Methods to assess seasonal effects in epidemiological studies of infectious diseases--exemplified by application to the occurrence of meningococcal disease.

Seasonal variation in occurrence is a common feature of many diseases, especially those of infectious origin. Studies of seasonal variation contribute to healthcare planning and to the understanding of the aetiology of infections. In this article, we provide an overview of statistical methods for the assessment and quantification of seasonality of infectious diseases, as exemplified by their application to meningococcal disease in Denmark in 1995-2011. Additionally, we discuss the conditions under which seasonality should be considered as a covariate in studies of infectious diseases. The methods considered range from the simplest comparison of disease occurrence between the extremes of summer and winter, through modelling of the intensity of seasonal patterns by use of a sine curve, to more advanced generalized linear models. All three classes of method have advantages and disadvantages. The choice among analytical approaches should ideally reflect the research question of interest. Simple methods are compelling, but may overlook important seasonal peaks that would have been identified if more advanced methods had been applied. For most studies, we suggest the use of methods that allow estimation of the magnitude and timing of seasonal peaks and valleys, ideally with a measure of the intensity of seasonality, such as the peak-to-low ratio. Seasonality may be a confounder in studies of infectious disease occurrence when it fulfils the three primary criteria for being a confounder, i.e. when both the disease occurrence and the exposure vary seasonally without seasonality being a step in the causal pathway. In these situations, confounding by seasonality should be controlled as for any confounder.