Chowell Gerardo, Abdirizak Fatima, Lee Sunmi, Lee Jonggul, Jung Eunok, Nishiura Hiroshi, Viboud Cécile
School of Public Health, Georgia State University, Atlanta, Georgia, USA.
Division of Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA.
BMC Med. 2015 Sep 3;13:210. doi: 10.1186/s12916-015-0450-0.
The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015.
To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks.
A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal-Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %.
Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses.
自2012年以来,中东呼吸综合征(MERS)冠状病毒在阿拉伯半岛反复引发疫情。尽管MERS总体上人际传播潜力较低,但在医疗机构中偶尔会出现传播扩大的情况,这一模式让人想起2003年严重急性呼吸综合征(SARS)疫情的动态。在此,我们对MERS和SARS在大型医院聚集性疫情中的暴露模式和传播动态进行了直接比较,包括2015年韩国最近爆发的MERS疫情。
为评估韩国最近医院内爆发MERS疫情的意外性,并估计未来大型医院聚集性疫情的发生概率,我们基于个体层面数据和传播树信息,比较了先前报告的MERS和SARS医院聚集性疫情的暴露和传播模式。我们使用基于传播树数据的分支过程模型对MERS和SARS的医院内疫情进行了模拟,并推断了大型疫情的发生概率和特征。
相当一部分MERS病例与医疗机构有关,范围从2014年沙特阿拉伯吉达医院内疫情的43.5%到2013年沙特阿拉伯哈萨疫情以及2015年韩国疫情的100%。MERS和SARS医院内疫情均以早期医院内超级传播事件为特征,传播数在三到五个疾病代内降至1以下。MERS和SARS的暴露模式存在系统性差异:大多数MERS病例发生在与首例病例在同一机构就诊的患者中,而在整个疫情期间,SARS病例在医护人员中更为集中。然而,暴露模式在不同疾病代略有不同,尤其是对于SARS。此外,每个单一首例病例的二代病例分布在各个医院疫情中差异很大(Kruskal-Wallis检验;P<0.0001),MERS二代病例分布中的传播异质性明显高于SARS。模拟表明,SARS发生大型疫情(>100例)的概率比MERS高2倍(2%对1%);然而,由于传播异质性较高,MERS最大规模疫情的特征是发病高峰更为陡峭。发生比韩国聚集性疫情规模更大(n = 186)的MERS疫情的概率约为1%。
我们的研究表明,韩国疫情的发展过程与先前描述的涉及冠状病毒的医院聚集性疫情相似,早期超级传播事件导致了不成比例的大量二代感染,且在后续代次中传播潜力大幅下降。MERS和SARS在相对暴露模式和传播异质性方面的差异可能表明自2003年以来医院做法的变化或这些冠状病毒传播机制的差异。