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tonyhu@tulane.edu

W.Z. and T.Y.H. conceived the study, generated the hypotheses and designed the experiments. W.Z., F.Z., J.F., S.W., L.Z., D.B., L.Y., Y.X., B.N. and C.L. performed all the experiments and analysed the data. W.Z., C.J.L. and T.Y.H. wrote the manuscript. D.K., D.K.S., M.K. and A.J.R performed the P3 infection study. D.K. and D.K.S. conceived and designed the non-human primate study. B.S., S.L. and R.L. designed the portable device and the software for image processing. W.Z., C.J.L., S.M.L., J.S., J.N.E., Z.H. and T.Y.H. performed clinical experiments, and analysed and interpreted the clinical data. G.J.-S. and D.C.W. designed the parent PUSH trial study and obtained grant funding. I.N., L.M.C., D.C.W. and G.J.-S. developed the PUSH protocol and study. I.N., E.M.-O., D.C.W., L.M.C. and G.J.-S. assessed initial clinical data. J.S., I.N.N., L.M.C., S.M.L. and G.J.-S. analysed the primary trial data and/or subsequent TB diagnostic and clinical data. J.O., C.V., C.D.M., E.P.-T., E.A.G., D.T.N., N.N., H.P. and C.M.B. contributed to the clinical sample protocol for this study. All authors contributed to the writing of the manuscript and to its revision.

T.Y.H. and W.Z. have a provisional patent (‘Method of detecting TB in blood’) submitted through Tulane University. The rest of the authors declare no competing interests.

Subjects:

Research Funding:

This work was primarily supported by research funding from the National Institutes of Health (U01CA252965, R01HD090927, R01AI122932, R01AI113725, R21Al126361-01, W8IXWH1910926 and R01HD103511 to T.Y.H.; R03AI140977 to J.F.; and R01AI162152 to S.M.L.). Analysis regarding the PUSH cohort was funded by NIAID K23AI120793 (S.M.L.) and NIAID R21AI143341 (S.M.L.). The original PUSH cohort was funded by NICHD R01-HD023412 (G.J.-S.). The primate studies were funded by P51OD011133 (D.K. and D.K.S.), P51OD011104 (D.K.), U42OD10442 (D.K.), R01AI134245 (D.K.), R01IAI111914 (D.K.) and R01AI134240 (D.K. and D.K.S.). We thank L. Lewy for proofreading the manuscript.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Engineering
  • MYCOBACTERIUM-TUBERCULOSIS
  • LIPOARABINOMANNAN
  • SCATTERING
  • CHILDREN
  • CDC1551
  • ASSAY
  • CARE

Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples

Tools:

Journal Title:

NATURE BIOMEDICAL ENGINEERING

Volume:

Volume 6, Number 8

Publisher:

, Pages 979-+

Type of Work:

Article | Final Publisher PDF

Abstract:

Sensitive and specific blood-based assays for the detection of pulmonary and extrapulmonary tuberculosis would reduce mortality associated with missed diagnoses, particularly in children. Here we report a nanoparticle-enhanced immunoassay read by dark-field microscopy that detects two Mycobacterium tuberculosis virulence factors (the glycolipid lipoarabinomannan and its carrier protein) on the surface of circulating extracellular vesicles. In a cohort study of 147 hospitalized and severely immunosuppressed children living with HIV, the assay detected 58 of the 78 (74%) cases of paediatric tuberculosis, 48 of the 66 (73%) cases that were missed by microbiological assays, and 8 out of 10 (80%) cases undiagnosed during the study. It also distinguished tuberculosis from latent-tuberculosis infections in non-human primates. We adapted the assay to make it portable and operable by a smartphone. With further development, the assay may facilitate the detection of tuberculosis at the point of care, particularly in resource-limited settings.

Copyright information:

© The Author(s) 2022

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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