Jesse J Waggoner1,2, Leah C Katzelnick3, Raquel Burger-Calderon4, Julia Gallini5, Renee H Moore5, Guillermina Kuan6, Angel Balmaseda4,7, Benjamin A Pinsky8,9, Eva Harris3. 1. Department of Medicine, Emory University, Atlanta, Georgia, USA. 2. Department of Global Health, Rollins School of Public Health, Atlanta, Georgia, USA. 3. Division of Infectious Diseases and Vaccinology, School of Public Health, University of California Berkeley, Berkeley, California, USA. 4. Sustainable Sciences Institute, Managua, Nicaragua. 5. Biostatistics Collaboration Core, Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, USA. 6. Centro de Salud Sócrates Flores Vivas, Ministry of Health, Managua, Nicaragua. 7. Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua. 8. Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. 9. Department of Medicine, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, California, USA.
Abstract
BACKGROUND: Low preexisting anti-dengue virus (DENV) antibody levels are associated with elevated disease severity. While antibody-dependent enhancement of dengue is thought to be driven by viral load, this has not been conclusively shown. We evaluated the association between preinfection anti-DENV antibody titers, viral load, and disease severity among 133 dengue cases in a Nicaraguan pediatric cohort study. METHODS: Viral load was quantified in acute-phase serum by real-time reverse transcription polymerase chain reaction and analyzed in relation to preinfection antibody titer (measured by inhibition enzyme-linked immunosorbent assay) and dengue severity, categorized using 3 definitions. RESULTS: Higher viral load was significantly associated with dengue severity; for each increase of 1.0 log10 copies/mL, the odds of severe dengue increased approximately 50%, regardless of severity definition. Viral load at presentation and the odds of severe disease were highest among patients with low to intermediate preinfection antibody titers and lowest among those with the highest antibody titers. We showed the effect of preinfection antibody titer on disease severity was mediated by viral load for each of 3 dengue severity outcomes. CONCLUSIONS: This study demonstrates the association between preinfection anti-DENV antibody titer, serum viral load, and disease severity, and provides evidence for the mechanism of antibody-dependent enhancement in dengue cases.
BACKGROUND: Low preexisting anti-dengue virus (DENV) antibody levels are associated with elevated disease severity. While antibody-dependent enhancement of dengue is thought to be driven by viral load, this has not been conclusively shown. We evaluated the association between preinfection anti-DENV antibody titers, viral load, and disease severity among 133 dengue cases in a Nicaraguan pediatric cohort study. METHODS: Viral load was quantified in acute-phase serum by real-time reverse transcription polymerase chain reaction and analyzed in relation to preinfection antibody titer (measured by inhibition enzyme-linked immunosorbent assay) and dengue severity, categorized using 3 definitions. RESULTS: Higher viral load was significantly associated with dengue severity; for each increase of 1.0 log10 copies/mL, the odds of severe dengue increased approximately 50%, regardless of severity definition. Viral load at presentation and the odds of severe disease were highest among patients with low to intermediate preinfection antibody titers and lowest among those with the highest antibody titers. We showed the effect of preinfection antibody titer on disease severity was mediated by viral load for each of 3 dengue severity outcomes. CONCLUSIONS: This study demonstrates the association between preinfection anti-DENV antibody titer, serum viral load, and disease severity, and provides evidence for the mechanism of antibody-dependent enhancement in dengue cases.
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