Tolérance et efficacité de la méfloquine dans le traitement curatif de première intention de l'accès palustre simple à Plasmodium falciparum d'importation de l'enfant

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocPARIS-Académie Médecine (751065201) / SudocSudocFranceF

Tolérance et efficacité de la méfloquine dans le traitement de première intention de l'accès palustre simple à plasmodium falciparum d'importation chez l'enfant

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation d'un schéma de prise en charge de la méningite aigüe aux urgences pédiatriques (étude rétrospective de 214 cas)

Dans une méningite aigüe, une difficulté importante et fréquente rencontrée par les praticiens est de distinguer les méningites aseptiques des méningites bactériennes. L'étude a consisté à évaluer un document d'aide à la décision thérapeutique, proposé aux praticiens de l'hôpital Armand Trousseau depuis 1999. Ce travail est rétrospectif et a pris en compte 8 méningites bactériennes et 206 méningites aseptiques, hospitalisées entre le 1er janvier et le 30 octobre 2000, via les urgences de l'établissement. Après description exhaustive des cas de méningite, chaque critère inclus dans le document d'aide décisionnel a été évalué individuellement et en association avec les autres. L'association de 4 critères était statistiquement liée à l'existence d'une méningite bactérienne, avec une sensibilité de 100%, une spécificité de 99,5%, et une valeur prédictive négative de 100%. Nous avons proposé un nouveau document introduisant des données complémentaires par rapport au document originalPARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Critères anamnestiques et cliniques liés à l hospitalisation d un enfant de moins de cinq ans qui consulte aux urgences pour diarrhée aiguë

A l inverse de la bronchiolite, la prise en charge de la diarrhée aiguë (DA) ne repose pas sur des critères consensuels. L'objectif de cette étude est d'identifier les critères anamnestiques et cliniques liés à l hospitalisation. Cette étude prospective porte sur les enfants de moins de 5 ans consultant aux urgences de l hôpital Trousseau pour DA du 28 janvier au 17 février 2006. La DA est définie par l émission d au moins 3 selles molles ou liquides sur 24 heures. La cohorte compte 179 enfants. Le sexe, la prématurité, l âge supérieur à 3 mois, la fièvre, ne sont pas significativement liés à l hospitalisation. Un âge inférieur à 3 mois (OR=5,2, IC 95% [1,1-24,9], une perte de poids entre 5 et 10% (OR=2,8, IC 95% [0,9-8,4], plus de 5 selles dans les 12 dernières heures (OR>14, IC 95% [3,1-70], plus de 5 selles sur 24 heures (OR>3,5, IC 95% [1-12], plus de 2 vomissements dans les 12 dernières heures (OR>3, IC 95% [1-10], sont les éléments d anamnèse significativement liés à l hospitalisation. Un pli cutané (OR=18,1), la pâleur (OR=4,3), les muqueuses sèches (OR=16,1) et l irritabilité (OR=5,5) sont les critères cliniques, en dehors de l état de choc, qui sont significativement (p=0,001 respectivement) liés à l hospitalisation. Après ajustement, plus de 5 selles et plus de 2 vomissements sur les 12 dernières heures et une fréquence maximale de plus de 5 selles sur 24 heures restent significativement liés à l hospitalisation. En conclusion, cette étude permet d identifier les éléments anamnestiques et cliniques liés à l hospitalisation. Elle représente une étape préliminaire pour l élaboration d un guide de prise en charge de la diarrhée aiguë pédiatrique.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Le poids épidémiologique de la gastro-entérite aiguë aux urgences pédiatriques justifie-t-elle la vaccination des nourrissons en routine contre l'infection à rotavirus?

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude de l'immunité innée anti-rotavirus chez l'homme et vaccination rectale chez la souris fondées sur l'utilisation de pseudo-particules virales

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Le poids de la gastro-entérite aiguë aux urgences pédiatriques justifie-t-il la création d'un réseau de soins ambulatoires et une restructuration des services d'urgences ?

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Rearrangements of rotavirus genomic segment 11 are generated during acute infection of immunocompetent children and do not occur at random.

International audienceGroup A rotaviruses are the main cause of viral gastroenteritis in infants. The viral genome consists of 11 double-stranded RNA (dsRNA) segments. Dysfunction of the viral RNA polymerase can lead to gene rearrangements, which most often consist of partial sequence duplication of a dsRNA segment. Gene rearrangements have been detected in vivo during chronic infection in immunodeficient children or in vitro during passages at a high multiplicity of infection in cell culture, suggesting that these replication conditions lead to selective advantages favoring the recovery of viruses with rearranged genes. During acute rotavirus infection, the replication level is high, but the occurrence of rearrangement events has never been reported. By the use of a reverse transcription-PCR assay specifically designed to detect small numbers of copies of rearranged forms of segment 11 in a high background of its standard counterpart, we detected 12 rearrangement events among 161 cases (7.5%) of acute rotavirus infection in immunocompetent children. Strikingly, in all but one case, rearrangement took place at the same location within the short direct repeat AUGU sequence. For the unique case with a different rearrangement pattern, the rearrangement occurred within the direct repeat ACAAGUC that was specific for this isolate. In conclusion, we report the occurrence of segment 11 rearrangements during acute rotavirus infection in immunocompetent children. We show that under such conditions of infection, the viral RNA polymerase generates rearrangements which occur not at random but within direct repeats which might constitute hot spots for RNA recombination

Cost-effectiveness analysis of vaccination against rotavirus with RIX4414 in France.

International audienceBACKGROUND: It is estimated that annually 300 000 cases of rotavirus-induced gastroenteritis (RVGE) occur in children aged up to 5 years in France. A two-dose vaccine against rotavirus infection (RIX4414; Rotarix, GlaxoSmithKline), has been shown to be highly effective against severe RVGE. OBJECTIVE: This study evaluated the cost effectiveness of general vaccination against rotavirus using RIX4414 in France. METHODS: A Markov model simulated RVGE events and the associated outcomes and costs relating to general vaccination of infants against rotavirus infection using RIX4414 (Rotarix) in a birth cohort of children aged up to 5 years in France with a combined adjustment for age distribution with the seasonality of the infection. Costs and outcomes were estimated from a limited societal perspective, including direct medical costs paid out of pocket or by third-party payers, as well as the proportion of direct medical costs reimbursed by the health authorities. Indirect costs were not included in the base-case analysis. The primary outcome measure was the incremental cost per QALY. RESULTS: Vaccination with RIX4414 incurred an incremental cost of 44 583 Euro per QALY at a public price of 57 Euro per vaccine dose. Univariate sensitivity analyses showed that the parameters with the largest influence on the results were the transition probabilities of severe diarrhoea, seeking medical advice and emergency visits, utility scores of diarrhoea (mild) in children and infants, and the discount rate for benefits. Probabilistic multivariate sensitivity analysis confirmed these results. The acceptability curve indicated that 94% of the results were under an informal threshold of 50 000 Euro per QALY. Comparing our results with those of a recently published study using pooled data for two rotavirus vaccine products in France, the main differences are explained by differences in model structure and in data input values. They include a different age distribution of the infection, shorter duration of the at-risk period (3 years instead of 5 years), different vaccine efficacy, different unit cost data, different disease duration, and different disutility values for the health states in the model. There is a need for agreed standards to improve comparability of results from different studies. CONCLUSIONS: The results demonstrate that a generalized vaccination strategy with RIX4414 would be cost effective in France from a limited societal perspective, depending on the baseline assumptions for disease progression and on utility scores selected

Rotavirus Anti-VP6 Secretory Immunoglobulin A Contributes to Protection via Intracellular Neutralization but Not via Immune Exclusion

Immunoglobulin A (IgA) monoclonal antibodies (MAbs) directed at the conserved inner core protein VP6 of rotavirus, such as the IgA7D9 MAb, provide protective immunity in adult and suckling mice when delivered systemically. While these antibodies do not have traditional in vitro neutralizing activity, they could mediate their antiviral activity either by interfering with the viral replication cycle along the IgA secretory pathway or by acting at mucosal surfaces as secretory IgA and excluding virus from target enterocytes. We sought to determine the critical step at which antirotaviral activity was initiated by the IgA7D9 MAb. The IgA7D9 MAb appeared to directly interact with purified triple-layer viral particles, as shown by immunoprecipitation and immunoblotting. However, protection was not conferred by passively feeding mice with the secretory IgA7D9 MAb. This indicates that the secretory IgA7D9 MAb does not confer protection by supplying immune exclusion activity in vivo. We next evaluated the capacity of polymeric IgA7D9 MAb to neutralize rotavirus intracellularly during transcytosis. We found that when polymeric IgA7D9 MAb was applied to the basolateral pole of polarized Caco-2 intestinal cells, it significantly reduced viral replication and prevented the loss of barrier function induced by apical exposure of the cell monolayer to rotavirus, supporting the conclusion that the antibody carries out its antiviral activity intracellularly. These findings identify a mechanism whereby the well-conserved immunodominant VP6 protein can function as a target for heterotypic antibodies and protective immunity