{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:01:16Z","timestamp":1791475276235,"version":"4.3.4"},"reference-count":0,"publisher":"American Society of Tropical Medicine and Hygiene","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,13]]},"abstract":"<jats:p>Dengue virus (DENV) infection is associated with plasma leakage, which may progress to shock. The angiopoietin (Ang)\u2013tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (Tie-2) axis regulates endothelial permeability. We examined the clinical utility of Ang-1, Ang-2, and the Ang-2-to-Ang-1 ratio for prediction of progression to severe DENV in a prospective cohort study of children and young adults (age 1 to &lt;26\u2009years) with DENV infection. Ang-1, Ang-2, Tie-2 were measured at presentation to an outpatient clinic in the Philippines from stored plasma by multiplex Luminex<jats:sup>\u00ae<\/jats:sup> assay. Patients were followed prospectively to document the clinical course (hospitalization, length of stay, intravenous fluid resuscitation, and transfer to a higher level facility). We included 244 patients (median age 9\u2009years, 40% female). At presentation, 63 patients (26%) had uncomplicated dengue, 179 (73%) had dengue with warning signs, and 2 (0.82%) had severe dengue. One hundred eighty-one patients (74%) were hospitalized. Ang-1 levels were lower and Ang-2 higher in patients who required hospitalization. Ang-2-to-Ang-1 ratio &gt;1 was associated with a relative risk of hospitalization of 1.20 (95% CI: 1.03\u20131.36, <jats:italic>P =<\/jats:italic> 0.016). A higher Ang-2-to-Ang-1 ratio was associated with longer length of hospital stay, higher frequency of transfer to a higher level facility, larger intravenous fluid requirement, hemoconcentration, and thrombocytopenia. Angiopoietin-2 was correlated with procalcitonin (Kendall\u2019s \u03c4 = 0.17, <jats:italic>P<\/jats:italic> = 0.00012), a marker of systemic inflammation, as well as soluble vascular cell adhesion molecule-1 (\u03c4 = 0.22, <jats:italic>P<\/jats:italic> &lt;0.0001) and Endoglin (\u03c4 = 0.14, <jats:italic>P<\/jats:italic> = 0.0017), markers of endothelial activation. In conclusion, altered Ang-2-to-Ang-1 ratio can be detected early in the course of DENV infection and predicts clinically meaningful events (hospitalization, length of stay, and fluid resuscitation).<\/jats:p>","DOI":"10.4269\/ajtmh.24-0115","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T13:24:39Z","timestamp":1723555479000},"source":"Crossref","is-referenced-by-count":4,"title":["The Angiopoietin\u2013Tie-2 Axis in Children and Young Adults with Dengue Virus Infection in the Philippines"],"prefix":"10.4269","author":[{"given":"Hridesh","family":"Mishra","sequence":"first","affiliation":[{"name":"SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital Research Institute, Toronto, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Ngai","sequence":"additional","affiliation":[{"name":"SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital Research Institute, Toronto, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie M.","family":"Crowley","sequence":"additional","affiliation":[{"name":"SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital Research Institute, Toronto, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Tran","sequence":"additional","affiliation":[{"name":"SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital Research Institute, Toronto, Canada;"},{"name":"Public Health Ontario, Toronto, Canada;"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Salome Siose","family":"Painaga","sequence":"additional","affiliation":[{"name":"Lebumfacil\u2013Santa Ana Medical Center, Toledo, Philippines;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Yared","family":"Gaite","sequence":"additional","affiliation":[{"name":"Lebumfacil\u2013Santa Ana Medical Center, Toledo, Philippines;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, University of Alberta, Edmonton, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Kain","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada;"},{"name":"Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, UHN\u2013Toronto General Hospital, Toronto, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Hawkes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/aop\/article-10.4269-ajtmh.24-0115\/article-10.4269-ajtmh.24-0115.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/aop\/article-10.4269-ajtmh.24-0115\/article-10.4269-ajtmh.24-0115.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/aop\/article-10.4269-ajtmh.24-0115\/article-10.4269-ajtmh.24-0115.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T13:24:40Z","timestamp":1723555480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/aop\/article-10.4269-ajtmh.24-0115\/article-10.4269-ajtmh.24-0115.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,13]]},"references-count":0,"URL":"https:\/\/doi.org\/10.4269\/ajtmh.24-0115","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,13]]}}}