The belief that infectious agents may cause certain chronic diseases can be traced to the mid-19th century, when cancer was studied as a possible infectious disease. This effort met with little success. In the 1950s and 1960s, much more biomedical research was directed, again unsuccessfully, at the identification of microorganisms purported to cause a variety of chronic diseases. In recent years, however, the picture has begun to change. A number of chronic diseases have now been linked, in some cases definitively, to an infectious etiology: peptic ulcer disease with Helicobacter pylori, cervical cancer with several human papillomaviruses, Whipple's disease with Tropheryma whipplei, Lyme arthritis and neuroborreliosis with Borrelia burgdorferi, AIDS with the human immunodeficiency virus, liver cancer and cirrhosis with hepatitis B and C viruses, to name a few. Indeed, evidence continues to mount implicating microorganisms as etiologic agents of chronic diseases that have substantial morbidity and mortality, including atherosclerosis and cardiovascular disease, type 1 diabetes, inflammatory bowel disease, and a variety of neurological diseases. The proven and suspected roles of microbes does not stop with physical ailments; infections are increasingly being examined as associated causes of or possible contributors to a variety of serious, chronic neuropsychiatric disorders and to developmental problems, especially in children.

It also has become apparent that multiple pathogens sometimes interact in causing chronic diseases or rendering them more virulent. For example, people who have concomitant infection with hepatitis C virus and the organism that causes schistosomiasis—as many individuals do in some developing countries—often develop schistosomiasis much more rapidly than do people who are not 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.

TABLE S-1

Possible Infectious Etiologies for Chronic Diseases Discussed at the Workshop.

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.