Abstract: Background: Tuberculosis (TB) infection was responsible for an estimated 1.3 million deaths in 2017. Better diagnostic tools are urgently needed. We sought to determine whether accurate TB antigen detection in blood or urine has the potential to meet the WHO target product profiles for detection of active TB.
Materials and Methods: We developed Electrochemiluminescence (ECL) immunoassays for Lipoarabinomannan (LAM) and ESAT-6 detection with detection limits in the pg/ml range and used them to compare the concentrations of the two antigens in the urine and serum of 81 HIV-negative and -positive individuals with presumptive TB enrolled across diverse geographic sites.
Results: LAM and ESAT-6 overall sensitivities in urine were 93% and 65% respectively. LAM and ESAT-6 overall sensitivities in serum were 55% and 46% respectively. Overall specificity was ≥97% in all assays. Sensitivities were higher in HIV-positive compared to HIV-negative patients for both antigens and both sample types, with signals roughly 10-fold higher on average in urine than in serum. The two antigens showed similar concentration ranges within the same sample type and correlated.
Conclusions: LAM and ESAT-6 can be detected in the urine and serum of TB patients, regardless of the HIV status and further gains in clinical sensitivity may be achievable through assay and reagent optimization. Accuracy in urine was higher with current methods and has the potential to meet the WHO accuracy target if the findings can be transferred to a point-of-care TB test.
Competing Interests: TB, CMD and EM are employed by FIND (Geneva, Switzerland), a nonprofit organization that collaborates with industry partners. GBS, MT, AM, TP, DB, and SB are employed by Meso Scale Diagnostics LLC (Rockville, USA) and received funding from FIND and NIH. MK and KK are employed by Otsuka Pharmaceutical Co., Ltd (Tokyo, Japan). FIND, MSD, and Otsuka provided support in the form of salaries for authors [TB, CMD, EM, GBS, MT, AM, TP, DB, SB, MK and KK], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. TB and AP report patents in the field of LAM detection. The interests of authors do not alter the adherence to PLOS ONE policies on sharing data and materials. (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) All other authors declare no competing interests.
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