Diagnosing dengue fever can be challenging due to its nonspecific symptoms, which can mimic other viral or bacterial infections. Therefore, laboratory confirmation is crucial in confirming a diagnosis of dengue. The diagnostic approach includes the following methods:
1. Serological Tests:
A fourfold or greater increase in immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies in paired serum samples suggests dengue infection. This can be demonstrated through enzyme-linked immunosorbent assays (ELISA) such as:
- MAC-ELISA (for IgM)
- NS1-ELISA (for nonstructural protein 1)
- IgG ELISA
2. Molecular Testing (RT-PCR):
Reverse-transcriptase polymerase chain reaction (RT-PCR) is used to detect the dengue virus's genetic material in serum, cerebrospinal fluid (CSF), or autopsy tissue. It is particularly useful in the early stages of infection and provides a rapid, serotype-specific diagnosis. Unlike serological tests, RT-PCR is not affected by cross-reactivity with other flaviviruses, making it a more reliable diagnostic tool.
3. Viral Isolation:
Though less commonly used, dengue virus can be isolated from blood (serum or plasma), white blood cells, or autopsy samples.
Routine Laboratory Tests for Dengue
Several routine tests are critical for assessing the severity of dengue and monitoring for complications:
1. Complete Blood Count (CBC):
- Thrombocytopenia (platelet count < 100 x 10⁹/L) is a common feature of dengue and is often seen before the onset of shock.
- Leukopenia (low white blood cell count) is observed near the end of the febrile phase.
- Hematocrit levels should be monitored regularly, as an increase of more than 20% indicates hemoconcentration and can signal impending shock.
2. Metabolic and Liver Panels:
- Hyponatremia (low sodium) is common in severe dengue cases.
- Liver enzyme elevations (aspartate aminotransferase and alanine aminotransferase) are typically mild but can be elevated significantly in dengue hemorrhagic fever (DHF) with hepatitis.
- Low albumin levels may indicate plasma leakage and vascular permeability.
3. Coagulation Profile:
- Prolonged prothrombin time and activated partial thromboplastin time are indicative of clotting dysfunction, especially in patients with hemorrhagic manifestations.
- Low fibrinogen levels and elevated fibrin degradation products may point to disseminated intravascular coagulation (DIC).
4. Guaiac Test:
This test checks for occult (hidden) blood in stool and may reveal subtle signs of early bleeding in dengue patients.
Imaging and Additional Tests
1. Ultrasonography: This imaging modality is used to detect fluid accumulation (pleural effusion, ascites) and is useful for identifying plasma leakage, particularly in DHF. A thickened gallbladder wall is also commonly observed in severe cases.
2. Chest Radiography: X-rays may reveal right-sided pleural effusion, common in DHF and dengue shock syndrome (DSS).
3. Electrocardiography (ECG): While nonspecific, ECG may show changes related to fever, electrolyte imbalances, or medications, though the clinical significance of these changes is unclear.
4. Head CT Scan: In patients with altered consciousness, a head CT scan without contrast can help detect intracranial hemorrhage or cerebral edema, which may occur in severe dengue cases.
Serologic and PCR Testing
Early in Illness (First 5 Days): Laboratory confirmation is best achieved by detecting dengue virus genomic sequences via RT-PCR or NS1 antigen via immunoassay from a single acute-phase serum sample.
Later in Illness: Detection of IgM anti-DENV via ELISA is recommended after the first week of symptoms. The Centers for Disease Control and Prevention (CDC) advises using a combination of RT-PCR or NS1 antigen tests and IgM testing to confirm dengue infection, depending on the timing of symptom onset.
Classification and Reporting
Cases of dengue are classified as:
- Suspected Dengue: If symptoms align with the clinical description.
- Probable Dengue: If there are supportive serologic findings (positive IgM, hemagglutination-inhibition antibody titer > 1280).
- Confirmed Dengue: If laboratory confirmation is achieved.
In severe cases of dengue (hemorrhagic or shock syndrome), it’s essential to report the case to public health authorities, including details like patient demographics, recent travel history, and outcomes.
Conclusion
A comprehensive diagnostic workup for dengue includes a combination of serologic tests, molecular testing (RT-PCR), and routine laboratory evaluations. Ultrasonography and coagulation studies are essential for identifying complications like plasma leakage, while timely monitoring of hematocrit and platelet levels is crucial for detecting early signs of severe dengue, including hemorrhagic fever and shock.
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