Causal inference regarding infectious aetiology of chronic conditions: A systematic review

In Europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures, which is likely to increase with an ageing population. Tackling this predicament entails better understanding of the natural history of chronic diseases, particularly of the early preclinical phase. The aetiologic origin of chronic conditions has been investigated since long and infectious agents have been suspected since the last century.

The objective of this systematic review was to identify published evidence describing associations between infectious agents and chronic conditions and to evaluate the causal inference of such associations, primarily using Koch's postulates and Hill's criteria of causation. The systematic searches resulted in identification of 3136 publications, of which 148 publications were included in this analysis; we examined a total of 408 associations, and we found a wide diversity of infectious agents to be associated with chronic conditions. There were in total 75 different infectious agents and 122 different chronic conditions described, and the research area appeared diverse and explorative. The majority of associations were identified for chronic conditions of the digestive, circulatory, respiratory, and nervous system, as well as for neoplasms. The infectious agents most frequently being implicated in the aetiology of chronic conditions included human immunodeficiency virus, Helicobacter pylori, hepatitis B virus, hepatitis C virus, and Chlamydia pneumoniae.

By concentrating research efforts on a few promising areas, the human, economic, and societal burden arising from chronic conditions may be reduced.