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Report Information

Participants

Abdellrazeq, Gaber Alexandria University, Egypt;
Baker, John Michigan State University;
Bannantine, John National Animal Disease Center, USDA-ARS;
Barletta, Raul University of Nebraska-Lincoln;;
Bermudez, Luiz Oregon State University;
Bhattarai, Bikash Texas A&M;
Carter, Michael USDA-APHIS-VS;
Chambrlin, William St. Vincent Hospital, MT;
Chang, Yung Fu Cornell University;
Coussens, Paul MSU;
Eckstein, Torsten CSU;
Gröhn, Yrjö Cornell University-New York;
Hines II, Murray University of Georgia;
Johnson, Peter USDA-NIFA;
Kapur, Vivek Penn State;
Lein, Donald Cornell University-NY;
Maggioli, Mayana USDA-ARS;
McGill, Jodi NADC;
Olson, Kenneth KEO consulting;
Patton, Elisabeth Wisconsin Department of Agriculture;
Pithua, Patrick University of Missouri;
Roussey, Jon Michigan State University;
Smith, Rick MDARD;
Sreevatsan, Srinand University of Minnesota;
Talaat, Adel University of Wisconsin;
Telfer, Janice UMass Amherst;
Thacker, Eileen USDA-ARS;
Thompson, Gary Penn State;
Waters, Ray NADC;
Wells, Scott University of Minnesota;

Brief Summary of Minutes

The First Annual Mycobacterial Diseases of Animals Multistate Initiative (MDA) was held in conjunction with the Conference of Research Workers and Animal Diseases (CRWAD) on Sunday, December 2, 2012 (2:00 PM to 6:00 PM) in the Purdue/Wisconsin Room-6th floor at the Chicago Marriott Downtown Magnificent Mile.Opening Remarks:

Dr. Vivek Kapur (Chair) welcomed the participants, and reviewed the objectives for the MDA establishment (presentations). The MDA provides a way to maintain the infrastructure and carry forward the work initiated through JDIP and expand it to other mycobacterial diseases of animals. Presentation at the meeting highlighted much of the work completed, or currently underway, that was initiated through JDIP while looking at future research and education needs to address Johnes disease (JD) and bovine tuberculosis (bTB).

Dr. Michael Carter: APHIS Mycobacterial Research Priorities

APHIS has strong interest in applied research and transfer of the outcomes of the research to the field. He pointed out that APHIS is not a research agency, but does on occasion have year-end funding that can be used to fund some research. APHIS has resources like data sets and personnel, but there are more resources available for TB than JD at this point. The contact person for Johnes Program research and education needs is Dr. Dean Goeldner, Johnes Disease Program Coordinator. Although they have no specific research priorities and limited funding, they are interested in early diagnostics and vaccine development. The contact person for TB Program priority research and education needs is Dr. Alecia Naugle, TB Program Manager/Coordinator. Their emphasis is on improvement of existing diagnostics for TB and development of new methods. They also focus on the role of wildlife in TB transmission and mitigations. Current research priorities include the development of improved molecular epidemiological tools, evaluation of diagnostic tests for bovine TB, and development and validation of antigens for ante-mortem testing. To improve and confirm animal ID and traceability, they also focus on developing and implementing genotyping methods for cattle and sheep, and developing PCR protocols to differentiate TB from other Mycobacterial species in tissues. Their priority needs in wildlife include vaccine development and evaluation of efficacy and developing a better understanding of the role of specific wildlife species as a possible reservoir for M. bovis. A proposed first step in this area may be to establish an MOU for data sharing/publications that will be in place as opportunities for projects (with or without VS funding) arise. The agency is set to improve diagnostics TB at the national level at the cost of possible reduction in funding availability to JD, despite its pervasiveness in the dairy industry. JD has always relied on state run programs, but the policy might change in case of a confirmation of food safety risk of MAP. Finally, Dr. Carter commented that he has been a supporter of both TB and JD programs in the past and remains one, and he supports testing of the herds and carefully monitoring disease rather than implementing de-population programs that have uncertain benefits for long-term control.

Dr. Margo Holland - NIFA Animal Health Program Update 2011-2012
NIFA National Program Leader - Animal Health and Well Being Program

Dr. Holland reviewed the four NIFA Institutes: Institute of food production & sustainability, Institute of food safety & nutrition, Institute of bioenergy, climate, & environment, and Institute for youth, family, communities. There is also a center for International Programs. There was a trend of increase in Agriculture and Food Research Initiative (AFRI) funding from 1994 to 2010. It was unchanged from 2010-2012, but FY2013 fundingis uncertain. AFRI has five challenge areas for integrating research, education and extension grants and FY2011 funding: Childhood Obesity Prevention, Climate Change (applicable to this group), Global Food Security (applicable to this group), Food Safety, and Sustainable Bioenergy. The Foundational Program (making primarily research only awards) are as follows: Plant Health and Production and Plant Products, Animal Health and Production and Animal Products, Food Safety, Nutrition, and Health, Renewable Energy, Natural Resources, and Environment, Agriculture Systems and Technology, Agriculture Economics and Rural Communities. The Animal Health and Animal Production (applicable to this group), has a total funding of $18 million, with the available budget for a research project not exceeding $500,000 total (including indirect costs). Dr. Holland, reviewed 2011 funding, awardees, and the focus of the funding priority areas. Animal Health and Disease received $6.9 million in funding with 8.3% success rate in 2011. The question is who are the next generation of agricultural scientists? NIFA is leading a USDA-wide discussion on education/training/scholarship of next generation. Besides classical and advanced agricultural sciences, non-agricultural scientists (physicists, chemists, bioinformaticians, nutritionists, biomedical scientists), as well as, social, economic, policy-making, and communications areas. There is an annual award of $6M in total, with fellowship grants for post-doctoral (130k), pre-doctoral (75k) candidates with a duration of two years.They are nonrenewable awards. Project types fit into three categories of research (basic, translational), education (training), and extension (research, science, and curriculum based). She noted that in 2012, NIFA fellowship program had a success rate of 34% for both pre and post- doctoral program, and in 2011-2012 the success rate increased to 47% for pre and 36% for post- doctoral fellowship program.

Objective 1: Epidemiology

1.1 Dr. Scott Wells: Update on Epidemiology Research Needs related to Mycobacterial Diseases of Animals

Dr. Wells started by emphasizing the importance of both JD and bovine TB as Mycobacterial diseases in US cattle populations, and by comparing MAP (Johnes disease) and M. bovis (Bovine TB). He pointed out that both are similar pathogens, and are diagnosed based on antibody-based, culture and PCR (JD) and antibody-based, culture and PCR, skin test, and serologic assay (TB). However, where prevalence of Johnes disease is ~90% in dairy herds, the prevalence of Bovine TB is ~0% in cattle herds. Also, the government funding is low for MAP, where as the funding is high for M. bovis. Furthermore, because of animal health and production losses (JD), and animal trade restrictions and zoonotic risk (TB), there are established mitigation programs in place; however, the programs are voluntary for Johnes disease and mandatory for Bovine TB. The bTB program includes an eradication effort. New data indicates that we can control JD, but we yet have no data that confirm eradication of the disease. In cohort and clinical studies, control point data were collected at different modes of transmission. The objective of study on MAP infected dairy herds was to evaluate the effect of treatment on incidence of MAP in dairy cows. The treatment was replacement of dairy heifer calves using systematic allocation along with long-term follow-up to measure effect of treatment on health status. In case of TB, most of the country is free from infections, although there are periodic reports of positive animals in a limited number of states, causing action to be taken in those states. There are concerns related to bovine tuberculosis in legal crossing of over 1,000,000 cattle annually through US- Mexico border (traceability) and the wildlife reservoirs (white-tailed deer). There is a need to coordinate with Mexico as a research community, to produce more comprehensive data, and more accurate analysis of transmission pathways.

1.2 Dr. Yrio Grohn: Modeling Transmission and Control of Johnes disease and Bovine Tuberculosis in Dairy Farms

Dr. Grohn started his presentation by reviewing the similarities between JD and TB which included long latency period, difficulties to diagnose, poor/ no vaccine, and availability of no treatment. Relative to their differences, TB is considered an epidemic in US where as, JD is endemic in US costing the dairy industry over $200 million/year. He then presented three important reasons for developing a mathematical model of infection: for better understanding of transmission dynamics, assessing the effectiveness of control programs, and developing an economic model framework. The mathematical model of infection for MAP model is a Knowledge-based, compartmental (calf, heifer, cow) and individual-based, that uses deterministic (differential equations) and stochastic (Monte Carlo simulation) modeling approaches. The efficacy of control programs using this modeling approach could be evaluated using testing, management, and vaccination. The model could also perform an economic analysis by calculating the cost effective control strategies for Johnes disease and bTB. The future directions of the model will be to focus on: 1) MAP environmental transmission model (connection between phylogenetic data and epidemiological model); 2) MAP strain dynamics (strain competition, co-infection re-infection, environmental transmission); 3) Network modeling -animal movement network (transmission between herds); 4) Agent-based model (heterogeneity among individual animal and farm, involvement of multi-agents, like animal, farmer, policy maker, etc.). Creating a model for M. bovis is difficult due to its complex transmission and progression, ecological factors, and role of economic determinants. TB is rare, under strict animal movement control and trade restriction. While there are many models including both biological and economic models, there is a need for agent based and network models. There are still several questions that need to be answered: a) Role of deer in ecological models, spillover or reservoir and the question of density-based or management related b) Optimal control, agent-based modeling c) Optimal surveillance, Network modeling. There were questions and concerns related to the role vaccination play into the models, not predicting the clinical signs of poor vaccination. There were also questions concerning the effectiveness of the program, if the animals are not followed for a long period of time.

Objective 2: Diagnostics

2.1 Dr. Torsten Eckstein: Lipids as Diagnostic Tools for Mycobacterial Diseases in Animals

First Dr. Eckstein emphasized the current lack of a good diagnostic test for Johnes disease (JD). Current diagnostic kits are based on crude bacterial antigen extracts, and comparison with negative and positive standards. He then followed by pointing out that lipids of bacteria could be used as tools for diagnostics, vaccines, or adjuvants. ParaSafeTM (developed by Eckstein Diagnostics) is a new serological diagnostic test for Johnes disease in dairy cattle. It is an ELISA based diagnostic test, and is based on a lipid analog that his lab has found to be better than Para-LP-01. There is no pre-absorption, no comparison with positive or negative standards, and the antigen is chemically synthesized. It is 100% specific, but less sensitive. Para-LP-01 is used in animal model - cow vs goat and long-term study in experimentally infected animals. The current study is being done using a goat model (cheaper model). The goats are experimentally infected with MAP, and standard tests (Fecal culture, Serology, AGID), new diagnostic approaches (ELISpot, cytokine ELISA, Lipid-ELISA) performed. The development of infected vs uninfected status is being evaluated. They are still waiting for results to determine its effectiveness as a diagnostic tool.

2.2 Dr. Ray Sweeney: Develop and Implement New Generations of Diagnostic Tests for Johnes Disease

The emphasis of this talk was on the next generation of diagnostic tests and its purposes. The goal is to identify heavy shedders, and have more specific, sensitive, and convenient tests with faster results, at a lower cost! Milk ELISA is cheap and easy to attain using monoclonal Ab with automation increasing the capacity-throughput. There is also the handheld, cowside, and lateral flow tests. The cell-mediated immune response (IFN-gamma release assay) is more sensitive for comparison. For more sensitive organism detection, options are culture and PCR improvements, or phage amplification assay like FastPlaqueTB®. There is also the use of mathematical models to determine ideal sample collection times (shedding in calves before eclipse phase). Dr. Sweeney then reviewed the Next Generation of diagnostic tests, like other measures of host response (omics: lipid, protein, other metabolic responses), GI flora (bacterial genomics/microbiome). Ideas were also presented on the Next Generation of diagnostic tests, like stringent comparisons with existing diagnostic tests (JDIP), standards for reports of accuracy (adhere to standards), repository of samples, and more advanced methods for test development.

Objective 3: Biology and Pathogenesis

3.1 Dr. Luiz Bermudez: Improving understanding of Biology and Pathogenesis of Mycobacterium bovis

Animals get infected through respiratory and digestive tracts. Bacteria induce the formation of granuloma where bacteria replicate and transmit. Developing vaccine is problematic because of the unique biology in respiratory infection. Lab related infections are very different than normal, and overly artificial (bacteria may go to different places). However, biology does not necessarily follow the models. The host can deal with mycobacteria by using several defensive methods, including reactive oxygen radical production, nitric oxide production, autophagy, apoptosis, inhibition of antimicrobial peptides, or ubiquitination. We need to answer many questions like, how does bovine TB infection occur in natural settings? What is the phenotype of the organism at the time of infection? What are the innate mechanisms capable of protecting the host? Can we develop biological as well as system biology models to answer these critical questions? The challenge is that treatment with current therapeutic arsenal is impractical, and development of vaccine is uncertain. However, there is a promising strategy in the area of prevention of infection by improving the innate response. We need to increase our understanding of the pathogenesis of the infection.

3.2 Dr. John Bannantine: Biology and Pathogenesis of Johnes Disease: Challenges and Needs

This report outlined three general questions: Where are we today? Where are we going? What do we need to get there? MAP cells stay viable in feces for months. Once a host is infected, Map crosses epithelium, enters macrophage, and lowers normal apoptosis cycle. Dr. Bannantine presented literature review on the available knowledge including sequenced genomes, understanding of immune response, mechanism of Map invasion, known virulence genes, and available tools - new mycobacterial shuttle vectors (GFP tagged). The ultimate goal is to lower the impact of Johnes disease for dairy farmers and livestock producers by understanding the infection events that lead to Johnes disease, developing an efficacious vaccine to break transmission and shedding cycles, and addressing why the animal allows MAP cultivation to high numbers, yet growth is slow and fastidious in the lab. We can look at other simpler microbial systems, like Mycoplasma genitalium (smaller genome 525 genes) to develop a computer model of the whole cell. This model could describe the life cycle of a single cell, account for the specific function of every annotated gene product, and accurately predict a wide range of observable cellular behaviors. We need to develop and take advantage of more sophisticated computer models of the bacterium. We also need a better vaccine, rational strategy to ID subunit molecules and a national effort to test best available candidates. There are still unanswered questions including the relationship between Crohn's disease and MAP; understanding the trigger for transition from subclinical to clinical disease; and mechanisms for bacterial survival in host that may lead to development of new intervention strategies. The paradigm that human and bovine TB are very similar needs to be revisited, are there points where this breaks down? Clearly these are different organisms, and even small changes in the genome can result in very different disease manifestations. How many cases of human TB caused by bTB? Reported to be ~30% worldwide in some cases. Mucosal immunity is of important consideration; do we have the tools to look at that? Yes, but whether these are being really applied is unknown.

Objective 4: Development of new generations of vaccines

4.1 Dr. Adel Talaat - Old and New Approaches to Control bovine TB

This is an important matter affecting animal health, human contagion (cause 6% human cases), and of economic importance (global situation). The primary host is cattle but there are also other maintenance hosts (deer, possum, badgers) and spillover hosts (sheep, goats, horses, wild ruminants). The estimated host susceptibility transmission and prevalence is: cattle 0-40%, possum 1-10%, and deer 2-4%. In 2000, genomes of pathogenic and non-pathogenic isolates were sequenced. The results revealed 99% similarity between M. TB and M. bovis and extensive transcriptional differences. As for pathogenesis, aerosol causes 90% of the infections with10% from oral exposure. Macrophages are the primary site of infection, and stages of infection take 3-8 week for subclinical phase I, and 6 months to years for clinical phase II manifestation. The incidence in cattle is 10-15% in Africa, Asia, Latin America, but<0.5% for western countries. The cycle of transmission starts from a reservoir that includes the spillover hosts. To diagnose, there are conventional tests, skin testing serology culture necropsy and histopathology, molecular tests like RFLP, PCR, DNA probe and hybridization (presence but not necessarily active disease), and single intradermal comparative skin test, like comparing M. avium vs. M. bovis. Major risk factors include geographic location, importation of animals, contact with other animals, herd management, genetic factors (livestock replacement), and bacteria genetic factors. Recommended control measures from USDA are to test and kill, depopulate, kill wildlife, and for enzootic areas, testing and segregation, slaughter meat inspection, boiling milk and pasteurization. Vaccine choices include live attenuated vaccines, which are developed as a result of the establishment of a mutant library and targeted mutagenesis, recombinant vaccines that are non- pathogenic mycobacteria, lactobacilli as a delivery vehicle for antigens, and nano- vaccines that are liposomes and nano-emulsions for subunit vaccines. At the end, Dr. Talaat suggested using mice for TB screening protocols in development of an effective TB vaccine since they are a cheaper model to work with; however due to resistance concerns in mice it may be better to choose goat model instead.

4.2 Dr. Murray Hines II: Vaccine Development for Johne's Disease (JDIP program)

There is a well-recognized need to speed-up the process of vaccine development against JD. APHIS-VS funds were identified to help promote JD vaccine development through JDIP. The focus was on evaluating promising new candidate vaccines in appropriate models along with establishment of a peer-review mechanism. Dr. Hines gave a summary of JDIP establishment of the vaccine project as a part of USDA-NIFA CAP Project, RFA (08/09) cycle. It was developed with participation by 12 research institutes. Protocols for in-vitro and in-vivo studies were developed. 22 vaccine candidates were submitted to Penn State (Kapur), where they were cultured, blinded, and were sent out in groups of 5 for in-vitro screens to the U. of Minnesota (Sreevatsan), U. of Wisconsin (Talaat), and to Michigan State U. (Coussens) and to Cornell (Grohn) for data analysis. Based on the results from phase I screening, eight candidates were moved to Phase II with screening at Cornell (Chang) and Oregon (Bermudez) and to NADC (Bannantine) for blind breaking and data analysis. Five candidates passed and moved to Phase III at UGA (Hines II) where it is near completion. The results will be compared to Silirum® vaccine from Pfizer. For phase III, 80 goats from a known negative herd were vaccinated and challenged. Monthly AGID, ELISA, fecal culture and fecal PCR tests were run. Periodic PPD skin testing with M. bovis, M. avium and MAP PPDs were also measured. Samples were archived and will be made available to other JDIP investigators for follow-up studies. Dr. Hines stated that study is on-track and in final phase of analysis. Necropsies were performed October 11 - 16, 2012. ELSA, AGID, PPD Skin test, Histopathology, Lesion score and fecal PCR results are completed. Tissue PCR should be completed in a month, and HEY fecal and tissue cultures by end of Feb 2013. Final data analysis should be complete by June of 2013. He noted there is a need for more standardization on the TB side as well. Although there are many variations in the data for the different vaccines, based on preliminary results two vaccines look very good as there appears to be a reduction in fecal shedding. There was a question as to whether a vaccine for TB in cattle will be acceptable in US. It might be possible, if it were a subunit vaccine or could be purified with no cmi skin test possible. The major cost of BSL3 is the major problem with development a goat model for bovine TB is the cost of BSL3 space. It was suggested that it may be possible to get funding from NIH or the Gates Foundation and/or in may be possible to perform the testing for TB in other countries like New Zealand, or Brazil that do not require BSL3 and thus require less funding. There is also a need for a better test that could be performed at the US border, but this would not solve the problem entirely!

Extension/Outreach:

1. Dr. Daniel Grooms: Extension Objective Bovine TB

Dr. Grooms presentation started with a review of the bovine TB issues in MI, including two confirmed cases of human bovine TB in an elderly gentleman with multiple problems, and a hunter with cutaneous TB. He also reviewed what was proposed in the bTB CAP grant. He noted that farms in the bTB area are surrounded by forest, with forest grazing of cattle, backyard viewing for recreational viewing (feeders) common,, The deer population important to the economy of Michigan. Bovine TB in livestock has been controlled using intense surveillance, depopulation or quarantine of infected farms, movement restrictions, mandatory cattle ID including RFID since 2007, and wildlife risk mitigation programs. Effective control measure for bTB in wildlife includes surveillance, increased (targeted) hunting pressure, baiting and feeding restrictions, and research to understand bTB in the wildlife reservoir. Planning an eradication program requires continuous effort to reach out to multiple stakeholders, producers, wildlife enthusiasts, industry personnel, public, decision makers (legislators and granting agencies). Another objective of the program is education, extension/social/human dimensions. The primary goal of this objective is to provide veterinarians, producers, and other stakeholders with high quality, up-to-date information and education to foster a continued and cohesive approach to eradicating of bTB. Also developing modules to be used in various curricula as well as with 4H and FFA. Bovine tuberculosis is a serious disease of cattle and humans globally. This web site (BovineTB.org ) is being developed to help facilitate the dissemination of important information in the control and eradication of bTB. This project was part of the proposed TB-CAP Project, which was submitted to the USDA NIFA, but was not funded. Take home message, there is a need to think broadly beyond educating producers, and increase overall awareness.

2. Dr. Kenneth Olson: Develop and Deliver Education and Outreach Materials to Stakeholders- JDIP

Dr. Olsons presentation started off reviewing JDIPs accomplishments: cooperated with the VBJDCP on meeting education needs, provided tools for producers, shared information with other scientists, producers, and USDA and industry partners. VBJDCP education efforts provide certification and recertification for veterinarians, and DHIA Modules used in their quality certification program. Three modules were developed in collaboration with DHIA that areused with field and lab technicians that cover milk sampling and ELISA testing for MAP Screening. (http://ce.vetmed.wisc.edu/Johnes_Disease_Individual_Courses). Tools for producer programs include is an educational modules on Johne's disease for dairy, beef and small ruminant producers. The dairy module is available in both English and Spanish. JDIP also has had education information at producer meetings, including World Dairy Expo, National Institute for Animal Agriculture, USDA and DMI events. The WMMB, USDFRC, ADSA andDRPC assisted in spreading the word at World Dairy EXPO. Dr. Olson also met with editors and gave radio interviews. JDIP also has a regular newsletter (e-version on JDIP site), and collaborates with ADSA by providing proceedings for the Searchable Proceedings of Animal Conferences (S-PAC). Other outreach efforts include the National Johne's Education Initiative (www.johnesdisease.org), a website (johnes.org) at theUW vet school, and scientist interaction at JDIP Annual Meeting, ADSA-ASAS Joint Annual Meeting (Johnes Specific Sections, Johnes Interest Group), ICP presentations, and USAHA/NJWG presentations among other Scientific meetings. Dr. Olson as JDIP representative also attends DC meetings with USDA leadership (APHIS, ARS, NIFA), partner organizations (AVMA, IDFA, NMPF), and Congressional staff as well as taking part in priority setting at USDA stakeholder meetings. Looking to the future, multistate objectives include building awareness of MDA among stakeholders, sharing information on what has been and is being done through the MI with scientists, industry and government leaders, and providing information and tools to producers. We need to build on past efforts and include new collaborators, and continue to identify information needs and seek new ways to provide the information.

Closing Remarks:

Dr. Kapur thanked all the presenters and the participants and discussed the next steps:
MDA will write conference grants and seek outside support. We are delighted on the progress made by JDIP, and since the pipeline has been created, we can focus on bTB and make short-term progress in education and extension and work on visibility for future funding.

The second Annual Mycobacterial Diseases of Animals Multistate Initiative (MDA) will be held in conjunction with 117th USAHA Annual Meeting in San Diego, California on October 17-23, 2013.

The meeting was adjourned at 6:30 pm.

Accomplishments

Investigators have made considerable progress in the following areas: <br /> <br /> EpidemiologyDr. Yrjo Grohns group has led investigations on the development and refinement of mathematical models, algorithms, and testing strategies to help improve diagnostic testing for MAP, and better understand disease transmission and epidemiology.<br /> <br /> DiagnosticsDr. John Bannantines group has identified a MAP specific monoclonal antibody, 17A2, that can for the first time differentiate MAP from other Mycobacterium. This antibody has immense potential helping develop the next generation of diagnostic tests for JD and is currently being evaluated in the laboratories of several JDIP investigators. Also, Dr. Ray Sweeneys group continues to make progress in JD diagnostics. Samples have been collected from over 2000 cows located in herds in CA, PA, GA, TN, and MN and a subset have been identified for retention in the repository. The samples are coded, separated into individual testing aliquots, and frozen for storage and the results of these first ever head-to-head comparisons and benchmarking studies are expected during the summer of 2013. <br /> <br /> Vaccine developmentDr. Murray Hines, is in the final stages of phase 3 of the JDIP vaccine trial. The trial involved 5 experimental vaccines supplied by JDIP investigators compared with three control groups and was conducted in 80 goat kids in groups of 10 each. This will hopefully not only provide important lead candidates for identification of the next generation of vaccines, but a framework for community based evaluation of the most promising vaccine candidates and help leverage resources and shorten the timelines for translation of basic science discoveries into the clinic. <br /> <br /> ExtensionDrs Ken Olson and Jeannette McDonald have worked with the VBJDCP on meeting education needs, provided tools for producers, and shared information with other scientists, producers, industry partners, and USDA. VBJDCP education provides certification and recertification for veterinarians. Three modules (http://ce.vetmed.wisc.edu/Johnes_Disease_Individual_Courses) were developed in collaboration with DHIA that are used with field and lab technicians covering milk sampling and ELISA testing for MAP Screening. Tools for producer programs include an educational module on Johne's disease for dairy (in English and Spanish), beef and small ruminant producers. JDIP also has had education information at producer meetings, including World Dairy Expo, NIAG, USDA and DMI events. The WMMB, USDFRC, ADSA and DRPC assisted in spreading the word at World Dairy EXPO. JDIP also has a regular newsletter, and collaborates with ADSA by providing proceedings for the Searchable Proceedings of Animal Conferences. Other outreach efforts include the National Johne's Education Initiative (www.johnes disease.org), a website at the UW vet school (johnes.org), ADSA-ASAS Joint Annual Meeting, ICP, and USAHA/NJWG presentations among other meetings. JDIPs representative also attend DC meetings with USDA leadership, partner organizations, and Congressional staff as well as take part in priority setting at USDA stakeholder meetings.<br />

Publications

Aly SS, Anderson RJ, Whitlock RH, Fyock TL, McAdams SC, Byrem TM, Jiang J, Adaska JM, Gardner IA. (2012). Cost-effectiveness of diagnostic strategies to identify Mycobacterium avium subspecies paratuberculosis super-shedder cows in a large dairy herd using antibody enzyme-linked immunosorbent assays, quantitative real-time polymerase chain reaction, and bacterial culture, J Vet Diagn Invest., 24(5): 821-32. <br /> <br /> Bannantine JP, Lingle CK, Stabel JR, Ramyar KX, Garcia BL, Raeber AJ, Schacher P, Kapur V, Geisbrecht BV. (2012). MAP1272c encodes an NlpC/P60 protein, an antigen detected in cattle with Johne's disease, Clin Vaccine Immunol., 19(7): 1083-92.<br /> <br /> Bannantine JP, Wu CW, Hsu C, Zhou S, Schwartz DC, Bayles DO, Paustian ML, Alt DP, Sreevatsan S, Kapur V and Talaat AM. (2012). Genome Sequencing of Ovine Isolates of Mycobacterium avium subspecies paratuberculosis Offers Insights Into Host Association, BMC Genomics, 13(1): 89.<br /> <br /> Bermudez LE, Inderlied CB, Kolonoski P, Chee CB, Aralar P, Petrofsky M, Parman T, Green CE, Lewin AH, Ellis WY, Young LS. (2012). Identification of (+)-erythro-mefloquine as an active enantiomer with greater efficacy than mefloquine against Mycobacterium avium infection in mice, Antimicrob Agents Chemother, 56(8)<br /> <br /> Chen JW, Faisal SM, Chandra S, McDonough SP, Moreira MA, Scaria J, Chang CF, Bannantine JP, Akey B and Chang YF. (2012). Immunogenicity and protective efficacy of the Mycobacterium avium subsp. paratuberculosis attenuated mutants against challenge in a mouse model, Vaccine, 30(19): 3015-25.<br /> <br /> Chen JW, Scaria J, Chang YF. (2012). Phenotypic and transcriptomic response of auxotrophic Mycobacterium avium subsp. paratuberculosis leuD mutant under environmental stress, PLoS One, 7(6): e37884.<br /> <br /> Cho J, Tauer LW, Schukken YH, Gomez MI, Smith RL, Lu Z and Grohn YT. (2012). Economic analysis of Mycobacterium avium subspecies paratuberculosis vaccines in dairy herds, J Dairy Sci., 95(4): 1855-72.<br /> <br /> Coussens PM, Sipkovsky S, Murphy B, Roussey J, Colvin CJ. (2012). Regulatory T cells in cattle and their potential role in bovine paratuberculosis, Comp Immunol Microbiol Infect Dis., 35(3): 233-9.<br /> <br /> Espejo LA, Godden S, Hartmann WL, Wells SJ. (2012). Reduction in incidence of Johne's disease associated with implementation of a disease control program in Minnesota demonstration herds, J Dairy Sci. 95(7): 4141-52.<br /> <br /> Heuer C, Mitchell RM, Schukken YH, Lu Z, Verdugo C, Wilson PR. (2012). Modelling transmission dynamics of paratuberculosis of red deer under pastoral farming conditions, Pre Vet Med., 106(1): 63-74.<br /> <br /> Joshi D, Harris NB, Waters R, Thacker T, Mathema B, Krieswirth B, Sreevatsan S. (2012). Single nucleotide polymorphisms in the Mycobacterium bovis genome resolve phylogenetic relationships, J Clin Microbiol., 50(12): 3853-61. <br /> <br /> Kabara E, Coussens PM. (2012). Infection of Primary Bovine Macrophages with Mycobacterium avium Subspecies paratuberculosis Suppresses Host Cell Apoptosis, Front Microbiol., 3: 215.<br /> <br /> Lamont EA, Bannantine JP, Armien A, Ariyakumar DS and Sreevatsan S. (2012). Identification and characterization of a spore-like morphotype in chronically starved Mycobacterium avium subsp. paratuberculosis cultures, PLoS One, 7(1): e30648. <br /> Lamont EA, O'Grady SM, Davis WC, Eckstein T, Sreevatsan S. (2012). Infection with Mycobacterium avium subsp. paratuberculosis Results in Rapid Interleukin-1B Release and Macrophage Transepithelial Migration, Infect Immun., 80(9): 3225-35. <br /> <br /> Lim A, Steibel JP, Coussens PM, Grooms DL, Bolin SR. (2012). Differential gene expression segregates cattle confirmed positive for bovine tuberculosis from antemortem tuberculosis test-false positive cattle originating from herds free of bovine tuberculosis, Vet Med Int., 2012:192926.<br /> <br /> Lombard JE, Gardner IA, Jafarzadeh SR, Fossler CP, Harris B, Capsel RT, Wagner BA, Johnson WO. (2013). Herd-level prevalence of Mycobacterium avium subsp. paratuberculosis infection in United States dairy herds in 2007, Prev Vet Med, 108(2-3): 234-8.<br /> <br /> Lu Z, Schukken YH, Smith RL, Mitchell RM, Gröhn YT. (2013). Impact of imperfect Mycobacterium avium subsp. paratuberculosis vaccines in dairy herds: A mathematical modeling approach, Prev Vet Med, 108(2-3): 148-58. 22.<br /> <br /> McNamara M, Danelishvili L, Bermudez LE. (2012). The Mycobacterium avium ESX-5 PPE protein, PPE25-MAV, interacts with an ESAT-6 family Protein, MAV_2921, and localizes to the bacterial surface, Microb Pathog., 52(4): 227-38.<br /> <br /> McNamara M, Tzeng SC, Maier C, Zhang L, Bermudez LE. (2012). Surface proteome of "Mycobacterium avium subsp. hominissuis" during the early stages of macrophage infection, Infect Immun., 80(5): 1868-80.<br /> <br /> Mitchell RM, Medley GF, Collins MT and Schukken YH. (2012). A meta-analysis of the effect of dose and age at exposure on shedding of Mycobacterium avium subspecies paratuberculosis (MAP) in experimentally infected calves and cows, Epidemiol Infect., 140(2): 231-46. <br /> <br /> Stabel JR, Waters WR, Bannantine JP and Lyashchenko K. (2011). Mediation of Host Immune Responses after Immunization of Neonatal Calves with a Heat-Killed Mycobacterium avium subsp. paratuberculosis Vaccine, Clin Vaccine Immunol., 18(12): 2079-89.<br /> <br /> Sweeney RW, Collins MT, Koets AP, McGuirk SM, Roussel AJ. (2012). Paratuberculosis (Johne's disease) in cattle and other susceptible species, J Vet Intern Med., 26(6): 1239-50.<br /> <br /> Tavornpanich S, Wells SJ, Fossler CP, Roussel AJ and Gardner IA. (2012). Evaluation of an alternative method of herd classification for infection with paratuberculosis in cattle herds in the United States, Am J Vet Res., 73(2): 248-56. <br /> <br /> Wadhwa A, Bannantine JP, Byrem TM, Stein TL, Saxton AM, Speer CA, Eda S. (2012). Optimization of serum EVELISA for milk testing of Johne's disease, Foodborne Pathog Dis. 9(8): 749-54.<br /> <br />

Impact Statements

1. Application of mathematical models and epidemiologic analysis to help drive the continued improvement of our understanding of Mycobacterium avium subsp. paratuberculosis (MAP) on-farm transmission dynamics and assist in the identification of critical control points in the transmission chain.
2. development of benchmarked diagnostic assays, and the Continued development and validation of alternative sampling and testing strategies for detection of infected animals and herds.
3. Development and evaluation of new laboratory protocols for reducing timelines for rapid detection of infected animals.
4. A better understanding of the molecular mechanisms of infection and the role of supershedders and spore formation.
5. Development of standard approaches for the validation of vaccine candidates and evaluation of vaccine efficacy.
6. Identification of key genes, proteins and lipids in MAP for development of the next generation of diagnostic tests and vaccines.
7. Continued development and widespread use of an on-line JD veterinary certification program.
8. Development of community resources and opportunities to facilitate collaborations by hosting meetings for both scientists and stakeholders.

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Brief Summary of Minutes

Accomplishments

<p>Included in the meeting minutes.</p>

Publications

<p>Publications in addition to what is included in the meeting minutes, would be found in REEport under the specific station annual accomplishment reports.</p>

Impact Statements

1. Evaluation of vaccine candidates against MAP in controlled blinded studies.

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Brief Summary of Minutes

Accomplishments

Dr. Grohn leads the epidemiology research group, as they concentrate on the study design of clinical trial of vaccine and the assessment of vaccination effectiveness in farm animal populations against endemic infectious diseases. His research group has also designed a 3-step framework of a Bayesian modeling and simulation approach, and the model was experimented in a simulated case study for a killed whole-cell vaccine against paratuberculosis in dairy herds. Dr. Grohn was able to estimate key model parameters from the longitudinal prevalence data of the whole herd (adult animals) and the control and vaccinated groups in a vaccinated herd. Extension is led by Dr. Ken Olson, as they continue to collaborate with the VBJDCP to address education, share information, and provide tools for producers, other scientists, industry partners, and USDA. Dr. Olson also attends DC meetings with USDA leadership (APHIS, NIFA, ARS,), partner organizations (AVMA, IDFA, NMPF, NASDA, AFBF), and Congressional staff. Furthermore, his efforts concentrate on the awareness of the MDA MI among stakeholders, industry and government leaders. Dr. John Bannatine leads the diagnosis research group as they continue to research on the newly identified MAP specific monoclonal antibody, 17A2 that can for the first time differentiate MAP from other Mycobacterium. JDIP Vaccine development led by Dr. Murray Hines has reached its final stage, and publications are in the process. The data from the vaccine study will be published in the Frontiers in Microbiology Journal.

Publications

The attached meeting minutes contain a listing of the 13 posters presented at the morning and afternoon poster sessions. Please refer to that attachment for details.

Impact Statements

1. Application of an established mathematical model of infection in data collection from the longitudinal study done in three states (NY, PA, VT) for approximately 10 years.
2. Implementation of a faster test-and-removal plan with a 2-month testing interval in epidemic disease control of the bTB in cattle herds.
3. Establishment of a Bayesian computation (ABC with an efficient sequential Monte Carlo method) modeling and simulation approach to estimate the effectiveness of vaccination against infectious diseases in food animal populations.
4. Evaluation of vaccine efficacy and development of standard evaluation in the validation of vaccine candidates.
5. Comparison and evaluation of the fully sequenced two USA virulent M. bovis isolates.
6. Establishment of a sample repository from JDIP samples for further testing and evaluation.
7. Evaluation of vaccine candidates against MAP in controlled blinded studies.

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Participants

Included on the meeting minutes.

Brief Summary of Minutes

Accomplishments

<p>Accomplishments are detailed in the meeting minutes.</p>

Publications

<p>Publications in addition to what is included in the meeting minutes, would be found in REEport under the specific station annual accomplishment reports.</p>

Impact Statements

1. Development of a recombinant multi-stage DIVA vaccine against Johne’s disease

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Bannantine, John - USDA-ARS
Barletta, Raul - University of Nebraska–Lincoln
Bermudez, Luiz - Oregon State University
Coussens, Paul - Michigan State University
DeKuiper, Justin - Michigan State University
Frie, Meredith - Michigan State University
Grohn, Yrjo - Cornell
Holland, Margo - NIFA-USDA
Johnson, Peter - NIFA-USDA
Kapur, Vivek - Pennsylvania State University
Mohamed, Asmaa - Michigan State University
Olson, Ken - KEO Consulting
Quinn, Fred - University of Georgia
Rathnaiah, Govardhan - University of Nebraska–Lincoln
Smith, Becky - University of Illinois at Urbana-Champaign
Sporer, Kelly - Michigan State University
Talaat, Adel - University of Wisconsin
Wells, Scott - University of Minnesota

Brief Summary of Minutes

Accomplishments

<p>Accomplishments are included as part of the summary of the minutes with specific activities and outputs identified.</p>

Publications

<p>Publications for this multistate project would be reported in REEport under each stations's annual accomplishment report for their corresponding SAES project.</p>

Impact Statements

1. Providing veterinarians, producers of potentially impacted species, state and federal policy makers, and other stakeholders with accurate, high quality, up to date, and easy to access information and education to assist efforts that will effectively address mycobacterial diseases.

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