Dataset Information

Evaluation of a dengue NS1 antigen detection assay sensitivity and specificity for the diagnosis of acute dengue virus infection.

ABSTRACT:

Background

Currently, no dengue NS1 detection kit has regulatory approval for the diagnosis of acute dengue fever. Here we report the sensitivity and specificity of the InBios DEN Detect NS1 ELISA using a panel of well characterized human acute fever serum specimens.

Methodology/principal findings

The InBios DENV Detect NS1 ELISA was tested using a panel composed of 334 serum specimens collected from acute febrile patients seeking care in a Bangkok hospital in 2010 and 2011. Of these patients, 314 were found to have acute dengue by either RT-PCR and/or anti-dengue IgM/IgG ELISA. Alongside the InBios NS1 ELISA kit, we compared the performance characteristics of the BioRad Platelia NS1 antigen kit. The InBios NS1 ELISA Ag kit had a higher overall sensitivity (86% vs 72.8%) but equal specificity (100%) compared to the BioRad Platelia kit. The serological status of the patient significantly influenced the outcome. In primary infections, the InBios NS1 kit demonstrated a higher sensitivity (98.8%) than in secondary infections (83.5%). We found significant variation in the sensitivity of the InBios NS1 ELISA kit depending on the serotype of the dengue virus and also found decreasing sensitivity the longer after the onset of illness, showing 100% sensitivity early during illness, but dropping below 50% by Day 7.

Conclusion/significance

The InBios NS1 ELISA kit demonstrated high accuracy when compared to the initial clinical diagnosis with greater than 85% agreement when patients were clinically diagnosed with dengue illness. Results presented here suggest the accurate detection of circulating dengue NS1 by the InBios DENV Detect NS1 ELISA can provide clinicians with a useful tool for diagnosis of early dengue infections.

SUBMITTER: Hermann LL

PROVIDER: S-EPMC4183466 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Publications

Evaluation of a dengue NS1 antigen detection assay sensitivity and specificity for the diagnosis of acute dengue virus infection.

Hermann Laura L LL Thaisomboonsuk Butsaya B Poolpanichupatam Yongyuth Y Jarman Richard G RG Kalayanarooj Siripen S Nisalak Ananda A Yoon In-Kyu IK Fernandez Stefan S

PLoS neglected tropical diseases 20141002 10

<h4>Background</h4>Currently, no dengue NS1 detection kit has regulatory approval for the diagnosis of acute dengue fever. Here we report the sensitivity and specificity of the InBios DEN Detect NS1 ELISA using a panel of well characterized human acute fever serum specimens.<h4>Methodology/principal findings</h4>The InBios DENV Detect NS1 ELISA was tested using a panel composed of 334 serum specimens collected from acute febrile patients seeking care in a Bangkok hospital in 2010 and 2011. Of th ...[more]

PMID: 25275493

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Project description:BackgroundDengue virus (DENV) infection is one of the biggest challenges for human health in the world. In addition, a secondary DENV infection sometimes causes dengue hemorrhagic fever (DHF), which frequently leads to death. For this reason, accurate diagnosis record management is useful for prediction of DHF. Therefore, the demand for DENV rapid diagnosis tests (RDTs) is increasing because these tests are easy and rapid to use. However, commercially available RDTs often show low sensitivity for DENV and cross-reactivity against other flaviviruses, especially Zika virus (ZIKV).MethodsWe developed two types of novel DENV non-structural protein 1 (NS1) detection RDTs, designated TKK-1st and TKK-2nd kits. Specificities of the monoclonal antibodies (MAbs) used in these kits were confirmed by enzyme-linked immuno-sorbent assay (ELISA), dot blot, and western blot using recombinant NS1 proteins and synthetic peptides. For evaluation of sensitivity, specificity, and cross-reactivity of the novel DENV NS1 RDTs, we first used cultured DENV and other flaviviruses, ZIKV and Japanese encephalitis virus (JEV). We then used clinical specimens obtained in Bangladesh in 2017 for further evaluation of kit sensitivity and specificity in comparison with commercially available RDTs. In addition, RNA extracted from sera were used for viral genome sequencing and genotyping.ResultsEpitopes of three out of four MAbs used in the two novel RDTs were located in amino acid positions 100 to 122 in the NS1 protein, a region that shows low levels of homology with other flaviviruses. Our new kits showed high levels of sensitivity against various serotypes and genotypes of DENV and exhibited high levels of specificity without cross-reactivity against ZIKV and JEV. In clinical specimens, our RDTs showed sensitivities of 96.0% (145/151, TKK-1st kit) and 96.7% (146/151, TKK-2nd kit), and specificities of 98.0% (98/100, TKK-1st kit and TKK-2nd kit). On the other hand, in the case of the commercially available SD Bioline RDT, sensitivity was 83.4% (126/151) and specificity was 99.0% (99/100) against the same clinical specimens.ConclusionsOur novel DENV NS1-targeting RDTs demonstrated high levels of sensitivity and lacked cross-reactivity against ZIKV and JEV compared with commercially available RDTs.

Project description:UNLABELLED: / BACKGROUND: Dengue is the most important arthropod borne viral disease worldwide in terms of morbidity and mortality and is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Brazil is responsible for approximately 80% of dengue cases in the Americas, and since the introduction of dengue in 1986, a total of 5,944,270 cases have been reported including 21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many cell types and cause diverse clinical and pathological effects. The goal of the study was to investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from previously confirmed dengue fatal cases (n = 23) that occurred in 2002 in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: A total of 74 tissue specimens were available: liver (n = 23), lung (n = 14), kidney (n = 04), brain (n = 10), heart (n = 02), skin (n = 01), spleen (n = 15), thymus (n = 03) and lymph nodes (n = 02). We evaluated three tests for NS1 antigen capture: first generation Dengue Early ELISA (PanBio Diagnostics), Platelia NS1 (BioRad Laboratories) and the rapid test NS1 Ag Strip (BioRad Laboratories). The overall dengue fatal case diagnosis based on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag Strip was 34.7% (08/23), 60.8% (14/23) and 91.3% (21/23), respectively. The Dengue Early ELISA detected NS1 in 22.9% (17/74) of the specimens analyzed and the Platelia NS1 in 45.9% (34/74). The highest sensitivity (78.3%; 58/74) was achieved by the NS1 Ag Strip, and the differences in the sensitivities were statistically significant (p<0.05). The NS1 Ag Strip was the most sensitive in liver (91.3%; 21/23), lung (71.4%; 10/14), kidney (100%; 4/4), brain (80%; 8/10), spleen (66.6%, 10/15) and thymus (100%, 3/3) when compared to the other two ELISA assays. CONCLUSIONS/SIGNIFICANCE: This study shows the DENV NS1 capture assay as a rapid and valuable approach to postmortem dengue confirmation. With an increasing number of DHF and fatal cases, the availability of new approaches useful for cases confirmation plays an important tool for the disease surveillance.

Project description:IntroductionRapid diagnostic tests (RDTs) were evaluated, in this paper, for their utility as a reliable test, using resource-constrained studies. In most studies, NS1 antigen and immunoglobulin M (IgM)-based immunochromatographic tests (ICTs) were considered for acute phase detection. We aimed to evaluate the diagnostic accuracy of NS1, IgM, and NS1/IgM-based ICTs to detect acute dengue virus (DENV) infection in dengue-endemic regions.MethodsStudies were electronically identified using the following databases: MEDLINE, Embase, Cochrane Library, Web of Science, and CINAHL Plus. Keywords including dengue, rapid diagnostic test, immunochromatography, sensitivity, specificity, and diagnosis were applied across databases. In total, 15 studies were included. Quality assessment of the included studies was performed using the QUADAS-2 tool. All statistical analyses were conducted using RevMan, MedCalc, and SPSS software.ResultsThe studies revealed a total of 4135 individuals, originating largely from the Americas and Asia. The prevalence of DENV cases was 53.8%. Pooled sensitivities vs. specificities for NS1 (only), IgM (only) and combined NS1/IgM were 70.97% vs. 94.73%, 40.32% vs. 93.01%, and 78.62% vs. 88.47%, respectively. Diagnostic odds ratio (DOR) of DENV for NS1 ICTs was 43.95 (95% CI: 36.61-52.78), for IgM only ICTs was 8.99 (95% CI: 7.25-11.16), and for NS1/IgM ICTs was 28.22 (95% CI: 24.18-32.95). ELISA ICTs yielded a DOR of 21.36, 95% CI: 17.08-26.741. RT-PCR had a DOR of 40.43, 95% CI: 23.3-71.2. Heterogeneity tests for subgroup analysis by ICT manufacturers for NS1 ICTs revealed an χ2 finding of 158.818 (df = 8), p < 0.001, whereas for IgM ICTs, the χ2 finding was 21.698 (df = 5), p < 0.001.ConclusionNS1-based ICTs had the highest diagnostic accuracy in acute phases of DENV infection. Certain factors influenced the pooled sensitivity, including ICT manufacturers, nature of the infection, reference method (RT-PCR), and serotypes. Prospective studies may examine the best strategy for incorporating ICTs for dengue diagnosis.

Dataset Information

Evaluation of a dengue NS1 antigen detection assay sensitivity and specificity for the diagnosis of acute dengue virus infection.

Background

Methodology/principal findings

Conclusion/significance

Publications

Evaluation of a dengue NS1 antigen detection assay sensitivity and specificity for the diagnosis of acute dengue virus infection.

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