TY - JOUR
T1 - Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples
AU - Zheng, Wenshu
AU - LaCourse, Sylvia M.
AU - Song, Bofan
AU - Singh, Dhiraj Kumar
AU - Khanna, Mayank
AU - Olivo, Juan
AU - Stern, Joshua
AU - Escudero, Jaclyn N.
AU - Vergara, Carlos
AU - Zhang, Fangfang
AU - Li, Shaobai
AU - Wang, Shu
AU - Cranmer, Lisa M.
AU - Huang, Zhen
AU - Bojanowski, Christine M.
AU - Bao, Duran
AU - Njuguna, Irene
AU - Xiao, Yating
AU - Wamalwa, Dalton C.
AU - Nguyen, Duc T.
AU - Yang, Li
AU - Maleche-Obimbo, Elizabeth
AU - Nguyen, Nhung
AU - Zhang, Lili
AU - Phan, Ha
AU - Fan, Jia
AU - Ning, Bo
AU - Li, Chenzhong
AU - Lyon, Christopher J.
AU - Graviss, Edward A.
AU - John-Stewart, Grace
AU - Mitchell, Charles D.
AU - Ramsay, Alistair J.
AU - Kaushal, Deepak
AU - Liang, Rongguang
AU - Pérez-Then, Eddy
AU - Hu, Tony Y.
N1 - 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:
© 2022, The Author(s).
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85136620171&partnerID=8YFLogxK
U2 - 10.1038/s41551-022-00922-1
DO - 10.1038/s41551-022-00922-1
M3 - Article
C2 - 35986185
AN - SCOPUS:85136620171
VL - 6
SP - 979
EP - 991
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
SN - 2157-846X
IS - 8
ER -