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.