Abstract
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. 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. 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. 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.
Highlights
Development of rapid diagnostic tests for tuberculosis is a global priority
With sensitivity set at 85% for a triage test, the specificity of the best 3-antigen model was 34%
M. tuberculosis antigens were recognized by the immunoglobulin G (IgG) response during tuberculosis, no single antigen or multiantigen set performance approached World Health Organization (WHO) target product profile (TPP) criteria for clinical utility among Human immunodeficiency virus (HIV)-uninfected adults with presumed tuberculosis in high-volume, urban settings in tuberculosis-endemic countries
Summary
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. Adults who presented to ambulatory healthcare centers with symptoms suggestive of pulmonary tuberculosis in Peru and Vietnam were consecutively enrolled in the study. The site in Peru is a research institute in Lima that recruits patients from microscopy centers and district hospitals in a high tuberculosis prevalence area. The site in Vietnam is a tuberculosis and lung disease reference center in Ho Chi Minh City that recruits patients from its outpatient clinic. Recruitment was done in 2 phases: phase 1 was used to validate the field-based MBio platform against the reference assay before proceeding to the larger phase 2
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