Evaluation of the Diagnostic Accuracy of a New Biosensors-Based Rapid Diagnostic Test for the Point-Of-Care Diagnosis of Previous and Recent Dengue Infections in Malaysia

Abstract

Dengue is a major threat to public health globally. While point-of-care diagnosis of acute/recent dengue is available to reduce its mortality, a lack of rapid and accurate testing for the detection of previous dengue remains a hurdle in expanding dengue seroepidemiological surveys to inform its prevention, especially vaccination, to reduce dengue morbidity. This study evaluated ViroTrack Dengue Serostate, a biosensors-based semi-quantitative anti-dengue IgG (immunoglobulin G) immuno-magnetic agglutination assay for the diagnosis of previous and recent dengue in a single test. Blood samples were obtained from 484 healthy participants recruited randomly from two communities in Petaling district, Selangor, Malaysia. The reference tests were Panbio Dengue IgG indirect and capture enzyme-linked immunosorbent assays, in-house hemagglutination inhibition assay, and focus reduction neutralization test. Dengue Serostate had a sensitivity and specificity of 91.1% (95%CI 87.8–93.8) and 91.1% (95%CI 83.8–95.8) for the diagnosis of previous dengue, and 90.2% (95%CI 76.9–97.3) and 93.2% (95%CI 90.5–95.4) for the diagnosis of recent dengue, respectively. Its positive predictive value of 97.5% (95%CI 95.3–98.8) would prevent most dengue-naïve individuals from being vaccinated. ViroTrack Dengue Serostate’s good point-of-care diagnostic accuracy can ease the conduct of dengue serosurveys to inform dengue vaccination strategy and facilitate pre-vaccination screening to ensure safety.

Dengue Seroprevalence and Factors Associated with Dengue Seropositivity in Petaling District, Malaysia

“…DENV seroprevalence was determined using three different dengue serological tests as a composite reference standard to detect anti-dengue antibodies, which were (1) in-house hemagglutination inhibition (HI) assay, (2) in-house focus reduction neutralisation test (FRNT) adapted from the plaque reduction neutralisation test (PRNT), and (3) commercially available Panbio Dengue IgG indirect enzyme-linked immunosorbent assay (ELISA) (Abbott, Chicago, IL, USA). HI has been regarded as the gold standard for dengue serological diagnosis due to its high accuracy and ability to determine the exact titre of virus-neutralising antibodies [ 20 , 21 ]. The sensitivity of IgG ELISA is comparable to HI but has greater specificity than HI and is more feasible to be conducted [ 20 , 22 ].…”

The seroprevalence of SARS‐CoV‐2 infection in Malaysia: 7 August to 11 October 2020

“…Comparatively, the sensitivity and specificity of other SARS‐CoV‐2 total antibody RTKs ranged around 18.4–100.0% and 80.6–100.0%, respectively 22 . Although a direct comparison of diagnostic accuracy across different studies cannot be completed without assessing the underlying biases stemming from heterogeneity in different studies, 32 the low sensitivity of this particular RTK precludes its application in future seroprevalence studies 22 . Any COVID‐19 seroprevalence study using RTK should be based on a proper prior evaluation and adjusted for measurement bias to obtain a more accurate seroprevalence estimate 27,33 …”

“…In terms of the proportion of undiagnosed COVID-19 cases, apart from the study population and the accuracy of serological tests used, the main reasons for heterogeneity across studies could be the fundamental differences between countries and administrative entities in their definition of COVID-19 cases and contacts, the aggressiveness of contact tracing, testing availability and strategy, and other factors that would affect the yield of case detection relative to actual infection. [26][27][28][29][30] On the day we concluded our blood collection, 32 the low sensitivity of this particular RTK precludes its application in future seroprevalence studies. 22 Any COVID-19 seroprevalence study using RTK should be based on a proper prior evaluation and adjusted for measurement bias to obtain a more accurate seroprevalence estimate.…”

Performance Evaluation of a Dengue IgG Rapid Diagnostic Test Designed to Determine Dengue Serostatus as Part of Prevaccination Screening

“…Commercially available RDTs detecting anti-dengue IgG display high specificity and low flavivirus cross-reactivity in identifying prior dengue infection, but are suboptimal in sensitivity ( 6 – 8 ). Recent findings for new point-of-care dengue immunoassays developed for prevaccination screening indicated higher sensitivity than existing commercial dengue IgG-containing RDTs, but suboptimal specificity ( 10 – 12 ).…”