Soluble Urokinase-Type Plasminogen Activator Receptor as a Prognostic Marker of Ugandan Children at Risk of Severe and Fatal Malaria
Abstract Background Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hyp...
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| Veröffentlicht in: | Clinical infectious diseases 2023-02, Vol.76 (3), p.e1079-e1086 |
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| creator | Stefanova, Veselina Ngai, Michelle Weckman, Andrea M Wright, Julie K Zhong, Kathleen Richard-Greenblatt, Melissa McDonald, Chloe R Conroy, Andrea L Namasopo, Sophie Opoka, Robert O Hawkes, Michael Kain, Kevin C |
| description | Abstract
Background
Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria.
Methods
Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]).
Results
Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P < .0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P = .001; 1 vs 2, P < .001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P < .0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI}, .91–.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI, .91–.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI, .96–.98]; P < .0001).
Conclusions
Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials.
Current malaria diagnostic tests do not reliably identify children at risk of severe malaria and death. We identified soluble urokinase-type plasminogen activator receptor (suPAR) as a prognostic marker of severe and fatal malaria in Ugandan children. |
| doi_str_mv | 10.1093/cid/ciac457 |
| format | Article |
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Background
Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria.
Methods
Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]).
Results
Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P < .0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P = .001; 1 vs 2, P < .001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P < .0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI}, .91–.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI, .91–.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI, .96–.98]; P < .0001).
Conclusions
Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials.
Current malaria diagnostic tests do not reliably identify children at risk of severe malaria and death. We identified soluble urokinase-type plasminogen activator receptor (suPAR) as a prognostic marker of severe and fatal malaria in Ugandan children.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciac457</identifier><identifier>PMID: 35675322</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Biomarkers ; Child ; Humans ; Malaria - diagnosis ; Prognosis ; Prospective Studies ; Receptors, Urokinase Plasminogen Activator ; Uganda</subject><ispartof>Clinical infectious diseases, 2023-02, Vol.76 (3), p.e1079-e1086</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c320t-403212e253b9b1ac796af6cfbdbf475aa899c5a126638a7a84322c078e41504d3</citedby><cites>FETCH-LOGICAL-c320t-403212e253b9b1ac796af6cfbdbf475aa899c5a126638a7a84322c078e41504d3</cites><orcidid>0000-0001-6068-1272</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,1579,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35675322$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stefanova, Veselina</creatorcontrib><creatorcontrib>Ngai, Michelle</creatorcontrib><creatorcontrib>Weckman, Andrea M</creatorcontrib><creatorcontrib>Wright, Julie K</creatorcontrib><creatorcontrib>Zhong, Kathleen</creatorcontrib><creatorcontrib>Richard-Greenblatt, Melissa</creatorcontrib><creatorcontrib>McDonald, Chloe R</creatorcontrib><creatorcontrib>Conroy, Andrea L</creatorcontrib><creatorcontrib>Namasopo, Sophie</creatorcontrib><creatorcontrib>Opoka, Robert O</creatorcontrib><creatorcontrib>Hawkes, Michael</creatorcontrib><creatorcontrib>Kain, Kevin C</creatorcontrib><title>Soluble Urokinase-Type Plasminogen Activator Receptor as a Prognostic Marker of Ugandan Children at Risk of Severe and Fatal Malaria</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Abstract
Background
Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria.
Methods
Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]).
Results
Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P < .0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P = .001; 1 vs 2, P < .001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P < .0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI}, .91–.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI, .91–.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI, .96–.98]; P < .0001).
Conclusions
Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials.
Current malaria diagnostic tests do not reliably identify children at risk of severe malaria and death. We identified soluble urokinase-type plasminogen activator receptor (suPAR) as a prognostic marker of severe and fatal malaria in Ugandan children.</description><subject>Biomarkers</subject><subject>Child</subject><subject>Humans</subject><subject>Malaria - diagnosis</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Receptors, Urokinase Plasminogen Activator</subject><subject>Uganda</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1LxDAQxYMofp-8S04iSDVpkn4cZfELFEXdc5mm0zVutqlJK3j3DzfLrh49DPNgfu_BPEKOODvnrBQX2jRxQEuVb5BdrkSeZKrkm1EzVSSyEMUO2QvhnTHOC6a2yY5QWa5Emu6S7xdnx9oinXo3Nx0ETF6_eqRPFsLCdG6GHb3Ug_mEwXn6jBr7pYBAgT55N-tcGIymD-Dn6Klr6XQGXQMdnbwZ2_johoE-mzBf3l7wEz3SCNBrGMBGmwVv4IBstWADHq73PpleX71ObpP7x5u7yeV9okXKhkQykfIUUyXqsuag8zKDNtNt3dStzBVAUZZaAU-zTBSQQyHji5rlBUqumGzEPjld5fbefYwYhmphgkZroUM3hirNcimkilkRPVuh2rsQPLZV780C_FfFWbWsvYq1V-vaI328Dh7rBTZ_7G_PEThZAW7s_036AeDMjEk</recordid><startdate>20230208</startdate><enddate>20230208</enddate><creator>Stefanova, Veselina</creator><creator>Ngai, Michelle</creator><creator>Weckman, Andrea M</creator><creator>Wright, Julie K</creator><creator>Zhong, Kathleen</creator><creator>Richard-Greenblatt, Melissa</creator><creator>McDonald, Chloe R</creator><creator>Conroy, Andrea L</creator><creator>Namasopo, Sophie</creator><creator>Opoka, Robert O</creator><creator>Hawkes, Michael</creator><creator>Kain, Kevin C</creator><general>Oxford University Press</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>7X8</scope><orcidid>https://orcid.org/0000-0001-6068-1272</orcidid></search><sort><creationdate>20230208</creationdate><title>Soluble Urokinase-Type Plasminogen Activator Receptor as a Prognostic Marker of Ugandan Children at Risk of Severe and Fatal Malaria</title><author>Stefanova, Veselina ; Ngai, Michelle ; Weckman, Andrea M ; Wright, Julie K ; Zhong, Kathleen ; Richard-Greenblatt, Melissa ; McDonald, Chloe R ; Conroy, Andrea L ; Namasopo, Sophie ; Opoka, Robert O ; Hawkes, Michael ; Kain, Kevin C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c320t-403212e253b9b1ac796af6cfbdbf475aa899c5a126638a7a84322c078e41504d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biomarkers</topic><topic>Child</topic><topic>Humans</topic><topic>Malaria - diagnosis</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Receptors, Urokinase Plasminogen Activator</topic><topic>Uganda</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stefanova, Veselina</creatorcontrib><creatorcontrib>Ngai, Michelle</creatorcontrib><creatorcontrib>Weckman, Andrea M</creatorcontrib><creatorcontrib>Wright, Julie K</creatorcontrib><creatorcontrib>Zhong, Kathleen</creatorcontrib><creatorcontrib>Richard-Greenblatt, Melissa</creatorcontrib><creatorcontrib>McDonald, Chloe R</creatorcontrib><creatorcontrib>Conroy, Andrea L</creatorcontrib><creatorcontrib>Namasopo, Sophie</creatorcontrib><creatorcontrib>Opoka, Robert O</creatorcontrib><creatorcontrib>Hawkes, Michael</creatorcontrib><creatorcontrib>Kain, Kevin C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stefanova, Veselina</au><au>Ngai, Michelle</au><au>Weckman, Andrea M</au><au>Wright, Julie K</au><au>Zhong, Kathleen</au><au>Richard-Greenblatt, Melissa</au><au>McDonald, Chloe R</au><au>Conroy, Andrea L</au><au>Namasopo, Sophie</au><au>Opoka, Robert O</au><au>Hawkes, Michael</au><au>Kain, Kevin C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Soluble Urokinase-Type Plasminogen Activator Receptor as a Prognostic Marker of Ugandan Children at Risk of Severe and Fatal Malaria</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2023-02-08</date><risdate>2023</risdate><volume>76</volume><issue>3</issue><spage>e1079</spage><epage>e1086</epage><pages>e1079-e1086</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Abstract
Background
Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria.
Methods
Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]).
Results
Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P < .0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P = .001; 1 vs 2, P < .001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P < .0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI}, .91–.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI, .91–.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI, .96–.98]; P < .0001).
Conclusions
Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials.
Current malaria diagnostic tests do not reliably identify children at risk of severe malaria and death. We identified soluble urokinase-type plasminogen activator receptor (suPAR) as a prognostic marker of severe and fatal malaria in Ugandan children.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>35675322</pmid><doi>10.1093/cid/ciac457</doi><orcidid>https://orcid.org/0000-0001-6068-1272</orcidid></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Biomarkers Child Humans Malaria - diagnosis Prognosis Prospective Studies Receptors, Urokinase Plasminogen Activator Uganda |
| title | Soluble Urokinase-Type Plasminogen Activator Receptor as a Prognostic Marker of Ugandan Children at Risk of Severe and Fatal Malaria |
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