Sensitive electrochemiluminescence (ECL) immunoassays for detecting lipoarabinomannan (LAM) and ESAT-6 in urine and serum from tuberculosis patients

Tobias Broger, Michael Tsionksy, Anu Mathew, Todd L. Lowary, Abraham Pinter, Tatiana Plisova, Daniel Bartlett, Simone Barbero, Claudia M. Denkinger, Emmanuel Moreau, Kiyonori Katsuragi, Masanori Kawasaki, Payam Nahid, George B. Sigal

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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.

Original languageEnglish (US)
Article numbere0215443
JournalPloS one
Volume14
Issue number4
DOIs
StatePublished - Apr 2019

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Broger, T., Tsionksy, M., Mathew, A., Lowary, T. L., Pinter, A., Plisova, T., Bartlett, D., Barbero, S., Denkinger, C. M., Moreau, E., Katsuragi, K., Kawasaki, M., Nahid, P., & Sigal, G. B. (2019). Sensitive electrochemiluminescence (ECL) immunoassays for detecting lipoarabinomannan (LAM) and ESAT-6 in urine and serum from tuberculosis patients. PloS one, 14(4), [e0215443]. https://doi.org/10.1371/journal.pone.0215443