Epidemiological and statistical basis for detection and prediction of influenza epidemics

Abstract: A large number of emerging infectious diseases (including influenza epidemics) has been identified during the last century. The emergence and re-emergence of infectious diseases have a negative impact on global health. Influenza epidemics alone cause between 3 and 5 million cases of severe illness annually, and between 250,000 and 500,000 deaths. In addition to the human suffering, influenza epidemics also impose heavy demands on the health care system. For example, hospitals and intensive care units have limited excess capacity during infectious diseases epidemics. Therefore, it is important that increased influenza activity is noticed early at local levels to allow time to adjust primary care and hospital resources that are already under pressure. Algorithms for the detection and prediction of influenza epidemics are essential components to achieve this.Although a large number of studies have reported algorithms for detection or prediction of influenza epidemics, outputs that fulfil standard criteria for operational readiness are seldom produced. Furthermore, in the light of the rapidly growing availability of “Big Data” from both diagnostic and prediagnostic (syndromic) data sources in health care and public health settings, a new generation of epidemiologic and statistical methods, using several data sources, is desired for reliable analyses and modeling.The rationale for this thesis was to inform the planning of local response measures and adjustments to health care capacity during influenza epidemics. The overall aim was to develop a method for detection and prediction of influenza epidemics. Before developing the method, three preparatory studies were performed. In the first of these studies, the associations (in terms of correlation) between diagnostic and pre-diagnostic data sources were examined, with the aim of investigating the potential of these sources for use in influenza surveillance systems. In the second study, a literature study of detection and prediction algorithms used in the field of influenza surveillance was performed. In the third study, the algorithms found in the previous study were compared in a prospective evaluation study. In the fourth study, a method for nowcasting of influenza activity was developed using electronically available data for real-time surveillance in local settings followed by retrospective application on the same data. This method includes three functions: detection of the start of the epidemic at the local level and predictions of the peak timing and the peak intensity. In the fifth and final study, the nowcasting method was evaluated by prospective application on authentic data from Östergötland County, Sweden.In the first study, correlations with large effect sizes between diagnostic and pre-diagnostic data were found, indicating that pre-diagnostic data sources have potential for use in influenza surveillance systems. However, it was concluded that further longitudinal research incorporating prospective evaluations is required before these sources can be used for this purpose. In the second study, a meta-narrative review approach was used in which two narratives for reporting prospective evaluation of influenza detection and prediction algorithms were identified: the biodefence informatics narrative and the health policy research narrative. As a result of the promising performances of one detection algorithm and one prediction algorithm in the third study, it was concluded that both further evaluation research and research on methods for nowcasting of influenza activity were warranted. In the fourth study, the performance of the nowcasting method was promising when applied on retrospective data but it was concluded that thorough prospective evaluations are necessary before recommending the method for broader use. In the fifth study, the performance of the nowcasting method was promising when prospectively applied on authentic data, implying that the method has potential for routine use. In future studies, the validity of the nowcasting method must be investigated by application and further evaluation in multiple local settings, including large urbanizations.