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

Abstract

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 κ=0.85, accuracy=0.92), but not those with past secondary infection (κ=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.

Authors+Show Affiliations

Viroscience Department, Erasmus University of Rotterdam, The Netherlands. Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam. Institute for Virology and Immunology, University of Bern, Switzerland.Viroscience Department, Erasmus University of Rotterdam, The Netherlands.Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam.Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam.Viroscience Department, Erasmus University of Rotterdam, The Netherlands.Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam.Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam.Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam.Laboratory of Viral Diseases, National Institutes of Health, USA.Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University, University Park, PA, USA.Viroscience Department, Erasmus University of Rotterdam, The Netherlands.Oxford University Clinical Research Unit, Wellcome Trust Asia Program, Ho Chi Minh City, Vietnam. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31967302

Citation

Thao, Tran Thi Nhu, et al. "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, 2020.
Thao TTN, de Bruin E, Phuong HT, et al. Using NS1 flavivirus protein microarray to infer past infecting dengue virus serotype and number of past dengue virus infections in Vietnamese individuals. J Infect Dis. 2020.
Thao, T. T. N., de Bruin, E., Phuong, H. T., Thao Vy, N. H., van den Ham, H. J., Wills, B. A., ... Clapham, H. E. (2020). 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, doi:10.1093/infdis/jiaa018.
Thao TTN, et al. Using NS1 Flavivirus Protein Microarray to Infer Past Infecting Dengue Virus Serotype and Number of Past Dengue Virus Infections in Vietnamese Individuals. J Infect Dis. 2020 Jan 22; PubMed PMID: 31967302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Using NS1 flavivirus protein microarray to infer past infecting dengue virus serotype and number of past dengue virus infections in Vietnamese individuals. AU - Thao,Tran Thi Nhu, AU - de Bruin,Erwin, AU - Phuong,Huynh Thi, AU - Thao Vy,Nguyen Ha, AU - van den Ham,Henk-Jan, AU - Wills,Bridget A, AU - Tien,Nguyen Thi Hanh, AU - Le Duyen,Huynh Thi, AU - Trung,Dinh The, AU - Whitehead,Stephen S, AU - Boni,Maciej F, AU - Koopmans,Marion, AU - Clapham,Hannah E, Y1 - 2020/01/22/ PY - 2019/10/08/received PY - 2020/1/23/entrez KW - Antibody KW - Dengue KW - Flaviviruses KW - Protein microarray KW - Sero-epidemiology KW - Serology KW - Serosurveys KW - Transmission JF - The Journal of infectious diseases JO - J. Infect. Dis. N2 - 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 κ=0.85, accuracy=0.92), but not those with past secondary infection (κ=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. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/31967302/Using_NS1_flavivirus_protein_microarray_to_infer_past_infecting_dengue_virus_serotype_and_number_of_past_dengue_virus_infections_in_Vietnamese_individuals L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiaa018 DB - PRIME DP - Unbound Medicine ER -