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

Autor: Wenshu Zheng, Sylvia M. LaCourse, Bofan Song, Dhiraj Kumar Singh, Mayank Khanna, Juan Olivo, Joshua Stern, Jaclyn N. Escudero, Carlos Vergara, Fangfang Zhang, Shaobai Li, Shu Wang, Lisa M. Cranmer, Zhen Huang, Christine M. Bojanowski, Duran Bao, Irene Njuguna, Yating Xiao, Dalton C. Wamalwa, Duc T. Nguyen, Li Yang, Elizabeth Maleche-Obimbo, Nhung Nguyen, Lili Zhang, Ha Phan, Jia Fan, Bo Ning, Chenzhong Li, Christopher J. Lyon, Edward A. Graviss, Grace John-Stewart, Charles D. Mitchell, Alistair J. Ramsay, Deepak Kaushal, Rongguang Liang, Eddy Pérez-Then, Tony Y. Hu
Rok vydání: 2022
Předmět:
Zdroj: Nature Biomedical Engineering. 6:979-991
ISSN: 2157-846X
Popis: 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 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.
Databáze: OpenAIRE