Charles D Mitchell1, Tony Y Hu2, Liyan Mao3,4, Sylvia M LaCourse5, Soyeon Kim6, Chang Liu7, Bo Ning3, Duran Bao3, Jia Fan3, Christopher J Lyon3, Ziyong Sun4, Sharon Nachman8. 1. Department of Pediatrics, Division of Infectious Diseases and Immunology, University of Miami Miller School of Medicine, Batchelor Children's Research Institute, Room 286, 1580 NW 10th Avenue, Miami, FL, 33136, USA. cmitchel@med.miami.edu. 2. Center for Cellular and Molecular Diagnostics, Biochemistry and Molecular Biology, Tulane University School of Medicine, Room 474, 333 S. Liberty Street, New Orleans, LA, 70112, USA. tonyhu@tulane.edu. 3. Center for Cellular and Molecular Diagnostics, Biochemistry and Molecular Biology, Tulane University School of Medicine, Room 474, 333 S. Liberty Street, New Orleans, LA, 70112, USA. 4. Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 5. Departments of Medicine and Global Health, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, 98104, USA. 6. Frontier Science Foundation, Brookline, MA, 02115, USA. 7. Department of Chemical Engineering, Biomedical Engineering Program, University of South Carolina, Columbia, SC, 29208, USA. 8. Department of Pediatrics, State University of New York at Stony Brook, Stony Brook, NY, 11794, USA.
Abstract
BACKGROUND: Non-sputum methods are urgently needed to improve tuberculosis diagnosis and treatment monitoring in children. This study evaluated the ability of a serum assay quantifying a species-specific peptide of the Mycobacterium tuberculosis CFP-10 virulence factor via nanotechnology and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to diagnose tuberculosis in HIV-infected and HIV-uninfected infants. METHODS:Serum CFP-10 peptide signal was blinded evaluated in cryopreserved sera of 519 BCG-immunized, HIV-exposed infants (284 HIV-infected, 235 HIV-uninfected) from a multi-center randomizedplacebo-controlled isoniazid prophylaxistrial conducted in southern Africa between 2004 and 2008, who were followed up to 192 weeks for Mtb infection and TB. Children were classified as confirmed, unconfirmed, or unlikely tuberculosis cases using 2015 NIH diagnostic criteria for pediatric TB. RESULTS: In HIV-infected infants, CFP-10 signal had 100% sensitivity for confirmed TB (5/5, 95% CI, 47.8-100) and 83.7% sensitivity for unconfirmed TB (36/43, 95% CI 69.3-93.2), with 93.1% specificity (203/218, 95% CI 88.9-96.1). In HIV-uninfected infants, CFP-10 signal detected the single confirmed TB case and 75.0% of unconfirmed TB cases (15/20; 95% CI 50.9-91.3), with 96.2% specificity (177/184, 95% CI, 92.3-98.5). Serum CFP-10 achieved 77% diagnostic sensitivity for confirmed and unconfirmed TB (13/17, 95% CI, 50-93%) at ≤ 24 weeks pre-diagnosis, and both CFP-10-positivity and concentration declined following anti-TB therapy initiation. CONCLUSIONS: Serum CFP-10 signal exhibited high diagnostic sensitivity and specificity for tuberculosis in HIV-infected and HIV-uninfected infants and potential utility for early TB detection and monitoring of anti-TB treatment responses.
RCT Entities:
BACKGROUND: Non-sputum methods are urgently needed to improve tuberculosis diagnosis and treatment monitoring in children. This study evaluated the ability of a serum assay quantifying a species-specific peptide of the Mycobacterium tuberculosisCFP-10 virulence factor via nanotechnology and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to diagnose tuberculosis in HIV-infected and HIV-uninfected infants. METHODS: Serum CFP-10 peptide signal was blinded evaluated in cryopreserved sera of 519 BCG-immunized, HIV-exposed infants (284 HIV-infected, 235 HIV-uninfected) from a multi-center randomized placebo-controlled isoniazid prophylaxis trial conducted in southern Africa between 2004 and 2008, who were followed up to 192 weeks for Mtb infection and TB. Children were classified as confirmed, unconfirmed, or unlikely tuberculosis cases using 2015 NIH diagnostic criteria for pediatric TB. RESULTS: In HIV-infectedinfants, CFP-10 signal had 100% sensitivity for confirmed TB (5/5, 95% CI, 47.8-100) and 83.7% sensitivity for unconfirmed TB (36/43, 95% CI 69.3-93.2), with 93.1% specificity (203/218, 95% CI 88.9-96.1). In HIV-uninfected infants, CFP-10 signal detected the single confirmed TB case and 75.0% of unconfirmed TB cases (15/20; 95% CI 50.9-91.3), with 96.2% specificity (177/184, 95% CI, 92.3-98.5). Serum CFP-10 achieved 77% diagnostic sensitivity for confirmed and unconfirmed TB (13/17, 95% CI, 50-93%) at ≤ 24 weeks pre-diagnosis, and both CFP-10-positivity and concentration declined following anti-TB therapy initiation. CONCLUSIONS: Serum CFP-10 signal exhibited high diagnostic sensitivity and specificity for tuberculosis in HIV-infected and HIV-uninfected infants and potential utility for early TB detection and monitoring of anti-TB treatment responses.
Entities:
Keywords:
CFP-10; Mass spectrometry; Nanotechnology; Pediatric tuberculosis
Authors: Arturo Plascencia Hernández; Rodrigo M González Sánchez; Iván I Hernández Cañaveral; Antonio Luévanos Velázquez; Pedro A Martínez Arce; Alexander González Díaz; Manuel Sandoval Díaz; Yaxsier de Armas Rodríguez; Edilberto González Ochoa; Héctor Raúl Pérez Gómez Journal: PLoS One Date: 2022-03-10 Impact factor: 3.240