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

PLoS One. 2013 Jul 25;8(7):e68861. doi: 10.1371/journal.pone.0068861. Print 2013.

Abstract

Background: The global burden of disease has shifted from communicable diseases in children to chronic diseases in adults. This epidemiologic shift varies greatly by region, but in Europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures. A number of risk factors have been implicated in chronic diseases, such as exposure to infectious agents. A number of associations have been well established while others remain uncertain.

Methods and findings: We assessed the body of evidence regarding the infectious aetiology of chronic diseases in the peer-reviewed literature over the last decade. Causality was assessed with three different criteria: First, the total number of associations documented in the literature between each infectious agent and chronic condition; second, the epidemiologic study design (quality of the study); third, evidence for the number of Hill's criteria and Koch's postulates that linked the pathogen with the chronic condition. We identified 3136 publications, of which 148 were included in the analysis. There were a total of 75 different infectious agents and 122 chronic conditions. The evidence was strong for five pathogens, based on study type, strength and number of associations; they accounted for 60% of the associations documented in the literature. They were human immunodeficiency virus, hepatitis C virus, Helicobacter pylori, hepatitis B virus, and Chlamydia pneumoniae and were collectively implicated in the aetiology of 37 different chronic conditions. Other pathogens examined were only associated with very few chronic conditions (≤ 3) and when applying the three different criteria of evidence the strength of the causality was weak.

Conclusions: Prevention and treatment of these five pathogens lend themselves as effective public health intervention entry points. By concentrating research efforts on these promising areas, the human, economic, and societal burden arising from chronic conditions can be reduced.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Causality
  • Chlamydophila pneumoniae / isolation & purification
  • Chlamydophila pneumoniae / pathogenicity
  • Chronic Disease
  • Europe / epidemiology
  • Gram-Negative Bacterial Infections / epidemiology*
  • Gram-Negative Bacterial Infections / physiopathology
  • Gram-Negative Bacterial Infections / virology
  • HIV / isolation & purification
  • HIV / pathogenicity
  • Helicobacter pylori / isolation & purification
  • Helicobacter pylori / pathogenicity
  • Hepacivirus / isolation & purification
  • Hepacivirus / pathogenicity
  • Hepatitis B virus / isolation & purification
  • Hepatitis B virus / pathogenicity
  • Humans
  • Prevalence
  • Virus Diseases / epidemiology*
  • Virus Diseases / physiopathology
  • Virus Diseases / virology

Grants and funding

Research under this project was funded by the European Centre for Disease Prevention and Control (ECDC) and performed under an ECDC Specific Contract (Mapping Infectious Aetiology of Non-Communicable Chronic Diseases) Number OJ/2010/05/04-PROC/2010/021, with HERON Evidence Development LTD. ECDC staff specified the terms of reference for the project, helped design the search strategies, collected data and were involved in data analysis, interpretation of the findings, and writing of the manuscript.