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Proxy Clinical Markers for Shiga Toxin Load Help Determine Disease Severity


 

WASHINGTON — The severity of disease caused by Shiga toxin-producing bacteria may be tracked with a new scale under development that uses clinical markers of disease rather than direct measurement of toxin load, Dr. Martin M. Bitzan reported at a biodefense research meeting sponsored by the American Society for Microbiology.

“While the clinical diagnosis of hemolytic uremic syndrome appears straightforward, there are no defined criteria to describe and grade the severity of hemolytic uremic syndrome or of the preceding gastrointestinal disease,” Dr. Bitzan of the department of nephrology at Montreal Children's Hospital wrote in a poster presentation.

The inability to measure Shiga toxin in body fluids makes the development of proxy markers necessary, he and his colleague noted. Most of the infections in North America are due to Escherichia coli O157:H7.

The investigators developed a disease severity scale comprising four facets of Shiga toxin-producing infections: enteropathy (stool frequency, bloody diarrhea, abdominal pain); inflammation and vasculopathy (fever, peripheral leukocytosis, hypoalbuminemia); thrombotic microangiopathy (low hemoglobin and platelet levels); and nephropathy (hematuria, proteinuria, pyuria, hyponatremia, high serum creatinine).

They tested their scale on a database of 146 consecutive children aged 1–16 years with Shiga toxin-producing E. coli who had bloody (85%) or nonbloody (15%) diarrhea that resulted in partial (5%) or complete (13%) hemolytic uremic syndrome (HUS).

The scores of the children with HUS on all the scale's components except enteropathy became significantly worse 3–5 days after disease onset than children without the syndrome. The symptoms of those three components continued to be worse 11–14 days after disease onset, defined as the first day of diarrheal symptoms. Most children visited the ED for the first time 3 days after onset.

The scale is being validated in an international, prospective, observational study for disease follow-up.

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