Although implied by its name, Granger causality testing does not prove true causation in the epidemiologic sense. It originally is an econometric method to infer predictive value of one time series Table 4 . Short-term effects of influenza dynamics on pneumococcal risk using multivariable negative binomial regression analysis. over another and thus, rather than prove causation, adds a valuable piece to the overall interpretation of our analyses towards potential causation. With respect to ecological effects, it should be noted that we effectively treat influenza as an aggregate ''environmental'' exposure, in that we don't have influenza status on the individuals who develop invasive bacterial disease, which creates the risk of ecological effects, including ecological fallacy, in our study. There are practical barriers to formulating an adequately powered study that actually captured data on the temporal relationship between influenza and invasive bacterial disease at the level of the individual (e.g., through ongoing evaluation of individuals in the population for influenza infection, with subsequent identification of the [rare] individuals who developed invasive bacterial disease). Finally, with respect to measurement issues, for influenza A and B, we had to rely on public health surveillance data that are incomplete both because of under-reporting, and also because a majority of individuals with influenza never undergo virological testing [37] . Other exposures may have been misclassified because of measurement or population mobility. This misclassification should not have introduced bias into our study in the absence of correlation between pneumococcal risk and influenza or meteorological reporting but may have reduced our statistical efficiency. Nondifferential misclassification of exposures would mean that the effects reported here are likely to be lower-bound effects, with true effects being larger. Furthermore, the strong degree of agreement in our findings, across multiple methodological approaches, suggests that they are robust and not artifacts of the analytic approach taken.