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

Sabiiti, Wilber; Azam, Khalide; Farmer, Eoghan Charles William; Kuchaka, Davis; Mtafya, Bariki; Bowness, Ruth; Oravcova, Katarina; Honeyborne, Isobella; Evangelopoulos, Dimitrios; McHugh, Timothy Daniel; Khosa, Celso; Rachow, Andrea; Heinrich, Norbert; Kampira, Elizabeth; Davies, Geraint; Bhatt, Nilesh; Ntinginya, Elias N.; Viegas, Sofia; Jani, Ilesh; Kamdolozi, Mercy; Mdolo, Aaron; Khonga, Margaret; Boeree, Martin J.; Phillips, Patrick P. J.; Sloan, Derek; Hoelscher, Michael; Kibiki, Gibson und Gillespie, Stephen H. (2020): Tuberculosis bacillary load, an early marker of disease severity: the utility of tuberculosis Molecular Bacterial Load Assay. In: Thorax, Bd. 75, Nr. 7: S. 606-608

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 5.5log(10)eCFU/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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0040-6376
• Allianz-/Nationallizenz: Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
• Sprache: Englisch