Dataset Information

Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab.

ABSTRACT: An outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin-secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all patients were treated with the monoclonal anti-C5 antibody, eculizumab.The diagnosis of HUS was made based on haemolytic anaemia, low platelet count and acute kidney injury. Data were obtained from initial gastrointestinal symptoms to the end of follow-up 10 weeks after the start of eculizumab.Among 24 cases of STEC gastroenteritis, HUS developed in nine patients (eight adults and one child), 6 (median; range 3-12) days after digestive symptoms begun. The median (range) highest or lowest biological values were platelet count 26 (range 14-93) G/L; haemoglobin 6.6 (range 5-10.7) g/dL; LDH 1520 (range 510-2568) IU/L; creatinine 152 (range 48-797) µmol/L. All patients had extra-renal complications (liver 9, pancreas 5, brain 3 and heart 3). Two patients were dialysed, and one was ventilated. After failure of plasma exchange to increase platelets in the first three patients, eculizumab was administered in all nine patients, 0-4 days after HUS diagnosis (median 1 day). One patient with very severe neurological HUS received immunoadsorption. Outcome was favourable in all patients, with rapid normalization of haemoglobin, platelets, LDH levels, renal function and neurological improvement. There were no deaths and no serious adverse events related to eculizumab.Early treatment of O104:H4 STEC-HUS by eculizumab was associated with a rapid and efficient recovery. Controlled prospective evaluation of eculizumab in STEC-HUS is warranted.

SUBMITTER: Delmas Y

PROVIDER: S-EPMC3938298 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab.

Delmas Yahsou Y Vendrely Benoît B Clouzeau Benjamin B Bachir Hiba H Bui Hoang-Nam HN Lacraz Adeline A Hélou Sébastien S Bordes Cécile C Reffet Armel A Llanas Brigitte B Skopinski Sophie S Rolland Patrick P Gruson Didier D Combe Christian C

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20131128 3

<h4>Background</h4>An outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin-secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all patients were treated with the monoclonal anti-C5 antibody, eculizumab.<h4>Methods</h4>The diagnosis of HUS was made based on haemolytic anaemia, low platelet count and acute kidney injury. Data were obtained from initial gastrointestinal symptoms to th ...[more]

PMID: 24293658

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Project description:BACKGROUND: An Escherichia coli O104:H4 outbreak in Germany in summer 2011 caused 53 deaths, over 4000 individual infections across Europe, and considerable economic, social and political impact. This outbreak was the first in a position to exploit rapid, benchtop high-throughput sequencing (HTS) technologies and crowdsourced data analysis early in its investigation, establishing a new paradigm for rapid response to disease threats. We describe a novel strategy for design of diagnostic PCR primers that exploited this rapid draft bacterial genome sequencing to distinguish between E. coli O104:H4 outbreak isolates and other pathogenic E. coli isolates, including the historical hæmolytic uræmic syndrome (HUSEC) E. coli HUSEC041 O104:H4 strain, which possesses the same serotype as the outbreak isolates. METHODOLOGY/PRINCIPAL FINDINGS: Primers were designed using a novel alignment-free strategy against eleven draft whole genome assemblies of E. coli O104:H4 German outbreak isolates from the E. coli O104:H4 Genome Analysis Crowd-Sourcing Consortium website, and a negative sequence set containing 69 E. coli chromosome and plasmid sequences from public databases. Validation in vitro against 21 'positive' E. coli O104:H4 outbreak and 32 'negative' non-outbreak EHEC isolates indicated that individual primer sets exhibited 100% sensitivity for outbreak isolates, with false positive rates of between 9% and 22%. A minimal combination of two primers discriminated between outbreak and non-outbreak E. coli isolates with 100% sensitivity and 100% specificity. CONCLUSIONS/SIGNIFICANCE: Draft genomes of isolates of disease outbreak bacteria enable high throughput primer design and enhanced diagnostic performance in comparison to traditional molecular assays. Future outbreak investigations will be able to harness HTS rapidly to generate draft genome sequences and diagnostic primer sets, greatly facilitating epidemiology and clinical diagnostics. We expect that high throughput primer design strategies will enable faster, more precise responses to future disease outbreaks of bacterial origin, and help to mitigate their societal impact.

Dataset Information

Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab.

Publications

Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab.

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