Skip to main content
Article thumbnail
Location of Repository

Infant nasopharyngeal microbial ecology and the pneumococcal conjugate vaccine

By Brenda Anna Kwambana


The nasopharynx is an important reservoir of microbes some of which can cause serious mucosal and invasive disease. The impact of the 7-Valent Pneumococcal Conjugate Vaccine (PCV-7) on pharyngeal microbial ecology is not well characterized. The aim of this study is characterize the infant nasopharyngeal microbiome and subsequently to address the hypothesis that PCV-7 vaccination influences its development. Nasopharyngeal (NP) swabs were collected from neonates at birth, bi-weekly from zero to six months and bi-monthly from six to twelve months. High co-carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis was confirmed by species-specific PCR. Molecular-fingerprinting of the infant NP microbial communities combined with partial 16S rRNA gene showed that microbes are acquired rapidly after birth and that there are distinct microbial profiles over time and across individuals. Bar-coded 454 pyrosequencing of the 16S rRNA gene showed over 800 operational taxonomic units (genera). Streptococcus was the only genus present in all the NP communities. Six genera including Streptococcus, Haemophilus, Moraxella and Staphylococcus comprised over 80% of the infant NP microbiome. Most genera had low relative abundance (<1%) and their variable accounted for much of the diversity between individuals. Although early PCV-7 intervention did not appear to alter the abundance of Streptococcus, overall, the abundance of microbes was less turbulent among infants vaccinated early, before four months. Early intervention also appeared to alter the interactions between Streptococcus and several OTUs. Streptococcus was negatively correlated with Staphylococcus, Corynebacterium and Pseudomonas; this could play a major role in replacement. Preliminary data suggests that PCV-7 intervention may alter the development of the microbiome and microbial interactions within the nasopharynx. The long term implications of this finding for PCV-7 vaccination are yet to be determined, but continued surveillance of replacement in carriage and disease is necessary as immunisation with vaccines covering more serotypes are implemented

Publisher: University of Leicester
Year: 2011
OAI identifier:

Suggested articles


  1. (1994). A prospective cohort study on breast-feeding and otitis media in Swedish infants. Pediatr Infect Dis J
  2. (2011). A second-generation pneumococcal conjugate vaccine for prevention of pneumococcal diseases in children. Curr Opin Pediatr
  3. (1989). A: Effect of freezing on bacteriologic culturing of mastitis milk samples.
  4. (2004). A: Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska. J Infect Dis
  5. (2011). A: Mechanisms of Bacterial Resistance to Antibiotics in Infections of COPD Patients. Curr Drug Targets
  6. (2007). A: Nasopharyngeal co-colonization with Staphylococcus aureus and Streptococcus pneumoniae in children is bacterial genotype independent.
  7. (2011). A: Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study. Infect Immun
  8. (2010). AA: Association Between Composition of the Human Gastrointestinal Microbiome and Development of Fatty Liver With Choline Deficiency. Gastroenterology
  9. (2010). AC: Clonal analysis of the microbiota of severe early childhood caries. Caries Res
  10. (2001). AC: Materno-foetal transfer of H. influenzae and pneumococcal antibodies is influenced by prematurity and low birth weight: implications for conjugate vaccine trials. Vaccine
  11. (1996). AD: The biology of bacterial colonization and invasion of the respiratory mucosa. Eur Respir J
  12. (2007). Adderson E: Nontypeable Haemophilus influenzae and Streptococcus pneumoniae bind respiratory syncytial virus glycoprotein.
  13. (2006). Adderson EE: Respiratory viruses augment the adhesion of bacterial pathogens to respiratory epithelium in a viral species- and cell type-dependent manner.
  14. (2008). Adegbola CHAPTER [Bibliography] 158 |P a g e RA: Seasonality and outbreak of a predominant Streptococcus pneumoniae serotype 1 clone from The Gambia: expansion of ST217 hypervirulent clonal complex in West Africa.
  15. (2002). Adegbola R: The pneumococcus: carriage, disease and conjugate vaccines.
  16. (2007). Adegbola RA: Bacteraemia in patients admitted to an urban hospital in West Africa. BMC Infect Dis
  17. (2005). Adegbola RA: Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet
  18. (2008). Adegbola RA: Molecular epidemiology of pneumococci obtained from Gambian children aged 2-29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine. BMC Infect Dis
  19. (2008). Adegbola RA: Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian infants: a longitudinal study. Clin Infect Dis
  20. (2006). Adegbola RA: Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Clin Infect Dis
  21. (2007). Adegbola RA: Reemergence of Haemophilus influenzae type b (Hib) disease in The Gambia following successful elimination with conjugate Hib vaccine. Vaccine
  22. (2010). Adegbola RA: Transmission of Streptococcus pneumoniae in rural Gambian villages: a longitudinal study. Clin Infect Dis
  23. (2005). AE: Long-term effects on the nasopharyngeal flora of children following antimicrobial therapy of acute otitis media with cefdinir or amoxycillinclavulanate.
  24. (2009). Ageing and its possible impact on mucosal immune responses. Ageing Res Rev
  25. (2008). Ahrne S: Reduced diversity in the early fecal microbiota of infants with atopic eczema.
  26. (1999). Aires de Sousa M, Tomasz A: 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
  27. (2004). AJ: Haemophilus influenzae type b conjugate vaccines. Immunology
  28. (2006). AJ: New screening software shows that most recent large 16S rRNA gene clone libraries contain chimeras. Appl Environ Microbiol
  29. (2010). al: A catalog of reference genomes from the human microbiome. Science
  30. (1996). AL: A virulent nonencapsulated Haemophilus influenzae.
  31. (2009). al: The NIH Human Microbiome Project. Genome Res
  32. (2005). Anaerobes in the upper respiratory tract in infancy. Anaerobe
  33. (1988). Ansorge W: Automated Sanger dideoxy sequencing reaction protocol.
  34. (1941). Antagonistic Relations of Microorganisms. Bacteriol Rev
  35. (1999). Antibody response to outer membrane proteins of Moraxella catarrhalis in children with otitis media. Pediatr Infect Dis J
  36. Antivirulence drugs to target bacterial secretion systems.
  37. (2009). Assessment of the bacterial diversity of breast milk of healthy women by quantitative real-time PCR. Lett Appl Microbiol
  38. (2010). Backhed F: Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism.
  39. (2010). Backhed F: Microbes and Health Sackler Colloquium: Human oral, gut, and plaque microbiota in patients with atherosclerosis.
  40. (1990). 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
  41. (1987). Bacterial evolution. Microbiol Rev
  42. (2009). Bacterial population moves toward a colon-like community in the pouch after total proctocolectomy. Surgery
  43. (2006). Belkum A: Lack of Interference between Streptococcus pneumoniae and Staphylococcus aureus in HIV-infected individuals?
  44. (2011). Belkum A: The inverse correlation between Staphylococcus aureus and Streptococcus pneumoniae colonization in infants is not explained by differences in serum antibody levels in the Generation R Study. Clin Vaccine Immunol
  45. (2011). Bjarnsholt T: The implication of Pseudomonas aeruginosa biofilms in infections. Inflamm Allergy Drug Targets
  46. (1996). BM: A study of risk factors for pneumococcal disease among children in a rural area of west Africa.
  47. (1996). BM: Carriage of pneumococci after pneumococcal vaccination. Lancet
  48. (1991). BM: Etiology of acute lower respiratory tract infections in Gambian children: II. Acute lower respiratory tract infection in children ages one to nine years presenting at the hospital. Pediatr Infect Dis J
  49. (1999). BM: Etiology of serious infections in young Gambian infants. Pediatr Infect Dis J
  50. (1996). BM: Nasopharyngeal carriage of pneumococci in Gambian children and in their families. Pediatr Infect Dis J
  51. (1999). BM: Preparation for a pneumococcal vaccine trial in The Gambia: individual or community randomisation? Vaccine
  52. (1998). BM: Vaccination with a Haemophilus influenzae type b conjugate vaccine reduces oropharyngeal carriage of H. influenzae type b among Gambian children.
  53. (2010). BR: The ecology of nasal colonization of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus: the role of competition and interactions with host's immune response.
  54. (2010). BW: Revisiting pneumococcal carriage by use of broth enrichment and PCR techniques for enhanced detection of carriage and serotypes.
  55. (2002). C: Estimates of world-wide distribution of child deaths from acute respiratory infections. Lancet Infect Dis
  56. (2004). Cairney JW: Diversity and ecology of soil fungal communities: increased understanding through the application of molecular techniques. Environ Microbiol
  57. (2001). Carlone GM: Evaluation of a medium (STGG) for transport and optimal recovery of Streptococcus pneumoniae from nasopharyngeal secretions collected during field studies.
  58. (2009). CB: Neonatal innate TLR-mediated responses are distinct from those of adults.
  59. (2008). Cesarean delivery may affect the early biodiversity of intestinal bacteria.
  60. (2009). CG: Childhood bacterial respiratory diseases: past, present, and future. Pediatr Infect Dis J
  61. (2009). Change of intestinal microbiota with elemental diet and its impact on therapeutic effects in a murine model of chronic colitis. Dig Dis Sci
  62. (2004). Changes in oral microbial profiles after periodontal treatment as determined by molecular analysis of 16S rRNA genes.
  63. (2009). Changing epidemiology of invasive pneumococcal disease following increased coverage with the heptavalent conjugate vaccine in Navarre, Spain. Clin Microbiol Infect
  64. (2006). Chonmaitree T: Effect of pneumococcal conjugate vaccine on nasopharyngeal bacterial colonization during acute otitis media. Pediatrics
  65. (2008). Chonmaitree T: Microbial interactions during upper respiratory tract infections. Emerg Infect Dis
  66. (2010). CJ: Neonatal, postneonatal, childhood, and under-5 mortality for 187 countries, 1970-2010: a systematic analysis of progress towards Millennium Development Goal 4. Lancet
  67. (2009). Claud EC: 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis.
  68. (2008). CM: Bench-to-bedside review: Bacterial virulence and subversion of host defences. Crit Care
  69. (2008). Coamplification of eukaryotic DNA with 16S rRNA gene-based PCR primers: possible consequences for population fingerprinting of complex microbial communities. Curr Microbiol
  70. (2010). Collman RG: Disordered microbial communities in the upper respiratory tract of cigarette smokers. PLoS One
  71. (2010). Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut
  72. (2007). Cryopreservation of microalgae and cyanobacteria. Methods Mol Biol
  73. (2005). Culture-independent analysis of fecal microbiota in infants, with special reference to Bifidobacterium species.
  74. (2006). Current face of acute otitis media: microbiology and prevalence resulting from widespread use of heptavalent pneumococcal conjugate vaccine. Clin Ther
  75. (2007). Current issues in the management of acute bacterial sinusitis in children.
  76. (2004). DC: Serotype-specific pneumococcal antibodies in breast milk of Gambian women immunized with a pneumococcal polysaccharide vaccine during pregnancy. Pediatr Infect Dis J
  77. (2009). de Lencastre H: Streptococcus pneumoniae nasopharyngeal carriage in children attending day-care centers in the central region of Portugal, in the era of 7-valent pneumococcal conjugate vaccine. Microb Drug Resist
  78. (2010). Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.
  79. (2005). Detection and serotyping of Streptococcus pneumoniae from nasopharyngeal samples by PCR-based multiplex assay.
  80. (2004). Developing animal models for polymicrobial diseases. Nat Rev Microbiol
  81. (2007). Development of the human infant intestinal microbiota. PLoS Biol
  82. (2011). Dewhirst FE: Cultivable Anaerobic Microbiota of Severe Early Childhood Caries.
  83. (2002). DF: The effect of sampling time and sample handling on the detection of Staphylococcus aureus in milk from quarters with subclinical mastitis. Can Vet J
  84. (2009). DH: T-REX: software for the processing and analysis of T-RFLP data.
  85. (2006). Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol
  86. (2011). Differential effects of frozen storage on the molecular detection of bacterial taxa that inhabit the nasopharynx. BMC Clin Pathol
  87. (2008). Drancourt M: rpoB sequence-based identification of Mycobacterium avium complex species.
  88. (1981). Duerden BI: The development of the bacterial flora in normal neonates.
  89. (2004). E: Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children. Jama
  90. (2004). E: Community-wide vaccination with the heptavalent pneumococcal conjugate significantly alters the microbiology of acute otitis media. Pediatr Infect Dis J
  91. (2010). E: Evolving microbiology of complicated acute otitis media before and after introduction of the pneumococcal conjugate vaccine in France. Diagn Microbiol Infect Dis
  92. (2007). E: Pneumococcal conjugate vaccine does not influence Staphylococcus aureus carriage in young children with acute otitis media. Clin Infect Dis
  93. (2009). Early bacterial colonization induces toll-like receptor-dependent transforming growth factor beta signaling in the epithelium. Infect Immun
  94. (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
  95. (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
  96. (2008). EK: Pneumonia research to reduce childhood mortality in the developing world.
  97. (2009). Engstrand L: Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls.
  98. (2010). Engstrand L: Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One
  99. (1980). Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life.
  100. (1998). Epidemiology of invasive pneumococcal disease in the Western Region, The Gambia. Pediatr Infect Dis J
  101. (2008). Epstein SS: Short peptide induces an &quot;uncultivable&quot; microorganism to grow in vitro. Appl Environ Microbiol
  102. (1989). Erfle H: Automated Sanger DNA sequencing with one label in less than four lanes on gel.
  103. (2005). et al: Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial &quot;pan-genome&quot;.
  104. (2010). Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete. Epidemics
  105. (2008). Evolution of mammals and their gut microbes. Science
  106. (2000). Ewig S: Acute exacerbations in chronic obstructive pulmonary disease (COPD)--microbial patterns and risk factors. Monaldi Arch Chest Dis
  107. (2011). Exploring the oral microbiota of children at various developmental stages of their dentition in the relation to their oral health. BMC Med Genomics
  108. (2002). Fecal microbial diversity in a strict vegetarian as determined by molecular analysis and cultivation. Microbiol Immunol
  109. (1999). Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery.
  110. (2010). Fliegerova K: PCR-DGGE-based study of fecal microbial stability during the long-term chitosan supplementation of humans. Folia Microbiol (Praha)
  111. (2007). FO: SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res
  112. (2007). Forney LJ: Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women. Isme J
  113. (2010). FR: Microbiota of deciduous endodontic infections analysed by MDA and Checkerboard DNA-DNA hybridization.
  114. (2006). Freezing induces biased results in the molecular detection of Flavobacterium columnare. Appl Environ Microbiol
  115. (2002). Fresnadillo Martinez MJ: Dynamics of nasopharyngeal colonization by potential respiratory pathogens.
  116. (2011). Fujiyama Y: Comparison of the fecal microbiota profiles between ulcerative colitis and Crohn's disease using terminal restriction fragment length polymorphism analysis.
  117. Fujiyama Y: Fecal microbiota profile of crohn's disease determined by terminal restriction fragment length polymorphism (t-rflp) analysis. Aliment Pharmacol Ther
  118. (2004). G: T-RFLP combined with principal component analysis and 16S rRNA gene sequencing: an effective strategy for comparison of fecal microbiota in infants of different ages.
  119. (2006). Gaillot O: The sodA gene as a target for phylogenetic dissection of the genus Haemophilus and accurate identification of human clinical isolates.
  120. (2005). Gain and loss of multiple genes during the evolution of Helicobacter pylori. PLoS Genet
  121. (2007). GD: Characterization and modeling of the Haemophilus influenzae core and supragenomes based on the complete genomic sequences of Rd and 12 clinical nontypeable strains. Genome Biol
  122. (2009). Genetic diversity of the pneumococcal capsule: implications for molecular-based serotyping. Future Microbiol
  123. (1987). Genetic factors in Haemophilus influenzae type b disease susceptibility and antibody acquisition.
  124. (2003). Gillespie SH: Quantitative validation of media for transportation and storage of Streptococcus pneumoniae.
  125. (2008). Gillevet PM: Comparison of the diversity of the vaginal microbiota in HIV-infected and HIV-uninfected women with or without bacterial vaginosis.
  126. (2006). GK: Genomic diversity between strains of the same serotype and multilocus sequence type among pneumococcal clinical isolates. Infect Immun
  127. (2006). GL: Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol
  128. (2009). Global epidemiology of meningococcal disease. Vaccine
  129. (2005). Gober AE: Recovery of potential pathogens and interfering bacteria in the nasopharynx of otitis media-prone children and their smoking and nonsmoking parents. Arch Otolaryngol Head Neck Surg
  130. (2005). Gober AE: Recovery of potential pathogens and interfering bacteria in the nasopharynx of smokers and nonsmokers. Chest
  131. (2001). Golani I: Controlling the false discovery rate in behavior genetics research. Behav Brain Res
  132. (2005). GT: Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma hominis.
  133. (2003). H: Nasopharyngeal carriage of anaerobes during health and acute otitis media by two years of age. Diagn Microbiol Infect Dis
  134. (2011). Has the use of molecular methods for the characterization of the human oral microbiome changed our understanding of the role of bacteria in the pathogenesis of periodontal disease?
  135. (2002). Hellstrom S: Bacterial adherence to pharyngeal cells: in vitro studies with alpha-haemolytic streptococci and Haemophilus influenzae. Acta Otolaryngol
  136. (2002). Hellstrom S: Bacterial interference between pathogens in otitis media and alpha-haemolytic Streptococci analysed in an in vitro model. Acta Otolaryngol
  137. (2000). Hellstrom S: Inhibition of OM pathogens by alpha-hemolytic streptococci from healthy children, children with SOM and children with rAOM.
  138. (2004). Hermans PW: Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet
  139. (2009). Hernell O: Formula feeding skews immune cell composition toward adaptive immunity compared to breastfeeding.
  140. (2004). Herva E: Survival of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis frozen in skim milktryptone-glucose-glycerol medium.
  141. (2009). Heyderman RS: Absence of mucosal immunity in the human upper respiratory tract to the commensal bacteria Neisseria lactamica but not pathogenic Neisseria meningitidis during the peak age of nasopharyngeal carriage.
  142. (2006). HJ: Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrateproducing anaerobes from the human gut. Appl Environ Microbiol
  143. (1996). HS: Binding between outer membrane proteins of nontypeable Haemophilus influenzae and human nasopharyngeal mucin. Infect Immun
  144. (2008). Hugenholtz P: A renaissance for the pioneering 16S rRNA gene. Curr Opin Microbiol
  145. (2003). Identification of mixed bacterial DNA contamination in broad-range PCR amplification of 16S rDNA V1 and V3 variable regions by pyrosequencing of cloned amplicons.
  146. (2010). Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in infants and toddlers. Pediatrics
  147. (2000). Impact of antimicrobial therapy on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis in children with respiratory tract infections. Clin Infect Dis
  148. (2011). Improved detection of nasopharyngeal co-colonization by multiple pneumococcal serotypes using latex agglutination or molecular serotyping by microarray.
  149. (2007). Increased rates of intense nasopharyngeal bacterial colonization of Vietnamese children with radiological pneumonia.
  150. (2007). Indirect effects of childhood pneumococcal vaccination on pneumococcal carriage among adults and older children in Australian Aboriginal communities. Vaccine
  151. (2000). Infections of the upper respiratory tract, head, and neck. The role of anaerobic bacteria. Postgrad Med
  152. (2006). Interference between Streptococcus pneumoniae and Staphylococcus aureus: In vitro hydrogen peroxide-mediated killing by Streptococcus pneumoniae.
  153. (2002). Interference of nontypeable Haemophilus influenzae and Moraxella catarrhalis by Streptococcus oralis in adenoid organ culture: a possible strategy for the treatment of the otitisprone child. Ann Otol Rhinol Laryngol
  154. (2007). Interspecies interactions within oral microbial communities. Microbiol Mol Biol Rev
  155. (2011). Isolauri E: Initial dietary and microbiological environments deviate in normal-weight compared to overweight children at 10 years of age.
  156. (2007). Isolauri E: Maternal breast-milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease. Clin Exp Allergy
  157. (2009). JA: Epidemiology and risk factors for Staphylococcus aureus colonization in children in the post-PCV7 era. BMC Infect Dis
  158. (2007). JA: Validation of nasopharyngeal sampling and culture techniques for detection of Streptococcus pneumoniae in children in Kenya.
  159. (1994). JD: Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants. Pediatr Infect Dis J
  160. (2008). JK: Molecular analysis of the gut microbiota of identical twins with Crohn's disease.
  161. (2007). JK: Molecular fingerprinting of the fecal microbiota of children raised according to different lifestyles. Appl Environ Microbiol
  162. (2010). Keku TO: Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes
  163. (1995). KH: Phylogenetic identification and in situ detection of individual microbial cells without cultivation. Microbiol Rev
  164. (2008). Kieny MP: Optimising the use of conjugate vaccines to prevent disease caused by Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae. Vaccine
  165. (2008). KL: Changing epidemiology of invasive pneumococcal disease among White Mountain Apache persons in the era of the pneumococcal conjugate vaccine. Clin Infect Dis
  166. KL: Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project.
  167. (1999). Klugman KP: Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J Infect Dis
  168. (2010). KM: Comparison of Sanger sequencing, pyrosequencing, and melting curve analysis for the detection of KRAS mutations: diagnostic and clinical implications.
  169. (2004). Kokesova A: Commensal bacteria (normal CHAPTER [Bibliography] 155 |P a g e microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett
  170. (1985). Konopka A: Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu Rev Microbiol
  171. (2007). KP: Long-term effect of pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae--and associated interactions with Staphylococcus aureus and Haemophilus influenzae colonization--in HIV-Infected and HIV-uninfected children.
  172. (2008). KP: TRiFLe, a program for in silico terminal restriction fragment length polymorphism analysis with user-defined sequence sets. Appl Environ Microbiol
  173. (1997). Krystofik D: Exclusive breastfeeding protects against bacterial colonization and day care exposure to otitis media. Pediatrics
  174. (2009). Kyd JM: The incidence of Streptococcus pneumoniae otitis media is affected by the polymicrobial environment particularly Moraxella catarrhalis in a mouse nasal colonisation model. Microbes Infect
  175. (2009). L: The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) coadministered with DTPw-HBV/Hib and poliovirus vaccines: assessment of immunogenicity. Pediatr Infect Dis J
  176. (2006). Lack of association between the nasopharyngeal carriage of Streptococcus pneumoniae and Staphylococcus aureus in HIV-1-infected South African children. J Infect Dis
  177. (2006). Leach AJ: Measuring nasal bacterial load and its association with otitis media. BMC Ear Nose Throat Disord
  178. (2008). LJ: Advances in the use of terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA genes to characterize microbial communities. Appl Microbiol Biotechnol
  179. (2002). LL: Design and evaluation of 16S rRNA-targeted oligonucleotide probes for fluorescence in situ hybridization. Methods Mol Biol
  180. (2009). LL: Effect of freezing on PCR amplification of 16S rRNA genes from microbes associated with black band disease of corals. Appl Environ Microbiol
  181. (2008). LM: Cytomegalovirus and Epstein-Barr virus in breast milk are associated with HIV-1 shedding but not with mastitis. AIDS
  182. (2008). Lode H: Pneumococcal vaccines: mechanism of action, impact on epidemiology and adaption of the species.
  183. (2007). Long-term ecological impacts of antibiotic administration on the human intestinal microbiota.
  184. (1999). Marked differences in pneumococcal carriage and resistance patterns between day care centers located within a small area. Clin Infect Dis
  185. (2004). McCormick JB: Natural materno-fetal transfer of antibodies to PspA and to PsaA. Clin Exp Immunol
  186. (2004). McCullers JA: Respiratory viruses predisposing to bacterial infections: role of neuraminidase. Pediatr Infect Dis J
  187. (2007). Metabolic activity and phylogenetic diversity of reed (Phragmites australis) periphyton bacterial communities in a hungarian shallow soda lake. Microb Ecol
  188. (2004). Metagenomics: application of genomics to uncultured microorganisms. Microbiol Mol Biol Rev
  189. (2004). Metagenomics: genomic analysis of microbial communities. Annu Rev Genet
  190. (2007). Microbial ecology of the cystic fibrosis lung.
  191. (2009). Microbial symbiosis: in sickness and in health.
  192. (2000). Microbiology of the middle meatus: a comparison between normal adults and children.
  193. (2005). Milligan PJ: Elimination of Haemophilus influenzae type b (Hib) disease from The Gambia after the introduction of routine immunisation with a Hib conjugate vaccine: a prospective study. Lancet
  194. Modelling
  195. (2005). Molecular analysis of human oral microbiota.
  196. (2005). Molecular analysis of jejunal, ileal, caecal and recto-sigmoidal human colonic microbiota using 16S rRNA gene libraries and terminal restriction fragment length polymorphism.
  197. (1998). Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. Chem Biol
  198. (2010). Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol
  199. (2003). Nohynek H: Report from a WHO working group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae. Pediatr Infect Dis J
  200. (2003). Nudler E: RNA polymerase holoenzyme: structure, function and biological implications. Curr Opin Microbiol
  201. (2010). Nutrigenomics and IBD: the intestinal microbiota at the cross-road between inflammation and metabolism.
  202. (2009). O: Breastfeeding stimulates total and cow's milk-specific salivary IgA in infants. Pediatr Allergy Immunol
  203. (2008). O'Brien KL: Indirect effect of 7-valent pneumococcal conjugate vaccine on pneumococcal colonization among unvaccinated household members. Clin Infect Dis
  204. (2007). O'Brien KL: Strain characteristics of Streptococcus pneumoniae carriage and invasive disease isolates during a clusterrandomized clinical trial of the 7-valent pneumococcal conjugate vaccine. J Infect Dis
  205. (2007). O'Flaherty V: DNA extraction method affects microbial community profiles from soils and sediment. Appl Microbiol Biotechnol
  206. (2005). Obesity alters gut microbial ecology.
  207. (1999). Oral colonization by anaerobic bacteria during childhood: role in health and disease. Oral Dis
  208. (2009). P: Metagenomic study of the oral microbiota by Illumina high-throughput sequencing.
  209. (2009). Parameswaran GI: Moraxella catarrhalis, a human respiratory tract pathogen. Clin Infect Dis
  210. (2007). Paranasal sinuses and middle ear infections: what do they have in common? Pediatr Allergy Immunol
  211. (2005). Pawlina W: Histology : a text and atlas with correlated cell and molecular biology. 5th edn.
  212. (2010). PCR Deduction of Pneumococcal Serotypes. Centers for Disease Control and Prevention;
  213. (2009). Penades JR: Killing niche competitors by remote-control bacteriophage induction.
  214. (2011). Pettigrew MM: Microbial communities of the upper respiratory tract and otitis media in children. MBio
  215. (2001). PH: Efficacy of a pneumococcal conjugate vaccine against acute otitis media.
  216. (2007). PH: Longitudinal study on pneumococcal carriage during the first year of life in Bangladesh. Pediatr Infect Dis J
  217. (2008). Phylogenetic diversity based on rrs, atpD, recA genes and 16S-23S intergenic sequence analyses of rhizobial strains isolated from Vicia faba and Pisum sativum in Peru. Arch Microbiol
  218. (2009). Pichichero ME: Breast-feeding is associated with a reduced frequency of acute otitis media and high serum antibody levels against NTHi and outer membrane protein vaccine antigen candidate P6. Pediatr Res
  219. (2010). Pichichero ME: New patterns in the otopathogens causing acute otitis media six to eight years after introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis J
  220. (1999). PJ: Haemophilus influenzae type b meningitis in The Gambia after introduction of a conjugate vaccine. Lancet
  221. (2009). Pneumococcal capsular polysaccharide structure predicts serotype prevalence. PLoS Pathog
  222. (2008). Postnatal development of intestinal microflora as influenced by infant nutrition.
  223. Principi N: Differences in nasopharyngeal bacterial flora in
  224. (2010). PS: Epidemiology of nasopharyngeal carriage of respiratory bacterial pathogens in children and adults: cross-sectional surveys in a population with high rates of pneumococcal disease. BMC Infect Dis
  225. (2010). PS: Molecular fingerprinting reveals the presence of unique communities associated with paired samples of root canals and acute apical abscesses.
  226. (2004). PW: Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis
  227. (2009). pyrosequencing and microbial identification. Clin Chem
  228. (2007). Rapid characterization of the normal and disturbed vaginal microbiota by application of 16S rRNA gene terminal RFLP fingerprinting.
  229. (1998). RC: Sanger DNAsequencing reactions performed in a solid-phase nanoreactor directly coupled to capillary gel electrophoresis. Anal Chem
  230. (2008). RD: Survey of bacterial diversity in chronic wounds using pyrosequencing, DGGE, and full ribosome shotgun sequencing.
  231. (2007). Real-time PCR for determining capsular serotypes of Haemophilus influenzae.
  232. (2006). Real-time quantitative broad-range PCR assay for detection of the 16S rRNA gene followed by sequencing for species identification.
  233. (2009). Recurrent bacterial vaginosis. Curr Opin Infect Dis
  234. (2010). regional, and national causes of child mortality in 2008: a systematic analysis. Lancet
  235. (1999). Relman DA: Bacterial diversity within the human subgingival crevice.
  236. (2005). Relman DA: Diversity of the human intestinal microbial flora. Science
  237. (2008). Relman DA: The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol
  238. (1998). Report on world health,
  239. (2003). Review and re-analysis of domain-specific 16S primers.
  240. (1999). Risk factors for carriage of respiratory pathogens in the nasopharynx of healthy children. Ascanius Project Collaborative Group. Pediatr Infect Dis J
  241. (1990). RJ: Branhamella catarrhalis: antigenic determinants and the development of the IgG subclass response in childhood.
  242. (2008). RN: Serotype replacement and multiple resistance in Streptococcus pneumoniae after the introduction of the conjugate pneumococcal vaccine. Microb Drug Resist
  243. (2010). Rosado AS: Microbial community profiling using terminal restriction fragment length polymorphism (T-RFLP) and denaturing gradient gel electrophoresis (DGGE). Methods Mol Biol
  244. (1999). RU: Transplacental transmission of serotype-specific pneumococcal antibodies in a Brazilian population. Clin Diagn Lab Immunol
  245. (2005). S: Bacterial modulation of mucosal innate immunity. Mol Immunol
  246. (2010). Safety and Immunogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable Haemophilus Influenzae Protein D Conjugate Vaccine Coadministered with Dtpw-Hbv/Hib and Poliovirus Vaccines. Pediatr Infect Dis J
  247. (2008). Salivary Genomics, Transcriptomics and Proteomics: The Emerging Concept of the Oral Ecosystem and their Use in the Early Diagnosis of Cancer and other Diseases. Curr Genomics
  248. (2010). Sangild PT: Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis.
  249. (2007). Santosham M: Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial. J Infect Dis
  250. (2000). Sarvetnick N: The microbial product lipopolysaccharide confers diabetogenic potential on the T cell repertoire of BDC2.5/NOD mice: implications for the etiology of autoimmune diabetes. Clin Immunol
  251. (2008). Seasonal distribution of otitis media pathogens among Costa Rican children. Pediatr Infect Dis J
  252. (2006). Sequential multiplex PCR approach for determining capsular serotypes of Streptococcus pneumoniae isolates.
  253. (2007). Serotype replacement in invasive pneumococcal disease: where do we go from here? J Infect Dis
  254. (2009). Serotype replacement in perspective. Vaccine
  255. (2009). Severini A: Multiplex detection of bacteria associated with normal microbiota and with bacterial vaginosis in vaginal swabs by use of oligonucleotidecoupled fluorescent microspheres.
  256. SG: Activity and DNA contamination of commercial polymerase chain reaction reagents for the universal 16S rDNA real-time polymerase chain reaction detection of bacterial pathogens in blood. Diagn Microbiol Infect Dis,
  257. (2001). Shinagawa H: Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res
  258. (2003). simultaneous, and sensitive detection of staphylococci.
  259. (2011). Single-cell genomics reveals the lifestyle of Poribacteria, a candidate phylum symbiotically associated with marine sponges.
  260. (1991). Sips D: Bacteriological nasal flora in newborns indicating health and/or development of infection.
  261. (2010). Siqueira Jr JF: Microbiota of Dentinal Caries as Assessed by Reverse-Capture Checkerboard Analysis. Caries Res
  262. (2007). SM: The changing epidemiology of invasive Haemophilus influenzae disease, especially in persons > or = 65 years old. Clin Infect Dis
  263. (2009). Smeesters PR: Microbial interactions in the respiratory tract. Pediatr Infect Dis J
  264. (2005). Socransky SS: Differences in the subgingival microbiota of Swedish and USA subjects who were periodontally healthy or exhibited minimal periodontal disease.
  265. (2008). Sogin ML: Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing. PLoS Genet
  266. (2002). Species diversity--scale matters. Science
  267. (1997). Stackebrandt E: Determination of microbial diversity in environmental samples: pitfalls of PCR-based rRNA analysis. FEMS Microbiol Rev
  268. (2006). Stobberingh EE: Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics
  269. (2010). Study of inter- and intra-individual variations in the salivary microbiota.
  270. (2009). Sugiyama T: Diversity of mucosa-associated microbiota in active and inactive ulcerative colitis.
  271. (2007). Sun B: [Perliminary study on the aerobes distribution of nasal cavity from the healthy children and adults]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
  272. (2008). Symbiotic gut microbes modulate human metabolic phenotypes.
  273. (2001). Takala AK: Nasopharyngeal carriage of Streptococcus pneumoniae in Finnish children younger than 2 years old.
  274. (1997). TF: Antigenic heterogeneity and molecular analysis of CopB of Moraxella (Branhamella) catarrhalis. Infect Immun
  275. (2011). TF: Differential adaptation of microbial pathogens to airways of patients with cystic fibrosis and chronic obstructive pulmonary disease. FEMS Microbiol Rev
  276. (1999). The Ascanius Project Collaborative G: Risk factors for carriage of respiratory pathogens in the nasopharynx of healthy children. Pediatric Infectious Disease Journal
  277. (2000). The changing burden of pediatric bloodstream infections in
  278. (2009). The core gut microbiome, energy balance and obesity.
  279. (2008). The descriptive epidemiology of Streptococcus pneumoniae and Haemophilus influenzae nasopharyngeal carriage in children and adults in Kilifi district, Kenya. Pediatr Infect Dis J
  280. (2000). The effects of hormones on sex differences in infection: from genes to behavior. Neurosci Biobehav Rev
  281. (2008). The global epidemiology of childhood pneumonia 20 years on. Bull World Health Organ
  282. (2008). The Human Microbiome Project: getting to the guts of the matter in cancer epidemiology. Cancer Epidemiol Biomarkers Prev
  283. (2007). The interaction of host and pathogen factors in chronic obstructive pulmonary disease exacerbations and their role in tissue damage.
  284. (1999). The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position. FEMS Immunol Med Microbiol
  285. (2009). The pneumococcal pilus predicts the absence of Staphylococcus aureus co-colonization in pneumococcal carriers. Clin Infect Dis
  286. (2003). The potential indirect effect of conjugate pneumococcal vaccines. Vaccine
  287. (2000). The prevalence of potentially pathogenic bacteria in nasopharyngeal samples from individuals with a long-standing coughclinical value of a nasopharyngeal sample. Fam Pract
  288. (2005). The role of innate immune responses in the outcome of interspecies competition for colonization of mucosal surfaces. PLoS Pathog
  289. (2009). The rpoB gene as a tool for clinical microbiologists. Trends Microbiol
  290. (2005). The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects.
  291. (2009). The significance of serotype replacement for pneumococcal disease and antibiotic resistance. Adv Exp Med Biol
  292. (2003). Tiedje JM: The Ribosomal Database Project (RDP-II): previewing a new autoaligner that allows regular updates and the new prokaryotic taxonomy. Nucleic Acids Res
  293. (2005). Tiedje JM: The Ribosomal Database Project (RDP-II): sequences and tools for high-throughput rRNA analysis. Nucleic Acids Res
  294. (2009). Tiedje JM: The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucleic Acids Res
  295. (2009). Tsang RS: Invasive Haemophilus influenzae disease: changing epidemiology and host-parasite interactions in the 21st century. Infect Genet Evol
  296. (2006). Ubukata K: Study of upper respiratory tract bacterial flora: first report. Variations in upper respiratory tract bacterial flora in patients with acute upper respiratory tract infection and healthy subjects and variations by subject age.
  297. (2006). Upper respiratory tract bacterial carriage in Aboriginal and non-Aboriginal children in a semi-arid area of Western Australia. Pediatr Infect Dis J
  298. (1997). Vaccination against colonizing bacteria with multiple serotypes.
  299. (2011). Vermeire S: Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives. Gut
  300. (2010). Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature
  301. (2010). W: Using DGGE profiling to develop a novel culture medium suitable for oral microbial communities. Mol Oral Microbiol
  302. (2005). Weekly point prevalence of Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis in the upper airways of normal young children: effect of respiratory illness and season. Apmis
  303. (2008). What are the implications for childhood pneumonia of successfully introducing Hib and pneumococcal vaccines in developing countries? PLoS Med
  304. (1986). Woese CR: Ribosomal RNA phylogeny and the primary lines of evolutionary descent. Cell
  305. (2010). Xiang C: Analysis of oral microbiota in children with dental caries by PCR-DGGE and barcoded pyrosequencing. Microb Ecol
  306. (2010). Xiang C: Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis.
  307. (1996). Yagupsky P: Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.
  308. (2009). YJ: Rhinovirus enhances various bacterial adhesions to nasal epithelial cells simultaneously. Laryngoscope
  309. (1989). Ylikoski JS: Comparison of the nasal bacterial floras in two groups of healthy subjects and in patients with acute maxillary sinusitis.
  310. (2011). Zenilman JM: Macroscale spatial variation in chronic wound microbiota: A cross-sectional study. Wound Repair Regen

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.