Dengue Fever

Introduction:

Dengue is a febrile illness caused by infection with one of four dengue viruses (DENV) transmitted by Aedes aegypti or Aedes albopictus mosquitoes during the taking of a blood meal. Infection may be asymptomatic or present with a broad range of clinical manifestations including a mild febrile illness to a life-threatening shock syndrome. Numerous viral, host, and vector factors are thought to impact risk of infection, disease, and disease severity.

There are four closely related but serologically distinct DENV types of the genus Flavivirus, called DENV-1, DENV-2, DENV-3, and DENV-4. There is transient cross-protection among the four DENVs, which weakens and disappears over the months following infection; therefore, individuals living in a dengue-endemic area with all types co-circulating are at risk for infection with any and all DENV types.

The Aedes mosquito:

Dengue viruses are transmitted by the bite of an infected female Aedes (subgenus Stegomyia) mosquito. Both males and females require nectar for energy. Females require a blood meal as a source of appropriate protein for egg development. Globally, Aedes aegypti is the predominant highly efficient mosquito vector for dengue infection, but the Asian tiger mosquito, Aedes albopictus, and other Aedes species can also transmit dengue with varying degrees of efficiency.

 Dengue fever :

DF (also known as "break-bone fever") is an acute febrile illness defined by the presence of fever and two or more of the following but not meeting the case definition of DHF. (see 'Dengue hemorrhagic fever' below):

●Headache

●Retro-orbital or ocular pain

●Myalgia and/or bone pain

●Arthralgia

●Rash

●Hemorrhagic manifestations (eg, positive tourniquet test, petechiae, purpura/ecchymosis, epistaxis, gum bleeding, blood in emesis, urine, or stool, or vaginal bleeding)

●Leukopenia   

Dengue hemorrhagic fever :

The cardinal feature of DHF is plasma leakage due to increased vascular permeability as evidenced by hemoconcentration (≥20 percent rise in hematocrit above baseline), pleural effusion, or ascites. DHF is also characterized by fever, thrombocytopenia, and hemorrhagic manifestations (all of which may also occur in the setting of DF). (See 'Dengue fever' above.)

In the setting of DHF, the presence of intense abdominal pain, persistent vomiting, and marked restlessness or lethargy, especially coinciding with defervescence, should alert the clinician to possible impending DSS. (See 'Dengue shock syndrome' below.)

The criteria for DHF comprise a narrow definition that does not encompass all patients with clinically severe or complicated DENV infections.

According to the guidelines, a DHF diagnosis requires all of the following be present:

●Fever or history of acute fever lasting 2 to 7 days, occasionally biphasic

●Hemorrhagic tendencies evidenced by at least one of the following:

•A positive tourniquet test – The tourniquet test is performed by inflating a blood pressure cuff on the upper arm to a point midway between the systolic and diastolic pressures for 5 minutes. A test is considered positive when 10 or more petechiae per 2.5 cm (1 inch) square are observed. The test may be negative or mildly positive during the phase of profound shock. It usually becomes positive, sometimes strongly positive, if the test is conducted after recovery from shock. It is estimated that the tourniquet test is positive in 80 percent of patients with dengue.

•Petechiae, ecchymoses, or purpura.

•Bleeding from the mucosa, gastrointestinal tract, injection sites, or other locations.

•Hematemesis or melena.

●Thrombocytopenia (100,000 cells per mm3 or less) – This number represents a direct count using a phase-contrast microscope (normal is 200,000 to 500,000 per mm3). In practice, for outpatients, an approximate count from a peripheral blood smear is acceptable. In healthy individuals, 4 to 10 platelets per oil-immersion field (100x; the average of the readings from 10 oil-immersion fields is recommended) indicates an adequate platelet count. An average of 3 platelets per oil-immersion field is considered low (ie, 100,000 per mm3).

●Evidence of plasma leakage due to increased vascular permeability manifested by at least one of the following:

•A rise in the hematocrit equal to or greater than 20 percent above average for age, sex, and population.

•A drop in the hematocrit following volume-replacement treatment equal to or greater than 20 percent of baseline.

•Signs of plasma leakage such as pleural effusion, ascites, and hypoproteinemia.

Dengue shock syndrome :

DSS is DHF with marked plasma leakage that leads to circulatory collapse (shock) as evidenced by narrowing pulse pressure or hypotension.

For a diagnosis of DSS, all of the above four criteria for DHF must be present plus evidence of circulatory failure manifested by:

●Rapid and weak pulse.

●Narrow pulse pressure (20 mmHg [2.7 kPa]) or manifested by:

•Hypotension for age – Hypotension is defined to be a systolic pressure 80 mmHg (10.7 kPa) for those less than 5 years of age or 90 mmHg (12.0 kPa) for those greater than or equal to 5 years of age. Note that narrow pulse pressure is observed early in the course of shock, whereas hypotension is observed later or in patients who experience severe bleeding.

•Cold, clammy skin and restlessness.

Dengue without warning signs:

A presumptive diagnosis of dengue infection may be made in the setting of residence in or travel to an endemic area plus fever and two of the following [9]:

●Nausea/vomiting

●Rash

●Headache, eye pain, muscle ache, or joint pain

●Leukopenia

●Positive tourniquet test

Dengue with warning signs :

Dengue with warning signs of severe infection includes dengue infection as defined above in addition to any of the following [9]:

●Abdominal pain or tenderness

●Persistent vomiting

●Clinical fluid accumulation (ascites, pleural effusion)

●Mucosal bleeding

●Lethargy or restlessness

●Hepatomegaly >2 cm

●Increase in hematocrit concurrent with rapid decrease in platelet count

Severe dengue :

Severe DENV infection includes infection with at least one of the following:

●Severe plasma leakage leading to:

•Shock

•Fluid accumulation with respiratory distress

●Severe bleeding (as evaluated by clinician)

●Severe organ involvement:

•Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥1000 units/L

•Impaired consciousness

•Organ failure

Signs and symptoms :

On average, dengue becomes symptomatic after a 4- to 10-day incubation period (range, 3-14 days). Dengue symptoms usually last 2-7 days.

Many individuals with dengue may be asymptomatic. Many patients with dengue experience a prodrome of chills; rash, including erythematous mottling of the skin; and facial flushing, which may last 2-3 days. Children younger than 15 years who have dengue usually have a nonspecific febrile syndrome, which may be accompanied by a maculopapular rash. Dengue should be suspected in individuals who present with high fever (104°F/40°C), retro-orbital headache, muscle and joint pain, nausea, lymphadenopathy, vomiting, and rash and who have traveled within 2 weeks of symptom onset to an area where appropriate vectors are present and dengue transmission may be occurring.

Accompanying symptoms in patients with dengue may include any of the following:

Fever

Headache

Retro-orbital pain

Severe myalgias: Especially of the lower back, arms, and legs

Arthralgias: Usually of the knees and shoulders

Nausea and vomiting (diarrhea is rare)

Rash: A maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin sparing

Weakness, malaise, and lethargy

Altered taste sensation

Anorexia

Sore throat

Mild hemorrhagic manifestations (eg, petechiae, bleeding gums, epistaxis, menorrhagia, hematuria)

Lymphadenopathy

Diagnosis :

Demonstration of a fourfold or greater change in reciprocal immunoglobulin G (IgG) or IgM antibody titers to 1 or more dengue virus antigens in paired serum samples

Demonstration of dengue virus antigen in autopsy tissue via immunohistochemistry or immunofluorescence or in serum samples via enzyme immunoassay (MAC-ELISA, IgG ELISA, nonstructural protein 1 [NS1] ELISA, EIA)

Detection of viral genomic sequences in autopsy tissue, serum, or cerebral spinal fluid (CSF) samples via reverse-transcriptase polymerase chain reaction (RT-PCR) assay: RT-PCR provides earlier and more specific diagnosis.

Less frequently, isolation of the dengue virus from serum, plasma, leukocytes, or autopsy samples

PREVENTION :

Personal protection from infection

Mosquito repellants — Issues related to personal protection for prevention of mosquito bites are discussed separately. (See "Prevention of arthropod and insect bites: Repellents and other measures".)

Insecticide spraying — Distribution of insecticide-treated curtains was successful in reducing populations of A. aegypti mosquitoes for up to 18 months in several studies and was associated with reduced human and mosquito infections with DENV in one region, although use of the curtains declined with time. Insecticide spraying in response to dengue outbreaks is not highly effective, since A. aegypti mosquitoes frequently breed inside houses.

Vaccine development — Infection with one DENV type provides long-term protection against reinfection with that same type, supporting the feasibility of an effective dengue vaccine. 

Treatment :

No specific treatment for dengue fever exists.

While recovering from dengue fever, drink plenty of fluids. Call your doctor right away if you have any of the following signs and symptoms of dehydration:

Decreased urination

Few or no tears

Dry mouth or lips

Lethargy or confusion

Cold or clammy extremities

The over-the-counter (OTC) drug acetaminophen (Tylenol, others) can help reduce muscle pain and fever. But if you have dengue fever, you should avoid other OTC pain relievers, including aspirin, ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve). These pain relievers can increase the risk of dengue fever bleeding complications.

If you have severe dengue fever, you may need:

Supportive care in a hospital

Intravenous (IV) fluid and electrolyte replacement

Blood pressure monitoring

Transfusion to replace blood loss