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Novel diagnostic approaches in TB and MDR-TB and treatment response biomarkers - Latest enrolment updates at July 2020

Анализировать взаимосвязь между лекарственными вариантами в геноме туберкулеза и соответствующей восприимчивостью к лекарственным средствам in vitro для разработки инструмента поддержки принятия решений для выбора терапии второй линии в случае подозрения на МЛУ-ТБ. 

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The databases

TB diagnosis cohort 

The database builds on the existing TB Biomarkers Cohort, a multicentre MDR-TB longitudinal treatment cohort of blood/plasma and urine over time. The cohort contains samples from patients taken at time 0 (i.e. before treatment) and until treatment was completed (or failed). After a pilot analysis using a global profiling approach, 600 ul plasma are subjected to 1H-NMR and 3x untargeted UPLS-Mass Spectrometry analyses; a further pilot analysis is performed using the matching urine samples.  The objective is to find biomarkers for early identification of MDR TB. New features have been found and reported in our recent analysis of the existing sub-cohort of 48 urine samples which seem to be effective in discriminating tuberculosis from control group. The next step is to do 'proof of principle' analysis on sub-cohorts from Russia and Lithuania.  Initila Plasma biomarkers analysis on the cohort of patients samples (242) identified features which were found to be changing differentially across time in the DS and MDR cases, within the first 6 months of treatment. From the 40 markers reported in literature, it was possible to find at least one matching feature in the TB H2020 Plasma dataset assays for 24. An untargeted and targeted approach is adopted to identify mycobacterial specific lipids in urine samples for both rapid TB diagnosis and prognosis. Main research objectives include concentration of lipid in TB patient urine specimens and detect TB lipid signatures against a background of human lipid in patient specimens; to concentrate TB trans-renal DNA specimens and identify other suitable biomarkers; to collect sputum and urine specimens from 150 TB patients and TB subjects; to complete blinded evaluation of TB lipidomic and DNA concentration - detection approaches; to apply optimised conditions for TB DNA concentration and amplification to 1-10 ml volumes of urine from patients from existing cohorts with confirmed pulmonary TB compared with volunteer healthy urine and samples from patients with bacterial pyelonephritis. The DB data come from centers in Russia and Lithuania.

TB SIGLEC-1 cohort 

The research hypothesis is that the strong association between extrapulmonary disseminated form of TB and the presence of Siglec-1 null allele observed in the Swiss HIV-1 cohort and confirmed in other cohorts, is due to exosome mediated immunity early after MTB infection, that will be compromised in the absence of Siglec-1, which is necessary for exosome capture by APCs as previously demonstrated.
For confirming the hypothesis, the study first develops a small cohort of extra-pulmonary TB patients (15-30) with and without concurrent HIV in Russia in parallel with an equivalent cohort developed in Spain; then it evaluates the key polymorphisms using a PCR-based assay previously established for pulmonary TB patients. The DB data come from centers in Russia

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