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A ProMED-mail post <> ProMED-mail is a program of the International Society for Infectious Diseases <>

Date: Tue 29 Aug 2017
Source: Emerg Infect Dis Volume 23, Number 10--October 2017 [edited] <>

Mild Illness during Outbreak of Shiga Toxin-Producing _E. coli_ O157 Infections Associated with Agricultural Show, Australia
Shiga toxin producing _E. coli_ (STEC [or enterohemorrhagic _E. coli_, EHEC - Mod. LL]) is a major cause of serious human gastrointestinal illness and have the potential to cause life-threatening complications, such as hemolytic uremic syndrome (HUS) (1). An average of 0.4 cases of EHEC illness per 100 000 persons per year are reported to public health authorities in Australia (2). Disease severity can range from asymptomatic infection to serious and sometimes fatal illness, particularly in young children and the elderly (3,4).

Healthy ruminants, particularly cattle, are the reservoir for EHEC (5). Human infection with EHEC usually occurs as a result of inadvertent ingestion of fecal matter after consumption of contaminated food, water, or unpasteurized milk; contact with animals or their environments; or secondarily, through contact with infected humans (4,5). In the largest previously reported outbreak of EHEC illness in Australia in 1995, which was associated with consumption of mettwurst (uncooked, semidry, fermented sausages), HUS developed in 23 of the 51 case-patients identified, and there was 1 death (6).

The Study
A multidisciplinary incident management team was established to investigate an outbreak of EHEC illness associated with an annual agricultural show in Brisbane, Queensland, Australia, in August 2013. The incident management team defined primary and secondary outbreak cases. Persons with laboratory-confirmed EHEC infection associated with the outbreak and their household contacts were followed up until the point of microbiological evidence of clearance, which was defined as 2 consecutive negative stool samples collected more than 24h apart (7).

Case-patients and contacts with a high risk for transmission (persons under 5 years of age; persons unable to maintain good hygiene; or childcare, healthcare, aged care, or food preparation workers) were advised to avoid childcare and work settings in accordance with Queensland Health Guidelines (7). Enhanced surveillance measures were implemented to assist with case finding. Medical practitioners were requested to avoid use of antimicrobial drugs for suspected case-patients with EHEC infections because of previously reported associations between antimicrobial drug use and HUS. We developed a case-control study to obtain additional information related to animal contact, hand hygiene, and food consumption at the agricultural show. We analyzed data by using Epi Info 7 (Centers for Disease Control and Prevention, Atlanta, GA, USA). EHEC identified from human, environmental, and animal samples were serotyped for O and H antigens. Expression of Shiga toxin 1 (stx1) and stx2 genes was determined for selected isolates. Shiga toxin gene subtyping and whole-genome sequencing (WGS) analysis was performed.

During [21 Aug 2013] to [27 Sep 2013], we identified 57 outbreak-associated laboratory-confirmed case-patients with EHEC infection: 54 confirmed primary case-patients, 1 probable primary case-patient, and 2 secondary case-patients (Figure 1 [for figures, see original URL - Mod. LL]). Of the 57 cases-patients, 32 (56 percent) were female. Case-patients ranged in age from 1 to 77 (median 9) years; 31 (56 percent) case-patients were <10 years of age. Median incubation period after attending the agricultural show was 4 (range 1-11, 25th-75th percentile 3-5) days. Case-patients reported diarrhea (96 percent), abdominal pain (93 percent), bloody diarrhea (41 percent), and fever (32 percent) (Table 1). A total of 7 case-patients were hospitalized. No cases of HUS or deaths were reported.

Public Health Units followed up 40 case-patients until microbiological evidence of clearance; the remaining case-patients were lost to follow up. Median duration of EHEC excretion among primary case-patients was 18 (range 2-52) days (Table 2). After 27 days and 6 recurrent stools positive for EHEC, and after acute diarrheal illness had resolved, 1 child was given azithromycin on day 40 for 3 days to hasten decolonization. 2 consecutive stool specimens obtained more than 48 h after treatment with antimicrobial drugs was stopped were negative for EHEC in this child. This patient did not have any adverse effects from azithromycin treatment.

A total of 45 of 55 primary case-patients and 28 household contacts who attended the agricultural show were included in the case-control study. Median age of case-patients was 8 (range 1-77) years, and median age of controls was 38 (range 1-70) years. We showed by using univariate analysis that case-patients were not more likely than controls to have entered the animal nursery at the show. Case-patients were more likely than controls to have had contact with lambs or goats, fed the animals, or had their hands licked by animals.

We identified the same multilocus variable number tandem repeat and stx subtype genotype of _E. coli_ O157:H- in human case-patients, animal bedding from the animal nursery before disposal, and fecal samples collected from lambs, goats, and calves. WGS and read mapping to an _E. coli_ O157 reference genome showed that of the human, animal, and environmental isolates analyzed, all contained an IS1203v insertion that resulted in deletion of the first 494 bp of the stx2c subunit A gene (Figure 2). Expression of stx2 was not detected in these isolates by Immunocard STAT! EHEC (Meridian Bioscience, Cincinnati, OH, USA) and Shiga toxin Quik Chek (Alere, Waltham, MA, USA) lateral flow devices. No additional stx2 genes were identified, and no disruptions were detected in the stx1 gene regions of any of the isolates.

We found that EHEC infection was associated with feeding lambs or goats, feeding animals, and having the hands licked by animals. The course of _E. coli_ O157 infection was relatively mild; no cases of HUS were associated with this outbreak. Heiman et al. found that of 4928 cases of 390 _E. coli_ O157 illness outbreaks in the USA during 2003-2012, HUS was detected in 299 cases (6 percent of illnesses) (8). HUS cases with stx1+/stx2 _E. coli_ O157 isolates have been reported (9,10). We speculate that the absence of severe complications in this outbreak might have been caused, in part, by disruption of the stx2 subunit A gene by the IS1203v insertion, which resulted in lack of expression or a nonfunctional Stx2 toxin.

The proportion of case-patients reporting bloody diarrhea (19/46, 41 percent) was also lower than previously reported. Ethelberg et al. reported that 69 percent (56/81) of case-patients in Denmark infected with _E. coli_ O157 had bloody diarrhea (11). A recent retrospective cohort study reported that 61 percent (2027/3323) of symptomatic case-patients infected with _E. coli_ O157 Public Health England had bloody diarrhea. Bloody diarrhea was reported to be a risk factor for HUS (odds ratio 2.10; p = 0.001) (12). In the outbreak we studied, children under 5 years of age were less likely than older children and adults to report bloody diarrhea. EHEC infection should be actively considered for young children with non-bloody diarrhea who were exposed to potential sources of EHEC.

In this outbreak, 1 child was given azithromycin for 3 days to hasten decolonization some weeks after the acute diarrheal illness had resolved. Antimicrobial drugs are generally not recommended to hasten EHEC decolonization because of major associations with HUS (13). Recommendations to avoid high risk activities (such as childcare attendance) might place a major socioeconomic burden on EHEC carriers and their families. Further studies are required to assess whether WGS can provide useful information for safe administration of antimicrobial drugs for treatment of acute illness caused by EHEC, or when chronic shedding becomes established.

Our comprehensive study of a large outbreak _E. coli_ O157 illness, characterized by an IS1203v insertion disrupting the stx2c subunit A gene, showed mild clinical illness and an absence of HUS. Further characterization by virulence studies on isolates with this stx2c subunit A gene disruption might provide further insights into the mild illness caused by this strain.

1. Karmali MA, Steele BT, Petric M, Lim C: Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing _Escherichia coli_ in stools. Lancet. 1983;1: 619-620.
2. Australian Government Department of Health: National notifiable disease surveillance system. Commonwealth of Australia 2016 [cited 2016 Sep 1]. <>
3. Paton JC and Paton AW: Pathogenesis and diagnosis of Shiga toxin-producing _Escherichia coli_ infections. Clin Microbiol Rev. 1998;11: 450-479. Available at: <>.
4. Tarr PI, Gordon CA and Chandler WL: Shiga-toxin-producing _Escherichia coli_ and haemolytic uraemic syndrome. Lancet. 2005;365: 1073-1086. Available at: <>.
5. Farrokh C, Jordan K, Auvray F, et al: Review of Shiga-toxin-producing _Escherichia coli_ (STEC) and their significance in dairy production. Int J Food Microbiol. 2013;162: 190-212. Available at: <>.
6. CDC: Community outbreak of hemolytic uremic syndrome attributable to _Escherichia coli_ O111:NM--South Australia 1995. MMWR Morb Mortal Wkly Rep. 1995;44:550-551, 557-558. Available at: <>.
7. Queensland Health: Shiga toxin-producing _Escherichia coli_ (STEC) infection. The State of Queensland 2013 [cited 2016 Sep 25]. Available at: <>.
8. Heiman KE, Mody RK, Johnson SD, Griffin PM and Gould LH: _Escherichia coli_ O157 Outbreaks in the United States, 2003-2012. Emerg Infect Dis. 2015;21: 1293-1301. Available at: <>.
9. Jelacic S, Wobbe CL, Boster DR, et al: ABO and P1 blood group antigen expression and stx genotype and outcome of childhood _Escherichia coli_ O157:H7 infections. J Infect Dis. 2002;185: 214-219. Available at: <>.
10. Kim YB, Okuda J, Matsumoto C, et al: Isolation of an _Escherichia coli_ O157:H7 strain producing Shiga toxin 1 but not Shiga toxin 2 from a patient with hemolytic uremic syndrome in Korea. FEMS Microbiol Lett. 1998;166: 43-48. Available at: <>.
11. Ethelberg S, Olsen KE, Scheutz F, et al: Virulence factors for hemolytic uremic syndrome, Denmark. Emerg Infect Dis. 2004;10: 842-847. Available at: <>.
12. Launders N, Byrne L, Jenkins C, Harker K, Charlett A and Adak GK: Disease severity of Shiga toxin-producing _E. coli_ O157 and factors influencing the development of typical haemolytic uraemic syndrome: a retrospective cohort study, 2009-2012. BMJ Open. 2016;6:e009933. Available at: <>.
13. Freedman SB, Xie J, Neufeld MS, Hamilton WL, Hartling L and Tarr PI: Alberta Provincial Pediatric Enteric Infection Team (APPETITE). Shiga toxin-producing _Escherichia coli_ infection, antibiotics, and risk of developing hemolytic uremic syndrome: a meta-analysis. Clin Infect Dis. 2016;62: 1251-1258. Available at: <>.

[Authors: Vasant BR, Stafford RJ, Jennison AV, et al]

Communicated by: ProMED-mail <>

[ProMED reported on this outbreak in 2013 when it occurred. It may well be the case that the IS1203v insertion that resulted in deletion of the first 494 bp of the stx2c subunit A gene may have been the cause of milder illness. Regarding azithromycin use, azithromycin and the carbapenem antimicrobial class are among a small group of antibacterials that do not appear to precipitate a higher risk of hemolytic uremic syndrome. Azithromycin was used for late clearance of the EHEC here and I have had anecdotal experience doing the same thing in an asymptomatic chronic carrier of EHEC O157 without any adverse effects. - Mod.LL

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[See Also:

E. coli EHEC - Australia (02): (VI) unpasteurized cosmetic milk
E. coli EHEC - Australia: (VI) unpasteurized milk, fatality

E. coli EHEC - Australia (06): (QL) petting zoo, O157
E. coli EHEC - Australia (05): (QL) petting zoo, O157
E. coli EHEC - Australia (04): (QL) petting zoo
E. coli EHEC - Australia (03): (QL) petting zoo
E. coli EHEC - Australia (02): (QL) petting zoo
E. coli EHEC - Australia: (QL) petting zoo

Published 21-08-2017 in Focus on , last update 30-08-2017


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