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 - 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.
UR - https://www.scopus.com/pages/publications/85136620171
UR - https://www.scopus.com/pages/publications/85136620171#tab=citedBy
U2 - 10.1038/s41551-022-00922-1
DO - 10.1038/s41551-022-00922-1
M3 - Article
C2 - 35986185
AN - SCOPUS:85136620171
SN - 2157-846X
VL - 6
SP - 979
EP - 991
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 8
ER -