title: A shorter time interval between first and second dengue infections is associated with protection from clinical illness in a school-based cohort in Thailand.
abstract: BACKGROUND
  Despite the strong association between secondary dengue virus (DENV) infections and dengue hemorrhagic fever (DHF), the majority of secondary infections are subclinical or mild. The determinants of clinical severity remain unclear, though studies indicate a titer-dependent and time-dependent role of cross-protective anti-DENV antibodies.
  
  
  METHODS
  Data from 2 sequential prospective cohort studies were analyzed for subclinical and symptomatic DENV infections in schoolchildren in Kamphaeng Phet, Thailand (1998-2002 and 2004-2007). Children experiencing ≥ 1 DENV infection were selected as the population for analysis (contributing 2169 person-years of follow-up).
  
  
  RESULTS
  In total, 1696 children had ≥ 1 DENV infection detected during their enrollment; 268 experienced 2 or more infections. A shorter time interval between infections was associated with subclinical infection in children seronegative for DENV at enrollment, for whom a second-detected DENV infection is more likely to reflect a true second infection (average of 2.6 years between infections for DHF, 1.9 for DF, and 1.6 for subclinical infections).
  
  
  CONCLUSIONS
  These findings support a pathogenesis model where cross-reactive antibodies wane from higher-titer, protective levels to lower-titer, detrimental levels. This is one of the first studies of human subjects to suggest a window of cross-protection following DENV infection since Sabin's challenge studies in the 1940s.
authors: Department of Medicine, University of Minnesota Medical School, Minneapolis.
authors: Kathryn B
authors: KB
authors: Anderson
authors: Robert V
authors: RV
authors: Gibbons
authors: Derek A T
authors: DA
authors: Cummings
authors: Ananda
authors: A
authors: Nisalak
authors: Sharone
authors: S
authors: Green
authors: Daniel H
authors: DH
authors: Libraty
authors: Richard G
authors: RG
authors: Jarman
authors: Anon
authors: A
authors: Srikiatkhachorn
authors: Mammen P
authors: MP
authors: Mammen
authors: Buddhari
authors: B
authors: Darunee
authors: In-Kyu
authors: IK
authors: Yoon
authors: Timothy P
authors: TP
authors: Endy
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003429:Cross Reactions; D003715:Dengue / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012574:Schools; D013334:Students; D013785:Thailand / Q000453:epidemiology; D013997:Time Factors
chemical_list: D000914:Antibodies, Viral
keywords: antibodies; dengue; epidemiology; immunity; pathogenesis; prospective cohort study
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