Rethinking the trade-off hypothesis in evolutionary epidemiology.

The trade-off hypothesis plays a foundational role in the theoretical framework of modern evolutionary epidemiology, proposing that pathogen fitness is maximized at intermediate levels of virulence. Despite its influence on the study of host-pathogen interactions, the hypothesis has been criticized for its limited empirical support and the conceptual ambiguities surrounding the definition of virulence. This paper reassesses the scientific status of the trade-off hypothesis by interpreting the dependencies among epidemiological parameters as constitutive principles. Therefore, the results of the seminal 1982 work of Anderson and May are reinterpreted as a shift in the constitutive principles underpinning the paradigm of evolutionary epidemiology. This perspective provides a novel basis for evaluating the empirical support for the trade-off hypothesis and reassessing the debate regarding its validity.