The sensitivity and specificity of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough in Malawi

Fernandez-Reyes, D. et al. (2016) The sensitivity and specificity of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough in Malawi. PLoS ONE, 11(5), e0155101. (doi: 10.1371/journal.pone.0155101) (PMID:27171380) (PMCID:PMC4865214)

Abstract

Background: Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. Objective: To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Methods: Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Results: Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). Conclusion: The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

• Item Type: Articles
• Additional Information: PM was supported by the Wellcome Trust (grant number: WT089673).ELC was funded by a Wellcome Trust Senior Research Fellowship in Clinical Science (grant number: 091769/Z/10/Z). Research was funded by the Foundation on Innovative New Diagnostics (FIND), the Helse Nord Tuberculosis Initiative and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacPherson, Professor Peter
• Authors: Fernandez-Reyes, D., Nliwasa, M., MacPherson, P., Chisala, P., Kamdolozi, M., Khundi, M., Kaswaswa, K., Mwapasa, M., Msefula, C., Sohn, H., Flach, C., and Corbett, E. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2016 Nliwasa et al.
• First Published: First published in PLoS ONE 11(5):e0155101
• Publisher Policy: Reproduced under a Creative Commons licence