Bloody Diarrhea and Shiga Toxin Screening

Abstract

Source: Ardissino G, Vignati C, Masia C, et al. Bloody diarrhea and Shiga toxin-producing Escherichia coli hemolytic uremic syndrome in children: data from the ItalKid-HUS network. J Pediatr. 2021; 237:34-40. e1; doi: 10.1016/j.jpeds.2021.06.048Investigators from multiple institutions conducted an analysis of data from a screening program for Shiga toxin (Stx) in children with bloody diarrhea. The screening program was developed for identification of children with Shiga toxin-Escherichia coli (STEC) infection for early diagnosis of STEC hemolytic uremic syndrome (STEC-HUS) by the ItalKid-HUS Network. The network includes 63 pediatric units in Northern Italy. Stool samples in children with acute bloody diarrhea were tested for Stx genes (Stx1 and Stx2). Patients who were Stx gene positive were monitored for hemoglobinuria as an early sign of STEC-HUS. Main study outcomes included rate of Stx positivity among children with bloody diarrhea and development of STEC-HUS. Criteria for a diagnosis of STEC-HUS were platelet count <150,000 mm3 or 50% acute reduction in platelet count, non-immune-mediated hemolysis, and evidence of renal damage (elevated serum creatinine [Cr], proteinuria, or hematuria). The utility of hemoglobinuria as a sign of STEC-HUS in children with Stx gene-positive bloody diarrhea was determined. Finally, the analysis also included children diagnosed with ongoing STEC-HUS who were not screened for Stx. Laboratory findings and long-term adverse outcomes (chronic kidney disease [CKD], extrarenal sequelae, or death) in children diagnosed through the screening program were compared to those diagnosed with ongoing STEC-HUS with chi square tests.A total of 4,767 children with bloody diarrhea were screened for the Stx gene from 2010 through 2019. The median age of these children was 3.4 years. Among the 4,767 patients screened, 214 (4.5%) were positive for Stx, including 62 with Stx1, 97 with Stx2, and 55 with both genes. In the 214 children who were Stx positive, 34 developed STEC-HUS (15.9% of Stx positive patients and 0.71% of screened children with bloody diarrhea). All of those who developed STEC-HUS were positive for Stx2. Overall, the risk of STEC-HUS was 0% for those with Stx1, 23.7% for those with Stx2, and 12.7% for those with both. In 63 patients with Stx2 who were screened, the sensitivity of hemoglobinuria as a marker for STEC-HUS was 100% (95% CI, 95%, 100%). specificity was 85% (95% CI, 77%, 91%), positive predictive value was 68% (95% CI, 55%, 79%), and negative predictive value was 100% (95% CI, 93%, 100%). There were an additional 95 children diagnosed with ongoing STEC-HUS. These children had a significantly higher Cr at HUS diagnosis than those identified through the screening program; the rate of long-term adverse outcomes was 15.8% in these patients vs 2.9% in those screened (P = 0.051).The authors conclude that 0.71% of children with bloody diarrhea who were screened for Stx developed STEC-HUS.Dr Rosenthal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Bloody diarrhea dictates an evaluation of its cause. Among the most common causes in Western countries, STEC has been associated with HUS.1 The current researchers screened 4,767 children with bloody diarrhea for Stx; 214 were positive for Stx genes; 62 with Stx1, 97 with Stx2, and 55 with both genes. Notably, STEC-HUS developed only in children with Stx2 alone or in combination. In 63 patients with Stx2 who were screened, the sensitivity of hemoglobinuria as a marker for STEC-HUS was 100%.HUS is associated with a nonimmune hemolytic anemia, low platelet count, renal impairment, and multiorgan injury.1 The anemia is severe and microangiopathic, with fragmented red blood cells in the peripheral smear, circulating free hemoglobin, and elevated reticulocytes. Platelet count is <60,000/mm3 in most cases. Acute renal failure occurs in 55-70% of cases.2In 70% of cases in North America, STEC-HUS is secondary to infection with the E. coli serotype O157:H7.3 This serotype does not ferment sorbitol, making it distinguishable from most other fecal E. coli.4Unfortunately, there is no treatment of confirmed value for STEC-HUS, and care during the acute phase of the illness remains supportive. The use of antibiotics is controversial.5What have we learned from the current report? Among children with bloody diarrhea, STEC-HUS occurred only in those with Stx2 alone or in combination with Stx 1. Monitoring STEC patients with Stx2 with urine dipstick for hemoglobinuria can aid in recognizing renal complications early to optimize supportive care.Screen patients with bloody diarrhea for Stx, and if Stx2 positive, monitor for hemoglobinuria.STEC-HUS remains the leading cause of acute kidney injury in young children.6 Of import, early administration of intravenous fluids after timely diagnosis of STEC infection (sought by the current investigators) appears to decrease disease severity. (See AAP Grand Rounds. 2016;[5]:50.)6