Co-circulation of multiple enterovirus D68 subclades, including a novel B3 cluster, across Europe in a season of expected low prevalence, 2019/20.

Enterovirus D68 (EV-D68) was detected in 93 patients from five European countries between 1 January 2019 and 15 January 2020, a season with expected low circulation. Patients were primarily children (n = 67, median age: 4 years), 59 patients required hospitalisation and five had severe neurologic manifestations. Phylogenetic analysis revealed two clusters in the B3 subclade and subclade A2/D. This circulation of EV-D68 associated with neurological manifestations stresses the importance of surveillance and diagnostics beyond expected peak years.

Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.

BACKGROUND & AIMS: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. METHODS: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. RESULTS: Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00). CONCLUSIONS: Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.

Beta-trace protein--a marker of kidney function in children: "Original research communication-clinical investigation".

OBJECTIVES: To determine the pediatric reference interval for serum beta-trace protein (beta-TP) and to compare beta-TP with established LMW markers of GFR, i.e., cystatin C (CysC) and beta(2)-microglobulin (beta(2)-M). DESIGN AND METHODS: All three LMW markers were measured immunonephelometrically. In 106 children above the age of 2 years without evidence of kidney disease, non-parametric reference intervals were calculated. The relative rise of the GFR marker concentrations above the upper reference was studied in 107 samples from 96 patients covering the entire GFR range. RESULTS: Above 2 years, the reference range of beta-TP was constant at 0.43-1.04 mg/L. With decreasing Schwartz-GFR, there was a comparable rise in beta-TP and beta(2)-M, while CysC rose less in the group with GFR below 30 mL/min/1.73 m(2) (278+/-49% [CysC] versus 336+/-65% [beta-TP] and 342+/-76% [beta(2)-M]; p=0.043 and 0.027, respectively). CONCLUSIONS: These data confirm the potential of ss-TP as an endogenous GFR marker in children.

Esomeprazole-based 1-week triple therapy directed by susceptibility testing for eradication of Helicobacter pylori infection in children.

BACKGROUND: Poor compliance to therapy and antibiotic resistance are the main causes for failure of anti-Helicobacter pylori therapy. OBJECTIVE: To evaluate the effectiveness of esomeprazole-based triple therapy directed by susceptibility testing. METHODS: Symptomatic children with H. pylori infection, who underwent successful susceptibility testing and were colonized by no double-resistant strain, received 1-week triple therapy with esomeprazole, amoxicillin and either clarithromycin or metronidazole. Success of eradication was investigated by C-urea breath test. RESULTS: Fifty-eight children (median age, 11.4 years; range, 2.2-17.7 years; 81% immigrants) were included. Helicobacter pylori was resistant to clarithromycin in 5 (9%) and to metronidazole in 9 children (16%). Eradication was successful in 49 (92%) of 53 children receiving esomeprazole, amoxicillin and clarithromycin and in all 5 children treated with metronidazole instead of clarithromycin, resulting in an eradication rate of 93% (95% confidence interval, 83%-98%, intention-to-treat analysis). All 4 treatment failures occurred in immigrants with language problems; 2 of them were obviously noncompliant. CONCLUSION: Esomeprazole-based 1-week triple therapy directed by susceptibility testing is highly effective for eradication of H. pylori infection in children.