Child Health Division, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811, Australia.
Child Health Division, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811, Australia; School of Medicine, Griffith University, Gold Coast, QLD 4222, Australia.
Vaccine. 2018 Mar 20;36(13):1736-1742. doi: 10.1016/j.vaccine.2018.02.054. Epub 2018 Feb 23.
Nontypeable 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.
Paired 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 (≥10 colony-forming units/mL BAL) and age, sex, Indigenous status, antibiotic exposure, and PHiD-CV vaccination.
Of 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 (OR = 0.42, 95%CI 0.19-0.93), macrolide use (OR = 0.57, 95%CI 0.35-0.93) and increasing age (OR = 0.88, 95%CI 0.80-0.96). PHiD-CV vaccination had no impact on NTHi NP carriage.
PHiD-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.
非典型流感嗜血杆菌（NTHi）是迁延性细菌性支气管炎患儿最常见的细菌性下呼吸道感染病原体，与支气管扩张症的进展有关。我们旨在确定 10 价肺炎球菌结合型 NTHi 蛋白-D 疫苗（PHiD-CV）接种是否比未接种 PHiD-CV 的儿童降低了 NTHi 下呼吸道感染。我们独特的儿童疫苗接种方案和前瞻性 9 年支气管肺泡灌洗（BAL）采集为检验这一假说提供了一个独特的机会。
从 2007 年至 2016 年期间因慢性咳嗽接受支气管镜检查的 543 名儿童（2007-2016 年）中采集配对的 BAL 液和鼻咽（NP）拭子。纳入研究的儿童均接受过至少 2 剂一种肺炎球菌结合疫苗（PCV）和<2 剂另一种 PCV 疫苗的基础免疫。采用逻辑回归分析了 NTHi 下呼吸道感染（BAL 液≥10 菌落形成单位/mL）与年龄、性别、原住民身份、抗生素暴露和 PHiD-CV 疫苗接种之间的关系。
在 262 名接受 PCV7 疫苗接种、53 名接受 PHiD-CV 疫苗接种和 166 名接受 PCV13 疫苗接种的儿童中（62 名儿童的疫苗接种方案为混合方案，接种<2 剂 PCV 疫苗或缺少疫苗接种数据），分别有 89 名（34%）、9 名（17%）和 47 名（28%）儿童检测到 NTHi 下呼吸道感染。多变量回归分析显示，与 NTHi 下呼吸道感染减少相关的独立因素有 PHiD-CV 疫苗接种（OR=0.42，95%CI 0.19-0.93）、大环内酯类药物使用（OR=0.57，95%CI 0.35-0.93）和年龄增长（OR=0.88，95%CI 0.80-0.96）。PHiD-CV 疫苗接种对 NTHi 鼻咽部携带无影响。
与未接种 PHiD-CV 的儿童相比，接种 PHiD-CV 的儿童发生 NTHi 下呼吸道感染的可能性显著降低。PHiD-CV 可能是一种有效的干预措施，可降低患有慢性化脓性肺部疾病风险的儿童的 NTHi 支气管内感染。
