General Characteristics and Epidemiology
Basic features of dengue virus (DENV)
- Family: Flaviviridae
- Genus: Flavivirus
- RNA virus
- Single stranded
- Positive sense
- Icosahedral symmetry
- Size: 40–60 nm
Clinically relevant species
Four distinct serotypes (DENV 1–4) cause dengue infection.
- The leading cause of arthropod-borne viral disease in the world
- > 100 million humans affected annually
- The incidence is increasing.
- Found in > 100 countries
- Causes 20,000–25,000 deaths annually (primarily in children)
- Untreated severe dengue fever: 10% to 20%
- Treated severe dengue fever: 1%
- Geographic distribution:
- Southeast Asia
- Australia and Oceania
- Central and South America
- Middle East
- Humans (primary reservoir)
- Vector: female Aedes mosquitoes (primary mode of transmission)
- Blood transfusions
- Breast milk
- Organ transplantation
Host risk factors
- For dengue infection:
- Living in an endemic area
- Travel to an endemic region
- For severe disease:
- Previous dengue infection with a different serotype
- Young children
Viral replication cycle
- Virus attaches to receptors on a cell’s surface → endocytosis
- Acidification of endosome → fusion of cell and viral membranes → viral RNA released into cytoplasm
- Translation of RNA into viral proteins
- Assembly and budding of new virions (mechanism is poorly understood)
- Mosquito bite → subcutaneous injection of DENV into a human
- Replication occurs in local cells (target cells not yet identified, but potentially macrophages and dendritic cells)
- Spread to lymphatic system → viremia → dissemination to organs
- Innate and adaptive immune response
The majority of patients will be asymptomatic. Those with symptomatic disease may experience 3 phases: febrile, critical, and convalescent.
This phase occurs after an incubation period of 3–14 days and lasts 2–7 days.
- Sudden high fever
- Retro-orbital pain
- Lumbar back pain
- Severe myalgias and arthralgias (“breakbone” pain)
- Macular or maculopapular
- May be pruritic
- Nasal congestion
- Nausea and vomiting
- Abdominal pain
This phase is not seen in all cases and usually presents in patients who have had a previous dengue infection.
- ↓ Fever
- Systemic capillary leakage
- Pleural effusion
Dengue hemorrhagic fever:
- Petechiae, purpura, or ecchymosis
- Mucosal bleeding
- Hematemesis or melena
- Heavy menstrual bleeding
- Disseminated intravascular coagulation (DIC)
- Abdominal pain
- Altered mental status
Dengue shock syndrome:
- Organ dysfunction
- Can be lethal
- Gradual resorption of extravascular fluid
- Stabilization of vital signs
- Resolution of hemorrhage
- Pruritic, confluent erythematous rash may occur
- Profound fatigue (may last from days to weeks)
Diagnosis and Management
The diagnosis should be suspected in people living in or traveling from endemic areas.
- Confirmatory lab tests include:
- Serology (ELISA)
- Viral antigen detection
- PCR for viral RNA
- Viral culture (rarely useful)
- Supporting evaluation:
- ↑ Liver enzymes
- ↑ PT and PTT
- ↓ Fibrinogen
- Ultrasound → ascites
- X-ray → pleural effusion
There is no effective antiviral therapy, so management is supportive. This may include:
- Blood transfusions (as needed)
- Analgesia (avoid NSAIDs due to bleeding risk)
- Prevent mosquito bites
- Protective clothing
- Sleeping under a mosquito net
- Eliminating stagnant water around the home
- Decreases the risk of severe disease in previously infected patients
- Can increase the risk of severe disease in seronegative children
- Not approved for travelers to endemic regions
Comparison of Similar Flavivirus Species
|Organism||Yellow fever virus||Hepatitis C virus (HCV)||Dengue virus (DENV)|
- Zika virus: a Flavivirus that causes fever, conjunctivitis, and headache. An infection during pregnancy can result in microcephaly and developmental impairments in newborns. Diagnosis is established with serology or PCR. Management is supportive.
- Chikungunya virus: a virus belonging to the family Togaviridae and transmitted by Aedes mosquitoes. Patients present with abrupt onset of fever and myalgias. A symmetrical, bilateral polyarthralgia can occur in distal joints, as well as a generalized maculopapular rash. Diagnosis includes serology and PCR. Management is supportive.
- Malaria: mosquito-borne infectious disease caused by Plasmodium species. Malaria often presents with fever, rigors, diaphoresis, jaundice, abdominal pain, hemolytic anemia, hepatosplenomegaly, and renal impairment. A blood smear shows a single pleomorphic ring. Rapid testing for Plasmodium antigens can also be performed. Management requires a prolonged course of multiple antimalarial drugs.
- Leptospirosis: a disease caused by the gram-negative spirochete Leptospira. Bacteria shed in the urine of rodents and other animals can be transmitted to humans via contaminated water. A mild flu-like illness occurs in a majority of cases. In a minority of patients, icterohemorrhagic leptospirosis develops, manifesting as hemorrhage, renal failure, and jaundice. A bacterial culture takes weeks, so other diagnostic tests, such as serology and dark-field microscopy, are used. Treatment is primarily with penicillin.
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