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Discovery and Characterization of Potential Prognostic Biomarkers for Dengue Hemorrhagic Fever

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  • Division of Vector-Borne Diseases, Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal General Hospital R3-137, Montreal, Quebec H3G 1A4, Canada; 3FQRNT Centre for Host–Parasite Interactions, McGill University, Montreal, Quebec H3G 1A4, Canada

Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; however, 2–5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue.

Author Notes

* Address correspondence to B. Katherine Poole-Smith, Immunodiagnostic, Development and Research Lab Centers for Disease Control and Prevention, NCEZID, DVBD, Dengue Branch 1324 Calle Canada San Juan, PR 00920. E-mail: isd5@cdc.gov† These authors contributed equally to this work.

Financial support: This work was supported by the Centers for Disease Control and Prevention, the Sandler Foundation, the Foundation of the Montreal General Hospital and the Research Institute of the McGill University Health Centre.

Disclosure: B. Katherine Poole-Smith, Kay M. Tomashek, Elizabeth A. Hunsperger, and Momar Ndao are inventors on a patent “Detection of subject biomarker diagnostic assay for dengue fever and the differentiation of dengue hemorrhagic fever.” United States Patent WO/2013/130029 Sept 6, 2013. Momar Ndao and Brian J. Ward are inventors on a patent entitled “Biomarkers for Dengue. United States Patent US 2012/0021936 A1 Jan 26, 2012. B. Katherine Poole-Smith, Manuela Beltran, Kay M. Tomashek, and Elizabeth A. Hunsperger are employees of the U.S. Government. This work was prepared as part of their official duties.

Authors' addresses: B. Katherine Poole-Smith, Manuela Beltran, Kay M. Tomashek, and Elizabeth A. Hunsperger, Dengue Branch, Centers for Disease Control and Prevention, San Juan, PR, E-mails: isd5@cdc.gov, mvb6@cdc.gov, kct9@cdc.gov, and enh4@cdc.gov. Alexa Gilbert, AssureRx Canada, Toronto, Ontario, Canada, E-mail: alexa.gilbert@mail.mcgill.ca. Andrea L. Gonzalez, Environmental Health, University of Puerto Rico Graduate School of Public Health, San Juan, PR, E-mail: andrea.l.gonzalez@upr.edu. Brian J. Ward, National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada, E-mail: brian.ward@mcgill.ca. Momar Ndao, National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada, and FQRNT Centre for Host–Parasite Interactions, McGill University, Montreal, Quebec, Canada, E-mail: momar.ndao@mcgill.ca.

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