Multi-Country Evaluation of the Sensitivity and Specificity of Two Commercially-Available NS1 ELISA Assays for Dengue Diagnosis

Abstract

BackgroundEarly diagnosis of dengue can assist patient triage and management and prevent unnecessary treatments and interventions. Commercially available assays that detect the dengue virus protein NS1 in the plasma/serum of patients offers the possibility of early and rapid diagnosis.Methodology/Principal FindingsThe sensitivity and specificity of the Pan-E Dengue Early ELISA and the Platelia™ Dengue NS1 Ag assays were compared against a reference diagnosis in 1385 patients in 6 countries in Asia and the Americas. Platelia was more sensitive (66%) than Pan-E (52%) in confirmed dengue cases. Sensitivity varied by geographic region, with both assays generally being more sensitive in patients from SE Asia than the Americas. Both kits were more sensitive for specimens collected within the first few days of illness onset relative to later time points. Pan-E and Platelia were both 100% specific in febrile patients without evidence of acute dengue. In patients with other confirmed diagnoses and healthy blood donors, Platelia was more specific (100%) than Pan-E (90%). For Platelia, when either the NS1 test or the IgM test on the acute sample was positive, the sensitivity versus the reference result was 82% in samples collected in the first four days of fever. NS1 sensitivity was not associated to disease severity (DF or DHF) in the Platelia test, whereas a trend for higher sensitivity in DHF cases was seen in the Pan-E test (however combined with lower overall sensitivity).Conclusions/SignificanceCollectively, this multi-country study suggests that the best performing NS1 assay (Platelia) had moderate sensitivity (median 64%, range 34–76%) and high specificity (100%) for the diagnosis of dengue. The poor sensitivity of the evaluated assays in some geographical regions suggests further assessments are needed. The combination of NS1 and IgM detection in samples collected in the first few days of fever increased the overall dengue diagnostic sensitivity.

Evaluation of Commercially Available Assays for Diagnosis of Acute Dengue in Schoolchildren During an Epidemic Period in Medellin, Colombia

“…However, an early and precise dengue diagnostic is important for patient management, to avoid dengue severity and mortality and, ultimately, to control epidemics. 8,21,26 Our results agree with others who reported that the combination of two or more diagnostic strategies is needed to improve the diagnostic accuracy of DENV infection. 8,[21][22][23]26 Combining direct DENV detection and antibody-based tests seems to be a particularly promising strategy.…”

“…21,23 Guzman and others 8 also reported lower sensitivity of NS1 antigen detection in American countries (Nicaragua and Venezuela) compared with Asian countries. 8,24 The occurrence of secondary infections also seems to have an impact on the accuracy of IgM detection. Indeed, higher sensitivity of the anti-IgM SD Bioline Dengue Duo was evidenced in primary DENV infections compared with secondary infections.…”

“…However, it has to be stressed that many reports that granted acceptable performances to commercially available dengue assays used ELISAs as comparators instead of gold standard methods such as PRNT or HI. 8,21,23,26 A recent study showed that ELISPOT-MNT had a sensitivity of 95.6% and specificity of 88.2%, with a good correlation (R 2 = 0.7) with PRNT. 16 Because of its very high sensitivity, the use of ELISPOT-MNT as the comparative standard method in our study leads inevitably to lower statistics performances of the assays that are compared with it, which can explain the relatively low performances of both diagnostic strategies.…”

“…However, early diagnosis and good supportive care can improve patient management and decrease dengue mortality. 8 Thus, diagnostic assays with good sensitivity and specificity are needed to differentiate DENV infections from other febrile illness such as leptospirosis, malaria, chikungunya, Zika, influenza, and others.…”

Detection of Dengue Virus NS1 Antigen in Infected Aedes aegypti Using a Commercially Available Kit

“…The monoclonal antibody used in the test has been shown to detect the NS1 protein of all 4 DENV serotypes, albeit with some differences in sensitivity. 37 Moreover, Tan and others 28 showed that all 4 DENV serotypes could be readily detected in infected mosquitoes using the Dengue NS1 Ag Strip test from the same manufacturer as the Platelia Dengue NS1 kit. Nonetheless, it would be prudent to determine the ability to detect DENV-1, -3, and -4 NS1 in mosquitoes subjected to the simulated field collection conditions by use of the Platelia Dengue NS1 Ag kit.…”