Dataset Information

Clinical and Laboratory Predictors of Shiga Toxin-Producing Escherichia coli Infection in Children With Bloody Diarrhea.

ABSTRACT:

Objectives

Children with acute bloody diarrhea are at risk of being infected with Shiga toxin-producing Escherichia coli (STEC) and of progression to hemolytic uremic syndrome. Our objective was to identify clinical and laboratory factors associated with STEC infection in children who present with acute bloody diarrhea.

Methods

We performed a prospective cohort study of consecutive children younger than 18 years who presented with acute (<2-week duration) bloody diarrhea between August 1, 2013, and August 1, 2014. We excluded patients with a chronic gastrointestinal illness and/or an obvious noninfectious source of bloody stool. We obtained a standardized history and study laboratory tests, performed physical examinations, and recorded patient outcomes.

Results

Of the 135 eligible patients, 108 were enrolled; 27 declined consent. The median patient age was 3 years, and 56% were male. Ten (9%) patients tested positive for STEC (E coli O157:H7, n = 8; E coli O111, n = 1; E coli O103, n = 1), and 62 had negative stool culture results. Children infected with STEC were older (8.5 vs 3 years, respectively) (P < .001) and more likely to have abdominal tenderness (83% vs 17%, respectively) than those in the other groups. D-Dimer concentrations had a 70% sensitivity and 55% specificity for differentiating children with STEC from those with another cause of bloody diarrhea and 75% sensitivity and 70% specificity in differentiating children with a bacterial etiology from those with negative stool culture results.

Conclusion

Clinical assessment and laboratory data cannot reliably exclude the possibility that children with bloody diarrhea have an STEC infection and are at consequent risk of developing hemolytic uremic syndrome. Abnormal D-dimer concentrations (>0.5 ?g/mL) were insufficiently sensitive and specific for distinguishing patients with STEC from those with another bacterial cause of bloody diarrhea. However, this marker might be useful in identifying children whose bloody diarrhea is caused by a bacterial enteric pathogen.

SUBMITTER: McKee RS

PROVIDER: S-EPMC6097574 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

Clinical and Laboratory Predictors of Shiga Toxin-Producing Escherichia coli Infection in Children With Bloody Diarrhea.

McKee Ryan S RS Tarr Phillip I PI Dietzen Dennis J DJ Chawla Rachit R Schnadower David D

Journal of the Pediatric Infectious Diseases Society 20180801 3

<h4>Objectives</h4>Children with acute bloody diarrhea are at risk of being infected with Shiga toxin-producing Escherichia coli (STEC) and of progression to hemolytic uremic syndrome. Our objective was to identify clinical and laboratory factors associated with STEC infection in children who present with acute bloody diarrhea.<h4>Methods</h4>We performed a prospective cohort study of consecutive children younger than 18 years who presented with acute (<2-week duration) bloody diarrhea between A ...[more]

PMID: 29617871

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Project description:Many pathogens produce the ?-(1-6)-linked poly-N-acetylglucosamine (PNAG) surface polysaccharide that is being developed as a broadly protective antimicrobial vaccine. However, it is unknown whether systemically injected PNAG vaccines or antibodies would provide protective immunity against pathogens confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens for which effective immunotherapeutics are lacking. To ascertain whether systemic IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin 1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the conjugate vaccine were tested for bacterial killing and toxin neutralization in vitro and protection against infection in infant mice. Cell surface PNAG was detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1 potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and bactericidal activity. Following intraperitoneal injection, antibodies to both PNAG and Stx were needed for infant mouse protection against O157 STEC. These antibodies also mediated protection against the Stx2-producing O104:H4 strain that was the cause of a recent outbreak in Germany, although sufficient doses of antibody to PNAG alone were protective against this strain in infant mice. Our observations suggest that vaccination against both PNAG and Stx, using a construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective against a broad range of STEC serogroups. IMPORTANCE The presence of poly-N-acetylglucosamine (PNAG) on many pathogens presents an opportunity to target this one structure with a multispecies vaccine. Whether antibodies to PNAG can protect against pathogens confined to the gastrointestinal tract is not known. As Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria are serious causes of infection whose virulence is dependent on elaboration of Stx, we prepared a vaccine containing a synthetic nonamer of PNAG (9GlcNH2) conjugated to Shiga toxin 1b subunit (9GlcNH2-Stx1b) to evaluate bacterial killing, toxin neutralization, and protective efficacy in infant mice. All nine (100%) clinical strains of STEC from different serogroups expressed PNAG. Vaccine-induced antibody mediated in vitro killing of STEC and neutralization of both Stx1 and Stx2. Passive administration of antibody to the conjugate showed protection requiring immunity to both PNAG and Stx for O157 strains, although for an O104 strain, antibody to PNAG alone was protective. Immunity to PNAG may contribute to protection against STEC infections.

Dataset Information

Clinical and Laboratory Predictors of Shiga Toxin-Producing Escherichia coli Infection in Children With Bloody Diarrhea.

Objectives

Methods

Results

Conclusion

Publications

Clinical and Laboratory Predictors of Shiga Toxin-Producing Escherichia coli Infection in Children With Bloody Diarrhea.

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