Mycobacterium abscessus and Children with Cystic Fibrosis

We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years; range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients (6 male, 9 female; mean age 11.9 years; range 2.5–22 years) had at least one positive sample for this microorganism (versus 6 patients positive for M. avium complex), including 10 with >3 positive samples (versus 3 patients for M. avium complex). The M. abscessus isolates from 14 patients were typed by pulsed-field gel electrophoresis: each of the 14 patients harbored a unique strain, ruling out a common environmental reservoir or person-to-person transmission. Water samples collected in the cystic fibrosis center were negative for M. abscessus. This major mycobacterial pathogen in children and teenagers with cystic fibrosis does not appear to be acquired nosocomially

DC-SIGN Induction in Alveolar Macrophages Defines Privileged Target Host Cells for Mycobacteria in Patients with Tuberculosis

BACKGROUND: Interplays between Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) in human and host professional phagocytes, namely macrophages (Mφs) and dendritic cells (DCs), are central to immune protection against TB and to TB pathogenesis. We and others have recently shown that the C-type lectin dendritic cell–specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN; CD209) mediates important interactions between mycobacteria and human monocyte-derived DCs (MoDCs) in vitro. METHODS AND FINDINGS: In order to explore the possible role of DC-SIGN in M. tuberculosis infection in vivo, we have analysed DC-SIGN expression in broncho-alveolar lavage (BAL) cells from patients with TB (n = 40) or with other non-mycobacterial lung pathologies, namely asthma (n = 14) and sarcoidosis (n = 11), as well as from control individuals (n = 9). We show that in patients with TB, up to 70% of alveolar Mφs express DC-SIGN. By contrast, the lectin is barely detected in alveolar Mφs from all other individuals. Flow cytometry, RT-PCR, and enzyme-linked immunosorbent assay analyses of BAL-derived fluids and cells indicated that M. tuberculosis infection induces DC-SIGN expression in alveolar Mφs by a mechanism that is independent of Toll-like receptor-4, interleukin (IL)-4, and IL-13. This mechanism most likely relies on the secretion of soluble host and/or mycobacterial factors that have yet to be identified, as both infected and uninfected bystander Mφs were found to express DC-SIGN in the presence of M. tuberculosis. Immunohistochemical examination of lung biopsy samples from patients with TB showed that the bacilli concentrate in pulmonary regions enriched in DC-SIGN-expressing alveolar Mφs in vivo. Ex vivo binding and inhibition of binding experiments further revealed that DC-SIGN–expressing alveolar Mφs constitute preferential target cells for M. tuberculosis, as compared to their DC-SIGN(−) counterparts. In contrast with what has been reported previously in MoDCs in vitro, ex vivo DC-SIGN ligation by mycobacterial products failed to induce IL-10 secretion by alveolar Mφs, and IL-10 was not detected in BALs from patients with TB. CONCLUSION: Altogether, our results provide further evidence for an important role of DC-SIGN during TB in humans. DC-SIGN induction in alveolar Mφs may have important consequences on lung colonization by the tubercle bacillus, and on pulmonary inflammatory and immune responses in the infected host

Temporal Dynamics of Interferon Gamma Responses in Children Evaluated for Tuberculosis

BACKGROUND: Development of T-cells based-Interferon gamma (IFNgamma) assays has offered new possibilities for the diagnosis of latent tuberculosis infection (LTBI) and active disease in adults. Few studies have been performed in children, none in France. With reference to the published data on childhood TB epidemiology in the Paris and Ile de France Region, we considered it important to evaluate the performance of IGRA (QuantiFERON TB Gold In Tube(R), QF-TB-IT) in the diagnosis and the follow-up through treatment of LTBI and active TB in a cohort of French children. METHODOLOGY/PRINCIPAL FINDINGS: 131 children were recruited during a prospective and multicentre study (October 2005 and May 2007; Ethical Committee St Louis Hospital, Paris, study number 2005/32). Children were sampled at day 0, 10, 30, 60 (except Healthy Contacts, HC) and 90 for LTBI and HC, and a further day 120, and day 180 for active TB children. Median age was 7.4 years, with 91% of the children BCG vaccinated. LTBI and active TB children undergoing therapy produced significant higher IFNgamma values after 10 days of treatment (p = 0.035). In addition, IFNgamma values were significantly lower at the end of treatment compared to IFNgamma values at day 0, although the number of positive patients was not significantly different between day 0 and end of treatment. CONCLUSIONS/ SIGNIFICANCE: By following quantitative IFNgamma values in each enrolled child with LTBI or active TB and receiving treatment, we were able to detect an increase in the IFNgamma response at day 10 of treatment which might allow the confirmation of a diagnosis. In addition, a decline in IFNgamma values during treatment makes it possible for clinicians to monitor the effect of preventive or curative therapy

Asthme : dépistage et prévention chez l'enfant

Les manifestations allergiques, l’asthme en particulier, sont de plus en plusfréquentes dans tous les pays industrialisés. Il faut également remarquer quenon seulement la prévalence mais aussi la sévérité de l’asthme se sont fortementaccrues au cours des dernières années. Plusieurs études effectuées àtravers le monde montrent que, depuis 1960, la fréquence de l’asthme s’accroîtd’environ 6 % à 10 % par an chez l’enfant, quels que soient le pays ou l’ethnieétudiés. Elle est la première maladie chronique de l’enfant dans les paysdéveloppés. Cette augmentation ne semble pas procéder d’une modificationdes moyens de diagnostic ou d’une meilleure connaissance de l’affection.Si la prise en charge de l’asthme a nettement progressé depuis une vingtained’années, du fait d’une meilleure connaissance des mécanismes physiopathologiquesde la maladie et de l’arrivée sur le marché de nouvelles thérapeutiques,il reste cependant essentiel d’appréhender les facteurs à l’origine de saprogression foudroyante.Les facteurs à l’origine des maladies allergiques, et de l’asthme en particulier,sont de deux ordres, génétiques et environnementaux, d’importantes interactionsexistant entre eux. Si un certain nombre de gènes candidats pourl’immunopathologie de l’asthme sont en cours d’identification, des modificationsde ces gènes ne peuvent constituer une explication cohérente pourrendre compte de l’augmentation de la prévalence de l’asthme observée cesvingt dernières années. Les facteurs environnementaux apparaissent commel’explication la plus plausible : la pollution de l’air et les modifications dumode de vie, d’une part, la disparition de facteurs de résistance (infections aucours de la petite enfance), d’autre part, sont en première ligne des responsablespossibles.L’asthme est défini comme une obstruction bronchique réversible, spontanémentou sous l’effet de traitements bronchodilatateurs. Sur le plan physiopathologique,l’asthme est caractérisé par une inflammation de la muqueusebronchique. Cette inflammation est constante, plus ou moins importanteselon le stade de gravité de la maladie.La prise en charge des asthmatiques a largement bénéficié d’une meilleurecompréhension des mécanismes physiopathologiques impliqués dans le développementde la maladie. Cette meilleure connaissance a permis d’élaborerune stratégie thérapeutique cohérente et de proposer des schémas de traitementsappropriés aux différentes formes d’asthme.Cependant, si nous avons largement progressé dans la compréhension del’histoire naturelle et la prise en charge de l’asthme, il n’existe pas encore de traitement curateur de la maladie. C’est dire l’importance des mesures préventives,qui reposent avant tout sur l’éducation des patients, mais aussi desmédecins. La prévention primaire implique un processus dans lequel l’interventionprécède le développement de la maladie. La prévention secondaire apour objectif de prévenir le développement de la maladie chez un sujetprédisposé, par exemple atopique. Pour les patients chez qui le diagnosticd’asthme a été posé, la prévention tertiaire consiste en une modification del’environnement et la prescription d’un traitement pharmacologique adapté.Ce document constitue une bonne synthèse des travaux les plus représentatifsen épidémiologie, physiopathologie et clinique. Il indique les principalesrecommandations en prévention et éducation à la santé, à l’intention desdifférents acteurs impliqués dans la prise en charge de cette pathologie, etpropose quelques pistes de recherche qui mériteraient d’être développées

Immunochemical characterisation of structure and allergenicity of peanut 2S albumins using different formats of immunoassays

International audienc

Óxido nítrico em criança com asma persistente

OBJETIVO: Verificar as diferenças nos valores da fração exalada de óxido nítrico (FeNO) em asmáticos atópicos e não-atópicos em uso de tratamento antiinflamatório e comparar a FeNO com a função pulmonar MÉTODOS: Estudo transversal com 45 asmáticos persistentes moderados e graves, de 6 a 17 anos, selecionados consecutivamente, em uso de medicação antiinflamatória há pelo menos 1 ano. Os pacientes foram divididos em dois grupos: atópicos, isto é, com testes cutâneos positivos, e não-atópicos. As avaliações clínico-funcionais e a mensuração da FeNO foram realizadas concomitantemente. RESULTADOS: Houve predomínio do sexo masculino (62,5%),sendo que cerca de 85% pertenciam à faixa etária de 6 até 13 anos (média, 10,4 anos). Não foi encontrada, nos dois grupos, significância estatística para a presença de sintomas associados à asma (p = 0,07), rinite alérgica (p = 0,17), alergia alimentar (p = 0,09), necessidade de corticóide sistêmico (p = 0,10), antileucotrieno (p = 0,20) e anti-histamínico (p = 0,70), nem para os três parâmetros usados para avaliar a função pulmonar (VEF1, VEF1/CVF e FEF25-75%, p > 0,14). A freqüência de eczema (p < 0,005) e a FeNO (p < 0,001) foram mais elevadas entre os atópicos. CONCLUSÃO: Os resultados sugerem que, entre atópicos, a estabilidade clínica e funcional da asma não reflete, necessariamente, o efetivo controle do processo inflamatório, e que haja, talvez, maior chance de recidiva após a suspensão da medicação anti-inflamatória