Skip to content

Research at St Andrews

Model-based relationship between the molecular bacterial load assay and time-to-positivity in liquid culture

Research output: Contribution to journalArticle

DOI

Open Access Status

  • Embargoed (until 29/01/20)

Abstract

The molecular bacterial load (MBL) assay is a new tuberculosis biomarker which provides results in ∼4 hours. The relationship between MBL and time-to-positivity (TTP) has not been thoroughly studied and predictive models do not exist. We aimed to develop a model for MBL and identify the MBL-TTP relationship in patients. The model was developed on data from 105 tuberculosis patients from Malawi, Mozambique and Tanzania with joint MBL and TTP observations quantified from patient sputum collected for 12 weeks. MBL was quantified using polymerase chain reaction (PCR) of mycobacterial RNA and TTP using the Mycobacterial Growth Indicator Tube (MGIT) 960 system. Treatment consisted of isoniazid, pyrazinamide and ethambutol in standard doses together with rifampicin 10 or 35 mg/kg. The developed MBL-TTP model included several linked sub-models; a component describing decline of bacterial load in sputum, another component describing growth in liquid culture and a hazard model translating bacterial growth into a TTP signal. Additional components for contaminated and negative TTP samples were included. Visual predictive checks performed using the developed model gave good description of the observed data. The model predicted greater total sample loss for TTP than MBL due to contamination and negative samples. The model detected an increase in bacterial killing for 35 versus 10 mg/kg rifampicin (p=0.002). In conclusion, a combined model for MBL and TTP was developed that described the MBL-TTP relationship. The full MBL-TTP model or each sub-model used separately. Secondly, the model can be used to predict biomarker response for MBL given TTP data or vice versa in historical or future trials.
Close

Details

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
VolumeEarly
Early online date29 Jul 2019
DOIs
Publication statusE-pub ahead of print - 29 Jul 2019

    Research areas

  • Tuberculosis, Diagnostics, Treatment monitoring, Clinical trials

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. A tuberculosis molecular bacterial load assay (TB-MBLA)

    Sabiiti, W., Mtafya, B. A., Alferes De Lima, D., Dombay, E., Baron, V. O., Azam, K., Orascova, K., Sloan, D. J. & Gillespie, S. H., 6 Sep 2019, (Accepted/In press) In : Journal of Visualized Experiments.

    Research output: Contribution to journalArticle

  2. Molecular bacterial load assay (MBLA) concurs with culture on the NaOH-induced Mycobacterium tuberculosis loss of viability

    Mtafya, B., Sabiiti, W., Sabi, I., John, J., Sichone, E., Ntinginya, N. E. & Gillespie, S. H., 25 Jun 2019, In : Journal of Clinical Microbiology. 57, e01992-18.

    Research output: Contribution to journalArticle

  3. Heat-inactivation renders sputum safe and preserves Mycobacterium tuberculosis RNA for downstream molecular tests

    Sabiiti, W., Azam, K., Esmeraldo, E., Bhatt, N., Rachow, A. & Gillespie, S. H., Mar 2019, In : Journal of Clinical Microbiology. 57, 4, 8 p., e01778-18.

    Research output: Contribution to journalArticle

  4. OMNIgene.SPUTUM suppresses contaminants whilst maintaining Mycobacterium tuberculosis viability and obviates cold-chain transport

    Azam, K., Cadir, N., Madeira, C., Gillespie, S. H. & Sabiiti, W., 16 Feb 2018, In : ERJ Open Research. 4, 8 p., 00074-2017.

    Research output: Contribution to journalArticle

  5. Mycobacterial load assay

    Gillespie, S. H., Sabiiti, W. & Oravcova, K., 2017, Diagnostic Bacteriology: Methods and Protocols. Bishop-Lilly, K. A. (ed.). New York, NY: Humana Press/Springer, p. 89-105 17 p. (Methods in Molecular Biology; vol. 1616).

    Research output: Chapter in Book/Report/Conference proceedingChapter

Related by journal

  1. Moxifloxacin replacement in contemporary tuberculosis drug regimens is ineffective against persistent Mycobacterium tuberculosis: in the Cornell mouse model

    Liu, Y., Pertinez, H., Davies, G. R., Gillespie, S. H., Coates, A. R. & Hu, Y., Jul 2018, In : Antimicrobial Agents and Chemotherapy. 62, 7, 9 p., e00190-18.

    Research output: Contribution to journalArticle

  2. TonB-dependent receptor repertoire of pseudomonas aeruginosa for uptake of siderophore-drug conjugates

    Luscher, A., Moynie, L., Auguste, P. S., Bumann, D., Mazza, L., Pletzer, D., Naismith, J. H. & Köhlera, T., Jun 2018, In : Antimicrobial Agents and Chemotherapy. 62, 6, 11 p., e00097-18.

    Research output: Contribution to journalArticle

  3. Genetic determinants of the pharmacokinetic variability of rifampin in Malawian adults with pulmonary tuberculosis

    Sloan, D. J., McCallum, A. D., Schipani, A., Egan, D., Mwandumba, H. C., Ward, S. A., Waterhouse, D., Banda, G., Allain, T. J., Owen, A., Khoo, S. H. & Davies, G. R., 1 Jul 2017, In : Antimicrobial Agents and Chemotherapy. 61, 7, 9 p., e00210-17.

    Research output: Contribution to journalArticle

  4. Pharmacokinetics, tolerability, and bacteriological response of rifampin administered at 600, 900, and 1,200 milligrams daily in patients with pulmonary tuberculosis

    Aarnoutse, R. E., Kibiki, G. S., Reither, K., Semvua, H. H., Haraka, F., Mtabho, C. M., Mpagama, S. G., van den Boogaard, J., Sumari-de Boer, I. M., Magis-Escurra, C., Wattenberg, M., Logger, J. G. M., te Brake, L. H. M., Hoelscher, M., Gillespie, S. H., Colbers, A., Phillips, P. P. J., Plemper van Balen, G., Boeree, M. J. & PanACEA Consortium, 1 Nov 2017, In : Antimicrobial Agents and Chemotherapy. 61, 11, e01054-17.

    Research output: Contribution to journalArticle

ID: 260441860

Top