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

Sabiiti, W. et al. (2020) Tuberculosis bacillary load, an early marker of disease severity: the utility of tuberculosis Molecular Bacterial Load Assay. Thorax, 75(7), pp. 606-608. (doi: 10.1136/thoraxjnl-2019-214238) (PMID:32354738) (PMCID:PMC7361026)

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.

• Item Type: Articles
• Additional Information: Funding: This study was funded by European and Developing Countries Clinical Trials PartnershipSP.2011.41304.008, Innovative Medicines Initiative (FP7/2007- 2013).
• Keywords: Brief communication, 1506, 2313, tuberculosis, bacterial Infection, respiratory infection.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Oravcova, Dr Katarina
• Authors: Sabiiti, W., Azam, K., Farmer, E. C. W., 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. P. J., Sloan, D., Hoelscher, M., Kibiki, G., and Gillespie, S. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Thorax
• Journal Abbr.: 1468-3296
• Publisher: BMJ Publishing Group
• ISSN: 1468-3296
• Published Online: 30 April 2020
• Copyright Holders: Copyright © Author(s) (or their employer(s)) 2020
• First Published: First published in Thorax 75(7):606-608
• Publisher Policy: Reproduced under a Creative Commons Licence