| Conference Summary
Institute of Medicine Forum on Emerging Infections: Linking
Infectious Agents and Chronic Diseases
The belief that many long-recognized chronic diseases are
infectious in origin dates to the mid-nineteenth century, when
cancer was studied as a possible infectious disease. In the
1950s and 1960s, much biomedical research was unsuccessful in
confirming microbial causes of various chronic syndromes. Recent
years, however, are marked by successful identification of several
causal infectious agents of chronic disease such as Human papillomavirus
in cervical cancer, but challenges and controversies remain.
The Institute of Medicine’s Forum on Emerging Infections
recently sought to address this rapidly evolving field. To identify
cross-disciplinary contributions and challenges in determining
infectious causes of chronic diseases, the forum hosted a 2-day
workshop on October 21-22, 2002, Linking Infectious Agents
and Chronic Diseases: Defining the Relationship, Enhancing the
Research, and Mitigating the Effects. In response to invited
presentations, participants explored factors driving infectious
causes of chronic diseases to prominence, identified difficulties
in linking infectious agents with chronic conditions, and discussed
broad-based strategies and research programs that might advance
the field.
Invited experts provided research findings on a diverse range
of recognized and potential chronic sequelae of infection as
well as diverse pathogenic mechanisms from exposure to chronic
outcome. Cancers, demyelinating syndromes, cardiovascular disease,
neuropsychiatric diseases, hepatitis, and diabetes mellitus
were among the chronic conditions addressed. Ensuing discussions
noted gaps in knowledge and in the translation of research data
to health-care interventions for both accepted and speculative
causal associations. Workshop participants remarked on the likely
widespread clinical and public health implications of linking
infectious agents with chronic diseases that dominate health
care in economically established countries, including the United
States. The potential benefits of detecting and preventing causal
infections, and the risks of interventions against unproven
causal agents, are substantial. Workshop participants advocated
careful research to produce and appropriately translate validated,
reproducible data into clinical management to alleviate the
impact of chronic diseases.
Participants also recognized the potential impact of infectious
disease control on chronic diseases in economically developing
countries. Within 20 years, chronic diseases are expected to
represent a substantial proportion of their health burden. Presentations
on human T-cell lymphotropic virus type 1 infection and hepatitis
C-schistosomiasis coinfection demonstrated the impact
of progressive chronic infections that disproportionately affect
developing regions. These presentations emphasized the importance
of considering coinfections in chronic disease pathology. Data
on chronic outcomes of malaria in infected persons and unborn
children and of other coinfections emphasized these points.
Presentations also examined causal associations between enteric
or parasitic infections and long-term developmental disabilities,
as well as links between infectious agents and epilepsy. Coinfections
and common acute infections may represent an under-recognized
source of chronic pathology. In regions with limited health-care
resources, newly identified infectious causes of chronic diseases,
including tuberculosis and malaria, may require increased attention.
Against the backdrop of multiple microbes and multiple chronic
outcomes, participants attempted to identify research opportunities,
challenges, and barriers to understanding linkages between infections
and chronic syndromes, and ultimately efforts to mitigate the
impact of chronic diseases on human health. Recent developments
in technology, methodology, and collaborative research have
clearly advanced the ability to determine causal relationships.
However, the workshop highlighted numerous factors that complicate
identification and confirmation of one or more infectious roots
of a chronic disease—factors that current and future research
must address. These challenges include possible multifactorial
pathogenesis such as interactions between environmental and
genetic (host and microbe) influences; how the timing of infection
determines final chronic outcome; and the “hit-and-run”
nature of certain microbes that may be eliminated before chronic
disease becomes apparent. Additional challenges include differentiating
the roles of acute, persistently active, latent, and recurrent
infection in pathogenesis; the possible singular role of certain
species or strains in producing chronic sequelae; the influence
of coinfections in defining final pathology; difficulty detecting
latent infection before or when chronic disease is diagnosed;
differences in the sensitivity and specificity of detection
assays in different tissues; difficulty culturing certain microbes;
and the lack of adequate methods to identify novel or rare microbes,
viruses, and other pathogens. Equally complex is balancing investment
in potential infectious causes of multifactorial, high burden
diseases with that for rarer conditions that may have one primary
cause, infection.
Participants noted that recently developed molecular and immunologic
techniques (e.g., representational difference analysis, gene-chip
profiling of host and microbe, immune response profiling, proteomics)
offer new ways to overcome several obstacles to identifying
potential etiologic agents. However, continued investment in
new technologies or improving existing methods remains key to
overcoming challenges. Defining the temporal relationship between
infection and chronic disease with appropriate technology is
critical to translating science into effective clinical strategies
that intervene against infection to prevent or minimize chronic
disease.
Discussion further emphasized that scientifically sound, new
technologies must be applied to and guided by a foundation of
epidemiologic clues from well-designed studies and surveillance
systems. A multipronged approach will be critical. Research
and public health activities need to facilitate appropriate
linkage of existing and newly designed databases, ensuring quality
surveillance and epidemiology that better characterize infectious
and chronic diseases with their distributions and potential
associations. Many settings demand longitudinal investigations
to complement case-control or cross-sectional studies, requiring
longer term investment. Detecting and confirming causal associations
will require study of both larger cohorts and at-risk subpopulations.
Improved coordination between basic and clinical scientists,
pathologists, and epidemiologists is critical to these goals.
Networks and collaborative teams are needed to develop and demand
the necessary standardized case definitions (for the infection
and the chronic outcome), new and adequate specimen collections
with pedigree databases, and comparable methods of analysis.
Overall discussions emphasized two major themes of the workshop:
1) the need to define the nature and scope of future research
that balances global efforts among the various chronic syndromes
and 2) development of a coordinated and systematic strategy
to maximize resource use and overcome the inherent technologic,
epidemiologic, and organizational challenges in this field.
A published summary of the workshop that includes individually
authored papers by workshop presenters will be available in
early 2003 from the National Academy Press (available from:
URL: www.nap.edu or 800-624-6242).
Additional information about the activities of the Forum on
Emerging Infections can be found at URL: http://www.iom.edu
under the Board on Global on Health or by contacting 202-334-3992.
Presented with permission.
Siobhán O’Connor, Thomas M. Shinnick, and Christopher
E. Taylor. Institute of
Medicine Forum on Emerging Infections: Linking Infectious Agents
and Chronic
Diseases. Emerging Infectious Diseases [serial online] 2002
Dec [cited 2003 Apr
28];8. Available from: URL: http://www.cdc.gov/ncidod/EID/vol8no12/02-0717.htm
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