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Estimating the proportion of vaccine-induced hospitalized dengue cases among Dengvaxia vaccinees in the Philippines.

ABSTRACT: Background: Dengvaxia was used in the Philippines to vaccinate 9-10-year-old school children, living in areas highly endemic for dengue. After about 830,000 had received at least 1 of 3 recommended doses, risks of enhanced disease in dengue-naïve vaccinees were reported. Methods: We used Phase 3 trial data to derive the proportions of cases of hospitalised and severe dengue that might have been prevented by the Philippines vaccination programme and, among those cases that may occur in vaccinees, what proportions are likely to arise in those who were seropositive or seronegative for dengue at the time of first vaccination and what proportion in the latter group may be enhanced disease attributable to the vaccine. Results: Assuming about 15% of vaccinees were dengue naïve at vaccination and the effects of the vaccine are independent of the number of doses received, we estimate that, in the 5 years following vaccination, the number of cases of severe disease in the vaccinated population will be reduced by about 70%. Among vaccinees who do develop severe disease, about half the cases will be due to vaccine breakthrough in seropositive vaccinees, and about a quarter will be excess cases in seronegative vaccinees that will have occurred as a consequence of vaccination. Conclusions: Overall, the Philippine dengue vaccination programme will likely prevent a substantial number of severe dengue cases and, among those that do occur, the majority are likely to be breakthrough disease in seropositive vaccinees and a minority attributable to the excess risk of enhanced disease in seronegative vaccinees.

SUBMITTER: Flasche S

PROVIDER: S-EPMC6880258 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Estimating the proportion of vaccine-induced hospitalized dengue cases among Dengvaxia vaccinees in the Philippines.

Flasche Stefan S Wilder-Smith Annelies A Hombach Joachim J Smith Peter G PG

Wellcome open research 20191031

<b>Background:</b> Dengvaxia was used in the Philippines to vaccinate 9-10-year-old school children, living in areas highly endemic for dengue. After about 830,000 had received at least 1 of 3 recommended doses, risks of enhanced disease in dengue-naïve vaccinees were reported. <b>Methods:</b> We used Phase 3 trial data to derive the proportions of cases of hospitalised and severe dengue that might have been prevented by the Philippines vaccination programme and, among those cases that may occur ...[more]

PMID: 31815190

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Project description:BackgroundIn 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.MethodsDuring 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.ResultsOur 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.ConclusionsOur 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.

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Estimating the proportion of vaccine-induced hospitalized dengue cases among Dengvaxia vaccinees in the Philippines.

Publications

Estimating the proportion of vaccine-induced hospitalized dengue cases among Dengvaxia vaccinees in the Philippines.

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