An agent-based model of dengue virus transmission shows how uncertainty about breakthrough infections influences vaccination impact projections
An agent-based model of dengue virus transmission shows how uncertainty about breakthrough infections influences vaccination impact projections
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DOI：
10.1371/journal.pcbi.1006710
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发表时间：
2019-03-01
影响因子：
4.3
通讯作者：
Smith, David L.
中科院分区：
文献类型：
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作者：
Perkins, T. Alex;Reiner, Robert C., Jr.;Smith, David L.
预防性疫苗接种是减少传染病负担的有力工具，因为它结合了对接种者的直接保护和通过群体免疫对他人的间接保护。计算模型通过预测疫苗接种对公共卫生的影响，在制定疫苗接种战略方面发挥着重要作用。然而，这种预测受到许多因素的不确定性的影响。例如，许多疫苗效力试验侧重于测量对疾病的保护，而不是对感染的保护，留下了突破性感染的程度（即，疾病得到改善，但感染未受阻碍）。我们在这项研究中的目标是量化突破性感染的不确定性导致疫苗接种影响的不确定性的程度，重点是登革热疫苗。为了现实地解释登革病毒（DENV）传播中的多种形式的异质性，这可能对间接保护的动态产生影响，我们使用了一个随机的，基于代理的DENV传播模型，该模型由秘鲁伊基托斯市十多年的实证研究提供信息。在对9岁儿童进行20年80%覆盖率的常规疫苗接种后，在突破性感染的不确定性范围内，预测避免疾病发作的比例变化了1.76倍（95%CI：1.54-2.06）。这相当于在疫苗有效性不确定性范围0.268（95% CI：0.210-0.329）内预测的疫苗接种影响范围。直到突破性感染的不确定性可以解决经验，我们的研究结果表明，它在疫苗接种impacts.Author摘要疫苗的影响模型会计的重要性是保障公共卫生的各种传染病的威胁的重要工具。在作出关于疫苗接种投资的决定时，计算模型为决策者提供了疫苗接种效益的预测。有许多类型的不确定性会影响这些预测，例如关于疫苗接种在多大程度上降低了人们患病风险的统计不确定性。虽然疫苗试验很好地解释了这种类型的不确定性，但另一种不同类型的不确定性往往没有得到解释：疫苗是完全阻止感染还是只是减轻疾病症状的严重程度。在后者的情况下，会发生突破性感染，这意味着接种疫苗的人受到保护，但那些没有从群体免疫中获得很少或根本没有间接利益的人。针对一种新获得许可的登革热疫苗，我们开发并应用了一种新的登革热病毒传播模拟模型，以评估突破性感染的不确定性对疫苗接种影响的不确定性的影响程度。我们发现，与仅通过降低疾病症状严重程度来提供保护的疫苗相比，预防突破性感染的疫苗能够使疫苗接种的影响增加近一倍。
Prophylactic vaccination is a powerful tool for reducing the burden of infectious diseases, due to a combination of direct protection of vaccinees and indirect protection of others via herd immunity. Computational models play an important role in devising strategies for vaccination by making projections of its impacts on public health. Such projections are subject to uncertainty about numerous factors, however. For example, many vaccine efficacy trials focus on measuring protection against disease rather than protection against infection, leaving the extent of breakthrough infections (i.e., disease ameliorated but infection unimpeded) among vaccinees unknown. Our goal in this study was to quantify the extent to which uncertainty about breakthrough infections results in uncertainty about vaccination impact, with a focus on vaccines for dengue. To realistically account for the many forms of heterogeneity in dengue virus (DENV) transmission, which could have implications for the dynamics of indirect protection, we used a stochastic, agent-based model for DENV transmission informed by more than a decade of empirical studies in the city of Iquitos, Peru. Following 20 years of routine vaccination of nine-year-old children at 80% coverage, projections of the proportion of disease episodes averted varied by a factor of 1.76 (95% CI: 1.54-2.06) across the range of uncertainty about breakthrough infections. This was equivalent to the range of vaccination impact projected across a range of uncertainty about vaccine efficacy of 0.268 (95% CI: 0.210-0.329). Until uncertainty about breakthrough infections can be addressed empirically, our results demonstrate the importance of accounting for it in models of vaccination impact.Author summary Vaccines are vital tools for safeguarding public health from a variety of infectious disease threats. When decisions are being made about investments in vaccination, computational models provide decision makers with projections of the benefits of vaccination. There are many types of uncertainty that can affect these projections, such as statistical uncertainty about the extent to which vaccination reduces one's risk of experiencing disease. While this type of uncertainty is well accounted for by vaccine trials, a different type of uncertainty often is not: whether the vaccine blocks infection altogether or simply reduces the severity of disease symptoms. In the case of the latter, breakthrough infections occur, meaning that those who are vaccinated are protected but those who are not receive little or no indirect benefit from herd immunity. Focusing on a newly licensed vaccine for dengue, we developed and applied a new simulation model of dengue virus transmission to assess the extent to which uncertainty about breakthrough infections contributes to uncertainty about vaccination impact. We found that a vaccine that prevents breakthrough infections is capable of nearly doubling the impact of vaccination as compared to a vaccine that confers protection solely by reducing the severity of disease symptoms.