Reduced nontypeable Haemophilus influenzae lower airway infection in children with chronic endobronchial suppuration vaccinated with the 10-valent pneumococcal H. influenzae protein D conjugate vaccine

Abstract

BackgroundNontypeable Haemophilus influenzae (NTHi), the most common bacterial lower airway infection in children with protracted bacterial bronchitis, is associated with progression to bronchiectasis. We determined whether vaccination with 10-valent pneumococcal NTHi protein-D conjugate vaccine (PHiD-CV) reduced NTHi lower airway infection compared to children not PHiD-CV-vaccinated. Our unique childhood vaccination schedule and prospective 9-year bronchoalveolar lavage (BAL) collection provided an exclusive opportunity to examine this hypothesis. MethodsPaired BAL fluids and nasopharyngeal (NP) swabs were collected from 543 children (2007–2016) undergoing bronchoscopy for chronic cough. Children who received a primary course of ≥2 doses of one pneumococcal conjugate vaccine (PCV) and <2 doses of another PCV were included in each vaccine group. Logistic regression determined associations between NTHi lower airway infection (≥104 colony-forming units/mL BAL) and age, sex, Indigenous status, antibiotic exposure, and PHiD-CV vaccination. ResultsOf 262 PCV7-vaccinated, 53 PHiD-CV-vaccinated and 166 PCV13-vaccinated children (62 had mixed schedules, <2 PCV doses or missing vaccination data), NTHi lower airway infection was detected in 89 (34%), 9 (17%) and 47 (28%), respectively. On multivariate regression, significant independent factors associated with reduced NTHi lower airway infection were PHiD-CV vaccination (ORadjusted = 0.42, 95%CI 0.19–0.93), macrolide use (ORadjusted = 0.57, 95%CI 0.35–0.93) and increasing age (ORadjusted = 0.88, 95%CI 0.80–0.96). PHiD-CV vaccination had no impact on NTHi NP carriage. ConclusionsPHiD-CV-vaccinated children were significantly less likely to have NTHi lower airway infection than children not PHiD-CV-vaccinated. PHiD-CV is likely an effective intervention for reducing NTHi endobronchial infection in children at risk of chronic suppurative lung diseases.