Dengue virus infection: Prevention and treatment
- Stephen J Thomas, MD
Stephen J Thomas, MD
- Professor and Chief, Division of Infectious Diseases
- State University of New York, Upstate Medical University
- Alan L Rothman, MD
Alan L Rothman, MD
- University of Rhode Island
- Anon Srikiatkhachorn, MD
Anon Srikiatkhachorn, MD
- Associate Professor
- University of Rhode Island
- Siripen Kalayanarooj, MD
Siripen Kalayanarooj, MD
- Professor of Pediatrics
- Rangsit University
- Consultant, WHO Collaborating Centre for Case Management of Dengue/DHF/DSS
- Queen Sirikit National Institute of Child Health (QSNICH)
Dengue is a febrile illness caused by a flavivirus transmitted by the bite of an Aedes aegypti mosquito. There are four dengue virus types (DENV-1, DENV-2, DENV-3, and DENV-4), all of which are capable of inducing severe disease (dengue hemorrhagic fever [DHF]/dengue shock syndrome [DSS]). Dengue is endemic in more than 100 countries in tropical and subtropical regions and causes an estimated 390 million infections annually worldwide, of which 96 million are clinically apparent .
The likelihood for development of severe dengue is highest among individuals who develop a second dengue infection caused by a different virus type from the first infection (known as secondary or heterotypic infection) . Thus, severe disease occurs primarily among individuals in areas where multiple serotypes circulate simultaneously. Infection with dengue virus provides long-term protection against the particular serotype that caused the disease, supporting the feasibility of developing an effective vaccine. However, infection provides only short-lived immunity to the other three dengue virus serotypes.
There are numerous documents providing guidance on the optimal approaches to managing dengue [3-6]. Data from well-designed randomized controlled trials are limited. The guidance in this document largely agrees with published guidelines and is also based on the contributors' clinical experience in management of complex dengue infections.
Measures to prevent dengue infection and supportive treatment for dengue virus infection will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of infection are discussed separately. (See "Dengue virus infection: Epidemiology" and "Dengue virus infection: Clinical manifestations and diagnosis".)
Dengue virus transmission occurs when susceptible hosts, dengue viruses, and mosquitoes capable of transmission are co-located in space and time. Infection risk exists for anyone living in or traveling in a dengue-endemic region, especially in tropical Asia, Central and South America, and the Caribbean. In most of these regions, dengue virus transmission occurs year-round. However, the greatest risk of infection tends to be seasonal or during a recognized outbreak.
- Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature 2013; 496:504.
- Mizumoto K, Ejima K, Yamamoto T, Nishiura H. On the risk of severe dengue during secondary infection: a systematic review coupled with mathematical modeling. J Vector Borne Dis 2014; 51:153.
- Centers for Disease Control and Prevention. Dengue Case Management. http://www.cdc.gov/dengue/resources/DENGUE-clinician-guide_508.pdf (Accessed on September 08, 2015).
- World Health Organization. Dengue haemorrhagic fever: Diagnosis, treatment, prevention and control, 2nd ed. WHO, Geneva 1997. http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/ (Accessed on September 13, 2016).
- World Health Organization. Dengue: Guidelines for diagnosis, treatment, prevention and control, New edition. WHO, Geneva 2009. http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf (Accessed on September 13, 2016).
- World Health Organization. Handbook for clinical management of dengue. WHO, Geneva 2012. http://www.wpro.who.int/mvp/documents/handbook_for_clinical_management_of_dengue.pdf (Accessed on September 13, 2016).
- Gubler DJ. Aedes aegypti and Aedes aegypti-borne disease control in the 1990s: top down or bottom up. Charles Franklin Craig Lecture. Am J Trop Med Hyg 1989; 40:571.
- Andersson N, Nava-Aguilera E, Arosteguí J, et al. Evidence based community mobilization for dengue prevention in Nicaragua and Mexico (Camino Verde, the Green Way): cluster randomized controlled trial. BMJ 2015; 351:h3267.
- Kay B, Vu SN. New strategy against Aedes aegypti in Vietnam. Lancet 2005; 365:613.
- Hales S, van Panhuis W. A new strategy for dengue control. Lancet 2005; 365:551.
- Vanlerberghe V, Villegas E, Oviedo M, et al. Evaluation of the effectiveness of insecticide treated materials for household level dengue vector control. PLoS Negl Trop Dis 2011; 5:e994.
- Loroño-Pino MA, García-Rejón JE, Machain-Williams C, et al. Towards a Casa Segura: a consumer product study of the effect of insecticide-treated curtains on Aedes aegypti and dengue virus infections in the home. Am J Trop Med Hyg 2013; 89:385.
- Halstead SB. Selective primary health care: strategies for control of disease in the developing world. XI. Dengue. Rev Infect Dis 1984; 6:251.
- Iturbe-Ormaetxe I, Walker T, O' Neill SL. Wolbachia and the biological control of mosquito-borne disease. EMBO Rep 2011; 12:508.
- Lambrechts L, Ferguson NM, Harris E, et al. Assessing the epidemiological effect of wolbachia for dengue control. Lancet Infect Dis 2015; 15:862.
- Endy TP, Nisalak A, Chunsuttitwat S, et al. Relationship of preexisting dengue virus (DV) neutralizing antibody levels to viremia and severity of disease in a prospective cohort study of DV infection in Thailand. J Infect Dis 2004; 189:990.
- Monath TP. Dengue and yellow fever--challenges for the development and use of vaccines. N Engl J Med 2007; 357:2222.
- Durbin AP, Whitehead SS. Dengue vaccine candidates in development. Curr Top Microbiol Immunol 2010; 338:129.
- Guirakhoo F, Pugachev K, Zhang Z, et al. Safety and efficacy of chimeric yellow Fever-dengue virus tetravalent vaccine formulations in nonhuman primates. J Virol 2004; 78:4761.
- World Health Organization. Questions and Answers on Dengue Vaccines. http://www.who.int/immunization/research/development/dengue_q_and_a/en/ (Accessed on February 04, 2016).
- Guy B, Guirakhoo F, Barban V, et al. Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses. Vaccine 2010; 28:632.
- Capeding MR, Tran NH, Hadinegoro SR, et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet 2014; 384:1358.
- Villar L, Dayan GH, Arredondo-García JL, et al. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med 2015; 372:113.
- Hadinegoro SR, Arredondo-García JL, Capeding MR, et al. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. N Engl J Med 2015; 373:1195.
- Olivera-Botello G, Coudeville L, Fanouillere K, et al. Tetravalent Dengue Vaccine Reduces Symptomatic and Asymptomatic Dengue Virus Infections in Healthy Children and Adolescents Aged 2-16 Years in Asia and Latin America. J Infect Dis 2016; 214:994.
- Dengue vaccine: WHO position paper – July 2016. Wkly Epidemiol Rec 2016; 91:349.
- WHO (2009). Dengue: guidelines for diagnosis, treatment, prevention and control - new edition. WHO, Geneva 2009.
- WHO 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 2011.
- World Health Organization. Dengue haemorrhagic fever: Diagnosis, treatment, prevention and control, 2nd edition. WHO, Geneva 1997. http://apps.who.int/iris/bitstream/10665/41988/1/9241545003_eng.pdf (Accessed on December 07, 2016).
- Kalayanarooj S, Vaughn DW, Nimmannitya S, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997; 176:313.
- Ngo NT, Cao XT, Kneen R, 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.
- Dung NM, Day NP, Tam DT, et al. Fluid replacement in dengue shock syndrome: a randomized, double-blind comparison of four intravenous-fluid regimens. Clin Infect Dis 1999; 29:787.
- Wills BA, Nguyen MD, Ha TL, et al. Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med 2005; 353:877.
- Lam PK, Tam DT, Diet TV, et al. Clinical characteristics of Dengue shock syndrome in Vietnamese children: a 10-year prospective study in a single hospital. Clin Infect Dis 2013; 57:1577.
- Mitrakul C, Poshyachinda M, Futrakul P, et al. Hemostatic and platelet kinetic studies in dengue hemorrhagic fever. Am J Trop Med Hyg 1977; 26:975.
- Thomas L, Kaidomar S, Kerob-Bauchet B, et al. Prospective observational study of low thresholds for platelet transfusion in adult dengue patients. Transfusion 2009; 49:1400.
- Khan Assir MZ, Kamran U, Ahmad HI, et al. Effectiveness of platelet transfusion in dengue Fever: a randomized controlled trial. Transfus Med Hemother 2013; 40:362.
- 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.
- Kalayanarooj S. The Southeast Asia Regional Office (WHO) Guidelines for Clinical Management of Dengue and Dengue Hemorrhagic Fever. In: Dengue and Dengue Hemorrhagic Fever, 2nd ed, Gubler DG, Ooi EE, Vasudeva S, Farrar J (Eds), CAB International, Oxfordshire, UK 2014.
- Clinical Practice Guidelines of Dengue/Dengue Hemorrhagic Fever Management for Asian Economic Community, Kalayanarooj S, Vangveeravong M, Vatcharasaevee V (Eds), Bangkok Medical Publisher, Bangkok 2014.
- Chin CK, Kang BH, Liew BK, et al. Protocol for out-patient management of dengue illness in young adults. J Trop Med Hyg 1993; 96:259.
- Leo YS, Gan VC, Ng EL, et al. Utility of warning signs in guiding admission and predicting severe disease in adult dengue. BMC Infect Dis 2013; 13:498.
- Kalayanarooj S. Dengue classification: current WHO vs. the newly suggested classification for better clinical application? J Med Assoc Thai 2011; 94 Suppl 3:S74.
- Cao XT, Ngo TN, Kneen R, et al. Evaluation of an algorithm for integrated management of childhood illness in an area of Vietnam with dengue transmission. Trop Med Int Health 2004; 9:573.
- 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.
- Lee VJ, Lye DC, Sun Y, Leo YS. Decision tree algorithm in deciding hospitalization for adult patients with dengue haemorrhagic fever in Singapore. Trop Med Int Health 2009; 14:1154.
- Potts JA, Gibbons RV, Rothman AL, et al. Prediction of dengue disease severity among pediatric Thai patients using early clinical laboratory indicators. PLoS Negl Trop Dis 2010; 4:e769.
- Panpanich R, Sornchai P, Kanjanaratanakorn K. Corticosteroids for treating dengue shock syndrome. Cochrane Database Syst Rev 2006; :CD003488.
- Tam DT, Ngoc TV, Tien NT, et al. Effects of short-course oral corticosteroid therapy in early dengue infection in Vietnamese patients: a randomized, placebo-controlled trial. Clin Infect Dis 2012; 55:1216.
- Zhang F, Kramer CV. Corticosteroids for dengue infection. Cochrane Database Syst Rev 2014; :CD003488.
- Dimaano EM, Saito M, Honda S, et al. Lack of efficacy of high-dose intravenous immunoglobulin treatment of severe thrombocytopenia in patients with secondary dengue virus infection. Am J Trop Med Hyg 2007; 77:1135.
- Chuansumrit A, Wangruangsatid S, Lektrakul Y, et al. Control of bleeding in children with Dengue hemorrhagic fever using recombinant activated factor VII: a randomized, double-blind, placebo-controlled study. Blood Coagul Fibrinolysis 2005; 16:549.
- Salgado D, Zabaleta TE, Hatch S, et al. Use of pentoxifylline in treatment of children with dengue hemorrhagic fever. Pediatr Infect Dis J 2012; 31:771.
- Noble CG, Shi PY. Structural biology of dengue virus enzymes: towards rational design of therapeutics. Antiviral Res 2012; 96:115.
- Krishnan MN, Garcia-Blanco MA. Targeting host factors to treat West Nile and dengue viral infections. Viruses 2014; 6:683.
- Johnson AJ, Roehrig JT. New mouse model for dengue virus vaccine testing. J Virol 1999; 73:783.
- Schul W, Liu W, Xu HY, et al. A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. J Infect Dis 2007; 195:665.
- Nguyen NM, Tran CN, Phung LK, et al. A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J Infect Dis 2013; 207:1442.
- Low JG, Sung C, Wijaya L, et al. Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet Infect Dis 2014; 14:706.
- Whitehorn J, Nguyen CV, Khanh LP, et al. Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis 2016; 62:468.
- Endemic areas
- - Mosquito control
- - Vaccination
- TREATMENT APPROACH
- Phases of infection and clinical assessment
- - Outpatient management
- - Inpatient management
- Management of fever
- Management of plasma leakage
- - Treatment of shock
- Management of bleeding
- ALTERNATIVE MANAGEMENT APPROACHES
- FUTURE DIRECTIONS
- INFORMATION FOR PATIENTS