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

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. NguyenLi 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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)979-991
Number of pages13
JournalNature Biomedical Engineering
Volume6
Issue number8
DOIs
StatePublished - Aug 2022

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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