期刊
JOURNAL OF INFECTIOUS DISEASES
卷 209, 期 3, 页码 360-368出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit436
关键词
dengue; epidemiology; antibodies; immunity; pathogenesis; prospective cohort study
资金
- United States Army Medical Research and Materiel Command, Ft Detrick, MD, USA
- CDC [1R36CK00104]
- NIH [P01 AI034533]
- Military Infectious Diseases Research Program (MIDRP)
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.
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