title: Feasibility and Operational Performance of Tuberculosis Detection by Loop-Mediated Isothermal Amplification Platform in Decentralized Settings: Results from a Multicenter Study.
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.
authors.affiliation: Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland.
authors.forename: Christen M
authors.initials: CM
authors.lastname: Gray
authors.affiliation: Makerere University College of Health Science, Kampala, Uganda.
authors.forename: Achilles
authors.initials: A
authors.lastname: Katamba
authors.affiliation: Mahatma Gandhi Institute of Medical Sciences, Sevagram, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Narang
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Giraldo
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Carlos
authors.initials: C
authors.lastname: Zamudio
authors.affiliation: The National TB Reference Laboratory, Kampala, Uganda.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Mahatma Gandhi Institute of Medical Sciences, Sevagram, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Narang
authors.affiliation: FIND India, New Delhi, India.
authors.forename: C N
authors.initials: CN
authors.lastname: Paramasivan
authors.affiliation: Forschungszentrum Borstel, National Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Hillemann
authors.affiliation: Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland.
authors.forename: Pamela
authors.initials: P
authors.lastname: Nabeta
authors.affiliation: Department of Medicine and Center for Emerging Pathogens, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Amisano
authors.affiliation: Department of Medicine and Center for Emerging Pathogens, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: David
authors.initials: D
authors.lastname: Alland
authors.affiliation: Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, Netherlands KNCV Tuberculosis Foundation, The Hague, Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Cobelens
authors.affiliation: Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland catharina.boehme@finddx.org.
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Boehme
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D010568:Peru; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000175:diagnosis*; D014454:Uganda; D055815:Young Adult