This study seeks to determine key triggers of dengue hemorrhagic fever (DHF) in patients from Bangkok, Thailand. The researchers' central hypothesis is that DHF cases will demonstrate an elevated proportion of inflammatory macrophages and a unique cytokine expression profile early in infection that exacerbates endothelial cell permeability compared to dengue fever controls. Preliminary results from eight enrolled patients found an elevated frequency of inflammatory macrophages and increased expression of TNF-alpha and VEGF in acute samples from DHF cases versus controls, demonstrating that an early shift to inflammatory macrophages may be critical to increased vasoactive mediator levels and disease severity.

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Control/Tracking Number: 15­A­1957­ASTMH
Activity: Abstract
Current Date/Time: 4/7/2015 10:28:22 PM
Potential Triggers of Dengue Hemorrhagic Fever in Patients from Bangkok, Thailand
Author Block: James F. Kelley1, Pornsawan Leaungwutiwong2, Vivek R. Nerurkar1, In­Kyu Yoon3, Piyarat
Suntarattiwong4, Anon Srikiatkhachorn5
1Department of Tropical Medicine, Medical Microbiology and Pharmacology, and Northern Pacific Global Health
Program, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States, 2Department
of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University and Northern Pacific Global Health
Program, Bangkok, Thailand, 3Department of Virology, Armed Forces Research Institute of Medical Sciences,
Bangkok, Thailand, 4Infectious Diseases Unit, Department of Pediatrics, Queen Sirikit National Institute of Child
Health, Bangkok, Thailand, 5Department of Medicine, University of Massachusetts Medical School, Worcester, MA,
United States and Northern Pacific Global Health Program, Bangkok, Thailand
Abstract:
Dengue fever (DF), a mosquito­borne disease, is among the most significant global health challenges. After dengue
virus (DENV) infection, patients may progress to dengue hemorrhagic fever (DHF) within days. Evidence suggests
that vascular endothelial cell dysfunction, coagulation disorders and increased plasma leakage occur rapidly after
peak viremia and at defervescence, corresponding with elevated levels of circulating chemokines and cytokines. We
seek to determine key triggers of DHF as part of an ongoing case­control study at the Queen Sirikit National Institute
of Child Health in Bangkok Thailand. Our central hypothesis is that DHF cases demonstrate an elevated proportion of
inflammatory (M1) compared to resting (M2) macrophages and demonstrate a unique cytokine expression profile
early during infection that exacerbates endothelial cell permeability compared to DF controls. To date, we have
enrolled eight hospitalized febrile patients, collecting both acute and convalescent blood samples. Aliquots of fresh
blood were used to assess the frequency and vasoactive mediator expression profiles of CD14+ cells and subsets by
flow cytometry. Preliminary results demonstrate an elevated M1 frequency and increased expression of TNF­alpha
and VEGF in acute samples from DHF cases compared to controls. These data demonstrate that an early shift to M1
in DENV­infected patients may be critical to subsequently elevated vasoactive mediator levels and disease severity.
:
Category (Complete): Global Health
Presentation Preference (Complete): Poster
Keyword (Complete): Dengue virus ; Case­control study ; Bangkok, Thailand
Disclosures (Complete):
Response : I did not indicate a conflict of interest.
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