Hladish Thomas J, Pearson Carl A B, Chao Dennis L, Rojas Diana Patricia, Recchia Gabriel L, Gómez-Dantés Héctor, Halloran M Elizabeth, Pulliam Juliet R C, Longini Ira M
Department of Biology, University of Florida, Gainesville, Florida, United States of America.
Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.
PLoS Negl Trop Dis. 2016 May 26;10(5):e0004661. doi: 10.1371/journal.pntd.0004661. eCollection 2016 May.
Dengue vaccines will soon provide a new tool for reducing dengue disease, but the effectiveness of widespread vaccination campaigns has not yet been determined. We developed an agent-based dengue model representing movement of and transmission dynamics among people and mosquitoes in Yucatán, Mexico, and simulated various vaccine scenarios to evaluate effectiveness under those conditions. This model includes detailed spatial representation of the Yucatán population, including the location and movement of 1.8 million people between 375,000 households and 100,000 workplaces and schools. Where possible, we designed the model to use data sources with international coverage, to simplify re-parameterization for other regions. The simulation and analysis integrate 35 years of mild and severe case data (including dengue serotype when available), results of a seroprevalence survey, satellite imagery, and climatological, census, and economic data. To fit model parameters that are not directly informed by available data, such as disease reporting rates and dengue transmission parameters, we developed a parameter estimation toolkit called AbcSmc, which we have made publicly available. After fitting the simulation model to dengue case data, we forecasted transmission and assessed the relative effectiveness of several vaccination strategies over a 20 year period. Vaccine efficacy is based on phase III trial results for the Sanofi-Pasteur vaccine, Dengvaxia. We consider routine vaccination of 2, 9, or 16 year-olds, with and without a one-time catch-up campaign to age 30. Because the durability of Dengvaxia is not yet established, we consider hypothetical vaccines that confer either durable or waning immunity, and we evaluate the use of booster doses to counter waning. We find that plausible vaccination scenarios with a durable vaccine reduce annual dengue incidence by as much as 80% within five years. However, if vaccine efficacy wanes after administration, we find that there can be years with larger epidemics than would occur without any vaccination, and that vaccine booster doses are necessary to prevent this outcome.
登革热疫苗将很快为减少登革热疾病提供一种新工具，但广泛接种疫苗运动的有效性尚未确定。我们开发了一个基于主体的登革热模型，该模型描述了墨西哥尤卡坦半岛人群和蚊子之间的流动及传播动态，并模拟了各种疫苗接种方案，以评估这些条件下的有效性。该模型详细呈现了尤卡坦半岛的人口空间分布，包括180万人在37.5万户家庭以及10万个工作场所和学校之间的位置及流动情况。在可能的情况下，我们设计该模型使用具有国际覆盖范围的数据源，以便简化对其他地区的重新参数化。模拟和分析整合了35年的轻症和重症病例数据（如有可用的登革热血清型数据）、血清流行率调查结果、卫星图像以及气候、人口普查和经济数据。为了拟合那些没有直接可用数据支持的模型参数，如疾病报告率和登革热传播参数，我们开发了一个名为AbcSmc的参数估计工具包，并已将其公开。在将模拟模型与登革热病例数据拟合后，我们预测了传播情况，并评估了20年内几种疫苗接种策略的相对有效性。疫苗效力基于赛诺菲巴斯德公司疫苗“登革热疫苗”（Dengvaxia）的三期试验结果。我们考虑对2岁、9岁或16岁儿童进行常规接种，以及有无针对30岁人群的一次性补种活动。由于“登革热疫苗”的持久性尚未确定，我们考虑了具有持久或逐渐减弱免疫力的假设疫苗，并评估了使用加强剂量来应对免疫力减弱的情况。我们发现，使用具有持久效力疫苗的合理接种方案可在五年内将年度登革热发病率降低多达80%。然而，如果疫苗效力在接种后减弱，我们发现可能会出现比未接种疫苗时更大规模的疫情年份，并且需要使用疫苗加强剂量来防止这种情况发生。
