As with previous ICP, the number of papers presented on the relationship between Crohn’s Disease and Mycobacterium Paratuberculosis has grown, as knowledge of this complex organism and its potential to cause disease in humans, has grown.

The list of 9ICP presentations in the “Public Health” segment of the Colloquium are listed here

http://www.paratuberculosis.org/pubs/proc9/section6.htm

As acceptance of the relationship between MAP and CD grows, related papers are now being presented outside of the dedicated “Public Health” segment. The following paper discusses how the pathogenetic mechanisms of paratuberculosis in Johnes Disease and Crohn’s Disease can be compared in order to increase understanding of both; it was presented in the “Pathogenesis and Immunology” segment.

Role of Mycobacterium avium subsp. paratuberculosis in the pathogenesis of Crohn’s disease
http://www.paratuberculosis.org/pubs/proc9/abst4a.htm

Also of interest is the growing evidence that Mycobacterium avium subsp paratuberculosis may be a cause of Type-1 diabetes.

Association of Mycobacterium avium subsp. paratuberculosis with Type-1 diabetes, a possible trigger
http://www.paratuberculosis.org/pubs/proc9/abst181f_o3.htm

Paratuberculosis and Type I Diabetes -Mapping the TRIGR-
http://www.paratuberculosis.org/pubs/proc8/abst3b_o20.htm

Current thinking among researchers in the field is that MAP itself is mostly not the culprit in the tissue damage. MAP’s role is to initiate an inflammatory response in the bowel, through some unknown process/antigen/inflammatory-pathway. This immune response results in inflammation of bowel tissue, whereby the cells of the intestine physically separate, to allow immune cells, primarily macrophages and CD4 + CD8 T-cells, to reach the site of infection. This leads to “leaky gut” syndrome , which permits the contents of the bowel (most accurately described as being similar to the contents of a sewer), to leak through the bowel wall, resulting in a *massive* inflammatory response against the many microbes present in the fecal stream.

At this point, the inflammatory process becomes self re-inforcing, with consequent runaway production of inflammatory cytokines such as Tumor Necrosis Factor alpha (TNF-alpha), various Interleukins, Interleukin-antagonists, etc.

In some patients, this results in granuloma formation, as the massively overstimulated immune system tries to contain the original MAP infection, present inside macrophages, which are unable to kill the “phagocytosed” (i.e. “eaten”) MAP, which have immune evasion techniques to avoid being killed by macrophages. The infected macrophage goes into overdrive, producing copious quantities of inflammatory cytokines, which cause it to be surrounded by a layer of CD4 T-cells, and then another layer of CD8 T-cells: a granuloma is formed, which contains the mycobacterial infection and cuts off the flow of inflammatory cytokines, but also has the unfortunate consequence of causing significant permanent scarring, thus leading to stenosis/narrowing of the bowel, and eventually strictures.

In other patients, for reasons unknown (although possibly related to the failure of the Th1 inflammatory response), this granuloma formation does not take place. Instead, the flood of antigens from the bowel contents infects the bowel “transmurally”, i.e. through the entire thickness of the bowel, leading to all kinds of scarring, and in some unfortunates, the formation of fistulas, as well as all manner of secondary infections. It is this sub-group of patients that responds best to treatment with wide-spectrum antobiotics, since it is secondary microbial infections that are primarily responsible for the tissue damage, with these secondary non-mycobacterial microbes being susceptible to non-mycobacterial antibiotic treatment.

Since the National Institute of Allergy and Infectious Diseases (NIAID) hosted a workshop on possible infectious causes of Crohn’s Disease in 1998, attended by all of the PARA Board of Directors, including myself, PARA directors Cheryl Miller and Karen Meyer have worked tirelessly with both NIAID staff and with Crohn’s Disease researchers to obtain funding for those researchers who wish to investigate infectious causes of Crohn’s Disease.

The first spectacular success in this ongoing campaign to find a cure for Crohn’s Disease is the provision of US$1.8 million in funding for researchers who are investigating a infectious cause for Crohn’s Disease, with a strong emphasis on research into Mycobacterium avium subspecies paratuberculosis (MAP).

Further information from the PARA web site

http://www.crohns.org/

Among the researchers who have received research funding in this round are two members of PARA’s Scientific Advisory Council, Dr. Saleh Naser and Dr. Norman Pace.

http://www.crohns.org/council/naser.htm
http://www.crohns.org/council/pace.htm

The NIH funding involves not only the National Institute of Allergy and Infectious Diseases (NIAID), but also involves the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), the National Institute of Health that has more traditionally been associated with Crohn’s Disease research.

Specifically, the NIDDK has funded another member of the PARA Scientific Advisory Council, Dr. Fouad El-Zaatari, to continue his long and detailed research program on the role of paratuberculosis in Crohn’s Disease. Dr. El-Zaatari has received funding to continue, among other research, his pioneering work on “In-Situ Hybridization”.

The latter is a technique whereby paratuberculosis bacteria which are present in gut tissue can be labelled and made detectable by attaching, for example, x-ray opaque metal atoms to them. This technique has potential for use as a clinical diagnostic technique, particularly because it can detect the cell-wall-deficient forms of MAP which are believed to be involved in the pathogenesis of Crohn’s Disease.

More details on Dr. El-Zaatari and his work from the following URLs

http://www.crohns.org/para/el-zaatari.htm
http://www.paratuberculosis.org/members/el-zaatari.htm

More information on In-Situ Hybridization from

http://www.paratuberculosis.org/proc6/abst5_2.htm
http://www.paratuberculosis.org/proc7/abst6_p7.htm

You can read more from the following links
NIAID: Crohn’s Disease: Is There a Microbial Etiology? Recommendations for a Research Agenda
NIAID: Recommendations for a Research Agenda
PARA’s efforts benefit Crohn’s sufferers – NIH allocates $1.8 million to study infectious cause of Crohn’s

Momentous developments are afoot!!

====================================================
London, 5th Dec 2001.
UK Government adopts comprehensive strategy for eliminating MAP from milk.

The UK government today adopted a comprehensive strategy to prevent human exposure to the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). MAP is believed by a growing number of scientists to be a cause of Crohn’s Disease, a lifelong, debiliating and incurable bowel disease suffered mainly by the young.

The Advisory Committee on the Microbiological Safety of Food (ACMSF), which advises the UK Government Food Standards Agency, today approved a comprehensive program of measures aimed at eliminating MAP from retail milk, as purchased by consumers. Previous research commissioned by the ACMSF showed that live MAP could be cultured from approximately 2% of retail milk on sale in the United Kingdom.

The strategy adopted by the ACMSF shows that the UK Government is taking the issue of MAP and Crohn’s Disease extremely seriously. As the ACMSF says in its strategy document: “…. the Agency has put to one side the question of whether or not there is a link between MAP and Crohn’s Disease. The Agency believes that precautionary action to reduce human exposure to MAP should start now and should not be dependent on waiting for the link to be proven.”

Among the raft of measures approved by the ACMSF are:

– Increasing pasteurisation times from 15 seconds to 25 seconds. Although some dairies had voluntarily adopted this extended pasteurisation time in 1998, the more stringent conditions will now become standard government recommendation.

– Stricter quality monitoring of pasteurisation plants. Due to the potential for MAP to survive pasteurisation because of defective or improperly operated pasteurisation machinery, dairies and farms will be closely monitored to ensure that they are complying with regulations.

– Improvement of on-farm milking practices. Because a likely route for MAP to infect milk is faecal contamination, on-farm milking practices are to be closely studied to find the most effective method to prevent this contamination.

– Elimination of MAP infection from herds. The ACMSF is initiating a multi-pronged effort to eliminate MAP from herds of food animals, including improvement of existing diagnostics, a national survey to determine the prevalence of MAP infection in UK dairy herds, and development of a improved vaccination methods to protect animals from the infection.

– Alternative pasteurisation technologies. The ACMSF is coordinating several research projects which are assessing the effectiveness of several novel pasteurisation methods against MAP. The methods being studied include high-pressure homogenisation, double pasteurisation, microfiltration and bactofugation.

The timetable by which these measures will be implemented will be finalised in another ACMSF meeting, to be held in London in January
2002.

PARA greatly welcomes these developments, and commends the UK Government on its willingness to act in the best interests of its citizens and the best interests of the public health. However, there are some further measures which PARA would like to see the UK Government undertake.

o Labelling of extended pasteurisation. Since it is not possible for the UK Government to mandate 25 second pasteurisation for all UK milk, for reasons of European regulation, there will still be some 15 second pasteurised milk for sale in the UK. In order that Crohn’s Disease patients and their families be able to differentiate between 25 second and 15 second pasteurised milk, it is vital that the pasteurisation time be labelled on retail milk containers.

o Elimination of MAP from beef. Milk is not the only route for transmission of MAP to the human population. MAP can also be transmitted through beef from infected cows, and there is evidence to believe that the standard temperatures used for cooking of beef will not effectively kill the organism. Although the comprehensive strategy to deal with MAP in milk is a welcome start, it does not deal with the whole MAP problem.

Paratuberculosis Awareness & Research Association is non-profit organisation of Crohn’s Disease patients, their families and friends who are dedicated to the following goals

1. To promote awareness of the disease-causing potential of the bacterium Mycobacterium paratuberculosis in the national community of sufferers of Crohn’s Disease and Inflammatory Bowel Disease; in medical, veterinary and food research communities; in governmental agencies and in the public in general.

2. To promote clinical trials of therapy effective against MAP as treatment for Crohn’s Disease.

3. To promote mandated national testing programs to ensure that the milk/dairy, beef and other products on our grocery shelves are free of contamination with Mycobacterium avium subspecies paratuberculosis.

For further information, please visit the PARA web site at

http://www.crohns.org/

1. Thursday 30th March 2000 – Newsnight (BBC1 TV, 10 minute report)
2. Friday 31st March 2000 – Farming Today (BBC Radio 4, 12 minute report)
3. Sunday 2nd April – CountryFile (BBC1 TV, 12 minute report)
4. Sunday 2nd April – On the Record (Interview with Agriculture Minister)
5. Monday 3rd April – Farming Today (BBC Radio 4)

I have numbers 2, 3, 4, and 5 on tape, and hope to digitize them and make them available on the net, for you all to see first hand.

However, I am about to go away for at least three weeks, so it will probably be the end of this month before you get to see/hear them.

As you will understand when you see/hear the programmes themselves, this issue is far from old hat. The only reason why it keeps cropping up in the news is because STILL, despite continued warnings to the Food Safety and Health Authorities, almost nothing has been done about MAP and Crohn’s Disease. The risk of exposure to MAP and the possible resulting development of Crohn’s Disease is still born by one group alone: the consumer.

Until we get research funds to deal with this complicated problem, I’m afraid that the controversy is going to continue. What we in PARA are trying to do is to educate everyone involved on the the complexities of this situation, so that at least we can discuss the issue in common terms, rather than the rampant prejudice and polarization that characterizes this subject.

If you are at all concerned about this issue, or wish to read more, please visit the PARA web page, at

http://www.crohns.org/

For those of you living in Britain, consider yourself lucky that you have a truly free press. A combination of the large financial muscle of the Dairy Industry “Got Milk” advertising campaigns and the threat of “Oprah’s Hamburger” style SLAPP suits ensure that those on the other side of the Atlantic are denied the opportunity to see the other side of this very important story.

The most important point made for sellers of cattle was that if they make a statement “This cow does not have Johne’s disease”, then they are legally liable if the cow does actually turn out to have JD, a strongly possible occurrence due to the inaccuracy of current testing methods for JD. The only statement they can make is that “This cow has tested negative for Johne’s disease, by methods X, Y, and Z”.

It is possible that this principle might be extended to “Mycobacterium paratuberculosis does not cause Crohn’s disease”, which is the current position of the dairy and beef industries around the world. If/when proof that paratuberculosis causes Crohn’s is revealed, then they might be liable, since evidence is becoming much stronger that live Mycobacterium paratuberculosis are present in cattle derived foods.

With 1.5 million people with clinical Crohn’s disease around the world, and at least 400,000 people with clinical Crohn’s disease in the USA, it could result in a class-action lawsuit on a Big Tobacco Scale.

If I were in the cattle industry, I would be moving to eradicate Johne’s disease from herds of food animals now. Instead, the US Animal Health Association advocates a “Voluntary Certification” program, whereby volunteer farmers test their herd for Johne’s disease, and there is no obligation if they test positive. Such animals currently go into the food chain to make hamburgers.

More info on the USAHA meeting available from

http://www.crohns.org/media/index.htm

Info on the finding of Mycobacterium paratuberculosis in British retail milk available from

http://www.crohns.org/governments/uk.htm