title: Early clinical features of dengue virus infection in nicaraguan children: a longitudinal analysis.
abstract: BACKGROUND
  Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined.
  
  
  METHODS
  Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2-14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender.
  
  
  RESULTS
  One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness.
  
  
  CONCLUSIONS
  Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management.
authors.affiliation: Division of Epidemiology, School of Public Health, University of California, Berkeley, California, United States of America.
authors.forename: Hope H
authors.initials: HH
authors.lastname: Biswas
authors.forename: Oscar
authors.initials: O
authors.lastname: Ortega
authors.forename: Aubree
authors.initials: A
authors.lastname: Gordon
authors.forename: Katherine
authors.initials: K
authors.lastname: Standish
authors.forename: Angel
authors.initials: A
authors.lastname: Balmaseda
authors.forename: Guillermina
authors.initials: G
authors.lastname: Kuan
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
mesh_terms: D000293:Adolescent; D000818:Animals; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003715:Dengue / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D003716:Dengue Virus / Q000472:pathogenicity*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009527:Nicaragua; D013997:Time Factors