Tuberculosis bacillary load, an early marker of disease severity and treatment response: the utility of tuberculosis Molecular Bacterial Load Assay

Wilber Sabiiti, Khalide Azam, Eoghan Farmer, Davis Kuchaka, Bariki Mtafya, Ruth Bowness, Katarina Oravcova, Isobella Honeyborne, Dimitrios Evangelopoulos, Timothy D McHugh, Celso Khosa, Andrea Rachow, Norbert Heinrich, Elizabeth Kampira, Geraint Davies, Nilesh Bhatt, Elias N Ntinginya, Sofia Viegas, Ilesh Jani, Mercy KamdoloziAaron Mdolo, Margaret Khonga, Martin J Boeree, Patrick PJ Phillips, Derek James Sloan, Michael Hoelscher, Gibson Kibiki, Stephen Henry Gillespie

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Abstract

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.
Original languageEnglish
Pages (from-to)606-608
Number of pages3
JournalThorax
Volume75
Issue number7
Early online date30 Apr 2020
DOIs
Publication statusPublished - Jul 2020

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