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

摘要 鼻咽(NP)与共生生物和病原体的定植是常见的，并且 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 细菌定植是引起急性呼吸道疾病和侵袭性疾病的重要原因。呼吸性 病毒和细菌也表现出在ARI发病机制中重要的相互作用。不久的最初阶段 在感染呼吸道细菌或感染呼吸道病毒后，尤其重要的是，向 急性呼吸窘迫综合征风险增加。肺炎链球菌、金黄色葡萄球菌和其他定植细菌通常也表达抗生素。 可以在共生生物体之间转移或交换的抗性基因。 在许多情况下为SARS-CoV-2大流行控制实施了广泛的缓解战略， 包括使用面罩、居家命令和学校停课。总的来说，这些努力是 与SARS-CoV-2的社区传播减少有关。此外，在这些期间进行的生态研究 期间还显示流感、呼吸道合胞病毒和肺炎链球菌病的中断。 这些活动非常重要，使包括疫苗在内的现有预防战略的成功相形见绌， 这些药物只能针对少数呼吸道病原体，而且其范围和有效性有限。 了解缓解策略对外来呼吸道病原体定植活动的影响 SARS-CoV-2将为了解感染动态和减轻这些常见疾病的负担提供信息 然而，目前无法预防的感染。 在两年的同一时期，我们在秘鲁利马进行了以家庭为基础的密集ARI监测 连续年份：2019年，恰好在新冠肺炎大流行之前，2020年，在SARS-CoV-2活动高峰期。 我们的目标是利用这一独特的平台来描述家庭感染和感染的模式 在有和没有采取缓解策略的情况下，通过开展两项具体的 目的：1)检验缓解策略与a)较少的殖民获取有关的假设 呼吸道细菌，b)较少感染呼吸道病毒，较短的定植/检测时间， 并减少了这些病原体在秘鲁半城市家庭的儿童和成人之间的传播， 2)检验缓解策略与较少的获取、较短的持续时间相关的假设 减少鼻咽耐药基因的家庭传播 秘鲁半城市地区家庭中的儿童和成人。对这些影响的详细了解 临床相关呼吸道病原体定植动态的缓解策略可能会提供信息 有针对性的应用，以减少急性呼吸道感染和肺炎的全球影响，特别是对非传染性疾病的感染 然而，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.