Volume 82, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Dengue infection can be challenging to diagnose early in the course of infection before severe manifestations develop, but early diagnosis can improve patient outcomes and promote timely public health interventions. We developed age-based predictive models generated from 2 years of data from an enhanced dengue surveillance system in Puerto Rico. These models were internally validated and were able to differentiate dengue infection from other acute febrile illnesses with moderate accuracy. The accuracy of the models was greater than either the current World Health Organization case definition for dengue fever or a proposed modification to this definition, while requiring the collection of fewer data. In young children, thrombocytopenia and the absence of cough were associated with dengue infection; for adults, rash, leucopenia, and the absence of sore throat were associated with dengue infection; in all age groups, retro-orbital pain was associated with dengue infection.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Gubler DJ, , 1998. The global pandemic of dengue/dengue haemorrhagic fever: current status and prospects for the future. Ann Acad Med Singapore 27: 227234. [Google Scholar]
  2. Gibbons RV, Vaughn DW, , 2002. Dengue: an escalating problem. BMJ 324: 15631566.[Crossref] [Google Scholar]
  3. World Health Organization, 1997. Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. Second edition. Geneva: World Health Organization. [Google Scholar]
  4. Rigau-Perez JG, , 2006. Severe dengue: the need for new case definitions. Lancet Infect Dis 6: 297302.[Crossref] [Google Scholar]
  5. Phuong CX, Nhan NT, Kneen R, Thuy PT, Thien CV, Nga NT, Thuy TT, Solomon T, Stepniewska K, Willis B, Dong Nai Study Group, 2004. Clinical diagnosis and assessment of severity of confirmed dengue infections in Vietnamese children: is the world health organization classification system helpful? Am J Trop Med Hyg 70: 172179. [Google Scholar]
  6. Bandyopadhyay S, Lum LC, Kroeger A, , 2006. Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever. Trop Med Int Health 11: 12381255.[Crossref] [Google Scholar]
  7. Deen JL, Harris E, Wills B, Balmaseda A, Hammond SN, Rocha C, Dung NM, Hung NT, Hien TT, Farrar J, , 2006. The WHO dengue classification and case definitions: time for a reassessment. Lancet 368: 170173.[Crossref] [Google Scholar]
  8. World Health Organization, 2009. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control. Third edition. Geneva: World Health Organization. [Google Scholar]
  9. Wills BA, Nguyen MD, Ha TL, Dong TH, Tran TN, Le TT, Tran VD, Nguyen TH, Nguyen VC, Stepniewska K, White NJ, Farrar JJ, , 2005. Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med 353: 877889.[Crossref] [Google Scholar]
  10. Farrar J, Focks D, Gubler D, Barrera R, Guzman MG, Simmons C, Kalayanarooj S, Lum L, McCall PJ, Lloyd L, Horstick O, Dayal-Drager R, Nathan MB, Kroeger A, , 2007. Towards a global dengue research agenda. Trop Med Int Health 12: 695699.[Crossref] [Google Scholar]
  11. Potts JA, Rothman AL, , 2008. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations. Trop Med Int Health 13: 13281340.[Crossref] [Google Scholar]
  12. Hammond SN, Balmaseda A, Perez L, Tellez Y, Saborio SI, Mercado JC, Videa E, Rodriguez Y, Perez MA, Cuadra R, Solano S, Rocha J, Idiaquez W, Gonzalez A, Harris E, , 2005. Differences in dengue severity in infants, children, and adults in a 3-year hospital-based study in Nicaragua. Am J Trop Med Hyg 73: 10631070. [Google Scholar]
  13. Deparis X, Murgue B, Roche C, Cassar O, Chungue E, , 1998. Changing clinical and biological manifestations of dengue during the dengue-2 epidemic in French Polynesia in 1996/97–description and analysis in a prospective study. Trop Med Int Health 3: 859865.[Crossref] [Google Scholar]
  14. Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S, Kunentrasai N, Viramitrachai W, Ratanachu-eke S, Kiatpolpoj S, Innis BL, Rothman AL, Nisalak A, Ennis FA, , 1997. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 176: 313321.[Crossref] [Google Scholar]
  15. Kittigul L, Pitakarnjanakul P, Sujirarat D, Siripanichgon K, , 2007. The differences of clinical manifestations and laboratory findings in children and adults with dengue virus infection. J Clin Virol 39: 7681.[Crossref] [Google Scholar]
  16. Premaratna R, Pathmeswaran A, Amarasekara ND, Motha MB, Perera KV, de Silva HJ, , 2009. A clinical guide for early detection of dengue fever and timing of investigations to detect patients likely to develop complications. Trans R Soc Trop Med Hyg 103: 127131.[Crossref] [Google Scholar]
  17. Ramos MM, Tomashek KM, Arguello DF, Luxemburger C, Quiñones L, Lang J, Muñoz-Jordan JL, , 2008. Early clinical features of dengue infection in Puerto Rico. Trans R Soc Trop Med Hyg 103: 878884.[Crossref] [Google Scholar]
  18. Ramos MM, Arguello DF, Luxemburger C, Quinoñes L, Muñoz JL, Beatty M, Lang J, Tomasek KM, , 2008. Epidemiological and clinical observations on patients with dengue in Puerto Rico: results from the first year of enhanced surveillance—June 2005–May 2006. Am J Trop Med Hyg 79: 123127. [Google Scholar]
  19. Hollowell JG, van Assendelft OW, Gunter EW, Lewis BG, Najjar M, Pfeiffer C, Centers for Disease Control and Prevention, National Center for Health Statistics, 2005. Hematological and iron-related analytes–reference data for persons aged 1 year and over: United States, 1988–94. Vital Health Stat 11 247: 1156. [Google Scholar]
  20. Chien LJ, Liao TL, Shu PY, Huang JH, Gubler DJ, Chang GJ, , 2006. Development of real-time reverse transcriptase PCR assays to detect and serotype dengue viruses. J Clin Microbiol 44: 12951304.[Crossref] [Google Scholar]
  21. Johnson BW, Russell BJ, Lanciotti RS, , 2005. Serotype-specific detection of dengue viruses in a fourplex real-time reverse transcriptase PCR assay. J Clin Microbiol 43: 49774983.[Crossref] [Google Scholar]
  22. Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Santayakorn S, Puttisri P, Hoke CH, , 1989. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg 40: 418427. [Google Scholar]
  23. Swets JA, , 1988. Measuring the accuracy of diagnostic systems. Science 240: 12851293.[Crossref] [Google Scholar]
  24. Fischer JE, Bachmann LM, Jaeschke R, , 2003. A readers' guide to the interpretation of diagnostic test properties: clinical example of sepsis. Intensive Care Med 29: 10431051.[Crossref] [Google Scholar]
  25. Steyerberg EW, Harrell FE, Jr Borsboom GJ, Eijkemans MJ, Vergouwe Y, Habbema JD, , 2001. Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol 54: 774781.[Crossref] [Google Scholar]
  26. Chadwick D, Arch B, Wilder-Smith A, Paton N, , 2006. Distinguishing dengue fever from other infections on the basis of simple clinical and laboratory features: application of logistic regression analysis. J Clin Virol 35: 147153.[Crossref] [Google Scholar]
  27. Dietz VJ, Gubler DJ, Rigau-Perez JG, Pinheiro F, Schatzmayr HG, Bailey R, Gunn RA, , 1990. Epidemic dengue 1 in Brazil, 1986: evaluation of a clinically based dengue surveillance system. Am J Epidemiol 131: 693701. [Google Scholar]
  28. Kumar R, Tripathi P, Tripathi S, Kanodia A, Pant S, Venkatesh V, , 2008. Prevalence and clinical differentiation of dengue fever in children in northern India. Infection 36: 444449.[Crossref] [Google Scholar]
  29. Low JG, Ooi EE, Tolfvenstam T, Leo YS, Hibberd ML, Ng LC, Lai YL, Yap GS, Li CS, Vasudevan SG, Ong A, , 2006. Early dengue infection and outcome study (EDEN)—study design and preliminary findings. Ann Acad Med Singapore 35: 783789. [Google Scholar]
  30. Karande S, Gandhi D, Kulkarni M, Bharadwaj R, Pol S, Thakare J, De A, , 2005. Concurrent outbreak of leptospirosis and dengue in Mumbai, India, 2002. J Trop Pediatr 51: 174181.[Crossref] [Google Scholar]
  31. Bruce MG, Sanders EJ, Leake JA, Zaidel O, Bragg SL, Aye T, Shutt KA, Deseda CC, Rigau-Perez JG, Tappero JW, Perkins BA, Spiegel RA, Ashford DA, , 2005. Leptospirosis among patients presenting with dengue-like illness in Puerto Rico. Acta Trop 96: 3646.[Crossref] [Google Scholar]
  32. Buchy P, Vo VL, Bui KT, Trinh TX, Glaziou P, Le TT, Le VL, Bui TC, , 2005. Secondary dengue virus type 4 infections in Vietnam. Southeast Asian J Trop Med Public Health 36: 178185. [Google Scholar]
  33. McBride WJ, Mullner H, LaBrooy JT, Wronski I, , 1998. The 1993 dengue 2 epidemic in Charters Towers, North Queensland: clinical features and public health impact. Epidemiol Infect 121: 151156.[Crossref] [Google Scholar]
  34. Phuong HL, de Vries PJ, Nga TT, Giao PT, Hung LQ, Binh TQ, Nam NV, Nagelkerke N, Kager PA, , 2006. Dengue as a cause of acute undifferentiated fever in Vietnam. BMC Infect Dis 6: 123.[Crossref] [Google Scholar]
  35. Nunes-Araujo FR, Ferreira MS, Nishioka SD, , 2003. Dengue fever in Brazilian adults and children: assessment of clinical findings and their validity for diagnosis. Ann Trop Med Parasitol 97: 415419.[Crossref] [Google Scholar]
  36. Suwandono A, Kosasih H, Nurhayati Kusriastuti R, Harun S, Ma'roef C, Wuryadi S, Herianto B, Yuwono D, Porter KR, Beckett CG, Blair PJ, , 2006. Four dengue virus serotypes found circulating during an outbreak of dengue fever and dengue haemorrhagic fever in Jakarta, Indonesia, during 2004. Trans R Soc Trop Med Hyg 100: 855862.[Crossref] [Google Scholar]
  37. Watt G, Jongsakul K, Chouriyagune C, Paris R, , 2003. Differentiating dengue virus infection from scrub typhus in Thai adults with fever. Am J Trop Med Hyg 68: 536538. [Google Scholar]
  38. Gamble J, Bethell D, Day NP, Loc PP, Phu NH, Gertside IB, Farrar JF, White NJ, , 2000. Age-related changes in microvascular permeability: a significant factor in the susceptibility of children to shock? Clin Sci (Lond) 98: 211216.[Crossref] [Google Scholar]
  39. Karavanaki K, Polychronopoulou S, Giannaki M, Haliotis F, Sider B, Brisimitzi M, Dimitriou C, Scordias G, Marangou F, Stamatiadou A, Avionitis S, , 2006. Transient and chronic neutropenias detected in children with different viral and bacterial infections. Acta Paediatr 95: 565572.[Crossref] [Google Scholar]
  40. Monto AS, , 1994. Studies of the community and family: acute respiratory illness and infection. Epidemiol Rev 16: 351373.[Crossref] [Google Scholar]
  41. Monto AS, , 2002. Epidemiology of viral respiratory infections. Am J Med 112 (Suppl 6A): 4S12S.[Crossref] [Google Scholar]
  42. Kapoor HK, Bhai S, John M, Xavier J, , 2006. Ocular manifestations of dengue fever in an East Indian epidemic. Can J Ophthalmol 41: 741746.[Crossref] [Google Scholar]
  43. Pek DC, Teoh SC, , 2007. Ocular manifestations in dengue fever. Can J Ophthalmol 42: 755756.[Crossref] [Google Scholar]
  44. Su DH, Bacsal K, Chee SP, Flores JV, Lim WK, Cheng BC, Jap AH, ; Dengue Maculopathy Study Group, 2007. Prevalence of dengue maculopathy in patients hospitalized for dengue fever. Ophthalmology 114: 17431747.[Crossref] [Google Scholar]
  45. Lim WK, Mathur R, Koh A, Yeoh R, Chee SP, , 2004. Ocular manifestations of dengue fever. Ophthalmology 111: 20572064.[Crossref] [Google Scholar]
  46. Sanjay S, Wagle AM, Au Eong KG, , 2009. Dengue optic neuropathy. Ophthalmology 116: 170.[Crossref] [Google Scholar]
  47. Tan CS, Teoh SC, Chan DP, Wong IB, Lim TH, , 2007. Dengue retinopathy manifesting with bilateral vasculitis and macular oedema. Eye 21: 875877.[Crossref] [Google Scholar]
  48. Gupta A, Srinivasan R, Setia S, Soundravally R, Pandian DG, , 2009. Uveitis following dengue fever. Eye 23: 873876.[Crossref] [Google Scholar]
  49. Kanungo S, Shukla D, Kim R, , 2008. Branch retinal artery occlusion secondary to dengue fever. Indian J Ophthalmol 56: 7374.[Crossref] [Google Scholar]
  50. Bacsal KE, Chee SP, Cheng CL, Flores JV, , 2007. Dengue-associated maculopathy. Arch Ophthalmol 125: 501510.[Crossref] [Google Scholar]
  51. Seet RC, Quek AM, Lim EC, , 2007. Symptoms and risk factors of ocular complications following dengue infection. J Clin Virol 38: 101105.[Crossref] [Google Scholar]
  52. Wilder-Smith A, Earnest A, Paton NI, , 2004. Use of simple laboratory features to distinguish the early stage of severe acute respiratory syndrome from dengue fever. Clin Infect Dis 39: 18181823.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 14 Sep 2009
  • Accepted : 09 Feb 2010
  • Published online : 05 May 2010

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error