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Clin Infect Dis. 2017 Apr 1;64(7):947-955. doi: 10.1093/cid/cix023.

Diagnostic Performance of Tuberculosis-Specific IgG Antibody Profiles in Patients with Presumptive Tuberculosis from Two Continents.

Author information

1
FIND, Geneva, Switzerland.
2
Section of Paediatrics, Imperial College London, United Kingdom.
3
Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
4
MBio Diagnostics Inc., Boulder, Colorado.
5
Department of Philosophy, Carnegie Mellon University, Pittsburgh, Pennsylvania.
6
Lionex GmbH, Braunschweig, Germany.
7
Statens Serum Institut, Copenhagen, Denmark.
8
Public Health Research Institute, Rutgers New Jersey Medical School, New Brunswick.

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.

KEYWORDS:

antibodies; biomarkers; diagnosis; serologic tests; tuberculosis

PMID:
28362937
PMCID:
PMC5848306
DOI:
10.1093/cid/cix023
[Indexed for MEDLINE]
Free PMC Article

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