Clinical severity and molecular characteristics of circulating and emerging rotaviruses in young children attending hospital emergency departments in France.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up to investigate the virological and clinical features of RVA infections and to detect the emergence of potentially epidemic strains in France. From 2009 to 2014, RVA-positive stool samples were collected from 4800 children <5 years old attending the paediatric emergency units of 16 large hospitals. Rotaviruses were then genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. Genotyping of 4708 RVA showed that G1P[8] strains (62.2%) were predominant. The incidence of G9P[8] (11.5%), G3P[8] (10.4%) and G2P[4] (6.6%) strains varied considerably, whereas G4P[8] (2.7%) strains were circulating mostly locally. Of note, G12P[8] (1.6%) strains emerged during the seasons 2011-12 and 2012-13 with 4.1% and 3.0% prevalence, respectively. Overall, 40 possible zoonotic reassortants, such as G6 (33.3%) and G8 (15.4%) strains, were detected, and were mostly associated with P[6] (67.5%). Analysis of clinical records of 624 hospitalized children and severity scores from 282 of them showed no difference in clinical manifestations or severity in relation to the genotype. The relative stability of RVA genotypes currently co-circulating and the large predominance of P[8] type strains may ensure vaccine effectiveness in France. The surveillance will continue to monitor the emergence of new reassortants that might not respond to current vaccines, all the more so as all genotypes can cause severe infections in infants.

A prospective study of nosocomial-infection-related mortality assessed through mortality reviews in 14 hospitals in Northern France.

AIM: To determine the number of deaths associated with nosocomial infection (NI) occurring in French hospitals, and to evaluate the role of hospital mortality reviews in assessing the preventability of NI-associated death. METHODS: The study considered 13,537 consecutive deaths occurring in 14 French hospitals in 2007 and 2008. An expert commission including attending physicians and nurses determined the likelihood that deaths could be attributed to NI, and the preventability of NI and death. FINDINGS: Medical records of the 2355 eligible patients with a McCabe score of 0 or 1 who died more than 48 h after admission were reviewed. Among them, 33% had at least one NI. Death was attributable to NI in 182 patients, and was considered preventable in 35 cases. Among these, 10 deaths were unexpected. CONCLUSION: Extrapolating these figures nationally, approximately 3500 [95% confidence interval (CI) 2605-4036] deaths attributable to NI occur in France annually. Among these, approximately 1300 NIs (95% CI 357-2196) and 800 deaths (95% CI 51-1481) can be considered preventable. Hospital mortality review commissions can help to improve the quality of health care by identifying circumstances associated with NI contributing to death, and targeting specific preventative measures. Such hospital commissions should involve all healthcare personnel.

Eosinophil counts in upper digestive mucosa of Western European children: variations with age, organs, symptoms, Helicobacter pylori status, and pathological findings.

AIM: The aim of the study was to measure the number of eosinophils per high-power field (eos/HPF) according to age, organs, and clinical symptoms and to compare the results to histological characteristics of the upper digestive tract mucosa in children. PATIENTS AND METHODS: A systematic prospective assessment of 284 esophagus, 342 antrum, 453 corpus, and 167 duodenum biopsies was carried out in 316 girls and 366 boys referred for endoscopy (median age 9 months), eos/HPF, and histological analysis. RESULTS: Counts (mean-max SD) were as follows: esophagus 1.73 to 50 eos/HPF (5.35), antrum 3.27 to 40 (4.7), corpus 2.11 to 38 (3.76), and duodenum 4.80 to 46 (7.7). Counts >15 eos/HPF were found in 2.8% esophagi, 3.5% corpora, 4.9% antra, and 10.7% duodena. Duodenal eos/HPF were significantly higher than those of esophageal, corporeal, and antral. Mucosal eos/HPF increased with age in esophagus and antrum. The highest esophageal eos/HPF were significantly associated with recurrent abdominal pain, and with anemia in antrum, corpus, and duodenum. Major and/or minor histological features of eosinophilic esophagitis were seen in 9 of 10 esophagi with 5 to 15 eos/HPF and 7 of 8 esophagi with >15 eos/HPF. Eosinophils per high-power field were significantly correlated with histological antral and corporeal gastric inflammation. Helicobacter pylori-positive children had higher eosinophils per high-power field than H pylori negative ones both in esophagus and in antrum. CONCLUSIONS: The present study shows that in a western European country mucosal hypereosinophilia is rare. Mucosal eosinophil counts increase from esophagus to duodenum, and also with age in esophagus and antrum. The highest eos/HPF in the esophagus are associated with recurrent abdominal pain and in the corpus, antrum, and duodenum with anemia. Features of eosinophilic esophagitis are rare but detectable in association with counts as low as 6 eos/HPF.

A novel immunoassay using recombinant allergens simplifies peanut allergy diagnosis.

BACKGROUND: Double-blind placebo-controlled food challenge (DBPCFC) is currently considered the gold standard for peanut allergy diagnosis. However, this procedure that requires the hospitalization of patients, mostly children, in specialized centers for oral exposure to allergens may cause severe reactions requiring emergency measures. Thus, a simpler and safer diagnosis procedure is needed. The aim of this study was to evaluate the diagnostic performance of a new set of in vitro blood tests for peanut allergy. METHODS: The levels of IgE directed towards peanut extract and recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 7, and Ara h 8 were measured in 3 groups of patients enrolled at 2 independent centers: patients with proven peanut allergy (n=166); pollen-sensitized subjects without peanut allergy (n=61), and control subjects without allergic disease (n=10). RESULTS: Seventy-nine percent of the pollen-sensitized patients showed IgE binding to peanut, despite their tolerance to peanut. In contrast, combining the results of specific IgE to peanut extract and to recombinant Ara h 2 and Ara h 6 yielded a peanut allergy diagnosis with a 98% sensitivity and an 85% specificity at a positivity threshold of 0.10 kU/l. Use of a threshold of 0.23 kU/l for recombinant Ara h 2 increased specificity (96%) at the cost of sensitivity (93%). CONCLUSION: A simple blood test can be used to diagnose peanut allergy with a high level of precision. However, DBPCFC will remain useful for the few cases where immunological and clinical observations yield conflicting results.

In French children, primary gastritis is more frequent than Helicobacter pylori gastritis.

The aim of this study was to analyze the histological characteristics according to the updated Sydney classification (intensity of gastritis, degree of activity, gastric atrophy, intestinal metaplasia, and Helicobacter pylori) in symptomatic children referred for upper gastrointestinal endoscopy. A 4-year retrospective descriptive study was carried out in 619 children (282 females and 337 males), median age 3.75 years (15 days to 17.3 years) referred for endoscopy. Six gastric biopsies were done (three antrum and three corpus) for histological analysis (n = 4), direct examination and H. pylori culture (n = 2). H. pylori status was considered positive if at least two out of three tests were positive and negative if all three tests were negative. The results showed that only 66 children (10.66%) were H. pylori positive. Histological antral and corpus gastritis was detected in, respectively, 53.95% and 59.12% of all cases, most of them of mild grade 1. Antral and corpus activity was grade 1 in 18.57% and 20.03% of cases. H. pylori-positive versus H. pylori-negative children did differ in terms of moderate and marked histological gastritis and grade 2 or 3 activities. One girl had moderate gastric atrophy and another one moderate intestinal metaplasia, both being H. pylori negative. The findings indicate that primary antrum and corpus gastritis is 5.3 and 6.9 times, respectively, more frequent than H. pylori gastritis in French children, with usually mild histological gastritis and activity. Gastric atrophy and intestinal metaplasia are rare.

[Incidence and risk factors of HCV infection in a cohort of intravenous drug users in the North and East of France]. / Incidence et facteurs de risque de la séroconversion au virus de l'hépatite C dans une cohorte d'usagers de drogue intraveineux du nord-est de la France.

BACKGROUND: In order to evaluate the incidence and risk factors of infection by hepatitis C virus (HCV) among intravenous drug users we conducted a prospective cohort study of HCV and HIV negative IVDU in the North and East of France. METHODS: Two hundred and thirty-one IVDU who had injected drug at least once in their lifetime and were negative for anti-HCV and anti-HIV were followed-up every three months over a 12-month period. Serum anti-HCV and anti-HIV antibodies were tested at inclusion in the study and at the end of the follow-up. Data on injection practices and behaviours were collected at inclusion and at each visit, and a test for anti-HCV antibodies was performed on a saliva sample. When this proved positive, an ELISA test for serum anti-HCV antibodies was carried out. RESULTS: Of the 231 participants included, 165 (71.4%) underwent a final HCV and HIV serum test. The incidence was nil for HIV infection and 9% (95% CI: 4.6-13.4) person-years for HCV infection. Among IVDU who injected at least once during the last 6 months HCV infection incidence was 11% (95% CI: 4.7-17.1) person-years. The multivariate analysis carried out on the inclusion data found female sex alone to be an independent predictive factor of HCV seroconversion. In a Cox proportional hazard multivariate analysis that took into account time-dependent exposures and covariates, we found that syringe and cotton sharing were, after adjusting for other covariates, the only independent predictive factors of HCV seroconversion: hazard ratio: 6.3 [corrected] (95% CI: 1.1-35.4; [corrected] p<0.05) and 16.4 (95% CI: 1.4-190.6; [corrected] p<0.05), respectively. CONCLUSION: The transmission of the HCV virus persists among French IVDU despite an ongoing national harm reduction program. Injecting material and cotton sharing are the two major determinants of transmission in this cohort.

Fast-electron transport and heating of solid targets in high-intensity laser interactions measured by K alpha fluorescence.

We present experimental results on fast-electron energy deposition into solid targets in ultrahigh intensity laser-matter interaction. X-ray K alpha emission spectroscopy with absolute photon counting served to diagnose fast-electron propagation in multilayered targets. Target heating was measured from ionization-shifted K alpha emission. Data show a 200 microm fast-electron range in solid Al. The relative intensities of spectrally shifted Al K alpha lines imply a mean temperature of a few tens of eV up to a 100 microm depth. Experimental results suggest refluxing of the electron beam at target rear side. They were compared with the predictions of both a collisional Monte Carlo and a collisional-electromagnetic, particle-fluid transport code. The validity of the code modeling of heating in such highly transient conditions is discussed.

Incidence and risk factors of HCV and HIV infections in a cohort of intravenous drug users in the North and East of France.

In order to evaluate the incidence and risk factors of infection by hepatitis C virus (HCV) among injecting drug users (IDUs), we conducted a prospective cohort study of HCV- and human immunodeficiency virus (HIV)-negative IDUs in the North and East of France. A total of 231 HCV and HIV IDUs who had injected drugs at least once in their lifetime were followed up every 3 months over a 12-month period. Serum anti-HCV and anti-HIV were tested at inclusion in the study and at the end of the follow-up. Data on injecting practices were collected at inclusion and at each visit. Of the 231 participants included, 165 (71.4%) underwent a final HCV and HIV serum test. The incidence was nil for HIV infection and 9/100 person-years (95% CI 4.6-13.4) for HCV infection. In a multivariable analysis, we found that syringe and cotton sharing were the only independent predictive factors of HCV seroconversion.

[Primary infected aneurysm of the infra-renal aorta:in situ or extra-anatomic bypass?]. / Anévrisme primitivement infecté de l'aorte sous-rénale. Pontage extra anatomique ou in situ?

There is no agreement in the literature as regards the best treatment for primary infected aneurysms. There is agreement concerning in situ treatment, inlay graft for supra-renal aneurysms. For infra-renal localizations no consensus has been reached. Most Authors prefer biological grafts over prosthetic materials for infected grafts or primary infected aneurysms. We report here a case of primary infected aneurysm treated in two stages. An initial axillo-bifemoral bypass was followed one Month later by aneurysmectomy and wide debridement of infected tIssue. Results were good at two years.

[Septic shock due to congenital disseminated toxoplasmosis?]. / Toxoplasmose congénitale disséminée responsable d'un choc septique?

Congenital toxoplasmosis secondary to maternal primary infection acquired late during pregnancy is generally asymptomatic at birth. We report a case of a newborn infant whose mother had been infected between the 27th and the 33rd week of gestation. No treatment had been given during gestation. The infant had a disseminated form of toxoplasmosis with hepatosplenomegaly, pneumonitis, purpura, hepatitis. On the third day of life, he developed shock. The patient died early despite therapy. Septic shock is unusual in congenital toxoplasmosis, although it has been described in immunocompromised patients, notably in patients infected with the human immunodeficiency virus.

[Rapid identification of pneumococcal antigenes in urines by the Now Streptococcus pneumoniae Binax test]. / Détection rapide des antigènes pneumococciques urinaires par le test Now Streptococcus pneumoniae Binax.

Streptococcus pneumoniae is responsible for many infectious conditions but probably with an underestimated incidence especially because of the fragility of the bacteria. The present study has evaluated a new test which detects a pneumococcal antigen in urine (Now S.p Binax). Urine samples from 181 children and 40 adults have been tested. All the patients presented with typical clinical signs of pneumococcal infection. Sensitivity = 91.7 %; specificity = 54.2 %; positive predictive value = 50 %; and negative predictive value = 92.9 % have been observed. Although the sensitivity and specificity were lower than those announced by the manufacturer, the test is easy to handle and provides a rapid argument for the diagnosis of pneumococcal infection, especially in the case of invasive infections like meningitis and bacteraemia.

Multicenter evaluation of strategies for serodiagnosis of primary infection with Toxoplasma gondii.

The diagnostic performance of single-serum assays for toxoplasma-specific immunoglobulin (Ig)M. IgA. IgG, and IgE antibodies and of different combinations of such antibody assays in 20 European reference centers was assessed. A panel of 276 sera, of which 73 came from patients who seroconverted within 3 months (acute infection), 49 from patients who had seroconverted 3-12 months earlier (convalescence), and 154 from subjects who had two IgG-positive samples obtained 12 months apart (past infection), was tested with 20 toxoplasma-antibody assays and 195 combinations. In general, every assay with high diagnostic sensitivity showed low diagnostic specificity, i.e. no assay performed alone could reliably distinguish acute from past infection. Furthermore, no single assay (or combination) could separate convalescence from the other stages of toxoplasma infection. However, excellent diagnostic performances were reached by sequential use of highly sensitive IgM assays and methods examining IgG avidity or stage specificity. IgA or IgM assays were less suitable for confirmation of toxoplasma-IgM positivity. This study documents the strength of test combinations in assessing the stage of toxoplasma infection.

Strategy for diagnosis of congenital toxoplasmosis: evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies.

In a study involving 14 laboratories supported by the European Community Biomed 2 program, we evaluated immunologic methods for the postnatal diagnosis of congenital toxoplasmosis (CT). Among babies born to mothers who seroconverted to positivity for toxoplasmosis during pregnancy, we analyzed 55 babies with CT on the basis of persistent anti-Toxoplasma immunoglobulin G (IgG) at 1 year of life and 50 control babies without anti-Toxoplasma IgG at 1 year of life in the absence of curative treatment with pyrimethamine-sulfonamides. We tested in-house methods such as the enzyme-linked immunofiltration assay (ELIFA) or Immunoblotting (IB) for the detection of IgG or IgM; these methods allowed comparison of the immunologic profiles of the mothers and the infants. We compared ELIFA and IB with a commercial enzyme immunoassay (EIA) or in-house immunosorbent agglutination assay (ISAGA) for the detection of IgM or IgA. The performances of combinations of methods were also assessed. A cumulative sensitivity of 98% during a 1-year follow-up was obtained with the ELIFA plus ISAGA combination. Only one case of CT was missed by the ELIFA plus ISAGA combination, whereas three cases were missed by the IB plus ISAGA combination, even though 48% of patients with CT were treated with pyrimethamine-sulfonamides, which are known to inhibit antibody neosynthesis. A similar performance was obtained with either ELIFA or IB in combination with EIA. The difference in performance between ELIFA plus ISAGA and IB plus ISAGA was not statistically significant (P = 0.31), and we conclude that both combinations of tests can be used for the diagnosis of CT in newborns.

[Toxoplasmosis serodiagnosis: comparison of Access Toxo IgM II assay compared to Axsym Toxo IgM and Vidas Toxo IgM assays]. / Sérodiagnostic de le toxoplasmose: comparaison de la trousse Access Toxo IgM II aux trousses Axsym Toxo IgM et Vidas Toxo IgM.

The Access Toxo IgM II test (Beckman Coulter Inc) was evaluated on 1,190 samples from toxoplasmosis serology requests, documented seroconversions, umbilical cord blood or venous blood from healthy newborn, and from newborns with congenital toxoplasmosis. Results were compared to those obtained with Vidas (bioMérieux) and Axsym (Abbott) assays, with Isaga as confirmatory technique. Results obtained with the Access test well correlate those with the Vidas (98.3%) and the Axsym (97.6%) assays. Less "bordeline" results are also observed with the Access test (0.22% versus 0.56% and 1.24% with Vidas and Axsym assays respectively). Results obtained from seroconverted patients prove that the Access assay is more sensitive than Vidas and Axsym assays, with respectively 2 and 4 samples detected earlier for 28 cases studied (recently seroconverted patients). Results obtained using prospective samples and with sequential sera obtained from patients with seroconversion clearly demonstrate that Access Toxo IgM II assay is perfectly adapted to toxoplasmosis diagnosis.

Diagnosis of congenital toxoplasmosis in the neonatal period: A multicenter evaluation.

OBJECTIVE: To evaluate different laboratory tests used to diagnose congenital toxoplasmosis in the neonatal period. STUDY DESIGN: A retrospective multicenter study of 294 pregnant women who experienced seroconversion for Toxoplasma gondii and subsequently delivered live-born infants. Fetal infection was assessed via specific IgM and IgA antibodies (cord and neonatal blood) and detection of T gondii in placenta and cord blood by mouse inoculation. RESULTS: Ninety-three (32%) of the 294 infants were congenitally infected. The sensitivity of IgA in cord blood and in neonatal blood was 64% and 66%; the sensitivity of IgM was 41% and 42%, respectively. Mouse inoculation of the placenta and cord blood had sensitivities of 45% and 16%. Positive results of the serologic tests in congenitally infected children correlated significantly with the gestational age at the time of maternal infection but was not significantly influenced by the administration of specific antiparasitic treatment during pregnancy. CONCLUSION: Specific T gondii IgA antibody is a more sensitive test than IgM for detecting congenital toxoplasmosis in the neonatal period. The overall specificity is better for serologic tests performed on neonatal blood than for those on cord blood. Neonatal screening with IgM or IgA antibodies will not detect the majority of children with congenital toxoplasmosis when the maternal infection occurred before the 20th week of pregnancy.

Prenatal diagnosis of congenital toxoplasmosis: a multicenter evaluation of different diagnostic parameters.

OBJECTIVE: Our purpose was to evaluate different methods of diagnosing congenital toxoplasmosis prenatally by amniocentesis and cordocentesis. STUDY DESIGN: In a retrospective multicenter study, we investigated consecutive women who had seroconversion for Toxoplasma gondii during pregnancy and who underwent either amniocentesis or cordocentesis or both to obtain a prenatal diagnosis of fetal toxoplasmosis. Data were obtained from 122 patients recruited in 6 different European Toxoplasma reference centers. Infants born to these mothers were followed up until 1 year of age to confirm or exclude congenital toxoplasmosis. Sensitivity, specificity, positive predictive value, and negative predictive value were measured for the following parameters: (1) detection of the parasite in amniotic fluid by mouse inoculation, (2) detection of the parasite in amniotic fluid by in vitro cell culture, (3) detection of Toxoplasma deoxyribonucleic acid in amniotic fluid by a polymerase chain reaction assay, (4) detection of the parasite in fetal blood by mouse inoculation, (5) detection of specific immunoglobulin M antibodies in fetal blood, and (6) detection of specific immunoglobulin A antibodies in fetal blood. RESULTS: The polymerase chain reaction test performed on amniotic fluid had the highest level of sensitivity (81%) and also a high level of specificity (96%). The combination of the polymerase chain reaction test and mouse inoculation of amniotic fluid increased sensitivity to 91%. The sensitivity of immunoglobulins M and A in fetal blood was 47% and 38%, respectively. In congenitally infected fetuses a negative correlation was observed between positive serologic parameters and gestational age at the time of maternal infection and at prenatal diagnosis. CONCLUSION: Congenital toxoplasmosis is best predicted by prenatal examination with the combination of T gondii polymerase chain reaction and mouse inoculation of amniotic fluid. The role of cordocentesis in the diagnosis of congenital toxoplasmosis is limited.

Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children's sequelae at age 1 year.

OBJECTIVE: Toxoplasmosis during pregnancy can cause fetal infection, with unpredictable sequelae in later life. We measured the effects of prenatal antibiotic therapy on the fetomaternal transmission of Toxoplasma gondii and on the appearance of sequelae in the congenitally infected child at age 1 year. STUDY DESIGN: In a multicenter study we investigated consecutive women with Toxoplasma seroconversion during pregnancy. Data were obtained from 144 women recruited in 5 different Toxoplasma reference centers. Through multivariate analysis we assessed the association between transmission and appearance of sequelae as a function of the following parameters: estimated gestational age at infection, administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy. RESULTS: Sixty-four of the 144 women (44%) gave birth to a congenitally infected infant. Multivariate analysis showed that transmission was predicted neither by whether antibiotics had been administered nor by the time lapse between infection and the start of antibiotic therapy, but only by the gestational age at which maternal infection occurred (P <.0001). Sequelae were found in 19 children (13%), 9 of whom (6%) had severe sequelae. Administration of antibiotics was predictive of the absence of sequelae (P =.026, odds ratio 0.30, 95% confidence interval 0.104-0.863), in particular the absence of severe sequelae (P =.007, odds ratio 0.14, 95% confidence interval 0.036-0.584). The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P =. 021). CONCLUSION: Prenatal antibiotic therapy after toxoplasmosis during pregnancy had no impact on the fetomaternal transmission rate but reduced the rate of sequelae among the infected infants. The early start of treatment resulted in a significant reduction in the number of severely affected infants.