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.
- bacterial Infection
- respiratory infection
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Correction notice This article has been corrected since it was published Online First. The funding statement has been amended.
Contributors Study design: SHG, TDMH, KO, WS, IH, AR, NH, MH, MJB, GSK, GM, MB. Literature search: SHG, IH, TDMH. Training: WS, SHG, KO, DE, IH, TDM. Data collection: KA, DK, BM, MK, AM, ECWF, GSK, MK, EK, NEN, NB, SV, IJ. Data analysis: PP, SHG, RB, WS, DS. Data interpretation: SHG, DE, WS, RB. Drafting the paper: WS, RB, DS, SHG. Figures and tables: WS, KA, ECWF, DE. Manuscript reviewing: All authors.
Funding This study was funded by European and Developing Countries Clinical Trials Partnership PanACEA 1 grants SP.2011.41304.008: PanAfrican Biomarker Expansion Programme, IP.2007.32011.011: Rapid Evaluation of Moxifloxacin in the treatment of sputum smear positive tuberculosis: REMoxTB (REMox I), IP.2007.32011.012: Rapid evaluation of high-dose rifampicin and other rifamycins in tuberculosis and IP.2007.32011.013: Evaluation of a novel TB drug (SQ109) to shorten and simplify TB treatment; supplemented by funding from Innovative Medicines Initiative (FP7/2007-2013).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Ethical approval for the study was obtained from relevant ethics committees in Tanzania (NIMR/HQ/R.8c/242), Mozambique (147/CNBS/14) and Malawi (P.08/13/1448) (detailed methods on line file 1).
Provenance and peer review Not commissioned; externally peer reviewed.
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