The Crohnie

BBC Televsion has produced a program about the high prevalence of Crohns Disease in Wales, its relationship to Mycobacterium avium subspecies paratuberculosis (MAP), and the presence of MAP in Welsh rivers.

You can watch the program online here (but unfortunately in very poor video quality, although the audio is fine). On the first page below, click the link “Watch the last show”.

http://www.bbc.co.uk/wales/programmes/sites/weekinweekout/index.shtml
http://www.bbc.co.uk/wales/programmes/sites/weekinweekout/updates/080325_crohns_disease.shtml

Leprosy is caused a member of genus Mycobacteria, M. leprae, and some forms of leprosy are treated by “tamping down the immune system” with anti-TNF agents, such as thalidomide. Steroids are also used for the treatment of leprosy[1].

FDA approves Thalidomide for Hansen’s disease side effect, imposes unprecedented restrictions on distribution.
http://www.fda.gov/bbs/topics/ANSWERS/ANS00887.html

Redeeming thalidomide
http://pubs.acs.org/hotartcl/mdd/00/jun/mddkling.html

Remicade’s anti-TNF activity might also be useful for leprosy (a known mycobacterial disease), but there haven’t been any trials of remicade/infliximab for Leprosy (Hansen’s Disease), presumably because the manufacturers know that the average third-world leper can’t afford $30K+ a year to be maintained on remicade, and thus won’t spend the huge money necessary for the relevant clinical trials.

But Thalidomide, the poor man’s anti-TNF drug, is long out of patent, and is cheap, and so gets used for the poor lepers. But there is a fightback in the leprosy medical community, primarily because of the nasty birth defects that Thalidomide causes.

No Role for Thalidomide in Leprosy
http://www.paho.org/English/AD/DPC/CD/thalidomide.htm

Thalidomide has been trialled for Crohn’s Disease.

Thalidomide reduces tumour necrosis factor {alpha} and interleukin 12 production in patients with chronic active Crohn’s disease
http://gut.bmjjournals.com/cgi/content/abstract/50/2/196

Thalidomide: New uses for notorious drug
http://www.mayoclinic.com/health/thalidomide/HQ01507

So the relative success of treatment of Crohn’s Disease with Remicade is NOT an argument against a mycobacterial cause. In fact, if the Crohn’s Disease to Leprosy analogy that has been made by some researchers[2,3] is true, then Remicade treatment in Crohn’s could be an argument FOR a mycobacterial cause.

1. Steroid prophylaxis for prevention of nerve function impairment in leprosy: randomised placebo controlled trial.
http://bmj.bmjjournals.com/cgi/content/abstract/328/7454/1459

2. Comparisons with leprosy, tuberculosis and Johne’s disease: is Crohn’s disease caused by a mycobacterium?
http://www.paratuberculosis.org/proc7/abst6_p6.htm

3. Mycobacterium avium subspecies paratuberculosis in the causation of Crohn’s disease
http://www.wjgnet.com/1007-9327/6/630.asp

I want to draw your attention to a recent epidemiological study from Wisconsin, which studied the epidemiology of both Crohn’s Disease, and IBD in general, in children in the state of Wisconsin. You can read an abstract of the study here

Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study.
http://www.ncbi.nlm.nih.gov/pubmed/14571234

Generally, the results of this study cast doubt on the belief that Crohn’s Disease and IBD are caused by a “genetic predisposition” or abnormality.

The most important points to note are

1. The researchers found that incidence rates of IBD were equal among all racial and ethnic groups. This casts doubt on the perceived wisdom that certain racial or ethnic groups are more “genetically susceptible” to Crohn’s Disease and IBD.

2. 89% of the new (incidence) cases of IBD described were non-familial, meaning that there was no family history of IBD in 89% of cases. This further casts doubt on “genetic susceptibility”.

3. There were no difference in the incidence rates between rural and urban areas.

4. The researchers found that there were more than twice as many cases of Crohn’s Disease as Ulcerative Colitis.

The researchers conclude their summary with this statement:

“This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohn’s disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.”

The conclusion that “environmental factors contribute to the pathogenesis” is an important one.

That there was a “surprisingly high incidence of pediatric IBD” mirrors results from neighbouring Minnesota, where Mayo Clinic researchs noted in 1998 that, in Minnesota, “No pediatric cases of Crohn’s disease were diagnosed before 1954, but 17% of patients diagnosed in the last two decades of [our] study period were under the age of 20 years.”

Crohn’s Disease in Olmsted County, Minnesota, 1940-1993: Incidence, Prevalence, and Survival
http://crohn.ie/archive/research/epidem/olmsted.htm

In the first recorded case of its kind, an unfortunate man in Germany who has HIV infection has tested culture positive for Mycobacterium avium subspecies paratuberculosis (MAP) infection of the intestine. He suffered consequent Crohns-like symptoms, including profuse diarrhoea, high temperature and severe weight loss.

The German researchers who diagnosed his condition warn that, given the high prevalence of MAP in European and US food animal herds, pasteurised milk could be a route for infection with MAP, and that immunocompromised patients are especially susceptible.

More info from

http://www.crohns.org/media/pr020724.htm
http://www.cdc.gov/ncidod/EID/vol8no7/01-0388.htm
http://www.ncbi.nlm.nih.gov/pubmed/12095444

I attended the UK Government meeting on MAP in milk last Wednesday, and wrote the following report.

====================================================
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/

The highest incidence and prevalence of Crohn’s Disease in the world were reported from Canada last year.

In the province of Manitoba, in the period 1989 to 1994, every year 14.6 people per 100,000 developed Crohn’s Disease. This rate is significantly higher than the previous record of 11 people per 100,000 per year from North Eastern Scotland, itself a very high figure.

Manitoba
http://www.ncbi.nlm.nih.gov/pubmed/10342800

Scotland
http://www.ncbi.nlm.nih.gov/pubmed/1634058

Manitoba is, of course, Canada’s dairy belt, being nestled beside the Great Lakes. The land there is very flat and wet, and the large number of lakes, streams and rivers are very interconnected.

It is becoming clear that water supplies are an important distribution route for MAP, as is evidenced by the saturation of Netherlands dairy herds with Bovine Johne’s Disease (up to 100% of herds in some areas).

If the water supply is an important vector for MAP infection in the human population, one would expect high yearly incidences of Crohn’s Disease in areas where there is a large population of cattle and where Bovine Johne’s Disease (BJD) is endemic. Among areas that fulfill these criteria are Wisconsin, Florida and the Netherlands.

However, either there are no Crohn’s Disease epidemiology figures available at all for these areas, or figures that are available are ten years out of date.

Which is why we need to make Crohn’s Disease a compulsorily reportable disease.

How else can we track the rampant progress of a disease which has spread to more people than HIV, in every country of the developed world, albeit much more slowly (Crohn’s taking 87 years instead of HIV’s 25-30 years).

Unfortunately, there is no information available on the epidemiology of either Crohn’s Disease or BJD in Saskatchewan.

Some information about Crohns in Asia and diet in Asia.

Crohns disease was almost unknown in most parts of Asia until very recently. If it did exist before the last few years, it is likely that it would have been confused with intestinal tuberculosis.

For a table of statistics of prevalence of Crohns disease across the world, including Hong Kong and Japan, with references to the medical studies that derived the figures, see the URLs

http://crohn.ie/archive/epidem.htm
http://crohn.ie/archive/epistats.htm

In this table you will find several studies which refer to migrants who move from countries with low CD prevalence to countries with high CD prevalance, for example Morrocans moving to Belgium, West Indians moving to England, and South Asians moving to England. In all cases, the migrants were as likely to develop CD as the people of their new home country, thus lending credence to the theory that CD is caused by an environmental agent.

A recent study in Japan searched for a correlation between diet change and development of CD. They found that CD was highly correlated with a change in diet from the traditional fish/vegetarian based diet to a more western meat/dairy based diet. A strong correlation was found between CD and Japanese people who had changed to a meat based diet, but the strongest correlation was found in Japanese people who had changed their diet to include dairy products. To see an abstract of this study, see the URL

http://crohn.ie/archive/research/misc/japprot.htm

A possible explanation for this high correlation is the fact there is a very high risk that dairy products contain bacteria of the species Mycobacterium paratuberculosis, an organism which has for years been theorized to cause Crohns disease. Recent studies have provided further evidence that CD is indeed caused by this enteric pathogen, which causes a chronic intestinal disease, identical to Crohns disease, in many species of animals, including sub-human primates, cattle, sheep, goats, dogs, deer, chickens, gerbils, horses, llamas, etc.

If you wish to read more about this topic, I have gathered together the relevent research into one web site. The URL for this site is

http://crohn.ie/archive/welcome.htm