study on hemolytic uremic syndrome [HUS] among hospitalized children with shiga toxin producing E. coli 0157:H7 infection

ABSTRACT

Diarrhea continues to be a major cause of childhood mortality and morbidity in developing countries. Although mortality from diarrheal diseases is declining, morbidity is not. The hemolytic uremic syndrome [HUS] has been reported to be a common complication in bloody diarrhea particularly that caused by entero-hemorrhagic E. coli, a subset of E. coli that produces potent cytotoxins known as shiga like toxins [STx] and the organism is therefore called shiga toxin producing E. coli [STEC]. The exact mechanism responsible for HUS, however, remains speculative. Endothelial injury, acute inflammatory response to STEC or its STx has been blamed. The aim of this work is to study the percentage frequency of STEC infection and the percentage frequency of HUS in a group of hospitalized diarrheal children with and without blood in stools. We also aim to study some of the inflammatory cytokines [TNF alpha, IL-8], vascular endothelial factors such as Endothelin-1 [Et-1] and nitric oxide [NO], and the angiogenic peptide released in response to endothelial injury [bFGF] in these cases. The study included 200 patients less than 5 years of age having acute diarrhea. Cases with protozoal infection were excluded from the study. All cases besides having thorough clinical history and examination, had stool culture and serotying of STEC 0157H7 on admission. For all cases renal function tests, full blood count and smear, serum sodium and potassium levels were measured. For cases with proven STEC 0157H7 infection, TNf alpha, IL-8, Et1, NO and bFGF were determined. The percentage frequency of STEC 0157H7 was 43%, of them 40% were in cases with blood in stools. The percentage frequency of HUS was 35%; all were cases with bloody diarrhea and STEC 0157 H7 infection. The percentage frequency of antibiotic administration among all cases was 67%. However among case with STEC infection that developed HUS 71% received antibiotics. Cases with STEC associated -HUS showed significantly younger mean age with significantly longer mean duration of hospitalization than the rest of case with STEC infection without HUS. They showed significantly higher percentage frequency of fever >/= 38°C, vomiting, hematuria, anuria, hypertension, CNS complications [seizures, encephalopathy, intractranial hemorrhage and brain infarction], and deaths than the rest of the cases. They also showed significantly lower mean sodium, hemoglobin, platelets and nitric oxide values and significdantly higher mean potassium, urea, creatinine, WBC count, PMNL, and reticulocytic count, TNF alpha, IL-8, Et-1, and bFGF correlated positively with creatinine and WBC but negatively with platelets. NO correlated negatively with TNF alpha, IL-8, Et-1, and bFGF. STEC infection is higher among the studied cases, pointing to the role of cross transmission among hospitalized patients. Hemolytic uremic syndrome complicates 35% of these cases. Diarrheal cases with HUS were associated with more serious complications such as hypertension, encephalopathy, and intracranial hemorrhage. These complications may cause permanent disability and sometimes have fatal outcome. Furthermore the duration of hospital stay was considerably longer than cases without HUS. In STEC associated HUS with these complications, the prognosis is usually grave than in the absence of such complications. Bad prognostic signs of HUS include younger age, leukocytosis >14,000, prolonged anuria and oliguria, persistent thrombocytopenia, as well as the presence of CNS complications