Human Para is pleased to share the consensus article from the 2017 MAP conference in Philadelphia. This effort represents a historic collaboration of the world’s experts on Mycobacterium avium spp. paratuberculosis (MAP), who are concerned about the impact of MAP on human health. The goal of this collaboration is to advance better treatment options for patients suffering from MAP-driven conditions.

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Dr. Nicole Parrish of the Johns Hopkins School of Medicine and Dr. Neil Goldberg of the University of Maryland, begin the presentation by discussing tuberculosis and the Wayne Model of Non-Replicating persistence, and how that model relates to MAP latency. Their research shows that MAP can convert from an aerobic (oxygen using) state to an anaerobic (non-oxygen) state similar to that seen in tuberculosis. The presentation concludes with a discussion of MAP antibiotic susceptibility and a case study where a combination of antibiotics led to cessation of Crohn’s disease and pyoderma gangrenosum.

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In these first two videos, Dr. Behr and Dr. Chamberlin introduce the conference, frame the issue of MAP and address the issue of causality.

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Dr. Collins gives an overview of MAP from a veterinary perspective, including where MAP is found in the environment, hallmarks of MAP infections in cows and other animals and detection methods. Contamination of MAP in food products and human exposure vehicles are discussed alongside solutions which can be implemented to stop the spread of MAP.

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Dr. Kapur, of Penn State, looks at the prevalence and cost of MAP infection in cattle, and discusses the diagnostics available, which are a particular challenge. It’s difficult to get accurate, early testing, so MAP infection spreads, especially in large herds. Interestingly, Dr. Kapur has found that certain MAP proteins appear early on in infection (as early as 2-3 months), but then are detected less frequently in clinical disease.

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Dr. Marcel Behr is a Full Professor of Medicine and Fellow of the Canadian Academy of Health Sciences as well as the Director of the McGill International TB Centre and Microbiologist-in-Chief at the hospital. Here, Dr. Behr talks about the nature of MAP as compared to tuberculosis, and explains the challenges of finding MAP in human samples and why some testing for MAP gives false positives. He explains the gold standard of culture for human MAP and why MAP may not be present the feces. Questions from the audience follow the presentation.

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Dr. McNees is an associate of Dr. David Graham in the Department of Molecular Virology and Microbiology at the Baylor College of Medicine in Houston, TX. She talks about their methods to detect MAP in human subjects using culture and PCR, and discusses their results. MAP was detected in 70% of Crohn’s disease patients and 48.9% of controls. When the disease is in the colon, more cases are MAP-positive.

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Dr. Shoor Vir Singh is a Principal Scientist at the Indian Council of Agricultural Research. He was unable to present at the 2017 MAP Conference due to a prior commitment, but has kindly provided his presentation materials. The presentation begins with an overview of MAP in India, and progresses to a detailed case study of a Crohn’s disease patient whose stool sample tested positive for Indian bison type MAP. After a year of antibiotic treatment, his Crohn’s disease symptoms had abated and MAP testing was negative. The antibiotic treatment regimen is detailed in Dr. Singh’s presentation. The final portion of the presentation describes treatment and control strategies for MAP in India, including an indigenous bison-type vaccine that is now available.

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“Understanding Crohn’s disease is not rocket science — It is far more complex.” In this presentation, John Aitken from Otakaro Pathways in New Zealand discusses his efforts to reliably culture MAP from human patients. The issue of dormancy is outlined, along with the results of a recent testing study conducted with a 28 subject cohort. A mechanism is proposed for how MAP behaves to cause disease in the human population.

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Dr. Bach is an Adjunct Professor in the Division of Infectious Diseases at the University of British Columbia in Vancouver, Canada. His research interests include understanding how pathogenic microorganisms successfully infect and multiply in humans, nanomedicine and antibody design. In his presentation, Dr. Bach discusses how MAP can survive in the macrophage and levels of antibodies found in Crohn’s patients vs. healthy control. Antibody levels are measured before and after traditional Crohn’s disease treatments are administered.

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Dr. Bull is is a Senior Lecturer in Infectious Diseases and Associate Dean of the Biological Research Facility at St. George’s University of London. His presentation discusses his research on dormant forms of MAP and why cattle is the preferred host.  He discusses factors which may activate MAP out of dormancy in vitro and what is known about the genetics and properties of human strains of MAP. Questions from the audience follow the presentation.

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Dr. Chamberlin is a gastroenterologist at the San Antonio Military Medical Center in Texas. In his talk, he presents evidence of healing in Crohn’s disease patients treated with antibiotics. He also reviews some of the literature on antibiotic treatment in Crohn’s disease and discusses the flawed Selby antibiotic trial. “Do antibiotics have a positive effect on Crohn’s disease? Absolutely.”

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Dr. J. Todd Kuenstner details 5 case studies of related patients diagnosed with combinations of Crohn’s disease, Complex Regional Pain Syndrome, Raynaud’s phenomenon, Type 1 Diabetes and Lymphangiomatosis who also tested positive for MAP. Two cases were successfully treated with antibiotics and ultraviolet blood irradiation therapy. A Q&A session follows the presentation.

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Dr. Harry Oken is an Internal Medicine practitioner and a professor at the University of Maryland. Here, he presents one of his most challenging cases which had some of the hallmarks of Crohn’s disease, and was eventually resolved by a regimen of 5 antibiotics. The patient tested positive for MAP, and Dr. Oken hypothesizes that the MAP infection damaged the nerves in the ileum, leading to disease. This report suggests that MAP may be able to cause a variety of chronic illnesses apart from Crohn’s disease.

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Dr. David Y. Graham is a gastroenterologist at the Baylor College of Medicine in Houston, TX. Here, he details a long term study conducted on Crohn’s disease incidence in the Kingdom of Bahrain. Over time, the rate of Crohn’s disease increased significantly from 4.8 cases per 100,000 to 8.0 cases per 100,000. PCR (IS900 series) testing for MAP DNA in Crohn’s patients revealed that 76.7% were positive after 1 test, but when the researchers repeated the test up to 4 times, 100% of the Crohn’s patients eventually tested positive for MAP DNA. Imported beef and dairy may provide an explanation for the increase in disease.

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Dr. Irene Grant is a Senior Lecturer in Microbiology and Food Safety at Queen’s University, Belfast Ireland. In her presentation, she explains and contrasts a variety of methods for detecting MAP in milk, details the latest advances from her lab including PMS-phage assay. which detects higher levels of MAP in milk and infant formula. Discussion of how PMS-phage assay for MAP could be applied to human blood samples and a Q&A session follows.

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Prof. Thomas Borody is a gastroenterologist who is the founder and Medical Director of the Centre for Digestive Diseases in Sydney, Australia. He has established novel therapies in gastrointestinal areas such as Inflammatory Bowel Disease, Irritable Bowel Syndrome, Parasite infestation, Resistant Helicobacter pylori and C. difficile. In this presentation, he discusses how he treats MAP-driven Crohn’s disease, treatment for fistulae, the synergy of infliximab and antibiotics, and antibiotics in treatment-naive patients. Anti-MAP therapy for pyoderma gangrenosum is also briefly discussed. A group of patients have long-term, medication free remission due to Anti-MAP therapy.

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Dr. Shafran is a gastroenterologist who has been practicing in the Orlando area since 1979. He has used Anti-MAP therapy as part of his practice, and talks about his experience treating patients, including why current therapies have no role in treating Crohn’s disease in his opinion. Research from Crohn’s patients who have been treated with antibiotics is presented. Deep mucosal healing and sustained remission was found in 11 patients over an 18 year period.

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Dr. Kalfus is a Medical Director at RedHill Biopharma, which is currently conducting a Phase III FDA trial of a specific combination of antibiotics in Crohn’s disease patients. In his presentation, Dr. Kalfus gives the reason behind triple therapy for MAP and how the three antibiotics were selected. He also talks about how the currently available Crohn’s therapies have some anti-MAP activity. MAP diagnostics, the Selby study and the ongoing RedHill study are also discussed.

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Dr. Greenstein is a researcher in the Laboratory of Molecular Surgical Research at the VA Medical Center in Bronx, NY. He presents his research explaining why he believes that the primary action of current Crohn’s disease therapies is really Anti-MAP, and hypothesizes that Crohn’s disease may be the tip of the MAP iceberg. The antimycobacterial effect of Vitamin D is also discussed.

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Dr. Chamberlin is a gastroenterologist at the San Antonio Military Medical Center in Texas. In his second presentation, he outlines why he believes that Crohn’s disease is both a disease of immune deficiency and also an infectious disease. The immune system is reviewed, differences in the innate and adaptive immune system are discussed, and genetic mutations which allow MAP to take advantage of certain immune pathways are detailed. Compounds which may stimulate autophagy like turmeric and Vitamin D are discussed. A Q&A session follows the presentation.

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Appearing by WebEx at the conference, Dr. Davis is a researcher and professor in the Department of Veterinary Microbiology and Pathology at Washington State University. Here, he summarizes the findings from his 27 year MAP study and provides an update on his progress in developing a cattle vaccine for MAP that may have insights into human MAP as well.

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Appearing at the conference via Webex, Dr. Sechi is a Professor of Microbiology at the University of Sassari, Sardinia, Italy. Sardinia is an island with some of the highest rates of autoimmune diseases in the world. MAP is commonly found in their ruminant population as well. Dr. Sechi’s research shows significantly higher rates of MAP in patients with autoimmune diseases like multiple sclerosis and Type 1 Diabetes. He presents some of that research here, and discusses a mechanism for MAP infection in these diseases which may differ than that in Crohn’s disease. Questions from the audience follow the presentation.

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Dr. Monif, the President of Infectious Disease Incorporated, presents his proposed mechanism on how MAP causes Crohn’s disease. Two factors: infection by MAP and subsequent loss of immunological tolerance, and repeated exposure to and adherence of MAP, combine to produce disease. A hypothetical debate between Robert Koch and Louis Pasteur about whether MAP is the cause of Crohn’s disease delves into the proof issues.

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Dr. Zhang is a pathologist and co-founder of PZM Diagnostics, a company which is testing the blood from potential Crohn’s patients for the presence of MAP. He details his research here, which includes rarely finding MAP in culture or PCR, but detecting the presence of other bacterial DNA in blood samples. Antibodies to MAP in were found in greater than 70% of patients. Sjogren syndrome antibody levels are discussed as well as cross reaction to human proteins and a proposed mechanism of disease.

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The following videos are the questions from the audience after each of the primary presentations from the 2017 MAP Conference. The audio is sometimes unclear, and has been adjusted when possible. Some of the Q&A sessions are included at the end of the speaker’s primary presentation, and are therefore not included here. The Q&A videos below can also be found under each individual speaker’s presentation page. They are compiled in this format for the ease of our viewers.

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The following videos are additional interviews that Human Para and Majestic Plural Studios conducted with some of the presenters. These videos can also be found under each individual speaker’s presentation page. They are compiled here for the ease of the viewers.

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