title: Sequential dengue virus infections detected in active and passive surveillance programs in Thailand, 1994-2010.
abstract: BACKGROUND
  The effect of prior dengue virus (DENV) exposure on subsequent heterologous infection can be beneficial or detrimental depending on many factors including timing of infection. We sought to evaluate this effect by examining a large database of DENV infections captured by both active and passive surveillance encompassing a wide clinical spectrum of disease.
  
  
  METHODS
  We evaluated datasets from 17 years of hospital-based passive surveillance and nine years of cohort studies, including clinical and subclinical DENV infections, to assess the outcomes of sequential heterologous infections. Chi square or Fisher's exact test was used to compare proportions of infection outcomes such as disease severity; ANOVA was used for continuous variables. Multivariate logistic regression was used to assess risk factors for infection outcomes.
  
  
  RESULTS
  Of 38,740 DENV infections, two or more infections were detected in 502 individuals; 14 had three infections. The mean ages at the time of the first and second detected infections were 7.6 ± 3.0 and 11.2 ± 3.0 years. The shortest time between sequential infections was 66 days. A longer time interval between sequential infections was associated with dengue hemorrhagic fever (DHF) in the second detected infection (OR 1.3, 95% CI 1.2-1.4). All possible sequential serotype pairs were observed among 201 subjects with DHF at the second detected infection, except DENV-4 followed by DENV-3. Among DENV infections detected in cohort subjects by active study surveillance and subsequent non-study hospital-based passive surveillance, hospitalization at the first detected infection increased the likelihood of hospitalization at the second detected infection.
  
  
  CONCLUSIONS
  Increasing time between sequential DENV infections was associated with greater severity of the second detected infection, supporting the role of heterotypic immunity in both protection and enhancement. Hospitalization was positively associated between the first and second detected infections, suggesting a possible predisposition in some individuals to more severe dengue disease.
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. augurivicky@gmail.com.|Faculty of Public Health, Mahidol University, Bangkok, Thailand. augurivicky@gmail.com.
authors.forename: Piraya
authors.initials: P
authors.lastname: Bhoomiboonchoo
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. anandan@afrims.org.
authors.forename: Ananda
authors.initials: A
authors.lastname: Nisalak
authors.affiliation: Faculty of Public Health, Mahidol University, Bangkok, Thailand. nutkamol.cha@mahidol.ac.th.
authors.forename: Natkamol
authors.initials: N
authors.lastname: Chansatiporn
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. InKyu.Yoon@afrims.org.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Yoon
authors.affiliation: Queen Sirikit National Institute of Child Health, Bangkok, Thailand. siripenk@gmail.com.
authors.forename: Siripen
authors.initials: S
authors.lastname: Kalayanarooj
authors.affiliation: Faculty of Public Health, Mahidol University, Bangkok, Thailand. mathuros.tip@mahidol.ac.th.
authors.forename: Mathuros
authors.initials: M
authors.lastname: Thipayamongkolgul
authors.affiliation: Department of Infectious Diseases, State University of New York, Syracuse, NY, USA. phncs@yahoo.com.
authors.forename: Timothy
authors.initials: T
authors.lastname: Endy
authors.affiliation: University of Rhode Island, Providence, RI, USA. alan_rothman@mail.uri.edu.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA. sharone.green@umassmed.edu.
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA. anons@afrims.org.
authors.forename: Anon
authors.initials: A
authors.lastname: Srikiatkhachorn
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. daruneeb@afrims.org.
authors.forename: Darunee
authors.initials: D
authors.lastname: Buddhari
authors.affiliation: Vical, Incorporated, San Diego, CA, USA. mpm112@yahoo.com.
authors.forename: Mammen P
authors.initials: MP
authors.lastname: Mammen
authors.affiliation: US Army Institute of Surgical Research, San Antonio, TX, USA. robertvgibbons@gmail.com.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Gibbons
mesh_terms: D017668:Age of Onset; D000914:Antibodies, Viral / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D003715:Dengue / Q000453:epidemiology*; D003716:Dengue Virus; D005260:Female; D006760:Hospitalization; D006761:Hospitals; D006801:Humans; D008297:Male; D011159:Population Surveillance / Q000379:methods*; D012307:Risk Factors; D019595:Severe Dengue / Q000453:epidemiology; D012720:Severity of Illness Index; D013785:Thailand / Q000453:epidemiology; D013997:Time Factors
chemical_list: D000914:Antibodies, Viral