{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:16:28Z","timestamp":1794028588786,"version":"4.8.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:00:00Z","timestamp":1608336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["084368\/Z\/07\/Z"],"award-info":[{"award-number":["084368\/Z\/07\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oxford University Clinical Research Unit","award":["077078\/Z\/05\/Z"],"award-info":[{"award-number":["077078\/Z\/05\/Z"]}]},{"name":"Oxford University Clinical Research Unit","award":["077078\/Z\/05\/A"],"award-info":[{"award-number":["077078\/Z\/05\/A"]}]},{"name":"Oxford University Clinical Research Unit","award":["089276\/B\/09\/Z"],"award-info":[{"award-number":["089276\/B\/09\/Z"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["FP7-281803"],"award-info":[{"award-number":["FP7-281803"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>One of the generally accepted constructs of dengue pathogenesis is that clinical disease severity is at least partially dependent upon plasma viremia, yet data on plasma viremia in primary versus secondary infections and in relation to clinically relevant endpoints remain limited and contradictory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using a large database comprising detailed clinical and laboratory characterization of Vietnamese participants enrolled in a series of research studies executed over a 15-year period, we explored relationships between plasma viremia measured by reverse transcription\u2013polymerase chain reaction and 3 clinically relevant endpoints\u2014severe dengue, plasma leakage, and hospitalization\u2014in the dengue-confirmed cases. All 4 dengue serotypes and both primary and secondary infections were well represented. In our logistic regression models we allowed for a nonlinear effect of viremia and for associations between viremia and outcome to differ by age, serotype, host immune status, and illness day at study enrollment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 5642 dengue-confirmed cases we identified 259 (4.6%) severe dengue cases, 701 (12.4%) patients with plasma leakage, and 1441 of 4008 (40.0%) patients recruited in outpatient settings who were subsequently hospitalized. From the early febrile phase onwards, higher viremia increased the risk of developing all 3 endpoints, but effect sizes were modest (ORs ranging from 1.12\u20131.27 per 1-log increase) compared with the effects of a secondary immune response (ORs, 1.67\u20137.76). The associations were consistent across age, serotype, and immune status groups, and in the various sensitivity and subgroup analyses we undertook.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Higher plasma viremia is associated with increased dengue severity, regardless of serotype or immune status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaa1840","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T23:04:07Z","timestamp":1607468647000},"page":"e1074-e1083","source":"Crossref","is-referenced-by-count":49,"title":["Higher Plasma Viremia in the Febrile Phase Is Associated With Adverse Dengue Outcomes Irrespective of Infecting Serotype or Host Immune Status: An Analysis of 5642 Vietnamese Cases"],"prefix":"10.1093","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2684-3041","authenticated-orcid":false,"given":"Nguyen Lam","family":"Vuong","sequence":"first","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"},{"name":"University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Than Ha","family":"Quyen","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Hanh","family":"Tien","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Minh","family":"Tuan","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital No. 1, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duong Thi Hue","family":"Kien","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phung Khanh","family":"Lam","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Thi Hoai","family":"Tam","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran","family":"Van Ngoc","sequence":"additional","affiliation":[{"name":"Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jaenisch","sequence":"additional","affiliation":[{"name":"Section of Clinical Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald B","family":"Geskus","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron P","family":"Simmons","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom"},{"name":"Institute for Vector-Borne Disease, Monash University, Clayton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget A","family":"Wills","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United 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