The spatial and temporal anatomy of seasonal influenza in the United States, 1972–2007

Bianca Malcolm, S. Morse
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The first chapter summarizes the current knowledge of the burden, morphology, and geography of influenza as well as limitations of prior studies. In the second chapter, weekly data on laboratory-confirmed influenza isolates from a national viral surveillance system (considered the “gold standard”) is compared with weekly pneumonia and influenza (P&I) mortality data from a national mortality surveillance system in order to determine if the timing of mortality data correlated well with the timing of viral surveillance data and was, therefore, a good measurement for determining the timing of annual influenza epidemics. Sufficient viral surveillance data for influenza is not available for the majority of the study period and its quality most likely varies geographically. This made it necessary for this study to use mortality data as a substitute. It was, therefore, critical for this dissertation to assess the reliability of mortality data as a measurement to determine the timing of annual influenza waves. In the third chapter, an analysis of monthly P&I mortality data was conducted to identify an average underlying wave of seasonal influenza spread in the United States, the spatial and temporal patterns of seasonal influenza in the U.S. from 1968 to 2008, and the dependence of the timing and spread of influenza on the dominant circulating influenza type or subtype in a given influenza season. Source locations of influenza transmission in the U.S. were also identified. The dependence of the spread process of seasonal influenza in the U.S. on distance and/or population was assessed in chapter four. Additionally, spatial clusters of P&I mortality rates at different phases of an average influenza wave were identified. An assessment of the effect of the introduction or reintroduction of a novel influenza virus subtype on the spatio-temporal dynamics of influenza spread in the U.S. was performed in the fifth chapter. In the sixth and final chapter, I conclude by summarizing the findings of these four studies. This research found that P&I mortality was a valid measure used to assess the timing of influenza epidemics. Additionally, seasonal influenza in the U.S. typically began in November, peaked in February, and ceased in May. Annual influenza epidemics lasted an average of 6.7 months and produced a small, but significant southward traveling wave of influenza across the United States, originating from northern states in September-October and moving toward southern states over a 4-month period. H3N2-prominent seasons were significantly shorter and faster in progression than H1N1-prominent seasons. 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Abstract

The Spatial and Temporal Anatomy of Seasonal Influenza in the United States, 1968-2008 Bianca Malcolm Seasonality has a major effect on the spatiotemporal dynamics of natural systems and their populations and is a driving force behind the transmission of influenza in temperate regions. Although the seasonality of influenza in temperate countries is widely recognized, inter-state spread of influenza in the United States has not been well characterized. This dissertation characterized the seasonality of influenza throughout the United States by using monthly pneumonia and influenza (P&I) mortality to model inter-state movement of seasonal influenza in the continental United States between 1968 and 2008. The first chapter summarizes the current knowledge of the burden, morphology, and geography of influenza as well as limitations of prior studies. In the second chapter, weekly data on laboratory-confirmed influenza isolates from a national viral surveillance system (considered the “gold standard”) is compared with weekly pneumonia and influenza (P&I) mortality data from a national mortality surveillance system in order to determine if the timing of mortality data correlated well with the timing of viral surveillance data and was, therefore, a good measurement for determining the timing of annual influenza epidemics. Sufficient viral surveillance data for influenza is not available for the majority of the study period and its quality most likely varies geographically. This made it necessary for this study to use mortality data as a substitute. It was, therefore, critical for this dissertation to assess the reliability of mortality data as a measurement to determine the timing of annual influenza waves. In the third chapter, an analysis of monthly P&I mortality data was conducted to identify an average underlying wave of seasonal influenza spread in the United States, the spatial and temporal patterns of seasonal influenza in the U.S. from 1968 to 2008, and the dependence of the timing and spread of influenza on the dominant circulating influenza type or subtype in a given influenza season. Source locations of influenza transmission in the U.S. were also identified. The dependence of the spread process of seasonal influenza in the U.S. on distance and/or population was assessed in chapter four. Additionally, spatial clusters of P&I mortality rates at different phases of an average influenza wave were identified. An assessment of the effect of the introduction or reintroduction of a novel influenza virus subtype on the spatio-temporal dynamics of influenza spread in the U.S. was performed in the fifth chapter. In the sixth and final chapter, I conclude by summarizing the findings of these four studies. This research found that P&I mortality was a valid measure used to assess the timing of influenza epidemics. Additionally, seasonal influenza in the U.S. typically began in November, peaked in February, and ceased in May. Annual influenza epidemics lasted an average of 6.7 months and produced a small, but significant southward traveling wave of influenza across the United States, originating from northern states in September-October and moving toward southern states over a 4-month period. H3N2-prominent seasons were significantly shorter and faster in progression than H1N1-prominent seasons. Moreover, influenza waves in the contiguous U.S. followed a general spatial contagion model, particularly at their peak, with high clusters of P&I rates found in Midwestern (North Dakota, Minnesota, South Dakota, Iowa, Nebraska, Kansas, Missouri, Arkansas, and Oklahoma), Southeastern (Kentucky, Tennessee, and West Virginia) and Northeastern States (New York, Vermont, Massachusetts, and Connecticut) at every phase of an epidemic. Finally, influenza waves that directly followed seasons that introduced or reintroduced a novel influenza subtype were significantly longer and slower in progression than the waves that introduced/reintroduced the novel virus. Identifying spatiotemporal patterns could improve epidemic prediction and prevention. This research determined the spatial and temporal characteristics of seasonal influenza in the U.S. and showed that these characteristics differed by dominant influenza subtype. Results of this research should aid public health professionals in refining influenza intervention strategies that include better placement and distribution of vaccines and other medicines.
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1972-2007年美国季节性流感的时空解剖
季节性对自然系统及其种群的时空动态具有重要影响,是温带地区流感传播背后的驱动力。虽然温带国家流感的季节性已得到广泛认识,但美国流感的州际传播尚未得到很好的描述。本论文通过使用每月肺炎和流感(P&I)死亡率来模拟1968年至2008年间美国大陆季节性流感的州际流动,从而表征了整个美国流感的季节性。第一章总结了目前对流感负担、形态和地理的认识以及先前研究的局限性。在第二章中,将来自国家病毒监测系统的实验室确诊流感分离株的每周数据(被认为是“金标准”)与来自国家死亡率监测系统的每周肺炎和流感(P&I)死亡率数据进行比较,以确定死亡率数据的时间是否与病毒监测数据的时间密切相关,因此,这是确定年度流感流行时间的良好衡量标准。在大部分研究期间,流感病毒监测数据不足,其质量很可能因地区而异。这使得本研究有必要使用死亡率数据作为替代。因此,评估死亡率数据作为确定年度流感波时间的测量的可靠性对于本论文至关重要。第三章对月度损益死亡率数据进行了分析,以确定美国季节性流感传播的平均潜在波,1968 - 2008年美国季节性流感的时空格局,以及流感时间和传播对特定流感季节主要流行流感类型或亚型的依赖关系。还确定了美国流感传播的源头地点。第四章评估了美国季节性流感传播过程对距离和/或人群的依赖性。此外,还确定了平均流感波不同阶段损失率的空间集群。第五章评估了引入或再引入一种新型流感病毒亚型对美国流感传播时空动态的影响。在第六章也是最后一章中,我对这四项研究的结果进行了总结。这项研究发现,损益死亡率是用于评估流感流行时间的有效措施。此外,美国的季节性流感通常在11月开始,2月达到高峰,5月停止。每年的流感流行平均持续6.7个月,在美国各地产生一股小规模但显著的向南传播的流感浪潮,于9月至10月从北部各州发源于南部各州,并在4个月的时间内向南部各州移动。h3n2显著季比h1n1显著季短且进展快。此外,美国邻近地区的流感波遵循一般的空间传染模式,特别是在高峰期,在流行病的每个阶段,中西部(北达科他州、明尼苏达州、南达科他州、爱荷华州、内布拉斯加州、堪萨斯州、密苏里州、阿肯色州和俄克拉荷马州)、东南部(肯塔基州、田纳西州和西弗吉尼亚州)和东北部各州(纽约州、佛蒙特州、马萨诸塞州和康涅狄格州)的损失率都很高。最后,在引入或重新引入新型流感亚型的季节之后直接出现的流感波比引入/重新引入新型病毒的流感波明显更长、进展更慢。识别时空格局有助于提高疫情预测和预防水平。本研究确定了美国季节性流感的时空特征,并表明这些特征因主要流感亚型而异。这项研究的结果应有助于公共卫生专业人员改进流感干预战略,包括更好地安置和分发疫苗和其他药物。
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