Dengue

Definitions

Bleeding diathesis - an abnormal propensity toward bleeding

Hematocrit - volume percentage of red blood cells in blood

Pleural cavity - fluid filled space surrounding lungs

Dengue Fever

  • Acute febrile diseases

  • Tropics and Africa

    • Geographical spread similar to Malaria but Dengue is found in urban areas

  • Dengue Hemorrhagic Fever

    • Bleeding diathesis (tendency) or disseminated intravascular coagulation caused by increased vascular permeability

  • Dengue Shock Syndrome - 20-30% of DHF cases

History

  • In 1944, Albert Sabin successfully isolated the virus and found that it belongs to the Flaviviridae virus family

Classification

  • Group: IV

  • Family: Flaviviridae

  • Genus: Flavivirus

    • WNV, Tich encephalitis, Yellow Fever, Zika

    • Enveloped, isoahedral nucleocapsid

E protein

  • Has 3 domains with folds based largely on Beta-sheets

  • Domain 2

    • Elongated, finger-like structure

    • Hydrophobic sequence that is conserved among all flaviviruses

Genes of Dengue

Structural

  • C & prM - E chaperone during assembly exocytosis, prevention of premature fusion

  • E - receptor binding and fusion activity, host range, tropisms, immunodominant epitopes

Nonstructural

  • NS1 and NS2A - blocking IFN signaling, helicase, NTPase, and serine protease

  • NS4B - inhibition of IFN signal transduction

  • NS5 - RdRP, methyltransferase

RdRP - RNA dependent RNA polymerase

Dengue Replication

  • Dengue binds o some receptor protein (DC-SIGN, DC-SIGN-R (Dendritic Cell-Specific ICAM3-Grabbing Nonintegrin-Related Protein), and CLEC5A), E protein plays a role

  • In cell, pH drops, conformational change of E protein, becomes hydrophobic, and viral membrane fuses with host membrane

Serotypes

  • Same Morphology and Genome size

  • Genetic Variation within serotypes

    • Different antigens

  • Life-time immunity and short term cross-immunity

  • All can cause severe and fatal disease

  • Hyperendemicity (constant presence at high levels) may occur

Dengue is 4 main viruses

  • 4 Serotypes

    • DEN-1

    • DEN-2

    • DEN-3

    • DEN-4

  • DEN-1 found in Pacific Islands

  • Historically, DEN-2 is the prevalent serotype found in Southeast Asia

    • Recently found in Jamaica

  • DEN-3 found in the Caribbean

  • But now all 4 strains are found almost everywhere

Transmission

  • Arbovirus - arthropod-borne virus

    • Human and primate host transmission

  • Vector: Aedes aegypti

    • Infected female mosquito

    • 10-day extrinsic incubation period (virus passes from intestinal tract to salivary glands)

    • Lays eggs and produces larvae in “artificial containers”

Pathogenesis

  • After bite, virus infects immature dendritic cells

  • Migration to lymph nodes

  • Incubation period of 3-6 days to viremia

Symptoms

  • High, prolonged fever

  • Severe headache

  • Painful eyes

  • Nausea

  • Vomiting

Symptoms-DHF

  • 4 Criteria Defined by WHO

    1. Fever, or recent history of acute fever

    2. Haemorrhagic manifestations

    3. Low platelet count

      1. < 100,000/mm

    4. Indications of plasma leakage

      1. Elevated hematocrit

      2. Low albumin

      3. Pleural (space around lungs) or other effusions

Viral Risk Factors for DHF

  • Higher risk for DHF in secondary infections

  • Higher risk in hyperendemic transmission

  • DEN-2 → DEN-3 → DEN-4 → DEN-1

Diagnosis

  • X-ray - reveals pleural effusion

  • Blood test - to look at hematocrit level

  • Tourniquet test - to determine patient’s haemorrhagic tendency

  • Serology test

  • PCR

Treatment

  • Supportive therapy such as rest and fluid intake

  • Aching symptoms - acetaminophen

  • Platelet transfusion

Prevention

  • Vector control

  • Vaccine development

    • Tetravalent vaccine - protection against all 4 serotypes

    • Chimeric vaccine - uses a yellow fever vaccine