布里斯托尔和巴斯住院成人侵袭性和非侵袭性肺炎链球菌病的趋势：2006-2022年回顾性队列研究

摘要(中文译文)

肺炎球菌监测通常侧重于经微生物学阳性确认的病例，且收集的临床数据有限。文献中大多数肺炎球菌研究聚焦于侵袭性呼吸道疾病。本研究纳入了一个涵盖全因肺炎球菌病的队列，包括非侵袭性疾病和非呼吸道侵袭性疾病，并附有详细的临床结局，从而能够更全面地了解肺炎球菌疾病负担，尤其是脑膜炎病例。本研究回顾性收集了2006年至2022年间三家医院住院的侵袭性和非侵袭性肺炎球菌病成人队列。比较了侵袭性和非侵袭性住院病例的人口学特征和结局。比较了不同临床表现的侵袭性疾病（尤其是脑膜炎）与侵袭性呼吸道疾病的特征。采用自助重采样法比较了侵袭性疾病中不同临床表现的血清型分布。在总计3719例全因肺炎球菌病中，1419例（38.2%）为侵袭性呼吸道疾病。非侵袭性疾病见于2033例（54.7%）。非侵袭性疾病的30天病死率低于侵袭性疾病（但具有临床意义）（11.7%对14.8%；P = 0.005），住院时间相似。在1686例侵袭性病例中，258例（15.3%）为呼吸道以外部位。172例表现为脑膜炎的病例较下呼吸道感染病例更年轻（54.9岁对66.8岁；P < 0.001），且入住重症监护室的比例较高（63.4%对下呼吸道感染10.2%；P < 0.001）。我们未发现不同临床表现之间血清型分布存在差异的证据。肺炎球菌病存在相当大的疾病负担，而聚焦于侵袭性呼吸道疾病的研究或仅关注培养阳性疾病的监测未能体现这一负担。脑膜炎病例的结局尤其差，但非侵袭性疾病也具有较高的病死率。鉴于脑膜炎中发现的血清型与侵袭性呼吸道疾病相同，我们预期针对呼吸道疾病的相同疫苗也应适用于脑膜炎的预防。

Abstract

Pneumococcal surveillance typically focuses on cases identified by positive microbiology and collects limited clinical data. The majority of pneumococcal studies in the literature focus on invasive respiratory disease. This study includes a cohort of all cause pneumococcal disease, including non-invasive disease and non-respiratory invasive disease with detailed clinical outcomes, allowing a more complete view of pneumococcal disease burden, and particularly meningitis cases. A longitudinal adult cohort of invasive and non-invasive pneumococcal disease inpatients in three hospitals between 2006 and 2022, was retrospectively collected. The demographics and outcomes of invasive and non-invasive hospitalised cases were compared. Features of invasive disease in different clinical presentations, particularly meningitis, were compared to invasive respiratory disease. Serotype distributions of different presentations in invasive disease were compared using bootstrap resampling. Out of a total 3719 all cause pneumococcal disease, 1419 cases (38.2%) were invasive respiratory disease. Non-invasive disease was seen in 2033 cases (54.7%). Non-invasive disease had a lower (but clinically substantial) 30 day case-fatality rate than invasive disease (11.7% versus 14.8%; P = 0.005), and similar lengths of stay in hospital. Among the 1686 invasive cases, 258 (15.3%) were outside the respiratory tract. The 172 cases presenting with meningitis were younger (54.9y vs. 66.8y; P < 0.001) than those with lower respiratory tract infection; and had high rates of intensive care admission (63.4% vs. LRTI 10.2%; P < 0.001). We found no evidence of a different serotype distribution between different clinical presentations. There is a substantial burden of pneumococcal disease that is not represented by studies that focus on invasive respiratory disease, or by surveillance that focus only on culture positive disease alone. Outcomes are particularly poor in the case of meningitis, but non-invasive disease also has a high case fatality rate. Given the same serotypes are found in meningitis as invasive respiratory disease, we anticipate that the same vaccines that target respiratory disease should be relevant to the prevention of meningitis.

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