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Tuberculosis bacillary load, an early marker of disease severity and treatment response : the utility of tuberculosis Molecular Bacterial Load Assay
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dc.contributor.author | Sabiiti, Wilber | |
dc.contributor.author | Azam, Khalide | |
dc.contributor.author | Farmer, Eoghan | |
dc.contributor.author | Kuchaka, Davis | |
dc.contributor.author | Mtafya, Bariki | |
dc.contributor.author | Bowness, Ruth | |
dc.contributor.author | Oravcova, Katarina | |
dc.contributor.author | Honeyborne, Isobella | |
dc.contributor.author | Evangelopoulos, Dimitrios | |
dc.contributor.author | McHugh, Timothy D | |
dc.contributor.author | Khosa, Celso | |
dc.contributor.author | Rachow, Andrea | |
dc.contributor.author | Heinrich, Norbert | |
dc.contributor.author | Kampira, Elizabeth | |
dc.contributor.author | Davies, Geraint | |
dc.contributor.author | Bhatt, Nilesh | |
dc.contributor.author | Ntinginya, Elias N | |
dc.contributor.author | Viegas, Sofia | |
dc.contributor.author | Jani, Ilesh | |
dc.contributor.author | Kamdolozi, Mercy | |
dc.contributor.author | Mdolo, Aaron | |
dc.contributor.author | Khonga, Margaret | |
dc.contributor.author | Boeree, Martin J | |
dc.contributor.author | Phillips, Patrick PJ | |
dc.contributor.author | Sloan, Derek James | |
dc.contributor.author | Hoelscher, Michael | |
dc.contributor.author | Kibiki, Gibson | |
dc.contributor.author | Gillespie, Stephen Henry | |
dc.date.accessioned | 2020-05-05T11:30:08Z | |
dc.date.available | 2020-05-05T11:30:08Z | |
dc.date.issued | 2020-07 | |
dc.identifier | 266787733 | |
dc.identifier | c88bae49-dbb3-4734-9213-aba07b287e41 | |
dc.identifier | 85084320340 | |
dc.identifier | 000549873900017 | |
dc.identifier.citation | Sabiiti , W , Azam , K , Farmer , E , 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 PJ , Sloan , D J , Hoelscher , M , Kibiki , G & Gillespie , S H 2020 , ' Tuberculosis bacillary load, an early marker of disease severity and treatment response : the utility of tuberculosis Molecular Bacterial Load Assay ' , Thorax , vol. 75 , no. 7 , pp. 606-608 . https://doi.org/10.1136/thoraxjnl-2019-214238 | en |
dc.identifier.issn | 0040-6376 | |
dc.identifier.other | ORCID: /0000-0002-4090-5168/work/73701264 | |
dc.identifier.other | ORCID: /0000-0001-6537-7712/work/73701288 | |
dc.identifier.other | ORCID: /0000-0002-4742-2791/work/73702087 | |
dc.identifier.other | ORCID: /0000-0002-7888-5449/work/73701803 | |
dc.identifier.uri | https://hdl.handle.net/10023/19881 | |
dc.description | This work was supported by the European and Developing Countries Clinical Trials Partnership (EDCTP), [SP.2011.41304.008] and PreDiCT-TB consortium R [IMI Joint undertaking grant agreement number 115337], resources of which are composed of financial contribution from the European Union's Seventh Framework Programme [FP7/2007-2013] and EFPIA companies' in-kind contribution. | en |
dc.description.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. | |
dc.format.extent | 3 | |
dc.format.extent | 702644 | |
dc.language.iso | eng | |
dc.relation.ispartof | Thorax | en |
dc.subject | QR Microbiology | en |
dc.subject | RM Therapeutics. Pharmacology | en |
dc.subject | NDAS | en |
dc.subject | BDC | en |
dc.subject | R2C | en |
dc.subject | ~DC~ | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | QR | en |
dc.subject.lcc | RM | en |
dc.title | Tuberculosis bacillary load, an early marker of disease severity and treatment response : the utility of tuberculosis Molecular Bacterial Load Assay | en |
dc.type | Journal article | en |
dc.contributor.sponsor | European Commission | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Infection and Global Health Division | en |
dc.contributor.institution | University of St Andrews. Gillespie Group | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Centre for Biophotonics | en |
dc.contributor.institution | University of St Andrews. Global Health Implementation Group | en |
dc.contributor.institution | University of St Andrews. Infection Group | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | https://doi.org/10.1136/thoraxjnl-2019-214238 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | en |
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