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

<h3>Background</h3> Tuberculosis (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. <h3>Methods</h3> Treatment 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. <h3>Results</h3> Diagnostic 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. <h3>Conclusion</h3> The 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.