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PA-583 Revolutionising tuberculosis treatment response monitoring and developing research capacity in Africa: progress and potential of the tuberculosis molecular bacterial load assay

BackgroundTuberculosis (TB) treatment is long and complex. Here we summarise data from EDCTP-funded studies of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) as a TB treatment monitoring tool.MethodsTreatment naïve participants from four Sub-Saharan African countries were assessed for TB...

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Published in:BMJ global health 2023-12, Vol.8 (Suppl 10), p.A99-A99
Main Authors: Sabiiti, Wilber, Musisi, Emmanuel, Mtafya, Bariki, Mbelele, Peter, Azam, Khalide, Ntinginya, Nyanda Elias, Kuchaka, Davis, Kamdolozi, Mercy, Khosa, Celso, Ssengooba, Willy, Rachow, Andrea, Henreich, Norbert, Sloan, Derek J, Joloba, Moses, Davies, Gerry, Aarnouste, Rob, Boeree, Martin, Hoelscher, Michael, Kibiki, Gibson Sammy, Gillespie, Stephen H
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container_end_page A99
container_issue Suppl 10
container_start_page A99
container_title BMJ global health
container_volume 8
creator Sabiiti, Wilber
Musisi, Emmanuel
Mtafya, Bariki
Mbelele, Peter
Azam, Khalide
Ntinginya, Nyanda Elias
Kuchaka, Davis
Kamdolozi, Mercy
Khosa, Celso
Ssengooba, Willy
Rachow, Andrea
Henreich, Norbert
Sloan, Derek J
Joloba, Moses
Davies, Gerry
Aarnouste, Rob
Boeree, Martin
Hoelscher, Michael
Kibiki, Gibson Sammy
Gillespie, Stephen H
description BackgroundTuberculosis (TB) treatment is long and complex. Here we summarise data from EDCTP-funded studies of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) as a TB treatment monitoring tool.MethodsTreatment naïve participants from four Sub-Saharan African countries were assessed for TB diagnosis and treatment response using TB-MBLA compared to liquid culture (MGIT) and other standard-of-care tests. ResultsDiagnostic accuracy assessment using MGIT as gold standard showed TB-MBLA sensitivity, specificity, positive-and-negative-predictive values were 99%, 91%, 92% and 99% respectively among presumptive TB cases. TB-MBLA turn-around-time (clinic-laboratory-clinic) was 6log10eCFU/mL, was associated with failure to convert to negative by month-2 of treatment. Resolution of TB-MBLA-measured sputum bacillary load mirrored cough resolution, reduction of C-reactive protein levels in blood and correlated with MGIT culture time-to-positivity (Spearmans r= -0.5, p500 clinical/laboratory scientists trained in principles of molecular diagnostic development and implementation globally.ConclusionThe data shows that TB-MBLA is a robust assay for TB treatment response monitoring and anti-TB drug development. It has contributed to research capacity building across Africa and beyond.
doi_str_mv 10.1136/bmjgh-2023-EDC.241
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Here we summarise data from EDCTP-funded studies of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) as a TB treatment monitoring tool.MethodsTreatment naïve participants from four Sub-Saharan African countries were assessed for TB diagnosis and treatment response using TB-MBLA compared to liquid culture (MGIT) and other standard-of-care tests. ResultsDiagnostic accuracy assessment using MGIT as gold standard showed TB-MBLA sensitivity, specificity, positive-and-negative-predictive values were 99%, 91%, 92% and 99% respectively among presumptive TB cases. TB-MBLA turn-around-time (clinic-laboratory-clinic) was &lt;24h compared to 5–42 days of MGIT culture. 450 participants were assessed for treatment response across four studies. The pre-treatment bacillary load across cohorts was 5.33+1.33log10eCFU/mL which was cleared to zero in over 95% of the participants by month-6 of treatment. TB-MBLA revealed early bacillary load clearance in 7% (32/450) participants who achieved a stable negative TB-MBLA result by week-2 of treatment and was faster than MGIT to identify participants at a risk of disease relapse. High pre-treatment bacillary load =/&gt;6log10eCFU/mL, was associated with failure to convert to negative by month-2 of treatment. Resolution of TB-MBLA-measured sputum bacillary load mirrored cough resolution, reduction of C-reactive protein levels in blood and correlated with MGIT culture time-to-positivity (Spearmans r= -0.5, p&lt;0.0001) during treatment. Like MGIT, TB-MBLA demonstrated that regimens containing rifampicin-35mg/kg and rifampicin-20mg/kg-400mg-moxifloxacin cleared TB bacteria significantly faster than the standard-of-care regimen by month-2 of treatment, p=0.049 and p=0.008 respectively in DS-TB, and highlighted efficacy of bedaquiline-containing all oral regimen for DR-TB treatment. This work produced 5 African PhD graduates plus &gt;500 clinical/laboratory scientists trained in principles of molecular diagnostic development and implementation globally.ConclusionThe data shows that TB-MBLA is a robust assay for TB treatment response monitoring and anti-TB drug development. It has contributed to research capacity building across Africa and beyond.</description><identifier>EISSN: 2059-7908</identifier><identifier>DOI: 10.1136/bmjgh-2023-EDC.241</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd</publisher><subject>Abstracts of Poster and e-Poster Presentations ; Bacterial infections ; Medical research ; Medical treatment ; Tuberculosis</subject><ispartof>BMJ global health, 2023-12, Vol.8 (Suppl 10), p.A99-A99</ispartof><rights>Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2023 Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://gh.bmj.com/content/8/Suppl_10/A99.1.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttps://gh.bmj.com/content/8/Suppl_10/A99.1.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,55350,77660,77686</link.rule.ids><linktorsrc>$$Uhttps://gh.bmj.com/content/8/Suppl_10/A99.1.full$$EView_record_in_BMJ_Publishing_Group_Ltd$$FView_record_in_$$GBMJ_Publishing_Group_Ltd</linktorsrc></links><search><creatorcontrib>Sabiiti, Wilber</creatorcontrib><creatorcontrib>Musisi, Emmanuel</creatorcontrib><creatorcontrib>Mtafya, Bariki</creatorcontrib><creatorcontrib>Mbelele, Peter</creatorcontrib><creatorcontrib>Azam, Khalide</creatorcontrib><creatorcontrib>Ntinginya, Nyanda Elias</creatorcontrib><creatorcontrib>Kuchaka, Davis</creatorcontrib><creatorcontrib>Kamdolozi, Mercy</creatorcontrib><creatorcontrib>Khosa, Celso</creatorcontrib><creatorcontrib>Ssengooba, Willy</creatorcontrib><creatorcontrib>Rachow, Andrea</creatorcontrib><creatorcontrib>Henreich, Norbert</creatorcontrib><creatorcontrib>Sloan, Derek J</creatorcontrib><creatorcontrib>Joloba, Moses</creatorcontrib><creatorcontrib>Davies, Gerry</creatorcontrib><creatorcontrib>Aarnouste, Rob</creatorcontrib><creatorcontrib>Boeree, Martin</creatorcontrib><creatorcontrib>Hoelscher, Michael</creatorcontrib><creatorcontrib>Kibiki, Gibson Sammy</creatorcontrib><creatorcontrib>Gillespie, Stephen H</creatorcontrib><title>PA-583 Revolutionising tuberculosis treatment response monitoring and developing research capacity in Africa: progress and potential of the tuberculosis molecular bacterial load assay</title><title>BMJ global health</title><addtitle>BMJ Glob Health</addtitle><description>BackgroundTuberculosis (TB) treatment is long and complex. Here we summarise data from EDCTP-funded studies of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) as a TB treatment monitoring tool.MethodsTreatment naïve participants from four Sub-Saharan African countries were assessed for TB diagnosis and treatment response using TB-MBLA compared to liquid culture (MGIT) and other standard-of-care tests. ResultsDiagnostic accuracy assessment using MGIT as gold standard showed TB-MBLA sensitivity, specificity, positive-and-negative-predictive values were 99%, 91%, 92% and 99% respectively among presumptive TB cases. TB-MBLA turn-around-time (clinic-laboratory-clinic) was &lt;24h compared to 5–42 days of MGIT culture. 450 participants were assessed for treatment response across four studies. The pre-treatment bacillary load across cohorts was 5.33+1.33log10eCFU/mL which was cleared to zero in over 95% of the participants by month-6 of treatment. TB-MBLA revealed early bacillary load clearance in 7% (32/450) participants who achieved a stable negative TB-MBLA result by week-2 of treatment and was faster than MGIT to identify participants at a risk of disease relapse. High pre-treatment bacillary load =/&gt;6log10eCFU/mL, was associated with failure to convert to negative by month-2 of treatment. Resolution of TB-MBLA-measured sputum bacillary load mirrored cough resolution, reduction of C-reactive protein levels in blood and correlated with MGIT culture time-to-positivity (Spearmans r= -0.5, p&lt;0.0001) during treatment. Like MGIT, TB-MBLA demonstrated that regimens containing rifampicin-35mg/kg and rifampicin-20mg/kg-400mg-moxifloxacin cleared TB bacteria significantly faster than the standard-of-care regimen by month-2 of treatment, p=0.049 and p=0.008 respectively in DS-TB, and highlighted efficacy of bedaquiline-containing all oral regimen for DR-TB treatment. This work produced 5 African PhD graduates plus &gt;500 clinical/laboratory scientists trained in principles of molecular diagnostic development and implementation globally.ConclusionThe data shows that TB-MBLA is a robust assay for TB treatment response monitoring and anti-TB drug development. 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Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><jtitle>BMJ global health</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Sabiiti, Wilber</au><au>Musisi, Emmanuel</au><au>Mtafya, Bariki</au><au>Mbelele, Peter</au><au>Azam, Khalide</au><au>Ntinginya, Nyanda Elias</au><au>Kuchaka, Davis</au><au>Kamdolozi, Mercy</au><au>Khosa, Celso</au><au>Ssengooba, Willy</au><au>Rachow, Andrea</au><au>Henreich, Norbert</au><au>Sloan, Derek J</au><au>Joloba, Moses</au><au>Davies, Gerry</au><au>Aarnouste, Rob</au><au>Boeree, Martin</au><au>Hoelscher, Michael</au><au>Kibiki, Gibson Sammy</au><au>Gillespie, Stephen H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PA-583 Revolutionising tuberculosis treatment response monitoring and developing research capacity in Africa: progress and potential of the tuberculosis molecular bacterial load assay</atitle><jtitle>BMJ global health</jtitle><stitle>BMJ Glob Health</stitle><date>2023-12-17</date><risdate>2023</risdate><volume>8</volume><issue>Suppl 10</issue><spage>A99</spage><epage>A99</epage><pages>A99-A99</pages><eissn>2059-7908</eissn><abstract>BackgroundTuberculosis (TB) treatment is long and complex. Here we summarise data from EDCTP-funded studies of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) as a TB treatment monitoring tool.MethodsTreatment naïve participants from four Sub-Saharan African countries were assessed for TB diagnosis and treatment response using TB-MBLA compared to liquid culture (MGIT) and other standard-of-care tests. ResultsDiagnostic accuracy assessment using MGIT as gold standard showed TB-MBLA sensitivity, specificity, positive-and-negative-predictive values were 99%, 91%, 92% and 99% respectively among presumptive TB cases. TB-MBLA turn-around-time (clinic-laboratory-clinic) was &lt;24h compared to 5–42 days of MGIT culture. 450 participants were assessed for treatment response across four studies. The pre-treatment bacillary load across cohorts was 5.33+1.33log10eCFU/mL which was cleared to zero in over 95% of the participants by month-6 of treatment. TB-MBLA revealed early bacillary load clearance in 7% (32/450) participants who achieved a stable negative TB-MBLA result by week-2 of treatment and was faster than MGIT to identify participants at a risk of disease relapse. High pre-treatment bacillary load =/&gt;6log10eCFU/mL, was associated with failure to convert to negative by month-2 of treatment. Resolution of TB-MBLA-measured sputum bacillary load mirrored cough resolution, reduction of C-reactive protein levels in blood and correlated with MGIT culture time-to-positivity (Spearmans r= -0.5, p&lt;0.0001) during treatment. Like MGIT, TB-MBLA demonstrated that regimens containing rifampicin-35mg/kg and rifampicin-20mg/kg-400mg-moxifloxacin cleared TB bacteria significantly faster than the standard-of-care regimen by month-2 of treatment, p=0.049 and p=0.008 respectively in DS-TB, and highlighted efficacy of bedaquiline-containing all oral regimen for DR-TB treatment. This work produced 5 African PhD graduates plus &gt;500 clinical/laboratory scientists trained in principles of molecular diagnostic development and implementation globally.ConclusionThe data shows that TB-MBLA is a robust assay for TB treatment response monitoring and anti-TB drug development. It has contributed to research capacity building across Africa and beyond.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd</pub><doi>10.1136/bmjgh-2023-EDC.241</doi><oa>free_for_read</oa></addata></record>
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subjects Abstracts of Poster and e-Poster Presentations
Bacterial infections
Medical research
Medical treatment
Tuberculosis
title PA-583 Revolutionising tuberculosis treatment response monitoring and developing research capacity in Africa: progress and potential of the tuberculosis molecular bacterial load assay
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