@article{4864514c67244f678736abb0e5dec4bb,
title = "Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples",
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.",
keywords = "Animals, Cohort Studies, Extracellular Vesicles, Humans, Mycobacterium tuberculosis, Tuberculosis/diagnosis, Virulence Factors",
author = "Wenshu Zheng and LaCourse, {Sylvia M.} and Bofan Song and Singh, {Dhiraj Kumar} and Mayank Khanna and Juan Olivo and Joshua Stern and Escudero, {Jaclyn N.} and Carlos Vergara and Fangfang Zhang and Shaobai Li and Shu Wang and Cranmer, {Lisa M.} and Zhen Huang and Bojanowski, {Christine M.} and Duran Bao and Irene Njuguna and Yating Xiao and Wamalwa, {Dalton C.} and Nguyen, {Duc T.} and Li Yang and Elizabeth Maleche-Obimbo and Nhung Nguyen and Lili Zhang and Ha Phan and Jia Fan and Bo Ning and Chenzhong Li and Lyon, {Christopher J.} and Graviss, {Edward A.} and Grace John-Stewart and Mitchell, {Charles D.} and Ramsay, {Alistair J.} and Deepak Kaushal and Rongguang Liang and Eddy P{\'e}rez-Then and Hu, {Tony Y.}",
note = "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. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = aug,
doi = "10.1038/s41551-022-00922-1",
language = "English (US)",
volume = "6",
pages = "979--991",
journal = "Nature Biomedical Engineering",
issn = "2157-846X",
publisher = "Nature Publishing Group",
number = "8",
}