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bioRxiv · 10.1101/2020.09.02.280511

Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate of Mycobacterium tuberculosis in patients with multidrug-resistant tuberculosis in Tanzania

Mbelele, P. M.·Mpolya, E. A.·Sauli, E.·Mtafya, B.·Ntinginya, N. E.·Addo, K. K.·Kreppel, K.·Mfinanga, S.·Phillips, P. P. J.·Gillespie, S. H.·Heysell, S. K.·Sabiiti, W.·Mpagama, S.
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Abstract

BackgroundRifampin or multidrug-resistant-tuberculosis (RR/MDR-TB) treatment has transitioned to injectable-free regimens. We tested whether M. tuberculosis (Mtb) elimination rates measured by molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB antibiotic regimen. MethodsSerial sputa were collected from patients with RR/MDR- and drug-sensitive TB at day 0, 3, 7, 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable Mtb 16S rRNA in sputum for estimation of colony-forming-unit per mL (eCFU/mL). Mtb elimination rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures. ResultsAmong 37 patients with a total of 296 serial sputa; 7 patients received rifampin/isoniazid/pyrazinamide/ethambutol (RHZE), 8 an all-oral bedaquiline-based regimen, 9 an injectable and bedaquiline-containing regimen, and 13 an injectable-containing but bedaquiline-free regimen. The overall mean daily Mtb elimination was -0.24 [95% Confidence-Interval (CI); -0.39 to -0.08)] log10 eCFU/mL, and it varied with treatment-regimen (p < 0.001). Compared to the adjusted Mtb elimination of -0.17 (95% CI; -0.23 to -0.12) for the injectable-containing but bedaquiline-free reference regimen, the elimination rates were -0.62 (95% CI; -1.05 to -0.20) log10 eCFU/mL for the injectable and bedaquiline-containing regimen (p = 0.019), -0.35 (95% CI; -0.65 to -0.13) log10 eCFU/mL for the all-oral bedaquiline-based regimen (p = 0.054), and -0.29 (95% CI; -0.78 to +0.22) log10 eCFU/mL for RHZE (p = 0.332) ConclusionTB-MBLA distinguished Mtb elimination rates in sputa from patients receiving different treatment regimens, suggesting a reliable monitoring tool for RR/MDR-TB, that does not require mycobacterial culture.

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Mbelele, P. M., Mpolya, E. A., Sauli, E., Mtafya, B., Ntinginya, N. E., Addo, K. K., Kreppel, K., Mfinanga, S., Phillips, P. P. J., Gillespie, S. H., Heysell, S. K., Sabiiti, W., Mpagama, S.. 2020-09-03. Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate of Mycobacterium tuberculosis in patients with multidrug-resistant tuberculosis in Tanzania. https://doi.org/10.1101/2020.09.02.280511

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