Diagnostic accuracy and utility of three dengue diagnostic tests for the diagnosis of acute dengue infection in Malaysia

Abstract

Background: Dengue is an emerging infectious disease that infects up to 390 million people yearly. The growing demand of dengue diagnostics especially in low-resource settings gave rise to many rapid diagnostic tests (RDT). This study evaluated the accuracy and utility of ViroTrack Dengue Acute -a new biosensors-based dengue NS1 RDT, SD Bioline Dengue Duo NS1/IgM/IgG combo -a commercially available RDT, and SD Dengue NS1 Ag enzymelinked immunosorbent assay (ELISA), for the diagnosis of acute dengue infection. Methods: This prospective cross-sectional study consecutively recruited 494 patients with suspected dengue from a health clinic in Malaysia. Both RDTs were performed onsite. The evaluated ELISA and reference tests were performed in a virology laboratory. The reference tests comprised of a reverse transcription-polymerase chain reaction and three ELISAs for the detection of dengue NS1 antigen, IgM and IgG antibodies, respectively. The diagnostic performance of evaluated tests was computed using STATA version 12. Results: The sensitivity and specificity of ViroTrack were 62.3% (95%CI 55.6-68.7) and 95.0% (95%CI 91.7-97.3), versus 66.5% (95%CI 60.0-72.6) and 95.4% (95%CI 92.1-97.6) for SD NS1 ELISA, and 52.4% (95%CI 45.7-59.1) and 97.7% (95%CI 95.1-99.2) for NS1 component of SD Bioline, respectively. The combination of the latter with its IgM and IgG components were able to increase test sensitivity to 82.4% (95%CI 76.8-87.1) with corresponding decrease in specificity to 87.4% . Although a positive test on any of the NS1 assays would increase the probability of dengue to above 90% in a patient, a negative result would only reduce this probability to 23.0-29.3%. In contrast, this probability of false negative diagnosis would be further reduced to 14.7% if SD Bioline NS1/IgM/IgG combo was negative. Conclusions: The performance of ViroTrack Dengue Acute was comparable to SD Dengue NS1 Ag ELISA. Addition of serology components to SD Bioline Dengue Duo significantly improved its sensitivity and reduced its false negative rate such that it missed the fewest dengue patients, making it a better point-of-care diagnostic tool. New RDT like ViroTrack Dengue Acute may be a potential alternative to existing RDT if its combination with serology components is proven better in future studies.

Experience of a Tertiary Hospital in Singapore with Management of a Dual Outbreak of COVID-19 and Dengue

“…However, a study found that this combined sensitivity was only 82.4% (95% CI: 76.8–87.1), with a specificity of 87.4% (95% CI: 82.8–91.2); the probability of a false-negative diagnosis would be further reduced to 14.7% (95% CI: 11.4–18.6) if SD Bioline NS1 Ag/IgM/IgG combo was negative. 9 In the inpatient setting, dengue NS1 Ag and IgM test is performed on venous blood samples using enzyme-linked immunosorbent assay (EIA) methods, which has better sensitivity and specificity but with a longer turnaround time due to batch testing. Reverse transcription-PCR for dengue virus from blood and urine specimens is also available for additional confirmatory testing.…”

“…Dengue IgM may be a false positive in other conditions as well, such as malaria, other flaviviruses, or autoimmune conditions with a positive rheumatoid factor. [8][9][10] Establishing the diagnosis of dengue via RT-PCR is crucial to distinguish true coinfection from possible cross-reactivity. Among our COVID-19 cases with concomitant positive dengue IgM serology, only those with clinical indications were followed up with a dengue PCR blood test to exclude dengue infection.…”

“…7 Furthermore, there have been isolated case reports of false-positive dengue serology with rapid diagnostic tests (RDTs) in cases of COVID-19, making it difficult to distinguish the two entities. 3,8 Rapid serological tests play a key role in dengue diagnostics, 9 especially in low-resource settings where resource-intensive laboratory tests such as reverse transcription-PCR (RT-PCR) and ELISA may not be routinely available. 10 Thus, in healthcare systems facing twin outbreaks of both COVID- 19 and arboviral diseases such as dengue, pathways for the care of patients presenting with undifferentiated viral fever may need to be reworked to minimize the potential of healthcareassociated transmission from a previously unsuspected case of COVID-19.…”

Application of One-Step Reverse Transcription Droplet Digital PCR for Dengue Virus Detection and Quantification in Clinical Specimens

“…RDTs are inexpensive, and results are interpretable within a few minutes. However, the sensitivity and specificity of RDTs are limited [ 5 , 6 ]. RT-PCR is the standard method for confirming DENV infection because of its high sensitivity and specificity as well as a relatively short turnaround time compared to other methods such as virus isolation [ 1 ].…”

COVID-19 with dengue shock syndrome in a child: coinfection or cross-reactivity?

“… 3 The reported specificity of dengue NS1 antigen test is 87.4%–97.7% during the febrile phase. 4 To the best of our knowledge, there is no paediatric case reported yet with these two coinfections. We describe the first paediatric case of COVID-19 with positive dengue NS1 antigen and IgM antibody who presented to our paediatric intensive care unit with features of encephalitis, raised intracranial pressure (ICP) and shock.…”