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We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.

During a large outbreak of Shiga toxin−producing Escherichia coli illness associated with an agricultural show in Australia, we used whole-genome sequencing to detect an IS1203v insertion in the Shiga toxin 2c subunit A gene of Shiga toxin−producing E. coli. Our study showed that clinical illness was mild, and hemolytic uremic syndrome was not detected.

Strains from diarrheal illnesses could be transmitted from pigeons, but HUS-associated strains may derive from phage acquisition by isolates with larger virulence assets., Verotoxigenic Escherichia coli infections in humans cause disease ranging from uncomplicated intestinal illnesses to bloody diarrhea and systemic sequelae, such as hemolytic uremic syndrome (HUS). Previous research indicated that pigeons may be a reservoir for a population of verotoxigenic E. coli producing the VT2f variant. We used whole-genome sequencing to characterize a set of VT2f-producing E. coli strains from human patients with diarrhea or HUS and from healthy pigeons. We describe a phage conveying the vtx2f genes and provide evidence that the strains causing milder diarrheal disease may be transmitted to humans from pigeons. The strains causing HUS could derive from VT2f phage acquisition by E. coli strains with a virulence genes asset resembling that of typical HUS-associated verotoxigenic E. coli.

Diseases were associated with socioeconomic status and age of patients and with serotype of organism., Foodborne pathogens cause >9 million illnesses annually. Food safety efforts address the entire food chain, but an essential strategy for preventing foodborne disease is educating consumers and food preparers. To better understand the epidemiology of foodborne disease and to direct prevention efforts, we examined incidence of Salmonella infection, Shiga toxin–producing Escherichia coli infection, and hemolytic uremic syndrome by census tract–level socioeconomic status (SES) in the Connecticut Foodborne Diseases Active Surveillance Network site for 2000–2011. Addresses of case-patients were geocoded to census tracts and linked to census tract–level SES data. Higher census tract–level SES was associated with Shiga toxin–producing Escherichia coli, regardless of serotype; hemolytic uremic syndrome; salmonellosis in persons ≥5 years of age; and some Salmonella serotypes. A reverse association was found for salmonellosis in children

FoodNet has provided a foundation for food safety policy and illness prevention since 1996., The Foodborne Diseases Active Surveillance Network (FoodNet) provides a foundation for food safety policy and illness prevention in the United States. FoodNet conducts active, population-based surveillance at 10 US sites for laboratory-confirmed infections of 9 bacterial and parasitic pathogens transmitted commonly through food and for hemolytic uremic syndrome. Through FoodNet, state and federal scientists collaborate to monitor trends in enteric illnesses, identify their sources, and implement special studies. FoodNet’s major contributions include establishment of reliable, active population-based surveillance of enteric diseases; development and implementation of epidemiologic studies to determine risk and protective factors for sporadic enteric infections; population and laboratory surveys that describe the features of gastrointestinal illnesses, medical care–seeking behavior, frequency of eating various foods, and laboratory practices; and development of a surveillance and research platform that can be adapted to address emerging issues. The importance of FoodNet’s ongoing contributions probably will grow as clinical, laboratory, and informatics technologies continue changing rapidly.

Foodborne gastroenteritis results in a substantial amount of severe and disabling sequelae., In Australia circa 2010, 4.1 million (90% credible interval [CrI] 2.3–6.4 million) episodes of foodborne gastroenteritis occurred, many of which might have resulted in sequelae. We estimated the number of illnesses, hospitalizations, and deaths from Guillain-Barré syndrome, hemolytic uremic syndrome, irritable bowel syndrome, and reactive arthritis that were associated with contaminated food in Australia. Data from published studies, hospital records, and mortality reports were combined with multipliers to adjust for different transmission routes. We used Monte Carlo simulation to estimate median estimates and 90% CrIs. In Australia, circa 2010, we estimated that 35,840 (90% CrI 25,000–54,000) illnesses, 1,080 (90% CrI 700–1,600) hospitalizations, and 10 (90% CrI 5–14) deaths occurred from foodborne gastroenteritis–associated sequelae. Campylobacter spp. infection was responsible for 80% of incident cases. Reducing the incidence of campylobacteriosis and other foodborne diseases would minimize the health effects of sequelae.

This emerging clonal group harbors the extraintestinal virulence–associated plasmid pS88 and can induce invasive infections and death., We describe the epidemiology, clinical features, and molecular characterization of enterohemorrhagic Escherichia coli (EHEC) infections caused by the singular hybrid pathotype O80:H2, and we examine the influence of antibiotics on Shiga toxin production. In France, during 2005–2014, a total of 54 patients were infected with EHEC O80:H2; 91% had hemolytic uremic syndrome. Two patients had invasive infections, and 2 died. All strains carried stx2 (variants stx2a, 2c, or 2d); the rare intimin gene (eae-ξ); and at least 4 genes characteristic of pS88, a plasmid associated with extraintestinal virulence. Similar strains were found in Spain. All isolates belonged to the same clonal group. At subinhibitory concentrations, azithromycin decreased Shiga toxin production significantly, ciprofloxacin increased it substantially, and ceftriaxone had no major effect. Antibiotic combinations that included azithromycin also were tested. EHEC O80:H2, which can induce hemolytic uremic syndrome complicated by bacteremia, is emerging in France. However, azithromycin might effectively combat these infections.

In the context of a large outbreak of Shiga toxin–producing Escherichia coli O104:H4 in Germany, we quantified the timeliness of the German surveillance system for hemolytic uremic syndrome and Shiga toxin–producing E. coli notifiable diseases during 2003–2011. Although reporting occurred faster than required by law, potential for improvement exists at all levels of the information chain.

The diversity and relatedness of 100 Shiga toxin-producing Escherichia coli O91 isolates from different patients were examined by multilocus sequence typing. We identified 10 specific sequence types (ST) and 4 distinct clonal groups. ST442 was significantly associated with hemolytic uremic syndrome.

Multilocus sequence typing of 169 non-O157 enterohemorrhagic Escherichia coli (EHEC) isolated from patients with hemolytic uremic syndrome (HUS) demonstrated 29 different sequence types (STs); 78.1% of these strains clustered in 5 STs. From all STs and serotypes identified, we established a reference panel of EHEC associated with HUS (HUSEC collection).

The risk for diarrhea-associated HUS was higher for children infected with Escherichia coli O157 phage type (PT) 2 and PT21/28 than for those infected with other PTs., We conducted prospective surveillance of childhood hemolytic uremic syndrome (HUS) from 1997 to 2001 to describe disease incidence and clinical, epidemiologic and microbiologic characteristics. We compared our findings, where possible, with those of a previous study conducted from 1985 to 1988. The average annual incidence of HUS for the United Kingdom and Ireland (0.71/100,000) was unchanged from 1985 to 1988. The overall early mortality had halved, but the reduction in mortality was almost entirely accounted for by improved outcome in patients with diarrhea-associated HUS. The principal infective cause of diarrhea-associated HUS was Shiga toxin–producing Escherichia coli O157 (STEC O157), although in the 1997–2001 survey STEC O157 phage type (PT) 21/28 had replaced STEC O157 PT2 as the predominant PT. The risk of developing diarrhea-associated HUS was significantly higher in children infected with STEC O157 PT 2 and PT 21/28 compared with other PTs. Hypertension as a complication of HUS was greatly reduced in patients with diarrhea-associated HUS.

To the Editor: Hemolytic uremic syndrome (HUS) is a rare disorder characterized by microangiopathic hemolytic anemia, microthrombi, and multiorgan injury. HUS is one of the commonest causes of acute renal failure in children worldwide and is most frequently precipitated by infection with verotoxin-producing Escherichia coli (VTEC) such as E. coli O157 (1). However, non-O157 VTEC serotypes have been increasingly found in the development of HUS (2–4). Although previous surveillance of childhood HUS in Scotland identified E. coli O157 in >90% of cases, non-O157 serotypes have also been associated with HUS (5). In 2010, several particularly severe cases of HUS were reported to Health Protection Scotland by a consultant pediatric nephrologist. Subsequent tests identified the pathogen in these cases as E. coli O26. However, in a recent study of pediatric HUS cases in Europe, children infected with E. coli O26 did not exhibit different clinical signs and symptoms from patients infected with other VTEC serotypes (6). To establish whether the host pathophysiologic responses to E. coli O157 and E. coli O26 strains differed, we analyzed a cohort of children with HUS who were infected with these VTEC serotypes. In Scotland, most patients with pediatric thrombotic microangiopathy are referred to a specialist pediatric hospital, which immediately reports cases of HUS to Health Protection Scotland as part of national surveillance. To test the hypothesis that E. coli O26 was more virulent than E. coli O157, we performed an age-matched, nested case–case study of HUS patients and compared host clinical markers, treatment, and outcomes from pediatric cases in 2010. Data collection has been described elsewhere (5). The statistical significances of associations between categorical variables were investigated by using χ2, Fisher exact, Mann-Whitney, or t tests. All analyses were performed by using SPSS version 11 (SPSS Inc., Chicago, IL, USA) with a significance level of 5%. Although initial signs and symptoms were similar for both sets of cases, i.e., bloody diarrhea and abdominal pain, statistical analysis showed that children with O26-HUS were more likely to have neurologic complications and diabetes mellitus and require admission to the intensive care unit than O157-HUS patients (p = 0.02 for neurologic complications and diabetes and p = 0.04 for admission to an intensive treatment unit; Table). Table Characteristics of infection in children with Escherichia coli O157 versus E. coli O26, Scotland, 2010* All patients with HUS were oligoanuric, and the 2 groups did not differ with respect to this parameter. However, O26-HUS patients had significantly longer periods of anuria than O157-HUS patients (p = 0.04; Table) and were more likely to require treatment with hemofiltration than with peritoneal or hemodialysis (p = 0.001; Table). One patient with O26-HUS also experienced cardiomyopathy resulting in reduced left ventricular function. Our study illustrates the potential for increased severity of E. coli O26 infection in children. In Scotland, HUS is more commonly associated with E. coli O157 infection, and the outcome for children infected with this pathogen is much better than that reported in other studies (7,8). In this study, the clinical severity and outcomes for the children with O26-HUS were worse than for children requiring treatment for O157-HUS. We investigated the prehospital management of E. coli O157 and O26 patients in this cohort and found no difference in pharmacologic intervention or duration of delay in admission to hospital. In our cohort, vtx1 and vtx2 genes were detected in isolates from 2 of 3 patients. A diagnosis was made in the third patient by detection of E. coli O26 lipopolysaccharide–specific immunoglobulin M in serum; it was therefore not possible to confirm the presence of vtx genes. However, it is not unusual for VTEC to be undetectable in stool samples from patients with HUS, most likely because of intrahost bacteriophage lysis. Therefore, serodiagnosis of VTEC is considered a necessary adjunct to bacteriological confirmation of infection (9). A recent study suggests E. coli O26 exists as a highly dynamic group of organisms that can undergo verotoxin gene loss and be transferred during infection in humans, resulting in new pathogenic clones (10). Therefore, vtx2 gene acquisition by E. coli O26 may have contributed to increased virulence. Our study was limited by the small number of patients with pediatric O26-HUS. However, given the severity of the complications experienced by the children in this cohort, we believe it is necessary to communicate these findings promptly to the international community. We suggest that infection with E. coli O26 in children can result in more severe and complicated forms of HUS than those caused by E. coli O157. In contrast to the findings of Gerber et al., we found that there was a significant difference in neurologic complications between the 2 groups (2). Epidemiologic investigations found that 2 of the 3 children lived on farms and may have acquired infection while playing near their homes (the other was acquired through foreign travel). Risk communication of VTEC infection to parents of young children who live in farming communities remains problematic, perhaps because of the perception that immunity has been acquired. Although this suggestion may be true for adults, children are likely to be immunologically naive. Salient public health messages on simple precautionary behavior need to be regularly reinforced because prevention of VTEC infection prevents HUS.

The risk for illness associated with raw milk consumption is far greater than previously realized., Raw milk has frequently been identified as the source of foodborne illness outbreaks; however, the number of illnesses ascertained as part of documented outbreaks likely represents a small proportion of the actual number of illnesses associated with this food product. Analysis of routine surveillance data involving illnesses caused by enteric pathogens that were reportable in Minnesota during 2001–2010 revealed that 3.7% of patients with sporadic, domestically acquired enteric infections had reported raw milk consumption during their exposure period. Children were disproportionately affected, and 76% of those

To the Editor: Ethelberg et al. (1) report on a study of the determinants of hemolytic uremic syndrome resulting from Shiga toxin–producing Escherichia coli. The dataset is relatively small, and the authors use stepwise logistic regression models to detect small differences. This indicates that the authors were aware of the limitations of the statistical power of the study. Despite this, the study has an analytical flaw that seriously reduces the statistical power of the study. An often overlooked problem in building statistical models is that of endogeneity, a term arising from econometric analysis, in which the value of one independent variable is dependent on the value of other predictor variables. Because of this endogeneity, significant correlation can exist between the unobserved factors contributing to both the endogenous independent variable and the dependent variable, which results in biased estimators (incorrect regression coefficients) (2). Additionally, the correlation between the dependent variables can create significant multicollinearity, which violates the assumptions of standard regression models and results in inefficient estimators. This problem is shown by model-generated coefficient standard errors that are larger than true standard errors, which biases the interpretation towards the null hypothesis and increases the likelihood of a type II error. As a result, the power of the test of significance for an independent variable X1 is reduced by a factor of (1-r2(1|2,3,….)), where r(1|2,3,….) is defined as the multiple correlation coefficient for the model X1 = f(X2,X3,…), and all Xi are independent variables in the larger model (3,4). The results of this study clearly show that the presence of bloody diarrhea is an endogenous variable in the model showing predictors of hemolytic uremic syndrome, in that the diarrhea is shown to be predicted by, and therefore strongly correlated with, several other variables used to predict hemolytic uremic syndrome. Similarly, Shiga toxin 1 and 2 (stx1, stx2) genes are expected to be key predictors of the presence of bloody diarrhea, independent of strain, due to the known biochemical effects of that toxin (5,6). Because the strain is in part determined by the presence of these toxins, including both strain and genotype in the model means that the standard errors for variables for the Shiga-containing strains and bloody diarrhea symptom are likely to be too high, and hence the significance levels (p values) obtained from the regression models are higher than the true probability because of a type I error. This flaw is a particular problem with studies that use a conditional stepwise technique for including or excluding variables. The authors note that they excluded variables from the final model if the significance in initial models for those variables was less than an α level (p value) of 0.05. Given the inefficiencies due to the endogeneity of bloody diarrhea, as well as those that may result from other collinearities significant predictors were likely excluded from the study, although this cannot be confirmed from the data presented. The problems associated with the endogeneity of bloody diarrhea can be overcome by a number of approaches. For example, the simultaneous equations approach, such as that outlined by Greene (7), would have used predicted values of bloody diarrhea from the first stage of the model as instrumental variables for the actual value in the model for hemolytic uremic syndrome. Structural equations approaches, such as those suggested by Greenland (8), would also be appropriate. However, bloody diarrhea is not the only endogenous variable in their models, and extensive modeling would be necessary to isolate the independent effects of the various predictor variables. Given the small sample size, this may not be possible. The underlying problem in the study is the theoretical specifications for the model, in which genotypes, strains, and symptoms are mixed, despite reasonable expectations that differences in 1 level may predict differences in another. For example, the authors’ data demonstrate that all O157 strains contain the stx2 gene and have higher rates of causing hemolytic uremic syndrome and bloody diarrhea. This calls into question the decision to build an analytic model combining 3 distinct levels of analysis. Such a model depends on the independence of the variables to gain unbiased, efficient estimators. The model of the relationships one would develop from a theoretical perspective would predict the opposite (Figure). We expect that the genotypes (by definition) will predict the strain, and that strains have a differential effect on symptoms. The high level of intervariable correlation due to these relationships, coupled with the decision to exclude variables based on likely inefficient p values, raises questions concerning the reliability of the results and conclusions. In particular, the conclusions that strains O157 and O111 are not predictors of hemolytic uremic syndrome deserve to be revisited; other excluded variables may also be significant predictors when considered under an appropriate model. These problems point to the need to ensure proper specification of analytic models and to demonstrate due regard for the underlying assumptions of statistical models used. Figure Model for determining virulence factors for hemolytic uremic syndrome.

The mean annual incidence of hemolytic uremic syndrome in persons

Strains of Shiga toxin (Stx)–producing Escherichia coli (STEC) are differentiated by the O antigen on their outer membrane and are broadly classified as O157 or non-O157 STEC (1–3). The ability to produce Stx is a key virulence trait of STEC (1,3,4). STEC infections in humans often cause a self-limited diarrheal illness but can be complicated by hemorrhagic colitis or hemolytic uremic syndrome (1). Unlike other E. coli strains, serogroup O157 isolates do not ferment sorbitol and are readily identified by culture, appearing colorless on sorbitol MacConkey agar (1,2,4). Both O157 and non-O157 STEC can be identified by detecting Stx with nonculture assays that became commercially available in the United States in 1995 (2,4). The Centers for Disease Control and Prevention (CDC) published formal STEC testing recommendations for clinical laboratories in 2009, advocating that all stool specimens submitted for routine bacterial pathogen testing be simultaneously cultured for O157 STEC and tested with a nonculture assay to detect Stx. Use of this testing protocol ensures timely identification of all STEC infections (2,5). Exclusive testing for Stx delays specific identification of O157 STEC and may impede prompt detection of common-source outbreaks (2–4). Non-O157 STEC infection has been a nationally notifiable condition since 2000 (5). Although studies have documented the increased incidence of reported non-O157 STEC infections over the past decade, few have determined the proportion of laboratories that routinely test all submitted stool specimens for Stx and, to our knowledge, no study has quantified STEC testing practices by proportion of stool specimens processed for bacterial culture. Our objectives, therefore, were to quantify statewide STEC testing practice by proportion of stool specimens processed for bacterial culture and to determine the contribution of enhanced STEC testing practice to increased reported incidence of non-O157 STEC infections.

To the Editor: Gastroenteritis caused by Shiga toxin–producing Escherichia coli (STEC), associated with hemorrhagic colitis and hemolytic uremic syndrome (HUS), has been identified as a major health problem (1). Shiga toxin is essential for the development of HUS (2). Shiga toxin can be distinguished into Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2). The stx2f STEC variant is a distinct group within STEC (regarding virulence genes) and is known to cause relatively mild disease, although reports of human illness are scarce (3). During autumn 2013, a healthy 9-year-old boy in the Netherlands experienced fever, vomiting, and bloody diarrhea which persisted for days; he was admitted to the pediatric ward of a local hospital because of clinical signs of HUS with renal insufficiency: serum creatinine level 439 μmol/L (reference range 31–68 μmol/L); blood urea nitrogen concentration 34.1 mmol/L (reference range 3.3–5.6 mmol/L); thrombocytopenia (46 platelets/nL; reference range 150–450/nL); and low haptoglobin level. Hemoglobin levels decreased within 48 hours from 7.4 mmol/L to 5.5 mmol/L (reference range 6.9–8.4 mmol/L). His blood pressure was 127/82 (99th percentile for age and height). Renal insufficiency worsened over time, evidenced by maximum urea levels of 57.3 mmol/L and maximum creatinine levels of 744 μmol/L. Vomiting increased, and feeding became difficult. The boy was transferred to an academic nephrology center, where he received erythrocyte and thrombocyte infusions, then peritoneal dialysis. He received 1 prophylactic dose of cefazolin during insertion of the dialysis catheter. After 2 days, he entered a polyuric phase of renal failure; renal function normalized within a few weeks, however. To improve proteinuria, physicians prescribed a 3-month course of angiotensin-converting enzyme inhibitors after discharge. A fecal sample tested positive for STEC by PCR in a local laboratory. Five isolates were sent to the National Institute for Public Health and the Environment (RIVM) as part of the national STEC surveillance. By using PCR, 1 of the 5 tested positive for the stx2f gene and the attaching and effacing gene (eae), and negative for the genes stx1, stx2a-e, H7, O157, and enterohemorrhagic E. coli hemolysin (hly). Serotyping identified O8:H19. The other 4 isolates tested negative for all of the above-mentioned genes and were not serotyped. The family had stayed in a hotel in Turkey and returned to the Netherlands 5 days before onset of illness. The only reported contact with animals was with a parrot in the hotel. On return to the Netherlands, the boy had eaten filet americain, a sandwich spread made of raw beef. The day before disease onset, he attended a party where barbecue was served by a catering company. Since 2007, besides this reported case, 8 cases of STEC O8 were registered within the STEC surveillance system in the Netherlands: O8:H– (4 cases), O8:H19 (2 cases), O8:H8 (1 case), and O8:H9 (1 case). All 8 isolates were stx2a-e-positive and stx1-, stx2f-, eae- and hly-negative. Disease associated with these cases was relatively mild. During 2007–2010, a total of 13,545 human STEC infections were reported in Europe: 20 were registered as STEC O8; HUS did not develop in these case-patients (4). HUS developed in 2 patients infected with STEC O8 (O8:H2, O8:H19) in Germany during 1996–2000 (5); these isolates and all other isolates from HUS and non-HUS case-patients in this period tested negative for stx2f. During 2008–2011, 87 stx2f STEC infections were registered in the Netherlands (3). These infections were relatively mild; no HUS cases were registered. The virulence genes seen in the isolate of the described case, stx2f and eae, but no hly or other toxin genes, were also seen in 97% of stx2f STEC infections reported in the Netherlands (3). Besides being detected in humans, stx2f STEC has only been detected in pigeons (6). The cause of the severity of disease in this stx2f STEC case and the source of the infection could not be determined. The parrot in the hotel in Turkey could have been the source if birds are a reservoir of stx2f STEC. Conversely, the uncooked beef and barbecue cannot be ruled out, because O8:H19 has been found in cattle, pigs, and sheep (7). This case shows that STEC subgroups known to cause relatively mild disease can occasionally cause severe disease and that surveillance based upon a small group of serotypes underestimates the number of severe STEC infections and increases the chance of missing emerging serotypes.

To the Editor: Since the beginning of May 2011, a large outbreak of infections associated with Shiga toxin (Stx)–producing Escherichia coli (STEC) O104:H4 has occurred in Germany (1). The outbreak showed 3 unusual features: 1) a large proportion of case-patients with hemolytic uremic syndrome (HUS); 2) HUS in adults, although it usually affects children; and 3) frequent development of neurologic symptoms in patients when clinical and laboratory markers of HUS were improving (1,2). A second point-source outbreak caused by the same STEC O104 strain was reported in June 2011 in France (3). Both outbreaks were linked to eating fenugreek sprouts obtained from seeds produced in Egypt and distributed in Germany and other European countries (4). Instead of the attaching–effacing mechanism of adhesion to intestinal mucosa that is typical of STEC associated with severe human disease (5), the STEC O104 epidemic strain had genetic markers and an adhesion pattern (6) typical of enteroaggregative E. coli (EAEC), another group of diarrheagenic strains found frequently in developing countries (5). On basis of these findings, we reviewed our culture collection and found that an STEC strain (ED-703) from a case-patient with HUS in 2009 in Italy had the same combination of virulence factors as the strain from Germany: Stx2 production and enteroaggregative adhesion genetic markers. This strain, which had not been typed when it was isolated, showed positive PCR results for O104 (7) and H4 (8) antigen–associated genes and was agglutinated by an O104 antiserum (Statens Serum Institut, Copenhagen, Denmark). Pulsed-field gel electrophoresis showed a high degree of similarity (94.7%) with the outbreak strain from Germany (provided by M. Mielke, Robert Koch Institute, Berlin, Germany). In contrast with the outbreak strain, ED-703 did not produce extended-spectrum β-lactamases. The strain from our culture collection had been isolated from a 9-year-old girl admitted to the pediatric nephrology unit of the Ospedale Maggiore (Milan, Italy) on August 5, 2009, after 5 days of bloody diarrhea, vomiting, and abdominal pain. Diagnosis of HUS was based on the presence of hemolytic anemia, thrombocytopenia, and anuria. Neurologic symptoms (e.g., lethargy, diplopia, and nystagmus) occurred during hospitalization; magnetic resonance imaging showed signal abnormalities in the lenticular nuclei. Because of severe cardiac impairment with ejection fraction reduction and troponin increase, inotropic support and mechanical ventilation were temporarily needed. After improvement of clinical conditions, the patient was discharged, but she was readmitted a few days later because of headache, vomiting, confusion, dysarthria, hypertension, and visual impairment. Ischemic lesions were found by magnetic resonance imaging at fundus oculi. Neurologic status improved the next day, but the visual deficit persisted. Hemodialysis was needed for 2 months. Long-term sequelae of the disease were stage IV chronic kidney disease, hypertension, and severe visual impairment. Informed consent and an epidemiologic interview were obtained from the patient’s parents. The household, including her mother and 2 siblings (4 and 5 years of age), had traveled for 1 week to a resort in Tunisia; they had returned 3 weeks before the onset of the prodromal symptoms of HUS. Four days after their return, the youngest sister was hospitalized for 3 days because of bloody diarrhea, but no laboratory diagnosis was established. The mother reported having had watery diarrhea and abdominal pain on August 2. The patient history did not show any other usual risk factor for STEC infection, such as consumption of unpasteurized milk or dairy products, undercooked meat, or raw sprouts or direct exposure to ruminants or their manure. This finding suggests that the infection was probably acquired through person-to-person transmission. This case report confirms that strains of STEC O104 strictly related to the epidemic strain in Germany had already caused sporadic infections in Europe (9). Other cases have been documented in 2001 in Germany (6,9), in 2004 in France (9), and in 2010 in Finland in a patient with diarrhea who had traveled to Egypt (9). Both of the cases for which the information on the origin of the infection was available were related to travel to northern Africa, from which the seeds associated with both outbreaks could be traced (4). The history of this patient supports the hypothesis that ruminants would not have had a specific role in the transmission of STEC O104:H4, as already suggested by the epidemiologic features of the recent outbreaks (1,3). In fact, STEC O104 cannot be considered true STEC but rather EAEC strains that acquired the Stx2-coding phages by horizontal gene transfer, and EAEC is considered to be a human pathogen usually transmitted by the oral–fecal route (5). The clinical course of our patient closely resembles those of persons who had HUS associated with the German outbreak (1,2). The unusual combination of virulence factors of STEC and EAEC, already described in a group of STEC O111:H2 from an outbreak of HUS in France in 1996 (10), might confer a high degree of virulence to these strains. It also might explain the severity of the clinical findings associated with STEC O104:H4 infections.