Paratuberculosis and Crohn's Disease: Got Milk?
by Michael Greger, MD
Updated January 2001
Abridged
version
Printer
friendly version (144K, PDF)
Contents
Microbial foodborne illness is the largest class of emerging infectious
diseases. In 1999, the Centers for Disease Control (CDC) released the
latest figures on the incidence of US foodborne illness considered by the
Food and Drug Administration (FDA) to be the most complete estimate ever
compiled. Seventy-six million Americans every year get food poisoning,
more than double the previous estimate. In today's food safety lottery
there's a 1 in 4 chance you'll get sick, a 1 in 840 chance you'll be
hospitalized, and a 1 in 55,000 chance that an American will die from
foodborne illness annually.174
The CDC estimates 97% of foodborne illness is caused by animal foods.17
The latest United States Department of Agriculture (USDA) survey, for
example, found 9 out of 10 Thanksgiving turkeys contaminated with
Campylobacter, the most common cause of bacterial food poisoning in
the United States.175 And 75% of the
turkeys are contaminated with two or more foodborne diseases, most often
Salmonella as well, which are becoming dangerously resistant to
many of our best antibiotics.55
Although thousands die from food poisoning every year in the United
States, most sufferers only experience acute self-limited episodes. Up to
15% of those that contract Salmonella, however, go on to get
serious joint inflammation that can last for years. An estimated 100,000
to 200,000 people suffer from arthritis arising directly from foodborne
infections each year in the United States.101
The most feared complication of food poisoning, however, is
Guillain-Barr� syndrome, in which infection with Campylobacter can
lead to one being paralyzed for months on a ventilator. Up to 3800 cases
of Guillain-Barr� are triggered by infection with Campylobacter
every year in the United States.101
Some scientists now fear, though, that an even more serious disease may
be contaminating our food supply. Often touted as the Pulitzer Prize of
alternative journalism, a Project Censored Award was given to what was
considered one of the most censored stories of 1999 -- the connection
between Crohn's Disease and paratuberculosis bacteria in milk.20
Described as a human scourge,33
over a half million120 Americans
suffer from this devastating, lifelong condition95
with annual US medical costs in the billions.189
Crohn's sufferers experience profuse urgent diarrhea, nausea, vomiting,
and fevers.78 Because of the
diarrhea, many people are unable to leave their houses; others drive
around in recreational vehicles or mobile homes to keep a bathroom close
at hand.98 The director of the
National Association for Colitis and Crohn's Disease says the best way to
describe to nonsufferers how bad the disease can get is to have them think
of the worst stomach flu they ever had and then try to imagine living with
that every day.29
What happens is that the immune system starts attacking the lining of
the gut, which becomes swollen and inflamed.24
In extreme cases this painful embarrassing condition can affect any part
of the digestive system from the mouth to the anus.27
This inflammation narrows the digestive tract and can result in
excruciating pain during digestion as well as constant uncontrollable
bowel movements. Added discomforts associated with Crohn's disease include
severe joint pains, weight loss, and lack of energy.92
The intestines characteristically become so deeply ulcerated that they
take on a "cobblestone" appearance. The ulcers can actually eat right
through the gut wall and cause bleeding, abscesses, fistulas and
perforation.150 Passing food,
sometimes even just drink, through Crohn's damaged intestines can be
excruciatingly painful. In the words of one colorectal surgeon, "Crohn's
is a surgical disease. We wait until the patient can no longer withstand
the pain anymore, and then we perform surgery...and repeated surgeries
over time...ultimately, as recurrences happen and intestinal damage
occurs, we just cut and cut, in some cases, until there is no more
intestine that can be cut out."24
Tragically, Crohn's disease typically strikes people in their teens and
early twenties -- destroying their health.53
Children, adolescents, and young adults suddenly become faced with the
harsh reality of a lifetime of chronic pain, in and out of hospitals their
entire lives.27
The disease is mostly found in the United States, United Kingdom, and
Scandinavia.152 And it's on the
increase. The incidence in the United States, which has been increasing
steadily since the 1940s -- doubling, then tripling, then quadrupling89
-- is now approaching that of an epidemic.67
The most rapid increase has been seen in children. In the 1940s and early
1950s there were no recorded cases of Crohn's in teenagers. Currently, one
in every six new cases diagnosed are under age twenty.89
Dr. Crohn, who described one of the first series of cases back in 1932,149
wrote decades later "From this small beginning, we have witnessed the
evolution of a Frankenstein monster...."25
Crohn actually didn't discover Crohn's disease. The first person to
give it a clear description was a Scottish surgeon named Kennedy Dalziel
in 1913.23 He wrote, "I can only
regret that the etiology [cause] of the condition remains in obscurity,
but I trust that before long, further consideration will clear up the
difficulty."42 Eighty-eight years
later and the scientific community is still not sure what causes Crohn's,
but Dalziel had a hunch which a growing number of prominent scientists now
think may be correct.
About two decades earlier in 1895, German doctor H.A. Johne was the
first to describe the cause of a disease in cattle characterized by
chronic or intermittent profuse intractable diarrhea.190
Clinically, the disease in cattle was virtually identical to that which we
now know as human Crohn's disease.25
The gross pathology of the infected cow's intestines likewise had the same
cobblestone appearance; microscopically, the Crohn's diseased intestines
and the diseased cattle intestines were dead ringers.23
Dalziel wrote that the tissue characteristics were "so similar as to
justify a proposition that the diseases may be the same."42
He theorized that the disease in cattle and the disease in people were the
same entity.
The cattle disease, which became known as Johne's disease (pronounced
yo-neez), is known to be caused by a bacteria called Mycobacterium
paratuberculosis, also known as Mycobacterium avium subspecies
paratuberculosis, or MAP.183 MAP
belongs to an infamous class of microbes called mycobacteria which cause
diseases such as tuberculosis and leprosy. In fact, before Johne properly
distinguished MAP from other mycobacteria, the disease in cattle was
thought to be caused by intestinal bovine tuberculosis, hence the name
paratuberculosis or "tuberculosis-like."
Mycobacterium paratuberculosis is one of the most enigmatic
bacteria known.121 It lives inside
the hosts' cells, but has no known toxins and doesn't seem to damage the
cells.23 The damage, much like in
diseases like hepatitis, comes from the hosts' reaction to it. MAP
triggers a massive immune reaction against the body's own tissues in which
MAP is hiding, in this case the gut.26
It is known that M. paratuberculosis -- MAP -- causes Johne's
disease in cattle, but does it cause Crohn's disease in people?
Paratuberculosis bacteria seem to cause disease in almost every species
of animal so far studied.75 It's
reasonable to assume the same might happen in humans. ParaTB causes a
specific chronic inflammation of the intestines of cattle, sheep, deer,
rabbits, baboons, and three other species of primates.115
The problem for Dalziel was that he couldn't visualize the bug
microscopically in the surgically resected intestines of patients with
Crohn's.61
While one can easily pick out MAP in most cases of Johne's disease with
a simple light microscope, to this day attempts to stain and view MAP in
Crohn's disease has been largely unsuccessful.4
The landmark of most mycobacterial infections is the presence of acid-fast
bacilli, so called because the mycobacterial cell wall soaks up and
retains a particular acid stain.27
Although failure to see acid-fast bacilli in general is not uncommon,24
in the intestines of Johne's disease infected cattle, one can see swarms
of acid-fast bacilli; in Crohn's there are none. The mystery wasn't solved
until 1984, when Rodrick Chiodini, a microbiologist at Brown University's
Rhode Island Hospital published a landmark study in which he actually
cultured live paraTB germs from the gut walls of children with Crohn's
disease.23
It has now been well established that paratuberculosis (and some other
mycobacteria186) can shed their cell
walls and exist as what has been termed "cell wall deficient" or "spheroplast"
forms. Since it's the cell wall that picks up the stain, this form of the
bacteria cannot be detected using the acid-fast stain test.23
The bug, however, can then reform its cell wall even years later and
revert back to its normal stainable self, which is what happened in
Chiodini's lab.65 It is thought that
this cell wall deficient form is responsible for triggering the abnormal
immune response which leads to Crohn's disease.45
The next hurdle was the difficulty of consistently culturing the bug
from Crohn's sufferers' intestines.27
Although MAP has been independently isolated across three continents --
cultured from Crohn's tissue in California, Texas, France, Australia,
England, the Netherlands, and the Czech republic27
-- results are still relatively sparse and many labs have reported not
being able to culture it at all.115
This is not surprising.24
In order to isolate a specific bug from the multitude that exist
naturally in the intestine, one has to devise a decontamination technique
that kills other bacteria without harming the target bacterium, in this
case MAP. Without their protective cell walls, however, cell wall
deficient forms are almost impossible to culture because of the caustic
processing techniques required to isolate them.22
Even once isolated, MAP is very difficult to grow.68
Researchers have been trying since 1952 to grow mycobacteria from
surgically removed Crohn's disease tissue.46
It is thought that Chiodini succeeded where others had failed because of
his many years of experience, combined with access to modern culture
techniques and years of patient work.126
Some human isolates took up to six years to grow, even under extremely
precise culture and decontamination conditions.66
Earlier researchers failed to meet these stringent standards for culturing
the bacteria.83
Even modern labs have been found to be relying on faulty study design.66
Moreover, the differences in methods used between labs can be vast.24
Some labs still use fixed or frozen specimens or use only surface tissues
from superficial biopsies, when it's been shown that one should optimally
use fresh66 resected tissue, as MAP
tends to be found deep in the intestinal wall.166
Some labs working with nonspheroplast forms of MAP from cattle haven't
even been able to grow it. Even under the best circumstances, MAP is a
tough bug to grow.67
To this day, many infectious agents have eluded our attempts to grow
them in labs at all. For example, scientists have never been able to
isolate Mycobacterium leprae, the microbe responsible for leprosy.
Even Campylobacter, which we now know as the most significant
bacteria in food poisoning, wasn't identified as a human pathogen until
the 1970s, when culturing techniques enabling isolation were finally
developed.101
Complicating attempts to culture the bug in Crohn's, there seem to be
very few MAP actually involved in the disease process. This has a parallel
in other animals -- MAP bacteria in sheep and goat paratuberculosis are
often sparse or even undetectable147
-- and in other mycobacterial human diseases like a type of leprosy in
which just a few mycobacteria are capable of triggering a pathological
immune response.67
Obtaining Crohn's tissue samples is easy -- patients are all too
frequently having pieces of their bowel removed -- but growing MAP from
this tissue is so difficult that a nonculture-based method was needed.
This advance came in the late 1980s when new DNA fingerprinting techniques
arrived on the scene.70 Using DNA
probe technology similar to that used in forensic cases to pick up minute
amounts of DNA, one can determine the definite presence of paraTB without
needing to actually culture and grow it.144
No longer would researchers have to wait months or years for the
spheroplasts to revert back to normal and start growing again, one could
just target, with 100% certainty, MAP DNA.
Sixty-five percent of bowel samples from Crohn's patients came up
positive, compared to only 4% of those with the similar but different
disease ulcerative colitis.170 As
techniques for extracting and isolating DNA have become better and better,
MAP has been found in intestinal Crohn's tissue with increasingly positive
results.112 The reason more Crohn's
cases were not detected is because the test has a limited sensitivity,
especially when searching for a needle in a haystack in the gut which is
awash in the DNA of billions of other bacteria.153
DNA probe detection of other low abundance bacterial pathogens,
particularly in chronically inflamed tissues -- diseases like
tuberculosis, Lyme disease, brucellosis, and lymphocytic leprosy -- have
similarly been fraught with difficulty.155
Isolating chromosomal DNA from mycobacteria in general is experimentally
difficult.154 There are also other
substances in the gut that have been found to inhibit the test such as
bile salts and polysaccharides.192
Also accounting for uncertainty in the data27
is the frequent misdiagnosing of Crohn's disease. For example, it's been
shown that at least 20% of people diagnosed with Crohn's actually have a
different disease, such as ulcerative colitis.186
There is also considerable debate on whether or not Crohn's is a single
disease entity in the first place.23
Crohn's may be more of a catchall syndrome describing a number of
different conditions, some of which may not be caused by MAP.132
Either way, this makes it difficult to interpret data that show that not
all of those we consider to have Crohn's disease test positive for MAP.
As expected, some people without Crohn's -- healthy controls -- test
positive. Yet just because someone comes in contact with and harbors a
specific germ doesn't necessarily mean that person will come down with the
disease.65 It is estimated, for
example, that only a third of calves that ingest MAP ever develop Johne's.26
It is also possible, like closely related subspecies, that there are
different strains of MAP, some of which cause disease and some of which
don't.163 The important point is that
there has consistently been a highly significant specific association
between Mycobacterium paratuberculosis and Crohn's disease.24
Just because Crohn's sufferers are much more likely to have MAP found
in their gut does not necessarily mean that MAP caused the disease.
Another explanation of the finding could be that this is just an
opportunistic invasion of MAP into diseased tissue, leading to a chicken
and egg scenario of which came first.184
If MAP just has an affinity for inflamed tissue, however, one would expect
that one would also find MAP more frequently in biopsies of similar
diseases like ulcerative colitis, but this is not the case. Conversely, if
you look for the DNA of other nonspecific mycobacteria, one finds that
they are uniformly distributed between Crohn's patients versus controls.
This finding is consistent with the known environmental distribution of
mycobacteria, which are present in 30-50% of all environmental samplings
-- including water, soil, even air.24
So other mycobacteria people routinely come in contact with, even the
closely related Mycobacterium avium subspecies silvaticum, are
equally distributed among people whether they have Crohn's disease, or
colon cancer, or are completely healthy as one might expect.109
In medicine there is a method used to try to prove that a specific
pathogen causes a specific disease. The first person to definitively prove
that a disease was caused by a particular organism was Robert Koch, who
uncovered the bacterial origin of anthrax in 1876. Koch cultured the
bacteria from a diseased animal, gave anthrax to a healthy animal by
inoculating her or him with a pure culture of the bacilli, and then was
able to recover and reculture the bug once again.14 These
experiments fulfilled criteria proposed 36 years earlier by Henle as
necessary to establish a causal relation between a specific agent and a
specific disease. These criteria are now known as the Koch postulates.90
Not only are these experiments arguably unethical,162
they also can be unreliable in clinical medicine, as other animals may not
be susceptible to the same diseases that we are. For example, the case to
prove that H. pylori caused ulcers was hindered by animal research,
as rats and pigs were tested and seemed to be immune.107
For this and other reasons, there are some recognized infectious diseases
which have never fulfilled Koch's postulates. Leprosy, for example, has
still never fulfilled more than one of the four criteria, because it is
not possible to culture the culprit bacterium in the laboratory.
Nonetheless, Mycobacterium leprae is known to be the cause of
leprosy, and leprosy is known to be an infectious disease.105
So while not absolutely necessary to fulfill Koch's postulates to prove
causation, they are the most widely accepted method. So researchers set
out to the task and they succeeded -- twice.126
Chiodini fed chickens pure cultures of the paratuberculosis bacteria he
recovered from the surgically removed intestines of children with Crohn's
disease. The chickens then developed an intestinal disease resembling
Crohn's.108 In 1986, a different lab
fed infant goats a human strain of paratuberculosis and also found that
the bacteria induced a Crohn's-like intestinal disease in the goats. The
same strain was then recovered back from all of them.191
When asked why there continues to be so much resistance against the idea
of MAP as a cause of Crohn's disease, Chiodini replied "What you have to
realize is that there is a lot of politics in medicine. It's not whether
you have the proof of something, but whether or not the medical community
wants to accept it."19
Because there have been so many other failed attempts to figure out the
cause of Crohn's, the medical community is very leery of new proposed
causes, especially infectious ones.24
The gastrointestinal community maintains a healthy skepticism regarding
new pathogens as the cause of Crohn's disease, because different pathogens
suspected in the past, such as chlamydia and measles, have since been
disproven.143 Of all the pathogens
once thought associated with Crohn's in the 80 years it's been researched,
MAP is the only one directly cultured and the only one capable of causing
pathologically indistinguishable disease in other animals.49
The way that doctors test for the presence or absence of many
infectious diseases is by looking for specific antibodies that our immune
system uses to target the invader. When we test for HIV, for example, we
are not usually testing for the virus directly, we are looking for the
presence of anti-HIV antibodies.173
If they're found, we can be relatively certain the person has been exposed
to HIV. Similar searches have been launched for anti-MAP antibodies.
Unfortunately, scientists have had difficulty finding an antibody which is
specific for MAP.186 There are some
promising new suspects, however, which are thought to be unique to MAP and
have been found in 90% of Crohn's patients, but in less than ten percent
of those with ulcerative colitis.165
These results not only support the theory, but open new research
frontiers. A vaccine might be developed and the diagnosis of Crohn's may
soon be just a blood test away.120
Other potential lines of evidence include population studies. One would
expect that if paratuberculosis was causing Crohn's disease, then the
regions in which there is a high prevalence of Crohn's should overlap with
the regions with a high prevalence of paratuberculosis. While sufficient
data is lacking,161 a review of the
epidemiology of Johne's disease compared with the epidemiology of Crohn's
disease found just that.120 "Crohn's
disease has a very spotty distribution in the world," notes Dr. Walter
Thayer, an expert on the disease at Rhode Island Hospital who worked with
Chiodini to culture MAP from Crohn's patients. "But it's seen only in
milk-drinking areas -- Australia, southern Africa, Europe, the United
States, Canada, New Zealand. Interestingly, it's not seen in India, where
they do drink milk, but they boil it first."19
Critics point to Sweden, which has its share of Crohn's, but whose
cattle are reportedly paratuberculosis free. Unfortunately, the
surveillance testing has been limited.115
Michael Collins, veterinarian and microbiologist with the University of
Wisconsin, has written "We believe no region in the world is free of M.
paratuberculosis infection in its ruminant livestock. In all
likelihood, Johne's disease is to be found in every country. Being free of
the disease is probably more a function of how hard one has looked than a
true lack of incidence."35 We will
see a prime example of this in the discussion of Ireland.
Another perceived inconsistency in the link between paraTB and Crohn's
is the fact that Crohn's is found more often in urban, rather than rural
populations.143 Dairy farmers, for
example, do not seem to have higher rates of Crohn's.82
This is not dissimilar from other parallel diseases like bovine TB --
tuberculosis not paratuberculosis -- which, centuries ago, was responsible
for the deaths of hundreds of thousands of children who drank
unpasteurized milk.7 The association
between tuberculosis contracted by drinking milk and the rural community
was also weak, presumably because of the commercial marketing and
distribution of infected milk.202
Any explanation of Crohn's would have to account for the rapid increase
seen in this disease this century.178
The longest continuous study of the incidence of Crohn's disease is from
Wales, which reports a 4000% increase of the disease since the 1930s.140
This may be explained by the concurrent rise in paratuberculosis in
intensively farmed dairy herds throughout the century.66
Thayer asks also "What has happened to dairying in that time? Do you get
milk from your local dairy? No. You get it from big conglomerates that buy
from local dairies and pool all the milk. I think this is possibly the
reason the disease has spread so quickly."19
Two centuries ago, when milk drinking children were dying en masse from
bovine TB, one of the earliest signs that they had drunk milk from a
tuberculous cow was an infection of the lymph nodes that drained the
throat. Scientists think milk is also the source for human exposure to
paratuberculosis, so they wondered if the same thing happened with MAP.
Enter Nick Barnes, a 7-year-old boy who developed a painful swollen
lump on the right side of his neck. His family took him to see their
doctor, who decided it needed to be biopsied. The biopsy clearly showed he
was infected with paratuberculosis. This is significant because it was the
first definitive proof that paratuberculosis could infect human beings and
cause disease. He and his family waited. Five years later, Nick Barnes
came down with Crohn's disease.68
Despite the clear-cut case description of a human paratuberculosis
infection followed by the development of Crohn's, the medical community
continued to ignore the growing evidence indicting MAP. There are many
precedents of similar resistance to new ideas in the medical field.
Most ulcers are caused by the immune system attacking the lining of the
stomach. Doctors blamed stress, thinking this led to too much stomach acid
and the excess acid caused irritation which maybe triggered the attack. It
was treated the same way as Crohn's has been treated: symptomatic relief
of the inflammation and surgery. Then two Australian researchers cultured
a tiny bacterium from the lining of the stomach and hypothesized heresy --
that ulcers were actually caused by an infection.99
For almost a decade the researchers' ideas were dismissed and
ridiculed.39 The medical community
scoffed at the notion that bacteria could survive in stomach acid.107
One of the Australian researchers was so desperate that he actually drank
a vial of the bacteria to prove his point.99
What finally convinced the medical community, though, was that ulcers
disappeared when patients were treated with the right antibiotics.64
This discovery revolutionized thinking in medicine. The ulcer-causing
bacteria, H. pylori, is now known as the cause of most ulcers in
the world.90
Many scientists see a close parallel between the H. pylori story
and paraTB. Just as H. pylori bacteria were the real reason the
body was attacking the stomach lining in ulcers, researchers think that
the MAP bacteria are the reason the body is attacking the intestinal
lining in Crohn's. The proposition that ulcers were an infectious disease
was met by nearly universal skepticism in the medical community.107
As Dr. Hermon-Taylor, Chairman of the Department of Surgery at St.
George's Medical School in London and leading proponent of the
paraTB-Crohn's link, has noted, "And this [H. pylori] was a bug
that you could see by looking down the microscope, grow in a simple
culture system in the lab, test for immunologically pretty simply, and
ordinary tablets readily available to doctors could make it go away. And
it still took eight years for the penny to drop. Now we've got a bug [MAP]
that you can't see, can't grow, hides under the immunological radar, is a
bastard to kill, and the problem it's causing is far, far greater. If Rod
Chiodini and I are wrong, the magnitude of the problem will only be the
economic losses of farm animals, which is costing the United States
somewhere between $1.5 and $2 billion a year. If Rod Chiodini and I are
right, then, oh dear, oh dear. We have a big problem. It's going to take a
lot to put it right."19
The lesson researchers learned from stories like H. pylori90
was that their best bet at convincing the world that MAP causes Crohn's
lay in trying to cure Crohn's -- a disease thought incurable -- with
appropriate antibiotics.74 Of course,
there was no guarantee that even if the disease were caused by MAP that it
would respond to treatment.156 For
example, we can cure most pulmonary TB with antibiotics, but when TB
bacteria move from the lung to the intestine and cause intestinal TB, it
cannot typically be cured by antibiotics alone.23
Researchers, though, set out to try.
Before we knew that ulcers were treatable with simple antibiotics,
people underwent repeated grueling surgeries -- some almost as risky and
debilitating as Crohn's sufferers now undergo. Not only would a cure save
Crohn's sufferers from the surgeon's knife, but it would also protect them
from the toxic chemotherapy regimens currently used just for symptom
relief, which can include immunosuppressants like steroids, cancer chemo
agents,136 and even thalidomide.50
Researchers started trying antibiotics they thought might kill MAP in
Crohn's. Early results were disappointing,156
leading to much of the deep-seated resistance among clinicians to
accepting MAP as the cause of Crohn's.14
Yet in hindsight, it turns out that doctors were using the wrong
antibiotics, in the wrong combinations, for an inadequate period of time.
Perhaps because of the name similarity, many researchers assumed that
antibiotics effective against M. tuberculosis should also be
effective against M. paratuberculosis.189
They were wrong; when one actually tested antibiotics against MAP in a
lab, researchers found that it was in general resistant to anti-tuberculous
drugs.22 They didn't work in cows;23
they don't work in people.120
Another problem with some early studies was that they used monotherapy
-- meaning that they only used a single agent -- which is rarely, if ever,
effective in mycobacterial diseases because mycobacteria are so adept at
developing resistance.22 By giving
multiple antibiotics at once, one decreases the chance that resistance
will develop.
Adequate treatment duration had also been neglected. Mycobacterial
infections in general are difficult to eradicate; prolonged treatment is
required and relapses, either on treatment or off treatment, are common.156
Tuberculosis takes months to treat; leprosy takes years -- sometimes a
lifetime -- to treat. Our best estimate of how long it might take to rid
the body of MAP can be made by studying pathogens in the same species.
Infections caused by one of MAP's closest cousins (M. avium
intracellulare) routinely require treatment for 3-4 years with 3 or 4
different antibiotics.71 In some
cases, it took five antibiotics all used in combination for 5 years before
clinical improvement was achieved. We cannot expect trials using too few
drugs, the wrong drugs, or even the right drugs for too short a time, to
be successful.21
There are some factors which complicate any trial, even if the agents
are chosen and used appropriately. Crohn's can be a cyclical disease, with
periods of flare-ups and remissions, so approximately 20% of Crohn's
patients during a treatment period will spontaneously improve on their
own. The placebo effect is also expected to play a role in 30-40% of
patients undergoing short-term therapy. And as mentioned previously,
Crohn's is a poorly delineated disease -- 20% of people diagnosed with
Crohn's may actually have something else.186
There is also clinical, epidemiological, and molecular evidence indicating
that there are two distinct clinical manifestations of Crohn's disease,
which each may respond differently to treatment. These factors make it
difficult to evaluate any therapeutic intervention.150
Despite these hurdles, the latest results are quite promising.74
Instead of just blindly trying different antibiotics, scientists actually
endured the laborious task of testing the antibiotics one by one on MAP in
the lab. The breakthrough came in 1992 when the newly developed antibiotic
clarithromycin was found to be the most effective known killer of
Mycobacterium paratuberculosis. Many of the antibiotics used earlier
worked by blocking cell wall synthesis. But Crohn's is thought to be
caused by the spheroplast form of MAP which doesn't have a cell wall; it's
therefore no wonder these earlier drugs didn't work. Clarithromycin, and
an antibiotic called rifabutin, have a different mechanism of action,
blocking protein synthesis.157
Another reason why drugs like clarithromycin (called macrolides) work
against paraTB where others have failed is that MAP is an intracellular
pathogen. They live inside our cells (another reason why they're so hard
to see under a microscope). Only certain antibiotics, like macrolides, can
penetrate inside human cells and still work effectively.157
None of the previous MAP trials properly evaluated these newer macrolide
antibiotics.60 The time was ripe for
a trial of these newer agents in Crohn's disease.
The first trial took place in London, published 1997.60
Researchers chose to use rifabutin and clarithromycin because they seem to
complement or synergize with each other.157
The treatment was named RMAT, Rifabutin and Macrolide Antibiotic Therapy.
Fifty-two patients with Crohn's disease, most of whom had persistent
severe symptoms resistant to conventional treatment, were studied. Six
patients had to be excluded, due mostly to intolerance to the antibiotics,60
though in general the RMAT medications tend to have a much higher
tolerance rate and far fewer side effects than the current
immunosuppressive drugs used for Crohn's.120
The remaining 46 patients were treated with RMAT for about a year. Of the
46 patients who were able to tolerate RMAT, 43 went into clinical
remission, for a remission rate of 94%.60
A two-year follow-up was performed. The majority of patients in whom a
clinical remission was initially induced remained symptom free off of all
their previous medications.60 Similar
trials in other centers have reproduced these findings.9,10,16,44,167
The fact that some patients relapsed after treatment was stopped may point
to the difficulty in eradicating the organism or perhaps that they had
been re-infected.61 Hermon-Taylor,
one of the principal investigators of the original trial, is currently
recommending patients take RMAT regimen for at least 2 years. Among
patients who respond to treatment, remission occurs slowly over the first
three to six months of treatment. Symptoms often get worse before they get
better, as in the drug treatment of other chronic mycobacterial diseases
such as leprosy, perhaps due to the release of MAP antigens.
170
Based on this pilot study, RMAT has the highest reported remission rate
of any known treatment for Crohn's disease and the lowest reported relapse
rate, including all current immunosuppressive treatments.120
Thought to be an incurable disease, doctors seem to have been able to
induce profound long-term remissions in the majority (68.7%) of patients
with Crohn's disease.12 Not only do
patients stop having symptoms, but their intestines actually show evidence
of healing, an unprecedented achievement.164
"If this were cancer," said one RMAT researcher, "we would be calling
these long remissions a cure."98
Hermon-Taylor told the press "I've seen people who were without hope get
better like magic. I've been a doctor for nearly 40 years, and it's the
best thing I've ever seen in clinical medicine."19
Though the preliminary results of this and other pilot studies are
encouraging, Hermon-Taylor is the first to point out the limitations of
the study -- it was too small and there were no controls.185
"We were actually denied the funding to do a randomized control trial," he
said. "So I did the best that I could with what I've got."19
To date, according to the Cleveland Free Times article that won
1999's Project Censored Award, twenty-five of Hermon-Taylor's grant
proposals submitted both here and abroad were rejected.19
Chiodini estimates he's similarly submitted over two dozen grant
proposals to the National Institutes of Health, the USDA, and the Crohn's
and Colitis Foundation of America, but to no avail.19
Drug trials run in the United States have traditionally been supported by
the pharmaceutical industry, but just as H. pylori threatened to
deprive some of the largest corporations in the world of billions of
dollars (anti-ulcer medications were the world's best-selling prescription
drugs), the drug industry scores huge profits from increasingly complex
and expensive maintenance Crohn's treatments, which must be administered
for the rest of the patient's life.107
Needless to say, financial support from the corporate sector has not been
forthcoming.120
Nevertheless, these preliminary results must be reproduced to be
seriously considered. Larger scale controlled studies are currently in
progress to obtain better data.161
The most promising is a phase III clinical trial of RMAT in Australia
which has been designed as a double-blind, multi-center, controlled
clinical trial involving over 200 patients with Crohn's in at least seven
major cities across the continent.125
Unfortunately, they seem to be having a problem securing patients for the
study.111 A controlled RMAT trial has
also reportedly been initiated by the National Institutes of Health.39
Professor Hermon-Taylor, internationally known expert on Crohn's and
MAP genetics, who has researched the illness for 20 years, said: "If there
were no MAP I believe there would be almost no Crohn's disease. It is
certainly responsible for between 60 per cent and 90 per cent of all cases
and I would think that it is more likely to be 90 per cent."110
Obviously, everyone who's exposed to paraTB doesn't come down with Crohn's
disease, as is the case in virtually all infectious diseases. As mentioned
previously, just because one comes in contact with a pathogen does not
necessarily mean one comes down with the illness. Genetic and
environmental factors facilitate establishment, persistence, and
production of disease.45
H. pylori (the bacterium proven to cause ulcers), for example,
is one of the most common of all bacterial infections90
-- a third of Americans have H. pylori in their stomachs.99
A third of us, however, don't have ulcers;64
some people are susceptible and some are not. Similarly, only about one in
three hundred people exposed to tuberculosis actually come down with
active disease.19 Until we know why
some and not others fall ill, all one can do is to try to minimize
exposure to the pathogen. For example, people should not let those with
tuberculosis cough in their face.
Drinking milk from cows infected with Johne's disease is how people are
exposed to paratuberculosis. Based on DNA fingerprinting techniques, there
are two strains of MAP: one that affects cattle, and one that affects
goats and sheep. All human isolates so far have been of bovine origin,24
implicating milk.11 Milk is the
"logical" focus of exposure24 because
cows with Johne's disease secrete paraTB abundantly in their milk.158
Even sub-clinical cows -- those that are infected but appear perfectly
normal -- shed paraTB bacteria into their milk.24
Although these bacteria are found free-floating in milk, their
transmission may be facilitated by their presence inside pus cells.158
This is a particular problem in the United States, as we have the highest
permitted upper limit of milk pus cell concentration in the world --
almost twice the international standard of allowable pus cells (750,000/ml
vs. 400,000/ml)168 By US federal law,
Grade A milk is allowed to have over a drop of pus per glass of milk.6
These pus cells may facilitate the transmission of paraTB.158
In England, researchers took milk off grocery shelves and tested it for
the presence of paratuberculosis bacteria using DNA probes. Depending on
the time of the year, up to 25% of milk cartons contained paratuberculosis
DNA.104 Interestingly, the seasonal
variation coincided with the periods when Crohn's patients tend to suffer
relapses.61 The researchers tried to
culture live paraTB bugs from the milk, but were largely unsuccessful,
because cows' milk is such a stew of microbes that fungal overgrowth and
faster multiplying bacteria took over the samples.159
The question then remained, did the positive DNA samples in up to a
quarter of the milk supply indicate live or dead paratuberculosis
bacteria? Can paraTB survive pasteurization?
Historically, pasteurization had been established in order to kill
paraTB's cousin, bovine tuberculosis.179
TB was thought to be one of the most heat-resistant human pathogens, so
the temperature was set at approximately 62� C (144� F) for a half an
hour.179 Later, the disease Q fever
(caused by Coxiella burnetii) was discovered, so the temperature
was increased to 63� C.180 Now the
HTST method, which stands for High Temperature, Short Time, is
predominantly used -- 72� C (162� F), but only for 15 seconds.93
While 72� C kills most bacteria, paratuberculosis has been shown to
survive 15 seconds at 90� C (194� F).58
By hiding in milk in fat droplets, pus cells, and fecal clumps,189
paraTB might be able to survive at even higher temperatures.59
Second only to prions137 (which cause
mad cow disease), paratuberculosis is considered the most heat-resistant
pathogen in the human food supply.115
According to the Food and Agriculture Organization of the United
Nations, Johne's disease is one of the most serious diseases affecting the
cattle industry.139 Although it is
found in cattle populations throughout the world, the United States
appears to have the worst paratuberculosis problem on the planet.122
In 1997, the USDA released a long-awaited report of the national
prevalence of Johne's disease. Surveying over 2500 dairy producers,190
they showed that between 20 and 40% of US dairy herds were infected, a
figure that they concede is probably an underestimate.190
Since milk from an entire herd is likely to be pooled together in tankers
for transport to processing plants, all the milk from 20 to 40% of US
dairies is likely to be contaminated.85
Just as Crohn's disease is increasing in the human population -- it may
be no coincidence that the United States also has the world's highest
incidence of Crohn's ever recorded116
-- Johne's disease is spreading among dairy cattle.19
Johne's disease is spread primarily by the fecal-oral route. One can
imagine how a cow with intractable diarrhea can thoroughly contaminate her
surroundings133 and just a few bits
of swallowed manure can potentially infect a calf.133
Overtly infected animals, losing up to 300 lb of body weight in one week106
can shed as many as ten hundred trillion bugs a day.30
One can also imagine what intensive modern farming practices have done for
the disease.85 Grazing bigger and
bigger numbers of cattle on smaller and smaller plots of land is one of
the reasons this dreaded disease is such a growing threat.81
And every time animals are transported between farms, new herds may be
infected. If no changes are made, the dairy herd infection rate is
expected to reach 100%.115
With the growing Johne's epidemic, US governmental regulatory agencies
have been in a bind. The only thing allegedly standing between people and
the paratuberculosis bacterium are 15 seconds at 72� C.37
The government has had to somehow convince the families of Crohn's
patients who started to ask questions that pasteurization was foolproof.
The problem was that the preponderance of the scientific evidence was
against them -- almost every study ever done simulating pasteurization
conditions showed that paraTB survived the 15 seconds at 72� C.67
So USDA scientists designed their own experiment, which they published in
1997.
Critics accuse the USDA of trying to ensure that no paraTB would
survive in their pasteurization experiment by first crippling the
bacteria. Very irregularly, with no precedent in the scientific literature
for using this type of approach,56
the USDA describes beginning their experiment by first "starving" the MAP
bacteria,124 exposing them to
high-frequency sound waves, and freezing them -- a technique that has been
shown conclusively to weaken MAP.56
They were also criticized for making a number of methodological mistakes
and omissions.18,124
Then, allegedly to make absolutely sure not a single bug would grow, they
used an inadequate culture media124
and report culturing them for only 2 to 3 months.172
It is widely accepted that the minimum time it takes to ensure the growth
of paraTB is 4 months.124
It is perhaps not surprising that no MAP grew from the pasteurized milk
in their experiment. The researchers concluded: "Results indicate that the
transmission of live paraTB bacteria via pasteurized milk is unlikely."
Despite fifteen19 years of better
research to the contrary,121 based on
that single questionable study, in a letter dated February 9, 1998, Joseph
Smucker, the leader of the FDA's Milk Safety Team wrote, "After a review
of the available literature on this subject, it is the position of FDA
that the latest research shows conclusively that commercial pasteurization
does indeed eliminate this hazard."201
The FDA has argued that earlier pasteurization studies used
unrealistically high levels of MAP that wouldn't be expected to exist
naturally in the raw milk supply.201
This is not a tenable criticism, primarily because the studies in question
followed the published guidelines on the proper challenge concentration in
the design of thermal inactivation studies.57
Also, the concentration of MAP in raw milk is unknown. Cattle infected
with Johne's disease have uncontrollable diarrhea, which "sprays" out from
them in liquid form. Due to the close proximity of the cow's anus to her
udders, it is unavoidable that an infected cow's udders will be smeared
with feces, potentially leading to the contamination of her milk with high
numbers of Mycobacterium paratuberculosis.124
The feces contaminating her milk can have as many as a trillion paraTB
bugs per gram.142
Despite its shortcomings, the USDA study continues to be cited and the
rest of the scientific literature ignored by the government and the
agricultural press.62 Hoard's
Dairyman, for example, cited the USDA study and concluded that
"pasteurization destroys this dangerous disease."100
The year after the USDA study was published, assertions such as this one
were conclusively proven to be wrong.
The only way to demonstrate for sure that live paraTB bacteria survive
pasteurization is to culture a colony of living paratuberculosis bacteria
from retail pasteurized milk off the grocery shelf. In 1998, that is just
what researchers did. Choosing Ireland, which has the highest per capita
milk consumption in the European Union,117
investigators went to 16 retail outlets and got 31 cartons of milk which
were pasteurized at commercial dairies large and small.36
Six grew out live paraTB, 19% -- almost 1 in 5.65
This caused a national food scare with daily front page headlines, not a
word of which crossed the Atlantic.
In an editorial entitled "Media and Censorship," the editor-in-chief of
the Cleveland Free Times wrote: "The dairy lobby is notoriously
powerful inside the Washington DC beltway. And a tax on dairy farmers
helps the dairy industry spread its advertising dollars around generously
(most notably the 'Got Milk?' ad campaign), to the point where the
wholesomeness of milk goes virtually unquestioned in the media. How else
can it be explained that the possible link between a bacterium in milk and
Crohn's disease is virtually unknown in the United States, despite
front-page coverage in England and other places around the world?"135
When the results of the Irish study were released, crisis management
specialists called the ramifications "enormous," "horrific." Dairy
industry experts described it as a "significant blow to the industry,"
"accelerating the long-term decline of milk," and noting "It's not a
market that can just bounce back."198
Dairy industry leaders reacted angrily to the suggestion that
pasteurization was inadequate. The British National Dairy Council's
"Information Officer," said she wished the investigators had contacted the
industry before publishing their scientific findings.52
Responding to public pressures, the British government initiated a
nationwide thousand-sample survey of retail pasteurized milk. The
announcement splashed headlines all over Europe, but there was still no
word in the American press.19 The
preliminary findings of the British government's survey were released in
April 2000. Three percent92 -- 3 out
of every one hundred cartons of milk off the shelves -- grew out live
paratuberculosis bacteria.97,159
Based on the detection threshold of these tests, each quart had to contain
at least about a million paraTB germs to come up positive.66
A year and a half earlier, after the announcement that milk was
contaminated by at least paraTB DNA, the three British supermarket giants
-- Tesco, Sainsbury, and Safeway -- announced that milk pasteurization
time would be increased from 15 seconds to 25 seconds, to reassure the
public that their products were safe.13
The finding of live paratuberculosis bacteria in retail milk over a year
later has fueled the skepticism that the 10 second change would make any
difference.94 The change was not
based on science -- in fact, there is a suggestion that some paraTB can
survive pasteurization temperatures for 9 minutes73
or longer.172
Despite the release of these findings, Nick Brown, the British
agriculture minister said on national television: "I drink pasteurized
milk and it is safe to do so...with confidence," a claim reminiscent of a
previous minister's assurances about beef from cattle infected with mad
cow disease.196 According to the
Royal Statistical Society, contaminated beef still has the worst-case
scenario potential of killing 13 million people who consumed it and are
currently incubating the disease which Britain's health secretary called
the worst form of death imaginable.8
The same assurances are echoed in the United States. For example, the
director of the USDA National Animal Disease Center, feeling assured that
pasteurization eliminated any health threat said, "I don't hesitate to
feed [milk] to my 8-year-old."187 The
FDA chooses to continue to base national safety policy on the single
flawed USDA study,97 even now that
the study has been superseded by proof that its conclusions are wrong (the
United States mandates virtually the same pasteurization method that is
used in Britain and Ireland).2
The FDA's continued insistence that pasteurization eliminates the risk
of contracting paraTB -- despite clear evidence to the contrary -- puzzled
Kurt Gutknecht, the editor of the highly respected industry publication
Wisconsin Agriculturist. He called up Joe Smucker, the leader of the
FDA's Milk Safety Team, and asked him about the FDA's official "commercial
pasteurization does indeed eliminate this hazard" statement. Smucker
replied that he did not have "clearance from the FDA" to speak to him on
the subject. Surprised at Smucker's reluctance to talk to him, the editor
went to the official FDA spokesperson, who described the refusal of an FDA
official to not respond directly to press inquiries as "very unusual."
Gutknecht turned his attention back to the Milk Safety Team which no
longer returned his phone calls.48
The industry and/or131 government
knows, however, what kind of time bomb they're sitting on.61
According to one industry expert, the incrimination of MAP in human
disease would cause enormous economic damage to animal agriculture
industries. An article in Milk Science International entitled "Is
Mycobacterium paratuberculosis a possible agent in Crohn's
Disease?" warns that "the present state of knowledge is...potentially
catastrophic for the dairy industry should existing information be used in
a sensationalist manner."96
Johne's disease is one of the most difficult diseases to recognize and
control.26 This is in part because of
MAP's ability to resist destruction in the natural environment. It has
reservoirs in pasture and, perhaps, in other animal populations.
Paratuberculosis has spread, for example, from dairy cattle to wild,
free-ranging white-tailed deer in the state of Connecticut.28
The chief reason that paraTB is so hard to prevent and control, however,
is its notoriously covert nature.
Paratuberculosis has been called a "spectral disease,"139
a "hidden threat,"171 an "insidious
problem for the nation's dairy herds."134
Although infections are usually initiated during calfhood, clinical
disease does not appear until adulthood.146
During this incubation period, which can last between 6 months151
and 15 years,186 the infection is
invisible.199 Sub-clinically infected
animals don't have diarrhea or other typical visible signs of Johne's, but
they are carriers and can shed the bacteria into the environment, giving
paraTB ample opportunity to become entrenched in a herd before it is
apparent that a problem even exists.129
In this way, the Johne's disease problem has been likened to the tip of
an iceberg -- the so-called "iceberg effect."199
By the time a single clinical case surfaces, five37
to fifteen63 or twenty190
others may be infected in the herd. If the clinically affected animal had
been born on the farm, a minimum of 25 other animals are probably infected
-- perhaps as many as 50 -- and less than 30% of those would be detectable
by currently available tests.199
Johne's may also be clinically hard to detect. While in some instances
the disease progresses relatively rapidly, with the interval between the
appearance of wasting and death measured in months, in other cases, after
the initial loss of condition, there may be no clinical deterioration for
long periods of time. Since the first signs of clinical disease are
progressive weight loss and a drop in milk production, farmers may just
cull the animal without requesting further diagnosis.148
Also, like Crohn's, Johne's can go into periods of remission which can
last for weeks or even months.26
Finally, Johne's can mimic other diseases like intestinal parasitism,
malnutrition, salmonellosis, winter dysentery, etc.190
Traditional control methods have involved culling infected animals and
using hygiene methods to prevent new infections.32
Removing infected animals alone has proven ineffective because of the
latency period and because the bacteria survive so well outside the body.
As one commentator noted, "An iceberg is not destroyed by the removal of
the tip!"138 Another proposal has
been to kill off the entire herd, an option termed "herd disposal." The
plan would then be to disinfect the barns and wait a year or so before new
animals are allowed to pasture. This measure will likely never be
initiated, though, because paraTB is so widespread that the resulting
financial burden would be considered too great.26
After culling, the next most effective action is considered to be
segregation of the infected animals.142
Strict hygiene, down to the washing of boots, is necessary to prevent
cross contamination -- only a few grams of manure are needed to infect a
calf.133 Surveys show that many of
these basic steps are not followed, however. For example, in approximately
a third of operations, the cows' udders are not routinely washed prior to
collecting colostrum or before nursing.190
While some calves are infected in utero,32
removing newborn calves from the mother immediately upon birth is
considered an effective control measure because it eliminates the
newborn's attempt to nurse and risk ingesting infectious manure.190
Currently, about two thirds of dairy operations report taking the calf
away from the mother within 24 hours.190
There are fears among the animal welfare community that Johne's disease
management will intensify this irresponsible69
practice.
Disposal of infectious feces creates quite a problem. Some industry
specialists have advocated special landfills, while others have made the
potentially hazardous proposal to "as a last resort, spread [it] on
permanent cropland."26
Despite its pervasiveness and its ability to severely impact milk
production and destroy whole herds of cattle, Johne's disease remains an
industry problem that is not openly discussed.106
In an article entitled "Johne's Disease: A Dairy Industry Perspective,"
Johne's is described as "something that farmers talk about secretly --
whisper behind hands." One dairy scientist stated that in all his years he
had never heard an open, frank discussion of Johne's disease and calls for
an end of the "whispering campaign."5
Dairy farmers try to hide the fact that they have the disease in their
dairy herds.61 As an article in
Cornell Veterinarian notes, "Farmers prefer not to acknowledge its
presence and enshroud suspect cases with secrecy."26
It is a problem that is kept out of sight and out of mind. As one dairy
farmer put it, "It's [Johne's] a dirty word. It's like AIDS -- you don't
talk about it."54
This conspiracy of silence extends beyond the producers to encompass
the entire industry to the point of interfering with scientific dialogue.24
From the Journal of Dairy Science: "Fear of consumer reaction...can
impede rational open discussion of scientific studies."34
Without doubt, says Chiodini, "the dairy and regulatory industries are
concerned vocally...but their concern is limited to the possibility of
'bad press' to the industry rather than a concern for the truth or public
health."24
The secrecy has successfully bred ignorance. Over a century after the
disease was identified, almost half of all dairy farmers nationally
surveyed by the USDA didn't know anything about the disease.106
And those with the largest herds -- the herds most likely to be infected106
-- were found least likely to have known of the disease.195
Karen Meyer, then executive director of the nonprofit Paratuberculosis
Awareness & Research Association (PARA), placed the blame on the
representatives of the dairy industry. At a meeting of the USDA's United
States Animal Health Association (USAHA), she challenged dairy producers
to become more proactive. "If there are organizations you have been
relying on for your information and to protect your interests, they have
failed you miserably."118 "I think we
underestimate farmers," she told the Wisconsin Agriculturist. "If
they even thought they were making someone sick, it would break their
hearts."61
The USDA has been accused of continuing to keep its head in the sand.
Industry specialists blame the federal government for "grossly
underfunding" research, with less than one percent of its animal disease
grant budget allocated to Johne's.61
As Alan Kennedy, a co-founder of PARA and himself a sufferer of Crohn's
disease remarked, "yet another case of CJD -- Conflicting Job
Description." The USDA is mandated to regulate animal industries and food
safety, but it is also responsible for promoting these same agricultural
products.201
The first US case of Johne's was discovered in Pennsylvania in 1908.182
Almost a century later there is still no mandated control program,138
even though as far back as 1922 scientists published warnings of the
danger posed by the disease and outlined effective methods of controlling
and eradicating it. Efforts to control and eradicate Johne's disease have
been grossly inadequate.61 "In the 75
years following the release of that publication, there's very little that
any state has done to try to control the disease," says Collins, the
University of Wisconsin veterinary researcher. Meanwhile, as predicted in
1922, the disease has continued to spread silently and surely. According
to the USDA's figures, there are now three quarters of a million cattle
infected with paraTB in the United States.130
The reason that Johne's has spread to such a degree is because there
have been no direct constraints on the transport of infected animals.142
Almost without exception, paratuberculosis is introduced into a herd
through the addition of an asymptomatic, infected carrier animal. Almost
every infected herd can trace the infection to the purchase of an infected
cow183 that appeared healthy when
offered for sale.194 Disturbingly,
the USDA found that dairy farmers with infected herds were no less likely
to sell replacement cows to other farms than owners of noninfected herds.190
Regulatory vets know and accept this fact, acknowledging that movement
restrictions on infected animals must exist for an effective control
program. However, as described in the Veterinary Clinics of North
America, "if the voluntary program imposes movement restrictions, it
could quickly become a regulatory program and not have widespread support
and participation from the livestock industry."169
In fact, the Code of Federal Regulations (part 80) was recently
changed to remove restrictions on the interstate movement of Johne's
disease positive animals.127 The
change was made because of pressure from the livestock industry.169
Though not putting its money where its mouth is, the USDA insists that
the agency is doing everything it can with regard to Johne's disease.61
The USDA, for example, cites the formation of the National Johne's Working
Group (NJWG) in 1994. However, the executive committee of the group is
composed of three people: one is John Adams of the National Milk Producers
Federation and another is Gary Weber, a director of the National
Cattleman's Beef Association.201
For those that remember the Oprah Winfrey mad cow fiasco, Weber was the
cattleman defending cow cannibalism. "Now keep in mind," he said on that
show, "before you -- you view the ruminant animal, the cow, as simply a
vegetarian -- remember that they drink milk." Years earlier, in response
to activists' requests that farmers discontinue the practice of feeding
rendered animal protein to animals raised for slaughter, he told industry
publication Food Chemical News that the cattle industry could
indeed find economically feasible alternatives to such a practice, but
that the cattlemen's association did not want to "set a precedent of being
ruled by activists."137
Not surprisingly, the NJWG has officially come out against making
Johne's a reportable disease, advocating that all attempts at control be
voluntary.169 In a moment of rare
candor, one NJWG member explained why: "If the farmers have to report
positive cows, then it will be like the sheep scrapie [mad sheep disease]
program. Instead of reporting the disease, the farmers will 'shoot, shovel
and shut up.'"119
A year earlier, a national paratuberculosis certification program had
been started in order to identify low risk herds, but only 1% of dairy
operations reported participating in the program, citing associated costs.190
Less than 15% of the dairy producers appear to test for Johne's.106
In 1997, the NJWG set up a similar program designed to be more affordable,15
but again chose to keep it strictly optional, relying on the "livestock
industry in each state to sell its economic advantage to its members."169
As a concession to the industry, there is still no federally mandated
Johne's disease control program.169
Some states have Johne's control programs, but without exception they are
noncompulsory.123 Just as government
deregulation of industry may have led to the mad cow disaster in Europe,
the lack of industry accountability may also play a pivotal role in the
human consequences of the paratuberculosis epidemic.114
The United States is being left behind in the worldwide race to
eliminate paraTB.118 The Netherlands,
one of Europe's largest dairy exporters, has pledged to eradicate
paratuberculosis by the end of this year by instigating a compulsory
eradication program.189 "To minimize
the risk of human exposure to paratuberculosis" is one of the explicit
reasons given for the Dutch program.47
Sweden seems to be closest to winning the battle, probably because it was
the first country whose control efforts were nonvoluntary.141
Australia is currently also certifying herds with a view to eradication.72
Although there are currently no restrictions on international trade as a
result of the disease,106 that may
well change and potentially threaten America's $700 million dairy product
export industry.189
Mike Collins began his messages to both the Johne's Disease Committee
and the general session of the USAHA with the same words: "Don't shoot the
messenger."73 Rather than
participating in serious dialogue around the issue, the dairy industry has
been accused of spending its energies slinging mud at researchers in the
field,61 giving lip service, and
vainly hoping it just all blows away.24
Christine Rossiter, senior extension veterinarian with the Cornell
University Veterinary Diagnostic Laboratory, told the Wisconsin
Agriculturist that those who decide to address the issue are put at
risk and there's "no value placed by the industry on a person who wants to
do something about Johne's. Nobody wants to take it on."61
At an international colloquium on paratuberculosis, Chiodini expressed
his view that the current focus of the American dairy industry "could put
the industry in the same light as the tobacco industry, being accused of a
cover-up and faced with all sorts of liabilities."24
Paul Strandberg, Assistant Attorney General of the State of Minnesota
warned the Johne's Disease Committee that if they chose to be less than
forthright about the possible link between milk and beef and Crohn's
Disease, they could wind up on 60 Minutes in the middle of a media
circus.119
In order to put the problem in perspective and get the issue out in the
open, the consumer movement needs to get a study of retail milk supplies
in the United States funded. That is the recommendation of PARA.121
That is the recommendation of researchers in the field.124
Not only has industry allegedly "totally ignored" this approach,24
one observer wrote that it would be "political suicide" for a researcher
in the United States to even suggest such a thing.61
However, there have been two brave souls. Year after year, Chiodini and
Hermon-Taylor, world-recognized authorities on MAP and Crohn's, have
submitted proposals to the USDA and to the FDA to test retail milk
supplies, and year after year their proposals have been rejected.62
At a meeting of the USAHA, a resolution was debated on whether or not
to recommend that the USDA test retail dairy products in the United States
for the presence of live paraTB bacteria. John Adams, the National Milk
Producers Federation executive member of the NJWG, was quite vocal in his
opposition: "The FDA has already stated their position. They are confident
that pasteurized milk is safe. We don't need to test retail milk."119
Steve Merkel, a founding member of PARA whose wife has suffered with
Crohn's disease since 1960,19
replied: "With all due respect, sir, if milk is as safe as you say it is,
then retail testing will simply confirm that fact. Are you afraid of
retail milk testing because you are afraid of what you might find?" The
resolution was voted down by an overwhelming majority.119
PARA kept at it. Finally, in 1999, PARA successfully submitted two
resolutions to the Johne's Disease Committee, one recommending the testing
of retail milk and milk products for the presence of live MAP and another
recommending research to determine what cooking temperatures are needed to
reliably kill MAP in ground beef. Although both resolutions passed
unanimously in open committee, they were later voted down behind closed
doors. PARA saw this as the USAHA going on record as deliberately choosing
ignorance about the presence of MAP in food products for human
consumption.119
The USAHA tried to justify why the resolutions were quashed: "During
the discussions of these resolutions, there was much concern about the
feasibility of end-product testing of milk and meat for an organism that
science has not confirmed as being the cause of Crohn's in humans, and the
usage of this information." In the opinion of PARA, as expressed in a
letter to the USAHA president-elect, "this statement presents USAHA as not
only primarily self-serving, but further, is blatantly contemptuous of
both its own member producers and the American public." The letter
concludes "We at PARA are saddened that USAHA has chosen to be part of the
problem rather than part of the solution."119
The USAHA statement reveals the gamble the industry is willing to take.
In Britain, when asked what the industry planned to do about
paratuberculosis, spokespersons said that it was "something that bears
watching"201 but that they "preferred
to defer action" until paraTB is proven to cause disease in humans.84
This sounded all too familiar to the British public after the mad cow
debacle, where the beef industry made the same wager -- and lost.177
According to some social science studies, it was the British public
authorities' decade-long insistence on the safety of beef that did the
most damage to the public trust.79
The American dairy industry is similarly gambling not only with the
health of consumers, but with their own financial health. The financial
impact of paraTB is enormous;30
paratuberculosis currently costs the American livestock industry over a
billion dollars a year.61 A collapse
in consumer confidence could raise that figure much higher.
"If MAP is ultimately shown not to be the cause of Crohn's disease,"
Chiodini argues, "then the industries have taken the appropriate position
of 'lip-service,' to give an image of concern."24
If, however, -- as PARA phrased it in an open letter to the industry --
"dairy products become associated with the dreadful, life-destroying
disease known as Crohn's disease, your markets may also collapse and may
never recover. The image of dairy foods as being necessary for good
nutrition, carefully propagated and nurtured by you for decades, may be
destroyed."124
At the present time, only testing of milk has been conducted (and only
in the United Kingdom). All other dairy products have been neglected
(cheese, yogurt, etc.). The only safe policy would be either to test all
milk before it is used to make other dairy products or to test all dairy
products. One third of cheese produced in the United States, for example,
is made from raw unpasteurized milk, in which one could expect the highest
levels of paraTB bacteria.101 Cheese
manufacturers rely on the salty acidic environment of cheese to inhibit
bacterial growth,181 but MAP is
resistant to such conditions.181 Even
less robust mycobacteria can survive in soft cheese for at least 3 months
and in hard cheese for up to 10 months.76
Reportedly, at the University of Wisconsin, there is currently a research
project which is investigating the survival of Mycobacterium
paratuberculosis in cheese.86
Since MAP can survive freezing for at least a year,88
products such as ice cream may also be implicated.26
Ice cream may also come from less rigorously pasteurized milk.121
Other dairy products like butter, yogurt, and infant formula must also be
high research priorities.124
The standard veterinary recommendation when a cow is diagnosed with
Johne's is to have her sent to slaughter. Beef from Johne's cattle is not
prevented from being sold for human consumption because paratuberculosis
is not officially considered a human pathogen. End-stage animals, their
bodies dripping with literally trillions of paratuberculosis bacteria, are
ground straight into hamburger meat.123
When Crohn's patient advocates found out that infected tissues from
animals with severe clinical paratuberculosis were funneled into the human
food supply, they were described as, not surprisingly, "abhorred and
nauseated."201
In the advanced stages of Johne's disease, MAP bacteria course through
the cow's blood stream, infecting her internal organs, and possibly her
muscle tissue (so far, no one has tried culturing MAP from a cow's muscle
tissue). Even if the muscle tissue didn't contain large numbers of MAP
before the infected cow's death, when she's slaughtered it seems
impossible to ensure that feces do not contaminate the various tissues
that are taken from her, as evidenced by the numerous E. coli food
poisoning deaths in recent years.123
As a scientist put it: "Consequently, both preharvest and postharvest
contamination of food products originating from cattle is plausible."34
Although Americans eat 2.6 billion pounds of culled dairy cows
annually, most hamburger meat comes from cattle raised for beef. In 1984,
about one percent of US beef cattle were found positive for Johne's
disease. Research is ongoing at the USDA to determine the current
prevalence of Johne's disease in beef cattle, but since Johne's is such a
hidden disease, is not reportable, and is not the subject of a mandatory
control program, one might suspect that the incidence has increased
significantly as it has in the dairy cattle population.123
In spite of this situation, lack of awareness among beef producers is even
greater than in dairy producers. The USDA Center for Animal Health
Monitoring reports that 69.8% of US beef producers "had not heard of it [Johne's]
before." And less then 10% of producers had any knowledge beyond name
recognition.43
MAP bacteria probably survive standard cooking temperatures.
Mycobacterium paratuberculosis is the most heat-resistant
mycobacterium present in retail beef.103
Even well-cooked meat may contain live paraTB. The USDA recommends that
hamburgers be cooked to 71� C (160� F). An unpierced roast or steak need
only reach an internal temperature of 63� C (145� F). Studies show
prolonged exposure to at least 74� C (165� F) may be necessary to
eliminate the paratuberculosis bug.123
Mycobacterium paratuberculosis is also resistant to nitrites and
the smoking process used in sausage production.102
MAP may contaminate other meats as well -- paratuberculosis is suspected
in pigs and chickens.139
Milk may be more dangerous to consume than meat, though, in regards to
paratuberculosis. MAP is thought to survive digestion when carried in a
vehicle like milk, because -- as designed by nature -- milk buffers the
stomach environment to a near-neutral pH. In meat however, MAP's ability
to survive digestion by stomach acid is less certain.
Municipal water supplies must also be assessed for risk because surface
waters contaminated by agricultural run-off feed the domestic water
supplies of many communities in the United States.115
One of the reasons why paraTB has been called a "superbug" is because of
its ability to survive in the environment for prolonged periods.160
Mycobacteria like paraTB are one of the oldest forms of life. They have
survived on this planet for over a billion years which has allowed them to
adapt.67 In the environment, MAP has
a thick, waxy cell wall which protects it121
-- it can last for 9 months in mud,139
almost a year in manure,76 and two
years in water. Standard domestic water treatment such as filtration and
chlorination are probably ineffective against paraTB.115
There have been a few disconcerting143
reports of MAP bacteria cultured from drinking water, both in Europe188
and from the water supply of a major American city.14
Europe's Drinking Water Inspectorate has commissioned a study into the
distribution and fate of MAP in drinking water treatment;91
the same inquiry should be happening here.
The development last year with the most serious ramifications was
published in the April 2000 issue of the American Journal of
Gastroenterology. Knowing that cows with Johne's disease shed
paratuberculosis into their breast milk, researchers wondered whether
paratuberculosis bacteria could be detected in the milk of human mothers
with Crohn's disease. Researchers also knew that there were reports of
mothers with other mycobacterial diseases like leprosy shedding bacteria
into their milk. So they examined two mothers with Crohn's who had just
given birth and found paratuberculosis bacteria growing in both the
mothers' breast milk, but not in the breast milk from control mothers
without Crohn's. While breast-feeding has not been found to be a risk
factor for Crohn's and may, for unknown reasons, actually have a
protective effect,143 the presence of
MAP in the breast milk of mothers with Crohn's not only adds support to
the role of MAP in the pathogenesis of Crohn's disease,112
but shows how new generations could be exposed to paraTB.158
Despite the fact that M. paratuberculosis is now a known human
pathogen, it continues to be tolerated in our food supply.74
After finding of MAP in their retail milk supply, the Food Safety
Authority of Ireland (FSAI) now requires that cattle infected with Johne's
be excluded from the food supply. The flesh from an infected cow is no
longer considered fit for human consumption and her milk is simply dumped.176
Karen Meyer of PARA commented, "The government of Ireland is to be
commended for exercising the precautionary principle. Instead of trying to
sweep the problem under the rug, they acted swiftly to give human health
priority over special interests."77
The paratuberculosis problem in Ireland is minimal compared to that of
the United States. According to the chief executive of the FSAI, of the
7.6 million cattle in Ireland, there are only 12 reported cases of Johne's
disease. Nineteen percent of Irish retail milk samples grew out live
paraTB and researchers only found 12 cases of Johne's disease in the
entire country. Obviously, as the FSAI concedes, this may be an
underestimate, but in the United States the paratuberculosis problem is
exponentially worse. The estimated prevalence in the United States is some
20,000 times greater than that of Ireland.1
If any country should be preventing contamination of the human food
supply it should be the United States, which has the highest prevalence of
Johne's disease in the world.122 At
their Fall 2000 meeting, however, the NJWG continued to propose only
voluntary measures to protect cattle health and no measures to protect
human health.197 The removal of
clinically infected animals from the human food supply alone has been
modeled as having a highly significant impact.113
This could evidently be accomplished with relative ease, but as yet there
has been little effort to do so.74
When asked how long it would take to clean up America's herds if suddenly
no milk from Johne's-positive cows could be sold, one Johne's Disease
Committee member said, "About six months."119
The consumer movement also needs to fight to make Crohn's a reportable
illness.92 The official FDA stance
that pasteurization eliminates MAP is no longer tenable and must be
continuously confronted with the British retail milk studies which put an
end to the pasteurization debate once and for all. An extensive Freedom of
Information Act search must be initiated to unearth suppressed documents.
For example, seven years ago, Canada's agriculture department produced a
food safety risk assessment paper concluding that the paraTB-Crohn's link
was something about which to be concerned. The document, however, was
stamped "Protected. Not for Distribution" and was as such buried.19
These are the kinds of documents the consumer movement needs to get a hold
of.
In Dr. Hermon-Taylor's view, "There is overwhelming evidence that we
are sitting on a public health disaster of tragic proportions."40
Europe's Scientific Committee on Animal Health and Animal Welfare,
however, concluded that the currently available evidence was insufficient
to confirm or disprove the theory.145
This uncertainty should not impede the government from taking concrete
steps to prevent further potential human catastrophe. If the British
government had acknowledged the precautionary principle, many lives may
have been saved. The same exact things being said now about paraTB, "We'll
wait and see," were those things said about mad cow disease. Once proof
comes around, however, it may be too late.177
The precautionary principle is the basis for most European
environmental law and is playing an increasingly important role in health
policies worldwide.51 Basically, it
states, "If one has a reasonable suspicion that something bad might be
going to happen, one has an obligation to try to stop it."200
An ounce of prevention is worth a pound of cure.
On a personal level, the Crohn's advocacy group Action Research
recommends that people who want to reduce their risk of infection or
reinfection -- especially those with Crohn's disease, or their close
relatives (who might be genetically predisposed) -- should stop eating
dairy products unless they are effectively boiled first.38
PARA recommends that cheese should be heated to the temperature of boiling
water, 100� C (212� F), to reduce the threat. Thus, grilling cheese under
direct heat for a few minutes (so that it "bubbles"), or cooking it in
oven-baked meals, such as oven-baked lasagna, should effectively sterilize
the cheese. The same applies to other dairy products, such as milk,
yogurt, or butter.86
The reason the industry doesn't pasteurize all milk at that temperature
to be safe, is because it could affect the taste of the milk. As the FSAI
put it, "there is an upper temperature beyond which unacceptable changes
to the taste of milk start to occur."31
Steve Merkel of PARA would have governments mandate raising the minimum
pasteurization temperature to levels that ensured safety regardless, "even
if it means that milk doesn't taste the same as it did. Human health must
take precedence over taste."80
Stricter pasteurization may not be the answer, though. Although there
is recent evidence that living MAP bacteria cause Crohn's,83
even dead MAP may be able to trigger disease.31
For example, one of the reasons that the vaccine for Johne's is so seldom
used is because it is so dangerous to handle.106
Even though the vaccine is made out of killed MAP bacteria, the human
immune system can react so violently just to the presence of MAP proteins,
that accidentally injected into humans (or purposefully into other
primates), the MAP vaccine causes a chronic progressive inflammation which
can last for years128 or may even
necessitate amputation of the injection site.22
Closely related bugs like leprosy can have similar effects.115
So even if MAP is pasteurized to death, drinking the remnants of the
bacteria may still cause a problem.
With this in mind, it may be more prudent to avoid dairy altogether.
Although ingesting relatively few organisms may be able to cause
infection, the human infective dose is not known.186
It is also not known how heavily the milk supply is contaminated in this
country. The most esteemed pediatrician of all time, Dr. Benjamin Spock,
advised that children be raised vegan, with zero exposure to dairy
products for a variety of reasons.193
Especially considering the risk of paratuberculosis in milk, this would
seem sensible advice, particularly for children and adolescents.110
There is a wide variety of dairy product substitutes -- soy and rice
milks, cheeses, ice creams, yogurts, etc. -- making animal-derived dairy
products unnecessary.
Because the spread of Johne's disease is related to stocking density,
the epidemic of Johne's disease is one more indictment of factory farming.3
The unnatural concentration of animals raised for slaughter, for example,
has led to other human tragedies including the single worst epidemic in
recorded world history, the 1918 influenza pandemic.41
In that case, the unnatural density and proximity of pigs and ducks raised
for slaughter led to the deaths of upwards of 40 million people.87
This potential crisis is also an indictment of an industry that
continues to risk public safety and a government that seems to protect
business interests over those of the consumer. As Karen Meyer recently
told the LA Times, "There comes a point in time where consumer
health takes precedence over commercial concerns."97
Every few hours, another child in this country is diagnosed with
Crohn's disease and may be condemned to a life of chronic suffering.62
The balance of evidence strongly suggests a causative link between
Mycobacterium paratuberculosis and Crohn's disease.145
This public health issue has been at the periphery of the dairy industry's
agenda for years, a nagging concern on the back burner.61
The consumer movement needs to move it to the front burner and needs to
turn up the heat.
References
- 21,000 to be more exact, dividing the US prevalence .034 per (USDA:
APHIS: VS, CEAH, NAHMS. Johne's Disease on US Dairy Operations.
Fort Collins, CO: NAHMS; 1997 Oct. N245.1097) by the Irish prevalence
1.6x10-6 per (Statement in relation to UK MAFF announcement. FSAI Press
Release; 1998 Aug 11).
- 72� C for 15 seconds in the US and 71.7� C for 15 seconds in the UK
per (Lund BM, Donnelly CW, Rampling A. Heat resistance of
Mycobacterium paratuberculosis. Lett Appl Microbiol
2000;31:184-5).
- Adamson C, McGowan P. Blame placed on intensive farming. The
Times (London) 2000 Oct 26:10-1.
- Andus T, et al. Etiology and pathophysiology of inflammatory bowel
disease. Hepatogastroenterology 2000;47:29-43.
- Arbuthnot A. Johne's disease: a dairy industry perspective. In:
Milner AR, Wood PR, editors. Johne's Disease. Melbourne,
Australia: CSIRO Publications; 1989. p. 99-103.
- Assuming a billion lymphocytes/ml as a reasonable defining
concentration of pus, regulations per (Heeschen WH. Codex regulations
and food safety. Bulletin of the International Dairy Federation
1997;319:24), a standard 20 drops/ml, and a "glass" as 500 cc, Grade A
milk may have more than seven drops of pus per glass.
- Atkins P, Brassley P. Mad cow and Englishmen. History Today
1996;46:14.
- Bleifuss J. A 21st century plague? Britain's mad cows may harbinger
the deaths of millions. In These Times 2000 Feb 7:2.
- Borody TJ, et al. Treatment of severe Crohn's disease (CD) using
rifabutin-macrolide-clofazimine combination: interim report. Am J
Gastroenterol 1998;114(4):G3842.
- Borody TJ, et al. Treatment of severe Crohn's disease (CD) using
rifabutin-macrolide-clofazimine combination: results at 30-37 months.
Gut 2000;46:A1334.
- Boyce N. Milk theory stirs up bowel disease experts. New
Scientist 1998 Feb 7.
- Brooks A. Quality of UK milk to be studied. BMJ 1998;317:491.
- Brown D. Milk heat treatment increased. The Daily Telegraph
1998 Aug 12.
- Brown ST, et al. Mycobacterium paratuberculosis in Crohn's
disease. In: Chiodini RJ, Hines ME II, Collins MT, editors.
Proceedings of the 5th International Colloquium on Paratuberculosis;
1996 Sep 29-Oct 4; Madison, Wisconsin. International Association for
Paratuberculosis; 1996. p. 316-23.
- Bulaga LL, Collins MT. US voluntary Johne's disease herd status
program for cattle. In: Manning EJB, Collins MT, editors. Proceedings
of the 6th International Colloquium on Paratuberculosis; 1999 Feb
14-18; Melbourne, Australia. International Association for
Paratuberculosis; 1999.
- Cann PA, Bramble MG. An open pilot study of antimicrobial agents in
the management of resistant Crohn's disease. Gut 2000;46:A1335.
- Centers for Disease Control and Prevention. CDC surveillance
summaries. MMWR 1996;45:35.
- Cerf O, Griffiths MW. Mycobacterium paratuberculosis heat
resistance. Lett Appl Microbiol 2000;30:341-3.
- Chamberlain L. Lactose intolerant. Cleveland Free Times 1999
Jun.
- Chamberlain L. Media and censorship: a Project Censored Award is a
dubious achievement. Cleveland Free Times 2000 Apr 12-18.
- Chiodini RJ. Antimicrobial agents and Crohn's disease: do they have
a therapeutic role? Ital J Gastroenterol Hepatol 1998
Dec;30(6):593-8.
- Chiodini RJ. Crohn's disease and the mycobacterioses. Clin
Microbiol Rev 1989;2:90-117.
- Chiodini RJ. Historical overview and current approaches in
determining a mycobacterial etiology of Crohn's disease. In: Mulder CJJ,
Tytgat GNJ, editors. Is Crohn's Disease a Mycobacterial Disease?
Dordrecht, The Netherlands: Kluwer Academic Publishers; 1992. p. 1-15.
- Chiodini RJ. M. paratuberculosis in foods and the public
health implications. In: Chiodini RJ, Hines ME II, Collins MT, editors.
Proceedings of the 5th International Colloquium on Paratuberculosis;
1996 Sep 29-Oct 4; Madison, Wisconsin. International Association for
Paratuberculosis; 1996. p. 353-65.
- Chiodini RJ. Mycobacterium paratuberculosis: an emerging
human pathogen. In: Proceedings of the 2nd International Colloquium
on Paratuberculosis; Alfort, France. International Association for
Paratuberculosis; 1988. p. 141-5.
- Chiodini RJ, et al. Ruminant paratuberculosis (Johne's disease): the
current status and future prospects. Cornell Veterinarian
1984;74:218-62.
- Chiodini RJ, Rossiter CA. Paratuberculosis: a potential zoonosis?
Vet Clin North Am Food Anim Pract 1996 Jul;12(2):457-67.
- Chiodini RJ, van Kruiningen HJ. The prevalence of paratuberculosis
in culled New England cattle. Cornell Veterinarian
1986;76:91-104.
- Clark S. That gut feeling. Sunday Times 1996 Jul 28.
- Cocito C, et al. Paratuberculosis. Clin Microbiol Rev
1994;7:328-45.
- Collins JD, et al. Mycobacterium Paratuberculosis: Does It
Contribute to Crohn's Disease? Dublin: FSAI; 2000.
- Collins MT. Diagnosis and control of paratuberculosis. In: Chiodini
RJ, Collins MT, Bassey EOE, editors. Proceedings of the 4th
International Colloquium on Paratuberculosis; 1994 Jul 17-21;
Cambridge, United Kingdom. International Association for
Paratuberculosis; 1994. p. 325-44.
- Collins MT. M. paratuberculosis in foods and the public
health implications. In: Chiodini RJ, Hines ME II, Collins MT, editors.
Proceedings of the 5th International Colloquium on Paratuberculosis;
1996 Sep 29-Oct 4; Madison, Wisconsin. International Association for
Paratuberculosis; 1996. p. 352.
- Collins MT. Mycobacterium paratuberculosis: a food-borne
pathogen? J Dairy Sci 1997;80:3445-8.
- Collins MT, Manning EJB. Johne's Disease: The International
Perspective. Madison, WI: Dept. of Pathobiological Sciences;
University of Wisconsin School of Veterinary Medicine.
http://www.iol.ie/~alank/CROHNS/johneint.htm
- Comerford C. Milk in link to stomach disease. The Independent
(London) 1998 Aug 11:2.
- Crohn's & Colitis Foundation of America, Inc. NIH seeks answers on
M. paratuberculosis and Crohn's. 1998 Dec 30.
http://www.ccfa.org/news/news1230.htm
- Crohn's and milk blamed on rabbits. The Herald (Glasgow) 1998
Aug 12:4.
- Crohn's disease may be caused by bacteria similar to TB microbe.
Biotechnology Newswatch 1999 Jul 5:5.
- Crohn's link with bacteria in milk. Chemist & Druggist 2000
Jan 29:11.
- Daily GC, Ehrlich PR. Development, Global Change, and the
Epidemiological Environment. Stanford, CA: Stanford University;
1995. Paper #0062.
- Dalziel TK. Chronic interstitial enteritis. BMJ 1913 Oct
25:1058-70.
- Dargatz DA, Wells SJ, Ott SL. Johne's disease and US cow-calf
operations. In: Manning EJB, Collins MT, editors. Proceedings of the
6th International Colloquium on Paratuberculosis; 1999 Feb 14-18;
Melbourne, Australia. International Association for Paratuberculosis;
1999.
- Douglas A. An open pilot study of antimicrobial therapy in patients
with unresponsive Crohn's disease. Gut 2000;46:A11.
- El-Zaatari FAK, Graham DY. Mycobacterial etiology of Crohn's
disease. In: Mulder CJJ, Tytgat GNJ, editors. Is Crohn's Disease a
Mycobacterial Disease? Dordrecht, The Netherlands: Kluwer Academic
Publishers; 1992.
- Engstrand L. Mycobacterium paratuberculosis and Crohn's
disease. Scand J Infect Dis 1995;98 Suppl:27-9.
- Experts from around the world gather to discuss paratuberculosis,
Johne's disease, and Crohn's disease. PARA News Release; 1999 Feb 19.
http://www.crohns.org/media/colloq.htm
- FDA claims milk safe, evades farm magazine editor's questions. PARA
News Release; 1998 Jul 20.
http://www.crohns.org/media/pr200798.htm
- Filder HM, et al. Specific detection of Mycobacterium
paratuberculosis DNA associated with granulomatous tissue in Crohn's
disease. Gut 1994;35:506-10.
- Fishman SJ, et al. Thalidomide therapy for Crohn's disease.
Gastroenterology 2000;199:596-602.
- Foster KR, Vecchia P, Repacholi MH. Science and the precautionary
principle. Science 2000 May 12:979-81.
- Freeman M. Angry reaction to Crohn's disease allegation. Farmers
Guardian 2000 Jan 28:7.
- Freyer FE. Lawsuit: hospital thwarted disease research. The
Providence Journal-Bulletin 1994 Oct 9:1B.
- Galloway JA. USDA reviewing milk safety standards; bacteria-disease
link examined. Wisconsin State Journal 1995 Feb 1:1A.
- Glynn MK, Bopp C, Dewitt W, et al. Emergence of multidrug-resistant
Salmonella enterica serotype Typhimurium DT104 infections in the
United States. N Engl J Med 1998;338:1333-8.
- Grant IR. Does Mycobacterium paratuberculosis survive current
pasteurization conditions? Appl Environ Microbiol 1988;64:2760.
- Grant IR, Ball HJ, Rowe MT. Effect of high-temperature, short-time (HTST)
pasteurization on milk containing low numbers of Mycobacterium
paratuberculosis. Lett Appl Microbiol 1998;26(2):166-70.
- Grant IR, Ball HJ, Rowe MT. Effect of higher pasteurization
temperatures, and longer holding times at 72� C, on the inactivation of
Mycobacterium paratuberculosis in milk. Lett Appl Microbiol
1999 Jun;28(6):461-5.
- Grant IR, Ball HJ, Rowe MT. A novel staining technique for assessing
clumping and viability of Mycobacterium paratuberculosis cells
during pasteurization. In: Chiodini RJ, Hines ME II, Collins MT,
editors. Proceedings of the 5th International Colloquium on
Paratuberculosis; 1996 Sep 29-Oct 4; Madison, Wisconsin.
International Association for Paratuberculosis; 1997.
- Gui GPH, et al. Two-year outcomes analysis of Crohn's disease
treated with rifabutin and macrolide antibiotics. J Antimicrob
Chemother 1997 Mar;39(3):393-400.
- Gutknecht K. Dire warnings about Johne's disease: a wake-up call for
the dairy industry? Wisconsin Agriculturist 1997 Dec.
- Gutknecht K. A needling question: does pasteurization really kill
M. paratuberculosis? Wisconsin Agriculturist 1998 Jul.
- Hansen D, Rossiter C. Clinical description and epidemiology of
Johne's disease in cattle. NJWG, a subcommittee of the Johne's Disease
Committee of the USAHA; 1999-2000 series.
- Helicobacter pylori in peptic ulcer disease. NIH Consensus
Statement 1994 Feb 7-9;12(1):1-23.
- Hermon-Taylor J. The causation of Crohn's disease and treatment with
antimicrobial drugs. Ital J Gastroenterol Hepatol 1998
Dec;30(6):607-10.
- Hermon-Taylor J. Mycobacterium paratuberculosis as a chronic
enteric pathogen in humans. In: Chiodini RJ, Collins MT, Bassey EOE,
editors. Proceedings of the 4th International Colloquium on
Paratuberculosis; 1994 Jul 17-21; Cambridge, United Kingdom.
International Association for Paratuberculosis; 1994. p. 174-80.
- Hermon-Taylor J, et al. Mycobacteria and the aetiology of Crohn's
disease. Inflamm Bowel Dis 1994.
http://www.iol.ie/~alank/CROHNS/paratub.htm
- Hermon-Taylor J, et al. Mycobacterium paratuberculosis
cervical lymphadenitis followed five years later by terminal ileitis
similar to Crohn's disease. BMJ 1998 Feb 7.
- Highly esteemed Professor of Animal Science Temple Grandin describes
the practice in Oliver W. Sacks' An Anthropologist on Mars
(1996): "That's one sad, unhappy, upset cow. She wants her baby, hunting
for it. It's like grieving, mourning -- not much written about it.
People don't like to allow them thoughts or feelings."
- History of Johne's disease. University of Wisconsin; 1997 Feb 19.
http://www.vetmed.wisc.edu/pbs/johnes/history.html
- Hornick DB. Nontuberculous mycobacterial lung disease. Chest
1988;93:550-5.
- Hoy A. Disease threat to a million sheep. Sydney Morning Herald
1997 Jul 30.
- Hulse V. Mad Cows and Milk Gate. Phoenix, OR: Marble Mountain
Publishing; 1996.
- Hulten K. Antibacterial therapy for Crohn's disease: a review
emphasizing therapy directed against mycobacteria. Dig Dis Sci
2000;45:445-56.
- Infective agents -- mycobacteria. Inflamm Bowel Dis 1997:131.
- Institute for Food Science and Technology. Mycobacterium
paratuberculosis and milk. Food Science and Technology Today
1998;12:223-7.
- Ireland bans milk, meat from cows infected with suspected Crohn's
bug. PARA News Release; 2000 Oct 6.
http://www.crohns.org/media/pr061000.htm
- Isselbacher KJ, et al. Harrison's Principles of Internal
Medicine. 13th ed. New York: McGraw-Hill; 1994.
- Jacob M, Hellstr�m T. Policy understanding of science, public trust,
and the BSE-CJD crisis. J Hazard Mater 2000;78:303-17.
- January 2000 FSAI report: Mycobacterium paratuberculosis --
does it contribute to Crohn's disease? PARA News Release; 2000 Oct 6.
http://www.crohns.org/media/pr061000.htm
- Johne's disease -- a growing threat to dairymen. Hoard's Dairyman
1981 Mar 25:456-60.
- Jones PH, et al. Chronic gastrointestinal diseases in dairy farmers
in England and the Welsh borders: is there an association between
Crohn's disease and bovine paratuberculosis? 9th Symposium for the
International Society for Veterinary Epidemiology and Economics;
2000 Aug 6-11; Breckenridge, Colorado.
- Kennedy A. Biopsy studies of Crohn's disease.
http://www.iol.ie/~alank/CROHNS/biopsy.htm
- Kennedy A. Does mycobacteria cause Crohn's disease?
http://www.iol.ie/~alank/CROHNS/welcome.htm
- Kennedy A. The prevalence of BJD (bovine Johne's disease).
http://www.iol.ie/~alank/CROHNS/johne.htm
- Kennedy A. Why IBD sufferers should only consume UHT or
ultra-pasteurized dairy products.
http://www.iol.ie/~alank/CROHNS/uhtmilk.htm
- Kiple KF, editor. The Cambridge World History of Human Disease.
Cambridge: Cambridge University Press; 1993.
- Larsen AB, et al. Survival time of Mycobacterium paratuberculosis.
Am J Vet Res 1956 Jul:549-51.
- Loftus EV, et al. Crohn's disease in Olmsted County, Minnesota,
1940-1993: incidence, prevalence, and survival. Gastroenterology
1998;114:1161-8.
- Lorber B. Are all diseases infectious? Ann Intern Med 1996
Nov 15;125:844-51.
- Lord Burlison. Crohn's disease. Debate in the House of Lords. 2000
Jun 19:Column 82.
- Lord Greenway. Ibid.
- Lord McColl. Ibid.
- Lord Turnberg. Ibid.
- Manning J. Milk may be linked to intestinal illness. Milwaukee
Journal Sentinel 1996 Sep 6:7.
- Mason O, Rowe MT, Ball HJ. Is Mycobacterium paratuberculosis
a possible agent in Crohn's disease? Implications for the dairy
industry. Milk Science International 1997;52:311-6.
- Maugh TH II. Milk may be the carrier of Crohn's. Los Angeles
Times 2000 Sep 18:S1.
- Maugh TH II. Plenty of relief...and skepticism. Los Angeles Times
2000 Sep 18:S1.
- Maugh TH II. Spreading a new idea on disease: mounting evidence may
link viruses and bacteria to everything from gallstones to Alzheimer's.
Los Angeles Times 1999.
http://www.sonic.net/melissk/spreadin.html
- May 10, 1998 issue per (Business Wire. Anti-milk group exposes claim
that normal pasteurization kills dangerous bacterium in milk. 1998 Jul
14).
- McDowell RM, McElvaine MD. Long-term sequelae to foodborne disease.
USDA: APHIS: ORACBA. Rev Sci Tech 1997 Aug;16(2):337-41.
- Merkal RS, Crawford JA, Whipple DL. Heat inactivation of
Mycobacterium avium-Mycobacterium intracellulare complex organisms
in meat products. Appl Environ Microbiol 1979;38:831-5.
- Merkal RS, Whipple DL. Inactivation of Mycobacterium bovis in
meat products. Appl Environ Microbiol 1980;40:282-4.
- Millar D, et al. IS900 PCR to detect Mycobacterium
paratuberculosis in retail supplies of whole pasteurized cows' milk
in England and Wales. Appl Environ Microbiol 1996;62:3446-52.
- Mishina D, et al. On the etiology of Crohn disease. Proc Natl
Acad Sci U S A 1996 Sep;93:9816-20.
- Mohr P. Yanking Johne's chain: with management, testing, and
vaccinating, the Steins plan to get this disease under control. Dairy
Today 1997 Nov.
- Monmaney T. Marshall's hunch. New Yorker 1993 Sep 20:64-72.
- Morgan KL. Johne's and Crohn's. Lancet 1987 May 2:1017-9.
- Moss MT, et al. Polymerase chain reaction detection of
Mycobacterium paratuberculosis and Mycobacterium avium subspecies
silvaticum in long-term cultures from Crohn's disease and control
tissues. Gut 1992;33:1209-13.
- Murray I. Crohn's linked to bacteria in milk. The Times
(London) 2000 Jan 25;Home News.
- Mycobacterium paratuberculosis and Crohn's disease: a
PatientCommunity.com interview with Dr. Ira Shafran. 2000 Oct 19.
http://ibd.patientcommunity.com/features/shafran.cfm?link_id=1679
- Naser SA, Shafran I, Schwartz D. Isolation of Mycobacterium avium
subspecies paratuberculosis from breast milk of Crohn's disease
patients. Am J Gastroenterol 2000;95(4):1094-5.
- Nauta MJ, van der Giessen JWB. Human exposure to Mycobacterium
paratuberculosis via pasteurized milk: a modeling approach. Vet
Rec 1998 Sep 12:293-6.
- Newsinger J. The roast beef of Old England. Int J Health Serv
1997;27:243-6.
- NIAID. Crohn's Disease -- Is There a Microbial Etiology?
Recommendations for a Research Agenda; conference held 1998 Dec 14;
Bethesda, Maryland.
- Nunes GC, Ahlquist RE Jr. Increasing incidence of Crohn's disease.
Am J Surg 1983;145:546-81.
- O'Sullivan K. Food group says Irish milk is safe. The Irish Times
1998 Aug 12:3.
- PARA executive director addresses Johne's disease groups. PARA News
Release; 1999 Nov 24.
http://www.crohns.org/media/pr241199.htm
- PARA takes the case for retail testing to USAHA. PARA News Release;
1998 Oct 15.
http://www.crohns.org/media/pr151098.htm
- PARA. MAP & Crohn's disease research. 1999.
http://www.crohns.org/research/index.htm
- PARA. MAP in food: the case for retail testing. Presented to the
Food Safety Committee of the USAHA; 1998 Oct.
http://www.crohns.org/foodsafety/retail.htm
- PARA. MAP in the United Kingdom. 1999.
http://www.crohns.org/government/uk.htm
- PARA. Mycobacterium avium subspecies paratuberculosis in beef
products. 1999.
http://www.crohns.org/foodsafety/beef.htm
- PARA. Mycobacterium avium subspecies paratuberculosis in
dairy products. 1999.
http://www.crohns.org/foodsafety/dairy.htm
- PARA. Phase III clinical trial of anti-paratuberculosis antibiotic
therapy begins in Australia. 1999.
http://www.crohns.org/research/austrial.htm
- PARA. Scientific facts about Mycobacterium paratuberculosis
and Crohn's disease.
http://www.crohns.org/research/scientificfacts.htm
- Paratuberculosis regulations changed. J Am Vet Med Assoc
2000;216:1695.
- Patterson CJ, et al. Accidental self-inoculation with
Mycobacterium paratuberculosis bacterin (Johne's bacterin) by
veterinarians in Wisconsin. J Am Vet Med Assoc 1988;192:1197-9.
- Pell AN. Manure and microbes. J Dairy Sci 1997;80:2673-81.
- Per (USDA: APHIS: VS, CEAH, NAHMS. Johne's Disease on US Dairy
Operations. Fort Collins, CO: NAHMS; 1997 Oct. N245.1097) an
underestimate of 3.4% of all dairy cows infected. Per (Dargatz D, et al.
What Do I Need to Know About Johne's Disease in Beef Cattle?
USDA: APHIS: VS; 1999 Aug. N309.899.
http://www.aphis.usda.gov:80/vs/ceah/cahm/Beef_Cow-Calf/bf97john.htm)
.4% of all beef cattle infected. Per (National Research Council,
Institute of Medicine. The Use of Drugs in Food Animals.
Washington: National Academy Press; 1999) 10 million dairy cattle, 100
million beef cattle in the United States.
- Please read Noam Chomsky's work on the duplicity of corporations and
the state.
- Prantera C, et al. Crohn's disease and mycobacteria. Biomed
Pharmacother 1989;43:295-9.
- Proceedings of the 1999 Cornell Nutrition Conference for Feed
Manufacturers; 1999 Oct 19-21; Rochester, New York. Ithaca, NY:
Dept. of Animal Science; Cornell University; 1999. p. 130.
- Ibid, p. 132.
- Project censored. PARA Newsletter 2000 Jul:2.
- Rampton DS. Management of Crohn's disease. BMJ 1999;319:1480.
- Rampton S, Stauber J. Mad Cow USA: Could the Nightmare Happen
Here? Monroe, ME: Common Courage Press; 1997.
- Richards WD. Environmental acidity may be the missing piece in the
Johne's disease puzzle. In: Milner AR, Wood PR, editors. Johne's
Disease. Melbourne, Australia: CSIRO Publications; 1989. p. 99-103.
- Riemann HP, Abbas B. Diagnosis and control of bovine
paratuberculosis (Johne's disease). Adv Vet Med 1983;27:481-505.
- Rose JDR, et al. Cardiff Crohn's disease jubilee. Gut
1988;29:346-51.
- Rossiter CA. On-farm control of Johne's disease in cattle
populations. In: Chiodini RJ, Hines ME II, Collins MT, editors.
Proceedings of the 5th International Colloquium on Paratuberculosis;
1996 Sep 29-Oct 4; Madison, Wisconsin. International Association for
Paratuberculosis; 1996. p. 132-9.
- Rossiter CA, Burhans WS. Farm-specific approach to paratuberculosis
(Johne's disease) control. Vet Clin North Am Food Anim Pract 1996
Jul;12(2):383.
- Sartor RB. M. paratuberculosis in foods and the public health
implications. In: Chiodini RJ, Hines ME II, Collins MT, editors.
Proceedings of the 5th International Colloquium on Paratuberculosis;
1996 Sep 29-Oct 4; Madison, Wisconsin. International Association for
Paratuberculosis; 1996. p. 366-73.
- Schwartz D, et al. Mycobacterium avium subspecies
paratuberculosis in Crohn's disease is an affirmative! 99th American
Society of Microbiology General Meeting; 1999 May 30-Jun 3; Chicago,
Illinois.
- Scientific Committee on Animal Health and Animal Welfare.
Possible Links between Crohn's Disease and Paratuberculosis.
European Commission: Directorate -- General Health & Consumer
Protection; Directorate B -- Scientific Health Opinions; Unit B3. SANCO/B3/R16/2000.
Adopted 2000 Mar 21:4.
- Ibid:9.
- Ibid:12.
- Ibid:13.
- Ibid:14.
- Ibid:17.
- Ibid:21.
- Ibid:23.
- Ibid:30.
- Ibid:39.
- Ibid:40.
- Ibid:46.
- Ibid:48.
- Ibid:49.
- Ibid:50-51.
- Ibid:51.
- Ibid:53.
- See, for example, Tom Regan's book The Case for Animal Rights
(1985).
- Seldenrijk CA, et al. T-cellular immune reactions (in macrophage
inhibition factor assay) against Mycobacterium paratuberculosis,
Mycobacterium kansasii, Mycobacterium tuberculosis, Mycobacterium avium
in patients with chronic inflammatory bowel disease. Gut
1990;31:529-35.
- Shafran I, et al. Endoscopic healing of Crohn's after antibiotic
treatment. Gut 2000;46:A9.
- Shafran I, et al. Humoral immune response of Crohn's patients for
Mycobacterium avium subspecies paratuberculosis. Gut
2000;46:A9.
- Shafran I, et al. Identification of Mycobacterium avium
subspecies paratuberculosis in Crohn's disease. Gut
2000;46:A324.
- Shafran I, et al. Rifabutin and macrolide antibiotic treatment in
Crohn's patients identified serologically positive for Mycobacterium
avium subspecies paratuberculosis. Gut 2000;46:A782.
- Smith KL, Hogan JS. Milk quality -- a worldwide perspective.
Annual Proceedings of the National Mastitis Council; 1998; St.
Louis, Missouri.
- Sockett DC. Johne's disease eradication and control. Vet Clin
North Am Food Anim Pract 1996 Jul;12(2):431-9.
- Some cases of Crohn's disease appear to respond to antibiotic
treatment: evidence suggests that a mycobacterium has a role in the
illness; investigators have tested clarithromycin alone and in
combination with rifabutin. Infectious Disease News 1996 Jul.
- Stabel JR. Johne's disease: a hidden threat. J Dairy Sci
1998;81:283-8.
- Stabel JR, Steadham EM, Boilin CA. Heat inactivation of
Mycobacterium paratuberculosis in raw milk: are current
pasteurization conditions effective? Appl Environ Microbiol
1997;63:4975-7.
- Stainsby KJ, et al. Antibodies to Mycobacterium paratuberculosis
and nine species of environmental mycobacteria in Crohn's disease and
control subjects. Gut 1993;34:371-4.
- Stark C. New foodborne disease estimates from CDC. Cornell
Cooperative Extension Food and Nutrition 1999 Sep/Oct.
- Stark C. Turkey safety information from USDA. Cornell Cooperative
Extension Food and Nutrition 1998 Nov/Dec.
- Statement in relation to UK MAFF announcement. FSAI Press Release;
1998 Aug 11.
- Stuttaford T. Lack of proof led to disaster. The Times
(London) 2000 Oct 26:4.
- Suenaga K, et al. Serum antibodies to Mycobacterium
paratuberculosis in patients with Crohn's disease. Dig Dis Sci
1999;44:1202-7.
- Sung N, Collins MT. Thermal tolerance in Mycobacterium
paratuberculosis. Appl Environ Microbiol 1998;64:999-1005.
- Sung N, Kaspar CW, Collins MT. Determination of D-values in studies
on the thermal tolerance of Mycobacterium paratuberculosis. In:
Chiodini RJ, Hines ME II, Collins MT, editors. Proceedings of the 5th
International Colloquium on Paratuberculosis; 1996 Sep 29-Oct 4;
Madison, Wisconsin. International Association for Paratuberculosis;
1997.
- Sung N, Kaspar CW, Collins MT. Kinetics of nonthermal inactivation
of Mycobacterium paratuberculosis. In: Chiodini RJ, Hines ME II,
Collins MT, editors. Proceedings of the 5th International Colloquium
on Paratuberculosis; 1996 Sep 29-Oct 4; Madison, Wisconsin.
International Association for Paratuberculosis; 1997.
- Sweeney RW. Preface. Vet Clin North Am Food Anim Pract 1996
Jul;12(2).
- Sweeney RW. Transmission of paratuberculosis. Vet Clin North Am
Food Anim Pract 1996 Jul;12(2):305-11.
- Targan SR, Murphy LK. Clarifying the causes of Crohn's. Nat Med
1995;1:1241-3.
- This may be particularly important in that the subjects were also
given probiotics (like acidophilus) which may confound the results per (Suenaga
K, et al. Serum antibodies to Mycobacterium paratuberculosis in
patients with Crohn's disease. Dig Dis Sci 1999;44:1202-7).
- Thompson DE. The role of mycobacteria in Crohn's disease. J Med
Microbiol 1994;41:74-94.
- Tribune News Service. Pasteurized milk "safe." Chicago Tribune
1996 Sep 9:3.
- UK scientists link Crohn's to superbug in cows' milk. Canadian
Business and Current Affairs 1996 Jun 11;32(22):52.
- USAHA. Report of the USAHA Committee on Food Safety; 1998 Oct
5; Minneapolis, Minnesota.
- USDA: APHIS: VS, CEAH, NAHMS. Johne's Disease on US Dairy
Operations. Fort Collins, CO: NAHMS; 1997 Oct. N245.1097.
- van Kruiningen HJ, et al. Experimental disease in infant goats
induced by a mycobacterium isolated from a patient with Crohn's disease.
Dig Dis Sci 1986;31:1351-60.
- Wall S, et al. Identification of spheroplast-like agents isolated
from tissues of patients with Crohn's disease and control tissues by
polymerase chain reaction. J Clin Microbiol 1991;31:1241-5.
- Weiss R. What's the matter with milk? Health (ISSN:
1059-938X) 1993;7:18.
- Wells SJ. Herd-level risk factors for infection with
Mycobacterium paratuberculosis in US dairies and association between
familiarity of the herd manager with the disease or prior diagnosis of
the disease in that herd and use of preventive measures. J Am Vet Med
Assoc 2000;216:1450-7.
- Wells SJ, et al. Johne's disease on US dairy operations. In:
Chiodini RJ, Hines ME II, Collins MT, editors. Proceedings of the 5th
International Colloquium on Paratuberculosis; 1996 Sep 29-Oct 4;
Madison, Wisconsin. International Association for Paratuberculosis;
1996. p. 140-2.
- Westcott S. Minister "confident" over safety of milk. Press
Association Newsfile 2000 Apr 2.
- Western dairy producers introduce Johne's disease control proposal
but crucial human health issues missing from plan. PARA News Release;
2000 Oct 30.
http://www.crohns.org/media/pr301000.htm
- Whalley S. Milk drinkers cool over health scare. Reed Business
Information 1998 Aug 14:8.
http://www.reedbusiness.com/retail.htm
- Whitlock RH, Buergelt C. Preclinical and clinical manifestations of
paratuberculosis (including pathology). Vet Clin North Am Food Anim
Pract 1996 Jul;12(2):345-55.
- Wingspread Statement on the Precautionary Principle; 1998 Jan
23-25; Wingspread Conference Center, Racine, Wisconsin.
- World's foremost research minds target Crohn's disease. PARA News
Release; 1999 Jan 4.
http://www.crohns.org/media/pr040199.htm
- Zoonotic potential of Johne's disease: association of M.
paratuberculosis and Crohn's disease. 1997 Feb 19.
http://www.vetmed.wisc.edu/pbs/johnes/zoonoses.html