991074 Microbiologists Battle E. ColiOctober 26, 1999Albany, NY - A hundred cows awaited judging in a fairground barn. Groomed and pampered, they were the pride of their farms. One harbored a deadly germ. But nobody knew that. Not until later, when medical sleuths figured out what killed a 3-year-old girl and a 79-year-old man, and made more than 1,000 other fair-goers terribly sick. The malignant microbe at the Washington County Fair was Escherichia coli 0157:H7. Within less than a decade, the bacterium has gone from relative obscurity to major health threat, causing outbreaks of disease linked first to fast-food hamburgers, then lettuce, apple cider, alfalfa sprouts, and other foods. At the fair, it infected drinking water. A war has been waged on many fronts against the toxic bacteria since 1993, when an outbreak at Jack-in-the-Box restaurants in the Pacific Northwest infected more than 700 people and killed four. Regulators have tightened meat inspection requirements. Health officials have issued cooking and sanitation guidelines. Medical researchers have developed better diagnostic tests. Legislators have proposed the creation of a new federal food safety agency. But some scientists and consumer advocates say the ultimate solution may be to rout the enemy from its headquarters: the gut of the cow. “We're trying to completely eliminate it from cattle at some point,” said Dr. Robert Elder, a U.S. Department of Agriculture microbiologist in Clay Center, Neb. Normally, E. coli bacteria are beneficial inhabitants of the intestines of humans and other creatures. But 0157:H7 is a mutant strain. In humans, it destroys the intestinal wall and can cause hemolytic uremic syndrome, or HUS, which attacks the kidneys - sometimes fatally. Scientists believe the mutant strain was created when a virus infected benign E. coli and gave it a string of DNA from Shigella - a bacterium that causes severe, bloody diarrhea. In both Shigella and E. coli 0157:H7, as few as 10 germs can cause illness; by comparison, it takes about a billion salmonella bacteria to make you sick. An estimated 73,480 people a year are infected with E. coli 0157:H7, and about 600 of those cases are fatal, according to the federal Centers for Disease Control and Prevention. The outbreak at the end of August at the Washington County Fair, 33 miles north of Albany, resulted when a fairground well was contaminated by manure from a nearby cattle barn, according to investigators from the state Health Department and the CDC. Genetic testing indicated that the E. coli came from the digestive tract of a single cow, said Kristine Smith, a Health Department spokeswoman. The U. S. Department of Agriculture is sponsoring several research efforts aimed at ridding cattle and manure of toxic forms of E. coli. Complicating the effort is the fact that the bacteria don't make cows sick. Until recently, it wasn't even clear how widespread the organism was. Last year, scientists estimated that about 1% to 3% of cattle were infected with E. coli 0157:H7. Now, USDA researchers say it appears the number is much higher. “In every herd we've tested, there have been at least some animals positive for 0157,” Elder said. “The old methods used for testing cattle were not as sensitive as the tests we have developed here.” With the growing number of media reports of outbreaks, it may seem like E. coli is becoming more widespread, Elder said. But that's probably a misperception, he said. “I think five or 10 years ago the incidence (in cattle) was just as high, but now we're able to detect it better,” he said. “The same is true in the human field. We have better diagnostics to identify E. coli. Outbreaks in the past may have gone unreported because we didn't know what to look for.” Elder and others have been working on a technique called competitive exclusion, which would use benevolent bacteria, or probiotics, to destroy 0157:H7 or crowd it out of a cow's digestive tract. A similar technology has successfully been used to exclude salmonella bacteria from chickens. Last year, the Food and Drug Administration approved PREEMPT, a patented mixture of 29 bacteria that can be sprayed on newborn chicks to make them resistant to salmonella. However, Elder said cattle are more difficult to treat with such a process. For one thing, cattle are raised in less controlled conditions than chickens. Also, the physiology of a cow is also very different from that of a chicken. “A cow is a ruminant, a multi-stomached animal,” Elder said. “That's why E. coli does so well in them. It makes them very hard to treat with competitive exclusion. The rumen is basically a 30- or 40-gallon barrel that's loaded with bacteria.” The life cycle of cattle also makes them difficult to treat with competitive exclusion, Elder said. A broiler chicken is slaughtered at six to eight weeks of age, while beef cattle typically live for two years. “Competitive organisms can't stay in there continuously for that length of time,” Elder said. “It could possibly be used for a short-term treatment before cattle go to slaughter,” to keep fecal E. coli from contaminating meat. “But it wouldn't have prevented the New York outbreak,” which was related to manure on the ground. “The waterborne outbreaks like that in New York would take a different approach,” Elder said. “That takes a long-term treatment, probably a vaccination type program.” Several researchers are trying to develop an effective vaccine, including Elder and colleague James Keen. “The thing we're looking at is a vaccine not only against 0157, but also the 0111 and 026 E. colis,” Elder said. All three are mutant entero-hemorrhagic strains, meaning they produce the Shigella toxin that causes bloody diarrhea and HUS. Developing a vaccine against 0157:H7 in cattle is difficult, said Michael Doyle, director of the Center for Food Safety and Quality Enhancement at the University of Georgia. The problem is that, because the organism doesn't make cattle sick, it doesn't stimulate their immune system to make blood antibodies. “Traditional vaccines aren't likely to be effective for that reason,” Doyle said. Doyle is more optimistic than Elder is about competitive exclusion treatments in cattle. “We have selected three strains of good bacteria which produce anti-microbials that kill 0157,” said Doyle. In a recent study, the Georgia researchers exposed 20 adult cattle to 0157:H7, then gave 10 of them feed inoculated with the probiotic bacteria. After 33 days, the 10 animals that were not given probiotics were still positive for 0157:H7. Of the 10 that got the treatment, only one was still positive. An earlier study with calves had similar results. Additional studies are needed, not only to verify the results, but to see how long the effect would last and determine whether the animals would have to be continually fed probiotics to prevent 0157:H7 infection, Doyle said. He hopes to get FDA approval for a commercial probiotic that can be added to cattle feed. However, such a product is several years away, he said.
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