From the Guidelines
Dengue fever is caused by the dengue virus, which is transmitted to humans primarily through the bite of infected female Aedes mosquitoes, particularly Aedes aegypti. The virus then targets and replicates in various cells including monocytes, macrophages, and dendritic cells 1. As the virus multiplies, it spreads throughout the body, causing an immune response that leads to the characteristic symptoms of dengue fever. The body's immune reaction includes the release of cytokines and other inflammatory mediators that cause fever, pain, and vascular leakage.
Mechanisms of Dengue Fever
The mechanisms leading to dengue fever involve:
- The bite of an infected Aedes mosquito, which injects the virus into the bloodstream 1
- Replication of the virus in various cells, including monocytes, macrophages, and dendritic cells
- An immune response that leads to the release of cytokines and other inflammatory mediators, causing fever, pain, and vascular leakage
- Potential for antibody-dependent enhancement in secondary infections with a different dengue serotype, leading to more severe forms of dengue 1
Clinical Presentation
The clinical presentation of dengue fever can range from a mild febrile illness to more severe forms, such as dengue hemorrhagic fever or dengue shock syndrome 1. The symptoms of dengue fever include fever, headache, retro-orbital pain, myalgia, arthralgia, and rash. In severe cases, patients may experience increased vascular permeability, bleeding, and potentially fatal shock.
Management and Treatment
The management and treatment of dengue fever focus on supportive care, including fluid resuscitation and management of symptoms 1. In severe cases, patients may require hospitalization and close monitoring of their condition. The use of crystalloids and/or colloids for fluid resuscitation, as well as the administration of dopamine or epinephrine in patients with persistent tissue hypoperfusion, may be necessary 1.
From the Research
Mechanisms of Dengue Fever
The mechanisms that lead to dengue fever are complex and involve various factors, including:
- The transmission of the dengue virus (DENV) through the bite of an infected Aedes aegypti or Aedes albopictus mosquito 2, 3, 4
- The innate immune response to DENV infection, which includes the activation of immune cells and the production of inflammatory mediators 2, 5, 6
- The evasion of the innate immune system by the virus, which can lead to severe disease 5
- The role of antibody-dependent enhancement (ADE) in the development of more severe dengue infections, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) 3, 4
Innate Immune Response
The innate immune response to DENV infection is implemented by a variety of immune cells and inflammatory mediators, including:
- Blood monocytes, dendritic cells (DCs), and tissue macrophages, which are the main target cells of DENV infection 6
- Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs) and trigger downstream signaling pathways leading to the production of inflammatory cytokines, interferons (IFNs), and other molecules essential for the prevention of viral replication 6
- Type I interferon, complement, apoptosis, and autophagy, which are activated innate immune pathways that the virus can evade or exploit to exacerbate disease 5
Viral and Host Factors
Viral and host factors are related to the clinical outcome of dengue, including:
- The four serotypes of DENV (DENV1-4), which are antigenically distinct and can cause different clinical manifestations 2, 3, 4
- The genotype and structural proteins of the virus, which can affect the severity of the disease 4
- The immune status of the host, including the presence of neutralizing antibodies and the activation of immune cells, which can influence the outcome of the infection 3, 5