Principia aetiologica: taking causality beyond Koch's postulates.

There is no single accepted method to establish a causal relationship between an infective agent and its corresponding infectious disease. Different biomedical disciplines use a patchwork of distinct but overlapping approaches. To a greater or lesser extent these are based on criteria known as the Koch-Henle postulates, or 'Koch's postulates' for short. Deficiencies in Koch's postulates were recognized by their principal author shortly after their formulation. Now, over a century later, a more rigorous method to test causality has still to be finalized. One contender is a method that uses molecular methods to establish a causal relationship ('molecular Koch's postulates'). Recognizing the wider range of contemporary approaches used to build an argument for a causal relationship, the use of a more inclusive approach to establish proof of causality is proposed. This method uses an argument built from a series of assertions. Assertion 1: congruence or reproducible correlation of a taxonomically defined life form with the clinico-pathological and epidemiological features of infection. Assertion 2: consistency of the demonstrable biological response in the subject to an encounter with the prospective infective agent. Assertion 3: progressive or cumulative dissonance as an explanation for pathophysiological processes at every known level of biological organization in the subject. Assertion 4: curtailment of that pathophysiological process on the deliberate introduction of a specified biomedical intervention. Evidence to implicate the candidate biological entity as an initiator of or primer for cumulative dissonance places it in a subcategory of micro-organisms to be known as 'priobes'. A priobe is the sufficient and necessary antecedent cause of a pathophysiological process evident as an infectious disease.