Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data
Tuberculosis (TB) is the most common cause of death in people living with HIV (PLHIV), yet TB often goes undiagnosed since many patients are not able to produce a sputum specimen, and traditional diagnostics are costly or unavailable. A novel, rapid lateral flow assay, Fujifilm SILVAMP TB LAM (SILVA...
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| Veröffentlicht in: | PLoS medicine 2020-05, Vol.17 (5), p.e1003113-e1003113 |
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| creator | Broger, Tobias Nicol, Mark P Székely, Rita Bjerrum, Stephanie Sossen, Bianca Schutz, Charlotte Opintan, Japheth A Johansen, Isik S Mitarai, Satoshi Chikamatsu, Kinuyo Kerkhoff, Andrew D Macé, Aurélien Ongarello, Stefano Meintjes, Graeme Denkinger, Claudia M Schumacher, Samuel G |
| description | Tuberculosis (TB) is the most common cause of death in people living with HIV (PLHIV), yet TB often goes undiagnosed since many patients are not able to produce a sputum specimen, and traditional diagnostics are costly or unavailable. A novel, rapid lateral flow assay, Fujifilm SILVAMP TB LAM (SILVAMP-LAM), detects the presence of TB lipoarabinomannan (LAM) in urine, and is substantially more sensitive for diagnosing TB in PLHIV than an earlier LAM assay (Alere Determine TB LAM lateral flow assay [LF-LAM]). Here, we present an individual participant data meta-analysis of the diagnostic accuracy of SILVAMP-LAM in adult PLHIV, including both published and unpublished data.
Adult PLHIV (≥18 years) were assessed in 5 prospective cohort studies in South Africa (3 cohorts), Vietnam, and Ghana, carried out during 2012 to 2017. Of the 1,595 PLHIV who met eligibility criteria, the majority (61%) were inpatients, median age was 37 years (IQR 30-43), 43% had a CD4 count ≤ 100 cells/μl, and 35% were receiving antiretroviral therapy. Most participants (94%) had a positive WHO symptom screen for TB on enrollment, and 45% were diagnosed with microbiologically confirmed TB, using mycobacterial culture or Xpert MTB/RIF testing of sputum, urine, or blood. Previously published data from inpatients were combined with unpublished data from outpatients. Biobanked urine samples were tested, using blinded double reading, with SILVAMP-LAM and LF-LAM. Applying a microbiological reference standard for assessment of sensitivity, the overall sensitivity for TB detection was 70.7% (95% CI 59.0%-80.8%) for SILVAMP-LAM compared to 34.9% (95% CI 19.5%-50.9%) for LF-LAM. Using a composite reference standard (which included patients with both microbiologically confirmed as well as clinically diagnosed TB), SILVAMP-LAM sensitivity was 65.8% (95% CI 55.9%-74.6%), and that of LF-LAM 31.4% (95% CI 19.1%-43.7%). In patients with CD4 count ≤ 100 cells/μl, SILVAMP-LAM sensitivity was 87.1% (95% CI 79.3%-93.6%), compared to 56.0% (95% CI 43.9%-64.9%) for LF-LAM. In patients with CD4 count 101-200 cells/μl, SILVAMP-LAM sensitivity was 62.7% (95% CI 52.4%-71.9%), compared to 25.3% (95% CI 15.8%-34.9%) for LF-LAM. In those with CD4 count > 200 cells/μl, SILVAMP-LAM sensitivity was 43.9% (95% CI 34.3%-53.9%), compared to 10.9% (95% CI 5.2%-18.4%) for LF-LAM. Using a microbiological reference standard, the specificity of SILVAMP-LAM was 90.9% (95% CI 87.2%-93.7%), and that of LF-LAM 95.3% (95% CI 92.2%- |
| doi_str_mv | 10.1371/journal.pmed.1003113 |
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Adult PLHIV (≥18 years) were assessed in 5 prospective cohort studies in South Africa (3 cohorts), Vietnam, and Ghana, carried out during 2012 to 2017. Of the 1,595 PLHIV who met eligibility criteria, the majority (61%) were inpatients, median age was 37 years (IQR 30-43), 43% had a CD4 count ≤ 100 cells/μl, and 35% were receiving antiretroviral therapy. Most participants (94%) had a positive WHO symptom screen for TB on enrollment, and 45% were diagnosed with microbiologically confirmed TB, using mycobacterial culture or Xpert MTB/RIF testing of sputum, urine, or blood. Previously published data from inpatients were combined with unpublished data from outpatients. Biobanked urine samples were tested, using blinded double reading, with SILVAMP-LAM and LF-LAM. Applying a microbiological reference standard for assessment of sensitivity, the overall sensitivity for TB detection was 70.7% (95% CI 59.0%-80.8%) for SILVAMP-LAM compared to 34.9% (95% CI 19.5%-50.9%) for LF-LAM. Using a composite reference standard (which included patients with both microbiologically confirmed as well as clinically diagnosed TB), SILVAMP-LAM sensitivity was 65.8% (95% CI 55.9%-74.6%), and that of LF-LAM 31.4% (95% CI 19.1%-43.7%). In patients with CD4 count ≤ 100 cells/μl, SILVAMP-LAM sensitivity was 87.1% (95% CI 79.3%-93.6%), compared to 56.0% (95% CI 43.9%-64.9%) for LF-LAM. In patients with CD4 count 101-200 cells/μl, SILVAMP-LAM sensitivity was 62.7% (95% CI 52.4%-71.9%), compared to 25.3% (95% CI 15.8%-34.9%) for LF-LAM. In those with CD4 count > 200 cells/μl, SILVAMP-LAM sensitivity was 43.9% (95% CI 34.3%-53.9%), compared to 10.9% (95% CI 5.2%-18.4%) for LF-LAM. Using a microbiological reference standard, the specificity of SILVAMP-LAM was 90.9% (95% CI 87.2%-93.7%), and that of LF-LAM 95.3% (95% CI 92.2%-97.7%). Limitations of this study include the use of biobanked, rather than fresh urine samples, and testing by skilled laboratory technicians in research laboratories, rather than at the point of care.
In this study, we found that SILVAMP-LAM identified a substantially higher proportion of TB patients in PLHIV than LF-LAM. The sensitivity of SILVAMP-LAM was highest in patients with CD4 count ≤ 100 cells/μl. Further work is needed to demonstrate accuracy when implemented as a point-of-care test.</description><identifier>ISSN: 1549-1676</identifier><identifier>ISSN: 1549-1277</identifier><identifier>EISSN: 1549-1676</identifier><identifier>DOI: 10.1371/journal.pmed.1003113</identifier><identifier>PMID: 32357197</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Adults ; Ambulatory Care Facilities ; Analysis ; Antiretroviral therapy ; Biology and Life Sciences ; CD4 antigen ; Cell culture ; Female ; Funding ; Health sciences ; Highly active antiretroviral therapy ; HIV ; HIV Infections - complications ; HIV patients ; Hospitals ; Human immunodeficiency virus ; Humans ; Infectious diseases ; Lipopolysaccharides - analysis ; Male ; Medicine ; Medicine and Health Sciences ; Meta-analysis ; Mortality ; Point-of-Care Systems ; Prospective Studies ; Sputum ; Studies ; Supervision ; Tuberculosis ; Tuberculosis - diagnosis ; Tuberculosis, Pulmonary - diagnosis ; Urine</subject><ispartof>PLoS medicine, 2020-05, Vol.17 (5), p.e1003113-e1003113</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Broger 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>2020 Broger et al 2020 Broger et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c694t-7ab2ed9ecc975638d2ba58917b1944eef187e3d3f466ff0c30e9081216865bc53</citedby><cites>FETCH-LOGICAL-c694t-7ab2ed9ecc975638d2ba58917b1944eef187e3d3f466ff0c30e9081216865bc53</cites><orcidid>0000-0002-1366-4805 ; 0000-0002-5023-6658 ; 0000-0002-9046-6255 ; 0000-0003-1196-4414 ; 0000-0002-6028-3351 ; 0000-0002-6136-206X ; 0000-0002-3282-1650 ; 0000-0002-7216-7067 ; 0000-0001-8329-6158 ; 0000-0002-5398-9399 ; 0000-0002-7959-1055 ; 0000-0002-2288-077X</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/PMC7194366/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194366/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32357197$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Broger, Tobias</creatorcontrib><creatorcontrib>Nicol, Mark P</creatorcontrib><creatorcontrib>Székely, Rita</creatorcontrib><creatorcontrib>Bjerrum, Stephanie</creatorcontrib><creatorcontrib>Sossen, Bianca</creatorcontrib><creatorcontrib>Schutz, Charlotte</creatorcontrib><creatorcontrib>Opintan, Japheth A</creatorcontrib><creatorcontrib>Johansen, Isik S</creatorcontrib><creatorcontrib>Mitarai, Satoshi</creatorcontrib><creatorcontrib>Chikamatsu, Kinuyo</creatorcontrib><creatorcontrib>Kerkhoff, Andrew D</creatorcontrib><creatorcontrib>Macé, Aurélien</creatorcontrib><creatorcontrib>Ongarello, Stefano</creatorcontrib><creatorcontrib>Meintjes, Graeme</creatorcontrib><creatorcontrib>Denkinger, Claudia M</creatorcontrib><creatorcontrib>Schumacher, Samuel G</creatorcontrib><title>Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data</title><title>PLoS medicine</title><addtitle>PLoS Med</addtitle><description>Tuberculosis (TB) is the most common cause of death in people living with HIV (PLHIV), yet TB often goes undiagnosed since many patients are not able to produce a sputum specimen, and traditional diagnostics are costly or unavailable. A novel, rapid lateral flow assay, Fujifilm SILVAMP TB LAM (SILVAMP-LAM), detects the presence of TB lipoarabinomannan (LAM) in urine, and is substantially more sensitive for diagnosing TB in PLHIV than an earlier LAM assay (Alere Determine TB LAM lateral flow assay [LF-LAM]). Here, we present an individual participant data meta-analysis of the diagnostic accuracy of SILVAMP-LAM in adult PLHIV, including both published and unpublished data.
Adult PLHIV (≥18 years) were assessed in 5 prospective cohort studies in South Africa (3 cohorts), Vietnam, and Ghana, carried out during 2012 to 2017. Of the 1,595 PLHIV who met eligibility criteria, the majority (61%) were inpatients, median age was 37 years (IQR 30-43), 43% had a CD4 count ≤ 100 cells/μl, and 35% were receiving antiretroviral therapy. Most participants (94%) had a positive WHO symptom screen for TB on enrollment, and 45% were diagnosed with microbiologically confirmed TB, using mycobacterial culture or Xpert MTB/RIF testing of sputum, urine, or blood. Previously published data from inpatients were combined with unpublished data from outpatients. Biobanked urine samples were tested, using blinded double reading, with SILVAMP-LAM and LF-LAM. Applying a microbiological reference standard for assessment of sensitivity, the overall sensitivity for TB detection was 70.7% (95% CI 59.0%-80.8%) for SILVAMP-LAM compared to 34.9% (95% CI 19.5%-50.9%) for LF-LAM. Using a composite reference standard (which included patients with both microbiologically confirmed as well as clinically diagnosed TB), SILVAMP-LAM sensitivity was 65.8% (95% CI 55.9%-74.6%), and that of LF-LAM 31.4% (95% CI 19.1%-43.7%). In patients with CD4 count ≤ 100 cells/μl, SILVAMP-LAM sensitivity was 87.1% (95% CI 79.3%-93.6%), compared to 56.0% (95% CI 43.9%-64.9%) for LF-LAM. In patients with CD4 count 101-200 cells/μl, SILVAMP-LAM sensitivity was 62.7% (95% CI 52.4%-71.9%), compared to 25.3% (95% CI 15.8%-34.9%) for LF-LAM. In those with CD4 count > 200 cells/μl, SILVAMP-LAM sensitivity was 43.9% (95% CI 34.3%-53.9%), compared to 10.9% (95% CI 5.2%-18.4%) for LF-LAM. Using a microbiological reference standard, the specificity of SILVAMP-LAM was 90.9% (95% CI 87.2%-93.7%), and that of LF-LAM 95.3% (95% CI 92.2%-97.7%). Limitations of this study include the use of biobanked, rather than fresh urine samples, and testing by skilled laboratory technicians in research laboratories, rather than at the point of care.
In this study, we found that SILVAMP-LAM identified a substantially higher proportion of TB patients in PLHIV than LF-LAM. The sensitivity of SILVAMP-LAM was highest in patients with CD4 count ≤ 100 cells/μl. Further work is needed to demonstrate accuracy when implemented as a point-of-care test.</description><subject>Adult</subject><subject>Adults</subject><subject>Ambulatory Care Facilities</subject><subject>Analysis</subject><subject>Antiretroviral therapy</subject><subject>Biology and Life Sciences</subject><subject>CD4 antigen</subject><subject>Cell culture</subject><subject>Female</subject><subject>Funding</subject><subject>Health sciences</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV patients</subject><subject>Hospitals</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Lipopolysaccharides - analysis</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Meta-analysis</subject><subject>Mortality</subject><subject>Point-of-Care Systems</subject><subject>Prospective Studies</subject><subject>Sputum</subject><subject>Studies</subject><subject>Supervision</subject><subject>Tuberculosis</subject><subject>Tuberculosis - diagnosis</subject><subject>Tuberculosis, Pulmonary - diagnosis</subject><subject>Urine</subject><issn>1549-1676</issn><issn>1549-1277</issn><issn>1549-1676</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk9tu1DAQhiMEolB4AwSWkBBcZIljx1lzgVSVQ1eqqMSht9bEmWRdZe1gO4V9JN4SL91WXbQXoFzEsr_5Z_4ZTZY9ocWMspq-vnCTtzDMxhW2M1oUjFJ2J3tAKy5zKmpx99b5IHsYwkVRlLKQxf3sgJWsqqmsH2S_3hnorQvRaAJaTx70mriOALHuEgcSpwa9ngYXTCCjMzbmrss1eCSTNxbJYEYHHhpj3QqsBUsgBFiTznkyohuHDXJpbE9-mLgkJ4vzN-SIrDBCDqn89UY35TO2TVQ7wZCOOQHbEjfFEaJBG0kLER5l9zoYAj7e_g-zbx_efz0-yU_PPi6Oj05zLSSPeQ1Nia1ErWVdCTZvywaquaR1QyXniB2d18ha1nEhuq7QrEBZzGlJxVxUja7YYfbsSndMptW2y0GVvORcVJTLRCyuiNbBhRq9WYFfKwdG_blwvlfgU0MHVBJ40zBe81bUnFIKNXSCSxSILM2sS1pvt9mmJg1SJ7cehh3R3Rdrlqp3lyqNjzMhksDLrYB33ycMUa1M0DgMYNFNqW4ma1EzKjfOnv-F7ne3pXpIBoztXMqrN6LqSLBSVoWoeKLyPVSPFlORzmJn0vUOP9vDp6_FldF7A17tBCQm4s_YwxSCWnz5_B_sp39nz8532Re32CXCEJfBDVM0zoZdkF-B2rsQPHY3A6SF2mzrdafVZlvVdltT2NPbw78Jul5P9hv3ITrV</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Broger, Tobias</creator><creator>Nicol, Mark P</creator><creator>Székely, Rita</creator><creator>Bjerrum, Stephanie</creator><creator>Sossen, Bianca</creator><creator>Schutz, Charlotte</creator><creator>Opintan, Japheth A</creator><creator>Johansen, Isik S</creator><creator>Mitarai, Satoshi</creator><creator>Chikamatsu, Kinuyo</creator><creator>Kerkhoff, Andrew D</creator><creator>Macé, Aurélien</creator><creator>Ongarello, Stefano</creator><creator>Meintjes, Graeme</creator><creator>Denkinger, Claudia M</creator><creator>Schumacher, Samuel G</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7TK</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</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><scope>CZK</scope><orcidid>https://orcid.org/0000-0002-1366-4805</orcidid><orcidid>https://orcid.org/0000-0002-5023-6658</orcidid><orcidid>https://orcid.org/0000-0002-9046-6255</orcidid><orcidid>https://orcid.org/0000-0003-1196-4414</orcidid><orcidid>https://orcid.org/0000-0002-6028-3351</orcidid><orcidid>https://orcid.org/0000-0002-6136-206X</orcidid><orcidid>https://orcid.org/0000-0002-3282-1650</orcidid><orcidid>https://orcid.org/0000-0002-7216-7067</orcidid><orcidid>https://orcid.org/0000-0001-8329-6158</orcidid><orcidid>https://orcid.org/0000-0002-5398-9399</orcidid><orcidid>https://orcid.org/0000-0002-7959-1055</orcidid><orcidid>https://orcid.org/0000-0002-2288-077X</orcidid></search><sort><creationdate>202005</creationdate><title>Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data</title><author>Broger, Tobias ; Nicol, Mark P ; Székely, Rita ; Bjerrum, Stephanie ; Sossen, Bianca ; Schutz, Charlotte ; Opintan, Japheth A ; Johansen, Isik S ; Mitarai, Satoshi ; Chikamatsu, Kinuyo ; Kerkhoff, Andrew D ; Macé, Aurélien ; Ongarello, Stefano ; Meintjes, Graeme ; Denkinger, Claudia M ; Schumacher, Samuel G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c694t-7ab2ed9ecc975638d2ba58917b1944eef187e3d3f466ff0c30e9081216865bc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Adults</topic><topic>Ambulatory Care Facilities</topic><topic>Analysis</topic><topic>Antiretroviral therapy</topic><topic>Biology and Life Sciences</topic><topic>CD4 antigen</topic><topic>Cell culture</topic><topic>Female</topic><topic>Funding</topic><topic>Health sciences</topic><topic>Highly active antiretroviral therapy</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>HIV patients</topic><topic>Hospitals</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Lipopolysaccharides - analysis</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Meta-analysis</topic><topic>Mortality</topic><topic>Point-of-Care Systems</topic><topic>Prospective Studies</topic><topic>Sputum</topic><topic>Studies</topic><topic>Supervision</topic><topic>Tuberculosis</topic><topic>Tuberculosis - diagnosis</topic><topic>Tuberculosis, Pulmonary - diagnosis</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Broger, Tobias</creatorcontrib><creatorcontrib>Nicol, Mark P</creatorcontrib><creatorcontrib>Székely, Rita</creatorcontrib><creatorcontrib>Bjerrum, Stephanie</creatorcontrib><creatorcontrib>Sossen, Bianca</creatorcontrib><creatorcontrib>Schutz, Charlotte</creatorcontrib><creatorcontrib>Opintan, Japheth A</creatorcontrib><creatorcontrib>Johansen, Isik S</creatorcontrib><creatorcontrib>Mitarai, Satoshi</creatorcontrib><creatorcontrib>Chikamatsu, Kinuyo</creatorcontrib><creatorcontrib>Kerkhoff, Andrew D</creatorcontrib><creatorcontrib>Macé, Aurélien</creatorcontrib><creatorcontrib>Ongarello, Stefano</creatorcontrib><creatorcontrib>Meintjes, Graeme</creatorcontrib><creatorcontrib>Denkinger, Claudia M</creatorcontrib><creatorcontrib>Schumacher, Samuel G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Medicine</collection><jtitle>PLoS medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Broger, Tobias</au><au>Nicol, Mark P</au><au>Székely, Rita</au><au>Bjerrum, Stephanie</au><au>Sossen, Bianca</au><au>Schutz, Charlotte</au><au>Opintan, Japheth A</au><au>Johansen, Isik S</au><au>Mitarai, Satoshi</au><au>Chikamatsu, Kinuyo</au><au>Kerkhoff, Andrew D</au><au>Macé, Aurélien</au><au>Ongarello, Stefano</au><au>Meintjes, Graeme</au><au>Denkinger, Claudia M</au><au>Schumacher, Samuel G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data</atitle><jtitle>PLoS medicine</jtitle><addtitle>PLoS Med</addtitle><date>2020-05</date><risdate>2020</risdate><volume>17</volume><issue>5</issue><spage>e1003113</spage><epage>e1003113</epage><pages>e1003113-e1003113</pages><issn>1549-1676</issn><issn>1549-1277</issn><eissn>1549-1676</eissn><abstract>Tuberculosis (TB) is the most common cause of death in people living with HIV (PLHIV), yet TB often goes undiagnosed since many patients are not able to produce a sputum specimen, and traditional diagnostics are costly or unavailable. A novel, rapid lateral flow assay, Fujifilm SILVAMP TB LAM (SILVAMP-LAM), detects the presence of TB lipoarabinomannan (LAM) in urine, and is substantially more sensitive for diagnosing TB in PLHIV than an earlier LAM assay (Alere Determine TB LAM lateral flow assay [LF-LAM]). Here, we present an individual participant data meta-analysis of the diagnostic accuracy of SILVAMP-LAM in adult PLHIV, including both published and unpublished data.
Adult PLHIV (≥18 years) were assessed in 5 prospective cohort studies in South Africa (3 cohorts), Vietnam, and Ghana, carried out during 2012 to 2017. Of the 1,595 PLHIV who met eligibility criteria, the majority (61%) were inpatients, median age was 37 years (IQR 30-43), 43% had a CD4 count ≤ 100 cells/μl, and 35% were receiving antiretroviral therapy. Most participants (94%) had a positive WHO symptom screen for TB on enrollment, and 45% were diagnosed with microbiologically confirmed TB, using mycobacterial culture or Xpert MTB/RIF testing of sputum, urine, or blood. Previously published data from inpatients were combined with unpublished data from outpatients. Biobanked urine samples were tested, using blinded double reading, with SILVAMP-LAM and LF-LAM. Applying a microbiological reference standard for assessment of sensitivity, the overall sensitivity for TB detection was 70.7% (95% CI 59.0%-80.8%) for SILVAMP-LAM compared to 34.9% (95% CI 19.5%-50.9%) for LF-LAM. Using a composite reference standard (which included patients with both microbiologically confirmed as well as clinically diagnosed TB), SILVAMP-LAM sensitivity was 65.8% (95% CI 55.9%-74.6%), and that of LF-LAM 31.4% (95% CI 19.1%-43.7%). In patients with CD4 count ≤ 100 cells/μl, SILVAMP-LAM sensitivity was 87.1% (95% CI 79.3%-93.6%), compared to 56.0% (95% CI 43.9%-64.9%) for LF-LAM. In patients with CD4 count 101-200 cells/μl, SILVAMP-LAM sensitivity was 62.7% (95% CI 52.4%-71.9%), compared to 25.3% (95% CI 15.8%-34.9%) for LF-LAM. In those with CD4 count > 200 cells/μl, SILVAMP-LAM sensitivity was 43.9% (95% CI 34.3%-53.9%), compared to 10.9% (95% CI 5.2%-18.4%) for LF-LAM. Using a microbiological reference standard, the specificity of SILVAMP-LAM was 90.9% (95% CI 87.2%-93.7%), and that of LF-LAM 95.3% (95% CI 92.2%-97.7%). Limitations of this study include the use of biobanked, rather than fresh urine samples, and testing by skilled laboratory technicians in research laboratories, rather than at the point of care.
In this study, we found that SILVAMP-LAM identified a substantially higher proportion of TB patients in PLHIV than LF-LAM. The sensitivity of SILVAMP-LAM was highest in patients with CD4 count ≤ 100 cells/μl. Further work is needed to demonstrate accuracy when implemented as a point-of-care test.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32357197</pmid><doi>10.1371/journal.pmed.1003113</doi><orcidid>https://orcid.org/0000-0002-1366-4805</orcidid><orcidid>https://orcid.org/0000-0002-5023-6658</orcidid><orcidid>https://orcid.org/0000-0002-9046-6255</orcidid><orcidid>https://orcid.org/0000-0003-1196-4414</orcidid><orcidid>https://orcid.org/0000-0002-6028-3351</orcidid><orcidid>https://orcid.org/0000-0002-6136-206X</orcidid><orcidid>https://orcid.org/0000-0002-3282-1650</orcidid><orcidid>https://orcid.org/0000-0002-7216-7067</orcidid><orcidid>https://orcid.org/0000-0001-8329-6158</orcidid><orcidid>https://orcid.org/0000-0002-5398-9399</orcidid><orcidid>https://orcid.org/0000-0002-7959-1055</orcidid><orcidid>https://orcid.org/0000-0002-2288-077X</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1549-1676 |
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| subjects | Adult Adults Ambulatory Care Facilities Analysis Antiretroviral therapy Biology and Life Sciences CD4 antigen Cell culture Female Funding Health sciences Highly active antiretroviral therapy HIV HIV Infections - complications HIV patients Hospitals Human immunodeficiency virus Humans Infectious diseases Lipopolysaccharides - analysis Male Medicine Medicine and Health Sciences Meta-analysis Mortality Point-of-Care Systems Prospective Studies Sputum Studies Supervision Tuberculosis Tuberculosis - diagnosis Tuberculosis, Pulmonary - diagnosis Urine |
| title | Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data |
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