Judith Eve Lipton, MD: Summary of my personal experiences with MAP and my recommendations.

Follow-up to this post.

To People with Crohn’s Disease

I receive many letters from people around the world asking about treating Crohn’s disease with antibiotics, under the theory that Crohn’s disease is an infection caused by MAP, Mycobacterium avium subspecies paratuberculosis. I am a psychiatrist, not a gastroenterologist (GI), and not qualified to make specific suggestions about treating Crohn’s disease. I never treat any GI patients myself, and never did. I will never tell people specific doses or protocols for treating MAP because every patient is different. If you elect to learn more and follow this path, you will need your own local physician. I am only offering general information

All I can tell you is that I nearly died of infections following severe Crohn’s disease in 2004. I had severe abscesses the entire length of my large bowel. I responded to Remicade and steroids at first, but then could not stabilize on that regime. While recuperating from a hospitalization, I happened to learn about MAP by reading Dr. Saleh Naser’s article that appeared in LancetΘ (September 2004) about culturing MAP from the blood, biopsies, and breast milk of people with Crohn’s. I emailed many MAP professionals, and was referred to Dr. Thomas Borody in December 2004.

My primary care doctor, an internist, agreed to help me with the MAP protocol, although my GI doctor refused. Before starting the antibiotics, I had blood drawn for culture and PCR (DNA fingerprinting) and was negative for both, no sign of MAP. I started Dr. Borody’s protocol December 10, 2004. I took one more Remicade shot, in January 2005. By Spring 2005, I had no sign of Crohn’s, and I have not had any problem since then. My colonoscopies have been perfectly normal, as are my blood counts and inflammatory parameters. At Dr. Borody’s suggestion in May 2010, I stopped the antibiotics and feel just fine. I have had neither GI problems nor any sign of Crohn’s. I think Dr. Borody and my personal physician saved my life. My most recent colonoscopy, July 10, 2013, was totally normal with no sign of any inflammation.

The medicines I took were clarithromycin, Rifabutin, clofazimine, and ethambutol. I stopped the ethambutol very quickly, because it has the most toxicity, and I took the others for 5 years. DO NOT ATTEMPT TO TREAT YOURSELF, YOU NEED TO BE VERY CAREFUL WITH THE DOSES AND MONITORING THINGS LIKE YOUR EYESIGHT, BLOOD COUNTS, AND LIVER FUNCTION.

What I tell people is to do to a lot of research, using the following sites: My own blog on psychologytoday.com is in 3 parts:

http://www.psychologytoday.com/blog/pura-vida/201311/is-there-cure-crohnsdisease

http://www.psychologytoday.com/blog/pura-vida/201311/is-there-cure-crohns-part2

http://www.psychologytoday.com/blog/pura-vida/201402/treating-crohns-disease

In addition, I would suggest that you look at the following sites: http://www.johnes.org from the University of Wisconsin, School of Veterinary Medicine.

The International association for Paratuberculosis: www.paratuberculosis.org.

The RedHill Biopharma site that is conducting an orthodox and well regulated study of Dr. Borody’s protocol in Crohn’s patients, as well as developing a human MAP test: https://www.redhillbio.com/RedHill/Templates/showpage.asp?DBID=1&LNGID=1 &TMID=178&FID=1365&PID=0&IID=5148

Dr. Thomas Borody’s site, the Centre for Digestive Disease in Australia: http://www.cdd.com.au/.

Anti-MAP.org is a relatively new site that is a MAP/Crohn’s discussion group.

https://humanpara.org/ is a non-profit organization that has a collection of MAPrelated resources for both patients and health care professionals. They also plan to sponsor research into human MAP.

https://beststory.ca/ has a terrific summary of the science of MAP written by Dr. Michael Collins, head of the Johne’s Program at the University of Wisconsin. A second article, by Warren Perley, the senior editor and publisher of BestStory, was published in June, 2015.

http://crohnsmapvaccine.com is the web site maintained by Dr. John Hermon-Taylor and his daughter, Dr. Amy Hermon-Taylor. Dr. John HT is working on a virally vectored vaccine against MAP, with various colleagues at King’s College and Oxford University in the UK. There is a tremendous amount of information on this web site, including review articles, graphs, posters, and summaries. I am highly skeptical of this approach since virally vectored vaccines have not proven useful for other illnesses or in other species, but I certainly respect both John and Amy Hermon-Taylor.

Learn to use scholar.google.com and look up “MAP Crohn’s” or other combinations. Scholar does not have ads and only sends scientific references.

According to the World Health Organization, supplies of clofazimine can be obtained on a commercial basis from: Victoria Pharmacy Attention Dr. C. Egloff, Bahnhofstrasse 71, Zurich 8021 Switzerland. Email: info@pharmaworld.com, Website: www.pharmaworld.com.

You are not going to be able to call up your local gastroenterologist and say, hey, please treat me for MAP. The GI doctor may turn red or get angry or demean you if you do. This theory is not the received wisdom in the GI community. In fact, there are only 3 or 4 physicians in the world who are Board certified in gastroenterology, and who are willing to treat people for MAP. You might have more luck with an infectious disease specialist, because MAP is a germ that is related to TB and leprosy, and ID doctors are quite familiar with TB, leprosy, and mycobacterium avium complex, a disease common in people with HIV.

However, then you will hit a speed bump, because MAP cannot reliably be cultured or identified by DNA fingerprinting in humans. It is easy to diagnose Johne’s Disease (the animal equivalent of Crohn’s) in cows or goats. The germ is a great big rectangle (rod) that stains bright pink with a particular stain. However, for whatever reason, MAP can only be visualized in human blood or biopsies with very special research quality microscopes. It can be cultured in laboratories, but only a handful of labs in the world can do it, and there is no inter-rater reliability. There is no gold standard for culturing MAP. You can’t just go to a local lab and get a MAP test. Even DNA fingerprinting is unreliable, because DNA fingerprinting itself is subject to a lot of problems. For example, a positive DNA identification could mean that a person was exposed to MAP in the past, but has no active infection in the present. Many laboratories are at work trying to improve ways to identify human MAP, including improved DNA analysis, flow cytometry, and other fancy techniques. But right now, the situation is frustrating. You either have to try the MAP “cocktail” of antibiotics because the logic makes sense to you and a physician, and the risks are relatively low, or you’ll have to wait a few years until there are reliable human MAP tests.

This failure to be able to test for human MAP is one of the arguments against the MAP hypothesis put forth by the naysayers. There is an intense argument about whether human MAP meets “Koch’s postulates” to prove it is a zoonotic pathogen. These standards were developed by Robert Koch in the 19th century after he proved that anthrax was a human pathogen. To meet this standard, one should be able to find and grow a germ from the subject in a laboratory; and then transfer it to a healthy individual and recreate that disease. Koch didn’t give anthrax to people! He did this with laboratory animals. In the case of MAP, certain labs have been able to isolate MAP from human blood, breast milk, and biopsy specimens. One intrepid researcher then fed these bacteria to baby goats and the goats got Johne’s Disease! It would be immoral and unethical to take specimens of MAP and feed them to human infants, so nobody is proposing that. However, you need to be aware that there is no local or national laboratory that is certified to test your blood or biopsies for MAP. My own blood was
tested twice for MAP by culture and PCR and was negative both times, yet I have had a complete and sustained remission. In order for commercial laboratories to grow or test for a bacteria or virus, there need to be national standards for those tests. Those national standards do not exist yet for MAP testing.

The evidence that MAP is a zoonotic disease and a human pathogen comes from many areas:

1. Most ruminant mammals can develop Johne’s Disease, including animals normally consumed by people. These ruminants include cows, sheep, and goats.
2. Baby ruminants that consume milk from infected mothers develop Johne’s Disease.
3. Johne’s Disease is rising rapidly in the world.
4. Places like Wisconsin and Alberta that have a large number of cattle also have increasing prevalence of Crohn’s Disease.
5. Crohn’s Disease is rising, especially in young people and in countries that prior to 20th century cultural homogenization did not consume dairy products (like Japan).
6. Viable MAP, living MAP, can be found in retail pasteurized milk and infant formulas.
7. MAP can exist for a very long time in a spore form in biofilms. Thus, water sources that come from areas where infected animals poop may be contaminated with MAP.
8. There is no USDA or FDA prohibition against using animals with Johne’s Disease for milk or meat products. Sick cows are fed into the human food chain on a regular basis. This is because the USDA and FDA do not consider Johne’s Disease to be a zoonotic pathogen.
9. Specialized research laboratories have found MAP in human samples using culture, DNA fingerprinting, and special high magnification microscopes.
10. There is a gene correlated with Crohn’s Disease, called the NOD2/CARD15 mutation, and it specifically affects cell wall recognition factors in macrophages, the white cells that kill invading bacteria from the gut. There is evidence that this mutation especially affects cell wall recognition of mycobacteria. Therefore, a person with normal DNA can eat “MAP burgers” or drink “MAP shakes” for years with no problems, but a person with the NOD2/CARD15 mutation may get Crohn’s Disease. No, there is no way to be tested at local laboratories at this time for the mutation.
11. People like me who have been treated for MAP infection can go into a prolonged remission from Crohn’s Disease.
12. The costs and risks of antibiotic treatment for MAP are real, but in my opinion, are much less than the costs and risks of anti-tumor necrosis medications like Remicade and Humira.
13. There is no reason you cannot use other medications plus antibiotics for MAP, at least until you are comfortable with the protocol.

My advice is to “Grow your own doctor.” Learn about MAP and Crohn’s, then talk to your regular family doctor or internist. Get them interested. Snow them with data. Show them the science. I advocate making an old-fashioned 3-ring notebook, and printing out each and every scientific article that you read. Take that notebook to your favorite doctor and show it to him or her. If he or she is willing even to consider treating you, then one of the two international experts (Dr. John Hermon-Taylor in the UK and Dr. Thomas Borody in Australia) will coach your doctor to help you. The antibiotics used to treat MAP are conventional treatments for multi-drug resistant tuberculosis and leprosy, because MAP is related to TB and leprosy. These medications are not illegal, and at least in my case, insurance covered the whole thing. The only exception is clofazimine, an old-fashioned medication used to treat leprosy. In 2004, the company that made clofazimine in the US stopped making it because it was unprofitable; not many people in the US have leprosy. They gave the medication to the World Health Organization, to distribute in India and Bangladesh and other places where leprosy is still a problem. Now it is difficult to obtain clofazimine in the US and Canada, not because it is dangerous but because it is off the US formulary, except for leprosy. This is not an insurmountable problem. There are multiple claims on the internet of special diets and “augmented” regimes. I do not recommend these.

There is a new option developing for patients: a pharmaceutical company called Red Hill Bio purchased Dr. Borody’s combination medication, called Myoconda, and they have started a massive 3 continent study of the drug in the US, Canada, and Europe. They are looking for 250 patients in 60 study sites. The drug is a mixture of clofazimine, clarithromycin, and Rifabutin. You can read about the study here: http://www.redhillbio.com/productpipeline/rhb-104/. A complete description of this trial is at https://www.clinicaltrials.gov/ct2/show/study/NCT01951326?term=crohn%27s+dise ase& recr=Recruiting&rslt=Without&type=Intr&titles=rhb104&rank=1&show_locs=Y#locn

The triple antibiotic program for MAP for Crohn’s is not a treatment program that has been validated in placebo controlled double blind studies. Hopefully, the RedHill study will do just that. It is not “alternative.” It is based on highly sophisticated science, mostly done by veterinarians and microbiologists. It does not work for everybody. I just know it worked for me.

Best wishes for a full and complete recovery,

Judith Eve Lipton, MD
 
October 2017
(a revised version – originally published June 7, 2015)

Θ Naser, SA, Ghobrial, G, Romero, C, and Valentine, JF. Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn’s disease. Lancet. 2004; 364: 1039–1044.