Is IP-10 an Accurate Marker for Detecting M. tuberculosis-Specific Response in HIV-Infected Persons?

The suboptimal sensitivity of Interferon (IFN)-γ-based in-vitro assays, especially in immunocompromised individuals, emphasizes the need for alternative markers for diagnosing tuberculosis (TB). The objective of this study was to evaluate whether interferon-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-2 and interleukin (IL)-2 can be useful biomarkers for evaluating a specific response to RD1 antigens associated to active TB disease in HIV-infected individuals.The study was carried out in India, the country with the highest TB burden in the world. Sixty-six HIV-infected individuals were prospectively enrolled, 28 with active-pulmonary-TB and 38 without. The whole blood assay based on RD1-selected peptides (experimental test) and QuantiFERON-TB Gold In tube (QFT-IT) was performed. Plasma was harvested at day-1-post-culture and soluble factors were evaluated by ELISA. The results indicate that by detecting IP-10, the sensitivity of the experimental test and QFT-antigen (75% and 85.7% respectively) for active TB was higher compared to the same assays based on IFN-γ (42.9% and 60.7% respectively) and was not influenced by the ability to respond to the mitogen. By detecting IP-10, the specificity of the experimental test and QFT-antigen (57.9% and 13.2% respectively) for active TB was lower than what was reported for the same assays using IFN-γ-detection (78.9% and 68.4% respectively). On the other side, in vitro IL-2 and MCP-2 responses were not significantly associated with active TB.HIV infection does not impair RD1-specific response detected by IP-10, while it significantly decreases IFN-γ-mediated responses. At the moment it is unclear whether higher detection is related to higher sensitivity or lower specificity of the assay. Further studies in high and low TB endemic countries are needed to elucidate this

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

IP-10 response to RD1 antigens might be a useful biomarker for monitoring tuberculosis therapy

Background There is an urgent need of prognosis markers for tuberculosis (TB) to improve treatment strategies. The results of several studies show that the Interferon (IFN)-γ-specific response to the TB antigens of the QuantiFERON TB Gold (QFT-IT antigens) decreases after successful TB therapy. The objective of this study was to evaluate whether there are factors other than IFN-γ [such as IFN-γ inducible protein (IP)-10 which has also been associated with TB] in response to QFT-IT antigens that can be used as biomarkers for monitoring TB treatment. Methods In this exploratory study we assessed the changes in IP-10 secretion in response to QFT-IT antigens and RD1 peptides selected by computational analysis in 17 patients with active TB at the time of diagnosis and after 6 months of treatment. The IFN-γ response to QFT-IT antigens and RD1 selected peptides was evaluated as a control. A non-parametric Wilcoxon signed-rank test for paired comparisons was used to compare the continuous variables at the time of diagnosis and at therapy completion. A Chi-square test was used to compare proportions. Results We did not observe significant IP-10 changes in whole blood from either NIL or QFT-IT antigen tubes, after 1-day stimulation, between baseline and therapy completion (p = 0.08 and p = 0.7 respectively). Conversely, the level of IP-10 release to RD1 selected peptides was significantly different (p = 0.006). Similar results were obtained when we detected the IFN-γ in response to the QFT-IT antigens (p = 0.06) and RD1 selected peptides (p = 0.0003). The proportion of the IP-10 responders to the QFT-IT antigens did not significantly change between baseline and therapy completion (p = 0.6), whereas it significantly changed in response to RD1 selected peptides (p = 0.002). The proportion of IFN-γ responders between baseline and therapy completion was not significant for QFT-IT antigens (p = 0.2), whereas it was significant for the RD1 selected peptides (p = 0.002), confirming previous observations. Conclusions Our preliminary study provides an interesting hypothesis: IP-10 response to RD1 selected peptides (similar to IFN-γ) might be a useful biomarker for monitoring therapy efficacy in patients with active TB. However, further studies in larger cohorts are needed to confirm the consistency of these study results

Gestion de la mobilité dans une architecture d'accès multi-technologies

La forte augmentation des usages de services de données en situation de mobilité amène à anticiper des problèmes de congestion et de qualité de service dans les réseaux mobiles. Dans cette thèse, nous considérons une nouvelle approche d'architecture pour le support unifié de différentes technologies d'accès à travers la distribution à plat'' des fonctions réseau. Cette architecture se veut très simple; elle repose sur trois entités fonctionnelles uniquement : le nœud d'accès, en charge de fournir la connectivité et l'attachement au réseau; le terminal, capable de gérer un ou plusieurs attachements réseaux en fonction des technologies supportées; la passerelle d'interconnexion. Notre contribution se focalise sur le développement d'une nouvelle approche de gestion de la mobilité adaptée à cette architecture distribuée. Notre solution, baptisée DMA (Dynamic Mobility Anchoring), considère l'activation dynamique d'ancres de mobilité dans les nœuds d'accès. La gestion de la mobilité devient totalement distribuée entre ces nœuds alors que le reste du réseau utilise les mécanismes de routage IP standards. En complément de la mobilité, nous introduisons des mécanismes distribués de gestion de la veille des terminaux multi-interfaces permettant la transposition des solutions de paging IP aux réseaux hétérogènes distribués. En termes d'évaluation, nous nous basons sur le développement d'un modèle de simulation pour la gestion de la mobilité et sur une étude analytique pour les mécanismes de veille. Au delà de la validation fonctionnelle de DMA, les résultats montrent que notre approche distribuée, de par la suppression de la concentration des trafics mobiles dans des organes réseaux centralisés, permet une amélioration de la qualité de service offerte globalement aux utilisateurs mobiles. Nous mettons également en évidence les bénéfices de DMA pour l'opérateur en termes de facilité de passage d'échelle et de réduction des coûts d'ingénierie de réseaux.The observed mobile data services usage growth leads to anticipate congestion and quality of service issues in mobile networks. In this thesis, we consider a new architecture approach providing a unified support for different access technologies through a flat distribution of networking functions. This architecture aims to be very simple; it uses only three functional entities: the access node providing network and radio connectivity; the terminal, able to manage either one or several network attachments simultaneously; the interworking gateway. Our contribution focuses on the development of a new mobility management approach adapted to such a distributed architecture: DMA (Dynamic Mobility Anchoring). It considers dynamic mobility anchors activation in access nodes. Mobility management becomes hence fully distributed among those nodes whereas the rest of the network uses standard IP routing. In addition to mobility management, we introduce distributed idle mode management mechanisms adapted to multi-interfaces terminals, allowing the transposition of IP paging solutions to flat heterogeneous networks. For Evaluation purposes, we develop both a simulator and an analytical model for, respectively, distributed mobility management and idle mode support. Beyond to DMA functional validation, our results confirm that our distributed approach, thanks to the removing of mobile traffic concentration in centralised network nodes, enhances the quality of service provided to mobile users. We also outline operator s benefits brought by DMA in terms of mobile networks scalability, engineering and operational costs reduction.RENNES1-BU Sciences Philo (352382102) / SudocCESSON SEVIGNE-Télécom Breta (350512301) / SudocBREST-Télécom Bretagne (290192306) / SudocSudocFranceF

Evaluation of Three Techniques for Detection of Low-Level Methicillin-Resistant Staphylococcus aureus (MRSA): a Disk Diffusion Method with Cefoxitin and Moxalactam, the Vitek 2 System, and the MRSA-Screen Latex Agglutination Test

Very-low-level methicillin-resistant Staphylococcus aureus (MRSA), or class 1 MRSA, is often misdiagnosed as methicillin-susceptible S. aureus (MSSA). We evaluated the performances of three methods for detection of low-level methicillin resistance: the disk diffusion method using the cephamycin antibiotics cefoxitin and moxalactam, the Vitek 2 system (bioMérieux), and the MRSA-screen test (Denka). Detection of the mecA gene by PCR was considered to be the “gold standard.” We also determined the sensitivity of the oxacillin disk diffusion method with 5- and 1-μg disks and that of the Oxascreen agar assay with 6 mg of oxacillin liter(−1) for detection of MRSA. We compared the distributions of MICs of oxacillin and cefoxitin by the E-test (AB Biodisk), and those of moxalactam by dilutions in agar, for MRSA and MSSA isolates. The 152 clinical isolates of S. aureus studied were divided into 69 MSSA (mecA-negative) and 83 MRSA (mecA-positive) isolates, including 63 heterogeneous isolates and 26 class 1 isolates (low-level resistance). The cefoxitin and moxalactam disk diffusion tests detected 100% of all the MRSA classes: cefoxitin inhibition zone diameters were <27 mm, and moxalactam inhibition zone diameters were <24 mm. The Vitek 2 system and the MRSA-screen test detected 94 and 97.6% of all MRSA isolates, respectively. The sensitivities of the 5- and 1-μg oxacillin disks were 95.2 and 96.4%, respectively, whereas that of the Oxascreen agar screen assay was 94%. All of the tests except the 1-μg oxacillin disk test were 100% specific. For the class 1 MRSA isolates, the sensitivity of the Vitek 2 test was 92.3%, whereas those of the MRSA-screen test and the disk diffusion method with cefoxitin and moxalactam were 100%. Therefore, the cefoxitin and moxalactam disk diffusion methods were the best-performing tests for routine detection of all classes of MRSA

La recherche à l'IGN : activités 1992

Bulletin d'information de l'IGN N°61Ce compte rendu tient lieu à la fois de compte rendu d'activités du Service de la Recherche et de bilan de l'activité de recherche pour I'IGN. Au cours de l'année 1992, le découpage en thèmes de recherche tels qu'ils sont suivis par le CST a été redéfini, et au 1er janvier 1993, le laboratoire COGIT a été séparé en deux unités. Actuellement, le découpage en thèmes recoupe au mieux le découpage fonctionnel en laboratoires de recherche, et c'est selon ce plan que seront présentées les activités. Afin d'améliorer le suivi externe par le CST des activités de recherche de I'IGN, quatre groupes de travail correspondant aux quatre thèmes de recherche ont été constitués. Les membres de ces groupes, toutes personnalités extérieures à I'IGN, ont été choisis pour leur compétence scientifique personnelle dans les domaines concernés. Chacun des groupes est présidé par un membre titulaire du CS

Demographic and clinical characteristics of the HIV-infected individuals enrolled in the study.

<p><b>Footnotes: TB: tuberculosis; IQR: interquartile range; TST: tuberculin skin test; TST*: analyzed in 63/66; CD4⁺ T-cell counts**: analyzed in 50/66 individuals.</b></p

IL-2 and MCP-2 production in response to RD1 selected peptides and QFT-antigen in HIV-infected individuals.

<p>IL-2 (<b>A</b>) and MCP-2 (<b>B</b>) release in response to the RD1 selected peptides and QFT-antigen was evaluated at day 1 in the whole blood of patients with or without active TB. Horizontal lines indicate the median production. White circles indicate the individuals without active TB, black circles indicate the patients with active TB. No significant differences were found among the different comparisons performed.</p