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Mycobacterium Avium Paratuberculosis: Incidental Human Pathogen or Public Health Threat?

Institutions
American Society of Microbiology
Start date
2007
End date
2008
Objective
Mycobacterium avium subspecies paratuberculosis (MAP) is a soil microorganism and the etiologic agent of Johnes Disease (JD), a chronic and progressive enteric infection considered to be one of the most serious diseases affecting cattle and other domestic and wild animals, including sheep, goats, elk, and primates. Clinical progression of the disease includes severe diarrhea and weight loss, and the affected animals eventually either die or are killed. JD is prevalent in domestic animals worldwide; its economic impact in the U.S. alone is stunning, with an estimated loss of $1.5 billion every year. One study estimated the prevalence of MAP in U.S. cattle to be 1.6%, with a significantly higher prevalence in the dairy cattle subset. Studies in more localized herds of dairy cattle have produced even higher estimates; one estimated the prevalence of MAP in cattle in California to be 9.4%. The problem is even more serious in other countries: a study in Denmark estimated the prevalence of MAP in the dairy cattle to be 47%. Mounting evidence supports a role for MAP as an etiologic agent (although it may be one of several) of Crohns Disease (CD), a chronic relapsing inflammatory human disease of the gut. The possibility that MAP is involved in both JD and CD suggests that MAP could be transferred from cattle to humans. While the direct transfer has not been demonstrated, there is increasing evidence that some percentage of the milk supply is contaminated with MAP from the dairy cattle. We believe that MAP may be an underappreciated and emerging potential public health threat and deserves close examination of its role in the epidemiology of animal and human disease, determination of any food safety issues, and an evaluation of the events underlying MAP transmission from animals to humans. It is important to identify the gaps in our knowledge, and to focus new research to resolve these questions.
More information
NON-TECHNICAL SUMMARY: There is mounting evidence that supports a role for MAP as the etiologic agent of Crohn's Disease (CD), a chronic relapsing inflammatory human disease of the gut. The possibility that MAP is involved in both JD and CD suggests that MAP could be transferred from cattle to humans. While the direct transfer has not been demonstrated, there is increasing evidence that some percentage of the milk supply is contaminated with MAP from the dairy cattle. We believe that MAP may be an underappreciated and emerging potential public health threat and deserves close examination of its role in animal and human disease and an evaluation of the events underlying MAP transmission from animals to humans. This colloquium and its subsequent report will concentrate on the epidemiology of the MAP and will help to answer some of the questions about whether MAP is a food safety issue. The experts will meet for 2.5 days of deliberations, which will form the foundation of formal report. The report will include a succinct description of the issues, graphical representations, where appropriate, and recommendations for future action.

APPROACH: The American Academy of Microbiology (AAM) will convene a colloquium of 30-40 experts in animal health, agriculture, and human medicine in Salem, Massachusetts, June 15-17, 2007. Attendance at the colloquium is by invitation only, and participants are selected to ensure the greatest scientific balance and diversity. This inter-disciplinary approach will concentrate on the epidemiology of the MAP and will help to answer some of the questions about whether MAP is a food safety issue. The experts will meet for 2.5 days of deliberations, which will form the foundation of formal report. The report will include a succinct description of the issues, graphical representations, where appropriate, and recommendations for future action. The steering committee has composed a set of preliminary questions, intended to be the focus of the colloquium. Each group will discuss questions in the following areas--environmental/zoonotic sources of MAP and control measures; human MAP infection; potential role for MAP in CD; and gap analysis. The bulk of participants time will be spent in small working groups addressing these questions. There will be two general sessions that will bring all colloquium participants together. They will meet at the beginning of the colloquium and at the end to share their working group conclusions and recommendations and discuss any issues raised. Following the colloquium, a science writer (who will attend the colloquium), working closely with the steering committee chair, will develop a draft report for review by colloquium participants. The predicted contributions to the enhancement and improvement of science are: objective analysis of what is known about M. avium paratuberculosis as a public health problem; and recommendations for future research to clarify the gaps.

PROGRESS: 2007/06 TO 2008/05
OUTPUTS: Crohn's Disease (CD)is a devastating gastrointestinal disorder that afflicts 800,000 people in North America. A potential microbial agent of CD is Mycobacterium avium subspecies paratuberculosis (MAP), a microorganism that causes a similar gastrointestinal disease in ruminants called Johne's disease. People with CD have 7:1 odds of having a documented presence of MAP in blood or gut tissues than those who do not have CD, thus the association of MAP and CD is no longer in question (FIGURE-1 of published report). The critical issue today is not whether MAP is associated with CD, but whether MAP causes CD or is only incidentally present, not an inciter or participant in the disease process. If MAP is involved in the disease process of CD or other gastrointestinal disorders, then we need to determine how people are exposed to this microorganism, how to prevent that exposure, and how to treat the infection.The American Academy of Microbiology (AAM), the honorific leadership group of the American Society for Microbiology (ASM), convened a colloquium of 19 scientific experts (medicine, microbiology, veterinary pathology, epidemiology, infectious diseases, and food safety) and 7 sponsor representatives in June 2007 in Salem, MA,to describe the state of knowledge about the relationship between MAP and CD and to make recommendations for effective research that will move the field forward. The experts met for 2.5 days of deliberations, which formed the foundation of a formal report. Experts were divided into two working groups and each group deliberated issues in the following areas: Environmental/zoonotic sources of MAP and control measures; Human MAP infection; Potential role for MAP in CD; and Gap Analysis (what additional information/research is necessary to further clarify the role of MAP as a human pathogen). The closing session reviewed the consensus discussions and the experts reviewed and commented on a draft final report that includes a succinct description of the issues, graphical representations, where appropriate, and recommendations for future action. Results: A Symposium reporting the findings of the Colloquium was held at the ASM General Meeting in Boston, MA, June 2008.The full colloquium report, Mycobacterium avium paratuberculosis: Incidental Human Pathogen or Public Health Threat, will be published in print and electronically posted on the AAM website by August 2008. A specific outreach plan will be developed, including: -Press release announcing the report will be sent to relevant scientific publications, such as Science, Nature, as well as to popular science publications, e.g., Science News, Scientific American, Discover, Popular Science, and New Scientist.-Press release will be posted on EurekAlert, the web site for science journalists hosted by the American Association for the Advancement of Science (AAAS).-The report will be posted to the ASM website and announced to its 43,000 members through the "What's New" section of the Society's home page (http://www.asm.org).-Copies of the report will be provided to colloquium participants and supporters and member organizations of the International Union of Microbiological Societies.
PARTICIPANTS: Individuals. Carol Nacy, PI. Chair of Steering Committee; led development of working groups' issues for discussion; led colloquium opening and closing sessions; participated in working groups to ensure all issues were discussed and a consensus developed; reviewed participants' comments of draft report; and synthesized comments and finalized report. Partner Organizations: The following organizations provided financial support--U.S. Department of Agriculture, Animal and Plant Health Inspection Service (APHIS); U.S. Department of Agriculture, Cooperative State Research, Education, and Extension Service (CSREES); U.S. Department of Agriculture, Johne's Disease Integrated Program, BD; Broad Foundation; Canadian Foundation for Infectious Diseases; Crohn's & Colitis Foundation of Canada; Giaconda Limited; Hawk Corporation; Kauver Foundation; Oxford Immunotec; Sequella, Inc. and TREK Diagnostic Systems, Inc. Training: All participants were assigned to a working group. Every effort was made to ensure that the two groups were balanced in gender, scientific expertise, and geographic location. This mix guaranteed a balanced and comprehensive discussion, but also optimizes the participants' professional development by hearing other's opinions and experiences.
TARGET AUDIENCES: The report will be published in print and electronically; it will be posted on the AAM's web page. A specific outreach plan will be developed, including: Press release announcing the report will be sent to relevant scientific publications, such as Science, Nature, as well as to popular science publications, e.g., Science News, Scientific American, Discover, Popular Science, and New Scientist; Press release will be posted on EurekAlert, the web site for science journalists hosted by the American Association for the Advancement of Science (AAAS);The report will be posted to the ASM website and announced to its 43,000 members; Copies of the report will be provided to the leadership of the ASM, colloquium participants and supporters, and member organizations of the International Union of Microbiological Societies. Government agencies, industry, educators, and the scientific and lay communities have a strong need for objective, credible analyses, assessments, and recommendations on critical issues in microbiology. AAM colloquia are designed to evoke just such information. Our reports are viewed as unbiased statements of the issues and practical recommendations for the future.
PROJECT MODIFICATIONS: Not relevant to this project.

IMPACT: 2007/06 TO 2008/05
The general consensus of the experts was that there are certainly reasons to suspect a role for MAP in CD: MAP persists in contaminated soil and water, which links the environmental factor of CD to the disease. One genetic trait that is affiliated in certain patients with CD is the NOD2 gene, which regulates ability to respond appropriately to bacterial cell walls, thus the link between the genetic trait and MAP or other bacteria. MAP causes Johne's disease, an illness of cattle and other ruminants; the similarities of MAP disease in animals, for which the etiologic agent is known, and CD, for which the etiologic agent is unknown, provide a symptomatic link between agent and disease. MAP can survive standard milk pasteurization processes and has been identified in off-the-shelf milk, in cheese made from the milk of MAP-infected cattle, and in meat from Johne's diseased animals in retail grocery stores in the U.S. and the European Union (E.U.); these observations could provide the exposure route of CD patients to MAP. Finally, treatment of some CD patients with antibiotics that have activity on certain other Mycobacteria, although not specifically selected for their activity against MAP, provides short-term or long-term relief or remission of symptoms. Circumstantially, these observations appear to make a compelling case for MAP as involved in CD. On the other hand, the ability to definitively identify MAP as the cause of CD, or the cause of a significant number of CD cases, is stymied by the elusive characteristics the organism itself, the lack of broadly available and validated clinical tools to easily and definitively identify MAP in accessible tissues, and the late symptomatic stage at which CD is finally diagnosed, where the origin of the destructive inflammation could have been years before the patient sought medical care. Most important, however, is the lack of resources, financial and scientific, to generate the tools that clinicians and patients need to determine whether MAP is involved in the disease process or not.Based on these issues, the experts agreed that the following research topics were of high priority: Research to discover and standardize diagnostics that are both sensitive and specific for MAP in animals and in humans and can determine the source of MAP cultured from human tissue is imperative; virtually all the research topics that will clarify the role of MAP in CD rely on this. Research must also address the issue of MAP transmissibility: whether MAP strains isolated from animals or food are genetically identical to the MAP strains isolated from humans and whether MAP can be transmitted from human to human Research should also examine the potential virulence factors in human MAP isolates and develop better animal models for evaluating MAP effects on human hosts and for evaluating the effectiveness of potential therapies for MAP infection. Identifying novel MAP-specific antimicrobials and effective antibiotic treatment regimens for MAP infections is a clinical research priority.

Funding Source
Nat'l. Inst. of Food and Agriculture
Project source
View this project
Project number
DCR-2007-01772
Accession number
210372
Categories
Sanitation and Quality Standards
Bacterial Pathogens
Commodities
Meat, Poultry, Game
Dairy