Diagnostic Accuracy of NS1 ELISA and Lateral Flow Rapid Tests for Dengue Sensitivity, Specificity and Relationship to Viraemia and Antibody Responses

Abstract

BackgroundDengue is a public health problem in many countries. Rapid diagnosis of dengue can assist patient triage and management. Detection of the dengue viral protein, NS1, represents a new approach to dengue diagnosis.Methodology/Principal FindingsThe sensitivity and specificity of the Platelia NS1 ELISA assay and an NS1 lateral flow rapid test (LFRT) were compared against a gold standard reference diagnostic algorithm in 138 Vietnamese children and adults. Overall, the Platelia NS1 ELISA was modestly more sensitive (82%) than the NS1 LFRT (72%) in confirmed dengue cases. Both ELISA and LFRT assays were more sensitive for primary than secondary dengue, and for specimens collected within 3 days of illness onset relative to later time points. The presence of measurable DENV-reactive IgG and to a lesser extent IgM in the test sample was associated with a significantly lower rate of NS1 detection in both assays. NS1 positivity was associated with the underlying viraemia, as NS1-positive samples had a significantly higher viraemia than NS1-negative samples matched for duration of illness. The Platelia and NS1 LFRT were 100% specific, being negative in all febrile patients without evidence of recent dengue, as well as in patients with enteric fever, malaria, Japanese encephalitis and leptospirosis.Conclusions/SignificanceCollectively, these data suggest NS1 assays deserve inclusion in the diagnostic evaluation of dengue patients, but with due consideration for the limitations in patients who present late in their illness or have a concomitant humoral immune response.

Determination of Viremia and Concentration of Circulating Nonstructural Protein 1 in Patients Infected with Dengue Virus in Mexico

“…Commercial assays, such as the one used in this study, have been shown to be more sensitive for NS1 detection during primary infections than during secondary infections. 17,31,32 Our results also suggest that median concentrations of circulating NS1 are higher for infections caused by DENV-1 than by DENV-2. For this study, only primary infections could be compared.…”

Kinetics of Dengue Non-Structural Protein 1 Antigen and IgM and IgA Antibodies in Capillary Blood Samples from Confirmed Dengue Patients

“…21,22,28,29 In the present study, we provide serological evidence that all infected patients were secondary dengue cases, which could be expected, because dengue infection is endemic in Vietnam. Nevertheless, contrary to previous studies, 27,30,31 our results suggest that the sensitivity of NS1 detection assays is not significantly affected by the immune status of the patient, which is in agreement with a previous work by Castro-Jorge and others.…”

Co-Infection of Dengue Virus by Serotypes 1 and 4 in Patient From Medium Sized City From Brazil

“…This assay provides additional dengue diagnostic tool to the existing approaches of PCR, antibody capture ELISA and virus isolation 5,6,10,12,13,20,24,25,28 . Even though NS1 is a sensitive methodology for the detection of DENV it should never be used as the only methodology for DENV detection because it doesn't identify different serotypes 39 .…”