What is the cause of dengue fever, particularly in individuals who have recently traveled to or reside in tropical and subtropical regions?

Cause of Dengue Fever

Dengue fever is caused by the dengue virus (DENV), an enveloped RNA flavivirus with four distinct serotypes (DENV-1 through DENV-4), transmitted primarily through the bite of infected Aedes mosquitoes, particularly Aedes aegypti and Aedes albopictus. 1, 2

Viral Etiology

• The dengue virus is a positive-stranded enveloped RNA virus belonging to the family Flaviviridae, comprising three structural proteins and seven non-structural proteins 2
• Four antigenically distinct but closely related serotypes exist (DENV-1, DENV-2, DENV-3, and DENV-4), each capable of causing the full spectrum of disease 3, 2
• Infection with one serotype provides lifelong immunity to that specific serotype but only short-term cross-immunity to other serotypes, making secondary infections with different serotypes possible 3

Vector Transmission

• Day-biting mosquitoes of the genus Aedes, particularly Aedes aegypti, are the primary vectors of dengue fever 1
• Aedes albopictus serves as a secondary but increasingly important vector, especially in regions where it has been introduced through global trade and travel 4, 5
• The incubation period following an infected mosquito bite is typically 4-8 days before symptoms develop 1

Geographic Distribution and Epidemiology

• Dengue is endemic to tropical and subtropical regions, including Africa, South America, Southeast Asia, and the Western Pacific, with approximately 100-400 million symptomatic cases occurring annually worldwide 6, 2
• The disease has shown a ten-fold increase in worldwide case numbers, with 5.2 million cases registered in 2019 compared to 2000 4
• Climate change, rising temperatures, and increased humidity are creating favorable mosquito survival conditions in previously unaffected areas, leading to geographic expansion into southern and central Europe 4

Risk Factors for Severe Disease

• Secondary infection with a different dengue serotype increases the risk of severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) through antibody-dependent enhancement (ADE) 3, 2
• Waning maternal antibodies in infants during the latter half of the first year of life can enhance development of more severe infections in endemic areas 3
• The presence of comorbidities such as diabetes with hypertension increases the risk of DHF by 2.16-fold (AOR 2.16; 95% CI: 1.18-3.96) 1

Common Pitfall to Avoid

• Do not confuse dengue with other flavivirus infections such as Zika, yellow fever, Japanese encephalitis, or tick-borne encephalitis, as cross-reactivity in serological testing can occur due to shared antigenic properties 1, 7