Tuberculosis bacillary load, an early marker of disease severity and treatment response : the utility of tuberculosis Molecular Bacterial Load Assay
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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.
Sabiiti , W , Azam , K , Farmer , E , Kuchaka , D , Mtafya , B , Bowness , R , Oravcova , K , Honeyborne , I , Evangelopoulos , D , McHugh , T D , Khosa , C , Rachow , A , Heinrich , N , Kampira , E , Davies , G , Bhatt , N , Ntinginya , E N , Viegas , S , Jani , I , Kamdolozi , M , Mdolo , A , Khonga , M , Boeree , M J , Phillips , P PJ , Sloan , D J , Hoelscher , M , Kibiki , G & Gillespie , S H 2020 , ' Tuberculosis bacillary load, an early marker of disease severity and treatment response : the utility of tuberculosis Molecular Bacterial Load Assay ' , Thorax , vol. 75 , no. 7 , pp. 606-608 . https://doi.org/10.1136/thoraxjnl-2019-214238
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DescriptionThis work was supported by the European and Developing Countries Clinical Trials Partnership (EDCTP), [SP.2011.41304.008] and PreDiCT-TB consortium R [IMI Joint undertaking grant agreement number 115337], resources of which are composed of financial contribution from the European Union's Seventh Framework Programme [FP7/2007-2013] and EFPIA companies' in-kind contribution.
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