MacIntyre C Raina
School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052 Australia.
Environ Syst Decis. 2014;34(3):383-390. doi: 10.1007/s10669-014-9506-5. Epub 2014 Jul 25.
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerged infection in humans affecting the Arabian Peninsula, Europe, and North Africa. The source and persistence of the infection in humans remains unknown. The aim of this paper was to apply a risk analysis approach to the epidemiology of MERS-CoV and to understand the source of ongoing infections. The epidemiology of MERS-CoV was reviewed and compared to SARS. Each observed feature of MERS-CoV epidemiology was summarized and fitted to either an epidemic or one of two sporadic scenarios (either animal or deliberate release). As of May 2014, MERS-CoV has infected over 681 people and killed a further 204 over 2 years. In contrast, there were 8,273 cases and 775 deaths from SARS within 8 months. MERS-CoV has a more sporadic pattern unlike the clear epidemic pattern seen with SARS, and an unusual concentration of cases in the Middle East, without epidemics in other countries to which it has spread. SARS, with a higher reproductive number (R0), was eliminated from humans within 8 months of emerging, yet MERS-CoV, with a low R0 has persisted in humans over a far more prolonged period. This is at odds with the expected behavior of a virus with a low R0, which theoretically should not persist unless there are ongoing introductions of infection into humans, and poses the question A hospital outbreak in Al Ahsa, the Kingdom of Saudi Arabia (KSA), had a classic epidemic pattern with some human-to-human transmission. However, 3 different strains were identified in that outbreak, an unexpected and unexplained finding for what appears to be a single source outbreak. Since this outbreak in April 2013, there has been a large increase in new cases, mainly in KSA in April and May 2014, with no corresponding epidemics in other countries. Yet MERS-CoV was present in KSA over several mass gatherings (which predispose to epidemics), including the Hajj pilgrimage, without an epidemic arising. Furthermore, although the virus has been identified in bats and camels, the mode of ongoing transmission to humans remains uncertain. Although some cases appear to be transmitted from human to human, and a few have animal or camel exposure, many cases have no history of contact with either animals or human cases. A high proportion of asymptomatic or otherwise undetected cases have been postulated as an explanation for the unusual epidemiology, yet active surveillance does not support this. When the observed data were fitted to different disease patterns, the features of MERS-CoV fit better with a sporadic pattern, with evidence for either deliberate release or an animal source. There are many discrepancies in the observed epidemiology of MERS-CoV, which better fits a sporadic than an epidemic pattern. Possible explanations of the unusual features of the epidemiology include human-to-human transmission with a large proportion of undetected cases; or sporadic ongoing infections from a non-human source; or a combination of both. Possible sources of ongoing sporadic infection in humans include animals (camels appear the most likely source), or deliberate release. The latter could explain 3 strains being present in a single hospital outbreak. Genetic testing should be conducted to determine whether the virus is evolving to be more transmissible. Better ascertainment of mild or asymptomatic cases is also needed. Finally, the discrepant epidemiology warrants critical analysis of all possible explanations, and involvement of all stakeholders in biosecurity, and deliberate release must be seriously considered and at least acknowledged as a possibility.
中东呼吸综合征冠状病毒(MERS-CoV)是一种新出现的可感染人类的病毒,影响着阿拉伯半岛、欧洲和北非。该病毒在人类中的传染源及持续存在情况仍不明晰。本文旨在运用风险分析方法研究MERS-CoV的流行病学特征,并了解持续感染的源头。对MERS-CoV的流行病学情况进行了回顾,并与严重急性呼吸综合征(SARS)进行了比较。总结了MERS-CoV流行病学中观察到的每个特征,并将其与一种流行情况或两种散发情况(动物源性或蓄意传播)之一进行匹配。截至2014年5月,在两年多时间里,MERS-CoV已感染681多人,并导致另外204人死亡。相比之下,SARS在8个月内有8273例病例,775人死亡。与SARS呈现的明显流行模式不同,MERS-CoV具有更散发的模式,且病例异常集中在中东地区,在其传播到的其他国家并未出现疫情。SARS的基本传染数(R0)较高,在出现后的8个月内就从人类中消失了,而MERS-CoV的R0较低,却在人类中持续存在了更长时间。这与R0较低的病毒的预期行为不符,理论上,除非不断有感染传入人类,否则这种病毒不应持续存在,这就引发了一个问题。沙特阿拉伯王国(KSA)艾哈萨的一次医院暴发呈现出典型的流行模式,存在一定程度的人际传播。然而,在那次暴发中发现了3种不同的毒株,对于这似乎是单一源头的暴发来说,这是一个意外且无法解释的发现。自2013年4月这次暴发以来,新病例大幅增加,主要集中在2014年4月和5月的沙特阿拉伯,其他国家并未出现相应疫情。然而,MERS-CoV在沙特阿拉伯的几次大规模集会(这些集会易引发疫情)中都有出现,包括朝觐朝圣,但并未引发疫情。此外,尽管已在蝙蝠和骆驼中发现该病毒,但病毒持续传播给人类的方式仍不确定。虽然一些病例似乎是人际传播,少数病例有动物或骆驼接触史,但许多病例既无动物接触史也无人类病例接触史。有人推测,高比例无症状或未被发现的病例可解释这种异常的流行病学情况,但主动监测并不支持这一推测。当将观察到的数据与不同疾病模式进行匹配时,MERS-CoV的特征更符合散发模式,有证据表明是蓄意传播或动物源性。MERS-CoV观察到的流行病学情况存在许多差异,更符合散发而非流行模式。对这种异常流行病学特征的可能解释包括:人际传播且有很大比例未被发现的病例;或来自非人类源的散发持续感染;或两者兼而有之。人类中持续散发感染的可能来源包括动物(骆驼似乎是最可能的来源)或蓄意传播。后者可以解释在一次医院暴发中出现3种毒株的情况。应进行基因检测,以确定病毒是否正在进化从而更具传播性。还需要更好地查明轻症或无症状病例。最后,这种不一致的流行病学情况需要对所有可能的解释进行批判性分析,所有生物安全利益相关者都应参与其中,必须认真考虑蓄意传播的可能性,至少要承认这是一种可能性。