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Search for an E. coli defense

Weapons of choice include antibodies, biomarkers and early-detection kits.

September 25, 2006|Shari Roan | Times Staff Writer

Barbara and Mike Kowalcyk knew E. coli was a food-borne illness that could make people sick. But the Wisconsin couple were entirely unprepared for what they heard five years ago as their stricken 2-year-old son lay in a hospital bed nearby.

"The doctor sat my husband and I down in this little, tiny waiting room and said, 'Mr. and Mrs. Kowalcyk, we are so sorry -- this is possibly the worst thing that can happen to your child. There is no treatment. There is no cure,' " Barbara Kowalcyk recalled last week. "I could not believe there was nothing they could do. It was horrific."

Their son, Kevin, died of acute E. coli poisoning eight days later, and, true to the doctor's word, there was very little anyone could do.

That could change.

Part of the alarm over cases of E. coli poisoning, such as the current spinach-linked outbreak blamed on the 0 O157:H7 strain, has been the difficulty in treating the most severe cases -- when toxins produced by the bacterium cause kidney failure. But researchers have been working for two decades to learn more about the illness and now think they will eventually have ways to limit the damage.

"There is a tremendous urgency to find treatments," says Dr. Howard Trachtman, a pediatric nephrologist and expert on E. coli at Long Island Jewish Medical Center in New Hyde Park, N.Y. "It's a very serious disease. It affects previously healthy kids, and the morbidity is so high. Three to 5 percent die."

The O157:H7 strain releases a toxin, called Shiga toxin, that attacks the intestines, causing bloody diarrhea and intense cramping. Sometimes the intestines bleed and break down. The toxin also can cause hemolytic uremic syndrome, in which the kidneys shut down due to damage in the small blood vessels. Both complications can be fatal, but kidney failure causes most E. coli-related deaths.

Doctors are essentially helpless to reverse hemolytic uremic syndrome once the process has begun, Trachtman says.

Instead, they try to keep the patient hydrated while providing electrolytes to maintain the body's nutritional balance. Some patients need kidney dialysis, the use of a ventilator, blood transfusions and blood pressure medication to keep them alive while the body fights the infection and toxins.

With enough supportive care, most are able to pull through. The body's immune system fights off the infection, and the kidneys are able to heal themselves. A few patients -- usually children and elderly people, who have weaker immune systems -- are unable to recover.

Most people fare best if they seek medical help quickly and are admitted to a hospital with expertise in treating hemolytic uremic syndrome, says Dr. Phillip Tarr, a professor of pediatrics at Washington University School of Medicine in St. Louis. Tarr treated many of the children who fell ill in 1993 in the Pacific Northwest from E. coli poisoning involving contaminated, under-cooked meat. The O157:H7 strain was also blamed in that outbreak. Much of the current research focuses on intervening earlier in the biological process, before the kidneys fail.

Several research groups are trying to create antibodies to the Shiga toxin, substances that would recognize and help fight the poison.

"We're making headway on therapeutics designed to neutralize the Shiga toxin," says Tom Obrig, a professor of medicine at the University of Virginia and an expert on E. coli poisoning. "Some have been tested in animal models, and there are promising results for those."

One company, Caprion Pharmaceuticals Inc. in Montreal, announced last week that its anti-toxin antibodies had been proved safe in 40 healthy adult volunteers. The company plans to conduct clinical trials on the drug, Shigamabs, next year.

"I think the antibody approach is the furthest along," says Alison O'Brien, chair of microbiology and immunology at Uniformed Services University of the Health Sciences, a federal school of medicine and nursing in Bethesda, Md. "The belief is that if you give this early enough, you can neutralize the toxin," meaning that the toxin could be inactivated while it is in the bloodstream so that it cannot attach to the cells.

Other researchers are trying to develop drugs that protect the kidneys from severe damage by reducing toxin-induced inflammation.

"The toxin damages the host cells in the kidney, but it does it in a way where we think we can intervene," Obrig says. "The kidney damage doesn't occur for several days after the bloody diarrhea. So there is this window of opportunity."

Using standard anti-inflammatory drugs, such as aspirin, won't limit damage to kidney cells caused by Shiga toxin, he says. However, researchers have identified a specific class of chemicals called adenosine-based compounds that appear to reduce inflammation in the kidneys and in other areas of the body.

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