Fecal diagnostics in combination with serology: best test to establish STEC-HUS.

Kioa L Wijnsma,Nicole C A J Van De Kar,Elena Volokhina,Thea Van Der Velden,Sheila A M Van Bommel,Lambertus P Van Den Heuvel,Michiel F Schreuder

doi:10.1007/s00467-016-3420-7

Abstract

BackgroundIn the majority of pediatric patients, the hemolytic–uremic syndrome (HUS) is caused by an infection with Shiga toxin-producing Escherichia coli (STEC), mostly serotype O157. It is important to discriminate between HUS caused by STEC and complement-mediated HUS (atypical HUS) due to differences in treatment and outcome. As STEC and its toxins can only be detected in the patient’s stool for a short period of time after disease onset, the infectious agent may go undetected using only fecal diagnostic tests. Serum antibodies to lipopolysaccharide (LPS) of STEC persist for several weeks and may therefore be of added value in the diagnosis of STEC.MethodsAll patients with clinical STEC-HUS who were treated at Radboud University Medical Center between 1990 and 2014 were included in this retrospective single-center study. Clinical and diagnostic microbiological data were collected. Immunoglobulin M (IgM) antibodies against LPS of STEC serotype O157 were detected by a serological assay (ELISA).ResultsData from 65 patients weres available for analysis. Fecal diagnostic testing found evidence of an STEC infection in 34/63 patients (54 %). Serological evidence of STEC O157 was obtained in an additional 16 patients. This is an added value of 23 % (p < 0.0001) when the serological antibody assay is used in addition to standard fecal diagnostic tests to confirm the diagnosis STEC-HUS. This added value becomes especially apparent when the tests are performed more than 7 days after the initial manifestation of the gastrointestinal symptoms.ConclusionsThe serological anti-O157 LPS assay clearly makes a positive contribution when used in combination with standard fecal diagnostic tests to diagnose STEC-HUS and should be incorporated in clinical practice.

Highlights

Hemolytic–uremic syndrome (HUS) is diagnosed when the characteristics of hemolytic anemia, thrombocytopenia, and acute renal failure are present [1]
One patient died in the acute phase of the disease from a systemic inflammatory response syndrome combined with severe Shiga toxin-producing Escherichia coli (STEC)-hemolytic–uremic syndrome (HUS), as proven by positive results for both the fecal diagnostic tests and the serological assay
Various fecal diagnostic tests are recommended in the literature to establish an STEC infection as the cause of HUS [10], including stool cultures, shiga toxin (Stx) immunoassays, cell cytotoxicity assays, and PCR for Stx genes

Summary

Introduction

Hemolytic–uremic syndrome (HUS) is diagnosed when the characteristics of hemolytic anemia, thrombocytopenia, and acute renal failure are present [1]. There are different etiologies leading to HUS, with the Shiga toxin-producing Escherichia coli (STEC) HUS and complement-mediated atypical HUS (aHUS) being the most prominent ones. In more than 90 % of cases, HUS follows a gastrointestinal infection with STEC. Patients with STEC-HUS often recover spontaneously, with only a small number progressing to end-stage renal disease (ESRD) [6]. AHUS generally has a poor outcome, with 2–10 % mortality among patients in the acute phase of the disease and up to 50 % of patients progressing to ESRD [7]. In the majority of pediatric patients, the hemolytic–uremic syndrome (HUS) is caused by an infection with Shiga toxin-producing Escherichia coli (STEC), mostly serotype O157. It is important to discriminate between HUS caused by STEC and complement-mediated HUS (atypical HUS) due to differences in treatment and outcome. Serum antibodies to lipopolysaccharide (LPS) of STEC persist for several weeks and may be of added value in the diagnosis of STEC

Methods

Results

Conclusion