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

• Published in: bioRxiv
• Main Authors: Mbelele, Peter M, Mpolya, Emmanuel A, Elingarami Sauli, Mtafya, Bariki, Ntinginya, Nyanda E, Addo, Kennedy K, Kreppel, Katharina, Mfinanga, Sayoki, Phillips, Patrick Pj, Gillespie, Stephen H, Heysell, Scott K, Wilber Sabiiti, Mpagama, Stellah G
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 03.09.2020
• Subjects: Ethambutol; Isoniazid; Multidrug resistance; Pyrazinamide; Rifampin; rRNA 16S; Sputum; Tuberculosis
• DOI: 10.1101/2020.09.02.280511

Abstract Background Rifampin 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. Methods Serial 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. Results Among 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) Conclusion TB-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.