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Author(s): Julie Tottey[sup.1], Lucie Etienne-Mesmin[sup.2], Sandrine Chalançon[sup.2], Alix Sausset[sup.1], Sylvain Denis[sup.2], Carine Mazal[sup.2], Christelle Blavignac[sup.3], Guillaume Sallé[sup.1], Fabrice Laurent[sup.1], Stéphanie Blanquet-Diot[sup.2] and Sonia Lacroix-Lamandé[sup.1] Background The zoonotic disease cryptosporidiosis caused [...], Background Human cryptosporidiosis is distributed worldwide, and it is recognised as a leading cause of acute diarrhoea and death in infants in low- and middle-income countries. Besides immune status, the higher incidence and severity of this gastrointestinal disease in young children could also be attributed to the digestive environment. For instance, human gastrointestinal physiology undergoes significant changes with age, however the role this variability plays in Cryptosporidium parvum pathogenesis is not known. In this study, we analysed for the first time the impact of digestive physicochemical parameters on C. parvum infection in a human and age-dependent context using a dynamic in vitro gastrointestinal model. Results Our results showed that the parasite excystation, releasing sporozoites from oocysts, occurs in the duodenum compartment after one hour of digestion in both child (from 6 months to 2 years) and adult experimental conditions. In the child small intestine, slightly less sporozoites were released from excystation compared to adult, however they exhibited a higher luciferase activity, suggesting a better physiological state. Sporozoites collected from the child jejunum compartment also showed a higher ability to invade human intestinal epithelial cells compared to the adult condition. Global analysis of the parasite transcriptome through RNA-sequencing demonstrated a more pronounced modulation in ileal effluents compared to gastric ones, albeit showing less susceptibility to age-related digestive condition. Further analysis of gene expression and enriched pathways showed that oocysts are highly active in protein synthesis in the stomach compartment, whereas sporozoites released in the ileum showed downregulation of glycolysis as well as strong modulation of genes potentially related to gliding motility and secreted effectors. Conclusions Digestion in a sophisticated in vitro gastrointestinal model revealed that invasive sporozoite stages are released in the small intestine, and are highly abundant and active in the ileum compartment, supporting reported C. parvum tissue tropism. Our comparative analysis suggests that physicochemical parameters encountered in the child digestive environment can influence the amount, physiological state and possibly invasiveness of sporozoites released in the small intestine, thus potentially contributing to the higher susceptibility of young individuals to cryptosporidiosis. Keywords: Cryptosporidium, Apicomplexa, In vitro digestive model, Physicochemical parameters, Child and adult digestion

Introduction Urine oxalate excretion is low (normal value Oxalate is produced in the liver from glyoxylate transformation by lactate dehydrogenase type 5 (LDH5) isoenzyme and excreted in urine, with little [...], Increased urinary oxalate excretion (hyperoxaluria) promotes the formation of calcium oxalate crystals. Monogenic diseases due to hepatic enzyme deficiency result in chronic hyperoxaluria, promoting end-stage renal disease in children and young adults. Ethylene glycol poisoning also results in hyperoxaluria, promoting acute renal failure and frequently death. Stiripentol is an antiepileptic drug used to treat children affected by Dravet syndrome. It has been shown to inhibit neuronal lactate dehydrogenase 5 enzyme. As this isoenzyme is also the last step of hepatic oxalate production, we hypothesized that stiripentol would potentially reduce hepatic oxalate production and urine oxalate excretion. In vitro, stiripentol decreased the synthesis of oxalate by hepatocytes in a dose-dependent manner. In vivo, oral administration of stiripentol significantly reduced urine oxalate excretion in rats. Stiripentol protected the kidneys against calcium oxalate crystal deposits in acute ethylene glycol intoxication and chronic calcium oxalate nephropathy models. In both models, stiripentol significantly improved renal function. Patients affected by Dravet syndrome and treated with stiripentol had a lower urine oxalate excretion than control patients. A young girl affected by severe type I hyperoxaluria received stiripentol for several weeks, and urine oxalate excretion decreased by two-thirds. Stiripentol is a promising potential therapy against genetic hyperoxaluria and ethylene glycol poisoning.

Over the past decade, reported cases of malaria and associated deaths have declined in Africa (1). This decrease has led to a search for other causes of fever in Africa, [...]

In the United States, recreational water is a relatively uncommon source of Shiga toxin-producing Escherichia coli (STEC) O157 outbreaks (1). We describe an outbreak of STEC O157 infections among children [...]

Introduction Worldwide, over two million children are infected by human immunodeficiency virus type l (HIV-1). (1) Ninety per cent of them live in Africa, and only 38% of those who [...], Objective To assess 12-month survival, pharmacokinetics, immunologic and virologic efficacy, tolerance, compliance and drug resistance in HIV-infected children in Bobo-Dioulasso, Burkina Faso, receiving once-daily highly-active antiretroviral therapy as a combination of didanosine (DDI), lamivudine (3TC) and efavirenz (EFV). Methods In the ANRS 12103 open phase II trial, HIV-infected children were examined at inclusion and monthly thereafter. CD4+ T-lymphocyte (CD4) count, plasma concentration of ribonucleic acid (RNA) of human immunodeficiency virus type 1 (HIM-1) and haematologic and biochemical parameters were measured at baseline and every trimester. HIV-1 resistance testing was performed in case of viral escape. Drug plasma concentrations were determined with high-performance liquid chromatography. Findings From February 2006 to November 2007, 51 children (39% girls) with a mean age of 6.8 years were enrolled and treated for 12 months. At baseline, Z scores for mean weight-for-age and mean height-for-age were -2.01 and -2.12, respectively. Mean CD4% was 9.0. Median plasma HIV-1 RNA viral load was 5.51 [log.sub.10] copies per millilitre (cp/ml). Two children (3.9%) died and another 11 (22%) suffered 13 severe clinical events. At month 12, mean WAZ had improved by 0.63 (P< 0.001) and mean HAZ by 0.57 (P< 0.001). Mean CD4% had risen to 24 (P< 0.001). Viral load was below 300 RNA cp/ml in 81% of the children; HIV resistance mutations were detected in 11 (21.6%). Conclusion The once-a-day combination of DDI + 3TC + EFV is an alternative first-line treatment for HIV-1-infected children. Dose adjustment should further improve efficacy. Objectif Evaluer sur 12 mois la survie, la pharmacocinetique, l'efficacite immunologique et virologique, la tolerance, l'observance et la resistance au medicament chez des enfants infectes par le VlH a Bobo-Dioulasso, Burkina Faso, et qui recoivent une fois par jour une therapie antiretrovirale hautement active par une association de didanosine (DDI), de lamivudine (3TC) et d'efavirenz (EFV). Methodes Dans l'essai ouvert ANRS 12103 phase II, des enfants infectes par le VlH ont ete examines au moment de l'inclusion et ensuite chaque mois. Le taux de lymphocytes T CD4 (CD4), la concentration plasmatique d'acide ribonucleique (ARN) du virus de l'immunodeficience humaine type 1 (VlH-1), ainsi que des parametres hematologiques et biochimiques ont ete mesures au debut de l'etude et chaque trimesb'e. Le test de resistance au VIH-1 a ete effectue dans les cas d'evasion virale. Les concentrations plasmatiques de medicament ont ete determinees par chromatographie liquide a haute performance. Resultats De fevrier 2006 a novembre 2007, 51 enfants (39% de filles), avec une moyenne d'age de 6,8 ans, ont ete selectionnes et traites pendant 12 mois. Au debut de l'etude, les ecarts reduits pour le poids moyen par age et la taille moyenne par age etaient respectivement de -2,01 et -2,12. Le CD4 moyen etait 9,0%. La charge virale plasmatique mediane de I'ANR VIH-1 etait de 5,51 legue copies par millilitre (cp/ ml). Deux enfants (3,9%) sont decedes et 11 autres (22%) ont souffert 13 evenements cliniques severes. Au 12e mois, le WAZ moyen s'etait ameliore de 0,63 (P Conclusion L'association DDI + 3TC + EFV en une prise quotidienne est un traitement alternatif de premiere intention pour les enfants infectes au VIH-1. L'adaptation de la dose devrait encore ameliorer l'efficacite. Objetivo Evaluar a 12 meses la supervivencia, la farmacocinetica, la eficacia inmunologica y virologica, la tolerancia, el cumplimiento terapeutico y la resistencia a los medicamentos en ninos infectados con el VIH en Bobo-Dioulasso (Burkina Faso), que reciben una vez al dia un tratamiento antirretrovirico muy activo, constituido por la asociacion de didanosina (DDI), lamivudina (3TC) y efavirenz (EFV). Metodos En el ensayo clinico ANRS 12103, abierto y de fase II, se examino a los ninos infectados con el VIH en el momento de la inclusion y, a continuacion, mensualmente. Se midieron el recuento de linfocitos T [CD4.sup.+] (CD4), la concentracion plasmatica de acido ribonucleico (ARN) del virus de la inmunodeficiencia humana de tipo 1 (VlH-1) y los parametros hematologicos y bioquimicos, al inicio y cada trimestre. Las pruebas de resistencia al VIH-1 se realizaron en el caso de escape virico. Las concentraciones plasmaticas del farmaco se determinaron con cromatografia en fase liquida de alta resolucion. Resultados Desde febrero del 2006 a noviembre del 2007, 51 ninos (39% ninas) con una edad media de 6,8 anos fueron registrados y tratados durante 12 meses. Al inicio del estudio, las puntuaciones Z del peso medio por edad y la altura media por edad fueron -2,01 y -2,12 respectivamente. El % medio de CD4 fue 9,0. La carga virica media de RNA del HIV-1 en plasma fue de 5,51 [log.sub.10] copias por mililitro (cp/ml). Dos ninos (3,9%) murieron y otros 11 (22%) sufrieron 13 acontecimientos clinicos graves. En el mes 12, el WAZ medio (peso por edad segun la puntuacion Z) habia mejorado en un 0,63 (p < 0,001) y el HAZ medio (altura por edad segun la puntuacion Z) en 0,57 (p < 0,001). El % medio de CD4 habia subido a 24 (p < 0,001). La carga virica estaba por debajo de 300 ARN cp/ml en el 81% de los ninos; se detectaron mutaciones de resistencia al VlH en 11 (21,6%). Conclusion La asociacion de DDI + 3TC + EFV una vez al dia es un tratamiento alternativo de primera linea para los ninos infectados con el VIH-1. Un ajuste de la dosis deberia mejorar todavia mas la eficacia.

In 2001, the first draft of the human genome was published. (1 2) Paediatricians from all disciplines can look forward to important and novel insights into the genetic basis for [...]

To the Editor: We report findings from a household-based study on the protective effects of vaccination against pandemic (H1N1) 2009 among Japanese children. In Japan, prioritized vaccination started in October [...]