Difference between revisions of "Dengue Virus"

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|Meta description=Dengue virus is a systemic infection common in tropical areas that often has ocular manifestations.
 
|Meta description=Dengue virus is a systemic infection common in tropical areas that often has ocular manifestations.
 
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Dengue virus is an RNA virus of the flavivirus family with at least four distinct serotypes. It is the cause of dengue fever which is associated with headache, retro-orbital pain, joint and bone pain (hence "breakbone fever"), fever and rash. The most serious form of dengue infection is known as dengue hemorrhagic fever which is characterized by thrombocytopenia and potentially multi-system organ failure.
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= Disease Entity  =
 
= Disease Entity  =
  
 
== Disease  ==
 
== Disease  ==
* Dengue is a mosquito-borne viral illness that is spreading rapidly to become endemic in tropical and subtropical regions of the world.
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Dengue virus is an RNA virus of the flavivirus family with at least four distinct serotypes. It is the cause of dengue fever which is associated with headache, retro-orbital pain, joint and bone pain (hence "breakbone fever"), fever and rash. The most serious form of dengue infection is known as dengue hemorrhagic fever which is characterized by thrombocytopenia and potentially multi-system organ failure. Dengue is a mosquito-borne viral illness that is spreading rapidly to become endemic in tropical and subtropical regions of the world. Infection with one serotype results in long-term immunity only to that specific serotype, and not to the others therefore a person can be infected many times with the virus. Dengue often is difficult to diagnose, and a presumptive diagnosis often is established initially based on clinical signs and symptoms, while waiting for laboratory confirmation
* Dengue viruses are part of the <em>Flaviviridae </em>family; there are at least four dengue virus serotypes (DENV-1 to DENV-4), which result in a range of clinical manifestations, from asymptomatic, to mild febrile illness, to fatal plasma leakage and hemorrhagic shock.
 
* Infection with one serotype results in long-term immunity only to that specific serotype, and not to the others.
 
* Dengue often is difficult to diagnose, and a presumptive diagnosis often is established initially based on clinical signs and symptoms, while waiting for laboratory confirmation.
 
* For many patients, the disease is self-limited, ending with full recovery after fever resolves on about day 4 or 5.
 
* Other potentially life-threatening diagnoses, such as malaria and typhoid fever, should be included on the differential diagnosis.
 
 
* Prompt initiation of rehydration therapy with intravenous crystalloid and colloid infusions is the mainstay of treatment in patients with more severe dengue.
 
* Prompt initiation of rehydration therapy with intravenous crystalloid and colloid infusions is the mainstay of treatment in patients with more severe dengue.
* Current vector control efforts have not been sufficient to control dengue.
 
* No specific antiviral therapy exists at this time.
 
* A tetravalent dengue vaccine is in clinical trials.
 
  
 
== Etiology  ==
 
== Etiology  ==
[[File:Aedes aegypti.jpg|thumb]]
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The spread of Dengue fever occurs through a bite from an infected Aedes species (Ae. aegypti or Ae. albopictus)
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mosquito.  These same mosquitoes also transmit Zika and chikungunya.  Dengue
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can be transmitted during pregnancy to an unborn child or to a child in the
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perinatal period.  There is one case of
 +
spreading the virus through the breast milk. Rarely it is transmitted through
 +
the blood.[[File:Aedes aegypti.jpg|thumb]]
  
 
== Risk Factors  ==
 
== Risk Factors  ==
  
Travel to endemic areas and exposure to infected female ''Aedes aegypti'' mosquitoes.       
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Dengue is present in over 100 countries with the most common being the Americas, Caribbean, Western Pacific Islands, Australia, Asia, Africa, and the Middle East.  Each year 400 million people are infected with Dengue with 100 million symptomatic individuals and 22,000 deaths.  Recent outbreaks in the United States were in Hawaii, Florida, and Texas. Travel to endemic areas and exposure to infected female ''Aedes aegypti'' mosquitoes.       
  
 
       [[File:Global Dengue Burden 2014.jpg|Global Dengue Burden 2014|centre|frame]]
 
       [[File:Global Dengue Burden 2014.jpg|Global Dengue Burden 2014|centre|frame]]
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== Primary prevention  ==
 
== Primary prevention  ==
  
Avoidance of ''Aedes aegypti'' mosquitoes.  
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The best way to prevent a Dengue infection is to avoid mosquito bites.  These mosquitos will infect individuals during the daytime and night so wearing insect repellant at all times in at risk countries is advised. Other precautions that can be taken are wearing long sleeved shirts and pants and mosquito nets at night. 
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Dengvaxia ® is the vaccine that is available in select countries for 9-45 year-olds, in patients that have had a prior infection.  Recently, in May of 2019, the vaccine was approved in the United States for persons ages 9-16 living in a Dengue endemic area with a previous laboratory confirmed Dengue infection.  If given the vaccine without prior infection, one might have a more severe systemic illness then if had not had prior exposure to the vaccine.   
  
 
= Diagnosis  =
 
= Diagnosis  =
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== History  ==
 
== History  ==
  
Add text here
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Dengue fever manifests with symptomatic iillness in approximately 25% of patients with mild to severe disease.  Dengue is self limiting and can last from 2-7 days with the most common symptoms of joint pain, muscle soreness, eye pain,  nausea, vomiting, rash, and  fever. 1 out of 20 patients will develop the severe form which can lead to shock and bleeding. 
  
 
== Physical examination  ==
 
== Physical examination  ==
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== Medical therapy  ==
 
== Medical therapy  ==
  
The US Food and Drug Administration (FDA) has not approved any drugs against dengue, but substantial efforts are underway to develop antiviral compounds that target viral or host factors. Advances in acute-phase diagnostic assays make early diagnosis and treatment a more realistic scenario.  
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The US Food and Drug Administration (FDA) has not approved any drugs against dengue, but substantial efforts are underway to develop antiviral compounds that target viral or host factors. Advances in acute-phase diagnostic assays make early diagnosis and treatment a more realistic scenario.Prompt initiation of rehydration therapy with intravenous crystalloid and colloid infusions is the mainstay of treatment in patients with more severe dengue.  
  
 
== Complications  ==
 
== Complications  ==

Revision as of 23:31, June 9, 2019

Assigned editor:
Review:
Assigned status Update Pending
 by Jessica Shantha, MD on May 27, 2019.


Disease Entity

Disease

Dengue virus is an RNA virus of the flavivirus family with at least four distinct serotypes. It is the cause of dengue fever which is associated with headache, retro-orbital pain, joint and bone pain (hence "breakbone fever"), fever and rash. The most serious form of dengue infection is known as dengue hemorrhagic fever which is characterized by thrombocytopenia and potentially multi-system organ failure. Dengue is a mosquito-borne viral illness that is spreading rapidly to become endemic in tropical and subtropical regions of the world. Infection with one serotype results in long-term immunity only to that specific serotype, and not to the others therefore a person can be infected many times with the virus. Dengue often is difficult to diagnose, and a presumptive diagnosis often is established initially based on clinical signs and symptoms, while waiting for laboratory confirmation

  • Prompt initiation of rehydration therapy with intravenous crystalloid and colloid infusions is the mainstay of treatment in patients with more severe dengue.

Etiology

The spread of Dengue fever occurs through a bite from an infected Aedes species (Ae. aegypti or Ae. albopictus) mosquito.  These same mosquitoes also transmit Zika and chikungunya.  Dengue can be transmitted during pregnancy to an unborn child or to a child in the perinatal period.  There is one case of spreading the virus through the breast milk. Rarely it is transmitted through

the blood.

Aedes aegypti.jpg

Risk Factors

Dengue is present in over 100 countries with the most common being the Americas, Caribbean, Western Pacific Islands, Australia, Asia, Africa, and the Middle East.  Each year 400 million people are infected with Dengue with 100 million symptomatic individuals and 22,000 deaths.  Recent outbreaks in the United States were in Hawaii, Florida, and Texas. Travel to endemic areas and exposure to infected female Aedes aegypti mosquitoes.

Global Dengue Burden 2014
Aedes aegypti US 2017.JPG

General Pathology

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Pathophysiology

Dengue virus employs many mechanisms to utilize host cell machinery in order to facilitate viral replication. Dengue virus translation and replication occur in the endoplasmic reticulum of host cells, which experiences rearrangement and expansion during infection. Although the initial rearrangement is independent of the unfolded protein response (UPR),  dengue virus alters the UPR in order to cope with endoplasmic reticulum stress throughout infection.  Particular non-structural proteins (NS4A, NS2B/3) induce the UPR to slow host cell death during viral replication.  In addition, dengue virus leads to autophagy and regulates lipid metabolism to enhance replication,  and a functional autophagy pathway is essential to virus maturation and the production of infectious virions.

Dengue Pathophysiology.jpg

Primary prevention

The best way to prevent a Dengue infection is to avoid mosquito bites.  These mosquitos will infect individuals during the daytime and night so wearing insect repellant at all times in at risk countries is advised. Other precautions that can be taken are wearing long sleeved shirts and pants and mosquito nets at night. 

Dengvaxia ® is the vaccine that is available in select countries for 9-45 year-olds, in patients that have had a prior infection.  Recently, in May of 2019, the vaccine was approved in the United States for persons ages 9-16 living in a Dengue endemic area with a previous laboratory confirmed Dengue infection.  If given the vaccine without prior infection, one might have a more severe systemic illness then if had not had prior exposure to the vaccine.   

Diagnosis

  • Serologic testing with enzyme-linked immunosorbent assay (ELISA) or hemagglutinin inhibition
  • Viral antigen (NS1) detection
  • Viral isolation and identification using cell culture
  • Detection of viral RNA by polymerase chain reaction (PCR)

History

Dengue fever manifests with symptomatic iillness in approximately 25% of patients with mild to severe disease. Dengue is self limiting and can last from 2-7 days with the most common symptoms of joint pain, muscle soreness, eye pain, nausea, vomiting, rash, and fever. 1 out of 20 patients will develop the severe form which can lead to shock and bleeding.

Physical examination

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Ocular Signs

  • Uveitis
  • Maculopathy
  • Dengue Maculopathy: OCT-A

Ocular Symptoms

  • Photophobia
  • Decreased visual acuity

Clinical diagnosis

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Diagnostic procedures

Differential diagnosis

  • Chikungunya virus
  • Zika virus infection
  • Ebola virus
  • Hemorrhagic fever viruses
  • River Virus
  • Orbivirus
  • West Nile encephalitis
  • Roseola infantum
  • Scarlet fever
  • Idiopathic thrombocytopenic purpura
  • Influenza
  • Leptospirosis
  • Malaria
  • Meningitis
  • Rickettsial Infection
  • Rocky Mountain Spotted Fever (RMSF)
  • Typhus
  • Viral Hepatitis

Management

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General treatment

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Medical therapy

The US Food and Drug Administration (FDA) has not approved any drugs against dengue, but substantial efforts are underway to develop antiviral compounds that target viral or host factors. Advances in acute-phase diagnostic assays make early diagnosis and treatment a more realistic scenario.Prompt initiation of rehydration therapy with intravenous crystalloid and colloid infusions is the mainstay of treatment in patients with more severe dengue.

Complications

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Prognosis

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Additional Resources

https://www.cdc.gov/dengue/

References

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