Assessment of diagnostic and analytic performance of the SD Bioline Dengue Duo test for dengue virus (DENV) infections in an endemic area (Savannakhet province, Lao People's Democratic Republic)

Abstract

BackgroundRapid tests detecting both dengue virus (DENV) NS1 antigen and anti-DENV IgM and IgG antibodies facilitate diagnosis of dengue fever (DF) in resource-poor settings. Methodology/principal findings92 acute phase serum samples from patients with a PCR-confirmed DENV infection collected in Lao People's Democratic Republic (Lao PDR) in 2013 and 2015 were analyzed with the SD Bioline Dengue Duo test. A subset of 74 samples was additionally tested with the Platelia NS1 antigen test, the Panbio DENV μ-capture ELISA and the Panbio DENV IgG ELISA. IgM seroconversion was assayed using follow-up samples of 35 patients collected in the convalescent phase. 57.6%, 22.8% and 44.6% of acute phase serum samples tested positive in the SD Bioline Dengue Duo NS1, IgM, and IgG test, respectively. Diagnostic sensitivity of the SD Bioline Dengue Duo NS1 test strongly correlated with viral load, decreased rapidly over the acute phase of the disease, and was significantly reduced in presence of high anti-DENV IgG antibody titers resulting from secondary DENV infection. While a good concordance (Cohen's kappa 0.78) was found between the SD Bioline Dengue Duo NS1 test and the Platelia NS1 antigen ELISA, both the SD Bioline Dengue Duo IgM and IgG test displayed a significantly lower sensitivity than the corresponding ELISA tests. The SD Bioline Dengue Duo test is a valuable tool for diagnosis of DENV infections especially when analyzing early acute phase samples with high viral load. Nevertheless, in endemic areas, where secondary flavivirus infections are common, diagnostic sensitivity of the NS1 and IgM test components may be compromised. PLOS ONE Performance evaluation of the SD Bioline Dengue Duo test PLOS ONE | https://doi.org/10.1371/journal.pone.0230337 March 17, 2020 2 / 17 PLOS ONE Performance evaluation of the SD Bioline Dengue Duo test PLOS ONE | https://doi.org/10.1371/journal.pone.0230337 March 17, 2020 3 / 17 m/f gender, n (%) 49/43 (53.3/46.7) days post onset, median (range) 4 (1-11) Ct pan-DENV PCR, median (range) 30.8 (19.3-40.9) DENV1/2/3/4 serotype, n (%) 2/28/50/12 (2.2/30.4/54.3/13.0)WBC in 10 3 μl -1 , median (range) 2.9 (1.0-12.0) WBC < reference, n (%) 66 (71.7) PLT in 10 3 μl -1 , median (range) 107.0 (2.0-411.0) PLT < reference, n (%) 67 (72.8) m: male, f: female, WBC: white blood cells, PLT: platelets, Ct: threshold cycle; reference values are 4.0-11.0 x 10 3 per μl for WBC and 150.0-450.0 x 10 3 per μl for PLT.

Limited specificity of commercially available SARS-CoV-2 IgG ELISAs in serum samples of African origin

“…Recently, Lustig et al (11) reported false positive results of the Euroimmun Anti-SARS-CoV-2 IgA and IgG ELISAs in sera originating from donors with acute or past dengue virus (DENV) infection. In our study, 29 (21.6%) of the 134 Colombian donors tested positive in the SD Bioline Dengue Duo IgG Rapid Test (Alere/Abbott, USA), indicating a high titer of anti-DENV IgG antibodies (15). Indeed, two of the three Colombian sera testing positive in the spike-based Euroimmun Anti-SARS-CoV-2 ELISA (but negative in the nucleoprotein-based SARS-CoV-2 ELISAs) belonged to this subgroup.…”

Evaluation of VIDAS® diagnostic assay prototypes detecting dengue virus NS1 antigen and anti-dengue virus IgM and IgG antibodies

“…20,22 The lower sensitivity of the NS1 RDT has also been confirmed in independent studies. 15,19,23,33…”

“…Altogether, it is now acknowledged that the combined testing of DENV RNA and/or NS1 antigen with anti-DENV IgM and IgG serology increases the sensitivity of DENV infection diagnosis, by broadening the time window of diagnosis after onset of fever. 8,10,15–19 Because RT-PCR assays are complex and costly, albeit being highly accurate, healthcare providers are turning to easy-to-use ELISA- and RDT-based assays detecting DENV NS1 antigen and anti-DENV IgM and IgG antibodies. ELISA and RDT present both pros and cons.…”

“…8,12,19–22 Anti-DENV IgM and IgG ELISA can show poor specificity due to cross-reactivity with antibodies directed against other flaviviruses. 3,12,19,22,23 RDT are rapid, and easier to perform and to implement in field settings. However, the visual interpretation of RDT results is operator-dependent and can be a drawback.…”

Vector-borne diseases in pregnancy

“…IgM and IgG can also be falsely positive when testing for one virus in the presence of the other due to similar viral surface epitopes, which creates difficulties elucidating single versus dual infection. 49 Many commercial serological kits are available for dengue and some combine NS-1 ELISA to confer very high levels of detection of acute infection, 50 the high specificity of NS-1 ELISA for dengue virus is also highly advantageous in identifying true dengue infection. 51 Current Centers for Disease Control and Prevention (CDC) recommendations for symptomatic pregnant patients with suspected zika/dengue infection include collecting serum and urine samples within 12 weeks of onset of symptoms to test nucleic acid amplification test (NAAT) and IgM for dengue/zika.…”