Dengue

Overview

Dengue is an acute febrile illness that is caused by infection with any of 4 related positive-sense, single-stranded RNA viruses of the genus Flavivirus.

Dengue serotypes can lead to a wide spectrum of symptoms, including some which are extremely mild to those that may require medical intervention and hospitalization. There is no treatment for a dengue infection but the symptoms can be managed with professional care.

Dengue is common in more than 100 countries around the world. About 40 percent of the world’s population, 3 billion people, live in areas with a risk of dengue. In 2015, 2.35 million cases of dengue were reported in the Americas alone. Currently, there are 46 countries and territories reporting dengue cases to the Pan American Health Organization.

Dengue outbreaks occasionally occur in the continental United States but are common in the US territories of Puerto Rico, the US Virgin Islands, and American Samoa.

In the USA local dengue outbreaks most recently occurred in Hawaii (2015), Florida (2013), and Texas (2013). During 2019, the state of Florida reported locally-acquired dengue cases.

Dengue viruses are spread to people through the bite of an infected Aedes species (Ae. aegypti or Ae. albopictus) mosquito. 

Dengue vaccines

*  Dengvaxia - FDA approved for use in the USA, and in about 20 countries around the globe.

*  TAK-003 - Is an investigational live-attenuated tetravalent dengue vaccine, preventing dengue fever caused by any of the 4 serotypes of the dengue virus. Takeda's tetravalent dengue vaccine candidate TAK-003 is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all four vaccine viruses. On November 21, 2019: Takeda presented 18-month data from the pivotal Phase 3 Efficacy Study (TIDES).

*  TetraVax-DV-TV003 - TV003 is a live attenuated tetravalent Dengue vaccine currently in phase 2 evaluation. TV003 contains 10^3.3 plaque-forming units (PFU)/mL of rDEN1Δ30, 10^3.3 PFU/mL of rDEN2/4Δ30(ME), 10^3.3 PFU/mL of rDEN3Δ30/31-7164, and 10^3.3 PFU/mL of rDEN4Δ30. Administered by subcutaneous injection in the deltoid region of the upper arm.

Dengue Symptoms

The most common symptom of dengue is fever with any of the following:

  • Nausea, vomiting
  • Rash
  • Aches and pains (eye pain, typically behind the eyes, muscle, joint, or bone pain)
  • Any warning sign
  • Symptoms of dengue typically last 2–7 days.
  • Most people will recover after about a week.

Testing for Dengue

A blood test is the only way to confirm a dengue diagnosis. A healthcare provider may order blood tests to look for dengue or similar viruses, such as Zika or Chikungunya.

Dengue testing is used to determine whether a person with signs and symptoms and recent potential exposure have been infected with the dengue virus.  Additionally, the World Health Organization recommends that the vaccine only be given to persons with confirmed prior dengue virus infection. Dengue virus testing is not recommended for Asymptomatic patients or Preconception screening.

To accurately diagnose dengue virus infection, perform antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) with a nucleic acid amplification test (NAAT) on a single serum specimen collected within the first 10 days of illness.

There are several different types of blood tests that can indicate a dengue infection:

  • Molecular tests for dengue virus (PCR)—detect the presence of the virus itself; these tests can diagnose dengue fever up to 7 days after the onset of symptoms and can be used to determine which of the 4 different serotypes of dengue virus is causing the infection.
  • Antibody tests, IgM and IgG—detect antibodies produced by the immune system when a person has been exposed to the virus; these tests are most effective when performed at least 4 days after exposure.
  • Complete blood count (CBC)—to look for low platelet count typical of the later stages of the illness and to detect the decrease in hemoglobin, hematocrit, and red blood cell (RBC) count (evidence of anemia) that would occur with blood loss associated with severe dengue fever
  • Basic metabolic panel (BMP) – to monitor kidney function and look for evidence of dehydration.
  • Home Testing for Dengue Fever Ulta Labs

However, there is no FDA cleared test available to determine a previous dengue infection. Available non-FDA cleared tests may yield false-positive results (e.g., due to cross-reactivity with other flaviviruses).

Dengue Clinical Overview

A Dengue infection can be asymptomatic or show with a broad clinical spectrum that includes serious and non-serious ways of expression.  After incubation, the disease begins abruptly and goes through three phases: The Febrile, Critical, and Recovery stages:

1. Febrile Phase

This acute febrile phase lasts 2-7 days and is usually accompanied by skin flushing, erythema, generalized body pain, myalgia, arthralgia, headache, and retro-orbital pain. Minor hemorrhagic manifestations, such as petechiae and ecchymoses in the skin may occur. Patients, who improve after the initial fever, are considered dengue without warning signs. Problems that may arise in the febrile phase: dehydration, high fever associated with neurological disorders, and seizures in young children.

2. Critical Phase

After the fever abates, the patient may experience within the first 3-7 days of illness and increase of capillary permeability parallel with increased hematocrit levels. This marks the beginning of the critical phase with the highest risk of developing plasma leakage with or without hemorrhage, known as severe dengue. Patients who clinically worsen after the fever subsides should be monitored for warning signs and hemorrhagic manifestations. Problems that can occur in the critical phase: shock by plasma extravasation, severe bleeding, and serious organ impairment.

3. Recovery Phase

Most patients survive the acute phase (which does not exceed 48 to 72 hours), with timely initiation of judicious fluid management and careful monitoring of the patient during the critical phase, and enter the recovery or convalescent phase. There is a general improvement in the patient: appetite recovers, gastrointestinal symptoms improve, hemodynamic status stabilizes and diuresis increases. Problems that can occur in the recovery phase are overload (if intravenous fluid therapy has been excessive or has been extended in this period).

Updates

November 7, 2019:  Spain has reported two confirmed cases of dengue in men who have sex with men (MSM) residing in the municipality of Madrid in September. The most recent detected case is a man who did not travel outside of Spain recently. Further investigations showed that the virus is also similar to dengue viruses circulating in Cuba. He developed symptoms mid-September and he was laboratory-confirmed for dengue.

This case is classified as autochthonous.

After confirmation of this case, his partner, a male who presented similar symptoms starting the beginning of September, was tested and confirmed positive for dengue. This case had a recent travel history to Cuba and to the Dominican Republic at the end of August and beginning of September, this case is classified as imported. Entomological investigations at the place of residence of the men and surroundings were negative; no adult forms of Aedes albopictus were detected. The genetic sequencing confirmed that the virus strain of both cases is identical. The experts in Spain could not identify any case of sexual dengue transmission among MSM in literature and only found a reported case of sexual transmission from a woman to a man in South Korea.

Content sources:  World Health Organization, US Centers for Disease Control and Prevention, Pan American Health Organization, and the Precision Vaccinations news network.