Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples
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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 19, 2022
- Source ID
- 10.1038/s41551-022-00922-1
Entities
People
- Alistair J Ramsay
- Bo Ning
- Bofan Song
- Carlos Vergara
- Charles D. Mitchell
- Chenzhong Li
- Christine M. Bojanowski
- Christopher J. Lyon
- Dalton C. Wamalwa
- Deepak Kaushal
- Dhiraj Kumar Singh
- Duc T Nguyen
- Duran Bao
- Eddy Pérez-then
- Edward A Graviss
- Elizabeth Maleche-obimbo
- Fangfang Zhang
- Grace John-Stewart
- Ha Phan
- Irene Njuguna
- Jaclyn N. Escudero
- Jia Fan
- Joshua Stern
- Juan Olivo
- Lili Zhang
- Lisa M. Cranmer
- Mayank Khanna
- Nhung Nguyen
- Rongguang Liang
- Shaobai Li
- Shu Wang
- Sylvia M. Lacourse
- Tony Y. Hu
- Wenshu Zheng
- Yang Li
- Yating Xiao
- Zhen Huang
Organizations
- Division of Cancer Prevention, National Cancer Institute
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute of Allergy and Infectious Diseases
- United States Department of Defense