Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes encode differ in their in vitro and experimental phenotypes, but the human population-level impact of these differences is poorly understood. Using Shiga toxin-encoding bacteriophage insertion typing and real-time polymerase chain reaction, we genotyped isolates from 936 E. coli O157:H7 cases and verified HUS status via chart review. We compared the HUS risk between isolates with stx2a and those with stx2a and another gene and estimated additive interaction of the stx genes. Adjusted for age and symptoms, the HUS incidence of E. coli O157:H7 containing stx2a alone was 4.4% greater (95% confidence interval (CI) -0.3%, 9.1%) than when it occurred with stx1a. When stx1a and stx2a occur together, the risk of HUS was 27.1% lower (95% CI -87.8%, -2.3%) than would be expected if interaction were not present. At the population level, temporal or geographic shifts toward these genotypes should be monitored, and stx genotype may be an important consideration in clinically predicting HUS among E. coli O157:H7 cases.
Bibliographical noteFunding Information:
Funding: This study was funded by the Alberta Children’s Hospital Research Institute and the Cumming School of Medicine/Alberta Health Services Clinical Research Fund. G.A.M.T. was supported by a Canadian Institutes of Health Research Banting Postdoctoral Fellowship, Alberta Innovates Health Programs Postgraduate Fellowship, and University of Calgary Eyes High Postdoctoral Fellowship. T.S. was supported by a 2019 Alberta Innovates Summer Research Studentship. P.I.T. was supported by the Washington University Digestive Disease Research Core Center (ARAC Core) P30DK052574. S.B.F. was supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness.
© 2019 by the authors.
- Escherichia coli O157:H7
- Hemolytic uremic syndrome
- Shiga toxin-producing Escherichia coli
- Stx genes