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 language | English (US) |
---|---|
Pages (from-to) | 979-991 |
Number of pages | 13 |
Journal | Nature Biomedical Engineering |
Volume | 6 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2022 |
Keywords
- Animals
- Cohort Studies
- Extracellular Vesicles
- Humans
- Mycobacterium tuberculosis
- Tuberculosis/diagnosis
- Virulence Factors
ASJC Scopus subject areas
- Bioengineering
- Biotechnology
- Biomedical Engineering
- Medicine (miscellaneous)
- Computer Science Applications