Using NS1 flavivirus protein microarray to infer past infecting dengue virus serotype and number of past dengue virus infections in Vietnamese individuals

The use of multiplex microarray assays, in which antibodies are measured against multiple related antigens, is gaining increased focus for use in seroepidemiological studies to infer past transmission. We assess the performance of a flavivirus microarray assay for determining past dengue virus infection history in a dengue-endemic setting, Vietnam. We tested the microarray on samples from 1 and 6 months post-infection from DENV-infected patients (infecting serotype determined using RT-PCR during acute infection, past primary and secondary infection assessed using PRNT 6 months post-infection). Binomial models developed to discriminate past primary from secondary infection using the PMA titres had high AUC (0.90-0.97) and accuracy (0.84-0.86). Multinomial models developed to identify the most recent past infecting serotype using PMA titres performed well in those with past primary (average test-set kappa=0.85, accuracy=0.92), but not those with past secondary infection (kappa=0.24, accuracy=0.45). Our results suggests that the microarray will be useful in sero-epidemiological 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 dengue virus in dengue-endemic settings. Future work to validate these models should be undertaken in different transmission settings and with samples later after infection.