Mycobacterium avium paratuberculosis



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Mycobacterium avium paratuberculosis is the subspecies of Mycobacterium avium complex (MAC) that's seldom isolated because it's almost impossible to grow in culture. According to the Centers for Disease Control: "About 20 to 30 percent of people with AIDS get MAC disease." The subspecies paratuberculosis has been isolated in at least one AIDS patient. Even though MAC is pathogenic in AIDS patients, the paratuberculosis subspecies is almost universally considered non-pathogenic in humans.

Paratuberculosis in Non-humans

Mycobacterium avium paratuberculosis (MAP) is a bacterium that in dairy cows and numerous other mammals, causes Johne's (pronounced "yo-nees") disease—a contagious, slowly progressive, and usually fatal infection centered around the small intestines. The infection is spread when an animals ingests milk or feces from an infected animal, or the bacteria is passed to an offspring in the womb.

Once a calf swallows contaminated milk or feces, it passes to the ileum where macrophages are released by the immune system to fight the infection. Unlike other bacteria that are engulfed by macrophages and marked to be killed by other cells of the immune system, MAP bacteria make a home in macrophages where they thrive.

Researchers at the University of Liverpool recently discovered that MAP releases a molecule that causes an immune deficiency preventing macrophages of the immune system from killing E. coli—a species of bacteria commonly found in the intestines but normally kept in check by the immune system.

The immune system reacts to the infection and releases more macrophages but rather than kill the MAP bacteria, they provide a hospitable environment for MAP reproduction. The immune system also releases cytokines which cause inflammation of the intestines and malabsorption of nutrients.

Ruminants--animals that regurgitate undigested food--are more susceptible to MAP infection than non-ruminants, possibly because the MAP bacteria is spread with regurgitated food.

Because MAP reproduces extremely slowly, intestinal inflammation usually continues for years through periods of relative remission and relapse. Damage to the intestines accumulates usually until the animal grows older and dies.

Although MAP does not generally reproduce in the external environment, it can survive for more than a year. Cattle may become infected from feces in the pasture or the bacteria may be transferred to the calf in the womb. Younger cattle are generally more susceptible to infection than older cattle.

There are no apparent symptoms in the early stages of infection and no reliable test for infection. Since MAP is not considered a human pathogen, only about one in four herds in the U.S. are screened for MAP even though MAP is found in about three in four herds screened.

Seemingly healthy cattle with MAP infection produce milk for their young and for human consumption as milk or other dairy products. Some infected cattle that show signs of disease are slaughtered and sold for consumption as beef or beef byproducts while those that show no signs of disease are treated as healthy animals..

Most common species of bacteria that might appear in milk are killed by pasteurization as generally practiced in the U.S., but MAP is the bacteria that's too tough to die (like the town of Tombstone, Arizona). Studies have found viable MAP bacteria in samples of milk sold at retail.

MAP bacteria cause intestinal disease not only in cattle but also in other species including goats, sheep, bison, deer, elk, and non-human primates and its ability to cross species among mammals is well establised. So what about humans?

Paratuberculosis in Humans

MAP bacteria is known to cause infection in persons with Acquired Immune Deficiency Syndrome (AIDS), though it may be identified as part of Mycobacterium avium complex (MAC). It might be diagnosed broadly as Mycobacterium other than Tuberculosis (MOTT), as Nontuberculous Mycobacterium (NTM), or as Hot Tub Lung. The source of identified infection in AIDS patients is sometimes found to be contaminated water including tap water where Mycobacteria can live as long as one year. The lungs are a common site for these infections.

While MAP (or MAC) is known to be a common pathogen in persons with AIDS, less has been documented about MAP in paitients with other secondary immune deficiencies and with primary immune deficiencies.

Disregarding an overwhelming body of evidence suggesting that paratuberculosis causes intestinal disease in humans, the medical profession has maintained faith that humans are not susceptible to the effect that paratuberculosis has on other species.

Crohn's Disease (CD) in humans is an inflammatory disease that can affect any part of the gastrointestinal tract but most commonly affects the ileum. CD has traditionally been thought to be strictly an autoimmune diseases but the causal mechanism remains controversial.

The ileum is the only part of the gastrointestinal tract that contains Peyer's Patches which are a part of the immune system that provides protection from pathogenic organisms. Bacteria such as paratuberculosis encounter macrophages in Peyer's Patches and paratuberculosis infects macrophages. Cells in Peyer's Patches also function to identify invading organisms to initiate an immune response against that specific organism. Part of that immune response includes the release of cytokines which initiate inflammation.

In Crohn's Disease, the inflammation initiated by an immune response causes scarring and thickening of the wall of the intestines. Symptoms typically include abdominal pain, diarrhea, and malabsorption of nutrients. Since Vitamins B12 and D are primarily absorbed in the ileum, inflammation limited to the ileum can cause malabsorption of these vitamins even though other nutrients may be absorbed. Thickening of the intestinal wall can cause blockages. Fistulas—a sort fo black hole connecting to other organs—can also form. The damage varies between individuals so the symptoms vary as well. Weight loss, for example, is common in both Johne's Disease in cattle and Crohn's Disease in humans, but not all cattle with Johne's Disease lose weight nor do all humans with Crohn's Disease. Crohn's typically follows a course of remission and relapse.

Treatments for Crohn's Disease typically consists of drugs that reduce inflammation and suppress the immune system, antibiotics for opportunistic infections (none effective against mycobacteria), anti-diarrheals, and nutrition supplementation to treat malabsorption. Finally, severely damaged sections of the intestines are removed surgically in two-thirds to three-quarters of patients.

Some people are genetically predisposed to Crohn's; people of Jewish heritage are at increased risk; and African Americans are at decreased risk of developing Crohn's.

The prevalence of Johne's Disease in the United States has been increasing exponentially since its first discovery in 1908 and at the current rate, approximately 90% of herds will be infected by 2020. The incidence of Crohn's Disease has risen steadily over the past fifty years. Crohn's was first identified in 1932.

Crohn's Disease, Johne's Disease, and interestingly Multiple Sclerosis are more common in colder, wetter climates typically found in northern latitudes where there is less sunlight than near the equator.

Increased presence of both paratuberculosis and E. coli have been found in intestinal tissues from patients with Crohn's Disease, which could be explained by the discovery that paratuberculosis releases a molecule that prevents macrophages from killing E. coli.

Notes

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Outside Links

Waiting for the Legend Flak

Threats to public health have been covered up using easily disprovable urban legends or urban myths as a smoke screen and I'm waiting for this tactic to be used against MAP. Here's how it might work: Some minister who is clearly half a bubble off level is encouraged to claim that MAP causes homosexuality and he makes other claims paralleling the evidence that MAP causes Crohn's. His nonsense offends the LGBT community and is gleefully spread by the homophobic community resulting in a great conflict with lots of publicity. Then, a debunking Website financed in part by industry leaders announces "The Paratuberculosis Urban Legend". After that, whenever somebody talks about the MAP/Crohn's connection, they are immediately innundated by would-be debunkers anxious to show off their superior knowledge that Paratuberculosis is a disproven urban legend.

The rumor to be debunked might be that MAP breaks apart to create formaldehyde or something similar, but the scam is essentially the same.

Links

News

Link Found Between Crohn's Disease And E. Coli Bacteria, Science Daily, August 8, 2007

My thoughts

Crohn's Disease may be an effect with multiple causes and combinations of causes including autoimmunity, bacterial, viral, or parasitic infection, or a vicious cycle as the cycle proposed by Professor Martin Pall.

Significant damage to the intestinal wall could provide a doorway to opportunistic infection of other organs. As in cattle, mycobacteria could disseminate to cause other diseases. These secondary diseases could include gastritis, nephritis, thyroiditis, dermatitis, myocarditis (might appear as cardiac arrhythmias or cardiomyopathy), tinnitis, sinusitis, bronchitis, pneumonitis, and pleuritis (pleurisy). I've had them all. Mycobacteria infection might lead to Type I Diabetes, arthritis, fibromyalgia, and various diseases assumed to be autoimmune.

Recent research has found that MAP bacteria have an affinity for glial cells, which are cells of the nervous system that form the infrastruction for nerve cells. Production and maintenance of myelin sheathing around nerves relies on glial cells and if glial cells are infected by paratuberculosis, the myelin sheathing might fail as happens in Multiple Sclerosis. Such an infection might also draw an immune response that could damage the myelin sheathing.

If MAP infection is a cause or important cofactor in Crohn's Disease, treating Crohn's Disease by suppressing the immune system might enable MAP to disseminate throughout the body without resistance. No matter what the cause, suppression of the immune system could increase the risk of opportunistic infections. If Crohn's is entirely genetic autoimmunity, then why is the prevalence steadily increasing? Why does the inflammation increase in cold weather rather than warm weather?

Why hasn't there been more interest in research on MAP as a possible cause of Crohn's Disease? Is it for fear of loss to the dairy and beef industries? Is it because there's more money in designer drugs than in antibiotics? (How much did it cost the pharmaceutical industry when H. pylori bacteria was identified as a cause of peptic ulcers?) Are doctors resistant to change or afraid of leaving the herd? Will support agencies lose their funding if a cure is found? Are all of the above true?

What measures are being taken to ensure the safety of dairy products and to protect the public health from risks posed by MAP? Well, to the chargrin of dairy farmers, Congress has seen fit in recent years to drastically cut support for testing of cattle for MAP.

If you know of a doctor in the southwestern United States who treats MAP infection, please let me know.

Other diseases that may present like a MAP infection

 

Mycobacterium
(Family: Actinobacteria, Genus: Mycobacterium)

Mycobacterium are considered gram positive although they do not stain the same as most gram positive bacteria. They are considered acid-fast because they lack an outside cell membrane. They have a thick hydrophobic cell wall that contains waxy substances hence "myco-" in the name. Some species are very difficult to culture sometimes taking more than two years.

Mycobacterium infection is usually difficult to treat because mycobacteria have a strong cell wall that is resistant to many common antibiotics that work by damaging the cell walls. The strong cell walls also protect them from natural defenses of the immune system and from environmental factors. Most (except paratuberculosis) are susceptible to the antibiotics clarithromycin and rifamycin although there are some extremely antibiotic resistant strains.

Points to Ponder

Age of Exposure

Is age a factor in the effects of human exposure to MAP as it is with cows? Is the human immune system more able to resist infection if an infant is/was exposed at a later age or less able to resist infection in the elderly than in younger people? And what about others who are immune compromised?