title: Molecular bacterial load assay, a culture-free biomarker for rapid and accurate quantification of sputum Mycobacterium tuberculosis bacillary load during treatment.
abstract: A molecular assay to quantify Mycobacterium tuberculosis is described. In vitro, 98% (n = 96) of sputum samples with a known number of bacilli (10(7) to 10(2) bacilli) could be enumerated within 0.5 log(10). In comparison to culture, the molecular bacterial load (MBL) assay is unaffected by other microorganisms present in the sample, results are obtained more quickly (within 24 h) and are seldom inhibited (0.7% samples), and the MBL assay critically shows the same biphasic decline as observed longitudinally during treatment. As a biomarker of treatment response, the MBL assay responds rapidly, with a mean decline in bacterial load for 111 subjects of 0.99 log(10) (95% confidence interval [95% CI], 0.81 to 1.17) after 3 days of chemotherapy. There was a significant association between the rate of bacterial decline during the same 3 days and bacilli ml(-1) sputum at day 0 (linear regression, P = 0.0003) and a 3.62 increased odds ratio of relapse for every 1 log(10) increase in pretreatment bacterial load (95% CI, 1.53 to 8.59).
authors: Centre for Clinical Microbiology, M9, Department of Infection, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK. i.honeyborne@ucl.ac.uk
authors: Isobella
authors: I
authors: Honeyborne
authors: Timothy D
authors: TD
authors: McHugh
authors: Patrick P J
authors: PP
authors: Phillips
authors: Selina
authors: S
authors: Bannoo
authors: Anna
authors: A
authors: Bateson
authors: Nora
authors: N
authors: Carroll
authors: Felicity M
authors: FM
authors: Perrin
authors: Katharina
authors: K
authors: Ronacher
authors: Laura
authors: L
authors: Wright
authors: Paul D
authors: PD
authors: van Helden
authors: Gerhard
authors: G
authors: Walzl
authors: Stephen H
authors: SH
authors: Gillespie
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage; D058491:Bacterial Load / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology*; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents