Predicting Progression of STEC-HUS: Use of Shiga Toxin Subtype and Routine Laboratory Screening.

Read article Submitted by: Alex Humphrey and Emma BestPaediatric Infectious Diseases, Starship Children's Hospital,Tamaki Makaurau/Auckland Aotearoa, NZBackground: Haemolytic uremic syndrome (HUS) is a complication of Shiga toxin (Stx)-producing Escherichia coli (STEC) diarrhoeal infection. Predicting progression remains challenging, particularly for early identification and pre-emptive management strategies. This retrospective cohort study used five years (2015-2020) of real-world data from a large U.S. healthcare system, applying qPCR stool testing and electronic health record data to define HUS risk by STEC serotype (O157 vs not) and Shiga toxin profile (by stx1 and stx2 gene), to identify predictors of progression to HUS in children with STEC. Local guidelines stratified testing frequency by age, serogroup, and Shiga toxin type, recommending urinalysis, blood count, renal function (urea and creatinine), and blood pressure at intervals from none to twice weekly.Main Findings: Among 1071 children with STEC, 55 (5.1%) developed HUS, predominantly in those aged under 5 (78%). The highest-risk groups were STEC-type O157 with stx2 (risk of HUS progression 19.8%), O157 with both stx1 and stx2 (10.6%,) and non-O157 with stx2 (3.6%). No HUS occurred in children with O157 alone, O157 with stx1, or non-O157 with stx1 and stx2, and only HUS one case developed in 586 children with non-O157 stx1 alone. In multi-variate analysis (matched 1:4 for age, serotype and stx result), vomiting and dehydration were the only two statistically significant clinical risk factors for progression to HUS.Among 291 STEC-positive children monitored as outpatients, 15 developed HUS. Ten were admitted based on their first abnormal results, while others progressed after subsequent tests (3 on second, 1 on third, 1 on seventh). Several re-presented with clinical deterioration within a day of a previously normal result, highlighting the need for close monitoring despite initially reassuring results.Take home message: Hydration may reduce severity in those who develop HUS, and may prevent progression to HUS in the first instance (RCT ongoing NCT05219110). Therefore, early recognition of higher-risk profiles is likely important; the authors propose a risk based approach to this (see table 2 in article). Incorporating Shiga toxin subtype into clinical workflows supports risk-based decisions on follow-up, laboratory monitoring, and counselling around the strength of recommendations for invasive investigations and treatments. A systems-level approach involving PCR diagnostics, laboratory reporting, primary care and public health may reduce harm in high-risk cases while avoiding unnecessary intervention in low-risk children.

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