title: Efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine against acute otitis media and nasopharyngeal carriage in Panamanian children - A randomized controlled trial.
abstract: We previously reported 10-valent pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) efficacy in a double-blind randomized trial (ClinicalTrials.gov: NCT00466947) against various diseases, including acute otitis media (AOM). Here, we provide further analyses. In the Panamanian subset, 7,359 children were randomized (1:1) to receive PHiD-CV or control vaccine at age 2/4/6 and 15-18 months. Of these, 2,000 had nasopharyngeal swabs collected. AOM cases were captured when parents sought medical attention for children with AOM symptoms; surveillance was enhanced approximately 2 y into the study through regular telephone calls or home visits by study personnel, who advised parents to visit the clinic if their child had AOM symptoms. Mean follow-up was 31.4 months. Clinical AOM (C-AOM) cases were assessed by physicians and confirmed by otorhinolaryngologists. Middle ear fluid samples, taken from children with C-AOM after specific informed consent, and nasopharyngeal samples were cultured for pathogen identification. For 7,359 children, 2,574 suspected AOM cases were assessed by a primary healthcare physician; 649 cases were C-AOM cases as per protocol definition. From the 503 MEF samples collected, 158 resulted in a positive culture. In the intent-to-treat cohort (7,214 children), PHiD-CV showed VE against first C-AOM (24.0% [95% CI: 8.7, 36.7]) and bacterial (B-AOM) episodes (48.0% [20.3, 66.1]) in children <24 months, which declined thereafter with age. Pre-booster VE against C-AOM was 30.7% [12.9, 44.9]; post-booster, -6.7% [-36.4, 16.6]. PHiD-CV VE was 17.7% [-6.1, 36.2] against moderate and 32.7% [-20.5, 62.4] against severe C-AOM. VE against vaccine-serotype pneumococcal NPC was 31.2% [5.3, 50.3] 3 months post-booster, and 25.6% [12.7, 36.7] across all visits. NTHi colonization rates were low and no significant reduction was observed. PHiD-CV showed efficacy against C-AOM and B-AOM in children younger than 24 months, and reduced vaccine-serotype NPC.
authors.affiliation: a Department of Infectious Diseases , Hospital del Niño, Panama City, Panama; Distinguished Member of the SNI , Senacyt , Panama.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sáez-Llorens
authors.affiliation: b Department of Otorhinolaryngology Hospital del Niño , Panama City , Panama.
authors.forename: Stella
authors.initials: S
authors.lastname: Rowley
authors.affiliation: c Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT) , Panama City , Panama.
authors.forename: Digna
authors.initials: D
authors.lastname: Wong
authors.affiliation: c Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT) , Panama City , Panama.
authors.forename: Mirna
authors.initials: M
authors.lastname: Rodríguez
authors.affiliation: d Health Research International , Panama City , Panama.
authors.forename: Arlene
authors.initials: A
authors.lastname: Calvo
authors.affiliation: d Health Research International , Panama City , Panama.
authors.forename: Marisol
authors.initials: M
authors.lastname: Troitiño
authors.affiliation: d Health Research International , Panama City , Panama.
authors.forename: Albino
authors.initials: A
authors.lastname: Salas
authors.affiliation: d Health Research International , Panama City , Panama.
authors.forename: Vielka
authors.initials: V
authors.lastname: Vega
authors.affiliation: e GSK Vaccines , Panama City , Panama.
authors.forename: Maria Mercedes
authors.initials: MM
authors.lastname: Castrejón
authors.affiliation: f GSK Vaccines , Wavre , Belgium.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lommel
authors.affiliation: f GSK Vaccines , Wavre , Belgium.
authors.forename: Thierry G
authors.initials: TG
authors.lastname: Pascal
authors.affiliation: f GSK Vaccines , Wavre , Belgium.
authors.forename: William P
authors.initials: WP
authors.lastname: Hausdorff
authors.affiliation: f GSK Vaccines , Wavre , Belgium.
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
authors.affiliation: f GSK Vaccines , Wavre , Belgium.
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Guiñazú
authors.affiliation: e GSK Vaccines , Panama City , Panama.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ortega-Barría
authors.affiliation: f GSK Vaccines , Wavre , Belgium.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Yarzabal
authors.affiliation: f GSK Vaccines , Wavre , Belgium.
authors.forename: Lode
authors.initials: L
authors.lastname: Schuerman
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002353:Carrier State / Q000517:prevention & control*; D004311:Double-Blind Method; D004432:Ear, Middle / Q000382:microbiology; D005122:Exudates and Transudates / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology*; D007223:Infant; D008074:Lipoproteins / Q000276:immunology*; D008297:Male; D009305:Nasopharynx / Q000382:microbiology; D010033:Otitis Media / Q000517:prevention & control*; D010176:Panama; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: C586648:10-valent pneumococcal conjugate vaccine; D001426:Bacterial Proteins; D002352:Carrier Proteins; D018073:Haemophilus Vaccines; D007072:Immunoglobulin D; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; C067989:glpQ protein, Haemophilus influenzae
keywords: acute otitis media; children; efficacy; nasopharyngeal carriage; pneumococcal conjugate vaccination