Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples.

Subhamoy Pal,Tadeusz J Kochel,Allison L Dauner,Shuenn-Jue L Wu,Eric S Halsey,Brett M Forshey,Amy C Morrison,Indrani Mitra,Paquita Garcia,Baochuan Lin

doi:10.1371/journal.pone.0113411

Abstract

BackgroundEarly diagnosis of dengue virus (DENV) infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. Non-structural glycoprotein-1 (NS1) has proven to be a useful biomarker for early diagnosis of dengue. A number of rapid diagnostic tests (RDTs) and enzyme-linked immunosorbent assays (ELISAs) targeting NS1 antigen (Ag) are now commercially available. Here we evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis.Methodology/Principal FindingsRetrospective samples from South America were used to evaluate the following tests: (i) “Dengue NS1 Ag STRIP” and (ii) “Platelia Dengue NS1 Ag ELISA” (Bio-Rad, France), (iii) “Dengue NS1 Detect Rapid Test (1st Generation)” and (iv) “DENV Detect NS1 ELISA” (InBios International, United States), (v) “Panbio Dengue Early Rapid (1st generation)” (vi) “Panbio Dengue Early ELISA (2nd generation)” and (vii) “SD Bioline Dengue NS1 Ag Rapid Test” (Alere, United States). Overall, the sensitivity of the RDTs ranged from 71.9%–79.1% while the sensitivity of the ELISAs varied between 85.6–95.9%, using virus isolation as the reference method. Most tests had lower sensitivity for DENV-4 relative to the other three serotypes, were less sensitive in detecting secondary infections, and appeared to be most sensitive on Day 3–4 post symptom onset. The specificity of all evaluated tests ranged from 95%–100%.ConclusionsELISAs had greater overall sensitivity than RDTs. In conjunction with other parameters, the performance data can help determine which dengue diagnostics should be used during the first few days of illness, when the patients are most likely to present to a clinic seeking care.

Highlights

Up to 390 million dengue cases are thought to occur each year, and approximately 2.5 billion people are at risk for infection worldwide, with no vaccine or antiviral approved to reduce disease burden [1,2]
These samples were excluded from further analysis, as enzyme-linked immunosorbent assays (ELISAs) results alone were not considered to be specific enough to confirm acute dengue virus (DENV) infection
We found that ELISA kits had superior sensitivity when compared to rapid diagnostic tests (RDTs)

Summary

Introduction

Up to 390 million dengue cases are thought to occur each year, and approximately 2.5 billion people are at risk for infection worldwide, with no vaccine or antiviral approved to reduce disease burden [1,2]. Accurate and affordable diagnostic tests are a crucial component of combating this debilitating mosquito-borne infection. Such assays would permit early diagnosis of dengue and improve clinical management of patients. Diagnosis of dengue virus (DENV) infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. A number of rapid diagnostic tests (RDTs) and enzyme-linked immunosorbent assays (ELISAs) targeting NS1 antigen (Ag) are commercially available. We evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis

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