In 1993, 623 people in the western U.S. fell ill with a little-known bacteria called E. coli O157:H7. Ultimately, four children would die from their infections; many others suffered long-term medical complications. The bug was later traced to undercooked hamburger served at Jack in the Box restaurants. This outbreak thrust foodborne illness onto the national stage as a real and present threat, sparking a sea change in the way Americans and the government treat this issue. To commemorate the 20th anniversary of the 1993 Jack in the Box outbreak, Food Safety News has produced a series of retrospective stories chronicling the outbreak itself and how food safety in America has changed since that time. Many battles have been won in the war on E. coli since the Jack in the Box outbreak called nationwide attention to the problem in 1993. The federal government has deemed seven strains of E. coli adulterants in beef, epidemiologists have improved methods of outbreak detection, there is a vaccine that reduces E. coli shedding in cows and scientists have developed rapid tests for detecting the bacteria. But one obstacle that has not yet been overcome is the lack of treatment for the life-threatening hemolytic uremic syndrome (HUS) that can result from an E. coli infection. Today it is estimated that 10 to 15 percent of patients who contract a Shiga toxin-producing E. coli (STEC) infection develop HUS as a result. Diarrhea-associated HUS, the type that results from an STEC infection, remains the leading cause of kidney failure in children. While researchers have learned a great deal about HUS over the past 20 years, they have not yet discovered a way to prevent the onset of the disease once a patient contracts an E. coli infection. “There’s nothing you can do to make it better faster except for just supportive therapy,” says Dr. Sharon Andreoli, director of the Division of Pediatric Nephrology at the James Whitcomb Riley Hospital for Children. HUS occurs when the Shiga toxins released by E. coli bacteria move into the bloodstream. The toxins localize in the kidneys because these organs have the greatest concentration of the Shiga toxin’s receptor, globotriaosylceramide, located in the small blood vessels. Once attached here, Shiga toxins damage the cells that form the lining of the kidney’s blood vessels. The body then sends platelets to the site of the damage to induce clotting there. But these clots block the flow of red blood cells through the vessel, damaging the cells and leading to kidney injury or failure. Patients with HUS usually exhibit a low platelet count and anemia in addition to compromised kidney function. While doctors cannot prevent this harmful progression once it has begun, they can provide supportive care to try to reduce the severity and duration of a patient’s illness. Such measures include maintaining an appropriate salt/water balance in the patient’s body,  providing platelet transfusions to address bleeding and blood transfusions to address anemia, and treating symptoms such as high blood pressure or seizures as they arise. In severe cases, a patient may require dialysis, a therapy that performs the function of the damaged kidneys by cleaning toxins from the blood. These supportive measures, says Andreoli, have improved over the past 20 years. “There are better ways to dialyse kids, there are better ways to manage their complications and there are some different drugs to help them produce more urine,” she says. Of course, in order for any of these measures to be put to use, the doctor must identify a severe case of E. coli infection and the warning signs of HUS. Signs that a patient may be developing HUS include pale skin, fatigue, low grade fever, bruising easily and bleeding from the nose and mouth, following several days of diarrhea (due to the E. coli infection). “The most important thing is to recognize the patients at risk for it, and then make certain that they’re stable as can be when the kidneys shut down,” explains Phil Tarr, director of the Division of Pediatric Gastroenterology, Hepatology and Nutrition at the Washington University School of Medicine in St. Louis. The most crucial steps in HUS treatment are “early recognition of bloody diarrhea and supportive care,” he says. With these in place, “The majority of people get better.” When asked whether clinics and hospitals have improved their ability to quickly determine whether a patient is at risk for HUS, Tarr responded, “The answer is unequivocally yes.” Drugs to avoid Although doctors don’t have the magic pill for preventing HUS, they do know what meds not to give patients for fear of increasing the likelihood of HUS, namely antidiarrheals and antibiotics. Antidiarrheal drugs, which slow bowel activity, also slow the process of expelling harmful Shiga toxins. While the use of antibiotics to treat E. coli infection remains controversial, the majority of research shows that patients treated with antibiotics are more likely to develop HUS. When antibiotics attack E. coli, they split the bacteria open, causing a greater release of Shiga toxins. The drugs are also thought to promote the production of Shiga toxin by the bacteria. A review of 259 cases of E. coli O157:H7 infection in children published in March of 2012 in Clinical Infectious Diseases found that antibiotic use was associated with a higher risk of HUS, no matter the drug used. Tarr was the lead author of that paper. He says his team’s findings were consistent with existing literature on antibiotics and E. coli. But both of these E. coli no-nos were known in 1993. “We still don’t like to use antibiotics. We still don’t like to use antimotility agents,” says Andreoli. “But those things were all in place 20 years ago. That’s not something that’s new.” The progress lies in prevention Is anything new, then, in the fight against HUS? Yes, says Andreoli – the fact that doctors now have to report the disease to health authorities, who in turn can now identify outbreaks more quickly and prevent more cases. Before the Jack in the Box outbreak, E. coli was not recognized by the U.S. Centers for Disease Control and Prevention as a reportable disease, meaning that doctors didn’t have to report cases to health authorities. “Because of this outbreak, many clinical laboratories began screening stool samples for E. coli O157:H7, which resulted in the identification of many more cases and outbreaks,” notes CDC in its 1993 Summary of Notifiable Diseases. “In May 1993, the Council of State and Territorial Epidemiologists (CSTE) passed a resolution recommending that E. coli O157:H7 infection be made reportable by all states and territories.” By 1995, both E. coli and HUS had been added to the federal list of reportable diseases. “The management of the individual patient hasn’t changed, it’s just that you can now identify and stop the spread of [E. coli bacteria] so that there will be fewer patients that get HUS,” explains Andreoli.