title: Etiology of Acute Otitis Media in Children Less Than 5 Years of Age: A Pooled Analysis of 10 Similarly Designed Observational Studies.
abstract: Acute otitis media (AOM) is an important cause of childhood morbidity and antibiotic prescriptions. However, the relative importance of the well-known otopathogens, Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hflu), remains unclear because of a limited number of tympanocentesis-based studies that vary significantly in populations sampled, case definitions and heptavalent pneumococcal conjugate vaccine use.
  
  
  
  We conducted a pooled analysis of results from 10 AOM etiology studies of similar design, the protocols of which were derived from a common protocol and conducted in children 3 months to 5 years of age in different countries. Generalized estimating equations were used to account for within-study correlations.
  
  
  
  The majority, 55.5% (95% confidence interval: 47.0%-65.7%) of 1124 AOM episodes, were bacterial pathogen positive: 29.1% (24.8%-34.1%) yielded Hflu and 23.6% (19.0%-29.2%) Spn. Proportions of Hflu and Spn were higher and lower, respectively, in heptavalent pneumococcal conjugate vaccine-vaccinated children. Hflu and Spn were each isolated from 20% to 35% of children in every 1-year age range. Hflu was less likely to be isolated from first (vs. subsequent) episodes [relative risk (RR): 0.71 (0.60-0.84)]. Spn was more often isolated from sporadic (vs. recurrent) cases [RR: 0.76 (0.61-0.97)]; the opposite was true for Hflu [RR: 1.4 (1.00-1.96)]. Spn cases were more likely to present with severe (vs. mild) symptoms [RR: 1.42 (1.01-2.01)] and Hflu cases with severe tympanic membrane inflammation [RR: 1.35 (1.06-1.71)].
  
  
  
  Spn and Hflu remain the leading otopathogens in all populations examined. While associated with overlapping symptoms and severity, they exhibit some differences in their likelihood to cause disease in specific subpopulations.
authors.affiliation: From the *GSK Vaccines, Wavre, Belgium; †Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Saint-Maur-des-Fossés, CHI Créteil and UPEC, France; ‡Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, and §Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; ¶Unidad de Otorrinolaringologia, Hospital Dr Sotero del Rio, Puente Alto, Santiago, Chile; ‖Departamento de Infectologia, Instituto Nacional de Pediatría de la Secretaría de Salud (SSA), Mexico City, Mexico; **Otolaryngology Department, King Saud University & King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; ††ENT-Center, Prinzenweg 1, 82319 Starnberg, Germany; ‡‡Centros de Estudios Infectologia Pediatrica, Cali, Colombia; §§GSK Biologicals, Ciudad Panama, Panama; ¶¶Sección de ORL Pediátrica, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and ‖‖Otolaryngology Department, Faculty of Medicine Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Van Dyke
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pirçon
authors.forename: Robert
authors.initials: R
authors.lastname: Cohen
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Andrés
authors.initials: A
authors.lastname: Rosenblüt
authors.forename: Mercedes
authors.initials: M
authors.lastname: Macias Parra
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Mazrou
authors.forename: Gerhard
authors.initials: G
authors.lastname: Grevers
authors.forename: Pio
authors.initials: P
authors.lastname: Lopez
authors.forename: Laura
authors.initials: L
authors.lastname: Naranjo
authors.forename: Felix
authors.initials: F
authors.lastname: Pumarola
authors.forename: Nuntigar
authors.initials: N
authors.lastname: Sonsuwan
authors.forename: William P
authors.initials: WP
authors.lastname: Hausdorff
mesh_terms: D000208:Acute Disease / Q000453:epidemiology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006192:Haemophilus Infections / Q000453:epidemiology / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D010033:Otitis Media / Q000453:epidemiology / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000302:isolation & purification; D014611:Vaccination / Q000706:statistics & numerical data*
chemical_list: D000900:Anti-Bacterial Agents