TY - JOUR T1 - Tuberculosis bacillary load, an early marker of disease severity: the utility of tuberculosis Molecular Bacterial Load Assay JF - Thorax JO - Thorax DO - 10.1136/thoraxjnl-2019-214238 SP - thoraxjnl-2019-214238 AU - Wilber Sabiiti AU - Khalide Azam AU - Eoghan Charles William Farmer AU - Davis Kuchaka AU - Bariki Mtafya AU - Ruth Bowness AU - Katarina Oravcova AU - Isobella Honeyborne AU - Dimitrios Evangelopoulos AU - Timothy Daniel McHugh AU - Celso Khosa AU - Andrea Rachow AU - Norbert Heinrich AU - Elizabeth Kampira AU - Geraint Davies AU - Nilesh Bhatt AU - Elias N Ntinginya AU - Sofia Viegas AU - Ilesh Jani AU - Mercy Kamdolozi AU - Aaron Mdolo AU - Margaret Khonga AU - Martin J Boeree AU - Patrick P J Phillips AU - Derek Sloan AU - Michael Hoelscher AU - Gibson Kibiki AU - Stephen H Gillespie Y1 - 2020/04/30 UR - http://thorax.bmj.com/content/early/2020/05/18/thoraxjnl-2019-214238.abstract N2 - In this comparative biomarker study, we analysed 1768 serial sputum samples from 178 patients at 4 sites in Southeast Africa. We show that tuberculosis Molecular Bacterial Load Assay (TB-MBLA) reduces time-to-TB-bacillary-load-result from days/weeks by culture to hours and detects early patient treatment response. By day 14 of treatment, 5% of patients had cleared bacillary load to zero, rising to 58% by 12th week of treatment. Fall in bacillary load correlated with mycobacterial growth indicator tube culture time-to-positivity (Spearmans r=−0.51, 95% CI (−0.56 to −0.46), p<0.0001). Patients with high pretreatment bacillary burdens (above the cohort bacillary load average of 5.5log10eCFU/ml) were less likely to convert-to-negative by 8th week of treatment than those with a low burden (below cohort bacillary load average), p=0.0005, HR 3.1, 95% CI (1.6 to 5.6) irrespective of treatment regimen. TB-MBLA distinguished the bactericidal effect of regimens revealing the moxifloxacin—20 mg rifampicin regimen produced a shorter time to bacillary clearance compared with standard-of-care regimen, p=0.008, HR 2.9, 95% CI (1.3 to 6.7). Our data show that the TB-MBLA could inform clinical decision making in real-time and expedite drug TB clinical trials. ER -