The Diagnostic Sensitivity of Dengue Rapid Test Assays Is Significantly Enhanced by Using a Combined Antigen and Antibody Testing Approach

Abstract

BackgroundSerological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1) has been identified as an early marker for acute dengue, and is typically present between days 1–9 post-onset of illness but following seroconversion it can be difficult to detect in serum.AimsTo evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test.MethodologyThe clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples.Key ResultsIn Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6%) and 96% (95% CI: 92.2% to 99.8) respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1%) and 96.7% specificity (95% CI: 82.8% to 99.9%) compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers.ConclusionsThis study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.

Multicountry Prospective Clinical Evaluation of Two Enzyme-Linked Immunosorbent Assays and Two Rapid Diagnostic Tests for Diagnosing Dengue Fever

“…3C). Consistent with previous literature reports, the inclusion of the IgM line in the interpretation of positivity increased the overall sensitivity to Ͼ80% during this time period (40,41). Over time, the sensitivity of the NS1 line alone fell to 64% on days 4 to 7 p.s.o.…”

Comparison of Seven Commercial Antigen and Antibody Enzyme-Linked Immunosorbent Assays for Detection of Acute Dengue Infection

“…Recent studies have demonstrated the benefits of combining NS1 antigen and IgM antibody results for the diagnosis of dengue infections (2,11,19). NS1 antigen is detectable by commercial ELISAs in the first 7 to 9 days of infection, and IgM antibodies are detectable only after 4 to 5 days of infection (7,11,12); combining NS1 and IgM results allows for dengue diagnosis throughout the normal temporal spectrum of patient presentation.…”

Dengue: an update for clinicians working in non-endemic areas

“…Rapid tests, often combining NS1 detection with an antibody test, are also available and have a reasonable window of detection. 24 …”