J. Brouard

Co-infections virales lors des bronchiolites du nourrisson immunocompétent: étude prospective épidémiologique

The nature of viral infection was prospectively investigated in 202 immunocompetent infants with bronchiolitis. Nasal aspirates were evaluated by immunofluorescence assay, viral isolation technique and polymerase-chain-reaction-hybridization assay. In 55 infants (27%) more than one respiratory virus were detected. A Rotavirus was found in 40 infants (20%), without any relationship with the respiratory viral status, respiratory syncytial virus being the main virus (46/55), and the association of respiratory syncytial virus and adenovirus being the most frequent (21/55). No difference was found between monoviral infections on the one hand and simultaneous viral infections on the other hand according to age, weight, neonatal disease, past history of personal or familial atopy, central temperature, Silvermans index, oxygen dependency, length of hospitalization, microbiology data. There was no indication that simultaneous virus infections were associated with an increased severity of the bronchiolitis in immunocompetent infants.

Les virus des bronchiolites aiguës

In Normandy (France), human respiratory syncytial virus (hRSV) was detected in 64.1% of acute bronchiolitis in hospitalized children, rhinovirus in 26.8%, human metapneumovirus (hMPV) in 7.6%, and parainfluenza virus (PIV) in 3.4%. The viruses causing acute bronchiolitis in the community were hRSV (42%), rhinovirus (19.5%), coronavirus (8%), PIV (3.5%), and hMPV (2.5%). In 53.7% of the cases, hRSV infected infants (86.9%), 53.7% being less than 6 months of age. Of the hRSV cases, 48.2% were detected in November and December and 44.5% in January and February. The hRSV epidemic started the 1st or 2nd week of October but it varied from one year to another and from one region to another. hRSV acute bronchiolitis increased from 261 cases in epidemics from 1999-2003 to 341 cases from 2004-2009. Rhinoviruses gave acute bronchiolitis in 38.4% of cases. A rate of 54.6% of viruses was detected in September and October and 38.5% in March and April. A total of 34.2% of infected infants were under 6 months of age, 37.8% between 6 months and 2 years, and 19.5% were between 2 and 5 years old. hMPV epidemics coincided with hRSV epidemics, but they accounted for one-sixth the number of cases. HMPV infected infants (74%) who were older than those infected with hRSV, and the diagnosis was bronchiolitis (59%) and pneumonia (17%). PIV infections (about 100 cases per year) included PIV3 (62.7%), PIV1 (25.3%), and PIV2 (7.3%). PIV1 infections occurred every 2 years in the fall. PIV3 infections were observed every year during the fall and winter, with peaks of infections in the spring in the years without PIV1. There were acute cases of bronchiolitis in 29.8% of PIV3 infections and 18.3% in PIV1 infections.

Effect of Nebulized Hypertonic Saline Treatment in Emergency Departments on the Hospitalization Rate for Acute Bronchiolitis: A Randomized Clinical Trial

Importance Acute bronchiolitis is the leading cause of hospitalization among infants. Previous studies, underpowered to examine hospital admission, have found a limited benefit of nebulized hypertonic saline (HS) treatment in the pediatric emergency department (ED). Objective To examine whether HS nebulization treatment would decrease the hospital admission rate among infants with a first episode of acute bronchiolitis. Design, Setting, and Participants The Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) study was a multicenter, double-blind randomized clinical trial on 2 parallel groups conducted during 2 bronchiolitis seasons (October through March) from October 15, 2012, through April 15, 2014, at 24 French pediatric EDs. Among the 2445 infants (6 weeks to 12 months of age) assessed for inclusion, 777 with a first episode of acute bronchiolitis with respiratory distress and no chronic medical condition were included. Interventions Two 20-minute nebulization treatments of 4 mL of HS, 3%, or 4 mL of normal saline (NS), 0.9%, given 20 minutes apart. Main Outcomes and Measures Hospital admission rate in the 24 hours after enrollment. Results Of the 777 infants included in the study (median age, 3 months; interquartile range, 2-5 months; 468 [60.2%] male), 385 (49.5%) were randomized to the HS group and 387 (49.8%) to the NS group (5 patients did not receive treatment). By 24 hours, 185 of 385 infants (48.1%) in the HS group were admitted compared with 202 of 387 infants (52.2%) in the NS group. The risk difference for hospitalizations was not significant according to the mixed-effects regression model (adjusted risk difference, –3.2%; 95% CI, –8.7% to 2.2%; P = .25). The mean (SD) Respiratory Distress Assessment Instrument score improvement was greater in the HS group (–3.1 [3.2]) than in the NS group (–2.4 [3.3]) (adjusted difference, –0.7; 95% CI, –1.2 to –0.2; P = .006) and similarly for the Respiratory Assessment Change Score. Mild adverse events, such as worsening of cough, occurred more frequently among children in the HS group (35 of 392 [8.9%]) than among those in the NS group (15 of 384 [3.9%]) (risk difference, 5.0%; 95% CI, 1.6%-8.4%; P = .005), with no serious adverse events. Conclusions and Relevance Nebulized HS treatment did not significantly reduce the rate of hospital admissions among infants with a first episode of acute moderate to severe bronchiolitis who were admitted to the pediatric ED relative to NS, but mild adverse events were more frequent in the HS group. Trial Registration clinicaltrials.gov Identifier: NCT01777347

Allergie respiratoire et virus

Summary Viral respiratory tract infections are a major cause of wheezing in infants. Investigators determined that 80% to 85% of school-aged children with wheezing episodes were tested positive for virus. To more fully understand how viral respiratory tract infections influence asthma, investigators have evaluated the effect of respiratory tract injections on airway symptoms, function, and inflammation. Although the mechanisms by which respiratory viruses enhance lower airway inflammation are not established, cytokines may play a key role in this process. The respiratory epithelial cell is a principal host for respiratory virus replication und is likely to be the first source of cytokines during an acute infection. T cells orchestrate immune responses to both allergens and viruses, and regulate effector cells with virucidal and proinflammalory effects. Although studies demonstrate that virus-specific T cells may contribute to virus-induced lung disease, evidence to define the role of virus-specific T lymphocytes in asthma has not been fully established. Some injections early in life may also have an important immunoregular role in the subsequent development of allergy and asthma. Atopy is characterised by exaggerated Th-2 cell responses to commun allergens with secretion of cytokines such as IL-4 and IL-5 that promote IgE production and eosinophil activation. In contrast, childhood injections typically induce a Th-1 cell response, characterised by secretion oj interferon-γ which enhances the antiviral activities of effector cells. These two types of T cell responses are mutually antagonistic.

Virologie : l’apport de la biologie moléculaire dans le diagnostic microbiologique en pneumopédiatrie

Résumé Les outils traditionnels du diagnostic virologique comprennent la recherche antigénique directe par immunofluorescence (IF) ou test immunoenzymatique (EIA), et l’isolement en culture. Les techniques d’IF ou EIA ont une sensibilité en général légèrement inférieure à celle de la culture, mais elles permettent de détecter également une fraction d’échantillons faussement négatifs en culture. Les résultats de plusieurs équipes, utilisant des techniques de reverse transcription-polymerase chain reaction (RT-PCR), montrent que les méthodes moléculaires détectent plus d’échantillons positifs que les méthodes traditionnelles. Le travail est en cours pour élargir le nombre de virus identifiés par des RT-PCR multiplex et découvrir de nouveaux virus, tels le métapneumovirus humain, en cause dans les atteintes respiratoires de l’enfant. En conclusion, afin de concilier rapidité, contrôle des coûts et un fort taux de détection des virus respiratoires, l’utilisation combinée de l’IF et de la RT-PCR multiplex semble ce jour la meilleure façon de progresser dans le diagnostic des maladies respiratoires de l’enfant. Summary The conventionnal tools used for virological diagnosis include direct antigen detection by immunofluorescence (IFA) or an immunoenzymatic test (EIA), and viral isolation technique (VIT). In most cases, IFA and EIA have a slightly lower sensitivity than VIT but are also able to detect some VIT-negative samples. Results of several teams using RT-PCR technologies show that the molecular methods detect more positive cases than the conventional tools. Work is under way to expand the number of viruses detected by multiplex RT-PCR and to determine wether newly discovered viruses, such as human metapneumovirus, contribute to burden of paediatric lower respiratory infections. In conclusion, according to requirements of speed, low cost of the methods, and to achieve the highest rate of detection of respiratory viruses, the combined use of IFA and multiplex RT-PCR is today likely to be the best way to improve diagnosis of respiratory illnesses in children.

Rhinovirus durant l’enfance : asthme à l’adolescence ? Paradoxe de l’œuf et de la poule ?

L es études épidémiologiques soulignent l’association entre une infection respiratoire basse durant la petite enfance et le risque ultérieur de développement d’un asthme. L’avènement des techniques moléculaires d’identification virale a permis d’élargir considérablement la reconnaissance des différents virus en cause lors de ces infections. Les rhinovirus (HRV) sont responsables de la majorité des infections des voies respiratoires hautes d’évolution habituellement bénigne mais possèdent un tropisme pour les voies aériennes basses parfois marqué. Ils évoluent sur un mode épidémique avec généralement 2 pics, à l’automne et au printemps, mais peuvent être observés durant toute l’année. Ce sont des virus d’une grande diversité puisque plus de 100 sérotypes sont actuellement connus. Ils utilisent 2 types de récepteurs pour entrer dans la cellule. En fonction de cette spécificité, ils ont été divisés en 2 groupes. Le groupe majeur comporte 91 sérotypes dont le récepteur principal est CD54 ou intercellular adhesion molecule 1 (ICAM1) ; le groupe mineur regroupe 10 sérotypes et comporte les virus utilisant le low density lipoprotein receptor (LDLR). Ils appartiennent à la famille des picornaviridae, comme les entérovirus dont ils sont génétiquement très proches, et dont il est parfois difficile de les différencier. Les études phylogénétiques ont permis de séparer les rhinovirus en plusieurs groupes, HRV-A, HRV-B, HRV-C et récemment HRV-D [1]. Le rhinovirus 87 avait été classé à part ; il était apparenté aux entérovirus du groupe D et a été récemment reclassé comme entérovirus (EV68) responsable de bouffées épidémiques avec tropisme neurologique (paralysie flasque) mais aussi respiratoire plus sévère. Il n’y a donc pas « un » rhinovirus mais « des » rhinovirus avec une répartition des sérotypes très différente d’une année à l’autre, d’une saison à l’autre, mais également au cours d’une même saison. Les HRV peuvent infecter plusieurs fois un même enfant avec des sérotypes différents en raison d’une immunité croisée faible. La réponse antivirale implique les cellules de l’immunité amenant la synthèse et la libération de médiateurs immuno-inflammatoires, la cellule épithéliale bronchique y participe également. L’initiateur primaire de l’asthme est-il le virus ? Les sifflements viro-induits ne révèleraient-ils que les enfants déjà prédisposés à un asthme ultérieur ? Le phénotype siffleur épisodique viroinduit durant la prime-enfance est-il fixé ou n’est-il qu’une étape évolutive vers un asthme tardif déclenché par des facteurs multiples ?

SFP CO-70 - Etude de la variabilité génétique des virus de la rougeole de génotype D4

Objectif Cette etude a pour but d’analyser la variabilite des genes H et P complets de virus de la rougeole de genotype D4 identifies pendant l’epidemie qui a sevi en France de 2008 a 2011, afin de completer l’analyse du fragment hypervariable du gene N requis pour l’identification du genotype. Materiels et Methode Nous avons selectionne 100 prelevements detectes positifs pour le virus de la rougeole pendant cette epidemie. Soixante-quinze souches de virus de la rougeole ont pu etre amplifiees et sequencees pour les genes complets H et P. Resultats L’alignement et l’analyse phylogenetique des genes H, P et N mettent en evidence une variabilite genetique au sein du genotype D4 et permettent l’identification de plusieurs clusters, dont certains sont retrouves simultanement dans les arbres construits pour les genes H, P et N. L’analyse phylogenomique du pseudogene P/H chez des souches dont la sequence du gene N est identique permet la mise en evidence de plusieurs clusters. Certains regroupent des souches isolees sur une meme periode et avec des origines geographiques differentes. Conclusions cette etude montre un interet a etendre le sequencage aux genes P et H pour affiner la comprehension des mecanismes de diffusion d’une epidemie de rougeole.

Infections précoces dans l'enfance : amies ou ennemies?

Asthma prevalence has increased significantly; this increase appears to be relatively recent. The observed increases in this prevalence cannot be genetic in origin; on the other hand lifestyles have changed in many ways for environment or feeding. The hygiene hypothesis must be distinguished in terms whether one is addressing asthma or atopy. Although there are associations between asthma and atopy, they are not interchangeable. The pathogenic links between childhood infections and asthma require an undisputed definition of asthma. But many wheezing syndromes have been recognized in the pediatric age group, some overlap exists between these various phenotypes. The age at first severe infection seems to be crucial in determining the outcome of reinfection and suggests that the environment of the neonatal lung is a major determinant of disease and allergic patterns in later life.