The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

Marriott Nliwasa,Kruger Kaswaswa,Chisomo Msefula,Peter Macpherson,Mercy Kamdolozi,Palesa Chisala,Hojoon Sohn,Mphatso Mwapasa,Clare Flach,Mcewen Khundi,Elizabeth L Corbett

doi:10.1371/journal.pone.0155101

Abstract

BackgroundCurrent 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.ObjectiveTo 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.MethodsBetween 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.ResultsOf 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).ConclusionThe 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.

Highlights

Diagnosis of tuberculosis with highly accurate, rapid point of care tests is a key component of the WHO’s End Tuberculosis Strategy [1]
The sensitivity of Xpert1 MTB/RIF (77.5%, 95% confidence interval (CI): 61.5% to 89.2%) was similar to that of loop-mediated isothermal amplification (LAMP), p = 0.132
The sensitivity of LAMP was similar to Xpert1 MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity

Summary

Introduction

Diagnosis of tuberculosis with highly accurate, rapid point of care tests is a key component of the WHO’s End Tuberculosis Strategy [1]. LAMP is being considered as a potential replacement for smear microscopy in settings with low burden of multi-drug resistant tuberculosis, with potential cost-savings compared to Xpert MTB/RIF in peripheral laboratories with high volume of samples, and countries not eligible for low income country access prices [6]. A recent meta-analysis estimated a sensitivity of 80% and specificity of 96% for LAMP on sputum specimens compared to culture, but included studies were mostly from countries with low burden of HIV [7]. Rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence

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Results

Conclusion