Tuberculosis bacillary load, an early marker of disease severity: The utility of tuberculosis Molecular Bacterial Load Assay

Wilber Sabiiti, Khalide Azam, Eoghan Charles William Farmer, Davis Kuchaka, Bariki Mtafya, Ruth Bowness, Katarina Oravcova, Isobella Honeyborne, Dimitrios Evangelopoulos, Timothy Daniel 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 P.J. Phillips, Derek Sloan, Michael Hoelscher, Gibson Kibiki, Stephen H. Gillespie

Research output: Contribution to journalArticle

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
Volume2020
Issue number75
Early online date30 Apr 2020
DOIs
Publication statusE-pub ahead of print - 30 Apr 2020

Keywords

  • bacterial Infection
  • respiratory infection
  • tuberculosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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