title: Multicentre prospective study on dengue classification in four South-east Asian and three Latin American countries.
abstract: OBJECTIVE
  To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence-based classification that would better reflect clinical severity.
  
  
  METHODS
  We followed suspected dengue cases daily in seven countries across South-east Asia and Latin America and then categorised them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre-defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not.
  
  
  RESULTS
  A total of 2259 patients were recruited during 2006-2007 and 230 (13%) of the 1734 laboratory-confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue haemorrhagic fever. However, no three-tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression.
  
  
  CONCLUSIONS
  Based on these results, a revised classification system comprised of two entities, 'Dengue' and 'Severe Dengue', was proposed and has now been incorporated into the new WHO guidelines.
authors.affiliation: London School of Tropical Medicine and Hygiene, London, UK.
authors.forename: Neal
authors.initials: N
authors.lastname: Alexander
authors.forename: Angel
authors.initials: A
authors.lastname: Balmaseda
authors.forename: Ivo C B
authors.initials: IC
authors.lastname: Coelho
authors.forename: Efren
authors.initials: E
authors.lastname: Dimaano
authors.forename: Tran T
authors.initials: TT
authors.lastname: Hien
authors.forename: Nguyen T
authors.initials: NT
authors.lastname: Hung
authors.forename: Thomas
authors.initials: T
authors.lastname: Jänisch
authors.forename: Axel
authors.initials: A
authors.lastname: Kroeger
authors.forename: Lucy C S
authors.initials: LC
authors.lastname: Lum
authors.forename: Eric
authors.initials: E
authors.lastname: Martinez
authors.forename: Joao B
authors.initials: JB
authors.lastname: Siqueira
authors.forename: Tran T
authors.initials: TT
authors.lastname: Thuy
authors.forename: Iris
authors.initials: I
authors.lastname: Villalobos
authors.forename: Elci
authors.initials: E
authors.lastname: Villegas
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001210:Asia, Southeastern; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000145:classification* / Q000473:pathology; D003937:Diagnosis, Differential; D006801:Humans; D007223:Infant; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D019595:Severe Dengue / Q000145:classification / Q000473:pathology; D012720:Severity of Illness Index; D013020:South America; D014944:World Health Organization; D055815:Young Adult