title: The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Helse Nord Tuberculosis Initiative, Department of Microbiology, College of Medicine, Blantyre, Malawi.|Malawi-Liverpool-Welcome Trust Clinical Research Programme, Blantyre, Malawi.|Clinical Research Department, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom.
authors.forename: Marriott
authors.initials: M
authors.lastname: Nliwasa
authors.affiliation: Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom.|Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: MacPherson
authors.affiliation: Department of Surgery, College of Medicine, Blantyre, Malawi.
authors.forename: Palesa
authors.initials: P
authors.lastname: Chisala
authors.affiliation: Helse Nord Tuberculosis Initiative, Department of Microbiology, College of Medicine, Blantyre, Malawi.|Malawi-Liverpool-Welcome Trust Clinical Research Programme, Blantyre, Malawi.
authors.forename: Mercy
authors.initials: M
authors.lastname: Kamdolozi
authors.affiliation: Malawi-Liverpool-Welcome Trust Clinical Research Programme, Blantyre, Malawi.
authors.forename: McEwen
authors.initials: M
authors.lastname: Khundi
authors.affiliation: Helse Nord Tuberculosis Initiative, Department of Microbiology, College of Medicine, Blantyre, Malawi.
authors.forename: Kruger
authors.initials: K
authors.lastname: Kaswaswa
authors.affiliation: Helse Nord Tuberculosis Initiative, Department of Microbiology, College of Medicine, Blantyre, Malawi.
authors.forename: Mphatso
authors.initials: M
authors.lastname: Mwapasa
authors.affiliation: Helse Nord Tuberculosis Initiative, Department of Microbiology, College of Medicine, Blantyre, Malawi.
authors.forename: Chisomo
authors.initials: C
authors.lastname: Msefula
authors.affiliation: Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Canada.
authors.forename: Hojoon
authors.initials: H
authors.lastname: Sohn
authors.affiliation: Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Flach
authors.affiliation: Helse Nord Tuberculosis Initiative, Department of Microbiology, College of Medicine, Blantyre, Malawi.|Malawi-Liverpool-Welcome Trust Clinical Research Programme, Blantyre, Malawi.|Clinical Research Department, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Corbett
mesh_terms: D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D003371:Cough / Q000150:complications*; D005260:Female; D015658:HIV Infections / Q000175:diagnosis; D006801:Humans; D008295:Malawi; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000191:economics / Q000379:methods*; D011933:Reagent Kits, Diagnostic / Q000191:economics; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000150:complications* / Q000175:diagnosis* / Q000191:economics; D055815:Young Adult
chemical_list: D011933:Reagent Kits, Diagnostic