title: Low adiposity during early infancy is associated with a low risk for developing dengue hemorrhagic fever: a preliminary model.
abstract: Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection.
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Libraty
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Marcia
authors.initials: M
authors.lastname: Woda
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Kris
authors.initials: K
authors.lastname: Giaya
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Chido Loveness
authors.initials: CL
authors.lastname: Kathivu
authors.affiliation: Department of Immunology, Research Institute for Tropical Medicine, Manila, Philippines.
authors.forename: Luz P
authors.initials: LP
authors.lastname: Acosta
authors.affiliation: Department of Epidemiology, Research Institute for Tropical Medicine, Manila, Philippines.
authors.forename: Veronica
authors.initials: V
authors.lastname: Tallo
authors.affiliation: Department of Molecular Biology, Research Institute for Tropical Medicine, Manila, Philippines.
authors.forename: Edelwisa
authors.initials: E
authors.lastname: Segubre-Mercado
authors.affiliation: Department of Virology, Research Institute for Tropical Medicine, Manila, Philippines.
authors.forename: Analisa
authors.initials: A
authors.lastname: Bautista
authors.affiliation: Department of Medicine, Research Institute for Tropical Medicine, Manila, Philippines.
authors.forename: AnaMae
authors.initials: A
authors.lastname: Obcena
authors.affiliation: San Pablo City Health Office, San Pablo, Philippines.
authors.forename: Job D
authors.initials: JD
authors.lastname: Brion
authors.affiliation: Department of Medicine, Research Institute for Tropical Medicine, Manila, Philippines ; Department of Microbiology, Research Institute for Tropical Medicine, Manila, Philippines.
authors.forename: Rosario Z
authors.initials: RZ
authors.lastname: Capeding
mesh_terms: D050154:Adiposity; D000328:Adult; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007223:Infant; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D044342:Malnutrition / Q000378:metabolism / Q000821:virology; D015233:Models, Statistical; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012306:Risk; D019595:Severe Dengue / Q000453:epidemiology* / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D020738:Leptin; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP