Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, USA.
Quantitative Veterinary Epidemiology, Wageningen University and Research, Wageningen, The Netherlands.
BMC Med. 2022 Jun 16;20(1):202. doi: 10.1186/s12916-022-02405-1.
Despite large outbreaks in humans seeming improbable for a number of zoonotic pathogens, several pose a concern due to their epidemiological characteristics and evolutionary potential. To enable effective responses to these pathogens in the event that they undergo future emergence, the Coalition for Epidemic Preparedness Innovations is advancing the development of vaccines for several pathogens prioritized by the World Health Organization. A major challenge in this pursuit is anticipating demand for a vaccine stockpile to support outbreak response.
We developed a modeling framework for outbreak response for emerging zoonoses under three reactive vaccination strategies to assess sustainable vaccine manufacturing needs, vaccine stockpile requirements, and the potential impact of the outbreak response. This framework incorporates geographically variable zoonotic spillover rates, human-to-human transmission, and the implementation of reactive vaccination campaigns in response to disease outbreaks. As proof of concept, we applied the framework to four priority pathogens: Lassa virus, Nipah virus, MERS coronavirus, and Rift Valley virus.
Annual vaccine regimen requirements for a population-wide strategy ranged from > 670,000 (95% prediction interval 0-3,630,000) regimens for Lassa virus to 1,190,000 (95% PrI 0-8,480,000) regimens for Rift Valley fever virus, while the regimens required for ring vaccination or targeting healthcare workers (HCWs) were several orders of magnitude lower (between 1/25 and 1/700) than those required by a population-wide strategy. For each pathogen and vaccination strategy, reactive vaccination typically prevented fewer than 10% of cases, because of their presently low R values. Targeting HCWs had a higher per-regimen impact than population-wide vaccination.
Our framework provides a flexible methodology for estimating vaccine stockpile needs and the geographic distribution of demand under a range of outbreak response scenarios. Uncertainties in our model estimates highlight several knowledge gaps that need to be addressed to target vulnerable populations more accurately. These include surveillance gaps that mask the true geographic distribution of each pathogen, details of key routes of spillover from animal reservoirs to humans, and the role of human-to-human transmission outside of healthcare settings. In addition, our estimates are based on the current epidemiology of each pathogen, but pathogen evolution could alter vaccine stockpile requirements.
尽管一些人畜共患病病原体在人类中大规模爆发的可能性不大，但由于其流行病学特征和进化潜力，仍有几种病原体令人担忧。为了在这些病原体未来出现时能够有效应对，流行病防范创新联盟正在推进世界卫生组织优先考虑的几种病原体的疫苗开发。在这方面的一个主要挑战是预测对疫苗储备的需求，以支持疫情应对。
我们开发了一种针对新出现的人畜共患病的疫情应对建模框架，采用三种反应性疫苗接种策略来评估可持续疫苗生产需求、疫苗储备需求以及疫情应对的潜在影响。该框架结合了具有地理差异的人畜共患病溢出率、人际传播以及针对疾病爆发实施反应性疫苗接种活动的情况。作为概念验证，我们将该框架应用于四种优先病原体：拉萨病毒、尼帕病毒、中东呼吸综合征冠状病毒和裂谷热病毒。
对于全人群策略，每年的疫苗接种方案需求范围从拉萨病毒的超过 670,000 例（95%预测区间 0-3,630,000 例）到裂谷热病毒的 1,190,000 例（95%预测区间 0-8,480,000 例），而环形疫苗接种或针对医护人员（HCWs）的疫苗接种方案需求则要低几个数量级（在 1/25 到 1/700 之间）。对于每种病原体和疫苗接种策略，由于目前 R 值较低，反应性疫苗接种通常只能预防不到 10%的病例。针对医护人员的疫苗接种比全人群疫苗接种的效果更高。
我们的框架提供了一种灵活的方法，用于在一系列疫情应对场景下估计疫苗储备需求和需求的地理分布。我们模型估计中的不确定性突出了需要解决的几个知识空白，以便更准确地针对脆弱人群。这些空白包括掩盖每个病原体真实地理分布的监测空白、动物宿主向人类溢出的关键途径的详细信息，以及医疗保健环境之外人际传播的作用。此外，我们的估计基于每个病原体的当前流行病学，但病原体的进化可能会改变疫苗储备的需求。
