Dengue fever overview

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Dengue fever from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Dengue fever (IPA: ['deŋgeɪ]) and dengue hemorrhagic fever (DHF) are acute febrile diseases, found in the tropics and Africa, with a geographical spread similar to malaria.[1] One major difference, however, is that malaria is often eradicated in major cities, whereas dengue is often found in urban areas of developed tropical nations, like Singapore. Caused by one of four closely related virus serotypes of the genus Flavivirus, family Flaviviridae, each serotype is sufficiently different that there is no cross-protection and epidemics caused by multiple serotypes (hyperendemicity) can occur. Dengue is transmitted to humans by the Aedes aegypti (rarely Aedes albopictus) mosquito, which feeds during the day[2].

Historical Perspective

Outbreaks resembling dengue fever have been reported throughout history.[3] The first definitive case report dates from 1789 and is attributed to Benjamin Rush, who coined the term "breakbone fever" (because of the symptoms of myalgia and arthralgia). The disease was named Dengue in 1779. The viral etiology and the transmission by mosquitoes were only deciphered in the 20th century. Population movements during World War II spread the disease globally.

Classification

Current WHO guideline classifies dengue into non-severe and severe disease depending on whether there is severe plasma leakage, severe bleeding, or severe organ impairment. For practical purposes, non-severe cases can be further divided into two subgroups: those with warning signs and those without them. Patients with suspected dengue should be triaged and managed accordingly.[4]

Pathophysiology

Aedes aegypti is the principal mosquito vector of dengue fever viruses and is closely associated with humans and their dwellings. The Dengue fever virus also inhibits the human immune response.[5][6]

Causes

Dengue fever is caused by one of four different but related Dengue fever viruses. Aedes aegypti is the principal mosquito vector of dengue fever viruses.[7]

Differentiating Ebola from other Diseases

Dengue fever must be differentiated from other diseases that prevent with flu like symptoms fever, retro-orbital headache, fatigue, joint aches or arthralgias (joint aches), myalgias (muscle aches), nausea/vomiting, and lymphadenopathy (swollen lymph nodes). Diseases with similar symptoms include influenza, measles, rubella, malaria, Zika virus, and Yellow fever.[8]

Epidemiology and Demographics

Dengue is endemic throughout the tropics and subtropics and is a leading cause of febrile illness among travelers returning from the Caribbean, South America, and South and Southeast Asia, according to an analysis of data collected by the GeoSentinel Surveillance Network. Dengue occurs in more than 100 countries worldwide, including Puerto Rico, the US Virgin Islands, and US-affiliated Pacific Islands. Sporadic outbreaks with local transmission have occurred in Florida, Hawaii, and along the Texas-Mexico border. There are 40 million cases worldwide each year.

Risk Factors

Living or traveling to a region of the world where the infection is endemic is a risk factor for the disease. The presence of water-holding containers in and around the home needed for the mosquito's to complete their development sustains the reservoir for disease and is a risk factor. Risk factors for severe disease include being a neonate or young child, female sex, high body mass index, viral load, genetic polymorphisms and previous infection with DENV-1 if the patient contracts DENV-2 or DENV-3. Diabetes and asthma are risk factors for fatal disease.[9]

Natural History

Dengue fever generally lasts a week or more, and can rarely be complicated by bleeding, febrile convulsions and coma. The prognosis is good. Dengue fever can be life-threatening in people with chronic diseases such as diabetes and asthma.

Diagnosis

History and Symptoms

Dengue virus infection has a wide spectrum of clinical manifestations, ranging from asymptomic infection, to symptoms of non-severe disease (such as flu-like symptoms, fever, retro-orbital headache, fatigue, arthralgia, myalgia, nausea, vomiting, or lymphadenopathy), and to severe complications including signs of plasma leakage (such as pleural effusion or ascites), hemorrhagic tendencies (such as petechiae, ecchymoses, purpura, easy bruising at venipuncture sites, mucosal bleeding, gastrointestinal bleeding, hematemesis, or melena), and organ failure associated with shock.[4]

Physical Examination

The typical signs of Dengue Fever include a high fever with no localizing source of infection on physical examination. Occasionally petechia are present. The physical examination in Dengue fever should be directed toward identifying warning signs that the patient has or may develop severe disease warranting in-hospital observation and/or intensive treatment. These warning signs include tachycardia, postural hypotension, a narrow pulse pressure (<20 mm Hg) and / or frank hypotension could indicate intravascular volume depletion due to either dehydration or capillary leak; petechia, lethargy, restlessness, mucosal bleeding, pleural effusion, ascites, hepatomegaly, abdominal tenderness and pedal edema.[7]

Laboratory Findings

The earliest abnormality in the complete blood count is decreased white cell count (leukopenia), which usually occurs during the febrile phase and should alert the physician to a high probability of dengue. The platelet count usually begins to drop when the temperature is returning to normal and is followed by findings indicative of plasma leakage such as elevated hematocrit level and hypoproteinemia. However, the extent of hemoconcentration may be affected by dilutional effect from excessive fluid administration or significant hemorrhage from the gastrointestinal tract and the white cell count may increase as a result of stress response. Serology and virology tests are used to confirm the diagnosis of dengue virus infection.

Other Diagnostic Studies

Treatment

Medical Therapy

Currently, no effective antiviral agents are available to treat symptomatic dengue virus infection, and management remains supportive with emphasis on judicious fluid administration with oral rehydration solution or intravenous fluids. Acetyl-salicylic (aspirin) derivatives and other non-steroidal anti-inflammatory drugs should be avoided because of their potential to increase the risk of bleeding. Patients who have no complications and are able to tolerate oral fluids may be managed at home or as an outpatient. Development of any warning signs (See Group B or C below) suggests the need for intravenous fluid therapy and hospitalization. If the condition progresses to the Dengue shock syndrome, restoration of plasma volume with fluid boluses and/or blood transfusion is required to maintain adequate tissue perfusion.

Primary Prevention

There is no vaccine for Dengue fever, and the primary mode of preventing disease is through mosquito control and elimination of the reservoir of disease. Personal prevention consists of the use of mosquito nets, repellents containing NNDB or DEET, covering exposed skin, use of DEET-impregnated bednets, and avoiding endemic areas.[7]

Future or Investigational Therapies

References

  1. "CDC - Yellow Book: [4] Dengue Fever - CDC Traveler's Health". Retrieved 2007-05-20.
  2. "Dengue Fever – Information Sheet" - World Health Organization
  3. Gubler D (1998). "Dengue and dengue hemorrhagic fever". Clin Microbiol Rev. 11 (3): 480–96. PMID 9665979.
  4. 4.0 4.1 "Dengue haemorrhagic fever: diagnosis, treatment, prevention and control" (PDF).
  5. Diamond MS (2009). "Mechanisms of evasion of the type I interferon antiviral response by flaviviruses". J Interferon Cytokine Res. 29 (9): 521–30. doi:10.1089/jir.2009.0069. PMID 19694536.
  6. Jones M, Davidson A, Hibbert L, Gruenwald P, Schlaak J, Ball S; et al. (2005). "Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression". J Virol. 79 (9): 5414–20. doi:10.1128/JVI.79.9.5414-5420.2005. PMC 1082737. PMID 15827155.
  7. 7.0 7.1 7.2 "Dengue: guidelines for diagnosis, treatment, prevention and control" (PDF).
  8. Staples, J. Erin; Breiman, Robert F.; Powers, Ann M. (2009). "Chikungunya Fever: An Epidemiological Review of a Re‐Emerging Infectious Disease". Clinical Infectious Diseases. 49 (6): 942–948. doi:10.1086/605496. ISSN 1058-4838.
  9. "WHO: Dengue guidelines for diagnosis, treatment, prevention and control: new edition".

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