Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
Infect Immun. 2018 May 22;86(6). doi: 10.1128/IAI.00727-17. Print 2018 Jun.
All-cause otitis media (OM) incidence has declined in numerous settings following introduction of pneumococcal conjugate vaccines (PCVs) despite increases in carriage of nonvaccine pneumococcal serotypes escaping immune pressure. To understand the basis for the declining incidence, we assessed the intrinsic capacity of pneumococcal serotypes to cause OM independently and in polymicrobial infections involving nontypeable (NTHi) using samples obtained from middle ear fluid and nasopharyngeal cultures before PCV7/13 rollout. Data included samples from OM episodes (11,811) submitted for cultures during a 10-year prospective study in southern Israel and nasopharyngeal samples (1,588) from unvaccinated asymptomatic children in the same population. We compared data representing pneumococcal serotype diversity across carriage and disease isolates with and without NTHi coisolation. We also measured associations between the pneumococcal phenotype and the rate of progression from colonization to OM in the presence and absence of NTHi. Whereas pneumococcal serotype diversity was lower in single-species OM than in single-species colonization, levels of serotype diversity did not differ significantly between colonization and OM in mixed-species episodes. Serotypes differed roughly 100-fold in progression rates, and those differences were attenuated in polymicrobial episodes. Vaccine serotype pneumococci had higher rates of progression than nonvaccine serotypes. While serotype invasiveness was a weak predictor of the OM progression rate, efficient capsular metabolic properties-traditionally thought to serve as an advantage in colonization-predicted an enhanced rate of progression to complex OM. The lower capacity of nonvaccine serotypes to cause OM may partially account for reductions in all-cause OM incidence despite serotype replacement in carriage following rollout of PCVs.
所有原因中耳炎 (OM) 的发病率在许多情况下都有所下降，尽管非疫苗型肺炎球菌血清型的携带率增加，逃避了免疫压力。为了了解发病率下降的基础，我们评估了肺炎球菌血清型在独立和涉及非典型性（NTHi）的混合感染中引起 OM 的内在能力，使用的样本来自 PCV7/13 推出前从中耳液和鼻咽培养物中获得。数据包括来自 OM 发作的样本（11811 个），这些样本是在以色列南部进行的为期 10 年的前瞻性研究中提交进行培养的，以及来自同一人群中未接种疫苗的无症状儿童的鼻咽样本（1588 个）。我们比较了代表携带和疾病分离株中肺炎球菌血清型多样性的数据，这些分离株与 NTHi 共同分离的情况以及没有共同分离的情况。我们还测量了在存在和不存在 NTHi 的情况下，肺炎球菌表型与从定植到 OM 进展的速度之间的关联。尽管单种 OM 中的肺炎球菌血清型多样性低于单种定植，但混合感染中定植和 OM 之间的血清型多样性水平没有显著差异。血清型的进展率差异约为 100 倍，而在混合感染中，这些差异减弱。疫苗血清型肺炎球菌的进展率高于非疫苗血清型。虽然血清型侵袭性是 OM 进展率的一个弱预测因素，但有效的荚膜代谢特性——传统上被认为是定植优势的特征——预测了向复杂 OM 进展的增强速度。非疫苗血清型引起 OM 的能力较低，可能部分解释了尽管在 PCV 推出后携带率发生了血清型替代，但所有原因 OM 的发病率仍有所下降。
