title: Diagnostic Performance of Tuberculosis-Specific IgG Antibody Profiles in Patients with Presumptive Tuberculosis from Two Continents.
abstract: BACKGROUND
  Development of rapid diagnostic tests for tuberculosis is a global priority. A whole proteome screen identified Mycobacterium tuberculosis antigens associated with serological responses in tuberculosis patients. We used World Health Organization (WHO) target product profile (TPP) criteria for a detection test and triage test to evaluate these antigens.
  
  
  METHODS
  Consecutive patients presenting to microscopy centers and district hospitals in Peru and to outpatient clinics at a tuberculosis reference center in Vietnam were recruited. We tested blood samples from 755 HIV-uninfected adults with presumptive pulmonary tuberculosis to measure IgG antibody responses to 57 M. tuberculosis antigens using a field-based multiplexed serological assay and a 132-antigen bead-based reference assay. We evaluated single antigen performance and models of all possible 3-antigen combinations and multiantigen combinations.
  
  
  RESULTS
  Three-antigen and multiantigen models performed similarly and were superior to single antigens. With specificity set at 90% for a detection test, the best sensitivity of a 3-antigen model was 35% (95% confidence interval [CI], 31-40). With sensitivity set at 85% for a triage test, the specificity of the best 3-antigen model was 34% (95% CI, 29-40). The reference assay also did not meet study targets. Antigen performance differed significantly between the study sites for 7/22 of the best-performing antigens.
  
  
  CONCLUSIONS
  Although M. tuberculosis antigens were recognized by the IgG response during tuberculosis, no single antigen or multiantigen set performance approached WHO TPP criteria for clinical utility among HIV-uninfected adults with presumed tuberculosis in high-volume, urban settings in tuberculosis-endemic countries.
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Broger
authors.affiliation: Section of Paediatrics, Imperial College London, United Kingdom.
authors.forename: Robindra
authors.initials: R
authors.lastname: Basu Roy
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Filomena
authors.affiliation: MBio Diagnostics Inc., Boulder, Colorado.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Greef
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rimmele
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: Joshua
authors.initials: J
authors.lastname: Havumaki
authors.affiliation: Department of Philosophy, Carnegie Mellon University, Pittsburgh, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Danks
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schneiderhan-Marra
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: Christen M
authors.initials: CM
authors.lastname: Gray
authors.affiliation: Lionex GmbH, Braunschweig, Germany.
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Rosenkrands
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.affiliation: MBio Diagnostics Inc., Boulder, Colorado.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Husar
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Joos
authors.affiliation: Public Health Research Institute, Rutgers New Jersey Medical School, New Brunswick.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Gennaro
authors.affiliation: MBio Diagnostics Inc., Boulder, Colorado.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lochhead
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Denkinger
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Perkins
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010568:Peru; D015203:Reproducibility of Results; D012698:Serologic Tests / Q000379:methods / Q000592:standards; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D007074:Immunoglobulin G; C072681:Mycobacterium tuberculosis antigens
keywords: antibodies; biomarkers; diagnosis; serologic tests; tuberculosis