Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough...
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| Veröffentlicht in: | PloS one 2018-10, Vol.13 (10), p.e0206119-e0206119 |
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| creator | 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 |
| description | Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy.
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.
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.
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. |
| doi_str_mv | 10.1371/journal.pone.0206119 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0206119</identifier><identifier>PMID: 30352099</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Accuracy ; Adults ; Algorithms ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Blood ; C-reactive protein ; Chemokines ; Collaboration ; Cough ; Critical care ; Cytokines ; Diagnosis ; Diagnostic systems ; Diagnostic tests ; Epidemiology ; Health aspects ; Health screening ; HIV ; HIV patients ; Hospitals ; Human immunodeficiency virus ; Illnesses ; Infectious diseases ; Inflammation ; Interleukin 18 ; Interleukin 6 ; Laboratories ; Medical diagnosis ; Medicine ; Medicine and Health Sciences ; Microscopy ; Panels ; Patients ; Peripheral blood ; Proteins ; Public health ; Research and Analysis Methods ; Screening ; Sensitivity ; Smear ; Sputum ; Tuberculosis ; γ-Interferon</subject><ispartof>PloS one, 2018-10, Vol.13 (10), p.e0206119-e0206119</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Farr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Farr et al 2018 Farr et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-2a84b8d26d92d0754b6896db92aa39b65c1f3b2ab76a9b4c09eebc98ad0fa47d3</citedby><cites>FETCH-LOGICAL-c692t-2a84b8d26d92d0754b6896db92aa39b65c1f3b2ab76a9b4c09eebc98ad0fa47d3</cites><orcidid>0000-0003-3499-6419</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198956/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198956/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30352099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Farr, Katherine</creatorcontrib><creatorcontrib>Ravindran, Resmi</creatorcontrib><creatorcontrib>Strnad, Luke</creatorcontrib><creatorcontrib>Chang, Emily</creatorcontrib><creatorcontrib>Chaisson, Lelia H</creatorcontrib><creatorcontrib>Yoon, Christina</creatorcontrib><creatorcontrib>Worodria, William</creatorcontrib><creatorcontrib>Andama, Alfred</creatorcontrib><creatorcontrib>Ayakaka, Irene</creatorcontrib><creatorcontrib>Bbosa Nalwanga, Priscilla</creatorcontrib><creatorcontrib>Byanyima, Patrick</creatorcontrib><creatorcontrib>Kalema, Nelson</creatorcontrib><creatorcontrib>Kaswabuli, Sylvia</creatorcontrib><creatorcontrib>Katagira, Winceslaus</creatorcontrib><creatorcontrib>Aman, Kyomugisha Denise</creatorcontrib><creatorcontrib>Musisi, Emmanuel</creatorcontrib><creatorcontrib>Tumwine, Nuwagaba Wallen</creatorcontrib><creatorcontrib>Sanyu, Ingvar</creatorcontrib><creatorcontrib>Ssebunya, Robert</creatorcontrib><creatorcontrib>Davis, J Lucian</creatorcontrib><creatorcontrib>Huang, Laurence</creatorcontrib><creatorcontrib>Khan, Imran H</creatorcontrib><creatorcontrib>Cattamanchi, Adithya</creatorcontrib><title>Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy.
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.
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.
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.</description><subject>Accuracy</subject><subject>Adults</subject><subject>Algorithms</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>C-reactive protein</subject><subject>Chemokines</subject><subject>Collaboration</subject><subject>Cough</subject><subject>Critical care</subject><subject>Cytokines</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Diagnostic tests</subject><subject>Epidemiology</subject><subject>Health aspects</subject><subject>Health screening</subject><subject>HIV</subject><subject>HIV patients</subject><subject>Hospitals</subject><subject>Human immunodeficiency virus</subject><subject>Illnesses</subject><subject>Infectious diseases</subject><subject>Inflammation</subject><subject>Interleukin 18</subject><subject>Interleukin 6</subject><subject>Laboratories</subject><subject>Medical diagnosis</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Microscopy</subject><subject>Panels</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Proteins</subject><subject>Public health</subject><subject>Research and Analysis Methods</subject><subject>Screening</subject><subject>Sensitivity</subject><subject>Smear</subject><subject>Sputum</subject><subject>Tuberculosis</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0tv1DAQxyMEoqXwDRBEQkJw2MWP2LEvSFV5dKVKlXj0ak0cJ-vixFs7KfTb4-2m1Qb1gHywNf7Nfx72ZNlLjJaYlvjDpR9DD2658b1ZIoI4xvJRdoglJQtOEH28dz7InsV4iRCjgvOn2QFFlBEk5WFmP1loex8Hq_ONCY0PHfTa5L7JK-d9ndu-cdB1MPhwk3cQfpkQ84Tlw1iZoEfno4151MGY3vZt4pOO3ziTO3u9Nfy2wzo_XV08z5404KJ5Me1H2c8vn3-cnC7Ozr-uTo7PFppLMiwIiKISNeG1JDUqWVFxIXldSQJAZcWZxg2tCFQlB1kVGkljKi0F1KiBoqzpUfZ6p7tJqampS1ERTIqCUYxpIlY7ovZwqTbBprJulAerbg0-tApCaogzignZCKAMCNYFQwVA2TQCCdSUlGItktbHKdpYdabWph8CuJno_Ka3a9X6a8WxFJLxJPBuEgj-ajRxUJ2N2jgHvfHjbd6MSEkQSeibf9CHq5uoFlIB6fl8iqu3ouqYMclxSQVL1PIBKq3adFanL9XYZJ85vJ85JGYwf4YWxhjV6vu3_2fPL-bs2z12bcAN6-jdOFjfxzlY7EAdfIzBNPdNxkhtJ-KuG2o7EWqaiOT2av-B7p3uRoD-BVuxB1w</recordid><startdate>20181023</startdate><enddate>20181023</enddate><creator>Farr, 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Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Farr, Katherine</au><au>Ravindran, Resmi</au><au>Strnad, Luke</au><au>Chang, Emily</au><au>Chaisson, Lelia H</au><au>Yoon, Christina</au><au>Worodria, William</au><au>Andama, Alfred</au><au>Ayakaka, Irene</au><au>Bbosa Nalwanga, Priscilla</au><au>Byanyima, Patrick</au><au>Kalema, Nelson</au><au>Kaswabuli, Sylvia</au><au>Katagira, Winceslaus</au><au>Aman, Kyomugisha Denise</au><au>Musisi, Emmanuel</au><au>Tumwine, Nuwagaba Wallen</au><au>Sanyu, Ingvar</au><au>Ssebunya, Robert</au><au>Davis, J Lucian</au><au>Huang, Laurence</au><au>Khan, Imran H</au><au>Cattamanchi, Adithya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-10-23</date><risdate>2018</risdate><volume>13</volume><issue>10</issue><spage>e0206119</spage><epage>e0206119</epage><pages>e0206119-e0206119</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy.
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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30352099</pmid><doi>10.1371/journal.pone.0206119</doi><tpages>e0206119</tpages><orcidid>https://orcid.org/0000-0003-3499-6419</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-10, Vol.13 (10), p.e0206119-e0206119 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2124453113 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Accuracy Adults Algorithms Biological markers Biology and Life Sciences Biomarkers Blood C-reactive protein Chemokines Collaboration Cough Critical care Cytokines Diagnosis Diagnostic systems Diagnostic tests Epidemiology Health aspects Health screening HIV HIV patients Hospitals Human immunodeficiency virus Illnesses Infectious diseases Inflammation Interleukin 18 Interleukin 6 Laboratories Medical diagnosis Medicine Medicine and Health Sciences Microscopy Panels Patients Peripheral blood Proteins Public health Research and Analysis Methods Screening Sensitivity Smear Sputum Tuberculosis γ-Interferon |
| title | Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV |
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