不同地区人群SARS血清流行病学调查

目的分析严重急性呼吸综合征(Severe Acute Respiratory Syndrome，SARS)流行期间不同地区人群及SARS临床诊断病例血清特异性抗体(SARS-CoV IgG)变化规律以及健康人群是否存在隐性感染。方法采用酶联免疫方法(ELISA)及间接免疫荧光法(IFA)，对香港、澳门、北京、广州地区1453名健康人及广州和北京地区257例SARS临床诊断病例进行血清SARS—CoV IgG抗体检测，并跟踪检测患者病后不同时间(发病3～270d)血清抗体变化情况。结果4个地区健康人群(包括160名密切接触者)中，用ELISA法检出2例SARS—CoV IgG抗体阳性，阳性者进一步用IFA检测则为阴性；广州地区200名健康体检者同时采用ELISA和IFA检测，结果均为阴性。ELISA和IFA同时检测257例临床诊断病例发病20d后的血清SARS—CoV IgG抗体，2种方法检出的阳性率均为90％。ELISA法跟踪检测257例临床诊断病例发病后3～270d血清IgG抗体，抗体滴度在发病后4～6个月内随时间延长逐渐升高，多数病人抗体在第4～6个月达到高峰，并持续到第8个月，部分病人抗体达高峰后开始下降，但至第9个月仍阳性。结论健康人群中隐性感染率极低，血清SARS—CoV IgG抗体在病程后期有诊断价值，血清特异性抗体可持续9个月以上。     

Longitudinally profiling neutralizing antibody response to SARS coronavirus with pseudotypes

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike protein (S) is a major target for neutralizing antibodies. Retroviral SARS-CoV S pseudotypes have been constructed and used to develop an in vitro microneutralization assay that is both sensitive and specific for SARS-CoV neutralizing antibodies. Neutralization titers measured by this assay are highly correlated to those measured by an assay using replication-competent SARS-CoV. No cross-neutralization occurred with human sera known to contain antibodies to coronavirus strains OC43 and 229E. The pseudotype assay was used to profile neutralizing antibody responses against SARS-CoV S in sequential serum samples taken from 41 confirmed SARS patients during the 2003 outbreak in Hong Kong and shows long-lasting immunity in most recovered patients. The pseudotype assay does not require handling live SARS virus; it is a useful tool to determine neutralizing titers during natural infection and the preclinical evaluation of candidate vaccines.     

Animal models and antibody assays for evaluating candidate SARS vaccines: summary of a technical meeting 25-26 August 2005, London, UK

Severe acute respiratory syndrome (SARS) emerged in the Guangdong province of China in late 2002 and spread to 29 countries. By the end of the outbreak in July 2003, the CDC and WHO reported 8437 cases with a 9.6% case fatality rate. The disease was caused by a previously unrecognized coronavirus, SARS-CoV. Drawing on experience with animal coronavirus vaccines, several vaccine candidates have been developed and evaluated in pre-clinical trials. Available data suggest that vaccines should be based on the the 180kDa viral spike protein, S, the only significant neutralization antigen capable of inducing protective immune responses in animals. In the absence of clinical cases of SARS, candidate vaccines should be evaluated for efficacy in animal models, and although it is uncertain whether the United States Food and Drug Administration's "animal rule" would apply to licensure of a SARS vaccine, it is important to develop standardized animal models and immunological assays in preparation for this eventuality. This report summarizes the recommendations from a WHO Technical Meeting on Animal Models and Antibody Assays for Evaluating Candidate SARS Vaccines held on 25-26 August 2005 in South Mimms, UK, provides guidance on the use of animal models, and outlines the steps to develop standard reagents and assays for immunological evaluation of candidate SARS vaccines.     

珠海市动物从业人员SARS—CoV抗体血清流行病学研究

目的通过对动物从业人员以及其它健康人群感染SARS-CoV的血清学研究,揭示人群中SARS-CoV抗体水平,探讨动物作为传染源的传播途径.方法随机选取无SARS临床症状的健康动物从业人员以及其它健康人员等545人作为调查对象,使用统一调查表对调查对象进行个案调查,同时采集调查对象的血清,用ELISA法检测SARS-CoV抗体.结果共检测各种人群血样545份,其中动物从业人员血样269份,SARS-CoV抗体阳性率为8.18%;健康人群血样276份,阳性率为1.09%,动物从业人员SARS-CoV抗体阳性率和非从业人员SARS-CoV抗体阳性率比较有显著性差异.结论动物从业人员SARS-CoV抗体阳性率显著高于非从业人员,支持SARS-CoV源于野生动物的假设.     

太原市SARS临床确诊病例血清抗体和影像学资料随访分析

目的了解山西省太原市SARS临床确诊病例半年后的血清抗体水平、胸部和股骨头影像学的变化。方法对132例太原市2003年3月11日~7月5日临床确诊的SARS病例进行随访问卷调查、血清学抗体检测及肺部和股骨头影像学检查,并分析比较。结果SARS临床确诊病例半年后的主要症状为气短、关节肌肉痛、心悸和烦躁;女性患者各种症状的发生率均高于男性;血清抗体与心悸、烦躁和肌肉关节痛的发生情况有统计学关联;血清抗体阳性率与入院时间有关联。结论太原市SARS病例存在过度诊断现象,血清抗体阳性率随着入院时间的推移逐步下降;部分确诊病例出院后合并股骨头缺血性坏死改变。     

Utility of the aged BALB/c mouse model to demonstrate prevention and control strategies for severe acute respiratory syndrome coronavirus (SARS-CoV)

The causative agent of Severe Acute Respiratory Syndrome (SARS) was identified as a coronavirus (CoV) following the outbreak of 2002-2003. There are currently no licensed vaccines or treatments for SARS-CoV infections. Potential prevention and control strategies that show promise in vitro must be evaluated in animal models. The aged BALB/c mouse model for SARS supports a high level of viral replication in association with clinical illness and disease that mimics SARS in the elderly. We tested two preventive strategies, vaccination and passive transfer of serum antibody, to determine the extent of protection achieved against SARS-CoV challenge in this model. These approaches were able to achieve or induce antibody titers sufficient to reduce viral load, protect from weight loss and reduce or eliminate histopathologic changes in the lungs of aged mice. This study validates the utility of the aged BALB/c mouse model for evaluation of the efficacy of vaccines and immunoprophylaxis.     

发热患者SARS冠状病毒抗体分析

目的了解临床发热患者中是否存在严重急性呼吸综合征（SARS）冠状病毒（SARS-CoV）隐性感染或亚临床感染。方法对2003年5月～7月，SARS流行期间湖北地区临床发热患者373例血清进行SARS冠状病毒（SARS-CoV）抗体（IgG、IgM、N蛋白抗体）酶联免疫吸附法（ELISA）检测和分子生物学（RT—PCR）检测。结果373例发热患者中，检出冠状病毒抗体阳性者24例，阳性率6．43％（24／373），其中SARSIgG抗体、IgM抗体、N蛋白抗体阳性率分别为0．54％，1．34％和5．09％，但SARS-CoVRT—PCR检测均为阴性。结论临床发热患者可能存在SARS-CoV隐性或亚临床感染，患者体内产生针对SARS-CoV的保护性抗体，应具有免疫力和抵抗力。     

Immunofluorescence assay for serologic diagnosis of SARS

We evaluated an indirect immunofluorescence assay based on virus-infected cells for detecting anti-severe acute respiratory syndrome-associated coronavirus (SARS-CoV) immunoglobulin (Ig) G antibody. All confirmed SARS cases demonstrated seroconversion or fourfold rise in IgG antibody titer; no control was positive. Sensitivity and specificity of this assay were both 100%. Immunofluorescence assay can ascertain the status of SARS-CoV infection.     

SARS-CoV infection in a restaurant from palm civet

Epidemiologic investigations showed that 2 of 4 patients with severe acute respiratory syndrome (SARS) identified in the winter of 2003-2004 were a waitresss at a restaurant in Guangzhou, China, that served palm civets as food and a customer who ate in the restaurant ashort distance from animal cages. All 6 palm civets at the restaurant were positive for SARS-associated coronavirus (SARS-CoV). Partial spike (S) gene sequences of SARS-CoV from the 2 patients were identical to 4 of 5 Sgene viral sequences from palm civets. Phylogenetic analysis showed that SARS-CoV from palm civets in the restaurant was most closely related to animal isolates. SARS cases at the restaurant were the result of recent interspecies transfer from the putative palm civet reservoir, and not the result of continued circulation of SARS-CoV in the human population.     

广州市某野生动物市场从业人员携带SARS冠状病毒抗体状况调查

目的了解广州市新源野生动物市场从业人员严重急性呼吸综合征（SANS）抗体产生情况及其暴露果子狸的关系。方法对野生动物市场从业人员中的志愿者进行SARS病毒血清抗体监测，对监测结果结合果子狸在市场的存在情况进行分析。结果2003年5和12月、2004年1和7月、2005年6月，共5次分别对328、238、135、139和53名市场从业人员开展调查，SARS病毒IgG抗体检出率依次为25．61％、13．03％、12．59％、5．04％和9．43％，没有检测到SARS病毒IgM抗体。在接受2次以上随访调查的129人中，97人的血清抗体一直为阴性，博人一直为阳性；有13人从阳性转为阴性，有1人从阴性转为阳性。在清除果子狸后进入市场的工作人员，SARS病毒IgG抗体检测全部阴性。结论广州市新源野生动物市场从业人员SARS病毒抗体检出率和市场内果子狸的存在情况密切相关。     

Lack of SARS transmission and U.S. SARS case-patient

In early April 2003, severe acute respiratory syndrome (SARS) was diagnosed in a Pennsylvania resident after his exposure to persons with SARS in Toronto, Canada. To identify contacts of the case-patient and evaluate the risk for SARS transmission, a detailed epidemiologic investigation was performed. On the basis of this investigation, 26 persons (17 healthcare workers, 4 household contacts, and 5 others) were identified as having had close contact with this case-patient before infection-control practices were implemented. Laboratory evaluation of clinical specimens showed no evidence of transmission of SARS-associated coronavirus (SARS-CoV) infection to any close contact of this patient. This investigation documents that, under certain circumstances, SARS-CoV is not readily transmitted to close contacts, despite ample unprotected exposures. Improving the understanding of risk factors for transmission will help focus public health control measures.     

北京地区SARS康复者冠状病毒IgM、IgG抗体水平的变化

目的探讨SARS康复者康复后及其1年内血清冠状病毒IgG、IgM抗体的产生水平及动态变化,为该病的下一步预防和疫苗的保护效力提供依据.方法采用ELISA法对SARS康复者冠状病毒IgG、IgM抗体进行检测,对IgG或IgM抗体连续两次检测都为阳性者继续随访1年;对二者连续两次都为阴性者放弃随访;随访结果用stata 7.0软件分析.结果 81.2%的康复者连续两次IgG抗体检测阳性;18.8%的康复者连续两次IgG抗体阴性;对311例IgG抗体阳性者进行了1年的随访,除1例在出院后85 d时抗体变为阴性外,其他310例康复者1年后IgG抗体仍为阳性,但抗体平均水平下降了约35.8%;22例IgG抗体阳性康复者(2003年4月3日～5月21日出院)进行了IgM抗体检测,2003年5月30日检测时,22.7%的康复者IgM抗体阳性,2003年6月14日检测时,IgM抗体全为阴性.结论 IgM抗体在康复后短期内很快消失;约有81.2%的康复者能够产生IgG抗体;1年随访中,除1例康复者IgG抗体由阳性转为阴性外,其他IgG抗体阳性者1年后该抗体仍为阳性,但抗体水平有所下降.     

Revised U.S. surveillance case definition for severe acute respiratory syndrome (SARS) and update on SARS cases--United States and worldwide, December 2003

During the 2003 epidemic of severe acute respiratory syndrome (SARS), CDC and the Council of State and Territorial Epidemiologists (CSTE) developed surveillance criteria to identify persons with SARS. The surveillance case definition changed throughout the epidemic as understanding of the clinical, laboratory, and transmission characteristics of SARS-associated coronavirus (SARS-CoV) increased. On June 26, CSTE adopted a position statement to add SARS-CoV disease to the National Notifiable Disease Surveillance System (NNDSS). The position statement included criteria for defining a SARS case for national reporting. On November 3, CSTE issued a new interim position statement with a revised SARS case definition. This report summarizes the new U.S. surveillance case definition for SARS and updates reported cases of SARS worldwide and in the United States.     

广州市野生动物批发市场从业人员SARS冠状病毒感染的流行病学研究

目的　了解广州市野生动物市场从业人员SARS冠状病毒感染状况。方法　对 3家野生动物市场部分从业人员进行SARS冠状病毒IgG抗体血清学检测并回顾性调查急性呼吸道感染症状。结果　 6 35名从业人员中 ,SARS冠状病毒抗体检出率为 16 6 9%。 3家市场从业人员抗体检出率存在着差异 ,主营野生畜类动物的甲市场为 2 5 6 1% ,明显高于分别主营禽类、蛇类的乙市场和丙市场 (7 5 0 %和 6 80 % ) ;只经营果子狸者抗体检出率为 5 8 5 4 % ,明显高于只经营蛇类者的9 4 6 %。甲市场内 ,主营野生畜类者、市场管理者、从业人员子女、主营家禽家畜类者、主营蛇类者及经营冷冻类食品者等 6类人员随着接触野生畜类动物机会的减少 ,抗体检出率下降 ,依次为5 9 34%、2 0 5 9%、16 0 0 %、15 2 2 %、10 4 0 %和 9 6 8%。在SARS流行期间 ,有急性呼吸道感染症状者抗体检出率为 30 70 % ,高于无症状者的 2 0 0 8% ;抗体阳性者急性呼吸道感染症状发生率为4 9 2 8% ,高于阴性者的 30 35 %。结论　动物市场人员SARS冠状病毒感染可能与野生畜类动物 ,特别是果子狸有密切关系。在SARS流行期间 ,不排除存在着部分从业人员曾感染人SARS冠状病毒并发病 ,但由于临床表现不明显而被忽略的可能性     

Lack of SARS transmission among healthcare workers, United States

Healthcare workers accounted for a large proportion of persons with severe acute respiratory syndrome (SARS) during the worldwide epidemic of early 2003. We conducted an investigation of healthcare workers exposed to laboratory-confirmed SARS patients in the United States to evaluate infection-control practices and possible SARS-associated coronavirus (SARS-CoV) transmission. We identified 110 healthcare workers with exposure within droplet range (i.e., 3 feet) to six SARS-CoV-positive patients. Forty-five healthcare workers had exposure without any mask use, 72 had exposure without eye protection, and 40 reported direct skin-to-skin contact. Potential droplet- and aerosol-generating procedures were infrequent: 5% of healthcare workers manipulated a patient's airway, and 4% administered aerosolized medication. Despite numerous unprotected exposures, there was no serologic evidence of healthcare-related SARS-CoV transmission. Lack of transmission in the United States may be related to the relative absence of high-risk procedures or patients, factors that may place healthcare workers at higher risk for infection.     

广东省不同人群SARS病毒抗体水平调查

目的对不同人群进行SARS-IgG抗体水平检测，分析SARS流行规模和特征，评价暴露的危险性，了解人数中是否存在SARS病毒隐性感染，为寻找SARS病毒传染源提供线索。方法抽取7708份不同人群标本，按临床症状和暴露因素分为临床确诊SARS病人、病人或污染物的接触者、普通健康人群和动物销售人员4类，采用酶联免疫方法(ELISA)进行SARS-IgG抗体检测，用免疫荧光法(IFA)复核，并结合流行病学资料进行分析。结果127例临床确诊SARS病人抗体阳性率为66．9％；密切接触者中女性发病率高于男性；SARS病人或其污染物的密切接触者抗体阳性率为0．88％；动物销售人员为13．4％；野生哺乳动物销售者的抗体阳性率显著高于其他动物销售者，普通健康人群未检出抗体阳性。低年龄健康人群ELISA检测阳性率为2．06％，高于总体水平。结论人群总体抗体水平很低，普通健康人群无SARS冠状病毒抗体，但可能存在某种可与SARS冠状病毒起交叉反应的抗体；有无接触史是影响抗体阳性率的重要因素；密切接触者可能存在隐性感染；野生动物可能是本次SARS的传染源。     

SARS患者7年随访血清抗体变化规律及胃肠道免疫组化研究

目的 连续7年随访严重急性呼吸综合征(SARS)患者血清特异性IgM、IgG及N蛋白抗体滴度变化,应用胃肠镜观察胃肠道的病理改变并进行免疫组织化学研究.方法 应用免疫荧光(IFA)和双抗原夹心ELISA方法,对SARS患者发病1年后采用每隔1年检测一次血清SARS病毒(SARS-CoV)特异性IgM、IgG及N蛋白抗体滴度;用抗SARS-CoV N蛋白单克隆抗体对SARS恢复期患者胃肠道组织进行免疫组化研究.结果 14例SARS患者特异性IgG抗体1年后平均滴度为1/71(95%CI:1/58～1/85),连续追踪7年呈下降趋势,7年后大部分患者IgG抗体滴度消失,特异性IgM抗体1年后消失,N蛋白抗体1年后平均滴度为1/146(95%CI:1/122～1/171),与IgG抗体变化同时呈下降趋势.7年后其中9例患者检测N蛋白抗体全部为阴性,另5例临床症状较重的患者,N蛋白抗体仍检测阳性,其中3例N蛋白抗体滴度维持在1/156～1/210之间,2例N蛋白抗体滴度接近正常.该5例患者行胃肠镜检测和细胞免疫组化试验,血中N蛋白抗体检测阳性的3例患者胃组织黏液腺上皮细胞免疫组化呈阳性表达,大部呈胞浆着色.其中1例患者在肠组织浆液柱状上皮及间质细胞亦有表达,另2例血清N蛋白抗体检测接近正常的患者,细胞免疫组化为阴性.5例患者病理活检:1例明确诊断为"胃印戒细胞癌并直肠多发转移"、1例"胃息肉"、1例"浅表性胃窦炎",其余2例正常.结论 SARS患者血清特异性IgM、IgG、N蛋白抗体在恢复期呈下降趋势,7年后大部分消失;N蛋白抗体变化规律与病情轻重程度有关.     

SARS患者7年随访血清抗体变化规律及胃肠道免疫组化研究

目的 连续7年随访严重急性呼吸综合征(SARS)患者血清特异性IgM、IgG及N蛋白抗体滴度变化,应用胃肠镜观察胃肠道的病理改变并进行免疫组织化学研究.方法 应用免疫荧光(IFA)和双抗原夹心ELISA方法,对SARS患者发病1年后采用每隔1年检测一次血清SARS病毒(SARS-CoV)特异性IgM、IgG及N蛋白抗体滴度;用抗SARS-CoV N蛋白单克隆抗体对SARS恢复期患者胃肠道组织进行免疫组化研究.结果 14例SARS患者特异性IgG抗体1年后平均滴度为1/71(95%CI:1/58～1/85),连续追踪7年呈下降趋势,7年后大部分患者IgG抗体滴度消失,特异性IgM抗体1年后消失,N蛋白抗体1年后平均滴度为1/146(95%CI:1/122～1/171),与IgG抗体变化同时呈下降趋势.7年后其中9例患者检测N蛋白抗体全部为阴性,另5例临床症状较重的患者,N蛋白抗体仍检测阳性,其中3例N蛋白抗体滴度维持在1/156～1/210之间,2例N蛋白抗体滴度接近正常.该5例患者行胃肠镜检测和细胞免疫组化试验,血中N蛋白抗体检测阳性的3例患者胃组织黏液腺上皮细胞免疫组化呈阳性表达,大部呈胞浆着色.其中1例患者在肠组织浆液柱状上皮及间质细胞亦有表达,另2例血清N蛋白抗体检测接近正常的患者,细胞免疫组化为阴性.5例患者病理活检:1例明确诊断为"胃印戒细胞癌并直肠多发转移"、1例"胃息肉"、1例"浅表性胃窦炎",其余2例正常.结论 SARS患者血清特异性IgM、IgG、N蛋白抗体在恢复期呈下降趋势,7年后大部分消失;N蛋白抗体变化规律与病情轻重程度有关.