Impact of Pandemic Mitigation Efforts on Colonization and Transmission of Respiratory Pathogens and Antibiotic Resistance Genes

摘要 鼻咽（NP）定植有真菌和病原微生物是常见的， 动态过程虽然这些动态通常发生在健康状态下，但许多呼吸道病毒和 定植细菌是急性呼吸道疾病（ARI）和侵袭性疾病的重要原因。呼吸 病毒和细菌也表现出在ARI发病机理中重要的相互作用。初期不久， 在获得呼吸道细菌或感染呼吸道病毒后， ARI风险增加。S. pneumoniae、S.金黄色葡萄球菌和其他定植细菌也通常表达抗生素 耐药基因可能在共同定殖的生物体之间转移或交换。 在许多情况下，为控制SARS-CoV-2大流行实施了广泛的缓解战略， 包括使用面部覆盖物、呆在家里的命令和关闭学校。总的来说，这些努力是 与SARS-CoV-2的社区传播减少有关。此外，这些期间的生态研究 流感、呼吸道合胞病毒和S.肺炎病 这些活动的规模非常大，使包括疫苗在内的现有预防战略的成功相形见绌， 其仅可用于对抗少数呼吸道病原体，并且其范围和有效性有限。 了解缓解战略对在全球范围以外呼吸道病原体定殖活动的影响 SARS-CoV-2将为了解感染动态和减少这些常见疾病的负担提供信息。 但目前无法预防的感染。 在同一时期，我们在秘鲁的利马进行了密集的以家庭为基础的ARI监测， 连续两年：2019年，就在COVID-19大流行之前，以及2020年，SARS-CoV-2活动高峰期间。 我们的目标是利用这个独特的平台来描述家庭获得和感染的模式， 在有和没有缓解战略的时期，通过开展两项具体的 目的：1）检验缓解策略与以下假设相关：a）较少的殖民获取 呼吸道细菌，B）较少的呼吸道病毒感染，较短的定殖/检测持续时间， 并减少了这些病原体在秘鲁半城市家庭的儿童和成人中的传播， 和2）检验缓解策略与更少的收购、更短的持续时间相关的假设 的检测，并减少家庭传播的鼻咽抗生素耐药基因， 秘鲁半城市家庭中的儿童和成人。详细了解这些影响 临床相关呼吸道病原体定植动态的缓解策略可能会为 有针对性的应用，以减少ARI和肺炎的全球影响，特别是对于那些没有 但疫苗是可以预防的

ABSTRACT Nasopharyngeal (NP) colonization with commensal and pathogenic organisms is common and a dynamic process. While these dynamics typically occur in the healthy state, many respiratory viruses and colonizing bacteria are important causes of acute respiratory illness (ARI) and invasive disease. Respiratory viruses and bacteria also exhibit interactions that are important in ARI pathogenesis. The initial period shortly after acquisition of respiratory bacteria or infection with respiratory viruses is particularly critical, imparting an increase in ARI risk. S. pneumoniae, S. aureus, and other colonizing bacteria also commonly express antibiotic resistance genes that may be transferred or exchanged between co-colonizing organisms. Broad mitigation strategies were implemented for SARS-CoV-2 pandemic control in many settings, including use of face coverings, stay-at-home orders, and school closures. Collectively, these efforts were associated with reduced community transmission of SARS-CoV-2. In addition, ecologic studies during these periods also demonstrated interruptions in influenza, respiratory syncytial virus, and S. pneumoniae disease activity that were very substantial, dwarfing the success of existing preventive strategies, including vaccines, which are available against only few respiratory pathogens and limited in their scope and effectiveness. Understanding the impact of mitigation strategies on the activity of colonizing respiratory pathogens beyond SARS-CoV-2 would inform efforts to understand infection dynamics and reduce the burden of these common yet currently unpreventable infections. We conducted intensive household-based ARI surveillance in Lima, Peru during the same period in two consecutive years: 2019, just prior to the COVID-19 pandemic, and 2020, during peak SARS-CoV-2 activity. We aim to leverage this unique platform to characterize patterns of household acquisition and infection with respiratory pathogens during periods with and without mitigation strategies through the conduct of two Specific Aims: 1) To test the hypothesis that mitigation strategies are associated with a) fewer acquisitions of colonizing respiratory bacteria, b) fewer infections with respiratory viruses, shorter durations of colonization/detections, and reduced transmission of these pathogens among children and adults in households in semi-urban Peru, and 2) To test the hypothesis that mitigation strategies are associated with fewer acquisitions, shorter duration of detection, and reduced household transmission of nasopharyngeal antibiotic resistance genes among children and adults in households in semi-urban Peru. A detailed understanding of the impact of these mitigation strategies on the dynamics of colonization with clinically relevant respiratory pathogens may inform targeted applications to reduce the global impact of ARI and pneumonia, particularly for infections that are not yet vaccine-preventable.