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Simple Clinical and Laboratory Predictors of Chikungunya versus Dengue Infections in Adults

DOI: 10.1371/journal.pntd.0001786

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Background Dengue and chikungunya are co-circulating vector-borne diseases with substantial overlap in clinical presentations. It is important to differentiate between them during first presentation as their management, especially for dengue hemorrhagic fever (DHF), is different. This study compares their clinical presentation in Singapore adults to derive predictors to assist doctors in diagnostic decision-making. Methods We compared 117 patients with chikungunya infection diagnosed with reverse transcription-polymerase chain reaction (RT-PCR) with 917 dengue RT-PCR-positive adult patients (including 55 with DHF). We compared dengue fever (DF), DHF, and chikungunya infections by evaluating clinical characteristics of dengue and chikungunya; developing classification tools via multivariate logistic regression models and classification trees of disease etiology using clinical and laboratory factors; and assessing the time course of several clinical variables. Findings At first presentation to hospital, significantly more chikungunya patients had myalgia or arthralgia, and fewer had a sore throat, cough (for DF), nausea, vomiting, diarrhea, abdominal pain, anorexia or tachycardia than DF or DHF patients. From the decision trees, platelets <118×109/L was the only distinguishing feature for DF versus chikungunya with an overall correct classification of 89%. For DHF versus chikungunya using platelets <100×109/L and the presence of bleeding, the overall correct classification was 98%. The time course analysis supported platelet count as the key distinguishing variable. Interpretation There is substantial overlap in clinical presentation between dengue and chikungunya infections, but simple clinical and laboratory variables can predict these infections at presentation for appropriate management.


[1]  World Health Organization (2009) Fact sheet number 117. Dengue and dengue haemorraghic fever. Available:
[2]  World Health Organization (2008) Fact sheet number 327. Chikungunya. Available:
[3]  Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M (2007) Chikungunya, an epidemic arbovirosis. Lancet Infect Dis 7: 319–327. doi: 10.1016/S1473-3099(07)70107-X
[4]  Staples JE, Breiman RF, Powers AM (2009) Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis 49: 942–948. doi: 10.1086/605496
[5]  WHO (2009) Dengue: guidelines for diagnosis, treatment, prevention and control. World Health Organization, Geneva.
[6]  WHO (1997) Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2ed. World Health Organization, Geneva.
[7]  Lee VJ, Lye DCB, Sun Y, Fernandez G, Ong A, Leo YS (2008) Predictive value of simple clinical and laboratory variables for dengue hemorrhagic fever in adults. J Clin Virol 42: 34–39. doi: 10.1016/j.jcv.2007.12.017
[8]  Wills BA, Nguyen MD, Ha TL, Dong TH, Tran TN, et al. (2005) Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med 353: 877–889. doi: 10.1056/NEJMoa044057
[9]  Ingram PR, Mahadevan M, Fisher DA (2009) Dengue management: practical and safe hospital-based outpatient care. Trans R Soc Trop Med Hyg 103: 203–205. doi: 10.1016/j.trstmh.2008.07.007
[10]  Economopoulou A, Dominguez M, Helynck B, Sissoko D, Wichmann O, et al. (2009) Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005–2006 outbreak on Réunion. Epidemiol Infect 137: 534–541. doi: 10.1017/S0950268808001167
[11]  Halstead SB, Nimmannitya S, Margiotta MR (1969) Dengue and chikungunya virus infection in man in Thailand, 1962–1964. II. Observations on disease in outpatients. Am J Trop Med Hyg 18: 972–983.
[12]  Nimmannitya S, Halstead SB, Cohen SN, Margiotta MR (1969) Dengue and chikungunya virus infection in man in Thailand, 1962–1964. I. Observations on hospitalized patients with hemorrhagic fever. Am J Trop Med Hyg 18: 954–971.
[13]  Halstead SB, Udomsakdi S, Singharaj P, Nisalak A (1969) Dengue chikungunya virus infection in man in Thailand, 1962–1964. 3. Clinical, epidemiologic, and virologic observations on disease in non-indigenous white persons. Am J Trop Med Hyg 18: 984–996.
[14]  Hochedez P, Canestri A, Guihot A, Brichler S, Bricaire F, et al. (2008) Management of travelers with fever and exanthema, notably dengue and chikungunya infections. Am J Trop Med Hyg 78: 710–713.
[15]  Kularatne SA, Gihan MC, Weerasinghe SC, Gunasena S (2009) Concurrent outbreaks of Chikungunya and Dengue fever in Kandy, Sri Lanka, 2006–07: a comparative analysis of clinical and laboratory features. Postgrad Med J 85: 342–346. doi: 10.1136/pgmj.2007.066746
[16]  Taraphdar D, Sarkar A, Mukhopadhyay BB, Chatterjee S (2012) 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 86: 720–723. doi: 10.4269/ajtmh.2012.11-0704
[17]  Laoprasopwattana K, Kaewjungwad L, Jarumanokul R, Geater A (2012) Differential diagnosis of Chikungunya, dengue viral infection and other acute febrile illnesses in children. Pediatr Infect Dis J 31: 459–463. doi: 10.1097/INF.0b013e31824bb06d
[18]  Ooi EE, Goh KT, Gubler DJ (2006) Dengue prevention and 35 years of vector control in Singapore. Emerg Infect Dis 12: 887–893. doi: 10.3201/10.3201/eid1206.051210
[19]  Lee KS, Lai YL, Lo S, Barkham T, Aw P, et al. (2010) Dengue virus surveillance for early warning, Singapore. Emerg Infect Dis 16: 847–949. doi: 10.3201/eid1605.091006
[20]  Leo YS, Chow AL, Tan LK, Lye DC, Lin L, et al. (2009) Chikungunya outbreak, Singapore, 2008. Emerg Infect Dis 15: 836–837. doi: 10.3201/eid1505.081390
[21]  Win MK, Chow A, Dimatatac F, Go CJ, Leo YS (2010) Chikungunya fever in Singapore: acute clinical and laboratory features, and factors associated with persistent arthralgia. J Clin Virol 49: 111–114. doi: 10.1016/j.jcv.2010.07.004
[22]  Lee VJ, Lye DC, Sun Y, Leo YS (2009) Decision tree algorithm in deciding hospitalization for adult patients with dengue haemorrhagic fever in Singapore. Tropical Medicine & International Health 14: 1154–1159. doi: 10.1111/j.1365-3156.2009.02337.x
[23]  Barkham TM, Chung YK, Tang KF, Ooi EE (2006) The performance of RT-PCR compared with a rapid serological assay for acute dengue fever in a diagnostic laboratory. Trans R Soc Trop Med Hyg 100: 142–148. doi: 10.1016/j.trstmh.2005.05.015
[24]  Ng LC, Tan LK, Tan CH, Tan SS, Hapuarachchi HC, et al. (2009) Entomologic and virologic investigation of Chikungunya, Singapore. Emerg Infect Dis 15: 1243–1249. doi: 10.3201/eid1508.081486
[25]  Heinze G, Schemper M A (2002) Solution to the Problem of Separation in logistic regression. Statistics in Medicine 21: 2409–2419. doi: 10.1002/sim.1047
[26]  Heinze G (2006) A comparative investigation of methods for logistic regression with separated or nearly separated data. Statistics in Medicine 25: 4216–4226. doi: 10.1002/sim.2687
[27]  Breiman L (1984) Classification and regression trees. Belmont, Calif: Wadsworth International Group. X:358.
[28]  Ripley BD (1996) Pattern recognition and neural networks. Cambridge: Cambridge University Press. xi:403.
[29]  R Development Core Team (2011) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. Available:
[30]  Lunn D, Spiegelhalter D, Thomas A, Best N (2009) The BUGS project: Evolution, critique, and future directions,. Statistics in Medicine 28: 3049–3067. doi: 10.1002/sim.3680
[31]  Gubler DJ (1998) Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 11: 480–496.
[32]  Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, et al. (2010) Dengue: a continuing global threat. Nat Rev Microbiol 8: S7–S16. doi: 10.1038/nrmicro2460
[33]  Morens DM, Fauci AS (2008) Dengue and hemorrhagic fever: a potential threat to public health in the United States. JAMA 299: 214–216. doi: 10.1001/jama.2007.31-a
[34]  Gould EA, Gallian P, De Lamballerie X, Charrel RN (2010) First cases of autochthonous dengue fever and chikungunya fever in France: from bad dream to reality!. Clin Microbiol Infect 16: 1702–1704. doi: 10.1111/j.1469-0691.2010.03386.x
[35]  Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, et al. (2007) CHIKV study group. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 370: 1840–1846. doi: 10.1016/S0140-6736(07)61779-6
[36]  Rao TR (1971) Immunological surveys of arbovirus infections in South-East Asia, with special reference to dengue, chikungunya, and Kyasanur Forest disease. Bull World Health Organ 44: 585–591.
[37]  Eisenhut M, Schwarz TF, Hegenscheid B (1999) Seroprevalence of dengue, chikungunya and Sindbis virus infections in German aid workers. Infection 27: 82–85. doi: 10.1007/BF02560502
[38]  Ratsitorahina M, Harisoa J, Ratovonjato J, Biacabe S, Reynes JM, et al. (2008) Outbreak of dengue and Chikungunya fevers, Toamasina, Madagascar, 2006. Emerg Infect Dis 14: 1135–1137. doi: 10.3201/eid1407.071521
[39]  Chang SF, Su CL, Shu PY, Yang CF, Liao TL, et al. (2010) Concurrent isolation of chikungunya virus and dengue virus from a patient with coinfection resulting from a trip to Singapore. J Clin Microbiol 48: 4586–4589. doi: 10.1128/JCM.01228-10
[40]  Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L, et al. (2006) Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. PLoS Med 3: e263. doi: 10.1371/journal.pmed.0030263
[41]  Vazeille M, Moutailler S, Coudrier D, Rousseaux C, Khun H, et al. (2007) Two Chikungunya isolates from the outbreak of La Reunion (Indian Ocean) exhibit different patterns of infection in the mosquito, Aedes albopictus. PLoS One 2: e1168. doi: 10.1371/journal.pone.0001168
[42]  Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S (2007) A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog 3: e201. doi: 10.1371/journal.ppat.0030201
[43]  Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, et al. (2010) Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis 10: 142. doi: 10.1186/1471-2334-10-142
[44]  Tanner L, Schreiber M, Low JG, Ong A, Tolfvenstam T, et al. (2008) Decision tree algorithms predict the diagnosis and outcome of dengue fever in the early phase of illness. PLoS Negl Trop Dis 2: e196. doi: 10.1371/journal.pntd.0000196


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