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

Tran, Thi Nhu Thao; de Bruin, Erwin; Phuong, Huynh Thi; Thao Vy, Nguyen Ha; van den Ham, Henk-Jan; Wills, Bridget A; Tien, Nguyen Thi Hanh; Le Duyen, Huynh Thi; Trung, Dinh The; Whitehead, Stephen S; Boni, Maciej F; Koopmans, Marion; Clapham, Hannah E (2021). Using NS1 Flavivirus Protein Microarray to Infer Past Infecting Dengue Virus Serotype and Number of Past Dengue Virus Infections in Vietnamese Individuals. The journal of infectious diseases, 223(12), pp. 2053-2061. Oxford University Press 10.1093/infdis/jiaa018

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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.

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