Infection tuberculeuse latente

Résumé

L'infection tuberculeuse latente ou ITL, est la forme asymptomatique de portage de tuberculose, sans traduction clinique ou en l'ITL n'est pas contagieuse. On estime qu'un quart de la population mondiale est infecté, et que seulement 5 à 15% des personnes infectée non immunodéprimés développement la tuberculose maladie à partie de l'ILA. Dans 80% des cas la développent de l'affection se fait dans les deux ans qui suivent l'infection. Risque de progression vers la tuberculose maladie Certains sujets ont un risque supérieur de progression. Ce sont les : *Enfants de moins de 5 ans *Patients recevant un anti-TNF *Insuffisants rénaux chroniques *Infection par le VIH *Transplantés d’organe avec traitement *Patients sous immunosuppresseur *Diabétiques insulino-requérants *Patients sous corticothérapie orale *Fumeurs *Silicotiques *Patients atteints de certains cancers *Dénutris Le risque est réduit si les sujets contacts infectés ont été vaccinés par BCG ou s’ils reçoivent

Source officielle

https://fr.wikipedia.org/wiki/Infection_tuberculeuse_latente

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Regimens recommended to treat latent tuberculosis infection (LTBI) are 3 to 9 months long. A 2-month rifampin+pyrazinamide regimen is no longer recommended. Shorter regimens are highly desirable. Because substituting rifapentine for rifampin in the standard regimen for active tuberculosis halves the treatment duration needed to prevent relapse in mice, we hypothesized daily rifapentine-based regimens could shorten LTBI treatment to 2 months or less.

2009

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Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism

Neeraj Dhar, Ping Lu, John McKinney, Muhittin Emre Özdemir

Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved for treatment of multidrug-resistant tuberculosis in decades. Though BDQ has shown excellent efficacy in clinical trials, its early bactericidal activity during the first week of chemotherapy is minimal. Here, using microfluidic devices and time-lapse microscopy of Mycobacterium tuberculosis, we confirm the absence of significant bacteriolytic activity during the first 3-4 days of exposure to BDQ. BDQ-induced inhibition of ATP synthesis leads to bacteriostasis within hours after drug addition. Transcriptional and proteomic analyses reveal that M. tuberculosis responds to BDQ by induction of the dormancy regulon and activation of ATP-generating pathways, thereby maintaining bacterial viability during initial drug exposure. BDQ-induced bacterial killing is significantly enhanced when the mycobacteria are grown on non-fermentable energy sources such as lipids (impeding ATP synthesis via glycolysis). Our results show that BDQ exposure triggers a metabolic remodelling in mycobacteria, thereby enabling transient bacterial survival.

Nature Publishing Group2014

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Mycobacterium tuberculosis 18b, a streptomycin (STR)-dependent mutant that enters a viable but nonreplicating state in the absence of STR, has been developed as a simple model for drug testing against dormant bacilli. Here, we further evaluated the STR-starved 18b (SS18b) model both in vitro and in vivo by comparing the behavior of 22 approved and experimental tuberculosis drugs. Using the resazurin reduction microplate assay (REMA), rifampin (RIF), rifapentine (RPT), TMC207, clofazimine (CFM), and linezolid (LIN) were found to be active against SS18b in vitro, and their bactericidal activity was confirmed by determining the number of CFU. A latent 18b infection was established in mice, and some of the above-mentioned drugs were used for treatment, either alone or in combination with RIF. RIF, RPT, TMC207, CFM, and pyrazinamide (PZA) were all active in vivo, while cell wall inhibitors were not. A comparative kinetic study of rifamycin efficacy was then undertaken, and the results indicated that RPT clears latent 18b infection in mice faster than RIF. Intrigued by the opposing responses of live and dormant 18b cells to cell wall inhibitors, we conducted a systematic analysis of 14 such inhibitors using REMA. This uncovered an SS18b signature (CWPRED) that accurately predicted the activities of cell wall inhibitors and performed well in a blind study. CWPRED will be useful for establishing the mode of action of compounds with unknown targets, while the SS18b system should facilitate the discovery of drugs for treating latent tuberculosis.

Amer Soc Microbiology2012

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