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: Xavier Sáez-Llorens, Stella Rowley, Digna Wong, Mirna Rodríguez, Arlene Calvo, Marisol Troitiño, Albino Salas, Vielka Vega, Maria Mercedes Castrejón, Patricia Lommel, Thierry G Pascal, William P Hausdorff, Dorota Borys, Javier Ruiz-Guiñazú, Eduardo Ortega-Barría, Juan Pablo Yarzabal, Lode Schuerman
• Journal: Human vaccines & immunotherapeutics (Hum Vaccin Immunother) Vol. 13 Issue 6 Pg. 1-16 (06 03 2017) ISSN: 2164-554X [Electronic] United States
• PMID: 28368738 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 10-valent pneumococcal conjugate vaccine
• Bacterial Proteins
• Carrier Proteins
• Haemophilus Vaccines
• Immunoglobulin D
• Lipoproteins
• Pneumococcal Vaccines
• glpQ protein, Haemophilus influenzae

Topics

• Bacterial Proteins (immunology)
• Carrier Proteins (immunology)
• Carrier State (prevention & control)
• Double-Blind Method
• Ear, Middle (microbiology)
• Exudates and Transudates (microbiology)
• Female
• Follow-Up Studies
• Haemophilus Infections (prevention & control)
• Haemophilus Vaccines (administration & dosage, immunology)
• Humans
• Immunoglobulin D (immunology)
• Infant
• Lipoproteins (immunology)
• Male
• Nasopharynx (microbiology)
• Otitis Media (prevention & control)
• Panama
• Pneumococcal Infections (prevention & control)
• Pneumococcal Vaccines (administration & dosage, immunology)
• Treatment Outcome