Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Clinical manifestations and diagnosis of dengue virus infection

Alan L Rothman, MD
Anon Srikiatkhachorn, MD
Siripen Kalayanarooj, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Dengue is the most prevalent mosquito-borne viral disease; it is estimated that over 390 million dengue virus infections occur each year throughout the world, including 96 million that produce illness [1]. Symptomatic dengue virus infections can present with a wide range of clinical manifestations, from mild febrile illness to a life-threatening shock syndrome or organ dysfunction [2,3]. Both viral and host factors are thought to contribute to the manifestations of disease in each infected individual.

The various clinical features and the available methods for the diagnosis of dengue virus infections will be reviewed here. The pathogenesis and measures to prevent and treat the disease are discussed separately. (See "Pathogenesis of dengue virus infection" and "Prevention and treatment of dengue virus infection" and "Epidemiology of dengue virus infections".)


There are four closely related but serologically distinct dengue viruses, called DENV-1, DENV-2, DENV-3, and DENV-4, of the genus Flavivirus. There is only transient and weak cross-protection among the four serotypes; therefore, individuals living in an area of endemic dengue can be infected with up to four dengue serotypes in a lifetime. Multiple virus serotypes often co-circulate within the same region (hyperendemicity), causing periodic epidemics.


The typical clinical manifestations of dengue range from self-limited dengue fever (DF) to dengue hemorrhagic fever (DHF) with shock syndrome [4]. In cohort studies involving more than 3400 children in Southeast Asia and Latin America, virologically confirmed dengue was responsible for approximately 10 percent of episodes of acute febrile illness, with an incidence of 2.9 and 4.6 episodes per 100 person-years in Latin America and Asia, respectively; the incidence of DHF was less than 0.3 episodes per 100 person-years [5].

With wider availability of laboratory testing, there are increasing reports of unusual clinical manifestations, as discussed below [3]. The risk of severe disease is much higher in repeat infection than primary infection [6]. (See "Pathogenesis of dengue virus infection".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Dec 2016. | This topic last updated: Wed Oct 26 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature 2013; 496:504.
  2. Teixeira MG, Barreto ML. Diagnosis and management of dengue. BMJ 2009; 339:b4338.
  3. World Health Organization Regional Office for Southeast Asia. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. Revised and expanded version. SEARO Technical Publication Series, New Delhi, India 2011.
  4. Simmons CP, Farrar JJ, Nguyen vV, Wills B. Dengue. N Engl J Med 2012; 366:1423.
  5. L'Azou M, Moureau A, Sarti E, et al. Symptomatic Dengue in Children in 10 Asian and Latin American Countries. N Engl J Med 2016; 374:1155.
  6. Deen JL, Harris E, Wills B, et al. The WHO dengue classification and case definitions: time for a reassessment. Lancet 2006; 368:170.
  7. SABIN AB. Research on dengue during World War II. Am J Trop Med Hyg 1952; 1:30.
  8. Sharp TW, Wallace MR, Hayes CG, et al. Dengue fever in U.S. troops during Operation Restore Hope, Somalia, 1992-1993. Am J Trop Med Hyg 1995; 53:89.
  9. Endy TP, Chunsuttiwat S, Nisalak A, et al. Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, Thailand. Am J Epidemiol 2002; 156:40.
  10. Rigau-Pérez JG. The early use of break-bone fever (Quebranta huesos, 1771) and dengue (1801) in Spanish. Am J Trop Med Hyg 1998; 59:272.
  11. Shirtcliffe P, Cameron E, Nicholson KG, Wiselka MJ. Don't forget dengue! Clinical features of dengue fever in returning travellers. J R Coll Physicians Lond 1998; 32:235.
  12. Schwartz E, Mendelson E, Sidi Y. Dengue fever among travelers. Am J Med 1996; 101:516.
  13. Cobra C, Rigau-Pérez JG, Kuno G, Vorndam V. Symptoms of dengue fever in relation to host immunologic response and virus serotype, Puerto Rico, 1990-1991. Am J Epidemiol 1995; 142:1204.
  14. Trofa AF, DeFraites RF, Smoak BL, et al. Dengue fever in US military personnel in Haiti. JAMA 1997; 277:1546.
  15. Srikiatkhachorn A, Gibbons RV, Green S, et al. Dengue hemorrhagic fever: the sensitivity and specificity of the world health organization definition for identification of severe cases of dengue in Thailand, 1994-2005. Clin Infect Dis 2010; 50:1135.
  16. Cunha BA, Apostolopoulou A, Sivarajah T, Klein NC. Facial Puffiness in a Returning Traveler From Puerto Rico: Chikungunya, Dengue Fever, or Zika Virus? Clin Infect Dis 2016; 63:1264.
  17. Kalayanarooj S, Vaughn DW, Nimmannitya S, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997; 176:313.
  18. Potts JA, Rothman AL. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations. Trop Med Int Health 2008; 13:1328.
  19. Halstead SB. Dengue. Lancet 2007; 370:1644.
  20. World Health Organization. Dengue hemorrhagic fever: diagnosis, treatment, prevention, and control. 2nd ed. WHO, Geneva 1997.
  21. Phuong CX, Nhan NT, Kneen R, et al. 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 2004; 70:172.
  22. Tassniyom S, Vasanawathana S, Chirawatkul A, Rojanasuphot S. Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. Pediatrics 1993; 92:111.
  23. Díaz A, Kourí G, Guzmán MG, et al. Description of the clinical picture of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) in adults. Bull Pan Am Health Organ 1988; 22:133.
  24. Guzmán MG, Kourí G, Martínez E, et al. Clinical and serologic study of Cuban children with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Bull Pan Am Health Organ 1987; 21:270.
  25. Khor BS, Liu JW, Lee IK, Yang KD. Dengue hemorrhagic fever patients with acute abdomen: clinical experience of 14 cases. Am J Trop Med Hyg 2006; 74:901.
  26. Rigau-Pérez JG, Laufer MK. Dengue-related deaths in Puerto Rico, 1992-1996: diagnosis and clinical alarm signals. Clin Infect Dis 2006; 42:1241.
  27. Srikiatkhachorn A, Krautrachue A, Ratanaprakarn W, et al. Natural history of plasma leakage in dengue hemorrhagic fever: a serial ultrasonographic study. Pediatr Infect Dis J 2007; 26:283.
  28. Wilder-Smith A, Schwartz E. Dengue in travelers. N Engl J Med 2005; 353:924.
  29. Cao XT, Ngo TN, Wills B, et al. Evaluation of the World Health Organization standard tourniquet test and a modified tourniquet test in the diagnosis of dengue infection in Viet Nam. Trop Med Int Health 2002; 7:125.
  30. Nimmannitya S, Thisyakorn U, Hemsrichart V. Dengue haemorrhagic fever with unusual manifestations. Southeast Asian J Trop Med Public Health 1987; 18:398.
  31. Chhour YM, Ruble G, Hong R, et al. Hospital-based diagnosis of hemorrhagic fever, encephalitis, and hepatitis in Cambodian children. Emerg Infect Dis 2002; 8:485.
  32. Solomon T, Dung NM, Vaughn DW, et al. Neurological manifestations of dengue infection. Lancet 2000; 355:1053.
  33. Patey O, Ollivaud L, Breuil J, Lafaix C. Unusual neurologic manifestations occurring during dengue fever infection. Am J Trop Med Hyg 1993; 48:793.
  34. Misra UK, Kalita J, Syam UK, Dhole TN. Neurological manifestations of dengue virus infection. J Neurol Sci 2006; 244:117.
  35. Araújo FM, Araújo MS, Nogueira RM, et al. Central nervous system involvement in dengue: a study in fatal cases from a dengue endemic area. Neurology 2012; 78:736.
  36. Sahu R, Verma R, Jain A, et al. Neurologic complications in dengue virus infection: a prospective cohort study. Neurology 2014; 83:1601.
  37. Carod-Artal FJ, Wichmann O, Farrar J, Gascón J. Neurological complications of dengue virus infection. Lancet Neurol 2013; 12:906.
  38. Yacoub S, Griffiths A, Chau TT, et al. Cardiac function in Vietnamese patients with different dengue severity grades. Crit Care Med 2012; 40:477.
  39. Salgado DM, Eltit JM, Mansfield K, et al. Heart and skeletal muscle are targets of dengue virus infection. Pediatr Infect Dis J 2010; 29:238.
  40. Miranda CH, Borges Mde C, Matsuno AK, et al. Evaluation of cardiac involvement during dengue viral infection. Clin Infect Dis 2013; 57:812.
  41. Kirawittaya T, Yoon IK, Wichit S, et al. Evaluation of Cardiac Involvement in Children with Dengue by Serial Echocardiographic Studies. PLoS Negl Trop Dis 2015; 9:e0003943.
  42. Lee IK, Liu JW, Yang KD. Clinical characteristics, risk factors, and outcomes in adults experiencing dengue hemorrhagic fever complicated with acute renal failure. Am J Trop Med Hyg 2009; 80:651.
  43. Laoprasopwattana K, Pruekprasert P, Dissaneewate P, et al. Outcome of dengue hemorrhagic fever-caused acute kidney injury in Thai children. J Pediatr 2010; 157:303.
  44. Basu G, Chrispal A, Boorugu H, et al. Acute kidney injury in tropical acute febrile illness in a tertiary care centre--RIFLE criteria validation. Nephrol Dial Transplant 2011; 26:524.
  45. Huang SY, Lee IK, Liu JW, et al. Clinical features of and risk factors for rhabdomyolysis among adult patients with dengue virus infection. Am J Trop Med Hyg 2015; 92:75.
  46. Chan DP, Teoh SC, Tan CS, et al. Ophthalmic complications of dengue. Emerg Infect Dis 2006; 12:285.
  47. Tan LH, Lum LC, Omar SF, Kan FK. Hemophagocytosis in dengue: comprehensive report of six cases. J Clin Virol 2012; 55:79.
  48. Sharp TM, Gaul L, Muehlenbachs A, et al. Fatal hemophagocytic lymphohistiocytosis associated with locally acquired dengue virus infection - New Mexico and Texas, 2012. MMWR Morb Mortal Wkly Rep 2014; 63:49.
  49. Wilder-Smith A, Tambyah PA. Severe dengue virus infection in travelers. J Infect Dis 2007; 195:1081.
  50. Anderson KB, Chunsuttiwat S, Nisalak A, et al. Burden of symptomatic dengue infection in children at primary school in Thailand: a prospective study. Lancet 2007; 369:1452.
  51. Wichmann O, Gascon J, Schunk M, et al. Severe dengue virus infection in travelers: risk factors and laboratory indicators. J Infect Dis 2007; 195:1089.
  52. WHO (2009). Dengue: guidelines for diagnosis, treatment, prevention and control - new edition. WHO, Geneva 2009.
  53. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 2006; 354:119.
  54. Burt FJ, Rolph MS, Rulli NE, et al. Chikungunya: a re-emerging virus. Lancet 2012; 379:662.
  55. Taraphdar D, Sarkar A, Mukhopadhyay BB, Chatterjee S. A comparative study of clinical features between monotypic and dual infection cases with Chikungunya virus and dengue virus in West Bengal, India. Am J Trop Med Hyg 2012; 86:720.
  56. Lee VJ, Chow A, Zheng X, et al. Simple clinical and laboratory predictors of Chikungunya versus dengue infections in adults. PLoS Negl Trop Dis 2012; 6:e1786.
  57. Mohd Zim MA, Sam IC, Omar SF, et al. Chikungunya infection in Malaysia: comparison with dengue infection in adults and predictors of persistent arthralgia. J Clin Virol 2013; 56:141.
  58. Tanner L, Schreiber M, Low JG, et al. Decision tree algorithms predict the diagnosis and outcome of dengue fever in the early phase of illness. PLoS Negl Trop Dis 2008; 2:e196.
  59. Guzman MG, Kouri GP, Bravo J, et al. Dengue haemorrhagic fever in Cuba. II. Clinical investigations. Trans R Soc Trop Med Hyg 1984; 78:239.
  60. Kalayanarooj S, Chansiriwongs V, Nimmannitya S. Dengue patients at the Children’s Hospital, Bangkok: 1995-1999 review. Dengue Bulletin 2002; 26:33.
  61. Rigau-Pérez JG, Gubler DJ, Vorndam AV, Clark GG. Dengue surveillance--United States, 1986-1992. MMWR CDC Surveill Summ 1994; 43:7.
  62. Blacksell SD, Mammen MP Jr, Thongpaseuth S, et al. Evaluation of the Panbio dengue virus nonstructural 1 antigen detection and immunoglobulin M antibody enzyme-linked immunosorbent assays for the diagnosis of acute dengue infections in Laos. Diagn Microbiol Infect Dis 2008; 60:43.
  63. McBride WJ, Mullner H, LaBrooy JT, Wronski I. The 1993 dengue 2 epidemic in North Queensland: a serosurvey and comparison of hemagglutination inhibition with an ELISA. Am J Trop Med Hyg 1998; 59:457.
  64. Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrile phase: viremia and antibody responses. J Infect Dis 1997; 176:322.
  65. Blacksell SD, Newton PN, Bell D, et al. The comparative accuracy of 8 commercial rapid immunochromatographic assays for the diagnosis of acute dengue virus infection. Clin Infect Dis 2006; 42:1127.
  66. Yamada K, Takasaki T, Nawa M, et al. Antibody responses determined for Japanese dengue fever patients by neutralization and hemagglutination inhibition assays demonstrate cross-reactivity between dengue and Japanese encephalitis viruses. Clin Diagn Lab Immunol 2003; 10:725.
  67. van Panhuis WG, Gibbons RV, Endy TP, et al. Inferring the serotype associated with dengue virus infections on the basis of pre- and postinfection neutralizing antibody titers. J Infect Dis 2010; 202:1002.
  68. http://www.cdc.gov/media/releases/2012/p0620_dengue_test.html (Accessed on July 17, 2012).
  69. Centers for Disease Control and Prevention. CDC DENV-1-4 Real-Time RT-PCR Assay. Package insert. http://www.cdc.gov/dengue/resources/rt_pcr/CDCPackageInsert.pdf (Accessed on November 15, 2012).
  70. Rosen L, Khin MM, U T. Recovery of virus from the liver of children with fatal dengue: reflections on the pathogenesis of the disease and its possible analogy with that of yellow fever. Res Virol 1989; 140:351.
  71. Rosen L. The use of Toxorhynchites mosquitoes to detect and propagate dengue and other arboviruses. Am J Trop Med Hyg 1981; 30:177.
  72. Deubel V. The contribution of molecular techniques to the diagnosis of dengue infection. In: Dengue and Dengue Hemorrhagic Fever, Gubler DJ, Kuno G (Eds), CAB International, CAB International 1997. p.335.
  73. Sudiro TM, Ishiko H, Green S, et al. Rapid diagnosis of dengue viremia by reverse transcriptase-polymerase chain reaction using 3'-noncoding region universal primers. Am J Trop Med Hyg 1997; 56:424.
  74. Chien LJ, Liao TL, Shu PY, et al. Development of real-time reverse transcriptase PCR assays to detect and serotype dengue viruses. J Clin Microbiol 2006; 44:1295.
  75. Johnson BW, Russell BJ, Lanciotti RS. Serotype-specific detection of dengue viruses in a fourplex real-time reverse transcriptase PCR assay. J Clin Microbiol 2005; 43:4977.
  76. de Oliveira Poersch C, Pavoni DP, Queiroz MH, et al. Dengue virus infections: comparison of methods for diagnosing the acute disease. J Clin Virol 2005; 32:272.
  77. Hall WC, Crowell TP, Watts DM, et al. Demonstration of yellow fever and dengue antigens in formalin-fixed paraffin-embedded human liver by immunohistochemical analysis. Am J Trop Med Hyg 1991; 45:408.
  78. Libraty DH, Young PR, Pickering D, et al. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis 2002; 186:1165.
  79. Guzman MG, Jaenisch T, Gaczkowski R, et al. Multi-country evaluation of the sensitivity and specificity of two commercially-available NS1 ELISA assays for dengue diagnosis. PLoS Negl Trop Dis 2010; 4.
  80. Blacksell SD, Jarman RG, Gibbons RV, et al. Comparison of seven commercial antigen and antibody enzyme-linked immunosorbent assays for detection of acute dengue infection. Clin Vaccine Immunol 2012; 19:804.