The Crohnie

It will be great to finally see published the results of that double-blind, placebo-controlled and multi-center clinical trial: reliable data are desperately needed in this area.
http://www.crohns.org/treatment/austrial.htm

I expect to see results that show that RMATC (the Pharmacia trial is using RMAT + Clofazimine) is equally or more effective than existing treatments for Crohn’s Disease, and in a minority subgroup of patients, induces significantly longer clinical remission periods than existing treatments.

However, even when the results are published, we will still be in the following dissatisfactory position

1. We will not know in advance who will benefit from anti-MAP treatment and who will not.

2. If the treatment achieves a successful clinical outcome in any given patient, we will not know why.

3. If the treatment fails to achieve a successful clinical outcome, we will not know why. Which means that we will be unable to tell if the same treatment can be used again in the same patient, or if an alternative antibiotic treatment is required (e.g. due to antibiotic resistance).

4. We will not know the parameters which will define a successful end of the treatment period, e.g. organism clearance, antibody reduction, etc, etc. The currently proposed 2-year treatment period is essentially a guesstimate, based on experience with the treatment of related mycobacterial infections such as M avium subsp. avium. Since these antibiotics are expensive, and can be toxic, we need to be able to much more clearly define clinical outcome parameters. If 2 years is too short, then we risk antibiotic resistance. If 2 years is too long, then we need to reduce it. But we have little data to base conclusions upon.

5. We will not know if the treatment is microbiologically working in a patient with physical stricturing symptoms. RMAT treatment can accelerate stricture formation in a (hard to identify) subgroup of patients, due to fibrotic tissue formation, just as with other mycobacterial diseases. Physicians inexperienced with the protocol can misread the consequent temporary disimprovement in the patient’s clinical status as a treatment failure and take the patient off treatment, thus risking antibiotic resistance. We will have no tools, other than physician experience and intuition, to differentiate success from failure.

Or as Chiodini puts it, we will still be “at the whim of the individual physician”.

I believe that the bottom line is that most Gastroenterologists simply don’t know enough about infectious diseases, are not taught enough about infectious diseases: it’s not a large enough part of their educational, medical, or clinical culture. For example, some of the research published by gastroenterologists about anti-MAP antibiotic treatment for Crohn’s Disease displays fundamentally flawed reasoning and lack of microbiology experience.

I don’t find it at all strange that RMAT treatment was pioneered by a surgeon, John Hermon-Taylor. Fortunately, there are many excellent, open-minded and energetic gastroenterologists who are at the forefront of a fundamental rethink of Crohn’s Disease: Ira Shafran(Florida), Tom Borody(Sydney), Will Chamberlin(US Army), etc, etc. I’ve had the great fortune to work with all three: three things stand out about all of them: 1. They concern themselves deeply with the health of their patients, 2. they are not afraid to admit that they don’t know everything and are willing to learn, and 3. they are not driven by money.

Live Mycobacterium avium subspecies paratuberculosis (MAP) has been cultured from retail milk purchased from stores in California, Minnesota and Wisconsin.

This means that American consumers are being exposed to live bacteria that are known to cause Inflammatory Bowel Disease (Johne’s Disease) in a wide range of animals, including dairy and beef cattle, and is suspected of being a cause of human Crohn’s Disease.

The most important points are

1. From May 2002 through April 2003, milk was purchased from stores in California, Minnesota and Wisconsin – three of the USA’s top 5 milk-producing states. (The other two are New York and Pennsylvania.)

2. Milk was tested for presence of viable MAP, using methodologies created in the 1990’s by British researchers, to study the presence of MAP in retail milk in the UK. It has been known since 1998 that United Kingdom dairy products are contaminated with live MAP.

3. Of 702 US samples tested, 2.8 percent contained viable MAP – that is, MAP bacteria that was alive, capable of multiplying and establishing infection, and capable of causing Inflammatory Bowel Disease in susceptible species.

4. Rate of positives was similar among states, but there was a seasonal effect. More positive samples were found during July, August and September.

This study confirms what we in the Paratuberculosis Awareness and Research Association have long believed: that American consumers are eating and drinking food that contains a live and dangerous bacterium, through the medium of MAP-contaminated dairy products.

On average 2.8% of milk cartons were found to be contaminated. Assuming that the average milk consumer drinks from a single carton of milk per day, this means that the average milk consumer is exposed to live paratuberculosis on average ten times a year. Consuming from 2 different milk cartons per day, 20 times a year, etc. This applies particularly to children, who are encouraged to consume milk, for the calcium and protein content. An average American child living in Minnesota, California or Wisconsin, if they consume from one milk carton per day, will have been exposed to live paratuberculosis up to 100 times by their tenth birthday.

The published results apply only to milk. Although research has shown that the food treatment methodologies used to manufacture other dairy products, such as cheese, chocolate, whey, etc, are incapable of destroying MAP, no US research has sought to determine the percentage of these retail dairy products also contaminated with live MAP. The majority of Wisconsin milk is used for cheese manufacture. Recent scientific results have shown that the methods to manufacture cheddar cheese do not kill paratuberculosis.

To this date, the food safety regulators in the United States, the Food & Drug Admninistration (FDA), have taken no action on the presence of live paratuberculosis in milk, dairy and beef products. The time has now come for the FDA to revise its policy of inaction, and to act immediately to protect American consumers from this dangerous bacterium.

If you believe that the US Government should put the interests of the American public before the interests of American Dairy and Beef Industries, and act to eradicate MAP from human food, please visit the PARA web site for steps you can take to help.

1. Original datasheet from American retail milk study
http://www.johnes.org/newsfiles/109216471862392.html

2. Articles about live paratuberculosis contamination in human food
http://www.crohns.org/map_food

3. Articles about the relationship between Mycobacterium avium subspecies paratuberculosis and Crohn’s Disease.
http://www.crohns.org/articles
http://www.crohns.org/research
http://www.crohns.org/treatment

4. Government agencies with responsibility for regulating Food Safety.
http://www.crohns.org/governments

5. PARA’s work to get the US Congress to help address this problem.
http://www.crohns.org/congress

6. What you can do to help.
http://www.crohns.org/help

Persistence of Mycobacterium paratuberculosis during Manufacture and Ripening of Cheddar Cheese.

Donaghy JA, Totton NL, Rowe MT.

Agriculture, Food and Environmental Science Division (Food Microbiology Branch), Department of Agriculture and Rural Development for N. Ireland, Newforge Lane, Belfast BT9 5PX, N. Ireland, United Kingdom.

http://www.ncbi.nlm.nih.gov/pubmed/15294829

Model Cheddar cheeses were prepared from pasteurized milk artificially contaminated with high 10(4) to 10(5) CFU/ml) and low (10(1) to 10(2) CFU/ml) inocula of three different Mycobacterium paratuberculosis strains. A reference strain, NCTC 8578, and two strains (806PSS and 796PSS) previously isolated from pasteurized milk for retail sale were investigated in this study. The manufactured Cheddar cheeses were similar in pH, salt, moisture, and fat composition to commercial Cheddar. The survival of M. paratuberculosis cells was monitored over a 27-week ripening period by plating homogenized cheese samples onto HEYM agar medium supplemented with the antibiotics vancomycin, amphotericin B, and nalidixic acid without a decontamination step. A concentration effect was observed in M. paratuberculosis numbers between the inoculated milk and the 1-day old cheeses for each strain. For all manufactured cheeses, a slow gradual decrease in M. paratuberculosis CFU in cheese was observed over the ripening period. In all cases where high levels (>3.6 log(10)) of M. paratuberculosis were present in 1-day cheeses, the organism was culturable after the 27-week ripening period. The D values calculated for strains 806PSS, 796PSS, and NCTC 8578 were 107, 96, and 90 days, respectively. At low levels of contamination, M. paratuberculosis was only culturable from 27-week-old cheese spiked with strain 806PSS. M. paratuberculosis was recovered from the whey fraction in 10 of the 12 manufactured cheeses. Up to 4% of the initial M. paratuberculosis load was recovered in the culture-positive whey fractions at either the high or low initial inoculum.