coinfected. Exploring such pathogen interactions and their effects on the immune system represent rapidly burgeoning areas of scientific interest.1

This report summarizes a two-day workshop held by the Institute of Medicine’s Forum on Microbial Threats on October 21–22, 2002, to address this rapidly evolving field. Invited experts presented research findings on a range of recognized and potential chronic sequelae of infections, as well as on diverse pathogenic mechanisms leading from exposure to chronic disease outcomes. Cancers, cardiovascular disease, demyelinating syndromes, neuropsychiatric diseases, hepatitis, and type 1 diabetes were among the conditions addressed. Participants explored factors driving infectious etiologies of chronic diseases of prominence, identified difficulties in linking infectious agents with chronic outcomes, and discussed broad-based strategies and research programs to advance the field. Table S-1 lists the infectious agents and associated diseases discussed in this report.

Emerging infectious diseases are conceptualized either as newly identified or appreciated infectious illnesses and conditions, or as previously recognized syndromes that are newly attributed to infection. Some scientists now believe that a substantial portion of chronic diseases may be causally linked to infectious agents. Just as the germ theory opened the way for numerous discoveries about the sources of acute infections, changing ideas about the nature of both infectious diseases and chronic diseases, coupled with the advent of powerful new laboratory techniques, are leading to novel claims concerning the infectious origins of chronic diseases.


The traditional standards for establishing a microbial or bacterial cause of disease are those that were developed for acute infections. Known as “Koch’s postulates,” they state that the causal organism must be:

  1. present in diseased tissue;

  2. isolated and grown in pure culture outside the animal host;

  3. shown to induce the same disease when injected into a healthy animal; and

  4. isolated from the experimentally inoculated animal in pure culture and shown to be the same as the original agent.


It should be clearly noted throughout this summary report that the nature of the evidence for causality of a chronic disease from an infectious agent varies considerably. Each of the cases reviewed here represents a wide spectrum of the nature of the relationship between the infectious agent and the chronic disease. In some cases, the links are definitive (e.g., human papillomavirus and cervical cancer). In other cases, the relationship has only recently been investigated with little more than suspected associations from preliminary data (e.g., enteroviruses and Type I diabetes).

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