dire warnings about Johne's disease-could this be a causitive organism in AUTISM?
Dire Warnings About Johnes Disease
A wake-up call for the dairy industry?
by Kurt Gutknecht
For decades, a lot of dairy farmers havent taken Johnes disease seriously. No wonder. When push came to shove, neither has anyone else, including Congress.
That could change--and fast, triggered both by the staggering production losses inflicted by the disease and by mounting public health concerns.
Johnes (pronounced yo-neez) disease or paratuberculosis is a common ailment of cattle that was identified more than a century ago. It is characterized by chronic or intermittent diarrhea, emaciation and death. In the U.S. cattle industry, the disease causes losses estimated to exceed $1.5 billion per year.
First, the production losses, which, according to information from the National Animal Health Monitoring System (NAHMS), cost an average of $227 per cow annually in herds where more than 10% of cows are infected. The major culprit--farmers lack of familiarity with the disease, even though as far back as 1922, a UW Experiment Station publication warned of the danger posed by the disease and outlined effective methods of controlling and eradicating it.
"In the 75 years following the release of that publication, theres very little that any state has done to try to control the disease," says Michael Collins, a veterinarian and microbiologist with the UW School of Veterinary Medicine. Meanwhile, as predicted in 1922, the disease has continued to spread silently and surely. Cows may not show signs of infection for as long as 10 years. By the time the first cow is diagnosed, 10% of a herd is usually infected.
The recent NAHMS study attracted national attention with its finding that 20 to 40% of the dairy herds in the U.S. are infected. That shouldnt have come as a surprise to Wisconsin veterinarians because a similar survey in 1990 found one-third of the herds in the state were infected. Herd expansions have often accelerated the diseases spread.
Collins compares the spread of Johnes disease to the spread of prostate or breast cancer in humans. With early detection, the cancerous cells can be surgically removed. Wait, and a patients chance of recovery is poor.
The dairy industry has waited...and waited...and waited.
Christine Rossiter, senior extension veterinarian with the Cornell University Veterinary Diagnostic Laboratory, places some of the blame on the federal government, not only for "grossly underfunding" research but for murky federal regulations that have tended to keep the disease "underground."
Those who decide to address the issue are put at risk, she says, and theres "no value placed by the industry on a person who wants to do something about Johnes. Nobody wants to take it on. Its paralysis by analysis."
Wisconsin passed legislation in the early 1990s to help prevent spread of the disease, Collins says. The first act involved the principle of an implied warranty; that is, unless specified otherwise, an animal was assumed to be Johnes free. If not, the seller could be responsible for the resulting losses, whether it involved one cow or an entire herd.
A seller had two recourses--either provide test results showing the cow was Johnes free or write, "Not warranted free of Johnes disease" on a bill of sale.
"Unfortunately, nearly everyone accepts a bills of sale with that statement, which is often preprinted on forms used at major sales All I can say is purchasers deserve what they get if they choose not to use this buyer protection plan,"" Collins says. "I think the state should have done a better job of explaining to farmers how to use this law."
The law hasnt failed --it hasnt been used, Collins says.
The second Wisconsin law made the results of Johnes tests confidential except under carefully defined circumstances, thus eliminating the "black list" of herds that tested positive. The names of farmers with infected herds had previously been readily available to anyone.
The law provided economic incentives for sellers to test cattle for Johnes--if buyers had insisted on Johnes free cattle. They didnt and the industry is now dealing with the consequences. Ultimately, farmers will pick up most of the tab.
Farmers are expressing more interest in ridding their herds of Johnes, says Libby Balzer, district veterinarian and Johnes program manager for the Wisconsin Department of Trade and Consumer Protection. There were 9,000 diagnostic tests in 1991, 16,000 in 1995, and 30,000 in 1996. Nonetheless, thats a small fraction of the cows that could be tested. "We still have a long way to go," Balzer says.
Steve Kling, Taylor, Wis., says Johnes "just about devastated" his herd, afflicting about 90% of the farm-raised heifers that, weakened by the stress of calving, "withered away and died." Originally, his veterinarian thought the heifers were too young to be affected by the disease.
He has since cleaned up his herd, culling all infected animals and screening all animals that enter his herd. "I wish there was a way to get people more aware of the disease. I wouldnt have been aware of the problem unless it had happened to me. A lot of people tend to hide the fact that they have the disease in their dairy herds, but weve learned that the sooner you can identify and get rid of infected animals, the better."
Livestock losses alone clearly warrant action, Collins says. However, from 1992 to 1996, less than 1% of the money spent by the USDA National Research Initiative (NRI) Competitive Grants program, the single most important source of money for researchers studying animal diseases, was spent on Johnes disease.
According to Peter Johnson, NRIs division director for animal programs, few proposals are submitted concerning Johnes disease, and only partial funding is available for 20% of the proposals that pass review.
"In general, USDA funding for all areas of agricultural research is low," he says.
The NRI received $70 million when it was created in 1991. Congress was supposed to increase funding to $500 million. That hasnt happened. Last year, the NRI received $94 million.
Johns says he identified 44 projects concerning Johnes disease and paratuberculosis that were funded by the USDA, either through the NRI, formula funds or special grants. Two of these studies, both collaborative efforts between Cornell University and a Canadian laboratory, concerned the isolation of the organism from milk and meat.
Roger Johnson, microbiologist with Health Canadas Guelph (Ontario) Laboratory, says the studies largely concerned methodology and that the data concerning the presence of the organisms in raw milk "had not been analyzed."
Some countries have taken Johnes disease much more seriously. Australia has a national Johnes disease control program, a cooperative effort between the livestock industry and state veterinary services. The Netherlands has allocated $10 million for a national program to control Johnes disease and to certify herds as free of the disease.
Efforts to control and eradicate Johnes disease have "absolutely not" been adequate, says Robert Whitlock, with the University of Pennsylvanias School of Veterinary Medicine, who says more research is required to develop a more sensitive, readily available, and less costly method of diagnosis.
Even if farmers are becoming more aware of Johnes disease, what they dont know--and what their representatives in the diary industry seem reluctant to tell them--is the possible connection between Johnes disease in livestock and Crohns disease in humans.
The public health issue has been on the periphery of the dairy industrys agenda for years, a nagging concern thats never made it to the front burner. Most medical researchers studying Crohns disease think its an autoimmune disease.
Nonetheless, a core of researchers continue to provide troubling evidence of links between Johnes and Crohns disease. And many of those afflicted by Crohns disease are starting to pay attention--and some are embittered by the dairy industrys perceived reluctance to tackle the issue openly.
More than 500,000 people in the U.S. suffer from Crohns disease, a baffling and excruciatingly painful ailment that first manifests itself when patients are in the prime of life. The disease relentlessly infects the intestines, sometimes enough to require surgical removal and reliance on ostomy bags. The disease is incurable. The similarities between the symptoms of Crohns disease and Johnes disease--the asymptotic infection of the young, the diseases slow progression, and where it effects the intestines--have long attracted attention.
The "good "news is that theres no definitive proof that Mycobacterium paratuberculosis, which causes Johnes disease in livestock, also causes Crohns disease in humans.
Thats also the bad news. The lack of proof doesnt let the dairy industry off the hook, however. As a mother of a Crohns patient noted in an address to researchers studying Johnes disease, "The absence of evidence is not evidence of absence."
M. paratuberculosis is a wily and surreptitious organism, difficult to detect and nearly impossible to culture outside of its mammalian hosts (ranging from ruminants to primates), in which it is known to cause disease. It also takes a variety of guises in infected hosts. Once it gains a toehold, its nearly impossible to eradicate.
There are two forms of the organism, one that mainly infects cattle (the bovine strain) and one that primarily infects sheep and goats, (the sheep strain), says Rod Chiodini, a microbiologist associated with the Rhode Island Hospital at Brown University, who began studying the links between Johnes disease and Crohns disease in the early 1980s. All of the M. paratuberculosis organisms from humans have been the bovine strain.
Federal regulations are designed to deal with livestock diseases that pose a clear threat to public health, such as tuberculosis and brucellosis, but not Johnes disease, which falls into the gray area of a "close association" with Crohns disease, Rossiter says. The USDA has resisted attempts to enact regulations that would facilitate the control and eradication of the disease, she says..
And, like Johnes disease, theres precious little funding to study the relationship between M. paratuberculosis and Crohns disease. Most medical researchers dip into their own funds to continue their research, in part because the pharmaceutical industry is reluctant to fund research for an organism that hasnt been proven to cause a disease.
So far, differences in the rate of Crohns disease among various populations indicate that, if M. paratuberculosis is a cause, genetic susceptibility also plays a role, as does the age at which an individual is exposed to the organism.
Although Crohns disease is nor a rare disease (in the United Kingdom, for example, a researcher says there are as many cases as AIDS or tuberculosis) many patients are reluctant to publicize their condition.
The real battles are waged in the arcane prose of academic journals. "In science, confirmation of findings is what counts. Immunologists control the funding for this type of research, although we are making some breakthroughs," says Dr. David Graham, a gastroenterologist at Baylor University who has studied the links between M. paratuberculosis and Crohns disease for a decade. "Its hard to accept the concept that the organism is a pathogen that cant live outside its mammalian host. But its definitely been proven that M. paratuberculosis causes disease in other mammalian species."
Chiodini says several other pathogens cannot grow outside their mammalian hosts, including the mycobacteria M. tuberculosis and M. leprae.
"Everyone understands the implications of the possible connection between Johnes disease and Crohns disease," says Dr. John Hermon-Taylor, chairman of the department of surgery, St. Georges Hospital Medical School, London, England, and an internationally known expert on Crohns disease. "Our intention is not to create a massive scare, but to put the problem in perspective--out in the open."
The ability of infected animals, even those not showing any symptoms of infection, to shed the organism and its detection in 7% of the pasteurized milk tested in England between 1990 and 1995 shows "that humans are exposed to intact M. paratuberculosis, and that the possibility that some of these M. paratuberculosis are still viable is very high," he says.
Moreover, seasonal variation in the rate of infected samples (the organism was found in as many as 25% of the samples in September through November and in January through March) coincides with the periods when Crohns patients tend to suffer relapses.
Johnes manifests itself in a variety of forms, from cases where the bacteria are visible with no inflammation to cases where there are no visible bacteria but extreme inflammation, he says. Moreover, only a small percentage of infected animals with no microscopically visible organisms will react positively to an immunological test.
Dr. Hermon-Taylor says its often impossible to culture the M. paratuberculosis organism from animals known to be infected, so it shouldnt be surprising that its often difficult to detect the organism in humans, he says. However, with new DNA extraction techniques, the genome of the bacterium is regularly detected in Crohns patients.
"Its an organism that takes years to really figure out. Thats why so few people have successfully cultured it from humans. And in humans, it exists in such an amorphous form--sometimes appearing in the shape of a blob, an oval, or whatever--that some researchers think they can fin it anywhere," he adds, noting that a very specific gene probe is required to distinguish between M. paratuberculosis and 50 other species of mycobacterium most of which harmless, that infect humans.
"Its also easy to get negative results," Chiodini says. He knows of only six research labs that successfully culture the organism from humans. The first successful attempt to culture the organism in 1910 was an accident, occurring when M. paratuberculosis was left in culture dishes with another bacterium that provided a necessary growth factor.
When the evidence is considered, its difficult to argue the case that the organism is not involved. It is certain that M. paratuberculosis can be pathogenic in humans and that its very likely that it causes a significant proportion--even a substantial proportion--of Crohns disease in humans," Dr. Hermon-Taylor says.
He says 85% of Crohns patients derived "enormous benefit" when treated with a combination two new drugs effective against M. paratuberculosis--rifabutin and clarithromycin. The fact that patients relapse after treatment is stopped shows how difficult it is to eradicate the organism.
Whitlock disagrees. "Im open to the possibility that theres a link between Johnes and Crohns, but there are likely to be many mitigating circumstances, such as genetic factors. At this point, I think Johnes poses a relatively low risk (to public health)."
"We have enough worrisome information to provoke us into action," says Collins, who recently spent a year at a hospital in Copenhagen, Denmark, helping medical researchers evaluate the rate of M. paratuberculosis infections in patients with Crohns disease.
"How sad it would be if dairy farmers get blindsided by this issue. I would like to think we could support this research for purely animal health reasons, but that hasnt worked," Collins says.
"The dairy industry isnt interested in studying the connection between the two diseases," says Dr. Robert Greenstein, director of the Laboratory of Molecular Surgical Research, Veterans Affairs Medical Center, Bronx, N. Y., and associate professor of surgery at the Mount Sinai School of Medicine, N.Y.
For some, Greenstein has discovered the "smoking gun" that implicates M. paratuberculosis as a probable cause of Crohns disease.
Fragments of DNA can be derived from living or dead organisms, so the extraction of M. paratuberculosis DNA wasnt viewed as definitive proof that live bacteria were present in Crohns patients. However, Greenstein extracted RNA--.which only living organisms produce--of M. paratuberculosis from Crohns patients. Preliminary results also indicate that RNA of M. paratuberculosis occurs only in the most diseased areas of the lower intestine..
Rod Chiodini, a microbiologist associated with the Rhode Island Hospital at Brown University, began studying the links between Johnes disease and Crohns disease in the early 1980s.
"Professionally, theres no definitive proof that theres a link, but neither is it proven that theres not a link (between the two diseases). Personally, I would be very surprised if there was not a causal relationship with at least some forms of Crohns disease. Im not convinced that Crohns disease is a single disease," he says.
Chiodini says he has been "hammered" by representatives of the dairy industry who seize on minor discrepancies in research in an attempt to discredit the entire hypothesis and who ignore the increasing body of research showing links between Johnes and Crohns. "People jump into the field of M. paratuberculosis and Crohns without appreciating the vast body of research that precedes their studies,": he adds. Some come to simplistic conclusions, providing more grounds to those seeking to deny the links between Johnes and Crohns.
Several years ago, he and other researchers told the National Dairy Promotion and Research Board to publicize the possible relationship between the two diseases, and to fund research concerning the links. "There absolutely has not been an adequate response by the dairy industry. Since the mid-1980s, Ive told them (the dairy industry) many, many times that they are sitting on a time bomb. Funding research would cost less than one of their commercials," he says.
One of the critics of the possible link between Crohns and Johnes is Dr. Herbert van Kruiningen, professor of pathobiology at the University of Connecticut, Storrs, Conn. "If those who believed in the link (between Johnes and Crohns) were intellectually honest, theyd get out of the business," he says, claiming that those researching the links in the topic are cynically using the threat to public health to obtain funding.
"The medical community has passed on that idea. Twenty laboratories have looked at the issue and concluded its no longer a viable issue. In the entire history of recorded medical history, M. paratuberculosis has never been proven to induce a disease that looks like Crohns disease," he says. Instead, he believes Crohns may be related to other species of bacteria that are slowly transmissible, perhaps over a period of five or six years.
He also says theres no case of a farmer getting Crohns disease from working around Johnes infected livestock, even though farmers are at a high risk of contracting "tuberculosis, brucellosis, or a dozen other diseases" from infected animals.
Several medical researchers disagreed with Dr. van Kruiningens assertions about the failure to show that M. paratuberculosis induces a Crohns-like disease and the failure to diagnose Crohns disease in farmers.
"The issue is still very much a matter of scientific debate," says John Adams, director of milk safety and animal health for the National Milk Producers Federation. "Our group (the Johnes Working Group, a subcommittee of the U.S. Animal Health Association) looked into the matter and it appeared to us that the majority of scientific opinion supported no cause and effect relationship (between the two diseases," Adams says, citing the need for educational programs for producers.
However, many of "medical experts" that Adams says he relies on for advice disagree with his contention that the dairy industry was adequately addressing the public health aspects of Johnes disease.
The issue of whether M. paratuberculosis is killed by pasteurization is a major bone of contention for the dairy industry. Industry representatives criticize laboratory simulations of pasteurization as inaccurate, a conclusion supported by the results of a recent study by Judy Stabel, lead scientist for the Johnes Disease Research Project at the National Animal Disease Center, Ames, Iowa. When she used a laboratory -scale pasteurization unit, which heated milk to 72 degrees C for 15 seconds , all M. paratuberculosis organisms that had been used to inoculate raw milk were killed. "The flow of milk apparently distributes heat more uniformly and allows heat to penetrate the organism," Stabel says, noting that researchers in Australia reported similar findings.
Chiodini says the oft-cited Australian study is an example of how the real facts often get buried in the scientific literature. He says the Australians use a higher pasteurization temperature--and that the Australian researchers found M. paratuberculosis actually survives at the pasteurization temperatures used in the U.S.
Dr. Hermon-Taylor says Stabels statement is "very naive. She can say that about her study, but she cannot say that pasteurization is safe. Its entirely wrong and a dangerous assumption, one that goes against the balance of scientific evidence in the field," he says. One observer notes that it would be "political suicide" for a researcher in the United States to even suggest testing dairy products for M. paratuberculosis.
"The biggest problem to date is that M. paratuberculosis is not an easy organism to detect (in food)," says Ron Weiss, research program manager with the UW-Madisons Food Research Institute, which deals primarily with food-borne pathogens. He knows of no study in the U.S. concerning the presence of the organism in food.
Rossiter says its time to re-evaluate the efficacy of pasteurization standards, which were originally based on the time required to kill disease organisms in milk heated in a water bath.
Collins says pasteurization is not a central issue, considering the prevalence of the organism in the environment, including surface water, which 40% of Wisconsin residents use for drinking water. During his experiments, Greenstein reported culturing "M. paratuberculosis from the municipal water supply of a major city in the United States."
"Nearly every gastroenterologist will probably disagree with myhypothesis (that Crohns disease is caused by M. paratuberculosis)," Dr. Greenstein says. "Everyone has staked their careers that it (the cause of Crohns) is a primary autoimmune disease."
But he notes that conventional theories are often toppled. One recent example--proof that the bacterium H. pylori causes ulcers, a theory that was ridiculed for more than a decade.
Dr. Greenstein says many researchers have discounted the role of M. paratuberculosis in Crohns disease because they couldnt detect it by conventional staining methods. However he says there are two forms of M. paratuberculosis, one of which lacks cell walls--and the proteins to which stains adhere. Its this form that he thinks might cause Crohns disease.
As many as one-third of Crohns patients may require surgery to relieve intestinal obstruction while receiving appropriate antimycobacterial paratuberculosis therapy.
Dr. Greenstein says the intestinal obstruction may be an indication that the antibiotics permit the body to convert the aggressive (abscesses) form of the Crohns disease to the contained (obstructing) form. As an unfortunate consequence, the intestine narrows and blocks. This blockage must then be surgically relieved,, a phenomenon which also occurs during the treatment of tuberculosis meningitis, where antibiotics must be administered with another drug that prevents the obstruction of conduits that drain fluid from brain tissue..
"I have a testable hypothesis. Now I need support to conduct the appropriate clinical studies," Dr. Greenstein says. "No one will fund my studies. My proposals are thrown in the trash," he says, noting that his previous studies of the relationship between M. paratuberculosis and Crohns disease were "self-funded."
Heads rolled in pharmaceutical companies when H. pylori was proved to cause ulcers. Chiodini says companies arent making the same mistake again. Several are quietly trying to develop drugs that will be effective against M. paratuberculosis.
"Its clear that it (M. paratuberculosis) is present in our food supply, in milk and also in meat. There may be more than one cause of Crohns disease, but Im convinced that this is one," says Dr. Graham "It will cost the dairy industry a considerable amount of money to clean up herds, but it will have to be done eventually," he says. Dr. Graham hasnt received a grant to study the relationship between the organism and Crohns disease in 5 years, and has spent $100,000 of his own money on the research.
"I dont understand why Johnes disease isnt in the forefront of research objectives. Whether or not it (M. paratuberculosis) causes Crohns disease, I dont think they are desirable bacteria to have in our food, says. Karen Meyer, Temple Terrace, Fla., who spoke at the National Johnes Working Group at the annual meeting of the US Animal Health Association. Meyer is president of the Paratuberculosis Aggressive Research Association (PARA), a group encouraging more research in the links between Johnes and Crohns diseases. She watches her son struggle with Crohns disease (the disease usually first manifests itself in those 15 to 25 years of age). Her son is now undergoing the antibiotic regime pioneered by Dr. Hermon-Taylor. and faces what she hopes is his last bout of surgery. (Most Crohns patients undergo surgery two or three times.)
"I would never want to do anything to harm our farmers. I simply dont understand why 45% of the farmers surveyed dont know about Johnes disease. If it had been addressed when it should have been addressed, I dont think farmers would be facing this problem.
"Every day, 80 more children in the United States get Crohns disease. I cant give up. I will not give up.
"I think we underestimate farmers. If they even thought they were making someone sick, it would break their hearts," Meyer says.
Information about Johnes disease and links to other sites.
The web site of the Paratuberculosis Aggressive Research Association (PARA), P.O. Box 16219, Temple Terrace, FL 33687-6219, (813)989-9539.
Microbiological and molecular evidence suggests there may be an association between Mycobacterium paratuberculosis and Crohn's disease. Whether M. paratuberculosis actually causes Crohn's disease is not known; however, in light of scientific data, the International Association for Paratuberculosis supports the need for a focused research effort to determine the biological facts related to these issues in the interest of public health, animal health, and animal agriculture.
Position statement of the International Association for Paratuberculosis
There are numerous biological questions about this infectious disease that remain unanswered. Additionally, there is a desperate need for applied research on Johnes prevention through biosecurity measures, control on infected farms and herd certification program validity and cost effectiveness.
The Committee on Johnes Disease,US Animal Health Association.
This article is from the December issue of the Wisconsin Agriculturist. Used with the permission of the author.