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Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda

BACKGROUND: Improved systematic screening of high-risk groups is a key component of the tuberculosis (TB) elimination strategy endorsed by the World Health Organization (WHO). We used a multiplex microbead immunoassay to measure antibody responses to 28 M. tuberculosis (M.tb) antigens, and assessed...

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Autores principales: Shete, Priya B., Ravindran, Resmi, Chang, Emily, Worodria, William, Chaisson, Lelia H., Andama, Alfred, Davis, J. Lucian, Luciw, Paul A., Huang, Laurence, Khan, Imran H., Cattamanchi, Adithya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540581/
https://www.ncbi.nlm.nih.gov/pubmed/28767658
http://dx.doi.org/10.1371/journal.pone.0180122
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author Shete, Priya B.
Ravindran, Resmi
Chang, Emily
Worodria, William
Chaisson, Lelia H.
Andama, Alfred
Davis, J. Lucian
Luciw, Paul A.
Huang, Laurence
Khan, Imran H.
Cattamanchi, Adithya
author_facet Shete, Priya B.
Ravindran, Resmi
Chang, Emily
Worodria, William
Chaisson, Lelia H.
Andama, Alfred
Davis, J. Lucian
Luciw, Paul A.
Huang, Laurence
Khan, Imran H.
Cattamanchi, Adithya
author_sort Shete, Priya B.
collection PubMed
description BACKGROUND: Improved systematic screening of high-risk groups is a key component of the tuberculosis (TB) elimination strategy endorsed by the World Health Organization (WHO). We used a multiplex microbead immunoassay to measure antibody responses to 28 M. tuberculosis (M.tb) antigens, and assessed whether combinations of antibody responses achieve accuracy thresholds required for a TB screening test. METHODS: A random selection of plasma samples obtained from consecutive HIV-negative adults who were admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks’ but <6 months’ duration were analyzed for serological response to 28 M.tb antigens using an in-house multiplex microbead immunoassay. We compared the median difference of the antibody response to each antigen between patients with and without culture-confirmed TB, ranked each antigen according to variable importance (VIM), and assessed the sensitivity and specificity of combinations of antibody responses using an advanced classification algorithm, SuperLearner. RESULTS: Among the 237 patients included in the analysis, 119 (50%) were female, median age was 32 years (IQR 25, 46), and 113 (48%) had TB. Median antibody levels to eight antigens were significantly different between patients with and without TB. A panel including eight of the top ranked antigens had a sensitivity of 90.6% (95% CI 89.4, 93.8) and a specificity of 88.6% (95% CI 78.2, 97.6) (Ag85B, Ag85A, Ag85C, Rv0934-P38, Rv3881, BfrB, Rv3873, and Rv2878c). With sensitivity constrained to be >90%, specificity remained close to 70% with as few as 3 antigens included in the panels. CONCLUSIONS: Measuring antibody responses to combinations of antigens could facilitate TB screening and should be further evaluated in populations being targeted for systematic screening.
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spelling pubmed-55405812017-08-12 Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda Shete, Priya B. Ravindran, Resmi Chang, Emily Worodria, William Chaisson, Lelia H. Andama, Alfred Davis, J. Lucian Luciw, Paul A. Huang, Laurence Khan, Imran H. Cattamanchi, Adithya PLoS One Research Article BACKGROUND: Improved systematic screening of high-risk groups is a key component of the tuberculosis (TB) elimination strategy endorsed by the World Health Organization (WHO). We used a multiplex microbead immunoassay to measure antibody responses to 28 M. tuberculosis (M.tb) antigens, and assessed whether combinations of antibody responses achieve accuracy thresholds required for a TB screening test. METHODS: A random selection of plasma samples obtained from consecutive HIV-negative adults who were admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks’ but <6 months’ duration were analyzed for serological response to 28 M.tb antigens using an in-house multiplex microbead immunoassay. We compared the median difference of the antibody response to each antigen between patients with and without culture-confirmed TB, ranked each antigen according to variable importance (VIM), and assessed the sensitivity and specificity of combinations of antibody responses using an advanced classification algorithm, SuperLearner. RESULTS: Among the 237 patients included in the analysis, 119 (50%) were female, median age was 32 years (IQR 25, 46), and 113 (48%) had TB. Median antibody levels to eight antigens were significantly different between patients with and without TB. A panel including eight of the top ranked antigens had a sensitivity of 90.6% (95% CI 89.4, 93.8) and a specificity of 88.6% (95% CI 78.2, 97.6) (Ag85B, Ag85A, Ag85C, Rv0934-P38, Rv3881, BfrB, Rv3873, and Rv2878c). With sensitivity constrained to be >90%, specificity remained close to 70% with as few as 3 antigens included in the panels. CONCLUSIONS: Measuring antibody responses to combinations of antigens could facilitate TB screening and should be further evaluated in populations being targeted for systematic screening. Public Library of Science 2017-08-02 /pmc/articles/PMC5540581/ /pubmed/28767658 http://dx.doi.org/10.1371/journal.pone.0180122 Text en © 2017 Shete et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shete, Priya B.
Ravindran, Resmi
Chang, Emily
Worodria, William
Chaisson, Lelia H.
Andama, Alfred
Davis, J. Lucian
Luciw, Paul A.
Huang, Laurence
Khan, Imran H.
Cattamanchi, Adithya
Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda
title Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda
title_full Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda
title_fullStr Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda
title_full_unstemmed Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda
title_short Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda
title_sort evaluation of antibody responses to panels of m. tuberculosis antigens as a screening tool for active tuberculosis in uganda
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540581/
https://www.ncbi.nlm.nih.gov/pubmed/28767658
http://dx.doi.org/10.1371/journal.pone.0180122
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