Outbreak of hemolytic uremic syndrome with unusually severe clinical presentation caused by Shiga toxin-producing Escherichia coli O26:H11 in France.

BACKGROUND: In spring 2019, an outbreak of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC HUS) occurred in France. Epidemiological investigations made by Santé publique France in connection with microbiological investigations at the national reference center for STEC promptly identified a common exposure to consumption of raw cow's milk cheese, and confirmed a cluster affiliation of the E. coli O26:H11 outbreak strain. Here, we report the clinical characteristics of the patients, the treatment used, as well as the outcome at 1 month. METHOD: Patients with STEC HUS linked to the E. coli O26:H11 outbreak strain were identified from the national surveillance network of pediatric STEC HUS cases coordinated by Santé publique France. Clinical data were analyzed from the patients' hospital records obtained from the treating physicians. RESULTS: Overall, 20 pediatric cases of STEC HUS linked to the outbreak strain were identified. Their median age of the patients was 16 months (range: 5-60). Most of them presented with diarrhea but none had received prior antibiotherapy. A total of 13 patients required dialysis; 10 patients and four patients had central nervous system (CNS) and cardiac involvement, respectively. No deaths occurred. At the 1-month follow-up, only two patients had a decreased glomerular filtration rate, below 80 mL /min/1.73m2 and four had hypertension. One patient had neurological sequelae. CONCLUSION: The E. coli O26:H11 strain identified as the cause of an STEC HUS outbreak in France in spring 2019 is notable for the initial severe clinical presentation of the patients, with a particularly high frequency of CNS and cardiac involvement similar to the German E. coli O104:H4 outbreak described in 2011. However, despite the initial severity, the 1-month outcome was favorable in most cases. The patients' young age in this outbreak highlights the need to improve information and caregiver awareness regarding consumption of at-risk foods by young children as key preventive measures against STEC infections.

Acute tubulointerstitial nephritis in children and chronic kidney disease.

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a rare condition in children. The etiology, treatment, and outcome of childhood ATIN remain poorly understood. The long-term prognosis seems to be favorable; however, chronic kidney disease has been reported. This article describes clinical outcomes in a series of children with biopsy-proven ATIN. METHODS: All medical records with biopsy-proven ATIN between January 2006 and 2016 were retrospectively analyzed. The incidence, clinical features, etiology, treatment, and outcome were recorded for each patient. RESULTS: Over 10 years, ATIN was diagnosed in 25 cases (8%) based on 306 renal needle biopsies. The most frequent clinical signs were abdominal pain, asthenia/weight loss, and fever. A median glomerular filtration rate estimated at 30.1mL/min/1.73 m2 (16.5; 45.5). Drug-induced toxicity was the main etiology (eight patients). Other causes were TINU syndrome (tubulointerstitial nephritis and uveitis) (seven patients), infection (two patients), and toxic agents other than medication (one patient). No etiology was found in seven patients (idiopathic cases). Eighteen patients (72%) were treated with steroids. At the end of follow-up, eight patients presented chronic kidney disease, three hypertension, and three tubular dysfunction. Overall, renal function was highest in the idiopathic ATIN group and in children treated without delay. CONCLUSIONS: In a single-center 10-year series of biopsy-confirmed ATIN in children, drugs and TINU syndrome were the main etiologies of ATIN. This study suggests that children with idiopathic ATIN and prompt treatment have a better prognosis. In this series, occurrence of chronic kidney disease justified long-term follow-up.

Prenatal ethanol exposure and placental hCG and IGF2 expression.

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is the main cause of preventable non-genetic mental retardation. Diagnosis of prenatal exposure to ethanol (PEE) is based on questionnaires and biomarkers in perinatal matrices. Early diagnosis of FASD is important to mitigate secondary disabilities that will arise later in life. It is important to identify biomarkers related to cellular damage caused by PEE. The main objective was to identify novel candidate biomarkers from placental tissue using an in vitro model of exposure to ethanol and to support it in placental tissue obtained from pregnancies with PEE assessed by fatty acid esters in meconium samples. METHODS: First, hormone production was examined using two different human trophoblast cell lines, JEG3 and BeWo. Viable cell count by exclusion method was analyzed and human chorionic gonadotrophin (hCG) and insulin-like growth factor 2 (IGF2) were quantified by Western blot and ELISA. Second, these techniques were used in protein lysates from human placentas from pregnancies with and without exposure to ethanol. RESULTS: Both trophoblast cell lines showed a decrease in cell viability accompanied with apoptosis activation after a chronic ethanol treatment. Moreover, we showed an increase in the secretion of hCG and IGF2 in a dose-dependent manner. Interestingly, this increase was also observed in a set of human placenta tissue from fetuses exposed prenatally to ethanol. DISCUSSION: Ethanol exposure during pregnancy causes placenta cell damage, so altering its normal function. The specific hCG and IGF2 release pattern is a candidate surrogated biomarker of the damage due to PEE.

Ethanol cytotoxic effect on trophoblast cells.

Prenatal ethanol exposure may cause both, altered fetal neurodevelopment and impaired placental function. These disturbances can lead to growth retardation, which is one of the most prevalent features in Fetal Alcohol Syndrome (FAS). It is not known whether there is a specific pattern of cytotoxicity caused by ethanol that can be extrapolated to other cell types. The aim of this study was to determine the cytotoxic effects caused by sustained exposure of trophoblast cells to ethanol. The cytotoxic effect of sustained exposure to standard doses of ethanol on an in vitro human trophoblast cell line, JEG3, was examined. Viable cell count by exclusion method, total protein concentration, lactate dehydrogenase (LDH) activity and activation of apoptotic markers (P-H2AX, caspase-3 and PARP-1) were determined. Sustained exposure to ethanol decreased viable cell count and total protein concentration. LDH activity did not increased in exposed cells but apoptotic markers were detected. In addition, there was a dose-dependent relationship between ethanol concentration and apoptotic pathways activation. Sustained ethanol exposure causes cellular cytotoxicity by apoptotic pathways induction as a result of DNA damage. This apoptotic induction may partially explain the altered function of placental cells and the damage previously detected in other tissues.