Enterohemorrhagic E. coli infections

Since early May, an increased incidence of hemolytic uremic syndrome and bloody diarrhea related to infections with Shiga toxin-producing Escherichia coli has been observed in Germany, with most cases in the north of the country. Cases reported from other European countries had traveled to this area.

WHO was notified of the outbreak and published an international alert, sharing the information with health authorities in other countries.

The outbreak developed very rapidly. Most patients were aged 20 years or older (88%) and female (71%), instead of the traditional high-risk groups, which are young children and the elderly. The isolated E. coli was not the widely known O157:H7 strain but found to be an exceptional toxic strain O104:H4 bacterium, resistant to many antibiotics. As of July 4, when the outbreak seems to be phasing out, the total number of patients, most of them in Germany, exceeded 4,200: 897 developed hemolytic uremic syndrome (HUS) of whom 22 died. There have been 3,314 non-HUS cases, including 17 deaths. It has become a consignment of fenugreek seeds originating in Egypt; the animal source not yet identified.

This has become Germany’s largest ever, and one of the world’s deadliest, enterohemorrhagic E. coli (EHEC) outbreaks.

Shiga toxin-producing E. coli

E. coli is a common and normally harmless member of the gut microflora of most warm-blooded species. However, enteric disease may result if humans are infected with certain pathogenic E. coli strains. Certain Shiga toxin-producing E. coli (STEC), also known as verotoxigenic E. coli (VTEC), are of particular concern. In wild and domestic animals, predominantly cattle, infection with STEC strains seems to be fairly common, yet causes little or rather no disease.

These animals, therefore, act as reservoirs; most human cases are caused by food contaminated with zoonotic STEC of animal origin. Associated foods are uncooked beef (particularly ground beef), unpasteurized milk and juices (“fresh” apple cider), contaminated raw fruits and vegetables, or water. Person-to-person contamination can also occur.

EHEC comprise a subset of STEC serotypes that are commonly associated with bloody diarrhea and HUS; the latter complication could develop after the diarrhea is resolved and can cause acute kidney failure and even death. Treatment of HUS patients with antidiarrheal products or antibiotics is not usually recommended, as these may aggravate the symptoms by releasing the Shiga toxin from the bacteria in large amounts.

Other strains

In many countries, including the United Kingdom and the United States, E. coli O157:H7 is the most predominant foodborne EHEC. Infections with other serogroups, including members of O26, O91, O103, O104, O111, O113, O117, O118, O121, O128 and O145, are increasingly recognized as causes of hemorrhagic colitis and HUS.

Some of these organisms may be as significant in human disease as EHEC O157:H7; however, they are not recognized on the media used to isolate this organism, and many laboratories do not routinely screen for other strains.

In 1999, E. coli O157:H7 was estimated to cause more than 60,000 illnesses annually in the United States, 0.5% of all cases of foodborne disease (FBD) and 2.9% of deaths due to FBD. E. coli was found to be responsible for 9.5% of FBD outbreaks in an international study. Up to 10% of EHEC patients are thought to develop HUS, and the case-fatality rate for this is estimated to range from 2% to 7%, although for some outbreaks involving the elderly, the figure is as high as 50%. Outbreaks can be large. One EHEC O157 outbreak in Japan involved approximately 9,000 school children.

Animal-associated aspects of EHEC

Although many EHEC seem to be carried asymptomatically in animals, members of some non-O157 serogroups may cause enteric disease in young animals. In rabbits, EHEC O153 has been linked to a disease that resembles HUS.

Ruminants, especially cattle and sheep, are the major reservoirs for EHEC 0157:H7; bison and deer can be infected. This organism can sometimes be found in other mammals, including pigs, rabbits, horses, dogs, raccoons and opossums; and in birds, including chickens, turkeys, geese, pigeons, gulls, rooks and various other wild birds.

In some instances, it is not known whether a species normally serves as a reservoir host or if it is only a temporary carrier. For example, rabbits shedding EHEC O157:H7 have caused outbreaks in humans, but most infected rabbits have been found near farms with infected cattle.

The reservoir hosts for non-O157 EHEC are poorly understood. VTEC O103 has been found in cattle, sheep and goats, as well as in healthy and sick humans. EHEC O145 can occur in cattle, but less often than EHEC O26. One serotype, EHEC O145:H–, was isolated from a cat associated with a human case; whether the child infected the cat or the cat infected the child was uncertain. Domesticated rabbits appear to be reservoir hosts for EHEC O153:H– and O153:H7.

Prevention

Contaminated foods derived from cattle, particularly ground beef, are the most common source of infection. Animal fecal contamination of growing fruit and vegetables is another important source of this pathogen.

Some countries have adopted a policy of considering raw ground beef “adulterated” if it contains any E. coli O157:H7. This has led to large recalls of ground beef at enormous cost.

Control of pathogenic E. coli of animal origin requires the application of measures at all stages of the food chain, including on-farm. On-farm measures should be aimed at reducing intestinal colonization and shedding of the relevant bacteria, as well as reducing their persistence in the farm environment. These measures would also reduce human infection due to direct contact with the animals.

Vaccination and the use of probiotics and bacteriophages have been investigated as possible methods of reducing EHEC O157:H7 excretion in cattle. The probiotic Lactobacillus acidophilus culture appears to be effective and is widely used in the United States. The benefits of other specific measures are currently unclear. Testing and culling carriers of EHEC O157:H7, although a logical approach, may be ineffective, and there is also a lack of published data on the matter.

It must be remembered that pathogen-specific measures may be inefficient because they allow the emergence of other pathogens.

Among nonspecific measures, the management of manure and slurry is important. Good management practices, including maintaining hygienic troughs and pens, managing silage correctly, and avoiding overcrowding of animals, are relevant. Because fecal contamination of hides is the main source of E. coli contamination of meat, it is important to ensure that cattle are clean when sent to slaughter and that fecal contamination of carcasses during slaughter/dressing is avoided or removed.

Control measures for EHEC O157:H7 applied throughout the food chain have had a positive effect in the United States. Although some argue that control of EHEC O157:H7 should focus on harvest and post-harvest for both meat and leafy vegetables, this does not mean that pre-harvest control is unimportant. However, the potential for cross-contamination during transport and processing highlights the need for good post-harvest control besides measures applied on-farm.

E. coli, including EHEC, is not a reportable animal disease/agent; measures for the control of pathogenic E. coli are not provided in the International Animal Health Code of the World Organization for Animal Health (OIE). However, OIE and the Food and Agriculture Organization of the United Nations (FAO) have produced guidelines on good farming practices.

The US Department of Agriculture’s Food Safety and Inspection Service recommends the following preventive measures in households: Cook hamburgers and ground beef to a safe minimum internal temperature of 160·F; drink only pasteurized milk, juice or cider; rinse fruits and vegetables under running tap water, especially those that will not be cooked; wash hands with warm water and soap after changing diapers, using the bathroom, handling pets or having any contact with feces.

For more information:

• www.cfsph.iastate.edu/Factsheets/pdfs/e_coli.pdf
• web.oie.int/boutique/extrait/08knightjones523535.pdf

Arnon Shimshony, DVM, is associate professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Shimshony was Chief Veterinary Officer, state of Israel, from 1974 to 1999. Disclosure: Shimshony reports no relevant financial disclosures.

Follow InfectiousDiseaseNews.com on Twitter.