The role of influenza in the severity and transmission of respiratory bacterial disease.
The role of influenza in the severity and transmission of respiratory bacterial disease.
复制标题
流感在呼吸细菌疾病的严重程度和传播中的作用。
DOI：
10.1016/s2213-2600(14)70131-6
复制
发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Klugman KP
中科院分区：
文献类型：
--
作者：
Mina MJ;Klugman KP
流感病毒感染和呼吸道细菌感染均对全球发病率和死亡率造成重大负担。这些病原体的同时或连续感染表现为复杂且难以治疗的疾病过程，需要广泛的抗菌治疗并导致大量的超额死亡率，特别是在每年的流感季节和大流行期间。在宿主水平，流感病毒使呼吸道粘膜表面准备好过量细菌获取，这支持增加的携带密度和向下呼吸道的传播，同时极大地限制了先天性和适应性抗菌防御。在病毒介导的结构修饰、对连续感染的异常免疫应答和过度免疫病理学应答的驱动下，合并感染通过短期和长期偏离免疫稳态、抑制适当的病原体识别、丧失对组织损伤的耐受性和对严重细菌性疾病的易感性的普遍增加而被注意到。在人群水平上，这些影响转化为细菌水平传播的增加和抗菌治疗的过度使用。随着人们对未来可能发生的流感大流行的日益关注，过去十年我们对这些相互作用的理解取得了迅速进展。在这篇综述中，我们讨论了流感和呼吸道细菌合并感染的流行病学和临床重要性，包括为今天的调查奠定基础的基础工作，并详细介绍了我们对合并感染发病机制的结构和免疫机制的理解中最重要和最新的进展。我们描述和解释了已知的序列，从细菌动力学的传播和表型转变到这些过程背后的免疫学，细胞和分子修饰，并提出了进一步研究的途径，这些研究可能对预防和治疗策略最有价值，以最好地减轻未来流感大流行期间的过度疾病。
Infections with influenza viruses and respiratory bacteria each contribute substantially to the global burden of morbidity and mortality. Simultaneous or sequential infection with these pathogens manifests in complex and difficult-to-treat disease processes that need extensive antimicrobial therapy and cause substantial excess mortality, particularly during annual influenza seasons and pandemics. At the host level, influenza viruses prime respiratory mucosal surfaces for excess bacterial acquisition and this supports increased carriage density and dissemination to the lower respiratory tract, while greatly constraining innate and adaptive antibacterial defences. Driven by virus-mediated structural modifications, aberrant immunological responses to sequential infection, and excessive immunopathological responses, co-infections are noted by short-term and long-term departures from immune homoeostasis, inhibition of appropriate pathogen recognition, loss of tolerance to tissue damage, and general increases in susceptibility to severe bacterial disease. At the population level, these effects translate into increased horizontal bacterial transmission and excess use of antimicrobial therapies. With increasing concerns about future possible influenza pandemics, the past decade has seen rapid advances in our understanding of these interactions. In this Review, we discuss the epidemiological and clinical importance of influenza and respiratory bacterial co-infections, including the foundational efforts that laid the groundwork for today’s investigations, and detail the most important and current advances in our understanding of the structural and immunological mechanisms underlying the pathogenesis of co-infection. We describe and interpret what is known in sequence, from transmission and phenotypic shifts in bacterial dynamics to the immunological, cellular, and molecular modifications that underlie these processes, and propose avenues of further research that might be most valuable for prevention and treatment strategies to best mitigate excess disease during future influenza pandemics.