Model Answer
0 min readIntroduction
Dengue is a mosquito-borne viral infection that causes a spectrum of illness, ranging from asymptomatic infection to severe and potentially fatal Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). Caused by any of the four serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) of the Dengue virus, a flavivirus transmitted by *Aedes aegypti* and, to a lesser extent, *Aedes albopictus* mosquitoes, DHF is characterized by plasma leakage, hemorrhage, and thrombocytopenia. Globally, Dengue affects an estimated 100-400 million people annually, with significant morbidity and mortality, particularly in tropical and subtropical regions. Understanding the pathogenesis and accurate laboratory diagnosis are critical for effective clinical management and public health interventions.
Pathogenesis of Dengue Hemorrhagic Fever
The pathogenesis of DHF is complex and involves a dysregulated immune response, viral factors, and host genetic predisposition. It can be broadly divided into the following stages:
1. Viral Entry and Initial Replication
The Dengue virus enters the body through the bite of an infected mosquito, targeting skin dendritic cells. These cells migrate to regional lymph nodes, initiating viral replication. Subsequently, the virus disseminates to other tissues via the bloodstream, infecting monocytes, macrophages, and liver cells.
2. Immune Response and Antibody-Dependent Enhancement (ADE)
The innate immune response is activated, leading to the production of interferons and other cytokines. The adaptive immune response follows, generating both neutralizing and non-neutralizing antibodies. A crucial factor in DHF pathogenesis is Antibody-Dependent Enhancement (ADE). If a person previously infected with one serotype is subsequently infected with a different serotype, pre-existing non-neutralizing antibodies can bind to the new virus, facilitating its entry into Fc receptor-bearing cells (like macrophages) and enhancing viral replication. This leads to a higher viral load and a more severe disease course.
3. Vascular Permeability and Plasma Leakage
Increased vascular permeability is the hallmark of DHF. Several mechanisms contribute to this:
- Cytokine Storm: The excessive release of pro-inflammatory cytokines (TNF-α, IL-6, IL-8, IL-10) disrupts endothelial cell function, increasing permeability.
- Complement Activation: Dengue virus activates the complement system, generating anaphylatoxins (C3a, C5a) that increase vascular permeability.
- Direct Viral Effects: The virus may directly infect endothelial cells, causing damage and leakage.
- Antibody-Mediated Damage: Immune complexes formed during ADE can deposit in blood vessels, triggering inflammation and permeability.
Plasma leakage leads to hemoconcentration (increased hematocrit), hypovolemia, and potentially shock.
4. Hemorrhage and Thrombocytopenia
Thrombocytopenia (low platelet count) is common in DHF, resulting from:
- Bone Marrow Suppression: Viral infection can directly suppress bone marrow function.
- Increased Platelet Destruction: Antibody-mediated platelet destruction contributes to thrombocytopenia.
- Platelet Consumption: Platelets are consumed in the formation of microthrombi.
Hemorrhage occurs due to thrombocytopenia, endothelial dysfunction, and impaired coagulation. This can manifest as petechiae, purpura, epistaxis, gingival bleeding, and gastrointestinal bleeding.
Laboratory Diagnosis of Dengue Hemorrhagic Fever
Laboratory diagnosis of DHF relies on a combination of clinical findings and laboratory tests.
1. Complete Blood Count (CBC)
CBC reveals:
- Thrombocytopenia: Platelet count <100,000/µL is a key diagnostic criterion.
- Hemoconcentration: Elevated hematocrit due to plasma leakage.
- Leukopenia: Low white blood cell count, often with relative lymphocytosis.
2. Serological Tests
These tests detect antibodies against Dengue virus:
- ELISA (Enzyme-Linked Immunosorbent Assay): Detects IgM and IgG antibodies. IgM antibodies appear early in the infection (3-5 days after onset) and indicate recent infection. IgG antibodies appear later and persist for longer, indicating past infection.
- NS1 Antigen Detection: NS1 is a non-structural protein of the Dengue virus. NS1 antigen detection tests are useful in the early stages of infection (first 5 days) when IgM antibodies are not yet detectable.
- Hemagglutination Inhibition (HAI) Test: Historically used, but less sensitive and specific than ELISA.
3. Molecular Tests (PCR)
Real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) detects viral RNA in the acute phase of infection (first 5 days). PCR is highly sensitive and specific, allowing for early diagnosis and serotype identification. However, it is more expensive and requires specialized equipment.
4. Other Tests
These tests assess the severity of the disease:
- Liver Function Tests (LFTs): Elevated liver enzymes (AST, ALT) indicate liver involvement.
- Coagulation Studies: Assess for disseminated intravascular coagulation (DIC).
- Albumin Levels: Decreased albumin levels indicate plasma leakage.
| Test | Timing | Sensitivity | Specificity |
|---|---|---|---|
| NS1 Antigen | Days 1-5 | High | Good |
| IgM ELISA | Days 5-90 | Good | Good |
| IgG ELISA | >90 days | High | Moderate |
| RT-PCR | Days 1-5 | Very High | Very High |
Conclusion
Dengue Hemorrhagic Fever is a severe manifestation of Dengue virus infection, characterized by a complex interplay of viral factors, immune responses, and vascular permeability. Accurate and timely diagnosis, utilizing a combination of clinical assessment and laboratory tests like CBC, serological assays, and molecular techniques, is crucial for effective management and reducing mortality. Continued research into the pathogenesis of DHF and the development of effective vaccines and therapeutics remain vital public health priorities.
Answer Length
This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.