• Qaisar Ali Department of Medical of Laboratory Technology, Premier Institute of Health and Management Sciences (PIHMS), Peshawar
  • Irfan Kalam Department of Medical Laboratory Sciences (DMLS), Faculty of Health Allied Sciences (FHAS), Imperial College of Business Studies (ICBS), Lahore
  • Fazal Mabood
  • Muhammad Imran Department of Microbiology, University of Health Sciences (UHS), Lahore-Pakistan


Background: Dengue infection is a deadly global pandemic due to its fatal nature, being emerged from mild stage to turn into more severe stages and consequently causing casualties. it upsurges various phases, namely subclinical infection, undifferentiated febrile fever, Dengue fever (DF) and devastating states which often ends to life, they are Dengue haemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Dengue infection is a mosquito born disease which has engulfed many regions in general and tropical zone in particular, causing many casualties and has posed a threat to humanity, demanding strategies to resolve the global issue. It is reported that 50-200 million people fall prey to it globally by dint of its causative agents and imperative to mention that over proportional are the minor among the victims. Because of awful joint pain dengue fever is also named break bone fever. The common indicator in infected individuals is thrombocytopenia, coagulopathy and vasculopathy. Apart from supportive therapy, no aphoristic therapy has been introduced so far, however care may prove rescuer. Timely prognosis thwarts to enter it in deteriorating phase. In the list of laboratory diagnosis virus serology and detection of Ribonucleic acid are primed. In general, there's no specific decisive diagnostic biomarker present through which accurate and prompt prognosis can possible during the entire patient presentation time, particularly in case of secondary dengue infection. Although, through the advancement and commercialization of point-care combined tests, capable of tracking disease markers present during various phases of infection (viral non-structural protein 1 and immunoglobulin M), such evaluation massively improved the treatment through lab-based. Despite such improvements, major hurdles persist in the clinical management of patients with dengue infection, particularly lack of dependable biomarkers that have an efficacious prognostic gauge to predict steady progress to severe disease. In the described review both clinical and laboratory diagnosis of dengue infection have been highlighted, including concern regarding future accessibility.Keywords: Dengue shock syndrome; Dengue haemorrhagic fever; thrombocytopenia; Dengue fever

Author Biographies

Qaisar Ali, Department of Medical of Laboratory Technology, Premier Institute of Health and Management Sciences (PIHMS), Peshawar

Department of Medical of Laboratory Technology, Premier Institute of Health and Management Sciences (PIHMS), Peshawar

Irfan Kalam, Department of Medical Laboratory Sciences (DMLS), Faculty of Health Allied Sciences (FHAS), Imperial College of Business Studies (ICBS), Lahore

Department of Medical Laboratory Sciences (DMLS), Faculty of Health Allied Sciences (FHAS), Imperial College of Business Studies (ICBS), Lahore

Muhammad Imran, Department of Microbiology, University of Health Sciences (UHS), Lahore-Pakistan

Department of Microbiology, University of Health Sciences (UHS), Lahore-Pakistan


Thaithumyanon P, Thisyakorn U, Deerojnawong J, Innis BL. Dengue infection complicated by severe hemorrhage and vertical transmission in a parturient woman. Clin Infect Dis 1994;18(2):248–9.

DuPont HL, Steffen R. Textbook of travel medicine and health: BC Decker Hamilton; 2001.

Pancharoen C, Thisyakorn U, Thisyakorn C. Dengue infection. J Infect Dis Antimicrob Agents 2001;18(3):115–21.

Thisyakorn U, Thisyakorn C. Diseases caused by arboviruses--dengue haemorrhagic fever and Japanese B encephalitis. Med J Aust 1994;160(1):22–6.

Wilder-Smith A, Ooi EE, Vasudevan SG, Gubler DJ. Update on dengue: epidemiology, virus evolution, antiviral drugs, and vaccine development. Curr Infect Dis Rep 2010;12(3):157–64.

Gibbons RV, Vaughn DW. Dengue: an escalating problem. BMJ 2002;324(7353):1563–6.

Wilder-smith A, Foo W, Earnest A, Sremulanathan S, Paton NI. Seroepidemiology of dengue in the adult population of Singapore. Trop Med Int Health 2004;9(2):305–8.

Gubler DJ. The economic burden of dengue. Am J Trop Med Hyg 2012;86(5):743–4.

Thomas EA, John M, Kanish B. Mucocutaneous manifestations of dengue fever. Indian J Dermatol 2010;55(1):79–85.

Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 1998;11(3):480–96.

WHO. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition [Internet]. Geneva: World Health Organization; 2009 [cited 2019 Aprl 9]. (WHO Guidelines Approved by the Guidelines Review Committee). Available from:

Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. Dengue: a continuing global threat. Nat Rev Microbiol 2010;8(12 Suppl):S7–16.

Ramakrishnan L, Pillai MR, Nair RR. Dengue vaccine development: strategies and challenges. Viral Immunol 2015;28(2):76–84.

Halstead SB. Dengue in the Americas and Southeast Asia: do they differ? Rev Panam Salud Publica 2006;20(6):407–15.

Gubler DJ. Dengue, urbanization and globalization: the unholy trinity of the 21st century. Trop Med Health 2011;39(4 Suppl):S3–11.

WHO. Fact Sheet no. 117; Dengue and dengue haemorrhagic fever 2009.

Ferreira GL. Global dengue epidemiology trends. Rev Inst Med Trop São Paulo 2012;54:5–6.

Murray NEA, Quam MB, Wilder-Smith A. Epidemiology of dengue: past, present and future prospects. Clin Epidemiol 2013;5:299–309.

Gubler DJ. The global emergence/resurgence of arboviral diseases as public health problems. Arch Med Res 2002;33(4):330–42.

Shepard DS, Coudeville L, Halasa YA, Zambrano B, Dayan GH. Economic impact of dengue illness in the Americas. Am J Trop Med Hyg 2011;84(2):200–7.

Nimmannitya S. Dengue haemorrhagic fever: current issues and future research. Asian-Ocean J Paediatr Child Health 2002;1:1–21.

King CC, Wu YC, Chao DY, Lin TH, Chow L, Wang HT, et al. Major epidemics of dengue in Taiwan in 1981-2000: related to intensive virus activities in Asia. Dengue Bull 2000;24:1–10.

Endy TP, Nisalak A, Chunsuttiwat S, Libraty DH, Green S, Rothman AL, et al. Spatial and temporal circulation of dengue virus serotypes: a prospective study of primary school children in Kamphaeng Phet, Thailand. Am J Epidemiol 2002;156(1):52–9.

Messer WB, Gubler DJ, Harris E, Sivananthan K, de Silva AM. Emergence and global spread of a dengue serotype 3, subtype III virus. Emerg Infect Dis 2003;9(7):800.

Kouri G. Dengue: an update. Lancet Infect Dis 2002;2(1):33–42.

Guzmán MG, Kouri G. Advances in dengue diagnosis. Clin Diagn Lab Immunol 1996;3(6):621–7.

Young PR, Hilditch PA, Bletchly C, Halloran W. An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein NS1 in the sera of infected patients. J Clin Microbiol 2000;38(3):1053–7.

Cardosa MJ, Wang SM, Sum MSH, Tio PH. Antibodies against prM protein distinguish between previous infection with dengue and Japanese encephalitis viruses. BMC Microbiol 2002;2(1):9.

WHO. Prevention and Control of Dengue and Dengue Haemorrhagic Fever: Comprehensive Guidelines. New Delhi; 1999.

Thavara U, Tawatsin A, Chansang C, Kong-ngamsuk W, Paosriwong S, Boon-Long J, et al. Larval occurrence, oviposition behavior and biting activity of potential mosquito vectors of dengue on Samui Island, Thailand. J Vector Ecol 2001;26(2):172–80.

Perich M, Davila G, Turner A, Garcia A, Nelson M. Behavior of resting Aedes aegypti (Culicidae: Diptera) and its relation to ultra-low volume adulticide efficacy in Panama City, Panama. J Med Entomol 2000;37(4):541–6.

Vezzani D, Schweigmann N. Suitability of containers from different sources as breeding sites of Aedes aegypti (L.) in a cemetery of Buenos Aires City, Argentina. Mem Inst Oswaldo Cruz 2002;97(6):789–92.

Watts DM, Burke DS, Harrison BA, Whitmire RE, Nisalak A. Effect of temperature on the vector efficiency of Aedes aegypti for dengue 2 virus. Am J Trop Med Hyg 1987;36(1):143–52.

Platt KB, Linthicum KJ, Myint KS, Innis BL, Lerdthusnee K, Vaughn DW. Impact of dengue virus infection on feeding behavior of Aedes aegypti. Am J Trop Med Hyg 1997;57(2):119–25.

Joshi V, Mourya DT, Sharma RC. Persistence of dengue-3 virus through transovarial transmission passage in successive generations of Aedes aegypti mosquitoes. Am J Trop Med Hyg 2002;67(2):158–61.

King CA, Marshall JS, Alshurafa H, Anderson R. Release of vasoactive cytokines by antibody-enhanced dengue virus infection of a human mast cell/basophil line. J Virol 2000;74(15):7146–50.

Hayes EB, Gubler DJ. Dengue and dengue hemorrhagic fever. Pediatr Infect Dis J 1992;11(4):311–7.

Libraty DH, Young PR, Pickering D, Endy TP, Kalayanarooj S, Green S, 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(8):1165–8.

Ho LJ, Wang JJ, Shaio MF, Kao CL, Chang DM, Han SW, et al. Infection of human dendritic cells by dengue virus causes cell maturation and cytokine production. J Immunol 2001;166(3):1499–506.

Chakravarti A, Kumaria R. Circulating levels of tumour necrosis factor-alpha & interferon-gamma in patients with dengue & dengue haemorrhagic fever during an outbreak. Indian J Med Res 2006;123(1):25–30.

Lin CF, Lei HY, Shiau AL, Liu HS, Yeh TM, Chen SH, et al. Endothelial cell apoptosis induced by antibodies against dengue virus nonstructural protein 1 via production of nitric oxide. J Immunol 2002;169(2):657–64.

Halstead SB. Pathogenesis of dengue: challenges to molecular biology. Science 1988;239(4839):476–81.

Modhiran N, Watterson D, Muller DA, Panetta AK, Sester DP, Liu L, et al. Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity. Sci Transl Med 2015;7(304):304ra142.

Rigau-Pérez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue haemorrhagic fever. Lancet 1998;352(9132):971–7.

Yacoub S, Lam PK, Vu LHM, Le TL, Ha NT, Toan TT, et al. Association of microvascular function and endothelial biomarkers with clinical outcome in dengue: an observational study. J Infect Dis 2016;214(5):697–706.

Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S, Kunentrasai N, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997;176(2):313–21.

Mayxay M, Phetsouvanh R, Moore CE, Chansamouth V, Vongsouvath M, Sisouphone S, et al. Predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection in adults. Trop Med Int Health 2011;16(1):127–33.

Srikiatkhachorn A, Krautrachue A, Ratanaprakarn W, Wongtapradit L, Nithipanya N, Kalayanarooj S, et al. Natural history of plasma leakage in dengue hemorrhagic fever: a serial ultrasonographic study. Pediatr Infect Dis J 2007;26(4):283–90.

Nimmannitya S, Halstead SB, Cohen SN, Margiotta MR. Dengue and chikungunya virus infection in man in Thailand, 1962-1964. Observations on hospitalized patients with hemmorrhagic fever. Am J Trop Med Hyg 1969;18(6):954–71.

Yacoub S, Wills B. Predicting outcome from dengue. BMC Med 2014;12(1):147.

Yacoub S, Wills B. Dengue: an update for clinicians working in non-endemic areas. Clin Med (Lond) 2015;15(1):82–5.

Nimmannitya S. Clinical spectrum and management of dengue haemorrhagic fever. Southeast Asian J Trop Med Public Health 1987;18(3):392–7.

Lum LCS, Goh AYT, Chan PWK, El-Amin AL, Lam SK. Risk factors for hemorrhage in severe dengue infections. J Pediatr 2002;140(5):629–31.

Yacoub S, Wertheim H, Simmons CP, Screaton G, Wills B. Cardiovascular manifestations of the emerging dengue pandemic. Nat Rev Cardiol 2014;11(6):335–45.

Griffee MJ, Merkel MJ, Wei KS. The role of echocardiography in hemodynamic assessment of septic shock. Crit Care Clin 2010;26(2):365–82.

Potts JA, Gibbons RV, Rothman AL, Srikiatkhachorn A, Thomas SJ, Supradish PO, et al. Prediction of dengue disease severity among pediatric Thai patients using early clinical laboratory indicators. PLoS Negl Trop Dis 2010;4(8):e769.

Ali Q, Kalam I, Ullah S, Jamal A, Imran M, Ullah S, et al. Predictive value of IL-28B rs12979860 variants for peg-IFN, sofosbuvir plus ribavirin treatment of HCV infection in Pakistani population. Per Med 2018;15(6):503–10.

Ali Q, Jamal A, Imran M, Ullah S, Kalam I, Ullah S, et al. Correlation of IL28B rs12979860 genotype and gender with spontaneous clearance of HCV infection: a Pakistani cross-section study. Per Med 2018;15(6):495–502.

Kalam I, Ullah S, Ali Q, Jamal A, Waqar AB. Impact of IL28B gene variants (rs12979860) in peg-IFN therapy against Chronic Hepatitis B Pakistani patients. Adv Life Sci 2018;6(1):11–8.

Mahmuduzzaman M, Chowdhury AS, Ghosh DK, Kabir IM, Rahman MA, Ali MS. Serum transaminase level changes in dengue fever and its correlation with disease severity. Mymensingh Med J 2011;20(3):349–55.

Hunsperger EA, Sharp TM, Lalita P, Tikomaidraubuta K, Cardoso YR, Naivalu T, et al. Use of a rapid test for diagnosis of dengue during suspected dengue outbreaks in resource-limited regions. J Clin Microbiol 2016;54(8):2090–5.

Shu PY, Chen LK, Chang SF, Su CL, Chien LJ, Chin C, et al. Dengue virus serotyping based on envelope and membrane and nonstructural protein NS1 serotype-specific capture immunoglobulin M enzyme-linked immunosorbent assays. J Clin Microbiol 2004;42(6):2489–94.

Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol 1992;30(3):545–51.

Deubel V, Laille M, Hugnot JP, Chungue E, Guesdon JL, Drouet MT, et al. Identification of dengue sequences by genomic amplification: rapid diagnosis of dengue virus serotypes in peripheral blood. J Virol Methods 1990;30(1):41–54.

Najioullah F, Viron F, Césaire R. Evaluation of four commercial real-time RT-PCR kits for the detection of dengue viruses in clinical samples. Virol J 2014;11(1):164.

Alcon S, Talarmin A, Debruyne M, Falconar A, Deubel V, Flamand M. Enzyme-linked immunosorbent assay specific to Dengue virus type 1 nonstructural protein NS1 reveals circulation of the antigen in the blood during the acute phase of disease in patients experiencing primary or secondary infections. J Clin Microbiol 2002;40(2):376–81.

Bessoff K, Delorey M, Sun W, Hunsperger E. Comparison of two commercially available dengue virus (DENV) NS1 capture enzyme-linked immunosorbent assays using a single clinical sample for diagnosis of acute DENV infection. Clin Vaccine Immunol 2008;15(10):1513–8.

Vaughn DW, Nisalak A, Solomon T, Kalayanarooj S, Nguyen M, Kneen R, et al. Rapid serologic diagnosis of dengue virus infection using a commercial capture ELISA that distinguishes primary and secondary infections. Am J Trop Med Hyg 1999;60(4):693–8.

Levett PN, Branch SL, Edwards CN. Detection of dengue infection in patients investigated for leptospirosis in Barbados. Am J Trop Med Hyg 2000;62(1):112–4.

Cuzzubbo AJ, Endy TP, Nisalak A, Kalayanarooj S, Vaughn DW, Ogata SA, et al. Use of recombinant envelope proteins for serological diagnosis of dengue virus infection in an immunochromatographic assay. Clin Diagn Lab Immunol 2001;8(6):1150–5.

Vazquez S, Perez A, Ruiz D, Rodriguez R, Pupo M, Calzada N, et al. Serological markers during dengue 3 primary and secondary infections. J Clin Virol 2005;33(2):132–7.

Fry SR, Meyer M, Semple MG, Simmons CP, Sekaran SD, Huang JX, et al. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach. PLoS Negl Trop Dis 2011;5(6):e1199.

Muller DA, Depelsenaire AC, Young PR. Clinical and laboratory diagnosis of dengue virus infection. J Infect Dis 2017;215(Suppl_2):S89–95.



Most read articles by the same author(s)