsson. 2005. Dynamics of pneumococcal carriage among healthy Icelandic children attending day-care centers. Scand. J. Infect. Dis. 37:422428.
118. Tong, H.,, L. Fisher, and, T. DeMaria. 2000. Effect of adenovirus type 1 and influenza A virus on Streptococcus pneumoniae nasopharyngeal colonization and otitis media in the chinchilla. Ann. Otol. Rhinol. Laryngol. 109:10211027.
119. Trzcinski, K.,, C. Thompson,, R. Malley, and, M. Lipsitch. 2005. 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. 73:70437046.
120. van Kempen, M. J.,, J. S. Vermeiren,, M. Vaneechoutte,, G. Claeys,, R. H. Veenhoven,, G. T. Rijkers,, E. A. Sanders, and, I. J. Dhooge. 2006. Pneumococcal conjugate vaccination in children with recurrent acute otitis media: a therapeutic alternative? Int. J. Pediatr. Otorhi-nolaryngol. 70:275285.
121. van Rossum, A. M.,, E. S. Lysenko, and, J. N. Weiser. 2005. Host and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine model. Infect. Immun. 73:77187726.
122. Veenhoven, R.,, D. Bogaert,, C. Uiterwaal,, C. Brouwer,, H. Kiezebrink,, J. Bruin,, E. IJzerman,, P. Hermans,, R. de Groot,, B. Zegers,, W. Kuis,, G. Rijkers,, A. Schilder, and, E. Sanders. 2003. Effect of conjugate pneumococcal vaccine followed by polysaccharide pneumococcal vaccine on recurrent acute otitis media: a randomised study. Lancet 361:21892195.
123. Wadowsky, R.,, S. Mietzner,, D. Skoner,, W. Doyle, and, P. Fireman. 1995. Effect of experimental influenza A virus infection on isolation of Streptococcus pneumoniae and other aerobic bacteria from the oropharynges of allergic and nonallergic adult subjects. Infect. Immun. 63:11531157.
124. Watson, K.,, J. Bowman,, D. Murphy,, P. Jacoby,, T. Riley, and, D. Lehmann. 2006. Negative association between Streptococcus pneumoniae and Staphylococcus aureus in the nasopharynx of Aboriginal and non-Aboriginal children in the Kalgoorlie-Boulder area, Western Australia, abstr. PO7.08. Fifth Int. Symp. Pneumococci Pneumococcal Dis., Alice Springs, Central Australia, 2 to 6 April 2006.
125. Watson, K.,, K. Carville,, J. Bowman,, P. Jacoby,, T. V. Riuley,, A. J. Leach, and, D. Lehmann. 2006. Upper respiratory tract bacterial carriage in aboriginal and nonabo-riginal children in a semi-arid area of Western Australia. Pediatr. Infect. Dis. J. 25:782790.
126. Watt, J. P.,, K. L. O'Brien,, M. A. Bronsdon,, J. Elliott,, S. Katz,, J. Dallas,, R. Reid,, M. Santosham, and, C. G. Whitney. 2002. Impact of pneumococcal conjugate (PnCRM7) vaccination of children on pneumococcal carriage (PC) in unvaccinated adult family members, p. 23. Third Int. Symp. Pneumococci Pneumococcal Dis., Anchorage, AK, 5 to 8 May 2002.
127. Weiser, J. N.,, R. Austrian,, P. K. Sreenivasan, and, H. R. Masure. 1994. Phase variation in pneumococcal opacity: relationship between colonial morphology and nasopharyngeal colonization. Infect. Immun. 62:25822589.
128. World Health Organization. 2005. WHO Technical Report Series, vol. 927. Recommendations for the Production and Control of Pneumococcal Conjugate Vaccines. World Health Organization, Geneva, Switzerland.
129. Yeh, S. H.,, K. M. Zangwill,, H. Lee,, S. J. Chang,, V. I. Wong,, D. P. Greenberg, and, J. I. Ward. 2003. Heptavalent pneumococcal vaccine conjugated to outer membrane protein of Neisseria meningitidis serogroup b and nasopharyngeal carriage of Streptococcus pneumoniae in infants. Vaccine 21:26272631.
130. Zhang, J.,, K. Mostov,, M. Lamm,, M. Nanno,, S. Shimida,, M. Ohwaki, and, E. Tuomanen. 2000. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell Adhesion Commun. 102:827837.
131. Zhang, Q.,, J. Bernatoniene,, L. Bagrade,, A. J. Pollard,, T. J. Mitchell,, J. C. Paton, and, A. Finn. 2006. Serum and mucosal antibody responses to pneumococcal protein antigens in children: relationships with carriage status. Eur. J. Immunol. 36:4657.


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Table 1

Randomized controlled trials of PCV effect on NP carriage, trial description

Citation: O’Brien K, Dagan R, Mäkelä P. 2008. Nasopharyngeal Carriage, p 279-300. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch19
Generic image for table
Table 2

Randomized controlled trials of PCV effect on NP carriage, trial results

Citation: O’Brien K, Dagan R, Mäkelä P. 2008. Nasopharyngeal Carriage, p 279-300. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch19
Generic image for table
Table 3

Observational studies of PCV effect on NP carriage, study description

Citation: O’Brien K, Dagan R, Mäkelä P. 2008. Nasopharyngeal Carriage, p 279-300. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch19
Generic image for table
Table 4

Observational studies of PCV effect on NP carriage, study results

Citation: O’Brien K, Dagan R, Mäkelä P. 2008. Nasopharyngeal Carriage, p 279-300. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch19

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