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Thursday, 15 September 2016 12:11

Paper 2016_09

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Microfold Cells Actively Translocate Mycobacterium tuberculosis to Initiate Infection
Wednesday, 07 September 2016 08:27

Paper 2016_08

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A) Comment on: Delamanid susceptibility testing of Mycobacterium tuberculosis using the resazurin microtitre assay and the BACTEC™ MGIT™ 960 system   Comment by Graham Bothamley: Drug sensitivity testing for delaminid meets unexpected problems.  The manufacturers of delaminid, and coincidentally sponsors of the European Respiratory Society’s TB consilium, are called to account regarding drug sensitivity testing for delaminid.     B) Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB.
Monday, 01 August 2016 07:16

Paper 2016_07

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Global burden of drug-resistant tuberculosis in children: a mathematical modelling study; Dodd PJ, Sismanidis C, Seddon JA; Lancet Infect Dis. 2016 Jun 21.
Tuesday, 17 May 2016 13:12

Paper 2016_05

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An automated tuberculosis screening strategy combining X-ray-based computer-aided detection and clinical information
Tuesday, 19 April 2016 16:04

Paper 2016_04

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Prognostic value of interferon-γ release assays, a population-based study from a TB low-incidence country.
Tuesday, 29 March 2016 10:30

Paper 2016_03

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Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection
Tuesday, 08 March 2016 10:52

Paper 2016_02

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  Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis
Tuesday, 08 March 2016 10:45


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Dates: 19-21 September 2016 Venue: Kadetti Training Centre, Hollantilaisentie 11, Helsinki, Finland Programme (6.9.2016) Registration to the course via internet by 09.09.2016 Language: English
Tuesday, 08 March 2016 10:29

TBnet Academy 16

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  TBnet ACADEMY 2016   FREE FELLOWSHIP GRANTS 3 Day Tuberculosis Academy especially for residents, fellows, doctoral students and post-docs.
Monday, 11 January 2016 10:57

Paper 2016_01

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A bitter pill to swallow: the need for better medications for drug-resistant tuberculosis in children.
Wednesday, 16 December 2015 12:38

Paper 2015-12/2

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Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis
Wednesday, 16 December 2015 12:30

Paper 2015-12/1

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Beyond multidrug-resistant tuberculosis in Europe: a TBNET study
Tuesday, 17 November 2015 10:39

Paper 2015-10/1

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Uncoupling environmental pH and intrabacterial acidification from pyrazinamide susceptibility in Mycobacterium tuberculosis,
Tuesday, 17 November 2015 10:30

Paper 2015-11/1

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Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study   Timothy M Walker, Thomas A Kohl, Shaheed V Omar, Jessica Hedge, Carlos Del Ojo Elias, Phelim Bradley, Zamin Iqbal, Silke Feuerriegel, Katherine E Niehaus, Daniel J Wilson, David A Clifton, Georgia Kapatai, Camilla L C Ip, Rory Bowden, Francis A Drobniewski, Caroline Allix-Béguec, Cyril Gaudin, Julian Parkhill, Roland Diel, Philip Supply, Derrick W Crook, E Grace Smith, A Sarah Walker, Nazir Ismail, Stefan Niemann, Tim E A Peto, and the Modernizing Medical Microbiology (MMM) Informatics Group   Summary   Background Diagnosing drug-resistance remains an obstacle to the elimination of tuberculosis. Phenotypic drugsusceptibility testing is slow and expensive, and commercial genotypic assays screen only common resistancedetermining mutations. We used whole-genome sequencing to characterise common and rare mutations predicting drug resistance, or consistency with susceptibility, for all fi rst-line and second-line drugs for tuberculosis.   Methods Between Sept 1, 2010, and Dec 1, 2013, we sequenced a training set of 2099 Mycobacterium tuberculosis genomes. For 23 candidate genes identifi ed from the drug-resistance scientifi c literature, we algorithmically characterised genetic mutations as not conferring resistance (benign), resistance determinants, or uncharacterised. We then assessed the ability of these characterisations to predict phenotypic drug-susceptibility testing for an independent validation set of 1552 genomes. We sought mutations under similar selection pressure to those characterised as resistance determinants outside candidate genes to account for residual phenotypic resistance.   Findings We characterised 120 training-set mutations as resistance determining, and 772 as benign. With these mutations, we could predict 89·2% of the validation-set phenotypes with a mean 92·3% sensitivity (95% CI 90·7–93·7) and 98·4% specifi city (98·1–98·7). 10·8% of validation-set phenotypes could not be predicted because uncharacterised mutations were present. With an in-silico comparison, characterised resistance determinants had higher sensitivity than the mutations from three line-probe assays (85·1% vs 81·6%). No additional resistance determinants were identifi ed among mutations under selection pressure in non-candidate genes.   Interpretation A broad catalogue of genetic mutations enable data from whole-genome sequencing to be used clinically to predict drug resistance, drug susceptibility, or to identify drug phenotypes that cannot yet be genetically predicted. This approach could be integrated into routine diagnostic workfl ows, phasing out phenotypic drugsusceptibility testing while reporting drug resistance early.   Read more here
Thursday, 09 July 2015 14:39

TBnet Meeting

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  Our 10th TBnet meeting will take place on September 25th at the Academic Medical Center in Amsterdam, The Netherlands. Thanks a lot to our local host, Frank van Leth! See details here.
Saturday, 16 May 2015 16:46

Paper 2015-5/2

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Risk Assessment of Tuberculosis in Contacts by IFN-γ Release Assays. A Tuberculosis Network European Trials Group Study.   Am J Respir Crit Care Med.2015 May 15;191(10):1176-1184.   Zellweger JP, Sotgiu G, Block M, Dore S, Altet N, Blunschi R, Bogyi M, Bothamley G, Bothe C, Codecasa L, Costa P, Dominguez J, Duarte R, Fløe A, Fresard I, García-García JM, Goletti D, Halm P, Hellwig D, Henninger E, Heykes-Uden H, Horn L, Kruczak K, Latorre I, Pache G, Rath H, Ringshausen FC, Ruiz AS, Solovic I, Souza-Galvão ML, Widmer U, Witte P, Lange C; TBNET.   Abstract RATIONALE: Latent infection with Mycobacterium tuberculosis is defined by a positive IFN-γ release assay (IGRA) result in the absence of active tuberculosis. Only few, mostly monocentric studies have evaluated the role of IGRAs to predict the development of tuberculosis in recent contacts in low-incidence countries of tuberculosis.   OBJECTIVES: To analyze IGRA results and the effect of preventive chemotherapy on tuberculosis progression rates among recent contacts.   METHODS: Results from contact investigations at 26 centers in 10 European countries including testing for latent infection with M. tuberculosis by the QuantiFERON-TB Gold In-Tube (QFT) test or the T-SPOT.TB (TSPOT) were prospectively collected and analyzed.   MEASUREMENTS AND MAIN RESULTS: Among 5,020 contacts of 1,023 index cases, 25 prevalent secondary cases were identified at screening. Twenty-four incident cases occurred among 4,513 contacts during 12,326 years of cumulative follow-up. In those with a positive IGRA result, tuberculosis incidence was 0.2 (QFT) and 0 (TSPOT) per 100 patient-years when contacts received preventive chemotherapy versus 1.2 (QFT) and 0.8 (TSPOT) per 100 patient-years in those not treated (38 and 37 patients needed to be treated to prevent one case, respectively). Positive and negative predictive values were 1.9% (95% confidence interval [CI], 1.1-3.0) and 99.9% (95% CI, 99.7-100) for the QFT and 0.7% (95% CI, 0.1-2.6) and 99.7% (95% CI, 99.1-99.9) for the TSPOT.   CONCLUSIONS: Tuberculosis rarely developed among contacts, and preventive chemotherapy effectively reduced the tuberculosis risk among IGRA-positive contacts. Although the negative predictive value of IGRAs is high, the risk for the development of tuberculosis is poorly predicted by these assays.     PMID: 25763458 [PubMed - as supplied by publisher]    
Saturday, 16 May 2015 16:33

Paper 2015-5/1

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Counting pyrazinamide in regimens for multidrug-resistant tuberculosis.   Ann Am Thorac Soc. 2015 May;12(5):674-9. doi: 10.1513/AnnalsATS.201411-538OC. Franke MF, Becerra MC, Tierney DB, Rich ML, Bonilla C, Bayona J, McLaughlin MM, Mitnick CD. Abstract RATIONALE: For treatment of multidrug-resistant tuberculosis, World Health Organization (WHO) guidelines recommend four likely effective drugs plus pyrazinamide (PZA), irrespective of the likely effectiveness of PZA in an individual patient. Whether this regimen should be supplemented in the absence of likely PZA effectiveness is an open question. OBJECTIVES: The objectives of this study were to examine (1) whether individuals receiving four likely effective drugs (based on documented susceptibility or no prior exposure) experienced higher mortality during the intensive phase of treatment than those receiving five likely effective drugs and (2) whether the WHO-recommended regimen (four likely effective drugs plus PZA) may be compromised in individuals in whom PZA is not likely effective. METHODS: Among 668 patients, we compared the hazard of death across regimen groups characterized by the number of likely effective drugs and whether pyrazinamide was one of the likely effective drugs. MEASUREMENTS AND MAIN RESULTS: Relative to five likely effective drugs, regimens of four likely effective drugs and the WHO-recommended regimen used in individuals in whom PZA was not likely effective were associated with higher mortality rates (respectively, adjusted hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.35-6.09 and adjusted HR, 2.76; 95% CI, 0.92-8.27). The mortality rate for a regimen of five likely effective drugs with likely effective PZA was similar to that for the regimen of five likely effective drugs without PZA (HR, 1.00; 95% CI, 0.12-8.00). CONCLUSIONS: Mortality may be reduced by the inclusion of five likely effective drugs, including an injectable, during the intensive phase of treatment. If PZA is unlikely to be effective in an individual patient, these results suggest adding a different, likely effective drug.
Wednesday, 01 April 2015 11:03

Paper 2015-4/2

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Eur Respir J.2014 Nov 13. pii: erj01246-2014. [Epub ahead of print]   Availability, price and affordability of anti-tuberculosis drugs in Europe: A TBNET survey.   Günther G, Gomez GB, Lange C, Rupert S, van Leth F; on behalf of the TBNET.   Abstract Data on availability and cost of anti-tuberculosis (TB) drugs in relation to affordability at national level are scarce. We performed a cross-sectional study on availability and cost of anti-TB drugs at major TB-reference centres in 37 European countries. Costs of standardised treatment regimens used for pan-sensitive TB, multi-drug resistant (MDR), pre-extensively drug-resistant (XDR), and XDR-TB were compared using a purchasing power analysis. Affordability was evaluated in relation to monthly national gross domestic products per capita (GDP). At least one second-line injectable and either moxifloxacin or levofloxacin were available in all countries. Linezolid and clofazimine were available in 79% and 46% of the countries, respectively. Drug cost for XDR-TB was three-times more expensive than those for MDR-TB. The average price of treatment for pan-sensitive TB represented a maximum of 8.5% of the monthly GDP across countries, while for standard MDR-TB treatment this was <30% in only six countries and more than 100% in four countries. Treatment of XDR-TB represented more than 100% of a month's GDP in all countries where the regimen was available. High cost and limited availability of drugs for treatment of drug-resistant TB, particularly beyond resistance to first-line drugs, are a major impediment to successful TB control in Europe.   Full text here
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