Volume 86, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Dengue virus infections are a major cause of morbidity in tropical countries. Early detection of dengue hemorrhagic fever (DHF) may help identify individuals that would benefit from intensive therapy. Predictive modeling was performed using 11 laboratory values of 51 individuals (38 DF and 13 DHF) obtained on initial presentation using logistic regression. We produced a robust model with an area under the curve of 0.9615 that retained IL-10 levels, platelets, and lymphocytes as the major predictive features. A classification and regression tree was developed on these features that were 86% accurate on cross-validation. The IL-10 levels and platelet counts were also identified as the most informative features associated with DHF using a Random Forest classifier. In the presence of polymerase chain reaction-proven acute dengue infections, we suggest a complete blood count and rapid measurement of IL-10 can assist in the triage of potential DHF cases for close follow-up or clinical intervention improving clinical outcome.


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  1. San Martin JL, Brathwaite O, Zambrano B, Solórzano JO, Bouckenooghe A, Dayan GH, Guzmán MG, , 2010. The epidemiology of dengue in the Americas over the last three decades: a worrisome reality. Am J Trop Med Hyg 82: 128135.[Crossref] [Google Scholar]
  2. Martina BE, Koraka P, Osterhaus AD, , 2009. Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22: 564581.[Crossref] [Google Scholar]
  3. Graham RR, Juffrie M, Tan R, Hayes CG, Laksono I, Ma'roet C, Erlin, Sutaryo, Porter KR, Halstead SB, , 1999. A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. studies in 1995–1996. Am J Trop Med Hyg 61: 412419. [Google Scholar]
  4. Guzman MG, Kouri G, Bravo J, Valdes L, Vazquez S, Halstead SB, , 2002. Effect of age on outcome of secondary dengue 2 infections. Int J Infect Dis 6: 118124.[Crossref] [Google Scholar]
  5. Thomas L, Verlaeten O, Cabie A, Kaidomar S, Moravie J, Najioullah F, Plumelle Y, Fonteau C, Dussart P, Césaire R, , 2008. Influence of the dengue serotype, previous dengue infection, and plasma viral load on clinical presentation and outcome during a dengue-2 and dengue-4 co-epidemic. Am J Trop Med Hyg 78: 990998. [Google Scholar]
  6. Kliks S, , 1990. Antibody-enhanced infection of monocytes as the pathogenetic mechanism for severe dengue illness. AIDS Res Hum Retroviruses 6: 993998. [Google Scholar]
  7. Green S, Rothman A, , 2006. Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Curr Opin Infect Dis 19:: 429436.[Crossref] [Google Scholar]
  8. Rothman AL, , 2011. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 11: 532543.[Crossref] [Google Scholar]
  9. Ranjit S, Kissoon N, Jayakumar I, , 2005. Aggressive management of dengue shock syndrome may decrease mortality rate: a suggested protocol. Pediatr Crit Care Med 6: 6.[Crossref] [Google Scholar]
  10. Forshey BM, Guevara C, Laguna-Torres VA, Cespedes M, Vargas J, Gianella A, Vallego E, Madrid C, Aguayo N, Gotuzzo E, Suarez V, Morales AM, Beingolea L, Reyes N, Perez J, Negrete M, Rocha C, Morrison AC, Russell KL, Blair PS, , HMRCD Febrile Surveillance Working Group, 2010. Arboviral etiologies of acute febrile illnesses in western South America, 2000–2007. PLoS Negl Trop Dis 4: e787.[Crossref] [Google Scholar]
  11. Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV, , 1992. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol 30: 545551. [Google Scholar]
  12. World Health Organization (WHO), 1997. Dengue Haemorrhagic Fever: Diagnosis, Treatment, and Control. Geneva: World Health Organization. [Google Scholar]
  13. Iswaharan H, Rao J, , 2005. Spike and slab variable selection: frequentist and Bayesian strategies. Ann Stat 33: 730773.[Crossref] [Google Scholar]
  14. Stone M, , 1977. An asymptotic equivalence of choice of model by cross-validation and Akaike's criterion. J R Stat Soc, B 39: 4447. [Google Scholar]
  15. Hassa PO, Hottiger MO, Burkle A, , 2006. PARP-1 as novel coactivator of NF-kB in inflammatory disorders. , ed. PolyADP Ribosylation. Austin, TX: Landes Bioscience, 7587. [Google Scholar]
  16. Fawcett T, , 2006. An introduction to ROC analysis. Pattern Recognit Lett 27: 861874.[Crossref] [Google Scholar]
  17. Hanley JA, McNeil BJ, , 1982. The meaning and use of the area under a receiver operating characteristic curve. Radiology 143: 2936.[Crossref] [Google Scholar]
  18. Potts JA, Gibbons RV, Rothman AL, Srikiatkhachorn A, Thomas SJ, Supradish PO, Lemon SC, Libraty DH, Green S, Kalayanarooj S, , 2010. Prediction of dengue disease severity among pediatric Thai patients using early clinical laboratory indicators. PLoS Negl Trop Dis 4: e769.[Crossref] [Google Scholar]
  19. Tanner L, Schreiber M, Low JG, Ong A, Tolfvenstam T, Lai YL, Ng LC, Leo YS, Thi Poung L, Vasudevan SG, Simmons CP, Hibberd ML, Ooi EE, , 2008. Decision tree algorithms predict the diagnosis and outcome of dengue fever in the early phase of illness. PLoS Negl Trop Dis 2: e196.[Crossref] [Google Scholar]
  20. Saraiva M, O'Garra A, , 2010. The regulation of IL-10 production by immune cells. Nat Rev Immunol 10: 170181.[Crossref] [Google Scholar]
  21. Boonnak K, Dambach KM, Donofrio GC, Tassaneetrithep B, Marovich MA, , 2011. Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection. J Virol 85: 16711683.[Crossref] [Google Scholar]
  22. Chareonsirisuthigul T, Kalayanarooj S, Ubol S, , 2007. Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells. J Gen Virol 88: 365375.[Crossref] [Google Scholar]
  23. Bozza F, Cruz O, Zagne S, Azeredo EL, Nogueria RM, Assis EF, Bozza PT, Kubelka CF, , 2008. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC Infect Dis 8: 86.[Crossref] [Google Scholar]
  24. Chen LC, Lei HY, Liu CC, Shiesh SC, Chen SH, Liu HS, Lin YS, Wang ST, Shyu HW, Yeh TM, , 2006. Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients. Am J Trop Med Hyg 74: 142147. [Google Scholar]
  25. Chen RF, Yang KD, Wang L, Liu JW, Chiu CC, Cheng JT, , 2007. Different clinical and laboratory manifestations between dengue hemorrhagic fever and dengue fever with bleeding tendency. Trans R Soc Trop Med Hyg 101: 11061113.[Crossref] [Google Scholar]
  26. Perez AB, Garcia G, Sierra B, Alvarez M, Vázquez S, Cabrera MV, Rodriguez R, Rosario D, Martinez E, Denny T, Guzmán MG, , 2004. IL-10 levels in dengue patients: some findings from the exceptional epidemiological conditions in Cuba. J Med Virol 73: 230234.[Crossref] [Google Scholar]
  27. Mitrakul C, Poshyachinda M, Futrakul P, Sangkawibha N, Ahandrik S, , 1977. Hemostatic and platelet kinetic studies in dengue hemorrhagic fever. Am J Trop Med Hyg 26: 975984. [Google Scholar]
  28. Eu-Ahsunthornwattana N, Eu-ahsunthornwattana J, Thisyakorn U, , 2008. Peripheral blood count for dengue severity prediction: a prospective study in Thai children. Pediatrics 121: S127S128.[Crossref] [Google Scholar]

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  • Received : 19 Jul 2011
  • Accepted : 18 Nov 2011
  • Published online : 01 Feb 2012

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