Evaluation of a serum-based antigen test for tuberculosis in HIV-exposed infants: a diagnostic accuracy study

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-...

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Veröffentlicht in:BMC medicine 2021-05, Vol.19 (1), p.113-113, Article 113
Hauptverfasser: Mao, Liyan, LaCourse, Sylvia M., Kim, Soyeon, Liu, Chang, Ning, Bo, Bao, Duran, Fan, Jia, Lyon, Christopher J., Sun, Ziyong, Nachman, Sharon, Mitchell, Charles D., Hu, Tony Y.
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container_end_page 113
container_issue 1
container_start_page 113
container_title BMC medicine
container_volume 19
creator Mao, Liyan
LaCourse, Sylvia M.
Kim, Soyeon
Liu, Chang
Ning, Bo
Bao, Duran
Fan, Jia
Lyon, Christopher J.
Sun, Ziyong
Nachman, Sharon
Mitchell, Charles D.
Hu, Tony Y.
description 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 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-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
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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 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-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 &lt;= 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.</description><identifier>ISSN: 1741-7015</identifier><identifier>EISSN: 1741-7015</identifier><identifier>DOI: 10.1186/s12916-021-01983-w</identifier><identifier>PMID: 34001096</identifier><language>eng</language><publisher>LONDON: Springer Nature</publisher><subject>Antigens ; Antigens, Bacterial ; Biochemical assays ; Blood ; CFP-10 ; Child ; Children ; Cryopreservation ; Diagnosis ; Diagnostic systems ; Diseases ; Enrollments ; Evaluation ; General &amp; Internal Medicine ; HIV ; HIV infection ; HIV Infections - diagnosis ; Human immunodeficiency virus ; Humans ; Immunization ; Infant ; Infants ; Infants (Newborn) ; Infections ; Ionization ; Isoniazid ; Life Sciences &amp; Biomedicine ; Mass spectrometry ; Mass spectroscopy ; Medical diagnosis ; Medicine, General &amp; Internal ; Methods ; Monitoring ; Mycobacterium tuberculosis ; Nanoparticles ; Nanotechnology ; Pediatric research ; Pediatric tuberculosis ; Pediatrics ; Peptides ; Perinatal infection ; Placebos ; Prophylaxis ; Science &amp; Technology ; Scientific imaging ; Sensitivity ; Sensitivity and Specificity ; Serodiagnosis ; Sputum ; Technical Advance ; Time-of-flight mass spectrometry ; Tuberculosis ; Tuberculosis - diagnosis ; Virulence ; Virulence factors</subject><ispartof>BMC medicine, 2021-05, Vol.19 (1), p.113-113, Article 113</ispartof><rights>COPYRIGHT 2021 BioMed Central Ltd.</rights><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>6</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000651470900001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c594t-a91a2c0cd340d2fbfb065cb2ecec8b5785540e24f64d00e53fccaeaea3d60e343</citedby><cites>FETCH-LOGICAL-c594t-a91a2c0cd340d2fbfb065cb2ecec8b5785540e24f64d00e53fccaeaea3d60e343</cites><orcidid>0000-0001-8097-9631 ; 0000-0002-5166-4937</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/PMC8130139/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130139/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2116,27931,27932,39265,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34001096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao, Liyan</creatorcontrib><creatorcontrib>LaCourse, Sylvia M.</creatorcontrib><creatorcontrib>Kim, Soyeon</creatorcontrib><creatorcontrib>Liu, Chang</creatorcontrib><creatorcontrib>Ning, Bo</creatorcontrib><creatorcontrib>Bao, Duran</creatorcontrib><creatorcontrib>Fan, Jia</creatorcontrib><creatorcontrib>Lyon, Christopher J.</creatorcontrib><creatorcontrib>Sun, Ziyong</creatorcontrib><creatorcontrib>Nachman, Sharon</creatorcontrib><creatorcontrib>Mitchell, Charles D.</creatorcontrib><creatorcontrib>Hu, Tony Y.</creatorcontrib><title>Evaluation of a serum-based antigen test for tuberculosis in HIV-exposed infants: a diagnostic accuracy study</title><title>BMC medicine</title><addtitle>BMC MED</addtitle><addtitle>BMC Med</addtitle><description>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 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-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 &lt;= 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.</description><subject>Antigens</subject><subject>Antigens, Bacterial</subject><subject>Biochemical assays</subject><subject>Blood</subject><subject>CFP-10</subject><subject>Child</subject><subject>Children</subject><subject>Cryopreservation</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Diseases</subject><subject>Enrollments</subject><subject>Evaluation</subject><subject>General &amp; Internal Medicine</subject><subject>HIV</subject><subject>HIV infection</subject><subject>HIV Infections - diagnosis</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunization</subject><subject>Infant</subject><subject>Infants</subject><subject>Infants (Newborn)</subject><subject>Infections</subject><subject>Ionization</subject><subject>Isoniazid</subject><subject>Life Sciences &amp; Biomedicine</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medical diagnosis</subject><subject>Medicine, General &amp; Internal</subject><subject>Methods</subject><subject>Monitoring</subject><subject>Mycobacterium tuberculosis</subject><subject>Nanoparticles</subject><subject>Nanotechnology</subject><subject>Pediatric research</subject><subject>Pediatric tuberculosis</subject><subject>Pediatrics</subject><subject>Peptides</subject><subject>Perinatal infection</subject><subject>Placebos</subject><subject>Prophylaxis</subject><subject>Science &amp; Technology</subject><subject>Scientific imaging</subject><subject>Sensitivity</subject><subject>Sensitivity and Specificity</subject><subject>Serodiagnosis</subject><subject>Sputum</subject><subject>Technical Advance</subject><subject>Time-of-flight mass spectrometry</subject><subject>Tuberculosis</subject><subject>Tuberculosis - diagnosis</subject><subject>Virulence</subject><subject>Virulence factors</subject><issn>1741-7015</issn><issn>1741-7015</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNqNklGL1DAUhYso7rr6B3yQgiCCdE3SNG19EJZhdQcWfFFfw216M5Ohk6xJuuP8ezPTdZwRHyQPDel3zk0OJ8teUnJJaSPeB8paKgrCaEFo25TF5lF2TmtOi5rQ6vHR_ix7FsKKEFbVNX-anZWcEEpacZ6tr-9hGCEaZ3Onc8gD-nFddBCwz8FGs0CbRwwx187ncezQq3FwwYTc2Pxm_r3An3duBxurEx8-JI_ewMK6EI3KQanRg9rmIY799nn2RMMQ8MXD9yL79un66-ymuP3yeT67ui1U1fJYQEuBKaL6dM-e6U53RFSqY6hQNV1VN1XFCTKuBe8JwarUSgGmVfaCYMnLi2w--fYOVvLOmzX4rXRg5P7A-YUEn643oKQUuk6QpgXVcwUEGKcdB6hFK4jWInl9nLzuxm6NvUIbPQwnpqd_rFnKhbuXDS0JLdtk8PbBwLsfY4pSrk1QOAxg0Y1Bsoo1DWOMVwl9_Re6cqO3KaqJakXd8j_UAtIDUu4uzVU7U3klRMXLsia7sZf_oNLqcW2Us6hNOj8RvDkSLBGGuAxuGHfdCKcgm0DlXQge9SEMSuSumXJqpkzNlPtmyk0SvTqO8SD5XcUENBOwwc7poAxahQeMkFQBytP4tCN0ZuK-szM32pik7_5fWv4CTPX_tg</recordid><startdate>20210518</startdate><enddate>20210518</enddate><creator>Mao, Liyan</creator><creator>LaCourse, Sylvia M.</creator><creator>Kim, Soyeon</creator><creator>Liu, Chang</creator><creator>Ning, Bo</creator><creator>Bao, Duran</creator><creator>Fan, Jia</creator><creator>Lyon, Christopher J.</creator><creator>Sun, Ziyong</creator><creator>Nachman, Sharon</creator><creator>Mitchell, Charles D.</creator><creator>Hu, Tony Y.</creator><general>Springer Nature</general><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-8097-9631</orcidid><orcidid>https://orcid.org/0000-0002-5166-4937</orcidid></search><sort><creationdate>20210518</creationdate><title>Evaluation of a serum-based antigen test for tuberculosis in HIV-exposed infants: a diagnostic accuracy study</title><author>Mao, Liyan ; LaCourse, Sylvia M. ; Kim, Soyeon ; Liu, Chang ; Ning, Bo ; Bao, Duran ; Fan, Jia ; Lyon, Christopher J. ; Sun, Ziyong ; Nachman, Sharon ; Mitchell, Charles D. ; Hu, Tony Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-a91a2c0cd340d2fbfb065cb2ecec8b5785540e24f64d00e53fccaeaea3d60e343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antigens</topic><topic>Antigens, Bacterial</topic><topic>Biochemical assays</topic><topic>Blood</topic><topic>CFP-10</topic><topic>Child</topic><topic>Children</topic><topic>Cryopreservation</topic><topic>Diagnosis</topic><topic>Diagnostic systems</topic><topic>Diseases</topic><topic>Enrollments</topic><topic>Evaluation</topic><topic>General &amp; Internal Medicine</topic><topic>HIV</topic><topic>HIV infection</topic><topic>HIV Infections - diagnosis</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunization</topic><topic>Infant</topic><topic>Infants</topic><topic>Infants (Newborn)</topic><topic>Infections</topic><topic>Ionization</topic><topic>Isoniazid</topic><topic>Life Sciences &amp; Biomedicine</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medical diagnosis</topic><topic>Medicine, General &amp; Internal</topic><topic>Methods</topic><topic>Monitoring</topic><topic>Mycobacterium tuberculosis</topic><topic>Nanoparticles</topic><topic>Nanotechnology</topic><topic>Pediatric research</topic><topic>Pediatric tuberculosis</topic><topic>Pediatrics</topic><topic>Peptides</topic><topic>Perinatal infection</topic><topic>Placebos</topic><topic>Prophylaxis</topic><topic>Science &amp; Technology</topic><topic>Scientific imaging</topic><topic>Sensitivity</topic><topic>Sensitivity and Specificity</topic><topic>Serodiagnosis</topic><topic>Sputum</topic><topic>Technical Advance</topic><topic>Time-of-flight mass spectrometry</topic><topic>Tuberculosis</topic><topic>Tuberculosis - diagnosis</topic><topic>Virulence</topic><topic>Virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mao, Liyan</creatorcontrib><creatorcontrib>LaCourse, Sylvia M.</creatorcontrib><creatorcontrib>Kim, Soyeon</creatorcontrib><creatorcontrib>Liu, Chang</creatorcontrib><creatorcontrib>Ning, Bo</creatorcontrib><creatorcontrib>Bao, Duran</creatorcontrib><creatorcontrib>Fan, Jia</creatorcontrib><creatorcontrib>Lyon, Christopher J.</creatorcontrib><creatorcontrib>Sun, Ziyong</creatorcontrib><creatorcontrib>Nachman, Sharon</creatorcontrib><creatorcontrib>Mitchell, Charles D.</creatorcontrib><creatorcontrib>Hu, Tony Y.</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; 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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 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-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 &lt;= 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.</abstract><cop>LONDON</cop><pub>Springer Nature</pub><pmid>34001096</pmid><doi>10.1186/s12916-021-01983-w</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8097-9631</orcidid><orcidid>https://orcid.org/0000-0002-5166-4937</orcidid><oa>free_for_read</oa></addata></record>
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subjects Antigens
Antigens, Bacterial
Biochemical assays
Blood
CFP-10
Child
Children
Cryopreservation
Diagnosis
Diagnostic systems
Diseases
Enrollments
Evaluation
General & Internal Medicine
HIV
HIV infection
HIV Infections - diagnosis
Human immunodeficiency virus
Humans
Immunization
Infant
Infants
Infants (Newborn)
Infections
Ionization
Isoniazid
Life Sciences & Biomedicine
Mass spectrometry
Mass spectroscopy
Medical diagnosis
Medicine, General & Internal
Methods
Monitoring
Mycobacterium tuberculosis
Nanoparticles
Nanotechnology
Pediatric research
Pediatric tuberculosis
Pediatrics
Peptides
Perinatal infection
Placebos
Prophylaxis
Science & Technology
Scientific imaging
Sensitivity
Sensitivity and Specificity
Serodiagnosis
Sputum
Technical Advance
Time-of-flight mass spectrometry
Tuberculosis
Tuberculosis - diagnosis
Virulence
Virulence factors
title Evaluation of a serum-based antigen test for tuberculosis in HIV-exposed infants: a diagnostic accuracy study
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