Using NS1 Flavivirus Protein Microarray to Infer Past Infecting Dengue Virus Serotype and Number of Past Dengue Virus Infections in Vietnamese Individuals

Abstract

Background In recent years, researchers have had an increased focus on multiplex microarray assays, in which antibodies are measured against multiple related antigens, for use in seroepidemiological studies to infer past transmission. Methods We assess the performance of a flavivirus microarray assay for determining past dengue virus (DENV) infection history in a dengue-endemic setting, Vietnam. We tested the microarray on samples from 1 and 6 months postinfection from DENV-infected patients (infecting serotype was determined using reverse-transcription polymerase chain reaction during acute, past primary, and secondary infection assessed using plaque reduction neutralization tests 6 months postinfection). Results Binomial models developed to discriminate past primary from secondary infection using the protein microarray (PMA) titers had high area under the curve (0.90–0.97) and accuracy (0.84–0.86). Multinomial models developed to identify most recent past infecting serotype using PMA titers performed well in those with past primary infection (average test set: κ = 0.85, accuracy of 0.92) but not those with past secondary infection (κ = 0.24, accuracy of 0.45). Conclusions Our results suggest that the microarray will be useful in seroepidemiological studies aimed at classifying the past infection history of individuals (past primary vs secondary and serotype of past primary infections) and thus inferring past transmission intensity of DENV in dengue-endemic settings. Future work to validate these models should be undertaken in different transmission settings and with samples later after infection.

Age-seroprevalence curves for the multi-strain structure of influenza A virus

“…As large-scale multi-antigen serological approaches like this one become more common, it will become important to include field study components that allow for validation of results obtained from crosssectional data alone. The present approach taken for influenza virus should be expanded to other well-characterized multi-strain pathogens such as dengue 62,63 , norovirus [64][65][66] , and pneumococcus 67,68 to share lessons on which inferential methods and study designs are most appropriate for the precise and robust estimation of a broad range of epidemiological quantities.…”

Age-seroprevalence curves for the multi-strain structure of influenza A virus

“…As large-scale multi-antigen serological approaches like this one become more common, it will become important to include field study components that allow for validation of results obtained from cross-sectional data alone. The present approach taken for influenza virus should be expanded to other wellcharacterized multi-strain pathogens such as dengue 67,68 , norovirus [69][70][71] , and pneumococcus 72,73 to share lessons on which inferential methods and study designs are most appropriate for the precise and robust estimation of a broad range of epidemiological quantities.…”

Dengue Detection: Advances in Diagnostic Tools from Conventional Technology to Point of Care

“…The IgG sensitivity was 92%, while the specificity was 99%, whereas the IgM sensitivity was 86%, and the specificity was 98%. Recently, a study conducted by Thao et al has looked into Clenton's protein microarray and its ability to detect past DENV infections [203]. The researchers used the microarray to test DENV after 1 and 6 months of infection.…”

“…The study tested 368 serum specimens from 184 infected individuals (16 samples were omitted owing to not having control). Using their binomial model, they were able to have a 92% accuracy on primary past infections but only a 45% accuracy on past secondary infections [203]. Microarrays have many inherent benefits, such as high throughput and high sensitivity.…”