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National Research Council (US) Committee on Diagnosis and Control of Johne's Disease. Diagnosis and Control of Johne's Disease. Washington (DC): National Academies Press (US); 2003.

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Diagnosis and Control of Johne's Disease.

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7Conclusions and Recommendations

Based on its review and synthesis of the literature, evaluation of existing control and herd status programs, and input received at the public workshop, the Committee on the Diagnosis and Control of Johne's Disease reached the following general conclusions:

CONCLUSION 1. Johne's Disease (JD) is a significant animal health problem that warrants implementation of control programs tailored to specific animal species and specific segments of the agriculture industry. Furthermore, JD control deserves high priority from the USDA, individual states, and industry. The significance of the disease derives primarily from its consequences for animal and herd health, for the agriculture industry, and for national and international trade. The current concern about JD in industry and government agencies of a potential link with Crohn's disease in humans provide additional support for making JD control a high priority.

CONCLUSION 2. There remains insufficient evidence to prove or disprove that Mycobacterium avium subsp. paratuberculosis is a cause of some or all cases of Crohn's disease (CD) in humans; a new approach is needed to resolve the issue—one that is based on a research agenda that will provide answers to specific criteria set forward in Hill-Evans postulates. A causal link between Map and Crohn's disease remains a plausible hypothesis that warrants a new research approach and steps by industry and government agencies to identify and mitigate avenues of.

CONCLUSION 3. Available diagnostic tests and information about the biology of JD and methods to control it are adequate for immediate implementation of control programs.

CONCLUSION 4. There are significant gaps in knowledge about some areas relevant to control, and are discussed below under recommendations. The committee emphasizes that closing those gaps will improve control programs, although the need for information should not delay their implementation.

CONCLUSION 5. Control of JD will require a long-term commitment and iterative program implementation to maximize the chance of success. This commitment must come from all constituencies, including USDA, state agencies, and industry.

CONCLUSION 6. Because JD is currently of greatest concern to the dairy industry much of the emphasis in control recommendations is directed there. Other industries, however, should consider this an opportune time to deal aggressively with the disease, before infection prevalence increases and the disease becomes more widespread.

CONCLUSION 7. The USDA National Animal Health Monitoring System (NAHMS) prevalence surveys for JD have been a critical element in laying the groundwork for control programs.

CONCLUSION 8. The Voluntary Bovine Johne's Disease Control Program proposed by the National Johne's Working Group (NJWG) has most of the elements necessary for a successful control program, but prospects for success are and will be limited by a lack of uniform implementation among individual states.

CONCLUSION 9. The committee endorses the NWJG's efforts in educating producers and veterinarians, and advocates the expansion of these efforts.


JD control programs are based on knowledge about the transmission of Map, the organism's persistence in the environment, and methods for reducing exposure to Map in animal environments. Minimum requirements for control therefore include identification of major transmission points, diagnostic and screening tests capable of identifying shedders, mechanisms for intervention at major transmission points, individual animal identification and trace-back capabilities, sources of disease-free replacement stock, and follow-up surveillance strategies (Kennedy and Benedictus, 2001). Available data suggest that these requirements have been met for JD in domesticated hoofstock and lead to the following conclusions:

  • Most transmission of Map is through a fecal-oral route, but transmission also can occur in utero or via colostrum or milk.
  • Infected adult ruminants are the major transmission source of the organism.
  • Animals in the late preclinical or clinical stage of infection are more likely to shed high numbers of organisms than are early-stage infected animals.
  • Young animals (less than 6 months of age) are most susceptible, but older animals can be infected by heavy or prolonged exposure
  • Map can persist in water, manure, or other environmental sites for extended periods (one year or longer).
  • Introduction of new Map-infected animals is a primary means by which a herd or flock becomes infected.
  • Diagnostic and screening tests are adequate for detecting shedders at the individual animal and herd level, but tests are used best at the herd level.
  • Reporting ELISA results as likelihood ratios, rather than as a positive or negative test result, will be beneficial for control programs and could increase confidence in the tests.
  • Removal of late preclinical and clinical animals will greatly reduce Map organism numbers in the environment of an infected herd.
  • Removal of newborn calves from dams at birth (before suckling) can interrupt an important avenue of transmission.
  • Prevention of fecal contamination of feed, water, and the environment will reduce the opportunity for transmission of Map.
  • The NAHMS prevalence surveys should continue, with attention given to maximizing the data obtained from the samples collected through add-on projects and investigations.

National and International Control Programs

Compelling arguments exist for an expanded federal role in JD prevention and control in the United States. First, animal agriculture has recognized the serious economic consequences of the disease and identified it as a major animal health issue. U.S. animal agriculture has requested assistance addressing JD. Individual states have implemented JD programs, but the likelihood of their success is diminished by the lack of consistency across states and by the absence of federal program guidelines.

Second, the emergence of regional and national JD programs in Australia, Japan, and parts of Europe to certify the JD status of herds, flocks, and zones will increase pressure for additional government assurances of the JD status of animals and animal products destined for export. Japan is a major market for U.S. products. Australia and Europe are major competitors with the U.S. for animal and animal product markets. The U.S. must implement a national JD program in order to compete effectively in this emerging trade environment.

Third, there is some evidence that JD could be linked to Crohn's disease in humans. Definitively answering this question will require years of additional research. In the interim, pressure for JD prevention and control is likely to increase. Implementing a national JD prevention and control program will be a pragmatic step for U.S. government policy to address industry requests and trade competitiveness. Regardless of the eventual scientific conclusion regarding the putative Johne's-Crohn's link, a national program will improve the overall health of U.S. domesticated animals and the public's trust in the food supply.

Johne's disease is widespread in U.S. animal agriculture. A national prevention and control program can be implemented most successfully in an iterative fashion, each step building on the one before and setting the stage for the next. Much of the groundwork has come in NJWG's collaborative efforts. Industry organizations and university experts have cooperated with state and federal government officials to develop guidelines for state status and control programs that have been adopted in whole or in part by most states. Federal regulations have been adopted to limit the interstate transport of Map-positive animals. USDA's National Veterinary Service Laboratory has established a quality assurance program to ensure more consistent testing and greater confidence in results.


While the committee strongly endorses a Best Management Practices approach to control, it also felt that control programs should initially focus on JD to take advantage of growing support for control of the disease. In addition, it is anticipated that funding for various aspects of control will be more readily available through government-industry partnerships if control has an easily identifiable target, such as JD, rather than a broader concept of Best Management Practices. As control efforts progress, an incremental transition to a Best Management Practices approach should be more feasible.

RECOMMENDATION 1. An integrated, bottom-up approach to on-farm disease control is needed that meets the needs of the livestock producer and motivates behavioral change, with support at broader industry, state, and federal levels. Components of such a control program are described in Box 7–1.

Box Icon

BOX 7–1

Components of a Coordinated Industry/ Government JD Control Program. The following elements are important for a successful control program. At the farm level:

General outlines for a given type of management and husbandry situation will be the same, but must be sufficiently flexible to be easily adaptable to the specific circumstances of each farm. Finally, the information must be packaged and delivered in a manner that is in harmony with the information management style of the producer and motivates them to change their behavior. This motivation may require feedback signals in the form of market price differentials established through testing by the downstream purchaser of the farm product.

While control programs for dairy herds may be of highest priority, control programs for beef cattle, sheep, goats, and captive cervids should be developed and implemented. Control programs for zoo animals and wildlife should also be monitored to ensure that a non-domesticated animal reservoir does not compromise control efforts for any species. The committee also urges USDA to develop a system that encourages staff to publish data on the evolution, progress, and determinants of success of animal disease control programs.


The National Johne's Working Group has made education of cattle producers and veterinarians a high priority. However, the educational ‘push' from the herd veterinarian and other herd advisors, would be more effective when accompanied by a market incentive ‘pull' from food processors, distributers, and consumers for control to be implemented at the farm level. The committee endorses NJWG's effort, but offers the following additional recommendations for action by federal and state authorities to expand and improve cattle-education programs and initiate them for other species.

RECOMMENDATION 2. Commodity-oriented (dairy, beef, sheep, goat, llama, etc.) materials should be developed and standardized nationally and there should be a rationale and guidelines for development of control programs and certification plans. These should not be considered the same as national program standards, but they should provide an information base for participation in national programs.

RECOMMENDATION 3. Informational resources should be developed for practicing veterinarians that include guidance on diagnostic test selection, sample size and selection of animals for testing, interpretation of test results, risk assessment methods, writing herd plans, and monitoring compliance and progress.

RECOMMENDATION 4. Educational resources that emphasize control of risk factors (Best Management Practices) should be developed instead of materials that emphasize control of a single etiologic agent.

RECOMMENDATION 5. Training programs are needed for state Johne's coordinators, USDA personnel, practicing veterinarians, and laboratory personnel to ensure a uniform base of knowledge and practice.


The committee identified significant gaps in the current state of knowledge of the pathophysiology, immunology, diagnosis, and control of JD in domesticated livestock and wildlife. Choosing research projects needed to fill those gaps will be important to the success of any JD herd status and control programs, and is sufficiently complex for the committee to recommend the convening of a USDA panel to formulate consensus methods to address these research questions. The committee considered ongoing research to be important for the success of any control program and therefore felt that a research element should be integral to future program development. The committee developed recommendations in several areas described below.

Epidemiology of Map Infection and Johne's Disease

The committee felt that significant gaps exist in our understanding of the epidemiology of JD, which could affect the success of control programs being proposed. In particular, the committee recommends additional research on:

RECOMMENDATION 6. Age-dependent dose-response curves are needed to clarify the magnitude and significance of age-related susceptibility or resistance to infection and on the degree to which horizontal transmission occurs in different age groups. Use of epidemiological modeling would help to determine the best measure of infectivity.

With the increase in concentrated calf-rearing operations, there is an urgent need to investigate the possibility of horizontal transmission in young animals. Current control strategies also assume that horizontal transmission is insignificant in adults, but this should be confirmed because the success of control strategies could depend on this issue.

RECOMMENDATION 7. The effects of chronic, low-level exposure on infectivity and on the outcome of infection should be identified.

Much of the data on infectivity and age susceptibility has been derived from decades-old studies in which one or a few large infective doses typically were administered. Although this provides valuable information, because it does not mimic natural exposure, the conclusions that can be drawn from such studies are limited. It would be helpful to have a better understanding of the outcome of chronic, low-level, or intermittent exposure to Map in the environment.

Results of the two investigations proposed above will help regulators to establish a scientific basis for several control measures, such as how long to wait before restocking contaminated land, whether environmental decontamination can expedite the restocking process, and whether removal of calves from dams at birth is the best means of breaking the transmission cycle.

RECOMMENDATION 8. Experimental studies and field investigations of natural infection in nonruminant and ruminant wildlife in the United States should focus initially on native lagomorphs and other small mammals prevalent on or around livestock operations with endemic JD.

Recent investigations on the role of wildlife in the epidemiology of JD in livestock in Scotland, Australia, and the Czech Republic have yielded interesting results. The identification of endemic Map infection in Scotland has important ramifications for control programs there. Little work has been done in the United States on the susceptibility of nonruminant wildlife to Map infection. Determining the prevalence of Map infection in wildlife on or around livestock operations will be important to understanding the success or failure of any livestock JD control programs.

As control programs are implemented, they present several opportunities to take advantage of resulting “natural experiments.” The committee recommends that these opportunities not be lost.

RECOMMENDATION 9. Results of diagnostic testing, control practices, and other epidemiologic data should be evaluated, and used to answer remaining research questions, and to refine and optimize control programs.

RECOMMENDATION 10. The USDA NAHMS prevalence surveys should continue, with attention paid to maximizing the data obtained from the samples collected through “add-on” projects and investigations.

Diagnostics and Immunology

Although the committee acknowledges that available diagnostic tools are sufficient to implement control programs, significant deficiencies still exist. To address these important gaps, the committee recommends the following:

RECOMMENDATION 11. Epidemiologically sound sampling and sample-pooling protocols should be developed and validated to facilitate screening and monitoring of large cattle herds and sheep flocks.

Recent research in Australia suggests that pooling of sheep fecal samples could enable more cost-effective flock screening for control programs. This work should be repeated in the United States and expanded to include cattle. Another important need is for a rapid, sensitive test to detect the presence of Map in bulk-milk samples. This would promote more efficient and cost-effective collection of herd prevalence data, which will be important for control. Some promising studies have been conducted, but additional research is needed in this area.

RECOMMENDATION 12. Sensitive and specific serologic and fecal-culture methods should be developed and validated for use in sheep and goats.

The development of diagnostic tests for JD in sheep, goats, and other species has trailed that for cattle. Although much of the current control emphasis is on dairy cattle, development of more sensitive and specific tests is needed for these other species. Recent reports suggest that the difficulty in isolating sheep strains of Map by fecal culture has largely been overcome, but methods are still slow and not ideal for use in control programs.

RECOMMENDATION 13. Methods for detecting an early, specific immune response to Map should be developed.

There are no reliable tests to identify animals in the early stages of infection, before fecal shedding of Map begins. Early identification of infected animals would support control programs, especially for prepurchase testing of replacement animals. Exposure to other mycobacteria, such as M. avium subsp. avium, is likely to be common in cattle, so it is essential that any test to identify animals in the early stages of infection be highly specific for Map. This might require identification of unique antigenic epitopes in Map, against which an early immune response is generated.

Map Genome Studies

As the committee evaluated knowledge gaps and research needs, the importance of complete sequencing of the Map genome became evident. Sequencing would yield many benefits, including identification of unique Map antigens for development of diagnostic tests and vaccines, improvement of diagnostic methods based on polymerase chain reaction (PCR) and identification of potential virulence factors. The Map genome sequencing project at USDA's National Animal Disease Center is nearing completion, and the committee strongly recommends the following:

RECOMMENDATION 14. USDA and other agencies should seize the opportunity presented by the completion of the Map genome project to accelerate progress in JD research, diagnostic test improvement, and vaccine development.

Information about the completion of the project should be disseminated to the international research community for Johne's disease and for Crohn's disease, and the sequence data should be made available as soon as possible. Research funds should be directed to research and development projects that use the results of the Map genome project. The paucity of funds available for JD research has limited progress in several important areas. The completion of the Map genome project provides a unique opportunity to correct this oversight, and it should not be neglected.

Vaccine Development

Current vaccines for Map are highly problematic. There are conflicting data on their ability to reduce shedding of Map, and the fact that they generate cross-reactions to intradermal tests for M. bovis makes them unsuitable for widespread use in control programs. Because vaccines can expedite the reduction of disease prevalence, the committee recommends the following:

RECOMMENDATION 15. Research should be done on the nature and evolution of the immune response to Map, and ways to modulate the immune response to elicit protection should be studied.

RECOMMENDATION 16. Research is needed on the feasibility of using recombinant-vaccine technology to create a vaccine that generates a specific, protective immune response in livestock without interfering with diagnostic tests for JD, bovine tuberculosis, and other diseases.

Development of an efficacious vaccine will require identification of unique Map antigens that will elicit a protective immune response without generating cross-reactions to other mycobacteria, such as M. bovis. The Map genome project has the greatest potential for providing the basis for these advances.

Human and Animal Health

After evaluating all of the available evidence for a causal role for Map in Crohn's disease, the committee was of the unanimous opinion that the evidence was insufficient to either establish or refute a causal connection. However, a causal link between Map and Crohn's disease remains a plausible hypothesis that warrants additional study. The committee considered the following research to be important elements for the resolution of this question:

RECOMMENDATION 17. A blinded study should be done for the detection of Map and Map RNA-DNA in identical coded intestinal tissue samples sent to various laboratories using standardized methods for Map culture and detection. This will help clarify the degree to which conflicting research results have been the result of variations in methods versus operators.

RECOMMENDATION 18. A large-scale, double-blind, multicenter study should be done to detect the presence of Map and Map RNA-DNA in tissue specimens from patients with Crohn's disease, using the same standardized methods as above. The specimens should be stratified by type of disease, duration of disease, and treatment. Control subjects without Crohn's disease should be included in the study.

RECOMMENDATION 19. A large-scale, double-blind, multicenter study of the treatment of Crohn's disease patients with anti-Map combination antimicrobial therapy should be undertaken. The patients should be stratified by type of disease, duration of disease, and treatment, presence or absence of known susceptibility genes, treatment, and presence or absence of Map by culture or PCR methods. There also should be an appropriate control group of patients with Crohn's disease who do not receive anti-Map therapy.

RECOMMENDATION 20. A multicenter, double-blind study is needed to search for Map, Map antigens, and Map RNA-DNA in breast milk of lactating women with Crohn's disease compared to controls. Finding such in lactating women with Crohn's disease would provide strong support for the proposed connection between Map and Crohn's disease.

If a subset of CD patients responds to anti-Map therapy, or Map is otherwise implicated as a cause of CD in a subset of patients, research on methods to better identify this subset will be needed. Other research considered important by the committee included on-going studies of Crohn's susceptibility genes and familial tendencies, gene microarray studies to determine which genes are up- and down-regulated in Crohn's disease and animal models, especially genetically altered animals.

RECOMMENDATION 21. The National Institutes of Health or similar body should convene a panel with experts in gastroenterology, Crohn's disease, infectious disease, mycobacteriology, biostatistics, epidemiology, etc., to define the precise study designs and to rank order the various studies to be done.

Although the committee did not find sufficient evidence to implicate Map as a cause of Crohn's disease, there was consensus that efforts to identify and mitigate avenues of exposure to Map would be prudent while awaiting definitive resolution of this important question. Identifying environmental sources of Map also is an important element of JD control in livestock, so there is additional justification for such investigations. The committee therefore recommends researching the following projects:

RECOMMENDATION 22. Research should be conducted to determine the prevalence of viable Map in potable-water supplies, streams, ponds, and other bodies of water with potential for Map contamination. This could require development of better methods for identifying and quantifying Map in environmental samples.

RECOMMENDATION 23. Additional studies are needed to determine whether Map is present in retail milk or other dairy products, as well as in pasteurized colostrum or commercial colostrum replacers that are fed to calves.

RECOMMENDATION 24. Research should be done to determine the prevalence of viable Map in peripheral lymph nodes, muscle, and other tissues that are processed for human consumption.

RECOMMENDATION 25. Research should be done to determine the prevalence and concentration of Map in other environmental materials likely to be contaminated with ruminant manure and associated with exposure to humans or susceptible animals. Those materials could include composted manure, fruits and vegetables, pastures, and crops fed to livestock.

If a causal relationship is established between human Map infection and a subset of Crohn's disease cases, the above research recommendations will be essential for implementation of new control programs aimed at protecting public health by minimizing exposure to Map. Additional research would then be needed to develop methods for routine screening of dairy products, meat, and meat products for Map.

Copyright 2003 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK207645


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