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 |
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| Institution: | 1. Child Health Division, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811, Australia;2. School of Medicine, Griffith University, Gold Coast, QLD 4222, Australia;3. Department of Respiratory and Sleep Medicine, Queensland Children''s Health Service and Queensland University of Technology, Graham Street, South Brisbane, QLD 4101, Australia;1. GlaxoSmithKline, Wavre, Belgium;1. State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China;2. Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture), Hubei Key Laboratory of Animal Embryo and Molecular Breeding, Wuhan, Hubei 430064, China;3. State Key Laboratory of Agricultural Microbiology, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China;4. College of Life Sciences, Central China Normal University, Wuhan, Hubei 430079, China;1. National Reference Centre for Streptococcus pneumoniae, University Hospitals Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium;2. Department of Microbiology and Immunology, Katholieke Universiteit Leuven, Leuven, Belgium;1. Centre for Global Vaccine Research, Institute of Infection & Global Health, University of Liverpool, United Kingdom;2. Malawi-Liverpool-Wellcome Trust Laboratories, Blantyre, Malawi |
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| 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. |
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| Keywords: | Lower airway infection Protracted bacterial bronchitis Chronic suppurative lung disease Bronchiectasis Pneumococcal conjugate vaccine |
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