Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples
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Published:2022-08-19
Issue:8
Volume:6
Page:979-991
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ISSN:2157-846X
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Container-title:Nature Biomedical Engineering
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language:en
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Short-container-title:Nat. Biomed. Eng
Author:
Zheng Wenshu, LaCourse Sylvia M., Song Bofan, Singh Dhiraj KumarORCID, Khanna Mayank, Olivo Juan, Stern Joshua, Escudero Jaclyn N., Vergara Carlos, Zhang Fangfang, Li Shaobai, Wang Shu, Cranmer Lisa M.ORCID, Huang ZhenORCID, Bojanowski Christine M., Bao Duran, Njuguna Irene, Xiao Yating, Wamalwa Dalton C., Nguyen Duc T.ORCID, Yang Li, Maleche-Obimbo Elizabeth, Nguyen Nhung, Zhang Lili, Phan Ha, Fan Jia, Ning Bo, Li Chenzhong, Lyon Christopher J., Graviss Edward A.ORCID, John-Stewart GraceORCID, Mitchell Charles D., Ramsay Alistair J.ORCID, Kaushal Deepak, Liang Rongguang, Pérez-Then Eddy, Hu Tony Y.ORCID
Abstract
AbstractSensitive 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 twoMycobacterium tuberculosisvirulence 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.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases Division of Cancer Prevention, National Cancer Institute U.S. Department of Defense
Publisher
Springer Science and Business Media LLC
Subject
Computer Science Applications,Biomedical Engineering,Medicine (miscellaneous),Bioengineering,Biotechnology
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