克里米亚-刚果出血热医院感染爆发（翻译有奖）

潮水

Nosocomial Outbreak of Crimean-Congo Hemorrhagic Fever, Sudan
美国急性传染病杂志
Volume 16, Number 5–May 2010
Abstract
To confirm the presence of Crimean-Congo hemorrhagic fever in Sudan, we tested serum of 8 patients with hemorrhagic fever in a rural hospital in 2008. Reverse transcription–PCR identified Crimean-Congo hemorrhagic fever virus. Its identification as group III lineage indicated links to virus strains from South Africa, Mauritania, and Nigeria.

Crimean-Congo hemorrhagic fever virus (CCHFV; family Bunyaviridae, genus Nairovirus) is a tick-borne virus. Its tripartite RNA genome consists of small (S), medium, and large segments. The virus is distributed throughout much of Africa, Asia, and southern Europe (1–5). In some regions, the virus is responsible for annual outbreaks of hemorrhagic fever with high case-fatality rates; in others, it causes sporadic cases only. Because of its association with rapid-onset hemorrhagic fever and an ≈30% case-fatality rate, CCHFV is on the US Select Agent list of agents considered to have bioterrorism potential (2–5).

Distribution of CCHF largely mirrors that of its Ixodid tick hosts, particularly those of the genus Hyalomma (1). Persons become infected when bitten by virus-infected ticks or after contact with blood or tissue from viremic livestock or other persons. Outbreaks often involve persons in rural communities, such as shepherds, slaughterhouse workers, or medical staff of resource-poor hospitals. Despite presence of Hyalomma tick vectors in Sudan, no CCHF cases have been confirmed there. However, in the past 2 years, suspected CCHF outbreaks and sporadic cases in the Kordufan region of Sudan have been reported.

From a public health perspective, confirming CCHF in Sudan and determining which virus lineages may be present in this region will provide a more detailed understanding of the movement of virus strains and identification of areas at risk for CCHFV. We therefore analyzed an outbreak of hemorrhagic fever, including a nosocomial chain of transmission in a rural hospital in Sudan in 2008.

The Study
In October 2008, an outbreak of hemorrhagic fever was reported in Al-fulah, Kordufan, Sudan. The index patient was a 60-year-old man who had worked as a butcher. The source of his infection was suspected to have been tissues and blood of an infected animal, although follow-up investigation was unable to precisely determine the source. He was admitted to a rural hospital with an acute febrile hemorrhagic illness after 3 days of high fever, chills, and headache. He had taken antimalarial medication at home, but his condition did not improve. He had epistaxis, black bloody vomitus, and diarrhea on the last 2 days of his illness. He died on day 5 after onset of illness.

No protective gloves or antiseptic products were available at the hospital. Illness developed in a male nurse who had provided care to the index patient 6 days after the index patient had been admitted to the hospital and in the chief male nurse a few days after that. The index patient's sister was also considered to have a suspected case; she had sought care at the hospital after a heavy menstrual period that progressed to massive vaginal bleeding. The midwife who performed the gynecologic examination later became ill with high fever, vomiting of blood, and bloody diarrhea. As is tradition and social obligation in rural hospitals in this region, 2 relatives of the index patient had alternated caring for him (e.g., dressing him, changing his mattresses and bed sheets, nursing, and sleeping beside him) while he was in the hospital, and both acquired the infection (rapid onset of fever, headache, nausea, vomiting of blood, and bloody diarrhea). No details were available for 3 other patients with hemorrhagic fever associated with the hospital.

Of these 10 patients, 9 were admitted to a rural hospital in Al-fulah, where 6 continued to bleed, subsequently became comatose, and died. Records were unavailable for the other 3. In addition, 3 probable cases in the community were reported. Each of these 3 persons had a course of hemorrhagic disease and death that was compatible with CCHF; they had not been admitted to the hospital and could not be traced because of poor security conditions in the region. Patient ages varied from 15 to 70 years. Nosocomial transmission of the virus was likely the result of lack of personal protection for the hospital staff and the attending relatives, as has been often noted during previous outbreaks (6).

Figure

Figure. Phylogenetic relationship of Crimean-Congo hemorrhagic fever virus (CCHFV) full-length small (S) segments...

Of the patients for whom serum samples were available, 8 had evidence of acute CCHFV infection. Direct immunofluorescence assay detected no antibodies to CCHFV in any of the serum samples; however, all samples had been collected on days 1–3 of illness. Virus RNA extracted from each of the samples by QIAamp (QIAGEN GmbH, Hilden, Germany) was positive according to reverse transcription–PCR (RT-PCR) specific for CCHFV (7). The RNA was then used in RT-PCRs to amplify the entire virus S segment for complete sequencing as described (8). The full-length S segment nucleotide sequence of the strains from Sudan was 1,673 nt long, and the 8 viral sequences were identical with the exception of that from patient 4 (GenBank accession nos. GQ862371–2). A maximum-likelihood phylogenetic analysis of the S segment sequences placed the viruses from Sudan in group III (8), which is composed exclusively of viruses of African origin, including South Africa, Mauritania, and Nigeria (Figure). The highest nucleotide sequence identity was seen with strains from South Africa.

Conclusions
Laboratory confirmation of 8 cases of CCHF demonstrates the presence of this disease in Sudan. Genetic analysis of the viruses showed that the strain involved was similar to strains found in South Africa, Mauritania, and Nigeria.

Detailed analysis of virus outbreaks is often limited by the lack of appropriate high-containment facilities required for virus isolation. However, appropriately sampled and stored acute-phase serum samples can have high titers of the virus, which enable extraction of virus RNA and genome sequencing studies without prior amplification of the virus in cell culture. In this study, serum specimens from 8 patients who died were positive for CCHFV by RT-PCR. Lack of virus-specific antibodies 1–3 days after onset of illness can be explained by the severity and rapid course of the disease, which does not allow sufficient time for antibody production. Virus-specific antibodies are, however, generally seen later in the course of illness and in persons who survive the infection.

Antibody studies have suggested the presence of various arboviruses in Sudan (10,11). Indirect evidence for CCHFV in animals in Sudan came from finding CCHFV-specific antibodies in animals imported from Sudan: camels in Egypt (12) and sheep and goats in Saudi Arabia (13). The finding that the Al-fulah outbreak was caused by a CCHFV strain from genetic group III illustrates how different virus strains and lineages can move with livestock transport or possibly bird migrations. The genome plasticity of the virus is surprisingly high for an arthropod-borne virus. This genetic diversity appears to be the result of not only accumulation of mutations but also of frequent RNA segment reassortment and even RNA recombination (8,14,15).

Clearly, this CCHFV is present in Sudan, and physicians should consider CCHF as a diagnosis for hemorrhagic fever cases in the region. In addition, efforts to provide appropriate personal protective supplies and training to medical staff in rural areas should be increased to help minimize risk for caregivers.

Acknowledgments
We thank Serena Carroll for assistance with the virus phylogenetic analysis and Pierre Rollin for his support.

This study was made possible by invaluable assistance from the health officials and medical staff in Kordufan District, Sudan. We dedicate this article to the nurses who died as a result of providing care to CCHF patients in this resource-poor setting.

Dr Aradaib is the scientific research director at the National Ribat University and a professor of molecular medicine at the University of Khartoum, Sudan. His research interests focus on the study of epizootics, including viral hemorrhagic fevers.

潮水

克里米亚-刚果出血热(Crimean-Congo hemorrhagic fever)是欧、亚、非三大洲都有分布的蜱媒自然疫源性病毒疾病。人群普遍易感，感染发病以青壮年为多，但也有2.5～3 岁婴幼儿被感染。临床表现与其他型出血热相似，惟肾脏的损伤较为轻微。患者入院时多呈重症，病死率高达50%。本病因在克里米亚和刚果相继发现而得名。在国内首先发现于新疆巴楚，故我国又称新疆出血热。
　　症状：起病急骤，恶寒战栗，体温上升至39～41℃。头痛剧烈，尤以前额和颞部剧痛难忍，颜面呈痛苦表情。周身肌痛，四肢关节酸痛剧烈，甚至难以行走。

sx2

Ok,I will try to translate it ASAP.

sx2

Nosocomial Outbreak of Crimean-Congo Hemorrhagic Fever, Sudan
苏丹克里米亚-刚果出血热医院感染暴发
Volume 16, Number 5–May 2010
美国急性传染病杂志 16卷第5期，2010年5月
Abstract摘要
To confirm the presence of Crimean-Congo hemorrhagic fever in Sudan, we tested serum of 8 patients with hemorrhagic fever in a rural hospital in 2008.Reverse transcription–PCR identified Crimean-Congo hemorrhagic fever virus. Its identification as group III lineage indicated links to virus strains from South Africa, Mauritania, and Nigeria。为了证实克里米亚-刚果出血热在苏丹的存在，2008年我们在其一所乡村医院进行了8例出血热病人的血清实验。即应用逆转录聚合酶链反应方法（RT-PCR）鉴定出克里米亚-刚果出血热病毒。结果为克里米亚-刚果出血热家族III病毒证实与来自南非、毛里塔尼亚和尼日利亚的病毒株一致

Crimean-Congo hemorrhagic fever virus (CCHFV; family Bunyaviridae, genus Nairovirus) is a tick-borne virus. Its tripartite RNA genome consists of small (S), medium, and large segments. The virus is distributed throughout much of Africa, Asia, and southern Europe (1–5). 里米亚-刚果出血热病毒（缩写为CCHFV; 布尼雅病毒科；内罗病毒属 ) 是通过蜱传播的病毒，由短、中、长片段组成它的三维RNA基因组。病毒大多数分布于非洲、亚洲和南欧。

In some regions, the virus is responsible for annual outbreaks of hemorrhagic fever with high case-fatality rates; in others, it causes sporadic cases only. Because of its association with rapid-onset hemorrhagic fever and an ≈30% case-fatality rate, CCHFV is on the US Select Agent list of agents considered to have bioterrorism potential (2–5). Distribution of CCHF largely mirrors that of its Ixodid tick hosts, particularly those of the genus Hyalomma (1). Persons become infected when bitten by virus-infected ticks or after contact with blood or tissue from viremic livestock or other persons. 在一些地区，此病毒每年都导致了具高死亡率的里米亚-刚果出血热的暴发。其他地区，它只引起散发病例。因为具有快速暴发的出血热和30%的死亡率特征，CCHFV病毒被美国列为具有潜在生物恐怖的危险介质。 CCHF大多数以蜱为宿主，特别是璃眼蜱属(1)，人被带有病毒的蜱咬伤或接触带有病毒的牲畜和人的组织和血液后会被传染。
Outbreaks often involve persons in rural communities, such as shepherds, slaughterhouse workers, or medical staff of resource-poor hospitals. Despite presence of Hyalomma tick vectors in Sudan, no CCHF cases have been confirmed there. However, in the past 2 years, suspected CCHF outbreaks and sporadic cases in the Kordufan region of Sudan have been reported.From a public health perspective, confirming CCHF in Sudan and determining which virus lineages may be present in this region will provide a more detailed understanding of the movement of virus strains and identification of areas at risk for CCHFV. We therefore analyzed an outbreak of hemorrhagic fever, including a nosocomial chain of transmission in a rural hospital in Sudan in 2008. CCHF总是在乡村地区的人群中暴发，例如牧羊人、屠宰工人和资源贫乏的医院工作人员。尽管苏丹存在病毒媒体-璃眼蜱，但并无CCHF病例证实。直到最近2年，苏丹Kordufan 地区散发病例出现，才开始怀疑CCHF的暴发。从公共健康的角度出发，证实苏丹CCHF存在并且在这个地区能分离出病毒家族将有助于了解病毒株的活动和鉴定CCHFV病毒存在的高危区域。因此我们分析了2008年苏丹一所乡村医院一例出血热的暴发事件，包括了其医院感染的传播途径。

The Study研究
In October 2008, an outbreak of hemorrhagic fever was reported in Al-fulah, Kordufan, Sudan. The index patient was a 60-year-old man who had worked as a butcher. The source of his infection was suspected to have been tissues and blood of an infected animal, although follow-up investigation was unable to precisely determine the source. 2008年10月，在苏丹Al-fulah Kordufan地区，报告了一例出血热的暴发。源病人曾是一个屠宰工人，因此怀疑他的感染源来自感染动物的组织和血液，尽管追踪调查不能确认。

He was admitted to a rural hospital with an acute febrile hemorrhagic illness after 3 days of high fever, chills, and headache. He had taken antimalarial medication at home, but his condition did not improve. He had epistaxis, black bloody vomitus, and diarrhea on the last 2 days of his illness. He died on day 5 after onset of illness.在3天的高热，寒颤和头痛后，他以急性出血热被收入这所乡村医院。虽然在家时，他已服了抗疟疾药物，但病情并无改善。他死前2天还出现鼻出血，黑色的血样呕吐物和腹泻，病人发病5天后死亡。

No protective gloves or antiseptic products were available at the hospital. Illness developed in a male nurse who had provided care to the index patient 6 days after the index patient had been admitted to the hospital and in the chief male nurse a few days after that.The index patient's sister was also considered to have a suspected case; she had sought care at the hospital after a heavy menstrual period that progressed to massive vaginal bleeding. The midwife who performed the gynecologic examination later became ill with high fever, vomiting of blood, and bloody diarrhea. 由于医院无防护手套和不能提供消毒用品，一个护理这个源病人的男护士在其入院后的第6天开始发病，几天后一个男主管护师也发病了。源病人的妹妹也怀疑患有此病，她在月经期由于大量的阴道出血在医院接受过治疗。从事她的妇科检查的助产士后来也出现高热，吐血和血性腹泻等临床表现。
As is tradition and social obligation in rural hospitals in this region, 2 relatives of the index patient had alternated caring for him (e.g., dressing him, changing his mattresses and bed sheets, nursing, and sleeping beside him) while he was in the hospital, and both acquired the infection (rapid onset of fever, headache, nausea, vomiting of blood, and bloody diarrhea). No details were available for 3 other patients with hemorrhagic fever associated with the hospital.因为传统习俗和社会责任，源病人的二位亲戚在他住院时轮流照顾过他（例如：帮他穿衣，更换床垫床单，进行其他生活照顾和在病人床边睡觉陪护）。在病人住院期间时，照顾他的二个亲戚都发生了感染（快速发热，头疼，恶心，呕血和血性腹泻）。还有其他3位与医院有关的出血热病人，但无他们的详细记录。

Of these 10 patients, 9 were admitted to a rural hospital in Al-fulah, where 6 continued to bleed, subsequently became comatose, and died. Records were unavailable for the other 3. In addition, 3 probable cases in the community were reported. Each of these 3 persons had a course of hemorrhagic disease and death that was compatible with CCHF; they had not been admitted to the hospital and could not be traced because of poor security conditions in the region. Patient ages varied from 15 to 70 years. Nosocomial transmission of the virus was likely the result of lack of personal protection for the hospital staff and the attending relatives, as has been often noted during previous outbreaks (6). 10位病人中，9位被收入Al-fulah地区的乡村医院。有6位病人继续出血然后昏迷死亡。其他3位无相关记录。另外，报告了3例社区感染病例，每个病人都有与CCHF疾病相一致的出血和死亡。他们没有入院治疗，但这个地区治安状况很差，也不能被追踪调查。病人年龄在15岁至70岁之间。病毒在医院的传播原因可能与医务人员和病人照顾人的个人防护用品缺乏有关，这在以前的疾病暴发中没有引起注意。

Figure 图表

Figure. Phylogenetic relationship of Crimean-Congo hemorrhagic fever virus (CCHFV) full-length small (S) segments... 图表：克里米亚-刚果出血热病毒的亲缘关系，全长小片段（略）。

Of the patients for whom serum samples were available, 8 had evidence of acute CCHFV infection. Direct immunofluorescence assay detected no antibodies to CCHFV in any of the serum samples; however, all samples had been collected on days 1–3 of illness. Virus RNA extracted from each of the samples by QIAamp (QIAGEN GmbH, Hilden, Germany) was positive according to reverse transcription–PCR (RT-PCR) specific for CCHFV (7). The RNA was then used in RT-PCRs to amplify the entire virus S segment for complete sequencing as described (8)。在有血清标本的病人中，8个能证实为急性克里米亚-刚果出血热感染。直接免疫荧光法检测显示：在任一血清标本中都无CCHFV抗体存在，可能与血标本都是在发病的1-3天采集有关。德国的QIAamp (QIAGEN GmbH, Hilden) 应用特别针对CCHFV的PCR方法对每个标本提取的病毒RNA检测，结果均为阳性。.然后应用RT-PCRs以放大整个病毒RNA的S片段，完成了以下步骤：
The full-length S segment nucleotide sequence of the strains from Sudan was 1,673 nt long, and the 8 viral sequences were identical with the exception of that from patient 4 (GenBank accession nos. GQ862371–2). A maximum-likelihood phylogenetic analysis of the S segment sequences placed the viruses from Sudan in group III (8), which is composed exclusively of viruses of African origin, including South Africa, Mauritania, and Nigeria (Figure). The highest nucleotide sequence identity was seen with strains from South Africa. 来自苏丹病毒株S片段核苷酸序列的总长度为1，673 nt，并且除4号病人外，其他8个的病毒序列被确定。亲缘分析最大可能性是苏丹病毒S片段序列证实其为家族第3组，包含具有特征性的非洲来源病毒如南非，毛里塔尼亚和尼日利亚 （见图表)，最高级的核苷酸序列与南非的病毒株一致。

sx2

Conclusions结论
Laboratory confirmation of 8 cases of CCHF demonstrates the presence of this disease in Sudan. Genetic analysis of the viruses showed that the strain involved was similar to strains found in South Africa, Mauritania, and Nigeria. Detailed analysis of virus outbreaks is often limited by the lack of appropriate high-containment facilities required for virus isolation. However, appropriately sampled and stored acute-phase serum samples can have high titers of the virus, which enable extraction of virus RNA and genome sequencing studies without prior amplification of the virus in cell culture. 8例CCHF实验室研究证明在苏丹的CCHF病毒遗传分析结果显示病毒株与南非、毛里塔尼亚和尼日利亚的是一样的。由于无分离病毒的封闭设备，病毒暴发的细节分析是由受限制的。然而，及时的标本采集和保存了急性期的血清标本使研究者拥有了高滴度的病毒，在无病毒在细胞培养基的事前扩增情况下，促使完成了病毒RNA的提取及基因序列的研究。

In this study, serum specimens from 8 patients who died were positive for CCHFV by RT-PCR. Lack of virus-specific antibodies 1–3 days after onset of illness can be explained by the severity and rapid course of the disease, which does not allow sufficient time for antibody production.
Virus-specific antibodies are, however, generally seen later in the course of illness and in persons who survive the infection. 在这个研究中，应用RT-PCR方法证实了死去的8个CCHF病人的血清标本为阳性。发病后的1-3天缺乏相应病毒抗体可解释为因为处于疾病的严重和快速进展阶段，还没有足够的时间供抗体生成。然而，在成活的感染病人和疾病的后期可检测到特定抗体。

Antibody studies have suggested the presence of various arboviruses in Sudan (10,11). Indirect evidence for CCHFV in animals in Sudan came from finding CCHFV-specific antibodies in animals imported from Sudan: camels in Egypt (12) and sheep and goats in Saudi Arabia (13).
The finding that the Al-fulah outbreak was caused by a CCHFV strain from genetic group III illustrates how different virus strains and lineages can move with livestock transport or possibly bird migrations. 通过抗体的研究证实了苏丹存在多种虫媒病毒。间接证据是从来自苏丹出口的CCHFV感染动物（埃及的骆驼，沙特阿拉伯的绵羊和山羊）身上发现了CCHFV抗体。Al-fulah地区CCHFV的暴发是CCHFV家族第III组病毒株引起的，说明不同病毒株和谱可以随牲口的运输和鸟的迁移而转移。
The genome plasticity of the virus is surprisingly high for an arthropod-borne virus. This genetic diversity appears to be the result of not only accumulation of mutations but also of frequent RNA segment reassortment and even RNA recombination (8,14,15). Clearly, this CCHFV is present in Sudan, and physicians should consider CCHF as a diagnosis for hemorrhagic fever cases in the region. In addition, efforts to provide appropriate personal protective supplies and training to medical staff in rural areas should be increased to help minimize risk for caregivers.对虫媒病毒来说，病毒基因的可塑性是惊人的高。遗传多样性不但表现在突变的累积，而且表现在RNA片段的频繁重配甚至RNA的重组。明显地，CCHFV是在苏丹存在的，而且在这个地区，医生应该考虑诊断出血性病例为CCHF。并且，提供适当的个人防护用品、培训乡村地区的医务人员和帮助减少对照顾提供人的危险应该得到加强。

Acknowledgments致谢
We thank Serena Carroll for assistance with the virus phylogenetic analysis and Pierre Rollin for his support.This study was made possible by invaluable assistance from the health officials and medical staff in Kordufan District, Sudan. We dedicate this article to the nurses who died as a result of providing care to CCHF patients in this resource-poor setting. Dr Aradaib is the scientific research director at the National Ribat University and a professor of molecular medicine at the University of Khartoum, Sudan. His research interests focus on the study of epizootics, including viral hemorrhagic fevers.感谢Serena Carroll提供病毒遗传基因分析和Pierre Rollin的帮助支持。可以说没有苏丹Kordufan地区医疗官员和医务人员的无私协助，这个研究是不能完成的。同时我们将这篇文章奉献给在这个资源贫乏的医院因为护理病人而逝去的护士同胞们。Aradaib博士是National Ribat University大学的科研主任和苏丹University of Khartoum大学的分子医学教授。他重点关注包括病毒性出血热在内的家畜流行病学的研究。

(由于某些专业知识限制，不妥之处，望各位同仁指正。 译者：SX2）

潮水

index patient 可翻译为指示病例，指在一起暴发疫情中符合病例定义，最早发现和报告的病例。指示病例是暴发调查中最重要指标之一，为追踪疫情传播链、分析疫情暴发原因和提出控制措施等提供最直接和最关键的线索和提示。

潮水

In addition, efforts to provide appropriate personal protective supplies and training to medical staff in rural areas should be increased to help minimize risk for caregivers.
caregivers看护者

sx2

Thanks!While you are doing,while you are learning.