Feasibility and operational performance of tuberculosis detection by loop-mediated isothermal amplification platform in decentralized settings

Results from a multicenter study

Christen M. Gray, Achilles Katamba, Pratibha Narang, Jorge Giraldo, Carlos Zamudio, Moses Joloba, Rahul Narang, C. N. Paramasivan, Doris Hillemann, Pamela Nabeta, Danielle Amisano, David Alland, Frank Cobelens, Catharina C. Boehme

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1984-1991
Number of pages8
JournalJournal of clinical microbiology
Volume54
Issue number8
DOIs
StatePublished - Aug 1 2016

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Multicenter Studies
Tuberculosis
Confidence Intervals
Microscopy
India
Root Cause Analysis
Peru
Uganda
Humidity
Nucleic Acids
Temperature

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)

Cite this

Gray, Christen M. ; Katamba, Achilles ; Narang, Pratibha ; Giraldo, Jorge ; Zamudio, Carlos ; Joloba, Moses ; Narang, Rahul ; Paramasivan, C. N. ; Hillemann, Doris ; Nabeta, Pamela ; Amisano, Danielle ; Alland, David ; Cobelens, Frank ; Boehme, Catharina C. / Feasibility and operational performance of tuberculosis detection by loop-mediated isothermal amplification platform in decentralized settings : Results from a multicenter study. In: Journal of clinical microbiology. 2016 ; Vol. 54, No. 8. pp. 1984-1991.
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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.",
author = "Gray, {Christen M.} and Achilles Katamba and Pratibha Narang and Jorge Giraldo and Carlos Zamudio and Moses Joloba and Rahul Narang and Paramasivan, {C. N.} and Doris Hillemann and Pamela Nabeta and Danielle Amisano and David Alland and Frank Cobelens and Boehme, {Catharina C.}",
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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', Journal of clinical microbiology, vol. 54, no. 8, pp. 1984-1991. https://doi.org/10.1128/JCM.03036-15

Feasibility and operational performance of tuberculosis detection by loop-mediated isothermal amplification platform in decentralized settings : Results from a multicenter study. / Gray, Christen M.; Katamba, Achilles; Narang, Pratibha; Giraldo, Jorge; Zamudio, Carlos; Joloba, Moses; Narang, Rahul; Paramasivan, C. N.; Hillemann, Doris; Nabeta, Pamela; Amisano, Danielle; Alland, David; Cobelens, Frank; Boehme, Catharina C.

In: Journal of clinical microbiology, Vol. 54, No. 8, 01.08.2016, p. 1984-1991.

Research output: Contribution to journalArticle

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T1 - Feasibility and operational performance of tuberculosis detection by loop-mediated isothermal amplification platform in decentralized settings

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AU - Gray, Christen M.

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AU - Giraldo, Jorge

AU - Zamudio, Carlos

AU - Joloba, Moses

AU - Narang, Rahul

AU - Paramasivan, C. N.

AU - Hillemann, Doris

AU - Nabeta, Pamela

AU - Amisano, Danielle

AU - Alland, David

AU - Cobelens, Frank

AU - Boehme, Catharina C.

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N2 - 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.

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