Feasibility and Operational Performance of Tuberculosis Detection by Loop-Mediated Isothermal Amplification Platform in Decentralized Settings: Results from a Multicenter Study
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Date
2016
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Clinical Microbiology
Abstract
Currently available nucleic acid amplification platforms for tuberculosis (TB) detection are not designed to be simple or inexpensive
enough to implement in decentralized settings in countries with a high burden of disease. The loop-mediated isothermal
amplification platform (LAMP) may change this. We conducted a study in adults with symptoms suggestive of TB in India,
Uganda, and Peru to establish the feasibility of using TB-LAMP (Eiken Chemical Co.) in microscopy laboratories compared with
using smear microscopy against a reference standard of solid and liquid cultures. Operational characteristics were evaluated as
well. A total of 1,777 participants met the eligibility criteria and were included for analysis. Overall, TB-LAMP sensitivities
among culture-positive samples were 97.2% (243/250; 95% confidence interval [CI], 94.3% to 98.2%) and 62.0% (88/142; 95% CI,
53.5% to 70.0%) for smear-positive and smear-negative TB, respectively, but varied widely by country and operator. Specificities
ranged from 94.5% (446/472; 95% CI, 92.0% to 96.4%) to 98.0% (350/357; 95% CI, 96.0% to 99.2%) by country. A root cause
analysis identified high temperatures, high humidity, and/or low reaction volumes as possible causes for false-positive results, as
they may result in nonspecific amplification. The study was repeated in India with training focused on vulnerable steps and an
updated protocol; 580 participants were included for analysis. Specificity in the repeat trial was 96.6% (515/533; 95% CI, 94.7%
to 97.9%). To achieve acceptable performance of LAMP at the microscopy center level, significant training and infrastructure
requirements are necessary.
Description
Keywords
Feasibility, Tuberculosis Detection, Isothermal Amplification Platform, Decentralized Settings
Citation
Gray CM, Katamba A, Narang P, Giraldo J, Zamudio C, Joloba M, Narang R, Paramasivan CN, Hillemann D, Nabeta P, Amisano D, Alland D, Cobelens F, Boehme CC. 2016. Feasibility and operational performance of tuberculosis detection by loop-mediated isothermal amplification platform in decentralized settings: results from a multicenter study. J Clin Microbiol 54:1984 –1991. doi:10.1128/JCM.03036-15.