Diagnostic performance of tuberculosis-specific IgG antibody profiles in patients with presumptive tuberculosis from two continents.

Background Developing rapid diagnostic tests for tuberculosis (TB) is a global priority. A whole proteome screen identified M. tuberculosis antigens associated with serological responses in TB patients. We used WHO target product profile criteria for a detection test and a triage test to evaluate these antigens in a field-based assay and a reference bead-based assay. Methods Consecutive patients presenting to microscopy centers and district hospitals in Peru and to outpatient clinics at a TB reference center in Vietnam, were recruited. We tested blood samples from 755 HIV-uninfected adults with presumptive pulmonary TB to measure IgG antibody responses to 57 M. tuberculosis antigens using a field-based multiplexed serological assay and a 132-antigen reference assay. We evaluated single antigen performance, and models of all possible three-antigen combinations and multi-antigen combinations. Results Three-antigen and multi-antigen models performed similarly, and were superior to single antigens. With specificity set at 90% for a detection test, the best sensitivity of a three-antigen model was 35% (95% CI 31-40). With sensitivity set at 85% for a triage test, the specificity of the best three-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 TB, no single antigen or multi-antigen set performance approached WHO target product profile criteria for clinical utility among HIV-uninfected adults with presumed TB in high-volume, urban settings in TB endemic countries.