Question
Describe the pathogenesis and laboratory diagnosis of Dengue fever
Answer
Pathogenesis of Dengue fever Dengue virus (a Flavivirus, four serotypes DENV-1–4) is transmitted by the bite of an infective Aedes aegypti mosquito. The virus replicates in local dendritic cells and disseminates via lymphatics/blood to the reticuloendothelial system (liver, spleen, bone marrow), producing viraemia and a systemic cytokine response (TNF-α and others) responsible for fever, myalgia, and rash. In secondary infection with a different serotype, Antibody-Dependent Enhancement (ADE) occurs: pre-existing, non-neutralizing cross-reactive antibody from the first infection binds the new serotype without neutralizing it, but the antibody-virus complex is taken up more efficiently by Fc-receptor-bearing monocytes/macrophages, paradoxically enhancing viral entry and replication — driving a heightened cytokine storm that increases capillary permeability (causing plasma leakage), activates complement, and suppresses bone marrow (contributing to thrombocytopenia) — the pathogenic basis of dengue haemorrhagic fever and dengue shock syndrome.
Laboratory diagnosis
- NS1 antigen — detectable from day 1, before antibody develops, useful for early diagnosis.
- IgM ELISA — positive from about day 5 of illness, indicating recent infection.
- IgG ELISA — the IgM:IgG pattern helps distinguish primary from secondary infection.
- RT-PCR — detects viral RNA in the early viraemic phase, allows serotyping.
- Full blood count — thrombocytopenia and rising haematocrit (haemoconcentration, reflecting plasma leakage) are key supportive findings.
- Tourniquet test — a simple bedside test for capillary fragility.
WHO classical criteria for DHF: fever, haemorrhagic tendency, thrombocytopenia (≤100,000/μL), and evidence of plasma leakage (rise in haematocrit ≥20%, pleural effusion, ascites, or hypoproteinaemia).