A Meta-Analysis of the Diagnostic Accuracy of Two Commercial NS1 Antigen ELISA Tests for Early Dengue Virus Detection

Abstract

BackgroundDengue virus (DENV) NS1 antigen detection is regarded as an early diagnostic marker. Accordingly, several studies have evaluated the performance of tests that utilize NS1 capture, but the results of individual studies may be limited due to the restricted sample size of the patients recruited. Therefore, our objective was to perform a meta-analysis of the diagnostic accuracy of two commercial NS1 ELISAs (Panbio and Platelia).Methods and ResultsStudies of interest were found in PubMed, Embase and Google Scholar databases using defined inclusion/exclusion criteria. A total of 30 studies containing 12,105 total enrolled patients were included. The results were as follows: 1) Panbio assays showed low overall performance, sensitivity 66% (95% confidence interval (CI) 61–71), specificity 99% (95% CI 96–100), positive likelihood ratio (LR+) 98 (95% CI 20–464), negative likelihood ratio (LR-) 0.3 (95% CI 0.2–0.4), diagnostic odds ratio (DOR) 289 (95% CI 59–1412); 2) Platelia assays showed high overall performance, sensitivity 74% (95% CI 63–82), specificity 99% (95% CI 97–100), LR+ 175 (95% CI 28–1099), LR- 0.3 (95% CI 0.2–0.4), DOR 663 (95% CI 98–4478). The lowest sensitivity values were for secondary infections (57% [95% CI 47–67] and 66% [95% CI 53–77] for Panbio and Platelia, respectively) and for the detection of DENV4. Regarding clinical manifestations, the sensitivity of Platelia was 69% (95% CI 43–86) and 60% (95% CI 48–70) for fever and dengue hemorrhagic fever, respectively. In addition, the sensitivity of both tests was slightly lower for samples from Southeast Asia and Oceania.ConclusionDENV1 samples gave higher sensitivity results for both tests. We observed that factors negatively influencing the tests, such as the type of infection, geographical origins of samples and viral serotypes, require further investigation to optimize the diagnostic accuracy.

Dengue diagnosis in an endemic area of Peru: Clinical characteristics and positive frequencies by RT-PCR and serology for NS1, IgM, and IgG

“…This could be the result of immune complex formation during secondary infection, which impairs NS1 detection by ELISA (Buonora et al, 2017). Some studies have also reported lower NS1 ELISA sensitivity in DENV-4 infections compared with infections caused by other serotypes, in both primary and secondary infections (da Costa et al, 2014).…”

A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection

“…Since IgA also appears in the body fluids during the same time period as IgM, the combination of NS1 Ag and IgA antibody-based tests can serve as an alternative. NS1 Ag-based tests also had lower sensitivity during secondary infections [3][4][5]. NS1 Ag-based tests also had lower sensitivity during secondary infections [3][4][5].…”

“…However, recent studies have indicated that the sensitivity of NS1 antigen-based tests are lower in secondary infections and in DENV-4 serotype infections [3][4][5]. Nucleic acid-based tests offer the best opportunity for early diagnosis of dengue but are expensive and not available in resource-limited settings.…”

Increased sensitivity of NS1 ELISA by heat dissociation in acute dengue 4 cases

“…Some studies have also noticed lower NS1 sensitivity in DENV-4 compared to other serotypes, in both primary and secondary dengue [12, 13]. Furthermore, immune complex dissociation techniques have proven to be important for the early diagnosis of HIV infections and most recently DENV [9, 16].…”