Background. The aim of this study was to evaluate the long-term prognosis of children with hemolytic uremic syndrome (HUS). Methods. Over a 6-year period, 619 pediatric patients with the clinical diagnosis of HUS were registered in Austria and Germany, and a subset (n = 274) was prospectively followed up for 5 years. Results. Infection with enterohemorrhagic Escherichia coli (EHEC) was confirmed in 79% of cases. Five years after diagnosis, 70% of EHEC-infected patients (95% confidence interval [CI], .63–.76) were fully recovered. The remaining 30% had persistent hypertension (9%), neurological symptoms (4%), decreased glomerular filtration rate (7%), and/or proteinuria (18%). Hypertension and proteinuria developed in a total of 18% of patients who had no sequelae 1 year after the acute phase (95% CI, 12–26). Multivariate logistic regression analysis demonstrated an association between the use of plasma therapy during acute phase and poor long-term outcome (odds ratio, 2.9–13; 95% CI, 2.4–33; P < .05), but this treatment was also used more frequently in severe cases. In contrast, the use of antibiotic therapy in the diarrheal phase and other established risk factors for developing HUS, such as Shiga toxin 2 and EHEC serotypes traditionally considered to be “high risk,” were not associated with adverse long-term outcome. In particular, there was no difference between O157 and non-O157 EHEC. Conclusions. This study identified an association between the use of plasma treatment and poor long-term outcome and confirms already known risk factors for poor prognosis. Follow-up investigations for at least 5 years are recommended to detect late-emerging sequelae.

Infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of hemolytic uremic syndrome (HUS). Shiga toxins (Stxs), especially Stx2, are believed to represent major virulence factors of EHEC, contributing to HUS pathogenesis. Beside EHEC-associated HUS, there are hereditary atypical forms of HUS, which are mostly caused by mutations of complement regulators. The aim of the present study was to investigate whether or not complement is also involved in the pathogenesis of EHEC-induced typical HUS, by being activated either directly or indirectly by involvement of its inhibitors. Purified Stx2 markedly activated complement via the alternative pathway and was found to bind to factor H (FH), however, only when it was active. No apparent cleavage or destruction of FH was visible, and cofactor activity in fluid phase was unaffected, but clearly delayed for surface-attached FH, where it is essential for host cell protection. Binding studies using FH constructs revealed that Stx2 binds to short consensus repeats (SCRs) 6–8 and SCRs18–20, but not to SCRs16–17, i.e., to regions involved in the surface recognition function of FH. In conclusion, complement, and in particular FH, not only plays an important role in atypical HUS, but most probably also in EHEC-induced HUS.

Background. Enterohemorrhagic Escherichia coli (EHEC) O26 causes diarrhea and hemolytic uremic syndrome (HUS). Strains harboring the stx_1a gene prevail, but strains with stx_2a as the sole Shiga toxin–encoding gene are now emerging. The traits and virulence of the latter set of strains are unknown. We correlated stx genotypes of 272 EHEC O26 strains isolated in 7 European countries between 1996 and 2012 with disease phenotypes. We determined phylogeny, clonal structure, and plasmid gene profiles of the isolates and portray geographic and temporal distribution of the different subgroups. Methods. The stx genotypes and plasmid genes were identified using polymerase chain reaction, phylogeny was assigned using multilocus sequence typing, and clonal relatedness was established using pulsed-field gel electrophoresis. Results. Of the 272 EHEC O26 isolates, 107 (39.3%), 139 (51.1%), and 26 (9.6%) possessed stx_1a, stx_2a, or both genes, respectively. Strains harboring stx_2a only were significantly associated with HUS (odds ratio, 14.2; 95% confidence interval, 7.9–25.6; P < .001) compared to other stx genotypes. The stx_2a-harboring strains consist of 2 phylogenetically distinct groups defined by sequence type (ST) 21 and ST29. The ST29 strains are highly conserved and correspond by plasmid genes to the new virulent clone of EHEC O26 that emerged in Germany in the 1990s. This new clone occurred in 6 of the 7 countries and represented approximately 50% of all stx_2a-harboring EHEC O26 strains isolated between 1996 and 2012. Conclusions. A new highly virulent clone of EHEC O26 has emerged in Europe. Its reservoirs and sources warrant identification.