Costantino Valentina, Kunasekaran Mohana P, Chughtai Abrar A, MacIntyre Chandini R
School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
College of Public Service and Community Solutions, Arizona State University, 411 Central Avenue #750, Phoenix, AZ.
Mil Med. 2018 Jul 1;183(7-8):e200-e207. doi: 10.1093/milmed/usx092.
Globally eradicated in 1980, smallpox is listed as a category A bioterrorism agent. If smallpox were to re-emerge, it may be due to an act of bioterrorism or a laboratory accident, and the impact is likely to be severe. Preparedness against smallpox is subject to more uncertainty than other infectious diseases because it is eradicated, there is uncertainty about population immunity, and the current global health workforce has no practical experience or living memory of smallpox. In the event of re-emergence of smallpox, mathematical modeling plays a crucial role in improving the evidence base to inform preparedness, mitigation, and response activities. However, the predictions of mathematical models about outbreak magnitude and impact depend critically on the assumptions and disease parameters used. We aimed to identify modeling studies that would be applicable to re-emerging smallpox and to evaluate consistency and the certainty of the evidence published about the key parameters used.
We conducted a systematic review using PRISMA criteria, of assumptions used in modeling studies on duration of latent, prodromal, and infectious period, as well as the choice of the basic reproduction number (R0) for re-emerging smallpox. We performed a literature search using PubMED, Scopus, Web of Science, and EMBASE and included peer-reviewed articles that focused on smallpox models, stated at least three of the aforementioned parameters and published in English.
A total of 42 studies were selected for inclusion. There was general agreement on the duration of latent and prodromal periods, being 11-12 d (88%) and 3 d (59%), respectively. The duration of the infectious period varied from 4 to 20 d. Most models assumed 16 d (19%), 12 d (16.7%), and 8.6 d (12%) of infectiousness. In 25/34 studies, R0 ranged between 3 and 5, generally lower than the R0 calculated from past outbreaks.
Models of smallpox re-emergence also tend to use the same limited available historical data sources but assume a wide range of different estimates for key parameters. Models use very optimistic assumptions of decreased population immunity, despite high uncertainty about duration and magnitude of post-vaccination immunity. This review reveals a paradox. A substantial proportion of the modern population is unvaccinated, never exposed to boosting from wild-type smallpox, or immunocompromised; furthermore, vaccine-induced immunity wanes over time. Failure to consider these factors in a model will lead to underestimating the true impact of a re-emergent smallpox epidemic in the contemporary population.
天花于1980年在全球范围内被消灭，被列为A类生物恐怖主义制剂。如果天花再次出现，可能是由于生物恐怖主义行为或实验室事故，其影响可能很严重。与其他传染病相比，天花防范面临更多不确定性，因为天花已被消灭，人群免疫力存在不确定性，而且当前全球卫生人力没有天花的实际经验或鲜活记忆。在天花再次出现的情况下，数学建模在改进证据基础以指导防范、缓解和应对活动方面发挥着关键作用。然而，数学模型对疫情规模和影响的预测严重依赖所使用的假设和疾病参数。我们旨在确定适用于再次出现的天花的建模研究，并评估已发表的关于所使用关键参数的证据的一致性和确定性。
我们使用PRISMA标准对关于潜伏期、前驱期和传染期持续时间以及再次出现的天花的基本繁殖数（R0）选择的建模研究中所使用的假设进行了系统评价。我们使用PubMed、Scopus、科学网和EMBASE进行文献检索，纳入了专注于天花模型、陈述了上述至少三个参数并以英文发表的同行评审文章。
总共选择了42项研究纳入。对于潜伏期和前驱期的持续时间，分别为11 - 12天（88%）和3天（59%），存在普遍共识。传染期持续时间从4天到20天不等。大多数模型假设传染性为16天（19%）、12天（16.7%）和8.6天（12%）。在25/34项研究中，R0在3到5之间，通常低于根据过去疫情计算的R0。
天花再次出现的模型也倾向于使用相同的有限可用历史数据源，但对关键参数假设了广泛不同的估计。尽管疫苗接种后免疫力的持续时间和程度存在高度不确定性，但模型对人群免疫力下降使用了非常乐观的假设。本综述揭示了一个悖论。现代人群中有很大一部分未接种疫苗、从未接触过野生型天花的加强免疫或免疫功能低下；此外，疫苗诱导的免疫力会随着时间减弱。在模型中未能考虑这些因素将导致低估再次出现的天花疫情对当代人群的真实影响。
