Improving diagnosis and monitoring of treatment response in pulmonary tuberculosis using the molecular bacterial load assay (MBLA)

Sabiiti, W.; Azam, K.; Kuchaka, D.; Mtafya, B.; Bowness, R. E.; Oravcova, K.; Farmer, E.; Honeyborne, I.; Evangelopoulos, D.; McHugh, T. D.; Xiao, H.; Khosa, C.; Rachow, A.; Heinrich, N.; Kampira, E.; Davies, G.; Bhatt, N.; Ntinginya, N.; Viegas, S.; Jani, I.; Kamdolozi, M.; Mdolo, a.; Khonga, M.; Boeree, M. J.; Philips, P. P.; Sloan, D. J.; Hoelscher, M.; Kibiki, G.; Gillespie, S. H.

doi:10.1101/555995

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bioRxiv · 10.1101/555995

Improving diagnosis and monitoring of treatment response in pulmonary tuberculosis using the molecular bacterial load assay (MBLA)

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Abstract

ObjectivesBetter outcomes in tuberculosis require new diagnostic and treatment monitoring tools. In this paper we evaluated the utility of a marker of M. tuberculosis viable count, the Molecular Bacterial Load assay (MBLA) for diagnosis and treatment monitoring of tuberculosis in a high burden setting. MethodsPatients with smear positive pulmonary tuberculosis from two sites in Tanzania and one each in Malawi and Mozambique. Sputum samples were taken weekly for the first 12 weeks of treatment and evaluated by MBLA and mycobacterial growth indicator tube method (MGIT). ResultsThe results of high and low positive control samples confirmed inter site reproducibility. Over the 12 weeks of treatment there was a steady decline in the viable bacterial load as measured by the MBLA that corresponds to rise in time to a positive result (TTP) in the Mycobacterial Growth Indicator Tube. Both MBLA and MGIT provided similar time to test negativity. Importantly, as treatment progressed samples in MGIT were increasingly likely to be contaminated, which compromised the acquisition of results but did not affect MBLA samples. ConclusionsMBLA produces a reproducible measure of Mtb viable count comparable to that of MGIT that is not compromised by contamination in a real-world setting. As a molecular test, the results can be available in as little as four hours and could allow health care professionals to identify rapidly patients who are failing therapy.

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Sabiiti, W., Azam, K., Kuchaka, D., Mtafya, B., Bowness, R. E., Oravcova, K., Farmer, E., Honeyborne, I., Evangelopoulos, D., McHugh, T. D., Xiao, H., Khosa, C., Rachow, A., Heinrich, N., Kampira, E., Davies, G., Bhatt, N., Ntinginya, N., Viegas, S., Jani, I., Kamdolozi, M., Mdolo, a., Khonga, M., Boeree, M. J., Philips, P. P., Sloan, D. J., Hoelscher, M., Kibiki, G., Gillespie, S. H.. 2019-02-28. Improving diagnosis and monitoring of treatment response in pulmonary tuberculosis using the molecular bacterial load assay (MBLA). https://doi.org/10.1101/555995

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