Shiga Toxin: E. coli 0104:H4

Escherichia coli (E. coli) bacteria are commonly found in the gut of humans and animals. Most strains of E. coli do not cause harm in the bowels, although they can cause infections if they spread to urine or blood. However, a few strains have acquired characteristics that allow them to attach to cells in the gut, invade the lining of the gut and/or produce toxins that cause damage or secretory malfunctions of gut cells.

One such toxin, the "Shiga" toxin is capable of causing diarrhea that may be watery or bloody. Strains that produce Shiga toxin are also called 'STEC' strains. If an STEC strain also has acquired the ability to adhere to cells in the gut, it is referred to as an 'enterohemorrhagic E. coli' or EHEC. The most common EHEC is E. coli 0157:H7, but other variants exist, including the one that caused the 2011 E. coli outbreak that originated in Germany.

People acquire EHEC when they ingest material contaminated with infected fecal material. The fecal matter might come from eating contaminated food such as partially cooked ground beef, or raw produce such as bean sprouts. Touching the mouth or nose with contaminated hands also spreads disease. Hands become contaminated in many ways including petting animals in a children's zoo or touching an infected person. Even a small number of organisms can cause disease, so EHEC can spread easily and widely.

Symptoms start a few days after ingestion and usually begin with watery diarrhea that may become bloody. The diagnosis is confirmed by taking a sample of stool for culture and/or testing for the Shiga toxin.

Complications result when the Shiga toxin enters the bloodstream and include 'hemolytic uremic syndrome' or HUS. HUS causes kidney damage that may be temporary or permanent.

Other patients, especially the elderly, may develop a related condition called thrombotic thrombocytopenic purpura (TTP). TTP reduces platelet counts, causing both bleeding and clotting problems including stroke or seizures.

Patients with HUS have reduced urination and low blood counts (anemia). In general, children are more susceptible to HUS than adults, although this varies according to the EHEC strain. Most people with EHEC infection recover completely and usually fewer than 10% percent develop complications, although the risk may be higher in some outbreak situations, which apparently happened in Germany with the E. coli 0104:H4 strain.

Treatment involves replacing fluid losses and other supportive measures. Antibiotics are not usually helpful in treating E. coli infections caused by STEC or EHEC strains. In fact, there is some evidence that antibiotics might make the situation worse by increasing the risk of HUS by increasing toxin production.

Most patients are mildly ill and can be treated at home with oral fluids. However, patients with HUS may require dialysis. TTP may require a type of exchange transfusion called plasmapheresis. Antibiotics may be needed if the patient develops sepsis. There is an experimental treatment for HUS that involves a monoclonal antibody directed against complement activity by cleavage of the complement protein C5. It prevents the generation of the inflammatory peptide C5a and the cytotoxic membrane-attack complex stimulated by the Shiga toxin. The antibody, called eculizumab (Soliris), appears promising and it has been helpful in a few cases, but large-scale studies are lacking. It showed no benefit in the 2011 outbreak of E. coli 0104:H4 in Germany because it was often administered too late. 

The risk of getting an EHEC infection is reduced by good hand hygiene. Wash the hands frequently, especially before eating or preparing food is a good way to prevent disease transmission, and it is highly recommended to avoid eating raw, unwashed foods. Given the wide array of foodstuffs that can become contaminated, it is impossible to totally eliminate the risk of EHEC. However, thorough cooking or pasteurization will destroy the bacteria.