A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines
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RESEARCH ARTICLE
Open Access
A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines Joseph R. Biggs1* , Ava Kristy Sy2,3, Oliver J. Brady4,5, Adam J. Kucharski4,5, Sebastian Funk4,5, Mary Anne Joy Reyes2,3, Mary Ann Quinones2,3, William Jones-Warner1, Yun-Hung Tu1, Ferchito L. Avelino6, Nemia L. Sucaldito6, Huynh Kim Mai7, Le Thuy Lien7, Hung Do Thai7, Hien Anh Thi Nguyen8, Dang Duc Anh8, Chihiro Iwasaki9, Noriko Kitamura9, Lay-Myint Yoshida9, Amado O. Tandoc2, Eva Cutiongco-de la Paz10,11, Maria Rosario Z. Capeding3,10, Carmencita D. Padilla10,11, Julius Clemence R. Hafalla1 and Martin L. Hibberd1,10,11
Abstract Background: In dengue-endemic countries, targeting limited control interventions to populations at risk of severe disease could enable increased efficiency. Individuals who have had their first (primary) dengue infection are at risk of developing more severe secondary disease, thus could be targeted for disease prevention. Currently, there is no reliable algorithm for determining primary and post-primary (infection with more than one flavivirus) status from a single serum sample. In this study, we developed and validated an immune status algorithm using single acute serum samples from reporting patients and investigated dengue immuno-epidemiological patterns across the Philippines. Methods: During 2015/2016, a cross-sectional sample of 10,137 dengue case reports provided serum for molecular (anti-DENV PCR) and serological (anti-DENV IgM/G capture ELISA) assay. Using mixture modelling, we re-assessed IgM/G seroprevalence and estimated functional, disease day-specific, IgG:IgM ratios that categorised the reporting population as negative, historical, primary and post-primary for dengue. We validated our algorithm against WHO gold standard criteria and investigated cross-reactivity with Zika by assaying a random subset for anti-ZIKV IgM and IgG. Lastly, using our algorithm, we explored immuno-epidemiological patterns of dengue across the Philippines. (Continued on next page)
* Correspondence: [email protected] 1 Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to
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