The dengue virus (DENV) is a single-stranded RNA virus from the genus Flavivirus, consisting of four serotypes (DENV-1–4). Dengue disease poses a significant health burden, especially in tropical countries, including Indonesia. To understand the course of the disease, virological aspects and viral protein dynamics are key. One particularly important protein is Non-Structural Protein 1 (NS1), a glycoprotein actively released into circulation during the acute phase of infection.

NS1 has been proven to be an effective biomarker for detecting dengue infection from the first day of symptoms, even before IgM and IgG antibodies are detectable. Understanding its expression mechanisms in primary and secondary infections is essential for improving diagnostic accuracy and supporting rapid clinical decision-making.

1. Structure and Replication of the Dengue Virus

The dengue virus has a positive-sense RNA genome that encodes a single large polyprotein. This polyprotein is cleaved into structural and non-structural proteins, including NS1. NS1 exists in several forms:

• Monomer in the endoplasmic reticulum

• Dimer on the surface of infected cells

• Hexamer, which is secreted into the bloodstream

The hexameric NS1 is widely used in the development of antigen-based rapid tests due to its high concentration during the early viremic phase.

2. NS1 Expression in Primary and Secondary Infection

a. Primary Infection

In the first infection, the body has no pre-existing dengue-specific antibodies. As a result:

• NS1 levels are higher

• NS1 can be detected up to day 7

• NS1 test sensitivity tends to be higher

This makes NS1 an ideal marker for early diagnosis in primary infection.

b. Secondary Infection

During reinfection, cross-reactive antibodies from the previous infection can form immune complexes with NS1. Consequently:

• Free NS1 can be detected for a shorter period

• However, early NS1 levels remain high within the first 1–3 days of fever

• Combining NS1 detection with antibody (IgM/IgG) testing improves accuracy

These differences are important for interpreting rapid test or laboratory results.

3. Significance of NS1 in Diagnosis and Pathogenesis

a. Diagnostic Marker

NS1 can be detected from the first day of fever and serves as a crucial indicator for:

• Early diagnosis

• Clinical triage

• Monitoring acute infection

Early detection enables prompt supportive intervention, such as monitoring hematocrit and fluid balance.

b. Pathogenetic Role of NS1

NS1 is not only a marker but also contributes to dengue pathogenesis through:

• Complement activation

• Disruption of endothelial integrity

• Increased vascular permeability

These mechanisms contribute to plasma leakage, a hallmark of severe dengue.

4. ACCU-TELL® Dengue IgG/IgM/NS1 Combo Cassette (Whole Blood/Serum/Plasma) – A Solution for Accurate Early Detection

To support rapid and accurate diagnosis, antigen–antibody–based tools such as the ACCU-TELL® Dengue IgG/IgM/NS1 Combo Cassette (Whole Blood/Serum/Plasma) are available.

5. Advantages of the ACCU-TELL® Dengue IgG/IgM/NS1 Combo Cassette (Whole Blood/Serum/Plasma):

• Uses a rapid chromatographic immunoassay principle: allows easy interpretation through visible color lines within minutes

• CE-certified and registered with the Indonesian Ministry of Health (AKL KEMENKES RI)

• Two-year shelf life from the production date

• Accepts three sample types—whole blood, serum, and plasma—offering flexibility based on sample availability

• Results can be interpreted within 10 minutes, enabling immediate decision-making

• Clinically validated with the following performance:

  • IgG/IgM test: sensitivity 95.7%, specificity >99.9%, accuracy 99.3%

  • NS1 test: sensitivity 95.8%, specificity 96.2%, accuracy 96.1%

• Effectively detects IgG/IgM antibodies and NS1 antigen in whole blood, serum, or plasma

• Includes one buffer bottle for 20 tests

• Each box contains:
  a. Test cassette
  b. Plastic capillary pipette
  c. One buffer bottle
  d. Insert pack

Understanding dengue’s virological characteristics and NS1 expression dynamics provides a strong scientific basis for early diagnostic strategies. NS1 offers distinct advantages as an acute-phase biomarker in both primary and secondary infection, despite differing detection dynamics in each condition. Beyond diagnostics, NS1 also contributes to plasma leakage pathogenesis, making it a key factor in both clinical and biomedical contexts.

The application of diagnostic tools combining NS1 and antibody detection, such as the ACCU-TELL® Dengue IgG/IgM/NS1 Combo Cassette, can enhance diagnostic accuracy and help healthcare professionals provide timely management to prevent severe dengue complications.

References

1. Guzman, M. G., & Harris, E. (2015). Dengue. The Lancet, 385(9966), 453–465.

2. Young, P. R., Hilditch, P. A., Bletchly, C., & Halloran, W. (2000). An antigen capture ELISA reveals high levels of dengue virus NS1 protein in patient sera. Journal of Clinical Microbiology, 38(3), 1053–1057.

3. Muller, D. A., & Young, P. R. (2013). The flavivirus NS1 protein: molecular and structural biology, immunology, role in pathogenesis, and application as a diagnostic biomarker. Antiviral Research, 98(2), 192–208.

4. World Health Organization. (2020). Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control.

5. Libraty, D. H., et al. (2002). High circulating dengue NS1 levels early in illness correlate with dengue hemorrhagic fever development. Journal of Infectious Diseases, 186(8), 1165–1168.