title: Commercial serological antibody detection tests for the diagnosis of pulmonary tuberculosis: a systematic review.
abstract: BACKGROUND
  The global tuberculosis epidemic results in nearly 2 million deaths and 9 million new cases of the disease a year. The vast majority of tuberculosis patients live in developing countries, where the diagnosis of tuberculosis relies on the identification of acid-fast bacilli on unprocessed sputum smears using conventional light microscopy. Microscopy has high specificity in tuberculosis-endemic countries, but modest sensitivity which varies among laboratories (range 20% to 80%). Moreover, the sensitivity is poor for paucibacillary disease (e.g., pediatric and HIV-associated tuberculosis). Thus, the development of rapid and accurate new diagnostic tools is imperative. Immune-based tests are potentially suitable for use in low-income countries as some test formats can be performed at the point of care without laboratory equipment. Currently, dozens of distinct commercial antibody detection tests are sold in developing countries. The question is "do they work?"
  
  
  RESULTS
  We conducted a systematic review to assess the accuracy of commercial antibody detection tests for the diagnosis of pulmonary tuberculosis. Studies from all countries using culture and/or microscopy smear for confirmation of pulmonary tuberculosis were eligible. Studies with fewer than 50 participants (25 patients and 25 control participants) were excluded. In a comprehensive search, we identified 68 studies. The results demonstrate that (1) overall, commercial tests vary widely in performance; (2) sensitivity is higher in smear-positive than smear-negative samples; (3) in studies of smear-positive patients, Anda-TB IgG by enzyme-linked immunosorbent assay shows limited sensitivity (range 63% to 85%) and inconsistent specificity (range 73% to 100%); (4) specificity is higher in healthy volunteers than in patients in whom tuberculosis disease is initially suspected and subsequently ruled out; and (5) there are insufficient data to determine the accuracy of most commercial tests in smear microscopy-negative patients, as well as their performance in children or persons with HIV infection.
  
  
  CONCLUSIONS
  None of the commercial tests evaluated perform well enough to replace sputum smear microscopy. Thus, these tests have little or no role in the diagnosis of pulmonary tuberculosis. Lack of methodological rigor in these studies was identified as a concern. It will be important to review the basic science literature evaluating serological tests for the diagnosis of pulmonary tuberculosis to determine whether useful antigens have been described but their potential has not been fully exploited. Activities leading to the discovery of new antigens with immunodiagnostic potential need to be intensified.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, California, United States of America.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Steingart
authors.forename: Megan
authors.initials: M
authors.lastname: Henry
authors.forename: Suman
authors.initials: S
authors.lastname: Laal
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hopewell
authors.forename: Andrew
authors.initials: A
authors.lastname: Ramsay
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
authors.forename: Jane
authors.initials: J
authors.lastname: Cunningham
authors.forename: Karin
authors.initials: K
authors.lastname: Weldingh
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
mesh_terms: D000328:Adult; D000372:Agglutination Tests; D000907:Antibodies, Bacterial / Q000097:blood*; D001793:Blood Preservation; D015153:Blotting, Western; D002648:Child; D015897:Comorbidity; D003906:Developing Countries; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D015658:HIV Infections / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007616:Kaolin; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D011237:Predictive Value of Tests; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D012107:Research Design; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D011933:Reagent Kits, Diagnostic; D007616:Kaolin