Department of Immunology and Institute of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Division of Pulmonology, Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
J Infect. 2017 Jun;74(6):527-544. doi: 10.1016/j.jinf.2017.03.005. Epub 2017 Mar 16.
Acute pulmonary and cardiac injury remain significant causes of morbidity and mortality in those afflicted with severe pneumococcal disease, with the risk for early mortality often persisting several years beyond clinical recovery. Although remaining to be firmly established in the clinical setting, a considerable body of evidence, mostly derived from murine models of experimental infection, has implicated the pneumococcal, cholesterol-binding, pore-forming toxin, pneumolysin (Ply), in the pathogenesis of lung and myocardial dysfunction. Topics covered in this review include the burden of pneumococcal disease, risk factors, virulence determinants of the pneumococcus, complications of severe disease, antibiotic and adjuvant therapies, as well as the structure of Ply and the role of the toxin in disease pathogenesis. Given the increasing recognition of the clinical potential of Ply-neutralisation strategies, the remaining sections of the review are focused on updates of the types, benefits and limitations of currently available therapies which may attenuate, directly and/or indirectly, the injurious actions of Ply. These include recently described experimental therapies such as various phytochemicals and lipids, and a second group of more conventional agents the members of which remain the subject of ongoing clinical evaluation. This latter group, which is covered more extensively, encompasses macrolides, statins, corticosteroids, and platelet-targeted therapies, particularly aspirin.
急性肺部和心脏损伤仍然是严重肺炎球菌病患者发病率和死亡率的重要原因，即使在临床康复后数年，早期死亡风险仍持续存在。尽管在临床环境中尚未得到确凿证实，但大量证据（主要来自实验性感染的小鼠模型）表明，肺炎球菌、胆固醇结合、孔形成毒素、肺炎球菌溶血素（Ply）与肺部和心肌功能障碍的发病机制有关。本综述涵盖的主题包括肺炎球菌病的负担、风险因素、肺炎球菌的毒力决定因素、严重疾病的并发症、抗生素和佐剂治疗，以及 Ply 的结构及其在疾病发病机制中的作用。鉴于人们越来越认识到 Ply 中和策略的临床潜力，本综述的其余部分重点介绍了目前可用的治疗方法的最新进展，这些方法可能直接和/或间接地减轻 Ply 的损伤作用。这些方法包括最近描述的各种植物化学物质和脂质等实验性治疗方法，以及第二组更传统的药物，其成员仍然是正在进行的临床评估的主题。后者涵盖更广泛，包括大环内酯类、他汀类、皮质类固醇和血小板靶向治疗，特别是阿司匹林。
