Antibody-Dependent Enhancement of Severe Disease Is Mediated by Serum Viral Load in Pediatric Dengue Virus Infections. (1st April 2020)

• Record Type: Journal Article
• Authors: Waggoner, Jesse J; Katzelnick, Leah C; Burger-Calderon, Raquel; Gallini, Julia; Moore, Renee H; Kuan, Guillermina; Balmaseda, Angel; Pinsky, Benjamin A; Harris, Eva
• Is Part Of: Journal of infectious diseases. Volume 221:Number 11(2020)
• Page Start: 1846
• Page End: 1854
• Publication Date: 2020-04-01
• Subjects: dengue virus -- antibody-dependent enhancement -- viral load -- severity; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiz618
• Languages: English
• ISSNs: 0022-1899

Abstract

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. Abstract : Low preexisting anti-dengue virus antibody levels are associated with elevated disease severity. The current study demonstrates that this effect is mediated by viral load, providing evidence for the mechanism of antibody-dependent enhancement in dengue.