Taxonomy and Viral Properties
Dengue virus belongs to the family Flaviviridae and the genus Flavivirus. There are 4 viral serotypes. Although antigenically related, significant differences exist between them. A prior infection confers immunity only to the specific serotype that caused it (lasting no longer than 2 years), while cross-protection against other serotypes is partial and temporary. Therefore, reinfection can occur.
The pathogen is thermolabile, meaning it is rapidly destroyed by heat. It exhibits pronounced hemagglutinating activity: it can agglutinate human erythrocytes (group O), as well as those of geese and chickens.
In laboratories, the virus is cultured using:
- Animals: Newborn white mice are most commonly infected intracerebrally or intraperitoneally.
- Chicken embryos: By inoculation into the yolk sac.
- Cell cultures: A cytopathic effect is observed (especially with serotypes 2 and 3), and plaques are formed.
- Mosquito cells: Replication occurs with the formation of syncytia.
Epidemiology
Dengue fever is a zoonotic/vector-borne arboviral infection prevalent in tropical and subtropical regions (from 42° N to 40° S). The transmission route is vector-borne; a single bite from an infected mosquito is sufficient.
There are two epidemiological types:
- Urban: The source and reservoir is humans, and the vector is the mosquito Aedes aegypti.
- Sylvatic (Jungle): The reservoir includes non-human primates (in whom the disease is asymptomatic), lemurs, bats, and squirrels. The vector is Aedes niveus, which bites both animals and humans, carrying the virus into urban areas.
In nature, the virus persists through transovarial transmission: infected mosquitoes pass the pathogen on to their offspring.
Pathogenesis and Clinical Forms
The virus replicates in the salivary glands of the mosquito and enters the bloodstream upon a bite. The incubation period lasts from 3 to 15 days. The pathogenesis includes several phases: primary replication (in lymph nodes and endothelium), primary viremia (at the end of the incubation period), dissemination (involvement of target organs), and secondary viremia.
The disease can manifest in two forms:
- Classic form: Characterized by the clinical triad (fever, intoxication, hemorrhagic syndrome). A characteristic "dandy" gait is noted (due to severe muscle and joint pain, hence the term dandy), along with a biphasic temperature curve, lymphadenopathy, and a maculopapular rash on days 5–6. It is frequently asymptomatic.
- Hemorrhagic form: Develops acutely, accompanied by high fever, hepatomegaly, prominent petechiae, and bleeding. Mortality reaches 40–50% and is frequently complicated by shock syndrome.
The pathogenesis of the hemorrhagic form is explained by the immunopathological hypothesis (antibody-dependent enhancement, ADE). It occurs upon secondary infection with a different serotype, particularly in children. Virus-antibody complexes form, activating the complement system. The virus enters phagocytes and actively replicates within them, leading to a massive release of biologically active substances and severe capillary leak syndrome.
Microbiological Diagnostics
Research specimens include patient blood, autopsy material, or vector mosquitoes.
Two main methods are used:
- Virological (virus isolation): Bioassays using mosquitoes (inoculation into the thorax or head) or suckling mice, and cell culture inoculation. The virus is identified using indirect immunofluorescence assay (IFA) with monoclonal antibodies.
- Serological (antibody detection): Paired sera are analyzed. Reactions include neutralization (NT), hemagglutination inhibition (HI), complement fixation (CF), and ELISA.