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SUPPLEMENT. FOOD SAFETY CONCERNS OF VEROTOXIN-PRODUCING ESCHERICHIA COLI

Non-O157 Verotoxin-Producing Escherichia coli: A Problem, Paradox, and Paradigm

National Escherichia coli Reference Laboratory, Microbiological Diagnostic Unit, Public Health Laboratory, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3052, Australia

Abstract

The problems associated with identification and characterization of non-O157 verotoxin-producing Escherichia coli (VTEC) are discussed. The paradox of VTEC is that most reports of human illnesses are associated with serotypes such as O157:H7, O111:H^- (nonmotile), O26:H11, and O113:H21, which are rarely found in domestic animals. However, those VTEC serotypes commonly found in domestic animals, especially ruminants, rarely cause human illnesses. When they cause human illnesses, the symptoms are similar to those caused by the serotypes E. coli O157:H7, O111:H^-, O26:H11, and O113:H21. The impact of VTEC on human and animal health is also addressed. The VTEC and their toxicity are considered as a paradigm for emerging pathogens. The question on how such pathogens could arise from a basic commensal population is also addressed.

Key Words: Escherichia coli • food safety • cytotoxicity • food-borne pathogens • verotoxins

Verotoxin-producing Escherichia coli (VTEC) also known as Shiga toxin-producing E. coli (STEC) have emerged in the past two decades as important causes of morbidity and mortality in humans. With many of the outbreaks of VTEC infections being directly or indirectly associated with food, there have also been extensive economic losses to food processors and suppliers. Worldwide, most of the reported human illness outbreaks have been attributed to the O157:H7 serotype, which was first associated with two major outbreaks in the United States in 1982 (1). This serotype also has been reported as the cause of two major outbreaks in the West Coast of the United States (2) and an outbreak in Japan (3). In the wake of these and many other reported outbreaks due to E. coli O157:H7, several selective media have been developed to identify and characterize E. coli O157:H7. The earliest of these was based on the realization that E. coli O157:H7 strains do not ferment sorbitol, whereas the majority of other E. coli do (4). Other media designed specifically to select for these VTEC include CHROMagar O157 (5) and Rainbow agar O157 (6). Therefore, the use of these media and the reports on O157:H7 outbreaks have created the general perception that this serotype is the only VTEC of significant importance.

Although O157 VTEC probably emerged in late 1970s (7, 8), non-O157 VTEC (e.g., serogroups O18, O26, O111, and O128) have been known earlier to produce toxins that have toxic effects on African Green Monkey kidney (Vero) cells in cultures (9). Within three years from publishing this report (9), there were other reports linking VTEC to human illnesses in the United Kingdom (10) and New Zealand (11). In addition, a retrospective study has indicated that these VTEC isolates had been present for some time (12). A reexamination of reports of major human illness outbreaks has also suggested that VTEC may well have been involved. The major outbreak in the North Eastern United States in the 1950s is an example (13). Thus, by the 1980s, it was realized that a newly described group of pathogenic E. coli was the cause of many cases of human morbidity and mortality. By the end of the decade, Karmali (14) reviewed the occurrence of VTEC and noted a variety of serotypes.

Since the beginning of the 20th century, it had been realized that strains of Shigella dysenteriae Type 1 produce a potent toxin (15, 16), which was known as Shiga toxin. Studies in the 1980s on the nature and properties of the toxins involved showed a strong relationship between one of the toxins associated with VTEC and Shiga toxin (17). The antigenically distinct Shiga toxin 2 was described later (18), and its characteristics were evaluated (19). It was soon realized that the hemolytic uremic syndrome (HUS) frequently found in cases associated with outbreaks of VTEC infections was clinically similar to the condition originally described in association with S. dysenteriae Type 1 infections (20). As a result, a new group of pathogens (i.e., VTEC or STEC) with the ability to produce one or two toxins (verotoxin 1 [VT1] and verotoxin 2 [VT2]) was established. The problem, however, is that most laboratories around the world have been testing for VTEC O157 strains and totally ignoring other VTEC serotypes that may be as widespread in nature.

The Problem

Because large number of outbreaks of human illnesses were attributed to E. coli O157:H7, and due to the availability of several selective media designed for isolation of this serotype, many laboratories around the world have limited their screening of human or animal feces to E. coli O157:H7. However, there are over 60 VTEC serotypes that have been associated with human illnesses. Therefore, it seems unrealistic to attempt to screen humans or animals for one serotype such as O157:H7.

Non-O157 VTEC Associated with Human Illnesses.
From the first reports on VTEC (9–11), the importance of specific pathogenic VTEC serotypes (i.e., O26:H^- [nonmotile], O26:H11, O55:H7, O111:H^-, and O111:H8) was recognized. In late 1980s, several human illness (i.e., hemorrhagic colitis [HC] and HUS) outbreaks were reported worldwide and were attributed to non-O157:H7 serotypes. These include O4:H^-, O45:H2, O111:H^-, and O145:H^- in the United States (21), O4:H5 and O111:H2 in Australia (22), and O26:H11, O104:H2, O153:H25, and O163:H19 (23) as well as O5:H^-, O55:H7, and O103:H2 (24) in the United Kingdom.

It is worth noting that the number of human illness outbreaks due to VTEC (especially non-O157:H7) infection has increased dramatically in the past decade worldwide. Examples included O111:H^- in Italy (25) and Australia (26, 27), O111:H2 in Germany (28), O103:H2 in France (29), the United States (30), and Germany (31), O145:H5 in Japan (32), O104:H21 in the U.S. (33), and O111:H8 (34) in the United States. Other VTEC strains (e.g., H12, H16, and H30) belonging to the O118 serogroup seem to be continuously emerging as a major cause of human illnesses in many parts of the world (35). However, the question that needs to be addressed is whether these serotypes are newly emerging or have been around in the past without being detected.

Difficulty of Detection of Non-O157 VTEC.
The major problem in detecting non-O157 VTEC is that apart from producing verotoxin(s), they do not differ significantly in their biochemical characteristics from typical commensal E. coli. The only exception is the possible decreased ability to ferment carbohydrate-like substances (36). However, this characteristic has not been used in developing a medium for VTEC detection in a manner similar to that of sorbitol-MacConkey (SMAC) agar (4). Thus, it is the goal of microbiologists in this field to be able to select non-O157 VTEC by using a specialized medium as the case in selecting most O157 VTEC by using SMAC agar.

Detection Media Based on Enterohemolysin Production.
The observations by Beutin et al. (37) of a close association between cytotoxicity and production of a newly described hemolysin (i.e., Enterohemolysin; Ehly), led to development of media able to detect EHly-producing E. coli and, therefore, potentially VTEC (38). This Ehly can only be observed on media prepared with washed sheep erythrocytes rather than whole sheep blood. The use of these media in Australia has led to the realization that non-O157 VTEC are as important as O157 VTEC (39, 40), and has significantly increased the isolation rate of these food-borne pathogens. However, it should be noted that not all VTEC produce Ehly, and not all Ehly-positive strains are VTEC. The addition of antibiotics (i.e., vancomycin, cefixime, and cefsulodin) to the basic washed sheep blood agar media (41, 42) significantly enhanced the yield of VTEC and this vancomycin-cefixime-cefsulodin blood agar greatly facilitates the detection of the Ehly-positive variants of VTEC. Because exceptions such as the presence of sorbitol-fermenting E. coli O157 strains (43) exist, it is important to emphasize the presence of VTEC that do not produce Ehly as well as Ehly-producing E. coli that do not produce toxins.

Detection of Toxin Activity.
Having been originally described on the basis of inducing toxic effects on Vero cells (9), demonstration of the cytotoxic effects of VTEC on these cells remains the standard method of detection. It is important to emphasize that the effects of the verotoxins (VT1 and VT2) are similar. These toxins can be titrated and, thus, a quantitative measure of the amount present can be assessed. Neutralization studies with specific antibodies can also be performed. Of greatest importance is the fact that using Vero cells is the only means by which a possible third verotoxin will ever be found if such a toxin exists. Methods based on identifying specific antigens or specific base sequences on the genes that code for the toxins are likely to overlook potential new toxins. Although using the cytotoxic effects on Vero cells continues, it is still considered a detection method that is not very easily used in a routine laboratory. It requires a continuous supply of cells, specialized techniques, and time because the cytotoxic effects sometimes require several days to be detected.

Immunological Tests for VTEC.
As part of the early investigations of VTEC in the 1980s, their serological diversity was established (17–19). These studies also made available a number of antibodies that can be used for detection. For example, an immunoassay developed by Acheson et al. (44) uses the P1 glycoprotein from sheep hydatid cyst fluid to detect verotoxins. Other immunoassays use antibodies produced in one animal species to capture the toxins and antibodies produced in another to detect the captured antibodies. A number of these methods have been developed commercially and include tests using enzyme-linked immunoassay methods and latex agglutination. Although, in general, these tests are very successful in detecting VTEC, they are relatively expensive. For rapid identification, a commercial latex agglutination technique was developed (45). It is not only reproducible, but is also adaptable to detecting potential VTEC directly from primary isolation media (46).

DNA-Based Methods for VTEC Detection.
A number of assays based on polymerase chain reaction (PCR) for detection of VTEC have been developed over the years. In a recent review (47), 14 PCR systems that detect and subtype VTEC were summarized. Although different primers were used in most tests, they were generally successful in identification of the toxin genes. Only one system (48) gave nonspecific reaction with all the strains tested. Because there are 13 promising PCR systems available, it should not be difficult to select one that fits specific circumstances of a testing laboratory. However, it should be noted that any of these PCR systems is capable only of detecting the presence of a specific DNA sequence (i.e., toxin genes). This does not necessarily mean that the bacterium is capable of producing the toxins. Because fecal or food samples may contain substances that specifically inhibit the PCR, these samples may require initial processes before amplification. Specific DNA preparation methods or specific tests may have to be performed on cultures obtained from growing E. coli in selective or nonselective media.

Summary of the Problem.
Because of the increasing number of human illness outbreaks due to non-O157:H7 VTEC, many laboratories have explored potential development and adaptation of some of the techniques discussed above. However, several obstacles, (i.e., time, effort, and cost) are responsible for the slow expansion of using these techniques for routine testing. Even if these tests are used, they will only be able to determine if a non-O157 VTEC is indeed present in a given food, water, or fecal sample. These tests then will require a large range of specific E. coli antisera, both "O" and "H" to be able to characterize the VTEC serotype. Such full E. coli serotyping is currently only available in a few reference laboratories around the world. At the present time, it is relatively easy to identify E. coli O157 in a sample by using SMAC agar and testing the suspect colonies with a commercial serological reagent for O157. Unfortunately, this not only is impossible for many important non-O157 VTEC at present, but also may never be achievable.

The Paradox

Extensive studies worldwide have demonstrated the presence of different VTEC serotypes in the gastrointestinal tract of animals, especially ruminants, without causing them illnesses. Occasionally, the same VTEC serotypes are implicated in illnesses in preweaned ruminants. Also, there appears to be a certain host species-specificity with respect to the VTEC being carried. Of the nonruminants, pigs are the other main group of animals from which VTEC can be isolated. The presence of VTEC in swine is generally associated with sick young animals, and the VTEC infection seems confined to a very restricted group of serotypes (e.g., O138:H14, O138:H^-, O139:H1, O141:H4, O141:H^-, O149:H10, and O149:H19) that do not appear to be present in ruminants. These porcine non-O157 VTEC serotypes are generally not detected in the gastrointestinal tract of healthy humans.

Ecological Aspects of Non-O157 VTEC in Animals and Humans.
Fagan et al. (49) demonstrated that 61%, 38%, and 40% of fecal samples from healthy sheep, cattle, and goats, respectively, were VTEC positive. These results are in agreement with those reported in earlier studies (50–52). More recently, a Japanese study (53) showed VTEC prevalence rates of 46%, 66%, and 69% in calves, heifers, and cows, respectively. Most of the VTEC isolates detected in this study belonged to non-O157 serogroups including O8, O26, O84, O113, and O116. As discussed previously, there have been VTEC infections in humans for many years before being considered food-borne pathogens in the 1980s. The contamination of beef during slaughter also was recognized at that time. Apart from individuals closely associated with ruminants at the preharvest (farmers or ranchers) or postharvest (meat packers) levels, it appears that healthy humans do not normally carry VTEC (54, 55). These studies have also shown that the VTEC serotypes isolated from healthy humans were those commonly isolated from healthy ruminants.

The VTEC O26 Serogroup.
The O26 VTEC serogroup was among the first VTEC to be reported (10, 11). Of the 1560 reported strains of non-O157 VTEC, 105 (6.7%) belonged to the O26 serogroup. These VTEC O26 strains are summarized in Table I. This summary shows that these O26 strains appear to occur exclusively in cattle, their products, and humans. The ratio of isolations from sick and healthy cattle was 4:3, whereas this ratio was 76:3 in humans. Thus, these VTEC strains should be considered as pathogens for both cattle and humans.

The Paradigm

The Concept of the Paradigm.
All warm-blooded animals as well as humans carry E. coli in their intestines, with numbers as high as 10⁹/g of feces (62). Thus, it can be easily calculated that 10²¹ E. coli of human origin are shed daily into the environment. E. coli usually colonize in human infants within 4 days. Infants acquire their E. coli either from their mothers’ feces at birth or more rarely from the environment (63). E. coli are continuously ingested with food and replace part of the intestinal E. coli population (64). This creates the great variety of E. coli types present in human feces at any time (65). These various E. coli types are in constant flux and competition with each other and with other bacterial species in the human intestine. E. coli are also able to survive outside the intestines and have been isolated from most nonmarine aqueous environments, including pristine samples in tropical rain forests and water reservoirs designed for human use (66).

In the 1940s, it was realized that certain E. coli types can cause severe diarrhea, especially in infants (67). In the 1970s, Rowe et al. (68) indicated that a group of E. coli was responsible for a large number of the cases of travelers’ diarrhea. The pathogens were shown to produce one or two enterotoxins and were named the enterotoxigenic E. coli (ETEC). Occasional outbreaks of food-borne diarrhea in the developed countries were also attributed to these ETEC (69). The VTEC emerged since the early 1980s (9) as cases of outbreaks of human illnesses were reported.

The healthy human colonic E. coli community is diverse, and a clear distinction can be drawn between the resident and transient E. coli serotypes. Only special selective methodology will be able to characterize the transient types of E. coli. Changes in life patterns such as travel or eating out appear to cause a greater change in the colonic E. coli community than regular eating at home (64, 70, 71).

The changes in E. coli population in ruminants such as cattle and sheep are most probably similar to those occurring in humans. For example, grazing cattle and sheep will continuously be recontaminated with the E. coli strains that were shed by other members of their herds or flocks, respectively. It has been shown that during slaughter, dressing, and processing of ruminant carcasses, fecal E. coli can contaminate the meat surfaces (72).

For almost two decades, most VTEC studies concentrated only on E. coli O157:H7. A recent study (73), however, has shown that although a single outbreak was predominantly due to E. coli O111:H^-, other VTEC serotypes (e.g., O157:H7) were also involved. If only standard screening methods had been used, this outbreak would have been attributed to E. coli O157:H7. When VTEC isolates were recently compared over a 5-year period in Australia, it was found that VTEC other than O157:H7 were the major causes of human illnesses (40).

The concept of the VTEC paradigm is that out of commensal E. coli, there can emerge pathogenic variants that cause human illnesses. These pathogens differ from their commensal counterparts in their carriage of the virulence factors. There will also be strains among these commensal E. coli that carry some of the virulence factors, but cannot cause human illnesses.

When is a VTEC not a pathogen? The characteristics that are required for a commensal E. coli to establish itself within the human intestines and to compete with other E. coli as well as other bacterial species or types are obviously of great advantage to VTEC. The verotoxins have been demonstrated to be very potent toxins, with LD₅₀ levels for mice in the order of 10^-9 g (74). Also, many VTEC produce a variety of virulence factors that make them potent human pathogens. Despite being such potent human pathogens, they appear to be virtually harmless to ruminants, in which they are able to spread from animal to animal, from herd to herd, and across continents. The VTEC serotypes with a global distribution include O5:H^-, O26:H11, O91:H^-, O113:H21, O116:H21, O123:H^-, and O128:H2. Although VTEC comprise only a small proportion of the ruminant E. coli community, they have a selective advantage (75). This suggests that the factors providing VTEC with a competitive advantage in one niche (ruminants) may be the same factors that make them into pathogens in another host (humans).

Future Considerations

Our methods of producing, distributing, and handling food have changed extraordinarily in the past century. Many of these processes have created appropriate niches for food-borne pathogens. Such pathogens will continue to be difficult to identify, they will merge among the commensal groups, and will require extensive microbiological experience to be identified. It should be considered that more pathogenic E. coli will continue to emerge. There are already numbers of such variants, including the enteroaggregative E. coli, the diffuse adherent E. coli, the cytotoxic necrotizing factor-producing E. coli, the cytolethal distending toxin-producing E. coli, and probably many others. Therefore, pathogenic E. coli can be seen as a paradigm of potential future food-borne pathogens and probably other pathogens as well. The current heavy reliance on very specific tests based either on the use of specific nucleic acid sequences or monoclonal antibodies will become a severe disadvantage in detecting such newly emerging pathogens. Only the experienced and well-trained microbiologist with a keen eye, an open mind, and a strong sense of curiosity will be able to observe such new developments. It is in the hands of these scientists that the challenges of the twenty-first century should be placed.

Footnotes

¹ To whom requests for reprints should be addressed at National Escherichia coli Reference Laboratory, Microbiological Diagnostic Unit, Public Health Laboratory, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3052, Australia. E-mail: k.bettelheim{at}microbiology.unimelb.edu.au

References

1. Riley LW, Remis RS, Helgerson SD, McGee HB, Wells GJ, Davis BR, Herbert RJ, Olcott ES, Johnson LM, Hargrett NT, Blake PA, Cohen ML. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med 308:681–685, 1983.[Abstract]
2. Centers for Disease Control and Prevention. Update: multistate outbreak of Escherichia coli O157 infections in hamburgers: Western United States 1992–1993. Morbid Mortal Wkly Rep 42:258–263, 1993.[Medline]
3. Watanabe H, Wada A, Inagaki Y, Itoh K, Tamura K. Outbreaks of enterohaemorrhagic Escherichia coli O157:H7 infection by two different genotype strains in Japan. Lancet 348:381–382, 1996.
4. March SB, Ratnam S. Sorbitol-MacConkey medium for detection of Escherichia coli O157:H7 associated with haemorrhagic colitis. J Clin Microbiol 23:869–872, 1986.[Abstract/Free Full Text]
5. Bettelheim KA. Reliability of CHROMagar O157 for the detection of enterohaemorrhagic Escherichia coli (EHEC) O157 but not EHEC belonging to other serogroups. J Appl Microbiol 85:425–428, 1998.[Medline]
6. Bettelheim KA. Studies of Escherichia coli cultured on Rainbow agar O157 with particular reference to Enterohaemorrhagic Escherichia coli (EHEC). Microbiol Immunol 42:265–269, 1998.[Medline]
7. Ørskov F, Ørskov I, Villar JA. Cattle as a reservoir of verotoxin-producing Escherichia coli O157:H7. Lancet ii:276, 1987.
8. Feng P, Lampel KA, Karch H, Whittam TS. Genotypic and phenotypic changes in the emergence of Escherichia coli O157:H7. J Infect Dis 177:1750–1753, 1998.[Medline]
9. Konowalchuk J, Speirs JL, Stavric S. Vero response to a cytotoxin of Escherichia coli. Infect Immun 18:775–779, 1977.[Abstract/Free Full Text]
10. Wade WG, Thom BT, Evans N. Cytotoxic Enteropathogenic Escherichia coli. Lancet ii:1235–1236, 1979.
11. Wilson MW, Bettelheim KA. Cytotoxic Escherichia coli serotypes. Lancet i:201, 1980.
12. Bettelheim KA, Wilson MW. The enterotoxigenicity of strains of Escherichia coli isolated from the faeces of healthy people and cattle. J Hyg (Camb) 88:121–123, 1982.
13. Belnap WD, O’Donnell JJ. Epidemic gastroenteritis due to Escherichia coli O-111. J Pediatr 47:178–193, 1955.[Medline]
14. Karmali MA. Infection by verocytotoxin-producing Escherichia coli. Clin Microbiol Rev 2:15–38, 1989.[Abstract/Free Full Text]
15. Conradi H. Ueber lösliche, durch aseptische autolyse erhaltene Giftstoffe von Ruhr- und Typhus-Bazillen. Dtsche Med Wchschr 29:26–28, 1903.
16. Neisser M, Shiga K. Ueber freie Receptoren von Typhus- und Dysenteriebazillen und über das Dysenterietoxin. Dtsche Med Wchschr 29:61–62, 1903.
17. O’Brien AD, LaVeck GD, Thompson MR, Formal SB. Production of Shigella dysenteriae type 1-like cytotoxin by Escherichia coli. J Infect Dis 146:763–769, 1982.[Medline]
18. Strockbine NA, Marques LRM, Newland JW, Smith HW, Holmes RK, O’Brien AD. Two toxin-converting phages from Escherichia coli O157:H7 strain 933 encode antigenically distinct toxins with similar biological activities. Infect Immun 53:135–140, 1986.[Abstract/Free Full Text]
19. O’Brien AD, Holmes RK. Shiga and Shiga-like toxins. Microbiol Rev 51:206–220, 1987.[Free Full Text]
20. von Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. Hämolytisch-urämischessyndrome: beilaterale nierenrindennekrosen bei akuten erworbenen hämolytischen anämien. Schweiz Med Wchschr 85:905–909, 1955.
21. Tzipori S, Wachsmuth KI, Smithers J, Jackson C. Studies in gnotobiotic piglets on non-O157:H7 Escherichia coli serotypes isolated from patients with hemorrhagic colitis. Gastroenterology 94:590–597, 1988.[Medline]
22. Gunzburg S, Gracey M, Forbes D, Hewitt I, Bettelheim KA. Haemolytic-uraemic syndrome and verotoxigenic Escherichia coli. Med J Aust 149:54–55, 1988.[Medline]
23. Scotland SM, Rowe B, Smith HR, Willshaw GA, Gross RJ. Vero cytotoxin-producing strains of Escherichia coli from children with haemolytic uraemic syndrome and their detection by specific DNA probes. J Med Microbiol 25:237–243, 1988.[Abstract]
24. Dorn CR, Scotland SM, Smith HR, Willshaw GA, Rowe B. Properties of verocytotoxin-producing Escherichia coli of human and animal origin belonging to serogroups other than O157:H7. Epidemiol Infect 103:83–95, 1989.[Medline]
25. Caprioli A, Luzzi I, Rosmini F, Resti C, Edefonti A, Perfumo F, Farina C, Goglio A, Gianviti A, Rizzoni G. Community-wide outbreak of hemolytic-uremic syndrome associated with non-O157 verocytotoxin-producing Escherichia coli. J Infect Dis 169:208–211, 1994.[Medline]
26. Cameron S, Walker C, Beers M, Rose N, Anear E. Enterohaemorrhagic Escherichia coli outbreak in South Australia associated with consumption of mettwurst. Comm Dis Intell 19:70–71, 1995.
27. Paton AW, Ratcliff RM, Doyle MR, Seymour-Murray J, Davos D, Lancer JA, Paton JC. Molecular microbiological investigation of an outbreak of hemolytic-uremic syndrome caused by dry fermented sausage contaminated with Shiga-like toxin-producing Escherichia coli. J Clin Microbiol 34:1622–1627, 1996.[Abstract]
28. Morabito S, Karch H, Mariani-Kurkdjian P, Schmidt H, Minelli F, Bingen E, Caprioli A. Enteroaggregative, Shiga toxin-producing Escherichia coli O111:H2 associated with an outbreak of hemolytic-uremic syndrome. J Clin Microbiol 36:840–842, 1998.[Abstract/Free Full Text]
29. Mariani-Kurkdjian P, Denamur E, Milon A, Picard B, Cave H, Lambert-Zechovsky N, Loirat C, Goullet P, Sansonetti P, Elion J. Identification of a clone of Escherichia coli O103:H2 as a potential agent of hemolytic uremic syndrome in France. J Clin Microbiol 31:296–301, 1993.[Abstract/Free Full Text]
30. Tarr PI, Fouser LS, Stapleton AE, Wilson RA, Kim HH, Vary JC, Clausen CR. Hemolytic-uremic syndrome in a six-year-old girl after a urinary tract infection with Shiga-toxin-producing Escherichia coli O103:H2. N Engl J Med 335:635–638, 1996.[Free Full Text]
31. Karch H, Geitz C, Schmidt H. Increased Incidence of Infections with EHEC O103:H2.Notiziaro dell’Istituto Superiore di Sanita 10(3):2, 1997.
32. Kudoh Y, Kai A, Obata H, Kusunoki J, Monma C, Shingaki M, Yanagawa Y, Yamada S, Mtsushita S, Itoh T, Ohta K. Epidemiological Surveys on Verocytotoxin-Producing Escherichia coli Infections in Japan. In: Karmali MA, Goglio AG, Eds. Recent Advances in Verocytotoxin-Producing Escherichia coli Infections (Excerpta Medica International Congress Series 1072). Amsterdam, The Netherlands: Elsevier Science, pp53–56, 1994.
33. Centers for Disease Control and Prevention. Outbreak of acute gastroenteritis attributable to Escherichia coli serotype O104:H21: Helena, Montana, 1994. Morbid Mortal Wkly Rep 44:501–503, 1995.[Medline]
34. Bergmire-Sweat D, Marengo L, Pendergrass P, Hendricks K, Garcia M, Drumgoole R, Baldwin T, Kingsley K, Walsh B, Lang S, Prine L, Busby T, Trujillo L, Perrotta D, Hathaway A, Jones B, Jaiyeola A. Escherichia coli O111:H8 outbreak among teenage campers: Texas, 1999. J Am Med Assoc 283:2517, 2000.[Free Full Text]
35. Wieler LH, Busse B, Steinruck H, Beutin L, Weber A, Karch H, Baljer G. Enterohemorrhagic Escherichia coli (EHEC) strains of serogroup O118 display three distinctive clonal groups of EHEC pathogens. J Clin Microbiol 38:2162–2169, 2000.[Abstract/Free Full Text]
36. Bettelheim KA. Biochemical studies on enterohaemorrhagic Escherichia coli (EHEC). In: Kay D, Fricker C, Eds. Coliforms and E. coli Problem or Solution. Gateshead, Tyne, and Wear, UK: Royal Society of Chemistry, Atheneum Press, pp243–248, 1997.
37. Beutin L, Montenegro MA, Ørskov I, Ørskov F, Prada J, Zimmermann S, Stephan R. Close association of verocytotoxin (Shiga-like toxin) production with enterohemolysin production in strains of Escherichia coli. J Clin Microbiol 27:2559–2564, 1989.[Abstract/Free Full Text]
38. Bettelheim KA. Identification of enterohaemorrhagic Escherichia coli by means of their production of enterohaemolysin. J Appl Bacteriol 79:178–180, 1995.[Medline]
39. Bettelheim KA. A spectrum of verocytotoxigenic Escherichia coli. J Med Microbiol 47:1037–1038, 1998.[Medline]
40. Bettelheim KA. Enterohaemorrhagic Escherichia coli O157:H7: a red herring? J Med Microbiol 50:201–202, 2001.[Free Full Text]
41. Lehmacher A, Meier H, Aleksic S, Bockemühl J. Detection of hemolysin variants of Shiga toxin-producing Escherichia coli by PCR and culture on vancomycin-cefixime-cefsulodin blood agar. Appl Environ Microbiol 64:2449–2453, 1998.[Abstract/Free Full Text]
42. Hornitzky MA, Bettelheim KA, Djordjevic SP. The detection of Shiga toxin-producing Escherichia coli in diagnostic bovine faecal samples using vancomycin-cefixime-cefsulodin blood agar and PCR. FEMS Microbiol Lett 198:17–22, 2001.[Medline]
43. Karch H, Bielaszewska M. Sorbitol-fermenting Shiga toxin-producing Escherichia coli O157:H^- strains: epidemiology, phenotypic and molecular characteristics, and microbiological diagnosis. J Clin Microbiol 39:2043–2049, 2001.[Free Full Text]
44. Acheson DWK, Keusch GT, Lightowlers M, Donohue-Rolfe A. Enzyme-linked immunosorbent assay for Shiga toxin and Shiga-like toxin II using P1 glycoprotein from hydatid cysts. J Infect Dis 161:134–137, 1990.[Medline]
45. Chart H, Willshaw GA, Cheasty T. Evaluation of a reversed passive latex agglutination test for the detection of verocytotoxin (VT) expressed by strains of VT-producing Escherichia coli. Lett Appl Microbiol 32:370–374, 2001.[Medline]
46. Bettelheim KA. Development of a rapid method for the detection of verocytotoxin-producing Escherichia coli (VTEC). Lett Appl Microbiol 33:31–35, 2001.[Medline]
47. Bastian SN, Carle I, Grimont F. Comparison of 14 PCR systems for the detection and subtyping of stx genes in Shiga-toxin-producing Escherichia coli. Res Microbiol 149:457–472, 1998.[Medline]
48. Paton AW, Paton JC, Goldwater PN, Manning PA. Direct detection of Escherichia coli Shiga-like toxin genes in primary fecal cultures by polymerase chain reaction. J Clin Microbiol 31:3063–3067, 1993.[Abstract/Free Full Text]
49. Fagan PK, Hornitzky MA, Bettelheim KA, Djordjevic SP. Detection of Shiga-like toxin (stx1 and stx2), intimin (eaeA), and enterohemorhagic Escherichia coli (EHEC) hemolysin EHEC hlyA) genes in animal feces by multiplex PCR. Appl Environ Microbiol 65:868–872, 1999.[Abstract/Free Full Text]
50. Beutin L, Geier D, Steinrück H, Zimmermann S, Scheutz F. Prevalence and some properties of verotoxin (Shiga-like toxin)-producing Escherichia coli in seven different species of healthy domestic animals. J Clin Microbiol 31:2483–2488, 1993.[Abstract/Free Full Text]
51. Kudva IT, Hatfield PG, Hovde CJ. Characterization of Escherichia coli O157:H7 and other Shiga toxin-producing E. coli serotypes isolated from sheep. J Clin Microbiol 35:892–899, 1997.[Abstract]
52. Sidjabat-Tambunan H, Bensink J. Verotoxin-producing Escherichia coli from faeces of sheep, calves and pigs. Aust Vet J 75:292–293, 1997.[Medline]
53. Kobayashi H, Shimada J, Nakazawa M, Morozumi T, Pohjanvirta T, Pelkonen S, Yamamoto K. Prevalence and characteristics of Shiga toxin-producing Escherichia coli from healthy cattle in Japan. Appl Environ Microbiol 67:484–489, 2001.[Abstract/Free Full Text]
54. Stephan R, Hoelzle LE. Characterization of Shiga toxin type 2 variant B-subunit in Escherichia coli strains from asymptomatic human carriers by PCR-RFLP. Lett Appl Microbiol 31:139–142, 2000.[Medline]
55. Stephan R, Ragettli S, Untermann F. Prevalence and characteristics of verotoxin-producing Escherichia coli (VTEC) in stool samples from asymptomatic human carriers working in the meat processing industry in Switzerland. J Appl Microbiol 88:335–341, 2000.[Medline]
56. Djordjevic SP, Hornitzky MA, Bailey G, Gill P, Vanselow B, Walker K, Bettelheim KA. Virulence properties and serotypes of Shiga toxin-producing Escherichia coli from healthy Australian slaughter-age sheep. J Clin Microbiol 39:2017–2021, 2001.[Abstract/Free Full Text]
57. Pradel N, Boukhors K, Bertin Y, Forestier C, Martin C, Livrelli V. Heterogeneity of Shiga toxin-producing Escherichia coli strains isolated from hemolytic-uremic syndrome patients, cattle, and food samples in central France. Appl Environ Microbiol 67:2460–2468, 2001.[Abstract/Free Full Text]
58. Ramachandran V, Hornitzky MA, Bettelheim KA, Walker MJ, Djordjevic SP. The common ovine Shiga toxin 2-containing Escherichia coli serotypes and human isolates of the same serotypes possess a Stx2d toxin type. J Clin Microbiol 39:1932–1937, 2001.[Abstract/Free Full Text]
59. Piérard D, Stevens D, Moriau L, Lior H, Lauwers S. Isolation and virulence factors of verocytotoxin-producing Escherichia coli in human stools. Clin Microbiol Infect 3:531–540, 1997.[Medline]
60. Sperandio V, Kaper JB, Bortolini MR, Neves BC, Keller R, Trabulsi LR. Characterization of the locus of enterocyte effacement (LEE) in different enteropathogenic Escherichia coli (EPEC) and Shiga-toxin producing Escherichia coli (STEC) serotypes. FEMS Microbiol Lett 164:133–139, 1998.[Medline]
61. Paton AW, Srimanote P, Woodrow MC, Paton JC. Characterization of Saa, a novel autoagglutinating adhesin produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli strains that are virulent for humans. Infect Immun 69:6999–7009, 2001.[Abstract/Free Full Text]
62. Mitsuoka T, Hayakawa K. Die Faecalflora bei Menschen. I. Mitteilung: Die Zusammensetzung der Faecalflora der verschiedenen Altersgruppen. Zbl Bakt Parasit Hyg I Abt Orig A 223:333–342, 1972.
63. Bettelheim KA, Lennox-King SMJ. The acquisition of Escherichia coli by newborn babies. Infection 4:174–179, 1976.[Medline]
64. Shooter RA, Bettelheim KA, Lennox-King SMJ, O’Farrell S. Escherichia coli serotypes in the faeces of healthy adults over a period of several months. J Hyg (Camb) 78:95–98, 1977.
65. Bettelheim KA, Faiers M, Shooter RA. Serotypes of Escherichia coli in normal stools. Lancet ii:1224–1226, 1972.
66. Niemi RM, Niemi JS. Bacterial pollution of waters in pristine and agricultural lands. J Environ Qual 20:620–627, 1991.[Abstract/Free Full Text]
67. Bray J. Isolation of antigenically homogeneous strains of Bact. coli neapolitanum from summer diarrhea of infants. J Pathol Bacteriol 63:239–247, 1945.
68. Rowe B, Taylor J, Bettelheim KA. An investigation of travelers’ diarrhea. Lancet i:1–5, 1970.
69. Caprioli A, Falbo V, Ruggeri FM, Bisichia R, Casalino M, Donelli G. Comparison among enterotoxigenic strains of Escherichia coli isolated in Italy and Somalia. Eur J Epidemiol 4:251–255, 1988.[Medline]
70. Bettelheim KA, Cooke EM, O’Farrell SM, Shooter RA. The effect of diet on intestinal Escherichia coli. J Hyg (Camb) 79:43–45, 1977.
71. Majed NI, Bettelheim KA, Shooter RA, Moorhouse E. The effect of travel on faecal Escherichia coli serotypes. J Hyg (Camb) 8:481–487, 1978.
72. Bettelheim KA. The isolation of Escherichia coli from a sheep slaughtering line in an abattoir. Comp Immun Microbiol Infect Dis 4:93–100, 1981.[Medline]
73. Goldwater PN, Bettelheim KA. Escherichia coli O group serology of an haemolytic uraemic syndrome (HUS) epidemic. Scand J Infect Dis 32:385–394, 2000.[Medline]
74. Tesh VL, Burris JA, Owens JW, Gordon VM, Wadolkowski EA, O’Brien AD, Samuel JE. Comparison of the relative toxicities of Shiga-like toxin type I and type II for mice. Infect Immun 61:3392–3402, 1993.[Abstract/Free Full Text]
75. Bettelheim KA. Ecology of verotoxigenic Escherichia coli. Aust Vet J 75:912, 1997.[Medline]
76. Bielaszewska M, Janda J, Blahova K, Feber J, Potuzník V, Souckova A. Verocytotoxin-producing Escherichia coli in children with hemolytic uremic syndrome in the Czech Republic. Clin Nephrol 46:42–44, 1996.[Medline]
77. Bockemühl J, Aleksic S, Karch H. Serological and biochemical properties of Shiga-like toxin (Verotoxin)-producing strains of Escherichia coli, other than O-group 157, from patients in Germany. Zbl Bakt 276:189–195, 1992.
78. Bielaszewska M, Janda J, Blahova K, Srámkova L, Havlík J, Potuzník V. Verocytotoxin-producing Escherichia coli in children with hemolytic uremic syndrome and diarrhea in the Czech Republic. In: Karmali MA, Goglio AG, Eds. Recent Advances in Verocytotoxin-Producing Escherichia coli Infections (Excerpta Medica International Congress Series 1072). Amsterdam, The Netherlands: Elsevier Science, pp37–40, 1994.
79. Blanco M, Blanco JE, Blanco J, Mora A, Prado C, Alonso MP, Mourino M, Madrid C, Balsalobre C, Juarez AV. Distribution and characterization of faecal verotoxin-producing Escherichia coli (VTEC) isolated from healthy cattle. Vet Microbiol 54:309–319, 1997.[Medline]
80. Bokete TN, Whittam TS, Wilson RA, Clausen CR, Ocallahan CM, Moseley SL, Fritsche TR, Tarr PI. Genetic and phenotypic analysis of Escherichia coli with enteropathogenic characteristics isolated from Seattle children. J Infect Dis 175:1382–1389, 1997.[Medline]
81. Brooks HJL, Bettelheim KA, Todd B, Holdaway MD. Non-O157 vero cytotoxin producing Escherichia coli: aetiological agents of diarrhoea in children in Dunedin. New Zealand Comp Immun Microbiol Infect Dis 20:163–170, 1997.
82. Beutin L, Zimmermann S, Gleier K. Human infections with Shiga toxin-producing Escherichia coli other than serogroup O157 in Germany. Emerg Infect Dis 4:635–639, 1998.[Medline]
83. Clarke RC, Wilson JB, Read SC, Renwick S, Rahn K, Johnson RP, Alves D, Karmali MA, Lior H, McEwen SA, Spika J, Gyles CL. Verocytotoxin-producing Escherichia coli (VTEC) in the food chain: preharvest and processing perspectives. In: Karmali MA, Goglio AG, Eds. Recent Advances in Verocytotoxin-Producing Escherichia coli Infections (Excerpta Medica International Congress Series 1072). Amsterdam, The Netherlands: Elsevier Science, pp17–24, 1994.
84. Caprioli A, Luzzi I. VT2-producing E. coli O26:H11. Notiziaro dell’Istituto Superiore di Sanita 8:4, 1995.
85. Czirok E, Herpay M. National surveillance of VTEC infection (Hungary). Notiziaro dell’Istituto Superiore di Sanita 8:2, 1995.
86. Cobbold R, Desmarchelier P. A longitudinal study of Shiga-toxigenic Escherichia coli (STEC) prevalence in three Australian dairy. Vet Microbiol 71:125–137, 2000.[Medline]
87. Dorn CR, Francis DH, Angrick EJ, Wilgohs JA, Wilson RA, Collins JE, Jenke BH, Shawd SJ. Characteristics of verocytotoxin-producing Escherichia coli associated with intestinal colonization and diarrhea in calves. Vet Microbiol 36:149–159, 1993.[Medline]
88. Enami M, Nakasone N, Honma Y, Kakinohana S, Kudaka J, Iwanaga M. Expression of type I pili is abolished in verotoxin-producing Escherichia coli O157. FEMS Microbiol Lett 179:467–472, 1999.[Medline]
89. Fey PD, Wickert RS, Rupp ME, Safranek TJ, Hinrichs SH. Prevalence of non-O157:H7 Shiga toxin-producing Escherichia coli in diarrheal stool samples from Nebraska. Emerg Infect Dis 6:530–533, 2000.[Medline]
90. Goldwater PN, Bettelheim KA. The role of enterohaemorrhagic E. coli serotypes other than O157:H7 as causes of disease. In: Karmali MA, Goglio AG, Eds. Recent Advances in Verocytotoxin-Producing Escherichia coli Infections (Excerpta Medica International Congress Series 1072). Amsterdam, The Netherlands: Elsevier Science, pp57–60, 1994.
91. Giammanco A, Maggio M, Giammanco G, Morelli R, Minelli F, Scheutz F, Caprioli A. Characteristics of Escherichia coli strains belonging to enteropathogenic E. coli serogroups isolated in Italy from children with diarrhea. J Clin Microbiol 34:689–694, 1996.[Abstract]
92. Farina C, Goglio A, Conedera G, Minelli F, Caprioli A. Antimicrobial susceptibility of Escherichia coli O157 and other enterohaemorrhagic Escherichia coli isolated in Italy. Eur J Clin Microbiol Infect Dis 15:351–353, 1996.[Medline]
93. Huppertz HI, Rutkowski S, Busch DH, Eisebit R, Lissner R, Karch H. Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, Shiga toxin-producing E. coli, and E. coli expressing intimin and hemolysin. J Pediatr Gastroenteriol Nutr 29:452–456, 1999.[Medline]
94. Keskimäki M, Saari M, Heiskanen T, Siitonen A. Shiga toxin-producing Escherichia coli in Finland from 1990 through 1997: prevalence and characteristics of isolates. J Clin Microbiol 36:3641–3646, 1998.[Abstract/Free Full Text]
95. Ludwig K, Petric M, Blanchette V, Karmali M. Isolated thrombocytopenic purpura associated with infection due to verocytotoxin (Shiga toxin)-producing Escherichia coli serotype O26:H11. Clin Infect Dis 27:660–661, 1998.[Medline]
96. Mackenzie AMR, Lebel P, Orrbine E, Rowe PC, Hyde L, Chan F, Johnson W, McLaine PN. Sensitivities and specificities of premier E. coli O157 and premier EHEC enzyme immunoassays for diagnosis of infection with verotoxin (Shiga-like toxin)-producing Escherichia coli. J Clin Microbiol 36:1608–1611, 1998.[Abstract/Free Full Text]
97. Meng JH, Zhao SH, Doyle MP. Virulence genes of Shiga toxin-producing Escherichia coli isolated from food, animals and humans. Int J Food Microbiol 45:229–235, 1998.[Medline]
98. Miyamoto H. Statistical and Epidemiological Analyses on Food Poisonings and Infections and Applications by Microbiological Analyses, Project Research on Application of DNA and Phage Typing, etc. as Epidemiological Markers and Development of New Rapid Typings in Big Outbreak of Bacterial Food Poisonings. National Reports on "Emerging and Reemerging Infectious Diseases" 1997–1999; Ministry of Health and Welfare, Japan, 2000.
99. Piérard D, Stevens D, Moriau L, Lior H, Lauwers S. Three years PCR screening for VTEC in human stools in Brussels. In: Karmali MA, Goglio AG, Eds. Recent Advances in Verocytotoxin-Producing Escherichia coli Infections (Excerpta Medica International Congress Series 1072). Amsterdam, The Netherlands: Elsevier Science, pp33–36, 1994.
100. Pradel N, Livrelli V, De Champs C, Palcoux JB, Reynaud A, Scheutz F, Sirot J, Joly B, Forestier C. Prevalence and characterization of Shiga toxin-producing Escherichia coli isolated from cattle, food, and children during a one-year prospective study in France. J Clin Microbiol 38:1023–1031, 2000.[Abstract/Free Full Text]
101. Read SC, Clarke RC, Martin A, De Grandis SA, Hii J, Gyles CL. Polymerase chain reaction for detection of verocytotoxigenic Escherichia coli isolated from animal and food sources. Mol Cell Probes 6:153–161, 1992.[Medline]
102. Smith HR, Scotland SM, Willshaw GA, Wray C, McLaren IM, Cheasty T, Rowe B. Verocytotoxin production and the presence of VT genes in Escherichia coli strains of animal origin. J Gen Microbiol 134:829–834, 1988.[Medline]
103. Scheutz F. VTEC isolated from Danish patients, 1986–1994. Notiziaro dell’Istituto Superiore di Sanita 8:3, 1995.
104. Sandhu KS, Clarke RC, McFadden K, Brouwer A, Loouie M, Wilson J, Lior H, Gyles CL. Prevalence of the eaeA gene in verotoxigenic Escherichia coli strains from dairy cattle in Southwest Ontario. Epidemiol Infect 116:1–7, 1996.[Medline]
105. Schmidt H, von Maldeghem J, Frosch M, Karch H. Antibiotic susceptibilities of verocytotoxin-producing Escherichia coli O157 and non-O157 strains isolated from patients and healthy subjects in Germany during 1996. Antimicrob Chemother 42:548–550, 1998.
106. Sandhu KS, Clarke RC, Gyles CL. Virulence markers in Shiga toxin-producing Escherichia coli isolated from cattle. Can J Vet Res 63:177–184, 1999.[Medline]
107. Schmidt H, Geitz C, Tarr PI, Frosch M, Karch H. Non-O157:H7 pathogenic Shiga toxin-producing Escherichia coli: phenotypic and genetic profiling of virulence traits and evidence for clonality. J Infect Dis 179:115–123, 1999.[Medline]
108. Schurman RD, Hariharan H, Heaney SB, Rahn K. Prevalence and characteristics of Shiga toxin-producing Escherichia coli in beef cattle slaughtered on Prince Edward Island. J Food Protect 63:1583–1586, 2000.[Medline]
109. Tamura K, Sakazaki R, Murase M, Kosako Y. Serotyping and categorisation of Escherichia coli strains isolated between 1958 and 1992 from diarrhoeal diseases in Asia. J Med Microbiol 45:353–358, 1996.[Abstract]
110. Thomas A, Cheasty T, Frost JA, Chart H, Smith HR, Rowe B. Vero cytotoxin producing Escherichia coli, particularly serogroup O157, associated with human infections in England and Wales: 1992–1994. Epidemiol Infect 117:1–10, 1996.[Medline]
111. Takeda Y. Enterohemorrhagic Escherichia coli infection in Japan. Pediatr Int. 41:198–201, 1999.[Medline]
112. Wells JG, Shipman LD, Greene KD, Sowers EG, Green JH, Cameron DN Downes FP, Martin ML, Griffin PM, Ostroff SM, Potter ME, Tauxe RV, Wachsmuth IK. Isolation of Escherichia coli O157:H7 and other Shiga-like toxin-producing E. coli from dairy cattle. J Clin Microbiol 29:985–989, 1991.[Abstract/Free Full Text]
113. Wieler LH, Vieler E, Erpenstein C, Schlapp T, Steinrück H, Bauerfeind R, Byomi A, Baljer G. Shiga toxin-producing Escherichia coli strains from bovines: association of adhesion with carriage of eae and other genes. J Clin Microbiol 34:2980–2984, 1996.[Abstract]
114. Wilson JB, Clarke RC, Renwick SA, Rahn K, Johnson RP, Karmali MA, Lior H, Alves D, Gyles CL, Sandhu KS, McEwen SA, Spika JS. Vero cytotoxigenic Escherichia coli infection in dairy farm families. J Infect Dis 174:1021–1027, 1996.[Medline]
115. Verweyen HM, Karch H, Allerberger F, Zimmerhackl LB. Enterohemorrhagic Escherichia coli (EHEC) in pediatric hemolytic-uremic syndrome: A prospective study in Germany and Austria. Infection 27:341–347, 1999.[Medline]
116. Zhang WL, Bielaszewska A, Liesegang H, Tschäpe H, Schmidt H, Bitzan M, Karch H. Molecular characteristics and epidemiological significance of Shiga toxin-producing Escherichia coli O26 strains. J Clin Microbiol 38:2134–2140, 2000.[Abstract/Free Full Text]
117. Piérard D, Etterijck R, van Breynaert J, Moriau L, Lauwers S. Results of screening for verocytotoxin-producing Escherichia coli in faeces in Belgium. Europ J Clin Microbiol Infect Dis 9:198–201, 1990.[Medline]
118. Pryor W, Hodson H, McIntyre P, Bettelheim KA. Toxigenic Escherichia coli in uraemic haemolytic syndrome. Med J Aust 152:221–222, 1990.[Medline]
119. Allerberger F, Rossboth D, Dierich MP, Aleksic S, Schmidt H, Karch H. Prevalence and clinical manifestations of Shiga toxin-producing Escherichia coli infections in Austrian children. Eur J Clin Microbiol Infect Dis 15:545–550, 1996.[Medline]
120. Banatvala N, Debeukelaer MM, Griffin PM, Barrett TJ, Greene KD, Green JH, Wells JG. Shiga-like toxin producing Escherichia coli O111 and associated hemolytic-uremic syndrome: a family outbreak. Pediatr Infect Dis J 15:1008–1011, 1996.[Medline]
121. Huppertz HI, Busch D, Schmidt H, Aleksic S, Karch H. Diarrhea in young children associated with Escherichia coli non-O157 organisms that produce Shiga-like toxin. J Pediatr 128:341–346, 1996.[Medline]
122. Park CH, Gates KM, Vandel NM, Hixon DL. Isolation of Shiga-like toxin producing Escherichia coli (O157 and non-O157) in a community hospital. Diag Microbiol Infect Dis 26:69–72, 1996.[Medline]
123. Karch H, Huppertz HI, Bockemühl J, Schmidt H, Schwarzkopf A, Lissner R. Shiga toxin-producing Escherichia coli infections in Germany. J Food Protect 60:1454–1457, 1997.
124. Strockbine N, Sowers E, Greene K, Hayes P, Griffin P, Wells J. Characterization of Shiga toxin-producing non-O157 Escherichia coli from the United States, 1983–1997 [abstract]. VTEC ’97 3^rd International Symposium and Workshop on Shiga Toxin (Verocytotoxin)-Producing Escherichia coli Infections. Baltimore (MD): Lois Joy Galler Foundation for Hemolytic Uremic Syndrome, Inc.; 1997. p67. Abstract nr 235/III.
125. Asakura H, Makino S, Shirahata T, Tsukamoto T, Kurazono H, Ikeda T, Takeshi K. Detection and genetical characterization of Shiga toxin-producing Escherichia coli from wild deer. Microbiol Immun 42:815–822, 1998.
126. Gallien P, Karch H, Much C, Steinruck H, Lehmann S, Timm M, Richter H, Perlberg KW, Protz D. Subtyped eae-genes in Shiga toxin-producing Escherichia coli (STEC): occurrence in raw or undercooked food samples and comparison of isolates from faecal samples and stool samples. Fleischwirtschaft 80:84–89, 2000.
127. Hornitzky MA, Bettelheim KA, Djordjevic SP. The isolation of enterohaemorrhagic Escherichia coli O111:H^- from Australian cattle. Aust Vet J 78:636–637, 2000.[Medline]
128. Hall GA, Chanter N, Bland AP. Comparison in gnotobiotic pigs in lesions caused by verotoxigenic and non-verotoxigenic Escherichia coli. Vet Pathol 25:205–210, 1985.
129. Willshaw GA, Scotland SM, Smith HR, Rowe B. Properties of verocytotoxin-producing Escherichia coli of human origin of O groups other than O157. J Infect Dis 166:797–802, 1992.[Medline]
130. Willshaw GA, Smith HR, Roberts D, Thirlwell J, Cheasty T, Rowe B. Examination of raw beef products for the presence of verocytotoxin-producing Escherichia coli, particularly those of serogroup O157. J Appl Bacteriol. 75:420–426, 1993.[Medline]
131. Wilson JB, Clarke RC, Renwick SA, Rahn K, Johnson D, Alves D, Karmali MA, Lior H, McEwen SA, Spika J. Verocytotoxigenic Escherichia coli infection on dairy farms in Southern Ontario. In: Karmali MA, Goglio AG, Eds. Recent Advances in Verocytotoxin-Producing Escherichia coli Infections (Excerpta Medica International Congress Series 1072). Amsterdam, The Netherlands: Elsevier Science, pp61–64, 1994.
132. Sidjabat-Tambunan H, Bensink J, Bettelheim KA. Isolation of verocytotoxin-producing Escherichia coli from mutton carcasses. Aust Vet J 76:364–365, 1998.[Medline]
133. Starr M, Bennett-Wood V, Bigham AK, Dekoning-Ward TP, Bordun AM, Lightfoot D, Bettelheim KA, Jones CL, Robins-Browne RM. Hemolytic-uremic syndrome following urinary tract infection with enterohemorrhagic Escherichia coli: case report and review. Clin Infect Dis 27:310–315, 1998.[Medline]
134. Todd ECD, Szabo RA, MacKenzie JM, Martin A, Rahn K, Gyles C, Gao A, Alves D, Yee AJ. Application of a DNA hybridization-hydrophobic-grid membrane filter method for detection and isolation of verotoxigenic Escherichia coli. Appl Environ Microbiol 65:4775–4780, 1999.[Abstract/Free Full Text]
135. Bettelheim KA, Bensink JC, Sidjabat-Tambunan H. Serotypes of verocytotoxin-producing (Shiga toxin-producing) Escherichia coli isolated from healthy sheep. Comp Immun Microbiol Infect Dis 23:1–7, 2000.[Medline]
136. Piérard D, Van Damme L, Stevens D, Moriau L, Lauwers S. Detection of verocytotoxin-producing Escherichia coli in meat in Belgium. In: Karmali MA, Goglio AG, Eds. Recent Advances in Verocytotoxin-Producing Escherichia coli Infections (Excerpta Medica International Congress Series 1072). Amsterdam, The Netherlands: Elsevier Science, pp77–80, 1994.
137. Beutin L, Geier D, Zimmermann S, Aleksic S, Gillespie HA, Whittam TS. Epidemiological relatedness and clonal types of natural populations of Escherichia coli strains producing Shiga toxins in separate populations of cattle and sheep. Appl Environ Microbiol 63:2175–2180, 1997.[Abstract]
138. Blanco M, Blanco JE, Gonzalez EA, Mora A, Jansen W, Gomes TAT, Zerbini LF, Yano T, Decastro AFP, Blanco J. Genes coding for enterotoxins and verotoxins in porcine Escherichia coli strains belonging to different O:K:H serotypes: relationship with toxic phenotypes. J Clin Microbiol 35:2958–2963, 1997.[Abstract]
139. Gallien P, Richter H, Klie H, Timm M, Karch H, Perlberg KW, Steinrück H, Riemer S, Djuren M, Protz D. Detection of STEC and epidemiological investigations in surrounding of a HUS patient. Berlin Münch Tierarzt Wchscht 110:342–346, 1997.
140. Richter H, Klie H, Timm M, Gallien P, Steinruck H, Perlberg KW, Protz D. Verotoxin-producing E. coli (VTEC) in faeces from cattle slaughtered in Germany. Berlin München Tierarzt Wchsch 110:121–127, 1997.
141. Bonnet R, Souweine B, Gauthier G, Rich C, Livrelli V, Sirot J, Joly B, Forrestier C. Non-O157:H7 Stx2-producing Escherichia coli strains associated with hemolytic uremic syndrome in adults. J Clin Microbiol 36:1777–1780, 1998.[Abstract/Free Full Text]
142. Baker M, Bennett J, Nicol C. Emergence of verotoxigenic Escherichia coli (VTEC) in New Zealand. New Zealand Publ Hlth Rpt 6:9–12, 1999.
143. Gallien P, Much C, Perlberg KW, Protz D. Subtyping of stx-genes in Shiga toxin-producing Escherichia coli (STEC): presence in raw foods and correlation to other factors. Fleischwirtschaft 79:99–103, 1999.
144. McCluskey BJ, Rice DH, Hancock DD, Hovde CJ, Besser TE, Gray S, Johnson RP. Prevalence of Escherichia coli O157 and other Shiga toxin-producing E. coli in lambs at slaughter. J Vet Diag Invest 11:563–565, 1999.[Free Full Text]
145. Timm M, Klie H, Richter H, Gallien P, Perlberg KW, Lehmann S, Protz D. Detection and prevalence of verotoxin-producing Escherichia coli (VTEC) in raw sausages. Berlin Münch Tierarzt Wchscht 112:385–389, 1999.
146. Tokhi AM, Peiris JSM, Scotland SM, Willshaw GA, Smith HR, Roberts D, Cheasty T. A longitudinal study of verocytotoxin-producing Escherichia coli cattle calves in Sri Lanka. Epidemiol Infect 110:197–208, 1993.[Medline]
147. Asakura H, Makino S, Shirahata T, Tsukamoto T, Kurazono H, Ikeda T, Takeshi K. Detection and long-term existence of Shiga toxin (Stx)-producing Escherichia coli in sheep. Microbiol Immun 42:683–688, 1998.
148. Miyao Y, Kataoka T, Nomoto T, Kai A, Itoh T, Itoh K. Prevalence of verotoxin-producing Escherichia coli harbored in the intestine of cattle in Japan. Vet Microbiol 61:137–143, 1998.[Medline]
149. Heuvelink AE, Wernars K, de Boer E. Occurrence of Escherichia coli O157 and other verocytotoxin-producing E. coli in retail raw meats in The Netherlands. J Food Protect 59:1267–1272, 1996.
150. Stephan R, Kühn K. Prevalence of verotoxin-producing Escherichia coli (VTEC) in bovine coli mastitis and their antibiotic resistance patterns. Zbl Veterinärm B 46:423–427, 1999.
151. Bettelheim KA, Bowden DS, Doultree JC, Catton MG, Chibo D, Ryan NJP, Wright PJ, Gunesekere IC, Griffith JM, Lightfoot D, Hogg GG, Bennett-Wood V, Marshall JA. Combined infection of Norwalk-like virus and verotoxin-producing bacteria associated with a gastroenteritis outbreak. J Diarrh Dis Res 17:34–36, 1999.
152. Bettelheim KA, Brown JE, Lolokha S, Echeverria P. Serotypes of Escherichia coli that hybridized with DNA probes for genes encoding Shiga-like Toxin I, Shiga-like Toxin II and serogroup O157 enterohemorrhagic E. coli fimbriae isolated from adults with diarrhea in Thailand. J Clin Microbiol 28:293–295, 1990.[Abstract/Free Full Text]
153. Suthienkul O, Brown JE, Seriwatana J, Tienthongdee S, Sastravaha S, Echeverria P. Shiga-like-toxin producing Escherichia coli in retail meats and cattle in Thailand. Appl Environ Microbiol 56:1135–1139, 1990.[Abstract/Free Full Text]
154. Thomas A, Chart H, Cheasty T, Smith HR, Frost JA, Rowe B. Verocytotoxin-producing Escherichia coli particularly serogroup O157 associated with human infections in the United Kingdom. Epidemiol Infect 110:591–600, 1993.[Medline]
155. Cerqueira AMF, Tibana A, Guth BEC. High occurrence of Shiga-like toxin-producing Escherichia coli isolated from raw beef products in Rio de Janeiro City. Brazil J Food Protect 60:177–180, 1997.
156. Klie H, Timm M, Richter H, Gallien P, Perlberg KW, Steinrück H. Detection and occurrence of verotoxin-forming and/or Shiga toxin-forming Escherichia coli (VTEC and/or STEC) in milk. Berlin Münch Tierarzt Wchscht 110:337–341, 1997.
157. Beutin L, Müller W. Cattle and verotoxigenic Escherichia coli (VTEC), an old relationship. Vet Rec 142:283–284, 1998.[Medline]
158. Goldwater PN, Giles N, Bettelheim KA. An unusual case of microangiopathic haemolytic anaemia associated with enterohaemorrhagic Escherichia coli O113:H21 infection, a verocytotoxin-2/Shiga toxin-2 producing serotype. J Infect 37:302–304, 1998.[Medline]
159. Rahn K, Renwick SA, Johnson RP, Wilson JB, Clarke RC, Alves D, McEwen SA, Lior H, Spika J. Follow-up study of verocytotoxigenic Escherichia coli infection in dairy farm families. J Infect Dis 177:1139–1140, 1998.[Medline]
160. Hashimoto H, Mizukoshi K, Nishi M, Kawakita T, Hasui S, Kato Y, Ueno Y, Takeya R, Okuda N, Takeda T. Epidemic of gastrointestinal tract infection including hemorrhagic colitis attributable to Shiga toxin 1-producing Escherichia coli O118:H2 at a junior high school in Japan. Pediatrics 103:E21–E25, 1999.
161. Paton AW, Woodrow MC, Doyle MR, Lanser JA, Paton JC. Molecular characterization of a Shiga toxigenic Escherichia coli O113:H21 strain lacking eae responsible for a cluster of cases of hemolytic-uremic syndrome. J Clin Microbiol 37:3357–3361, 1999.[Abstract/Free Full Text]
162. Stephan R, Untermann F. Virulence factors and phenotypical traits of verotoxin-producing Escherichia coli strains isolated from asymptomatic human carriers. J Clin Microbiol 37:1570–1572, 1999.[Abstract/Free Full Text]

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