Browsing by Author "Mtafya, Bariki"

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Mycobactericidal effect of different regimens measured by molecular bacterial load assay among people treated for multidrug-resistant tuberculosis in Tanzania.
(American Society for Microbiology, 2021-02-03) Mbelele, Peter M; Mpolya, Emmanuel A; Sauli, Elingarami; Mtafya, Bariki; Ntinginya, Nyanda E; Addo, Kennedy K; Kreppel, Katharina; Mfinanga, Sayoki; Phillips, Patrick P J; Gillespie, Stephen H; Heysell, Scott K; Sabiiti, Wilber; Mpagama, Stellah G
Rifampicin or multidrug-resistant-tuberculosis (RR/MDR-TB) treatment has largely transitioned to regimens free of the injectable aminoglycoside component despite the drug class' purported bactericidal activity early in treatment. We tested whether () killing rates measured by molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB regimen. 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 16S rRNA in sputum for estimation of colony-forming-unit per mL (eCFU/mL). killing rates were compared among regimens using nonlinear-mixed-effects modelling of repeated measures. Thirty-seven patients produced 296 serial sputa: 13 patients received an injectable-containing but bedaquiline-free reference regimen, 9 received an injectable and bedaquiline-containing regimen, 8 received an all-oral bedaquiline-based regimen, and 7 patients were treated for drug-sensitive TB with conventional rifampin/isoniazid/pyrazinamide/ethambutol (RHZE). Compared to the adjusted killing of -0.17 (95% CI; -0.23 to -0.12) for the injectable-containing but bedaquiline-free reference regimen, the killing rates were -0.62 (95% CI; -1.05 to -0.20) log eCFU/mL for the injectable and bedaquiline-containing regimen (p = 0.019), -0.35 (95% CI; -0.65 to -0.13) log eCFU/mL for the all-oral bedaquiline-based regimen (p = 0.054), and -0.29 (95% CI; -0.78 to +0.22) log eCFU/mL for RHZE (p = 0.332). killing rates from sputa were higher among patients who received bedaquiline but were further improved with the addition of an injectable aminoglycoside.
Mycobactericidal Effects of Different Regimens Measured by Molecular Bacterial Load Assay among People Treated for Multidrug-Resistant Tuberculosis in Tanzania
(American Society for Microbiology, 2021-02-03) Mbelele, Peter; Mpolya, Emmanuel; Sauli, Elingarami; Mtafya, Bariki; Ntinginya, Nyanda; Addo, Kennedy; Kreppel, Katharina; Mfinanga, Sayoki; Phillips, Patrick; Gillespie, Stephen; Heysell, Scott; Sabiiti, Wilber; Mpagama, Stellah
Rifampin or multidrug-resistant tuberculosis (RR/MDR-TB) treatment has largely transitioned to regimens free of the injectable aminoglycoside component, despite the drug class’ purported bactericidal activity early in treatment. We tested whether Mycobacterium tuberculosis killing rates measured by tuberculosis molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB regimen. Serial sputa were collected from patients with RR/MDR- and drug-sensitive TB at days 0, 3, 7, and 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable M. tuberculosis 16S rRNA in sputum for estimation of colony forming units per ml (eCFU/ml). M. tuberculosis killing rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures. Thirty-seven patients produced 296 serial sputa and received treatment as follows: 13 patients received an injectable bedaquiline-free reference regimen, 9 received an injectable bedaquiline-containing regimen, 8 received an all-oral bedaquiline-based regimen, and 7 patients were treated for drug-sensitive TB with conventional rifampin/isoniazid/pyrazinamide/ethambutol (RHZE). Compared to the adjusted M. tuberculosis killing of −0.17 (95% confidence interval [CI] −0.23 to −0.12) for the injectable bedaquiline-free reference regimen, the killing rates were −0.62 (95% CI −1.05 to −0.20) log10 eCFU/ml for the injectable 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 the RHZE regimen (P = 0.332). Thus, M. tuberculosis killing rates from sputa were higher among patients who received bedaquiline but were further improved with the addition of an injectable aminoglycoside.
N-acetylcysteine modulates markers of oxidation, inflammation and infection in tuberculosis
(Elsevier, 2025-01-03) Mapamba, Daniel; Sabi, Issa; Lalashowi, Julieth; Sauli, Elingarami; Buza, Joram; Olomi, Willyhelmina; Mtafya, Bariki; Kibona, Michael; Velen, Kavindhran; Hoelscher, Michael
Background Half the global tuberculosis health burden is due to post-tuberculosis lung disease. Host-directed therapies have been proposed to reduce this burden. N-acetylcysteine (NAC) provides the conditionally essential amino acid cysteine required for synthesis of glutathione, an antioxidant thiol. We recently reported clinical outcomes of a trial of adjunctive NAC in patients with pulmonary tuberculosis, finding that NAC improved the secondary endpoint of recovery of lung function. Here we report the effects of NAC on biomarkers of oxidation, inflammation, and infection in that trial. Methods 140 adults with moderate or far-advanced pulmonary tuberculosis were randomly assigned to standard tuberculosis treatment with or without NAC 1200 mg twice daily for months 1-4. Sputum and blood samples were obtained at specified intervals to measure total glutathione, MTB-induced cytokines, haemoglobin, whole blood mycobactericidal activity (WBA), and sputum MTB burden. Results NAC treatment rapidly increased total glutathione (P<.0001), but levels did not reach those of healthy volunteers (P<.001). NAC reduced MTB-induced TNF-α (P =.011) without affecting IL-10, and accelerated the recovery of hemoglobin in participants with low values on entry. NAC did not affect killing in ex vivo whole blood culture but did slow the clearance of MTB from sputum (P=0.003). Conclusion Adjunctive NAC showed antioxidant and anti-inflammatory effects consistent with the amelioration of immunopathology seen in preclinical models. Two biomarkers of antimicrobial activity showed discordant results; neither demonstrated the enhanced antimicrobial effects seen preclinically. The reduction of oxidative stress and inflammation by NAC may explain its effects on the recovery of lung function post-TB.
Performance of Tuberculosis Molecular Bacterial Load Assay Compared to Alere TB-LAM in Urine of Pulmonary Tuberculosis Patients with HIV Co-Infections
(MDPI, 2023-02-23) Mapamba, Daniel; Sauli, Elingarami; Lalashowi, Julieth; Buza, Joram; John, Joseph; Mwaisango, Zawadi; Tarmo, Peter; Sabi, Issa; Rachow, Andrea; Ntinginya, Nyanda; Mtafya, Bariki
Alternative tools are needed to improve the detection of M. tuberculosis (M. tb) in HIV co-infections. We evaluated the utility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to lipoarabinomannan (LAM) to detect M. tb in urine. Sputum Xpert MTB/RIF-positive patients were consented to provide urine at baseline, weeks 2, 8, 16, and 24 of treatment for TB-MBLA, culture, and LAM. Results were compared with sputum cultures and microscopy. Initial M. tb. H37Rv spiking experiments were performed to validate the tests. A total of 63 urine samples from 47 patients were analyzed. The median age (IQR) was 38 (30–41) years; 25 (53.2%) were male, 3 (6.5%) had urine for all visits, 45 (95.7%) were HIV positive, of whom 18 (40%) had CD4 cell counts below 200 cells/µL, and 33 (73.3%) were on ART at enrollment. Overall urine LAM positivity was 14.3% compared to 4.8% with TB-MBLA. Culture and microscopy of their sputum counterparts were positive in 20.6% and 12.7% of patients, respectively. Of the three patients with urine and sputum at baseline, one (33.33%) had urine TB-MBLA and LAM positive compared to 100% with sputum MGIT culture positive. Spearman’s rank correction coefficient (r) between TB-MBLA and MGIT was −0.85 and 0.89 with a solid culture, p > 0.05. TB-MBLA has the promising potential to improve M. tb detection in urine of HIV-co-infected patients and complement current TB diagnostics.