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

• Type of Material: Article
• Authors: Wenshu Zheng, Tulane University; Sylvia M. LaCourse, University of Washington; Bofan Song, University of Arizona; Dhiraj Kumar Singh, Texas Biomedical Research Institute; Mayak Khanna, Louisiana State University; Juan Olivo, O&M Medical School; Joshua Stern, University of Washington; Jaclyn N. Escudero, University of Washington; Lisa Cranmer, Emory University; Tony Y. Hu, Tulane University
• Language: English
• Date: 2022-08-01
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41551-022-00922-1
• Title of Journal or Parent Work: NATURE BIOMEDICAL ENGINEERING
• Volume: 6
• Issue: 8
• Start Page: 979
• End Page: +
• Grant/Funding Information: 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: Engineering, Biomedical; SCATTERING; Technology; CHILDREN; LIPOARABINOMANNAN; CARE; Engineering; MYCOBACTERIUM-TUBERCULOSIS; ASSAY; CDC1551; Science & Technology
• Research Categories: Health Sciences, Public Health; Engineering, Biomedical

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.