Prevention and treatment of dengue virus infection
- Alan L Rothman, MD
Alan L Rothman, MD
- University of Rhode Island
- Anon Srikiatkhachorn, MD
Anon Srikiatkhachorn, MD
- Assistant Professor of Medicine
- University of Massachusetts Medical School
- Siripen Kalayanarooj, MD
Siripen Kalayanarooj, MD
- Consultant, DHF Center of Excellence
- Queen Sirikit National Institute of Child Health (QSNICH)
Dengue is a febrile illness that is caused by any one of four serotypes of this flavivirus (DENV-1, DENV-2, DENV-3, and DENV-4). It is endemic in more than 100 countries in tropical and subtropical regions of the world and causes an estimated 50 million infections annually worldwide [1-3].
Mild dengue disease and dengue fever (DF) contributes more than half of the total public health burden of dengue-associated illness . The more serious manifestations of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the major impetus for efforts to prevent infection . Epidemiologic studies have demonstrated that the greatest risk factor for the development of DHF or DSS is secondary infection with a different dengue serotype from the original infecting virus . Thus, severe disease occurs primarily in patients who reside in hyperendemic areas where multiple serotypes circulate simultaneously.
Dengue virus infection is a risk 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 risk of infection tends to be seasonal and can be expected to be highest during a recognized outbreak of dengue infections. The objectives of programs to prevent dengue infections differ depending upon whether local residents or visitors are targeted. There is no direct therapy available against the dengue virus, which increases the importance of prevention.
Measures to prevent dengue and supportive treatment for the different clinical features of dengue virus infection will be reviewed here. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of infection are discussed separately. (See "Epidemiology of dengue virus infections" and "Pathogenesis of dengue virus infection" and "Clinical manifestations and diagnosis of dengue virus infection".)
The greatest risk for dengue virus infection is among individuals residing in endemic areas, rather than travelers.
- Kalayanarooj S, Vaughn DW, Nimmannitya S, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997; 176:313.
- Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 1998; 11:480.
- World Health Organization. Geneva: WHO, 2002.
- 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.
- Halstead SB. The XXth century dengue pandemic: need for surveillance and research. World Health Stat Q 1992; 45:292.
- Burke DS, Nisalak A, Johnson DE, Scott RM. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 1988; 38:172.
- 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.
- Halstead SB. Selective primary health care: strategies for control of disease in the developing world. XI. Dengue. Rev Infect Dis 1984; 6:251.
- 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.
- Monath TP. Dengue and yellow fever--challenges for the development and use of vaccines. N Engl J Med 2007; 357:2222.
- 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.
- Pierson TC, Diamond MS. Molecular mechanisms of antibody-mediated neutralisation of flavivirus infection. Expert Rev Mol Med 2008; 10:e12.
- Sukupolvi-Petty S, Austin SK, Purtha WE, et al. Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes. J Virol 2007; 81:12816.
- 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.
- 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.
- Sabchareon A, Wallace D, Sirivichayakul C, et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet 2012; 380:1559.
- 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.
- Dengue: guidelines for diagnosis, treatment, prevention and control - new edition. World Health Organization, Geneva 2009, p. 1.
- 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.
- Rigau-Pérez JG, Laufer MK. Dengue-related deaths in Puerto Rico, 1992-1996: diagnosis and clinical alarm signals. Clin Infect Dis 2006; 42:1241.
- 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.
- 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.
- 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.
- 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.
- Nimmannitya S. Dengue hemorrhagic fever: Diagnosis and management. In: Dengue and Dengue Hemorrhagic Fever, Gubler DJ, Kuno G (Eds), CAB International, Wallingford 1997. p.133.
- 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.
- 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; 7: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.
- 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.
- Endemic areas
- - Mosquito control
- - Vaccination
- Early recognition of DHF/severe dengue
- Management of fever
- Management of significant bleeding
- Management of plasma leakage
- - Treatment of shock
- - Adjunctive therapies
- FUTURE DIRECTIONS
- INFORMATION FOR PATIENTS