E. coli O157:H7

Background and disease in humans:

E. coli O157:H7 is a specific serotype of E. coli that causes watery diarrhea, hemorrhagic colitis and hemolytic-uremia syndrome (HUS) in humans.

• Hemolytic-uremia syndrome is a potentially life-threatening condition characterized by hemolytic anemia, thrombocytopenia and renal failure.
  • It most commonly occurs following infection in children.
    • 2-7% of E. coli O157:H7-infected children develop HUS.

The O157:H7 strain is distinguished microbiologically from other E. coli by its inability to ferment sorbitol and, most importantly, by its production of "shiga-like" toxins (SLT I and II). (SLTs were so named because of their similarity to the toxin of Shigella- 5 receptor binding B subunits and one active A subunit create a holotoxin.)

• Shiga-like toxins damage vascular endothelium in people, leading to thrombotic lesions and DIC. (This does not occur in cattle because they lack the toxin receptors in their blood vessels.)
• The HUS syndrome probably reflects the same basic process, with thrombotic lesions in the kidneys.
• Of importance is the fact the O157:H7 is by no means the only serotype of E. coli that can produce these toxins and cause disease. In addition, other virulence factors (intimin adhesin, hemolysin) may also be involved in O157 pathogenesis.
• The use of antibiotics in humans for treatment of O157:H7 is controversial. They have not been shown to alter the course of disease in a positive way. In fact, use of antibiotics was a risk factor for more serious disease in one study, probably because of elimination of competing bacterial flora. Antibiotic-induced damage to the bacteria may also lead to enhanced release of SLTs.

What is the role of cattle as a reservoir of E. coli O157:H7?

Cattle have been implicated as the most important source of E. coli O157:H7. Prevalence estimates vary, but it appears that although a substantial percentage of both dairy herds and beef feedlots have infected animals, the actual number of individual infected animals at any one time is relatively low.

• The 2002 USDA NAHMS study found that 38.5% of dairy farms had at least one cow that was culture [+] when sampled, but only 4.3 % of individual cows were shedding the organism.
• Infection with O157:H7 is, however, subclinical in cattle and the duration of shedding may be quite variable and intermittent, making test and removal control programs impossible at this time.
• Dairy calves and heifers appear to shed the organism more often than adults. The peak time of infection is thought to be 3-18 months of age.
• Recovery of O157:H7 from beef feedlots is highest in pens from which the cattle had been in the feedlot for the shortest periods of time.

Is E. coli O157:H7 directly zoonotic?

• Two recent studies have demonstrated higher than expected rates of seropositivity to O157 among farm families.
  • There are also reports of toxigenic, though non-O157, E. coli infections among farm families in Ontario in which the human and cattle isolates were identical.
• There have been several reported incidents of transmission to children that visited or lived on a farm. In some of these cases, the bacterial isolates from the children and the cows were proven to be identical by pulse field gel electrophoresis.
  • In one case, transmission may have been via raw milk that was consumed on the farm.
• In May 2000 in Washington and November 2000 in Pennsylvania, 56 children were infected (19 required hospitalization) through contact with animals during school or family visits to farms.
• Approximately 26 people acquired O157:H7 in August 2001 in association with attendance at a county fair here in Wisconsin in Ozaukee County.
• The converse of increased risk for O157:H7 infections among farm families is the possibility that individuals from farms with repeated, low-level exposure may actually develop resistance to infection.

Food-borne E. coli O157:H7 infections in humans:

E. coli O157:H7 was first isolated in 1982 and gained prominence because of a number of well-publicized outbreaks associated with undercooked, fast-food hamburgers. But other foods have also been incriminated, including raw potatoes, raw milk, unpasteurized fruit juices and apple cider, lettuce/alfalfa sprouts/salads (at least 11 outbreaks in the U.S. since 1995), and possibly even sea eels in Japan!

• There is also evidence for waterborne infection via simply swimming in a contaminated lake or via consumption of contaminated water.
  • In 1999, nearly 1000 people were infected and at least 2 people died after consuming water at a county fair in upstate NY. The ground water- well at the fair was thought to have been contaminated by manure run-off from a cattle exhibit barn after a heavy rainfall and the unchlorinated water was used by vendors to make beverages and ice. (Note: some of these people were also infected with C. jejuni.

Can animals other than cattle be sources of human infection?

Deer:

• E. coli O157 has been isolated from deer, suggesting a possible wildlife source for infection. In one case, the organisms isolated from 2 deer and 5 cattle on a ranch in Texas had identical PFGE patterns.
  • In addition, infection has been associated with consumption of venison/jerky.
• Deer have been experimentally infected and shown to intermittently shed the organism as in cattle.

Pigs:

• SLT-producing E. coli have been isolated from pigs. The porcine "edema disease" variant of shiga-like toxin, SLT-IIe, was originally thought to be distinct from the toxins causing HUS in humans, but recent cases of HUS have been associated with swine isolates. In addition, a survey of pigs in Japan revealed ~ the same level of infection with O157:H7 in pigs as in the cattle population, and the presence of O157:H7 in the U.S. swine population has also been demonstrated recently. Finally, it also appears that O157:H7 strains can also persist in the intestinal tract of pigs, as well as cattle.

Dogs:

• The O157:H7 strain has been isolated from two asymptomatic dogs on a farm in Washington (along with cattle, a horse, two batches of stable flies and biofilms on water troughs on the farm!).
• There have been reports of dog-to-human transmission in Canada and the U.K., and a report of O157 isolation from a veterinary student's dog.
• A group of Greyhounds at a track in Alabama are reported to have been stricken with HUS-like disease.
  • Racing dogs are commonly fed raw beef, and E. coli O157:H7 was isolated from beef from "4D" [diseased, debilitated, down, dying ] cattle fed to the dogs.
  • Greyhounds may be an important research model for HUS.

Horses:

• There is a report of infection of a farmer with O157 after tending to a sick horse, from which an identical O157 isolate was obtained.

Can we eradicate E. coli O157:H7 as a public health concern by eradicating the organism on the farm...and can we even reasonably expect to do that?

Considerations:

• Both the lack of clinical disease in cattle and the intermittent nature of their shedding of E. coli O157:H7 make it extremely difficult to identify infected animals.
• Recent, though controversial, work suggests that feeding cattle a hay ration rather than grain can dramatically reduce E. coli infection and shedding.
• Additionally, inoculation of cattle with "probiotic" bacteria has been shown experimentally to reduce shedding of E. coli.

Contaminated buildings?:
E. coli O157 was recovered from the rafters, walls, and dust in a county fair building linked to human infections in Ohio in 2001 - airborne infection?

Overall, it may be possible in the future to impact the frequency of bovine infection and shedding through changes in management and feeding procedures. For the foreseeable future, however, the reality is that E. coli O157:H7 must be viewed as a foodborne zoonosis whose control rests with the consumer (cook your beef!). It cannot reasonably be eliminated at the farm level until a great deal more is known about risk factors for infection of cattle, immune responses and possible immunization strategies, additional reservoirs, etc.

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Salmonella typhimurium DT104

This is a specific serotype of Salmonella typhimurium that has been associated with multi-drug antibiotic resistance and serious disease in both animals and humans. It was first isolated in the United Kingdom in 1984 and was associated with human hospitalization rates approaching 50% and 5% mortality. Cattle mortality approached 40%. In addition, the rate of isolation of DT104 has skyrocketed in the United Kingdom, from 259 human cases in 1984 to 4,006 in 1996.

In the United States, DT104 was first isolated in 1985 and there have been 5 localized outbreaks reported in the United States: one in Vermont, two in Washington and two in California . The prevalence of DT104 is also growing in the United States. Data from 1995, 1998 and 1999 show that 28-31% of Salmonella typhimurium isolates have the R-type ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracycline) antibiotic resistance pattern of DT104.

• While infected cattle and their feces are clearly the most important risks for human exposure, it should be noted that multidrug-resistant Salmonella DT104 has also been isolated from 1-2% of cats in Scotland and from pet birds. Outbreaks of multi-drug resistant Salmonella have been documented among employees and clients of small animal practices and shelters in Idaho, Washington and Minnesota since 1999 in association with infected cats.

Salmonella newport isolates that are resistant to amoxicillin-clavulenic acid and cephalosporins, in addition to the antibiotic resistance spectrum of S. typhimurium DT104, are currently emerging as infections of both animals (cattle, pigs, chickens) and humans. This resistance pattern is of particular significance because ceftriaxone is a drug-of-choice for treating severe Salmonella infections in humans.

References:

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Angulo F.J. 1997. Multidrug resistant Salmonella typhimurium definitive type DT104. Emerg. Infect. Dis. 3:414.

Carlson, S.A. et al. 2002. Abomasitis associated with multiple antibiotic resistant Salmonella enterica serotype typhimurium phagetype DT104. Vet. Microbiol. 85:233-240.

Davis, M.A. et al. 1999. Changes in antimicrobial resistance among Salmonella enteritica serovar typhimurium isolates from humans and cattle in the northwestern United States, 1982-1997. Emerg. Infect. Dis. 5:802-806.

Fone, D.L. and R.M. Barker. 1994. Associations between human and farm animal infections with Salmonella typhimurium DT104 in Herefordshire. CDR Review 4:R136-R140.

Glynn, M.K. et al. 1998. Emergence of multidrug-resistant Salmonella enterica serotype typhimurium DT104 infections in the United States. N. Eng. J. Med. 338:1333-1338.

Low, J.C., B. Tennant and D. Munro. 1996. Multiple-resistant Salmonella typhimurium DT104 in cats. The Lancet 348:1391.

Ribot, E.M. et al. 2002. Salmonella enterica serotype typhimurium DT104 isolated from humans, United States, 1985, 1990, and 1995. Emerg. Infect. Dis. 8:387-391.

Spake, A. 1997. O is for outbreak. U.S. News and World Report Nov. 24: 70-84.

Zhao, S. et al. 2003. Characterization of Salmonella enterica serotype Newport isolated from humans and food animals. J. Clin. Microbiol. 41:5366-5371.