Sensitive and Prolonged Detection of Dengue Virus RNA in Whole Blood

Jesse J. Waggoner Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia;

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Victoria Stittleburg Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia;

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Muktha S. Natrajan Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia;

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Alejandra Paniagua-Avila Fundación para la Salud Integral de los Guatemaltecos, FUNSALUD, Quetzaltenango, Guatemala;

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Desiree Bauer Center for Global Health, Colorado School of Public Health, Aurora, Colorado;

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Daniel Olson Center for Global Health, Colorado School of Public Health, Aurora, Colorado;
Division of Infectious Diseases and Epidemiology, Department of Pediatrics, University of Colorado at Denver, Aurora, Colorado;

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Hana M. El Sahly Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas;

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Edwin J. Asturias Center for Global Health, Colorado School of Public Health, Aurora, Colorado;
Division of Infectious Diseases and Epidemiology, Department of Pediatrics, University of Colorado at Denver, Aurora, Colorado;

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Evan J. Anderson Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia;
Division of Infectious Diseases, Department of Pediatrics, Emory University, Atlanta, Georgia;

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Flor M. Munoz Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas;
Departments of Pediatrics, Section of Infectious Diseases, and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas

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ABSTRACT

Molecular detection of dengue virus (DENV) RNA from serum or plasma provides an accurate acute-phase diagnostic (< 7 days after symptom onset). Detection may be prolonged in whole blood, although data are limited. We tested for DENV by real-time reverse transcription–PCR in 345 paired acute-phase plasma and whole blood samples from individuals with a Flavivirus-like illness in southwestern Guatemala. In 18/18 cases with detectable DENV RNA in plasma, whole blood samples were positive and yielded similar cycle threshold values. In seven individuals with convalescent samples obtained 2–3 weeks later, DENV RNA remained detectable in whole blood but not plasma. In three additional cases, DENV RNA was only detectable in whole blood at the acute visit. In two cases, whole blood detection was linked to a virologically confirmed DENV infection 6–11 weeks earlier. Whole blood DENV RNA detection is sensitive for acute dengue infection and may remain positive for weeks to months.

Author Notes

Address correspondence to Jesse J. Waggoner, Division of Infectious Diseases, Department of Medicine, Emory University, 1760 Haygood Dr. NE, Rm. E-169, Atlanta, GA 30322. E-mail: jjwaggo@emory.edu

Disclosure: E. J. A has received personal fees from AbbVie, Pfizer, and Sanofi Pasteur for consulting, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi-Pasteur, Janssen, and Micron. He also serves on a safety monitoring board for Kentucky BioProcessing, Inc. F.M. Munoz has conducted clinical research unrelated to this manuscript supported by the CDC, Novavax, Regeneron, BioCryst, Alios, Janssen, Gilead, and Merck, and is a member of the Data Safety Monitoring Committee for studies conducted by Moderna, Pfizer, Meissa Vaccines, Virometix, and the National Institutes of Health.

Financial support: This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases (NIAID). Research was supported by a NIAID DMID Vaccine and Treatment Evaluation Unit (VTEU) award to Baylor College of Medicine (Contract no. HHSN27220130015I).

Authors’ addresses: Jesse J. Waggoner, Victoria Stittleburg, and Evan J. Anderson, Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA, E-mails: jesse.waggoner@emoryhealthcare.org, victoria.d.simmons@emory.edu, and evanderson@emory.edu. Muktha S. Natrajan, Centers for Disease Control and Prevention, RDB, Atlanta, GA, E-mail: qdz9@cdc.gov. Alejandra Paniagua-Avila, Fundación para la Salud Integral de los Guatemaltecos, FUNSALUD, Quetzaltenango, Guatemala, E-mail: alejandra.paniagua.fsigcu@gmail.com. Desiree Bauer, Center for Global Health, Colorado School of Public Health, Aurora, CO, E-mail: desiree.bauer@cuanschutz.edu. Daniel Olson and Edwin J. Asturias, Center for Global Health, Colorado School of Public Health, Aurora, CO, and Division of Infectious Diseases and Epidemiology, Department of Pediatrics, University of Colorado at Denver, Aurora, CO, E-mails: daniel.olson@childrenscolorado.org and edwin.asturias@childrenscolorado.org. Hana M. El Sahly, Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, E-mail: hana.elsahly@bcm.edu. Flor M. Munoz, Departments of Pediatrics, Section of Infectious Diseases, and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, E-mail: florm@bcm.edu.

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