title: Density, Serotype Diversity, and Fitness of Streptococcus pneumoniae in Upper Respiratory Tract Cocolonization With Nontypeable Haemophilus influenzae.
abstract: BACKGROUND
  Coinfections by Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) are frequently implicated in complex otitis media. Whereas upper respiratory tract carriage precedes disease for both pathogens, interactions between species in cocolonized hosts are poorly understood. We compared colonization densities and the diversity and fitness of pneumococcal serotypes in single-species and mixed-species colonization.
  
  
  METHODS
  We analyzed nasopharyngeal pneumococcal carriage and nasopharyngeal and oropharyngeal NTHi carriage in 13 541 samples collected over 6909 study visits from 769 children 2-30 months old in a 7-valent pneumococcal conjugate vaccine dosing trial. We measured density associations between the species and compared pneumococcal serotype diversity during and in the absence of NTHi colonization. We used logistic regression to quantify associations between NTHi colonization and previously published pneumococcal serotype factors related to fitness.
  
  
  RESULTS
  Densities of the 2 species were positively associated when they co-occur in the nasopharynx. NTHi colonization was associated with reduced pneumococcal serotype diversity among children 2-18 months old and was more prevalent among children carrying pneumococcal serotypes with greater capsular thickness, neutrophil resistance, and metabolic efficiency.
  
  
  CONCLUSIONS
  Pneumococcal-NTHi cocolonization is associated with an elevated density of both species and with reduced diversity and increased fitness of pneumococcal serotypes. NTHi colonization may create a selective environment favoring pneumococci with immune-evasive phenotypes.
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lewnard
authors.affiliation: Section of Biostatistics.
authors.forename: Amit
authors.initials: A
authors.lastname: Huppert
authors.affiliation: Pediatric Infectious Disease Unit, Soroka University Medical Center.|Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Noga
authors.initials: N
authors.lastname: Givon-Lavi
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Pettigrew
authors.affiliation: Section of Infectious Disease Epidemiology, Gertner Institute for Epidemiology and Health Policy Research.|Infectious Disease Unit, Sheba Medical Center, Ramat-Gan.
authors.forename: Gili
authors.initials: G
authors.lastname: Regev-Yochay
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Dagan
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Weinberger
mesh_terms: D002353:Carrier State / Q000276:immunology / Q000382:microbiology / Q000821:virology; D002675:Child, Preschool; D060085:Coinfection / Q000276:immunology / Q000382:microbiology* / Q000821:virology*; D005260:Female; D006192:Haemophilus Infections / Q000276:immunology / Q000382:microbiology / Q000821:virology; D006193:Haemophilus influenzae / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology / Q000821:virology; D009960:Oropharynx / Q000276:immunology / Q000382:microbiology / Q000821:virology; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology / Q000821:virology; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000821:virology; D022242:Pneumococcal Vaccines / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology* / Q000821:virology*; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000254:growth & development* / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Streptococcus pneumoniae; carriage; coinfection; interspecies interaction; nasopharynx; nontypeable Haemophilus influenzae