The spatial and temporal anatomy of seasonal influenza in the United States, 1968-2008

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 and 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 and 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 and 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 and 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 spatiotemporal 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 and 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 and 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