The discrepant epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV)
The discrepant epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV)
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DOI：
10.1007/s10669-014-9506-5
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发表时间：
2014-09-01
影响因子：
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通讯作者：
MacIntyre, C. Raina
中科院分区：
文献类型：
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作者：
MacIntyre, C. Raina
中东呼吸综合征冠状病毒(MERS-CoV)是一种新出现的人类感染，影响阿拉伯半岛、欧洲和北非。人类感染的来源和持久性尚不清楚。本文的目的是将风险分析方法应用于MERS冠状病毒的流行病学，并了解持续感染的来源。回顾了MERS冠状病毒的流行病学，并与SARS进行了比较。总结了MERS-CoV流行病学的每一种观察到的特征，并将其与一种流行病或两种零星情况(动物或故意放生)相适应。截至2014年5月，MERS冠状病毒已感染超过681人，并在两年内导致204人死亡。相比之下，8个月内有8273例SARS病例和775例死亡。与SARS的明确流行模式不同，MERS-CoV的模式更加零星，病例异常集中在中东，在它传播到的其他国家没有流行。具有较高繁殖数(R0)的SARS在出现后8个月内从人类中消失，但R0较低的MERS-CoV在人类中持续了更长的时间。这与低R0病毒的预期行为不符，从理论上讲，这种行为不应该持续下去，除非有持续的感染进入人类，并提出了一个问题：人类持续感染的来源是什么？沙特阿拉伯王国Al Ahsa的一次医院暴发具有典型的流行模式，存在一些人与人之间的传播。然而，在那次暴发中发现了3种不同的毒株，对于似乎是单一来源的疫情来说，这是一个意想不到和无法解释的发现。自2013年4月暴发以来，新增病例大幅增加，主要是2014年4月和5月在克什米尔地区，其他国家没有相应的疫情。然而，中东呼吸综合征冠状病毒在几次大规模集会(容易发生流行病)中出现在克萨，包括朝圣，但没有出现疫情。此外，尽管已经在蝙蝠和骆驼身上发现了这种病毒，但目前仍不确定向人类传播的方式。虽然一些病例似乎是人与人之间传播的，少数病例与动物或骆驼接触，但许多病例既没有与动物接触的历史，也没有接触人类病例的历史。很高比例的无症状或其他未被发现的病例被认为是对这种不寻常的流行病学的解释，然而积极的监测并不支持这一点。当观察到的数据与不同的疾病模式相匹配时，MERS-CoV的特征更符合零星模式，有证据表明是故意释放或来自动物来源。观察到的MERS冠状病毒的流行病学有许多差异，它更适合于零星的而不是流行的模式。对流行病学不寻常特征的可能解释包括：人与人之间的传播，有很大比例的未发现病例；或来自非人类来源的零星持续感染；或两者兼而有之。人类持续零星感染的可能来源包括动物(骆驼似乎是最有可能的来源)，或故意释放。后者可以解释在一次医院暴发中出现的3种菌株。应该进行基因测试，以确定病毒是否正在进化为更具传播性。还需要更好地确定轻微或无症状的病例。最后，由于流行病学的差异，需要对所有可能的解释进行批判性分析，并让所有利益攸关方参与生物安全，必须认真考虑并至少承认故意释放是一种可能性。
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 "what is the source of continuing infections in humans?" 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.