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Zika virus (ZIKV) exposure across flavivirus-endemic countries, including the Philippines, remains largely unknown despite sporadic case reporting and environmental suitability for transmission. Using laboratory surveillance data from 2016, 997 serum samples were randomly selected from suspected dengue (DENV) case reports across the Philippines and assayed for serological markers of short-term (IgM) and long-term (IgG) ZIKV exposure. Using mixture models, we re-evaluated ZIKV IgM/G seroprevalence thresholds and used catalytic models to quantify the force of infection (attack rate, AR) from age-accumulated ZIKV exposure. While we observed extensive ZIKV/DENV IgG cross-reactivity, not all individuals with active DENV presented with elevated ZIKV IgG, and a proportion of dengue-negative cases (DENV IgG-) were ZIKV IgG-positive (14.3%, 9/63). We identified evidence of long-term, yet not short-term, ZIKV exposure across Philippine regions (ZIKV IgG+: 31.5%, 314/997) which was geographically uncorrelated with DENV exposure. In contrast to the DENV AR (12.7% (95%CI: 9.1–17.4%)), the ZIKV AR was lower (5.7% (95%CI: 3–11%)) across the country. Our results provide evidence of widespread ZIKV exposure across the Philippines and suggest the need for studies to identify ZIKV infection risk factors over time to better prepare for potential future outbreaks.
Joseph Biggs; Ava Sy; Oliver Brady; Adam Kucharski; Sebastian Funk; Yun-Hung Tu; Mary Reyes; Mary Quinones; William Jones-Warner; James Ashall; Ferchito Avelino; Nemia Sucaldito; Amado Tandoc; Eva Cutiongco-De la Paz; Maria Capeding; Carmencita Padilla; Martin Hibberd; Julius Hafalla. Serological Evidence of Widespread Zika Transmission across the Philippines. Viruses 2021, 13, 1441 .
AMA StyleJoseph Biggs, Ava Sy, Oliver Brady, Adam Kucharski, Sebastian Funk, Yun-Hung Tu, Mary Reyes, Mary Quinones, William Jones-Warner, James Ashall, Ferchito Avelino, Nemia Sucaldito, Amado Tandoc, Eva Cutiongco-De la Paz, Maria Capeding, Carmencita Padilla, Martin Hibberd, Julius Hafalla. Serological Evidence of Widespread Zika Transmission across the Philippines. Viruses. 2021; 13 (8):1441.
Chicago/Turabian StyleJoseph Biggs; Ava Sy; Oliver Brady; Adam Kucharski; Sebastian Funk; Yun-Hung Tu; Mary Reyes; Mary Quinones; William Jones-Warner; James Ashall; Ferchito Avelino; Nemia Sucaldito; Amado Tandoc; Eva Cutiongco-De la Paz; Maria Capeding; Carmencita Padilla; Martin Hibberd; Julius Hafalla. 2021. "Serological Evidence of Widespread Zika Transmission across the Philippines." Viruses 13, no. 8: 1441.
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. Results Our modelled IgM and IgG seroprevalence thresholds were lower than kit-provided thresholds. Individuals anti-DENV PCR+ or IgM+ were classified as active dengue infections (83.1%, 6998/8425). IgG− and IgG+ active dengue infections on disease days 1 and 2 were categorised as primary and post-primary, respectively, while those on disease days 3 to 5 with IgG:IgM ratios below and above 0.45 were classified as primary and post-primary, respectively. A significant proportion of post-primary dengue infections had elevated anti-ZIKV IgG inferring previous Zika exposure. Our algorithm achieved 90.5% serological agreement with WHO standard practice. Post-primary dengue infections were more likely to be older and present with severe symptoms. Finally, we identified a spatio-temporal cluster of primary dengue case reporting in northern Luzon during 2016. Conclusions Our dengue immune status algorithm can equip surveillance operations with the means to target dengue control efforts. The algorithm accurately identified primary dengue infections who are at risk of future severe disease.
Joseph R. Biggs; Ava Kristy Sy; Oliver J. Brady; Adam J. Kucharski; Sebastian Funk; Mary Anne Joy Reyes; Mary Ann Quinones; William Jones-Warner; Yun-Hung Tu; Ferchito L. Avelino; Nemia L. Sucaldito; Huynh Kim Mai; Le Thuy Lien; Hung Do Thai; Hien Anh Thi Nguyen; Dang Duc Anh; Chihiro Iwasaki; Noriko Kitamura; Lay-Myint Yoshida; Amado O. Tandoc; Eva Cutiongco-De La Paz; Maria Rosario Z. Capeding; Carmencita D. Padilla; Julius Clemence R. Hafalla; Martin L. Hibberd. A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines. BMC Medicine 2020, 18, 1 -14.
AMA StyleJoseph R. Biggs, Ava Kristy Sy, Oliver J. Brady, Adam J. Kucharski, Sebastian Funk, Mary Anne Joy Reyes, Mary Ann Quinones, William Jones-Warner, Yun-Hung Tu, Ferchito L. Avelino, Nemia L. Sucaldito, Huynh Kim Mai, Le Thuy Lien, Hung Do Thai, Hien Anh Thi Nguyen, Dang Duc Anh, Chihiro Iwasaki, Noriko Kitamura, Lay-Myint Yoshida, Amado O. Tandoc, Eva Cutiongco-De La Paz, Maria Rosario Z. Capeding, Carmencita D. Padilla, Julius Clemence R. Hafalla, Martin L. Hibberd. A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines. BMC Medicine. 2020; 18 (1):1-14.
Chicago/Turabian StyleJoseph R. Biggs; Ava Kristy Sy; Oliver J. Brady; Adam J. Kucharski; Sebastian Funk; Mary Anne Joy Reyes; Mary Ann Quinones; William Jones-Warner; Yun-Hung Tu; Ferchito L. Avelino; Nemia L. Sucaldito; Huynh Kim Mai; Le Thuy Lien; Hung Do Thai; Hien Anh Thi Nguyen; Dang Duc Anh; Chihiro Iwasaki; Noriko Kitamura; Lay-Myint Yoshida; Amado O. Tandoc; Eva Cutiongco-De La Paz; Maria Rosario Z. Capeding; Carmencita D. Padilla; Julius Clemence R. Hafalla; Martin L. Hibberd. 2020. "A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines." BMC Medicine 18, no. 1: 1-14.
It is widely acknowledged that modifications to existing control interventions are required if South Africa is to achieve malaria elimination. Targeting indoor residual spraying (IRS) to areas where cases have been detected is one strategy currently under investigation in northeastern South Africa. This seroprevalence baseline study, nested within a targeted IRS trial, was undertaken to provide insights into malaria transmission dynamics in South Africa and evaluate whether sero-epidemiological practices have the potential to be routinely incorporated into elimination programmes. Filter-paper blood spots, demographic and household survey data were collected from 2710 randomly selected households in 56 study wards located in the municipalities of Ba-Phalaborwa and Bushbuckridge. Blood spots were assayed for Plasmodium falciparum apical membrane antigen-1 and merozoite surface protein-119 blood-stage antigens using an enzyme linked immunosorbent assay. Seroprevalence data were analysed using a reverse catalytic model to determine malaria seroconversion rates (SCR). Geospatial cluster analysis was used to investigate transmission heterogeneity while random effects logistic regression identified risk factors associated with malaria exposure. The overall SCR across the entire study site was 0.012 (95% CI 0.008–0.017) per year. Contrasting SCRs, corresponding to distinct geographical regions across the study site, ranging from <0.001 (95% CI <0.001–0.005) to 0.022 (95% CI 0.008–0.062) per annum revealed prominent transmission heterogeneity. Geospatial cluster analysis of household seroprevalence and age-adjusted antibody responses detected statistically significant (p < 0.05) spatial clusters of P. falciparum exposure. Formal secondary education was associated with lower malaria exposure in the sampled population (AOR 0.72, 95% CI 0.56–0.95, p = 0.018). Although overall transmission intensity and exposure to malaria was low across both study sites, malaria transmission intensity was highly heterogeneous and associated with low socio-economic status in the region. Findings suggest focal targeting of interventions has the potential to be an appropriate strategy to deploy in South Africa. Furthermore, routinely incorporating sero-epidemiological practices into elimination programmes may prove useful in monitoring malaria transmission intensity in South Africa, and other countries striving for malaria elimination.
Joseph Biggs; Jaishree Raman; Jackie Cook; Khumbulani Hlongwana; Chris Drakeley; Natashia Morris; Ishen Serocharan; Eunice Agubuzo; Philip Kruger; Aaron Mabuza; Alpheus Zitha; Elliot Machaba; Maureen Coetzee; Immo Kleinschmidt. Serology reveals heterogeneity of Plasmodium falciparum transmission in northeastern South Africa: implications for malaria elimination. Malaria Journal 2017, 16, 1 -13.
AMA StyleJoseph Biggs, Jaishree Raman, Jackie Cook, Khumbulani Hlongwana, Chris Drakeley, Natashia Morris, Ishen Serocharan, Eunice Agubuzo, Philip Kruger, Aaron Mabuza, Alpheus Zitha, Elliot Machaba, Maureen Coetzee, Immo Kleinschmidt. Serology reveals heterogeneity of Plasmodium falciparum transmission in northeastern South Africa: implications for malaria elimination. Malaria Journal. 2017; 16 (1):1-13.
Chicago/Turabian StyleJoseph Biggs; Jaishree Raman; Jackie Cook; Khumbulani Hlongwana; Chris Drakeley; Natashia Morris; Ishen Serocharan; Eunice Agubuzo; Philip Kruger; Aaron Mabuza; Alpheus Zitha; Elliot Machaba; Maureen Coetzee; Immo Kleinschmidt. 2017. "Serology reveals heterogeneity of Plasmodium falciparum transmission in northeastern South Africa: implications for malaria elimination." Malaria Journal 16, no. 1: 1-13.