Severe Dengue Infection

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Dengue has been called the most important mosquito-transmitted viral disease in terms of morbidity and mortality. ^[1] It is the most prevalent viral mosquito-borne disease, with over 2.5 billion humans at risk of exposure given it endemicity in more than 100 countries. ^{[2, 3]}

Dengue fever is a benign, acute febrile syndrome occurring in tropical regions. In a small proportion of cases, the virus causes increased vascular permeability that leads to a bleeding diathesis or disseminated intravascular coagulation (DIC) known as dengue hemorrhagic fever (DHF). ^[4]

The WHO estimates that 50-100 million cases of dengue infection occur annually, with approximately 500,000 of those cases resulting in dengue hemorrhagic fever (DHF), with an estimated 22,000 deaths per year, mostly in children. ^[3] Secondary infection by a different dengue virus serotype has been confirmed as an important risk factor for the development of DHF. ^{[5, 6, 7]}

In 20-30% of DHF cases, the patient develops shock, known as the dengue shock syndrome (DSS).

Worldwide, children younger than 15 years make up 90% of DHF cases. ^[8] In the Americas, however, DHF occurs in adults and children.

Dengue fever is not contagious through person-to-person contact.

Complications

Complications are rare but may include the following: ^[9]

Go to Dengue Infection, Pediatric Dengue, and Dermatologic Manifestations of Dengue for complete information on these topics.

WHO guidelines recommend obtaining a baseline hematocrit measurement. Thrombocytopenia and hemoconcentration are consistent findings in dengue infection. ^[10] When the plasma leakage phase starts to resolve, the hematocrit level begins to fall, making identification of significant occult hemorrhage difficult. Administer blood transfusion if significant hemorrhage ensues (GI bleeding may be profound). Administer fresh frozen plasma or platelets if DIC is extensive and the patient is hemodynamically unstable. Prophylactic platelet transfusions in a stable thrombocytopenic patient are not needed.

There is no specific pharmacologic treatment for dengue infection. Initiate early supportive care by administering isotonic NS solution intravenously, as clinically indicated, to maintain adequate blood pressure and adequate urine output of 0.5-1 mL/kg/hour. The plasma leakage period is short (24-48 hours), and intravenous fluids may be reduced based on clinical response.

Administer acetaminophen for fever control (not salicylates or ibuprofen, which can further hinder platelet function and increase bleeding complications). Glucocorticoids are not indicated.

Corticosteroids are not helpful.

No antiviral therapy is available.

Patients with suspected dengue infection who are maintaining adequate hydration orally and have no warning signs/symptoms may be treated on an outpatient basis with appropriate anticipatory guidance and outpatient follow-up within 24 hours for reassessment.

Admit the patient to the intensive care unit (ICU) in the setting of severe dengue infection (DHF or DSS); otherwise, admit to medicine ward for appropriate hydration, supportive care, and close reassessment. ^{[11, 12, 2]}

Admit patients with suspected dengue without warning signs who have concerning comorbid conditions that could affect their immune system and who are unable to follow up as an outpatient for daily reassessment. ^[2]

Dengue is generally a self-limited viral infection; however, in patients who develop the potentially catastrophic complications of DHF and DSS, survival is directly dependent on the hemodynamic support of patient through the disease manifestations. ^[10]

The rapid clinical response to aggressive fluids and electrolytes in even moribund children with DHF/DSS “is among the most dramatic events in clinical medicine.” Treated promptly, children in shock and coma can wake up and return to near normalcy within hours. ^[13]

Convalescence may be prolonged, with weakness and mental depression.

Continued bone pain, bradycardia, and premature ventricular contractions (PVCs) are common.

Pediatric deaths associated with dengue viral infection most commonly occur in infants younger than 1 year.

Dengue virus is a flavivirus (single-stranded RNA) transmitted by various mosquitoes. Person-to-person transmission does not occur. There are four subtypes of the dengue virus, named DENV1 through DENV4, which are antigenically distinct. This characteristic drives the predominant hypothesis of how clinically severe dengue infection develops since most individuals who develop DHF or DSS have had a prior infection with a nonhomologous dengue virus. DHF and DSS may evolve based on antibody-dependent enhancement through a secondary infection. It is believed that secondary dengue virus infections greatly increase the risk of developing elevated levels of cytokines known to drive the clinical manifestations of DHF and DSS through endothelial damage, vascular leakage, and hemorrhage. ^[2]

Dengue infection has three phases: (1) the febrile phase, (2) the critical phase, and (3) the recovery phase. The entire course of the illness is typically 7-10 days with each phase lasting approximately 48-72 hours. The febrile phase (the initial phase) coincides with the peak of viremia during the illness and rapidly resolves after the first three days. It is associated with nonspecific signs and symptoms. The critical phase is marked by vascular permeability and its resultant complications. It is during this time that the clinician must be vigilant in monitoring for warning signs of severe dengue. The recovery phase includes diuresis and resolution of the symptoms that mark the critical phase of the illness. ^[2]

Dengue virus infection is largely a clinical diagnosis. The WHO-TDR has developed a simplified and binary system of classification for dengue infection. They classify infection as either (1) dengue infection with or without warning signs or (2) severe dengue infection. ^{[2, 14]} Clinicians should suspect dengue infection in patients with possible exposure (travel or endemic) and fever and two of the following characteristics: ^{[2, 14]}

Warning signs for dengue include the following:  ^{[2, 14]}

Severe dengue infection diagnosis criteria include the following: ^{[2, 14]}

RNA PCR testing is available for DENV1-4 through the CDC for diagnosis during the first 5 days of infection (after this period, IgM ELISA testing is preferred), although this is unlikely to assist directly in emergency department management. ^[2] Information on how to obtain PCR testing in suspected cases can be found at https://www.cdc.gov/dengue/resources/TestpolEng_2.pdf.

Khursheed M, Khan UR, Ejaz K, Fayyaz J, Qamar I, Razzak JA. A comparison of WHO guidelines issued in 1997 and 2009 for dengue fever – single centre experience. J Pak Med Assoc. 2013 Jun. 63 (6):670-4. [Medline].

Caraballo, H and King K. Emergency department management of mosquito-borne illness: malaria, dengue, and West Nile virus. Emergency Medicine Practice. 2014. 16 (5):[Medline].

Centers for Disease Control and Prevention. Dengue. Available at https://www.cdc.gov/dengue/epidemiology/index.html. Accessed: May 14th, 2017.

Pok KY, Squires RC, Tan LK, Takasaki T, Abubakar S, Hasebe F, et al. First round of external quality assessment of dengue diagnostics in the WHO Western Pacific Region, 2013. Western Pac Surveill Response J. 2015 Apr-Jun. 6 (2):73-81. [Medline].

Teoh BT, Sam SS, Tan KK, Johari J, Shu MH, Danlami MB, et al. Dengue virus type 1 clade replacement in recurring homotypic outbreaks. BMC Evol Biol. 2013 Sep 28. 13(1):213. [Medline].

Chiang CY, Pan CH, Hsieh CH, Tsai JP, Chen MY, Liu HH, et al. Lipidated Dengue-2 Envelope Protein Domain III Independently Stimulates Long-Lasting Neutralizing Antibodies and Reduces the Risk of Antibody-Dependent Enhancement. PLoS Negl Trop Dis. 2013 Sep 19. 7(9):e2432. [Medline]. [Full Text].

Huy NT, Van Giang T, Thuy DH, Kikuchi M, Hien TT, Zamora J, et al. Factors associated with dengue shock syndrome: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2013 Sep 26. 7(9):e2412. [Medline]. [Full Text].

Malavige GN, Fernando S, Fernando DJ, Seneviratne SL. Dengue viral infections. Postgrad Med J. 2004 Oct. 80(948):588-601. [Medline]. [Full Text].

Puccioni-Sohler M, Rosadas C, Cabral-Castro MJ. Neurological complications in dengue infection: a review for clinical practice. Arq Neuropsiquiatr. 2013 Sep. 71(9B):667-71. [Medline].

World Health Organization. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. Available at http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/. Accessed: May 14th, 2017.

Bunnag T, Kalayanarooj S. Dengue shock syndrome at the emergency room of Queen Sirikit National Institute of Child Health, Bangkok, Thailand. J Med Assoc Thai. 2011 Aug. 94 Suppl 3:S57-63. [Medline].

Thomas L, Moravie V, Besnier F, Valentino R, Kaidomar S, Coquet LV, et al. Clinical presentation of dengue among patients admitted to the adult emergency department of a tertiary care hospital in Martinique: implications for triage, management, and reporting. Ann Emerg Med. 2012 Jan. 59 (1):42-50. [Medline].

Morens DM. Antibody-dependent enhancement of infection and the pathogenesis of viral disease. Clin Infect Dis. 1994 Sep. 19(3):500-12. [Medline].

World Health Organization and the Special Programme for Research and Training in Tropical Disease (TDR). Dengue – guidelines for diagnosis, treatment, prevention and control. New edition. 2009. Available at http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf?ua=1.

Sukhveer (Sukhi) Bains, MD, MA Assistant Professor of Clinical Emergency Medicine and Clinical Internal Medicine, University of Illinois at Chicago

Sukhveer (Sukhi) Bains, MD, MA is a member of the following medical societies: American College of Emergency Physicians, American College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Barry J Sheridan, DO Chief Warrior in Transition Services, Brooke Army Medical Center

Barry J Sheridan, DO is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Sanz Laniado Medical Center, Netanya, Israel

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, New York Academy of Medicine, New York Academy of Sciences, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center

William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Daniel D Price, MD Director of International Ultrasound, Department of Emergency Medicine, Alameda County Medical Center, Highland Hospital and Trauma Center

Daniel D Price, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Sharon R Wilson, MD Assistant Professor of Emergency Medicine, Department of Emergency Medicine, University of California at Davis Medical Center

Sharon R Wilson, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, American Association of University Women

Disclosure: Nothing to disclose.

Severe Dengue Infection

Research & References of Severe Dengue Infection|A&C Accounting And Tax Services
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