• GADE KALYANI Department of Pharmacology, Gautham College of Pharmacy, Bengaluru, Karnataka, India.
  • THANUSHREE N Department of Pharmacy Practice, Gautham College of Pharmacy, Bengaluru, Karnataka, India.



Dengue virus, Crystalloid fluid, Antibody-dependent enhancement, Attenuated vaccine, Serotype, Hematocrit levels


Objectives: As per the national survey data, the prevalence of dengue has been still rising consistently, and the burden of the disease is predominantly affecting the adults with progression toward the DF, dengue hemorrhagic fever, and dengue shock syndrome. The higher hospitalization rate result in massive mortality.

Methods: Vector control alone cannot reduce the transmission of viral infection, so effective vaccine development is made high priority.

Results: Several vaccine candidates including live attenuated, live chimeric, inactivated and many other vector vaccines are key elements needed to achieve the dengue public health targets. Global strategies like diagnosis, care management, outbreak preparedness and integrated surveillance, sustainable vector control, and future vaccine implementation are needed to be addressed.

Conclusion: This review mainly describes the dengue treatment challenges, in addition to a brief discussion of dengue vaccine challenges and future outlook on dengue that might help in making efficacious vaccine in near future.


Download data is not yet available.

Author Biography

GADE KALYANI, Department of Pharmacology, Gautham College of Pharmacy, Bengaluru, Karnataka, India.

Department of pharmaceutical chemistry and Department of pharmacology


Jennifer BP. Dengue fever and dengue haemorrhagic fever book review. Nurs J India 2006;11:246-7.

Tayade T. Emerging therapy for dengue. Int J Curr Pharm Res 2018;10:1-4.

Ayukekbong JA. Dengue virus in Nigeria: Current status and future perspective. Br J Virol 2014;1:106-111.

Nedjadi T, El-Kafrawy S, Sohrab SS, Desprès P, Damanhouri G, Azhar E. Tackling dengue fever: Current status and challenges. Virol J 2015;12:212.

Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG, et al. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis 2012;6:e1760.

Chotigeat UR, Kalayanarooj S, Nisalak A. Vertical transmission of dengue infection in Thai infants: Two case reports. Med Assoc Thai 2003;86 Suppl 3:628-32.

Raafat N, Blacksell SD, Maude RJ. A review of dengue diagnostics and implications for surveillance and control. Trans R Soc Trop Hyg 2019;113:653-60.

Srivastava VK, Suri S, Bhasin A, Srivastava L, Bharadwaj M. An epidemic of dengue haemorrhagic fever and dengue shock syndrome in Delhi: A clinical study. Ann Trop Paediatr 1990;10:329-34.

Soni A, Chugh K, Sachdev A, Gupta D. Management of dengue fever in ICU. Indian J Pediatr 2001;68:1051-5.

Wiwanitkit V. Dengue fever: Diagnosis and treatment. Expert Rev Anti Infect Ther 2010;8:841-5.

Da Fonseca BA, Fonseca SN. Dengue virus infections. Curr Opin Pediatr 2002;14:67-71.

Jahan F. Dengue fever (DF) in Pakistan. Asia Pac Fam Med 2011;10:1.

Lucas GN. Management of dengue haemorrhagic fever (DHF). Sri Lanka J Child Health 2009;29:107-8.

Biswas A, Pangtey G, Devgan V, Singla P, Murthy P, Dhariwal AC, et al. Indian national guidelines for clinical management of dengue fever. J Indian Med Assoc 2015;113:197-206.

Gupta E, Ballani N. Current perspectives on the spread of dengue in India. Infect Drug Resist 2014;7:337.

Gupta N, Srivastava S, Jain A, Chaturvedi U. Dengue in India. Indian J Med Res 2012;136:373-90.

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

Nimmannitya S. Management of dengue and dengue haemorrhagic fever. In: Monograph on Dengue/Dengue Haemorrhagic Fever. New Delhi, India: World Health Organization; 1993. p. 55-61.

Nhan NT, Phuong CX, Kneen R, Wills B, Van My N, Phuong NT, et al. Acute management of dengue shock syndrome: A randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis 2001;32:204-13.

Idrees S, Ashfaq UA. A brief review on dengue molecular virology, diagnosis, treatment and prevalence in Pakistan. Genet Vaccines Ther 2012;10:6.

Lye DC, Lee VJ, Sun Y, Leo YS. Lack of efficacy of prophylactic platelet transfusion for severe thrombocytopenia in adults with acute uncomplicated dengue infection. Clin Infect Dis 2009;48:1262-5.

Sharma A, Charles K, Chadee D, Teelucksingh S. Dengue hemorrhagic fever in Trinidad and Tobago: A case for a conservative approach to platelet transfusion. Am J Trop Med Hyg 2012;86:531-5.

Ooi EE, Gubler DJ. Dengue in Southeast Asia: Epidemiological characteristics and strategic challenges in disease prevention. Cad Saude Publica 2009;25:S115-24.

Elsinga J, Lizarazo EF, Vincenti MF, Schmidt M, Velasco-Salas ZI, Arias L, et al. Health seeking behaviour and treatment intentions of dengue and fever: A household survey of children and adults in Venezuela. PLoS Negl Trop Dis 2015;9:e0004237.

Deen J, von Seidlein L. Paracetamol for dengue fever: No benefit and potential harm? Lancet Glob Health 2019;7:e552-3.

Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over the counter NSAIDs. Ther Clin Risk Manage 2015;11:1061.

Guha-Sapir D, Schimmer B. Dengue fever: New paradigms for a changing epidemiology. Emerg Themes Epidemiol 2005;2:1.

Singhi S, Kissoon N, Bansal A. Dengue and dengue hemorrhagic fever: Management issues in an intensive care unit. J Pediatr (Rio J) 2007;83 Suppl 2:S22-35.

Hasan S, Jamdar SF, Alalowi M, Al Beaiji SM. Dengue virus: A global human threat: Review of literature. J Int Soc Prev Community Dent 2016;6:1.

Thisyakorn U, Thisyakorn C. Latest developments and future directions in dengue vaccines. Ther Adv Vaccines 2014;2:3-9.

Ghosh A, Dar L. Dengue vaccines: Challenges, development, current status and prospects. Indian J Med Microbiol 2015;33:3.

Ahamed SF, Rosario V, Britto C, Dias M, Nayak K, Chandele A, et al. Emergence of new genotypes and lineages of dengue viruses during the 2012-15 epidemics in southern India. Int J Infect Dis 2019;84:S34-43.

Innis BL, Eckels KH. Progress in development of a live-attenuated, tetravalent dengue virus vaccine by the United States army medical research and materiel command. Am J Trop Med Hyg 2003;69 Suppl 6:1-4.

Thomas SJ, Yoon IK. A review of Dengvaxia: Development to deployment. Hum Vaccin Immunother 2019;15:2295-314.

Bhamarapravati N, Sutee Y. Live attenuated tetravalent dengue vaccine. Vaccine 2000;18:44-7.

Guy B, Lang J, Saville M, Jackson N. Vaccination against dengue: Challenges and current developments. Ann Rev Med 2016;67:387-404.

Beaumier CM, Gillespie PM, Hotez PJ, Bottazzi ME. New vaccines for neglected parasitic diseases and dengue. Transl Res 2013;162:144-55.

Vannice KS, Roehrig JT, Hombach J. Next generation dengue vaccines: A review of the preclinical development pipeline. Vaccine 2015;33:7091-9.

Putnak R, Barvir DA, Burrous JM, Dubois DR, D’Andrea VM, Hoke CH, et al. Development of a purified, inactivated, dengue-2 virus vaccine prototype in Vero cells: Immunogenicity and protection in mice and rhesus monkeys. J Infect Dis 1996;174:1176-84.

Raviprakash K, Porter KR, Kochel TJ, Ewing D, Simmons M, Phillips I, et al. Dengue virus Type 1 DNA vaccine induces protective immune responses in rhesus macaques. J Gen Virol 2000;81:1659-67.

Fernandez S, Thomas SJ, De La Barrera R, Im-Erbsin R, Jarman RG, et al. An adjuvanted, tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques. Am J Trop Med Hyg 2015;92:698-708.

Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: Problems and prospects. Indian J Med Res 2005;121:639.

Qin E, Shi H, Tang L, Wang C, Chang G, Ding Z, et al. Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine. Vaccine 2006;24:1028-34.

Danko JR, Beckett CG, Porter KR. Development of dengue DNA vaccines. Vaccine 2011;29:7261-6.

Porter KR, Kochel TJ, Wu SJ, Raviprakash K, Phillips I, Hayes CG. Protective efficacy of a dengue 2 DNA vaccine in mice and the effect of CpG immuno-stimulatory motifs on antibody responses. Arch Virol 1998;143:997-1003.

Konishi E, Yamaoka M, Kurane I, Mason PW. A DNA vaccine expressing dengue Type 2 virus premembrane and envelope genes induces neutralizing antibody and memory B cells in mice. Vaccine 2000;18:1133-9.

Konishi E, Kosugi S, Imoto JI. Dengue tetravalent DNA vaccine inducing neutralizing antibody and anamnestic responses to four serotypes in mice. Vaccine 2006;24:2200-7.

Guy B, Nougarede N, Begue S, Sanchez V, Souag N, Carre M, et al. Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or Flavivirus-primed subjects. Vaccine 2008;26:5712-21.

Abdullah AA, Lee YK, Chin SP, Lim SK, Lee VS, Othman R, et al. Discovery of dengue virus inhibitors. Curr Med Chem 2020;19:45-8.

Halstead SB. Dengavaxia sensitizes seronegative to vaccine enhanced disease regardless of age. Vaccine 2017;35:6355-8.

Aguiar M, Stollenwerk N. Dengavaxia: Age as surrogate for serostatus. Lancet Infect Dis 2018;18:245.

Turner HC, Wills BA, Rahman M, Cuong HQ, Thwaites GE, Boni MF, et al. Projected costs associated with school-based screening to inform deployment of Dengvaxia: Vietnam as a case study. Trans R Soc Trop Med Hyg 2018;112:369-77.

Galula JU, Salem GM, Chang GJ, Chao DY. Does structurally mature dengue virion matter in vaccine preparation in post-Dengavaxia era. Hum Vaccin Immunother 2019;15:2328-36.

Aguiar M, Halstead SB, Stollenwerk N. Consider stopping dengvaxia administration without immunological screening.

Pasteur S. World’s First Dengue Vaccine, Approved in Mexico. Philippines: Dengavaxia; 2017.

Guy B, Almond JW. Towards a dengue vaccine: Progress to date and remaining challenges. Comp Immunol Microbiol Infect Dis 2008;31:239-52.

Thomas SJ. Developing a dengue vaccine: Progress and future challenges. Ann N Y Acad Sci 2014;1323:140-59.

Koh HL, Teh SY, Noordin NM, Sulaiman LH. Pharmacoeconomic evaluation for dengue vaccine pricing for Malaysia: Towards affordability, cost-effectiveness and sustainability. Asian J Pharm Clin Res 2017;10:12-5.

Alim A, Sarfraz A. Dengue vaccine: A road to dengue prevention. Int J Contemporary Med Res 2018;5:C6-9.

Murray NE, Quam MB, Wilder-Smith A. Epidemiology of dengue: Past, present and future prospects. Clin Epidemiol 2013;5:299.

Shepard DS, Halasa YA, Tyagi BK, Adhish SV, Nandan D, Karthiga KS, et al, INCLEN Study Group. Economic and disease burden of dengue illness in India. Am J Trop Med Hyg 2014;91:1235-42.

Zhu G, Liu T, Xiao J, Zhang B, Song T, Zhang Y, et al. Effects of human mobility, temperature and mosquito control on the spatiotemporal transmission of dengue. Sci Total Environ 2019;651:969-78.

Promprou S, Jaroensutasinee M, Jaroensutasinee K. Climatic Factors Affecting Dengue Haemorrhagic Fever Incidence in Southern Thailand.2005;29:41-8.

Xu L, Stige LC, Chan KS, Zhou J, Yang J, Sang S, et al. Climate variation drives dengue dynamics. P Natl Acad Sci U S A 2017;114:113-8.

Banu S, Hu W, Hurst C, Tong S. Dengue transmission in the Asia‐Pacific region: Impact of climate change and socio‐environmental factors. Trop Med Int Health 2011;16:598-607.

Naish S, Dale P, Mackenzie JS, McBride J, Mengersen K, Tong S. Climate change and dengue: A critical and systematic review of quantitative modelling approaches. BMC Infect Dis 2014;14:167.

Semenza JC, Sudre B, Miniota J, Rossi M, Hu W, Kossowsky D, et al. International dispersal of dengue through air travel: Importation risk for Europe. PLoS Negl Trop Dis 2014;8:e3278.

Tambo E, Chen JH, Zhou XN, Khater EI. Outwitting dengue threat and epidemics resurgence in Asia-Pacific countries: Strengthening integrated dengue surveillance, monitoring and response systems. Infect Dis Poverty 2016;5:56.

Stoddard ST, Forshey BM, Morrison AC, Paz-Soldan VA, Vazquez- Prokopec GM, Astete H, et al. House-to-house human movement drives dengue virus transmission. Proc Natl Acad Sci U S A 2013;110:994-9.

Kyle JL, Harris E. Global spread and persistence of dengue. Ann Rev Microbiol 2008;62:71-92.

Rezza G. Aedes albopictus and the reemergence of dengue. BMC Public Health 2012;12:72.

Struchiner CJ, Rocklöv J, Wilder-Smith A, Massad E. Increasing dengue incidence in Singapore over the past 40 years: Population growth, climate and mobility. PLoS One 2015;10:e0136286.

Kendall C, Hudelson P, Leontsini E, Winch P, Lloyd L, Cruz F. Urbanization, dengue, and the health transition: Anthropological contributions to international health. Med Anthropol Q 1991;5:257-68.

Akram DS, Ahmed S. Dengue fever. Infect Dis J 2005;14:124-5.

Chen WJ, Chen SL, Chien LJ, Chen CC, King CC, Harn MR, et al. Silent transmission of the dengue virus in Southern Taiwan. Am J Trop Med Hyg 1996;55:12-6.

Recker M, Vannice K, Hombach J, Jit M, Simmons CP. Assessing dengue vaccination impact: Model challenges and future directions. Vaccine 2016;34:4461-5.

Tuan NM, Nhan HT, Chau NV, Hung NT, Tuan HM, Van Tram T, et al. Sensitivity and specificity of a novel classifier for the early diagnosis of dengue. PLoS Negl Trop Dis 2015;9:e0003638.

World Health Organization. Dengue Vector Management: Report of a Regional Workshop Colombo, Sri Lanka. Geneva: World Health Organization; 2014.

Tapia-Conyer R, Méndez-Galván J, Burciaga-Zúñiga P. Community participation in the prevention and control of dengue: The patio limpio strategy in Mexico. J Paediatr Child Health 2012;32 Suppl 1:10-3.

Guo YH, Lai SJ, Liu XB, Li GC, Yu HJ, Liu QY. Governmental supervision and rapid detection on dengue vectors: An important role for dengue control in China. Acta Trop 2016;156:17-21.

Tapia-Conyer R, Betancourt-Cravioto M, Mendez-Galvan J. Dengue: An escalating public health problem in Latin America. J Paediatr Child Health 2012;32 Suppl 1:14-7.

Rafikov M, Rafikova E, Yang HM. Optimization of the Aedes aegypti control strategies for integrated vector management. J Appl Math 2015;2015:1-8.

World Health Organization. Integrated Vector Management to Control Malaria and Lymphatic Filariasis: WHO Position Statement. Geneva: World Health Organization; 2011.

Singh A, Taylor-Robinson AW. Vector control interventions to prevent dengue: Current situation and strategies for future improvements to management of Aedes in India. J Infect Dis Pathol 2017;2:2.

Naranjo DP, Qualls WA, Jurado H, Perez JC, Xue RD, Gomez E, et al. Vector control programs in Saint Johns county, Florida and Guayas, Ecuador: Successes and barriers to integrated vector management. BMC Public Health 2014;14:674.

Framework WG. Integrated Vector Management. Geneva, Switzerland: World Health Organization; 2004.

Sepulveda LS, Vasilieva O. Optimal control approach to dengue reduction and prevention in Cali, Colombia. Math Methods Appl Sci 2016;39:5475-96.

Lizzi KM, Qualls WA, Brown SC, Beier JC. Expanding integrated vector management to promote healthy environments. Trends Parasitol 2014;30:394-400.

Chanda E, Ameneshewa B, Bagayoko M, Govere JM, Macdonald MB. Harnessing integrated vector management for enhanced disease prevention. Trends Parasitol 2017;33:30-41.

Berg HV, Mutero CM, Ichimori K, World Health Organization. Guidance on policymaking for integrated vector management; 2012;1-11.

Mitchell‐Foster K, Ma BO, Warsame‐Ali S, Logan C, Rau ME, Lowenberger C. The influence of larval density, food stress, and parasitism on the bionomics of the dengue vector Aedes aegypti (Diptera: Culicidae): Implications for integrated vector management. J Vector Ecol 2012;37:221-9.

Mann RS, Kaufman PE. Natural product pesticides: Their development, delivery and use against insect vectors. Mini Rev Org Chem 2012;9:185-202.

Bharati M, Saha D. Multiple insecticide resistance mechanisms in primary dengue vector, Aedes aegypti (Linn.) from dengue endemic districts of Sub-Himalayan West Bengal, India. PLoS One 2018;13:e0203207.

Marques AM, Kaplan MA. Active metabolites of the genus piper against Aedes aegypti: Natural alternative sources for dengue vector control. Univ Sci 2015;20:61-82.

Kalaivani K, Senthil-Nathan S, Murugesan AG. Biological activity of selected Lamiaceae and Zingiberaceae plant essential oils against the dengue vector Aedes aegypti L. (Diptera: Culicidae). Parasitol Res 2012;110:1261-8.

Beula JM, Ravikumar S, Ali MS. Mosquito larvicidal efficacy of seaweed extracts against dengue vector of Aedes aegypti. Asian Pac J Trop Biomed 2011;1:S143-6.

Kalimuthu K, Lin SM, Tseng LC, Murugan K, Hwang JS. Bio-efficacy potential of seaweed Gracilaria firma with copepod, Megacyclops formosanus for the control larvae of dengue vector Aedes aegypti. Hydrobiologia 2014;741:113-23.

Bond JG, Marina CF, Williams T. The naturally derived insecticide spinosad is highly toxic to Aedes and Anopheles mosquito larvae. Med Vet Entomol Entomol 2004;18:50-6.

Subramaniam J, Kovendan K, Kumar PM, Murugan K, Walton W. Mosquito larvicidal activity of Aloe vera (Family: Liliaceae) leaf extract and Bacillus sphaericus, against chikungunya vector, Aedes aegypti. Saudi J Biol Sci 2012;19:503-9.

Kumar PM, Murugan K, Kovendan K, Panneerselvam C, Kumar KP, Amerasan D, et al. Mosquitocidal activity of Solanum xanthocarpum fruit extract and copepod Mesocyclops thermocyclopoides for the control of dengue vector Aedes aegypti. Parasitol Res 2012;111:609-18.

Sarwar MB. Elimination of dengue by control of Aedes vector mosquitoes (Diptera: Culicidae) utilizing copepods (Copepoda: Cyclopidae). IJBBE 2015;1:53-8.

Warikoo R, Kumar S. Impact of Argemone mexicana extracts on the cidal, morphological, and behavioral response of dengue vector, Aedes aegypti L. (Diptera: Culicidae). Parasitol Res 2013;112:3477-84.

Paulraj MG, Kumar PS, Ignacimuthu S, Sukumaran D. Natural insecticides from actinomycetes and other microbes for vector mosquito control. In: Herbal Insecticides, Repellents and Biomedicines: Effectiveness and Commercialization. New Delhi: Springer; 2016. p. 85-99.



How to Cite

KALYANI, G., and T. N. “THE DENGUE VACCINES: ASSESSMENT OF FUTURE PROSPECTS, TREATMENT, AND VACCINE CHALLENGES”. Asian Journal of Pharmaceutical and Clinical Research, vol. 13, no. 6, June 2020, pp. 4-9, doi:10.22159/ajpcr.2020.v13i6.37366.



Review Article(s)