title: Evaluation of host and viral factors associated with severe dengue based on the 2009 WHO classification.
abstract: BACKGROUND
  Dengue fever (DF) is the most prevalent arthropod-borne viral disease affecting humans. The World Health Organization (WHO) proposed a revised classification in 2009 to enable the more effective identification of cases of severe dengue (SD). This was designed primarily as a clinical tool, but it also enables cases of SD to be differentiated into three specific subcategories (severe vascular leakage, severe bleeding, and severe organ dysfunction). However, no study has addressed whether this classification has advantage in estimating factors associated with the progression of disease severity or dengue pathogenesis. We evaluate in a dengue outbreak associated risk factors that could contribute to the development of SD according to the 2009 WHO classification.
  
  
  METHODS
  A prospective cross-sectional study was performed during an epidemic of dengue in 2009 in Chiapas, Mexico. Data were analyzed for host and viral factors associated with dengue cases, using the 1997 and 2009 WHO classifications. The cost-benefit ratio (CBR) was also estimated.
  
  
  RESULTS
  The sensitivity in the 1997 WHO classification for determining SD was 75%, and the specificity was 97.7%. For the 2009 scheme, these were 100% and 81.1%, respectively. The 2009 classification showed a higher benefit (537%) with a lower cost (10.2%) than the 1997 WHO scheme. A secondary antibody response was strongly associated with SD. Early viral load was higher in cases of SD than in those with DF. Logistic regression analysis identified predictive SD factors (secondary infection, disease phase, viral load) within the 2009 classification. However, within the 1997 scheme it was not possible to differentiate risk factors between DF and dengue hemorrhagic fever or dengue shock syndrome. The critical clinical stage for determining SD progression was the transition from fever to defervescence in which plasma leakage can occur.
  
  
  CONCLUSIONS
  The clinical phenotype of SD is influenced by the host (secondary response) and viral factors (viral load). The 2009 WHO classification showed greater sensitivity to identify SD in real time. Timely identification of SD enables accurate early decisions, allowing proper management of health resources for the benefit of patients at risk for SD. This is possible based on the 2009 WHO classification.
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Código Postal 04510, México, DF, México. jomarpoa@hotmail.com.
authors.forename: Jorge O
authors.initials: JO
authors.lastname: Pozo-Aguilar
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Código Postal 04510, México, DF, México. veromon@yahoo.com.
authors.forename: Verónica
authors.initials: V
authors.lastname: Monroy-Martínez
authors.affiliation: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, UNAM, Sede del tercer Circuito Exterior, México, DF, México. ddiaz@ciencias.unam.mx.
authors.forename: Daniel
authors.initials: D
authors.lastname: Díaz
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Código Postal 04510, México, DF, México. barriosjacqueline22@gmail.com.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Barrios-Palacios
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP), Av. Universidad 655, Col. Santa María Ahuacatitlán 62508, Cuernavaca, Morelos, México. cramos@insp.mx.
authors.forename: Celso
authors.initials: C
authors.lastname: Ramos
authors.affiliation: Centro Regional de Investigación en Salud Pública, INSP. 4ª. Norte esquina con 19 Poniente, Código Postal 30700, Tapachula, Chiapas, México. aulloa@insp.mx.
authors.forename: Armando
authors.initials: A
authors.lastname: Ulloa-García
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Código Postal 04510, México, DF, México. sorjuana@ciencias.unam.mx.
authors.forename: Janet
authors.initials: J
authors.lastname: García-Pillado
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Código Postal 04510, México, DF, México. bhro@unam.mx.
authors.forename: Blanca H
authors.initials: BH
authors.lastname: Ruiz-Ordaz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D011446:Prospective Studies; D019595:Severe Dengue / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D012720:Severity of Illness Index; D014944:World Health Organization; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral