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Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV

BACKGROUND: Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. METHODS: Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and Ju...

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Autores principales: Farr, Katherine, Ravindran, Resmi, Strnad, Luke, Chang, Emily, Chaisson, Lelia H., Yoon, Christina, Worodria, William, Andama, Alfred, Ayakaka, Irene, Bbosa Nalwanga, Priscilla, Byanyima, Patrick, Kalema, Nelson, Kaswabuli, Sylvia, Katagira, Winceslaus, Aman, Kyomugisha Denise, Musisi, Emmanuel, Tumwine, Nuwagaba Wallen, Sanyu, Ingvar, Ssebunya, Robert, Davis, J. Lucian, Huang, Laurence, Khan, Imran H., Cattamanchi, Adithya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198956/
https://www.ncbi.nlm.nih.gov/pubmed/30352099
http://dx.doi.org/10.1371/journal.pone.0206119
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author Farr, Katherine
Ravindran, Resmi
Strnad, Luke
Chang, Emily
Chaisson, Lelia H.
Yoon, Christina
Worodria, William
Andama, Alfred
Ayakaka, Irene
Bbosa Nalwanga, Priscilla
Byanyima, Patrick
Kalema, Nelson
Kaswabuli, Sylvia
Katagira, Winceslaus
Aman, Kyomugisha Denise
Musisi, Emmanuel
Tumwine, Nuwagaba Wallen
Sanyu, Ingvar
Ssebunya, Robert
Davis, J. Lucian
Huang, Laurence
Khan, Imran H.
Cattamanchi, Adithya
author_facet Farr, Katherine
Ravindran, Resmi
Strnad, Luke
Chang, Emily
Chaisson, Lelia H.
Yoon, Christina
Worodria, William
Andama, Alfred
Ayakaka, Irene
Bbosa Nalwanga, Priscilla
Byanyima, Patrick
Kalema, Nelson
Kaswabuli, Sylvia
Katagira, Winceslaus
Aman, Kyomugisha Denise
Musisi, Emmanuel
Tumwine, Nuwagaba Wallen
Sanyu, Ingvar
Ssebunya, Robert
Davis, J. Lucian
Huang, Laurence
Khan, Imran H.
Cattamanchi, Adithya
author_sort Farr, Katherine
collection PubMed
description BACKGROUND: Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. METHODS: Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough ≥ 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to ≥ 90% as recommended for TB screening. RESULTS: The median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4–49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7–53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients. CONCLUSIONS: Direct measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common.
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spelling pubmed-61989562018-11-19 Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV Farr, Katherine Ravindran, Resmi Strnad, Luke Chang, Emily Chaisson, Lelia H. Yoon, Christina Worodria, William Andama, Alfred Ayakaka, Irene Bbosa Nalwanga, Priscilla Byanyima, Patrick Kalema, Nelson Kaswabuli, Sylvia Katagira, Winceslaus Aman, Kyomugisha Denise Musisi, Emmanuel Tumwine, Nuwagaba Wallen Sanyu, Ingvar Ssebunya, Robert Davis, J. Lucian Huang, Laurence Khan, Imran H. Cattamanchi, Adithya PLoS One Research Article BACKGROUND: Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. METHODS: Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough ≥ 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to ≥ 90% as recommended for TB screening. RESULTS: The median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4–49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7–53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients. CONCLUSIONS: Direct measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common. Public Library of Science 2018-10-23 /pmc/articles/PMC6198956/ /pubmed/30352099 http://dx.doi.org/10.1371/journal.pone.0206119 Text en © 2018 Farr 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
Farr, Katherine
Ravindran, Resmi
Strnad, Luke
Chang, Emily
Chaisson, Lelia H.
Yoon, Christina
Worodria, William
Andama, Alfred
Ayakaka, Irene
Bbosa Nalwanga, Priscilla
Byanyima, Patrick
Kalema, Nelson
Kaswabuli, Sylvia
Katagira, Winceslaus
Aman, Kyomugisha Denise
Musisi, Emmanuel
Tumwine, Nuwagaba Wallen
Sanyu, Ingvar
Ssebunya, Robert
Davis, J. Lucian
Huang, Laurence
Khan, Imran H.
Cattamanchi, Adithya
Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
title Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
title_full Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
title_fullStr Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
title_full_unstemmed Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
title_short Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
title_sort diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with hiv
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198956/
https://www.ncbi.nlm.nih.gov/pubmed/30352099
http://dx.doi.org/10.1371/journal.pone.0206119
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