,, 仇华吉,中国农业科学院哈尔滨兽医研究所/兽医生物技术国家重点实验室,哈尔滨 150069Eradication of Classical Swine Fever in China: Is It Far Away?
SUN Yuan,, QIU HuaJi,State Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences /Harbin Veterinary Research Institute, Harbin 150069通讯作者:
责任编辑: 林鉴非
收稿日期:2018-01-24接受日期:2018-05-4网络出版日期:2018-11-01
| 基金资助: |
Received:2018-01-24Accepted:2018-05-4Online:2018-11-01
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孙元, 仇华吉. 中国猪瘟净化之路：离我们还有多远?[J]. 中国农业科学, 2018, 51(21): 4169-4176 doi:10.3864/j.issn.0578-1752.2018.21.015
SUN Yuan, QIU HuaJi.
猪瘟（classical swine fever,CSF）是由猪瘟病毒（classical swine fever virus,CSFV）引起猪的一种以高热、出血和高死亡率为主要特征的接触性传染病[1],可造成严重的经济损失[2]。该病被世界动物卫生组织（OIE）列入须申报的动物传染病目录[3],我国将其列为一类动物疫病。《国家中长期动物疫病防治规划（2012-2020年）》将猪瘟列为5种优先防治和重点防范的一类动物疫病之一。我国老一辈科学家于上世纪50年代研制出闻名于世的猪瘟兔化弱毒疫苗（C株）,该疫苗对我国乃至世界范围内猪瘟的防控和根除发挥了至关重要的作用[4]。多个国家通过应用该疫苗结合科学合理的生物安全措施根除了猪瘟。我国早在上世纪中期就提出了消灭猪瘟的战略,数十年过去了,猪瘟仍在我国广泛存在,甚至局部流行,原因何在?中国的猪瘟净化之路还有多远?本文对世界和中国猪瘟的流行现状进行了介绍,深入分析了我国猪瘟净化的必要性和可行性,总结了欧美部分国家猪瘟净化的成功经验和再次暴发的教训,并对我国猪瘟净化思路和方案进行了探讨,以期为我国猪瘟的净化提供参考。
1 世界猪瘟分布和中国猪瘟的流行现状
猪瘟是严重危害养猪业的一种急性传染病,出现于200多年前[5]。世界各国对该病的防控和净化做出了巨大努力。2017年OIE发布的CSF全球流行报告显示,美国、加拿大、澳大利亚、欧盟等部分国家和地区已经成功根除了猪瘟[6],该病仍持续对亚洲、东欧、中南美洲大部及加勒比海地区造成严重危害,尤其对发展中国家的养猪业和食品安全影响较大,一些无猪瘟国家也面临着传入该病的高风险[7,8]。目前,猪瘟3大流行区为中南美洲、欧洲和亚洲。其中,中南美洲为疫情稳定区;东欧地区为流行活跃区;亚洲属于老疫区,由于控制措施不力,疫情形势依然严峻。资料表明,除南非、马达加斯加和毛里求斯外,非洲其他国家未见猪瘟爆发[2, 9-10]。猪瘟病毒有3个基因型和11个基因亚型。基因1型主要分布在南美、亚洲和俄罗斯;基因2型主要分布于欧洲、亚洲等。目前,我国流行的猪瘟病毒以2.1、2.2和1.1基因亚型为主,偶有2.3和3.4亚型,其中2.1亚型占优势[7, 11-20]。全球猪瘟亚型分布见表1。
Table 1
表1
表1全球猪瘟病毒基因亚型分布
Table 1
| 猪瘟病毒基因型 Genotypes of CSFV | 国家 Countries |
|---|---|
| 1.1 | 阿根廷、巴西、哥伦比亚、墨西哥、意大利、俄罗斯、印度、中国 Argentina, Brazil, Colombia, Mexico, Italy, Russia Federation, India, China |
| 1.3 | 洪都拉斯、危地马拉Honduras, Guatemala |
| 1.4 | 古巴Cuba |
| 2.1 | 南非、德国、荷兰、意大利、西班牙、比利时、克罗地亚、立陶宛、以色列、印度、韩国、中国、老挝 South Africa, Germany, The Netherlands, Italy, Spain, Belgium, Croatia, Lithuania, Israel, India, South Korea, China, Laos |
| 2.2 | 德国、意大利、捷克、马其顿、印度、尼泊尔、老挝、中国 Germany, Italy, Czech Republic, Former Yugoslav Republic of Macedonia, India, Nepal, Laos, China |
| 2.3 | 意大利、克罗地亚、法国、罗马尼亚、保加利亚、塞尔维亚、斯洛伐克、捷克、俄罗斯、中国 Italy, Croatia, France, Romania, Bulgaria, Serbia, Slovakia, Czech Republic, Russia Federation, China |
| 3.2 | 韩国South Korea |
| 3.4 | 中国台湾Taiwan of China |
新窗口打开|下载CSV
当前世界范围内猪瘟的流行发生了很大变化,经典强毒株引起的猪瘟在成年猪中少见,中等、低毒力猪瘟病毒引起的非典型猪瘟和持续性感染比较常见,造成的经济损失不容小视[3, 21-22]。当前我国猪瘟的流行形势和发病特点主要表现为：流行范围广,全国范围内均有流行,但以散发流行为主。目前猪瘟多见于仔猪,成年猪很少出现发病症状,但可持续带毒,并且可通过水平和垂直传播在猪场内恶性循环。非典型症状和繁殖障碍型猪瘟增多,临床上持续性感染（亚临床感染）和隐性感染增多,成为猪瘟流行最危险的传染源。另外,猪瘟与猪繁殖与呼吸综合征、伪狂犬病、猪细小病毒病、猪圆环病毒病等混合感染十分严重和普遍[23]。
2 中国猪瘟净化的必要性
2.1 养猪业在我国的重要地位
“粮猪安天下”,养猪业是攸关国计民生和“三农”问题的支柱产业。我国生猪屠宰量占全球近6成,猪肉消费量占全球的一半。2017年我国猪肉产量5 340万吨,生猪存栏43 325万头,出栏68 861万头,是全球第一大猪肉消费市场。据海关统计,2017年,我国累计进出口猪肉126.8万吨,进出口总额168.2亿元人民币。其中,进口猪肉121.7万吨,出口猪肉5.1万吨[24]。因此,我国猪肉出口有巨大空间。
2.2 猪瘟是制约养猪业发展的重大疫病之一
我国是世界第一养猪大国。随着养猪业的发展,规模化、集约化程度不断提高,由于种猪的引进、生猪转运量的增加,猪的传染病越来越多,疫病的控制难度越来越大,造成的经济损失也越来越严重。由于传染性强、致死率高等特点,猪瘟成为养殖户重点防范的主要疫病。如果防控不到位,一旦发病,损失将是巨大的。因此,养殖企业每年为防控猪瘟耗费了大量的人力、物力和财力。其中,种公猪、母猪一年要免疫2—4次,仔猪从出生到出栏要进行2次以上的免疫,防疫成本相当高。猪瘟疫苗免疫程序及成本分析见表2。Table 2
表2
表2猪场进行猪瘟疫苗免疫的程序及成本
Table 2
| 类别 Classes | 免疫次数（次） Vaccination times (times) | 免疫剂量（头份） Immunizing dose (unit per pig) | 疫苗成本1)（元） Cost of vaccine (RMB) | 人工成本1)（元） Cost of labor (RMB) |
|---|---|---|---|---|
| 母猪Sow | 2-4 | 4 | 3200 | 200 |
| 仔猪Piglets | 2 | 2 | 38400 | 960 |
| 公猪Boar | 2-4 | 4 | 100 | 80 |
| 合计Total | 41700 | 1240 | ||
新窗口打开|下载CSV
2.3 猪瘟对我国猪肉及相关制品贸易的巨大阻碍作用
猪瘟是世界各国重点防控的重大动物疫病之一,该病严重影响世界各国的猪肉及相关制品贸易。以美国为例,1962年暴发猪瘟后,有12个国家禁止从美国进口猪产品,其潜在市场价值估计每年有2 000万美元。猪瘟根除后,美国获得了这个潜在市场的准入机会,所获利润远大于根除猪瘟的开支。由于我国是猪瘟疫区,猪肉出口受到极大限制,目前只有少量猪肉产品销往港澳和俄罗斯等地。因此,猪瘟净化对提升我国的国际竞争力、开拓国际猪肉市场十分必要。
2.4 只有采取净化措施才能从根本上控制我国猪瘟的流行
猪瘟兔化弱毒疫苗由我国创制,很多国家应用该疫苗结合生物安全措施成功净化了猪瘟。而我国应用该疫苗60余年,为何至今未能根除猪瘟?分析主要有以下几点原因：（1）带毒种猪是主要根源;（2）先天性感染的仔猪产生免疫耐受;（3）混合感染与继发感染造成免疫抑制;（4）疫苗及免疫程序混乱;（5）生物安全防控措施不到位;（6）饲养管理、人员素质水平低;（7）相应的政策、法规等不健全。除此之外,C株疫苗不具有标记特性,不能够区分疫苗免疫和野毒感染,这给猪瘟的净化造成了较大的困难[25,26,27]。猪瘟在我国屡防不绝,其根源主要在于母猪带毒,临床上有3%—33%的种猪带毒,常导致免疫失败,造成我国猪瘟长期持续存在和散发流行。猪瘟病毒可通过胎盘传播给胎儿,这种先天性感染经常导致母猪流产、产木乃伊胎、死胎、弱仔。而且先天感染猪瘟的仔猪往往产生免疫耐受,变成持续性感染的带毒猪。如果这些猪用作后备种猪就可成为传染源。带毒母猪及先天感染仔猪可不断排毒,污染环境,感染其他健康猪。垂直传播与水平传播同时在一个猪场反复交替进行,造成了猪瘟感染的恶性循环。只有通过猪瘟的净化结合加强饲养管理和生物安全等综合性防控措施,才能彻底解决这一难题[23]。
猪瘟净化的效益非常可观,以美国根除猪瘟为例,在执行根除计划的16年间,共支出经费约1.40亿美元。在执行该计划前,美国由于猪瘟引起的年度损失5 740万美元,从1962年到1977年的损失共计约9.20亿美元,如果将通货膨胀的因素考虑在内,实际损失可能超过15亿美元,成功实施猪瘟根除计划的效益/成本约为13.2,这意味着在成功的根除计划中每投入1美元将会节约13.2美元的猪瘟防控支出。如果以一个更保守的折扣率（6%）计算,每1美元的花费将产生高达21.1美元的收益[23]。因此,投入必要的人力、物力开展猪瘟净化,是目前国内养猪业迫在眉睫的任务和使命。
3 欧美净化猪瘟的经验
欧盟于上世纪80年代实施了猪瘟净化项目,该项目首先采用C株疫苗免疫,当感染率降低到一定程度后,再采取非免疫结合扑杀策略,另外限制猪及猪产品的流通,从而使一些国家净化了猪瘟[28]。然而,在1997年,荷兰、德国、比利时、西班牙和意大利再次暴发了猪瘟。比利时当局立即扑杀了7个感染猪群和55个接触感染的猪群,在40 d内恢复猪瘟无疫状态,意大利利用同样方式取得了成功。这些国家猪瘟的再次暴发主要是由野猪及进口猪制品所引起[15, 28-29]。目前,宣布无猪瘟的国家和地区包括北美洲：加拿大、美国、墨西哥;南美洲：智利、巴拉圭以及巴西和哥伦比亚部分区域;大洋洲：澳大利亚、新西兰、新客利多尼亚;欧洲：法国、荷兰、比利时、卢森堡、瑞士、列支敦士登、奥地利、德国、波兰、斯洛伐克、捷克、罗马尼亚、丹麦、挪威、芬兰、瑞典、爱尔兰、英国、葡萄牙、西班牙、意大利、斯洛文尼亚。
总结欧美等国家成功净化猪瘟的经验,包括以下几方面：（1）早期疫苗免疫结合后期扑杀：开始使用疫苗密集免疫,当感染率降低到一定程度后,减少直至停止使用疫苗,主要依靠检测和扑杀[15];（2）持续监测：包括主动监测和被动监测,及时、快速地查出和清除感染猪,特别是持续感染带毒猪;（3）早、快、严、小反应机制：一旦出现疫情,需要迅速、果断处置,包括隔离疫点、扑杀病猪、限制动物流动、全面消毒等紧急措施;（4）生物安全措施：包括圈舍、人员、车辆、器具消毒,防止野猪散毒,采取猎杀、饵料免疫措施;（5）各方联动协作：政府、兽医主管部门、猪场、检测机构和科研单位等相互配合。
欧盟个别国家再次暴发猪瘟主要是由野猪感染传播所引起,家猪逃逸后与野猪接触增加了猪瘟感染与流行的机会。虽然欧盟采取了一些措施如投放口服诱饵疫苗来对野猪免疫,但是野猪猪瘟的感染率仍很高,主要由于诱饵疫苗大多被成年猪捕获,而易感性更高的仔猪获取的机会较小。另一方面,对野猪的监测和扑杀存在一定难度,致使猪瘟从野猪传入家畜的风险增大,如果防范不到位,就会导致猪瘟的再次暴发。
4 中国猪瘟净化的技术支撑
目前,我国已初步具备猪瘟净化的条件。当前猪瘟的流行率处于较低水平,猪瘟疫苗的生产工艺不断改进,质量不断提升;新型猪瘟标记疫苗的研制进展也非常顺利;相应的猪瘟检测、监测方法及与标记疫苗配套的鉴别诊断技术也已达到了国际水平。目前,我国已经有一项猪瘟标记疫苗即猪瘟病毒E2重组杆状病毒灭活疫苗获得了新兽药证书,另有数项猪瘟标记疫苗进入临床试验,包括猪瘟基因工程活疫苗（rAdV-SFV-E2株）、猪瘟基因工程亚单位疫苗（293T-E2）和猪瘟病毒E2重组杆状病毒载体灭活疫苗（WH-09株）等。除技术支撑外,我国养猪企业也意识到了猪瘟净化的重要性和必要性。养猪企业的生物安全水平也在不断提升,小型和散养模式不断减少。政府部门也在积极采取行动,制定相应的法规和政策,联合养殖户、企业、各地兽医部门等实施区域性的猪瘟净化。
5 中国猪瘟净化的挑战
虽然我国已初步具备了猪瘟净化的条件,但还有许多制约因素。目前,我国养猪模式多样化,养殖水平和条件、生物安全防控措施、人员素质和意识水平参差不齐,相应的政策法规等还不够完善。我国猪瘟的净化依然面临着巨大挑战。5.1 养殖模式多样化
我国的养猪业是由传统的家庭散养户发展起来的,目前正逐步地向规模化、专业化和集约化的现代养殖方向转型,但是发展的历史较短[30]。我国最大的养猪企业温氏集团发展规模化养猪也只有二三十年。目前我国的养猪模式包括散养、中小规模养殖及大型规模化养殖。散户和中小养殖户规模不一,养殖条件差,抵抗疾病风险的能力较低,养殖过程缺乏标准,一旦发病,缺乏有效的疫病防控手段和监管措施[31]。5.2 猪传染病种类复杂、混合感染多
目前,我国猪传染病的种类繁多,旧病未除,新病又增,疫病防控压力较大[28]。20世纪90年代以前,我国流行的主要猪病仅十余种,如猪瘟、猪丹毒、猪肺疫、仔猪副伤寒、猪支原体肺炎、仔猪大肠杆菌病、伪狂犬病、猪传染性萎缩性鼻炎等。改革开放以来,由于贸易及人员流通频繁,一些猪传染病传入我国（如猪繁殖与呼吸综合征、猪圆环病毒病等）,并快速传播、蔓延,给养猪业造成了巨大损失。另外,由于免疫压力及其他因素,使某些疫病非典型化,且发生了变异,如高致病性猪繁殖与呼吸综合征、伪狂犬病、猪流行性腹泻等。另一方面,多重感染、继发感染、混合感染已成为我国猪场较为普遍的发病形式,这给疫病的诊断及防控带来了很大困难。当前多数猪场同时存在多种病原的混合感染,其中猪瘟与猪繁殖与呼吸综合征、伪狂犬病、猪圆环病毒病及其他细菌病的混合感染较为普遍,这非常不利于猪瘟的防控和净化。另外。猪瘟的非典型性、隐性带毒、持续感染和免疫失败也是养猪生产中普遍存在的问题。
5.3 养猪从业人员素质和意识水平参差不齐
我国从事养猪产业的相关人员水平差别较大,大规模企业的人员素质较高,中小型规模以下养殖场的人员素质水平较低。散养户多以农户为主,文化水平低,效益差,对传染病的危害理解不到位,疫病防控意识淡薄且饲养管理能力低下。一旦有疫病暴发,很难有效控制,造成迅速流行。5.4 生物安全防控水平低
生物安全防控系统是控制动物疫病的最主要防线。我国中小型养猪企业,特别是散养户,几乎没有严格的隔离措施和消毒设施,很难抵抗疫病的侵袭。另外,动物调运管理、疫苗质量监管、疫苗审批制度等也严重影响着我国猪瘟的净化。6 中国猪瘟净化的思路
党的第十九次全国代表大会明确指出,我国已经进入了中国特色社会主义新时代。“两个一百年”奋斗目标与“中国梦”一起成为引领中国前行的时代号召。十九大报告已清晰擘画出全面建成社会主义现代化强国的时间表、路线图。在把我国建成富强、民主、文明、和谐、美丽的社会主义现代化强国的征程上,动物疫病的防控对我国畜牧业的发展起着非常关键的作用。因此,我们要以新时代中国特色社会主义思想为指导,将我国猪瘟净化的使命投映到“两个一百年”奋斗目标的坐标系中。在猪瘟的防控和净化上,我们同样牢固树立并切实贯彻“创新、协调、绿色、开放、共享”的发展理念,走中国特色的猪瘟净化之路。
6.1 中国猪瘟净化策略与模式
猪瘟净化具有重大意义,这是国家战略需求、产业需要,是大势所趋、势在必行。我国猪瘟净化过程有别于其他国家,猪瘟标记疫苗及相应配套的鉴别诊断技术对我国猪瘟的净化十分必要。净化前期还会大规模、高密度地使用猪瘟兔化弱毒疫苗,配合完善的生物安全防控措施,在提高养殖人员对猪瘟等猪病防控意识的前提下,将猪瘟的感染率及流行率控制在一定范围之内。随后要逐步使用猪瘟标记疫苗及配套的鉴别诊断方法,结合淘汰措施,逐渐达到猪瘟的净化。对我国来说,猪瘟净化状态的维持相当重要,相应的监测手段、方法、方案、措施等要进行充分地优化。6.2 中国猪瘟净化策略与方案
我国猪瘟净化的策略及方案要结合我国国情、养殖模式、养猪规模等,在借鉴欧美猪瘟净化经验的基础上,走中国特色的猪瘟净化之路。按照准备阶段→控制阶段→强制净化阶段→监测阶段→认证阶段程序,通过对猪瘟快速诊断试剂盒、疫苗毒株和致病毒株鉴别诊断方法的筛选和整合,免疫程序的调整,生物安全措施的综合实施,进行我国猪瘟的净化。6.2.1 基于C株疫苗的猪瘟净化
（1）疫苗的筛选：检验疫苗含量是否足够?有无牛病毒性腹泻病毒（BVDV）污染?接种后是否有异常反应?
（2）抗体监测：猪瘟疫苗免疫后不同时间点采血分离血清,检测猪瘟特异性抗体,根据血清学检测结果,将猪群进行分群,对抗体水平低和阴性的猪群加强免疫,抗体阳转则将其转入相应的抗体阳性群;淘汰抗体水平依然不合格的猪只。
（3）种猪筛查：在种猪群免疫时,对整个种猪群进行活体采集扁桃体或抗凝血样,然后应用荧光定量RT-PCR、RT-PCR或荧光抗体染色法对种猪和后备种猪进行猪瘟病毒野毒的检测。其中,抗原阳性的猪,需用另一种方法复核,如仍为阳性则淘汰。同时对血清样品进行抗体检测,阴性者需再次免疫。
（4）再次免疫：对于抗体为阴性的猪,接种猪瘟疫苗,3周后应用间接ELISA或阻断ELISA检测抗体,抗体仍为阴性者,坚决淘汰。
（5）重复上述程序：每半年或一年1次,3—4个循环。
当猪群抗原阳性率逐步下降,抗体合格率逐步提高后,对母猪开展抽查,商品猪的抽查比例可以逐步降低（1‰—5‰）。
（6）巩固和维持：逐步净化猪瘟,建立清净猪群。
6.2.2 基于标记疫苗的猪瘟净化
对于种猪群,最好使用标记疫苗和配套鉴别诊断进行猪瘟净化[32]。
（1）首先应用猪瘟标记疫苗对猪群进行全群免疫;
（2）应用配套的鉴别诊断方法（如Erns抗体检测试剂盒）对猪群进行抗体检测;
（3）剔除Erns抗体为阳性的猪;
（4）Erns抗体为阴性的猪,再用E2抗体检测试剂盒进行检测,E2抗体为阴性,则需要再次免疫,如果仍为阴性则淘汰;
（5）Erns抗体为阴性,E2抗体为阳性的猪,则需要用抗原检测方法进行验证,结果为阳性的直接淘汰,阴性的留为种用。
应用猪瘟标记疫苗进行猪瘟净化的流程见图1。
图1
新窗口打开|下载原图ZIP|生成PPT图1应用标记疫苗净化猪瘟示意图
Fig. 1Diagram of classical swine fever eradication by using marker vaccines
7 结语与展望
我国是世界第一养猪大国,但不是养猪强国,在畜牧业发展和动物疫病防控上,我国要体现大国的责任和担当,特别是在猪瘟净化上,我们不能无所作为,更不能把它带入下一个世纪,贻害子孙后代。猪瘟是危害养猪业的重大疫病。我国曾经研制出非常优秀的猪瘟兔化弱毒疫苗C株,该疫苗也为世界范围内许多国家猪瘟的净化做出了巨大贡献[29]。我们也憧憬有朝一日将我国猪瘟净化。我国猪瘟的净化需要多方的参与和协作,包括政府机构、养猪业者、科研机构、生物制品企业、兽医部门等,他们要在猪瘟净化的过程中各司其职,发挥各自的作用。政府机构颁布相应的政策、法规,建立市场准入机制,完善动物调运管理和疫苗质量监管、疫苗审批制度;养猪业者需提高生物安全意识、完善疫病防控措施,建立科学、合理的饲养管理模式;科研机构要投入大量的人力和物力进行相应疫苗、药物、诊断技术的研发和研制;同时对该病防控技术及知识进行普及和宣传;生物制品厂也要发挥作用,以生产和销售合格的生物制品为首要任务;兽医部门也要在疫病防控、技术指导和示范上发挥主体作用。
猪瘟仍然是当前制约我国养猪业发展的主要疫病,是当前规模化猪场必须面对和重点防控的疫病之一,但是只要从源头入手,抓好种猪群和后备猪群的猪瘟净化,就能切断猪瘟在猪场的循环链,结合科学合理的生物安全管理措施,我国定能实现猪瘟的净化。从历史必然性、战略必要性、现实可能性、技术可行性上分析,我们坚信,在多方的共同努力下,中国的猪瘟净化之路并不遥远。
参考文献 原文顺序
文献年度倒序
文中引用次数倒序
被引期刊影响因子
DOI:10.1016/S0378-1135(00)00137-1URLPMID:10785320 [本文引用: 1]
Classical swine fever virus is a spherical enveloped particle of about 40 60 nm in diameter with a single stranded RNA genome of about 12,300 bases with positive polarity, classified as a pestivirus within the family Flaviviridae. Natural hosts are domestic and wild pigs. The virus causes one of the most severe diseases in pigs world wide with grave economic consequences. The clinical picture of classical swine fever is variable, depending on the age of the affected animals and viral virulence. The virus is well characterised and reliable laboratory diagnostic procedures are available. In many parts of the world live attenuated vaccines are being used as a safe and efficient prophylactic tool. However, in EU Member States and several other countries vaccination is prohibited and CSF is controlled by a strict stamping out policy. In order to overcome the disadvantages of conventional vaccination inactivated marker vaccines have been developed that enable the distinction between vaccinated and infected animals. Whether these vaccines will be accepted as an additional tool in the framework of the stamping out policy is not yet decided.
DOI:10.1016/S0378-1135(00)00138-3URLPMID:10785321 [本文引用: 2]
A historical and current perspective is given of classical swine fever and its impact on pig production in different regions of the world. Data were obtained from a variety of sources including returns to the Office International des Epizooties, official government reports, other published material and local information through personal contacts. The disease has been recognized for about 170 years and efforts to control it by official intervention began in the nineteenth century. Despite this it remains a lingering problem in many parts of the world where it has both, an economic impact on swine production and a constraining effect on trade due to the measures necessary to prevent spread.
DOI:10.1016/S1090-0233(02)00112-0URLPMID:12618065 [本文引用: 2]
Although classical swine fever (CSF) has been well known for decades and epidemics still occur, clinical diagnosis continues to cause problems for veterinary practitioners. This is due to the extensive differential diagnosis, further complicated by the emergence of new diseases such as porcine reproductive and respiratory syndrome (PRRS) and porcine dermatitis and nephropathy syndrome (PDNS). In addition, acute, chronic and prenatal courses of CSF have to be distinguished. As a cause of considerable economical losses within the EU, control of CSF requires knowledge of the primary outbreaks and spread of the disease. Genetic typing of CSF virus isolates has proved to be a potent method of supporting epidemiological investigations. Phylogenetic analysis of CSF virus strains and isolates originating from different continents has allowed three genetic groups and several subgroups within these groups to be distinguished. Whereas isolates belonging to group 3 seem to occur solely in Asia, all CSF virus isolates of the 1990s isolated in the EU belonged to one of the subgroups within group 2 (2.1, 2.2, or 2.3) and were clearly distinct from former CSF reference viruses, which belong to group 1. Within the EU, different strategies are followed for the eradication of CSF in domestic pigs and in wild boar. While a strict non-vaccination policy is followed for domestic pigs, eradication of the disease in wild boar is more complex, and oral immunisation together with special hunting strategies have been applied. Recently, marker vaccines with a companion discriminatory test designed to allow differentiation between vaccinated animals and animals having recovered from field virus infection have been developed. Preliminary studies indicated that the discriminatory tests had a reduced sensitivity and specificity. Further improvements are therefore necessary before marker vaccines can be considered for emergency use in EU Member States. Prevention of CSF remains the main objective within the EU.
DOI:10.3321/j.issn:0578-1752.2005.08.026URLMagsci [本文引用: 1]
猪瘟是一种严重危害养猪业的毁灭性传染病。20世纪50年代中国首创了举世闻名的猪瘟兔化弱毒疫苗（即C株），随后创制了不同的疫苗制造工艺，如细胞培养苗、乳兔组织苗和牛体反应组织苗等。C株是一株非常安全的弱毒疫苗，对各种年龄和品种的猪都没有副作用，并且有良好的免疫效力，它能同时诱导体液免疫和细胞免疫应答，对不同基因型的猪瘟病毒株均能提供有效的免疫保护。免疫母猪通过母乳可对仔猪提供被动免疫保护，但过高水平的母源抗体会影响仔猪对C株疫苗的主动免疫应答。目前已经完成了包括C株及其亲本株在内的几十株猪瘟病毒的全基因组序列测定和注释，建立了猪瘟病毒的反向遗传操作系统，初步解析了猪瘟病毒主要基因的结构与功能，并构建了不同的反向遗传操作标记疫苗，赋予了C株疫苗新的生命和内涵。C株疫苗可以用于猪瘟的控制和根除，借助于C株疫苗密集接种和综合控制措施，有关国家有效地控制了猪瘟，甚至消灭了猪瘟。尽管如此，要在全球范围内根除猪瘟，今后依然有漫长的路要走，这可能有赖于对C株进行进一步改造和利用。
DOI:10.3321/j.issn:0578-1752.2005.08.026URLMagsci [本文引用: 1]
猪瘟是一种严重危害养猪业的毁灭性传染病。20世纪50年代中国首创了举世闻名的猪瘟兔化弱毒疫苗（即C株），随后创制了不同的疫苗制造工艺，如细胞培养苗、乳兔组织苗和牛体反应组织苗等。C株是一株非常安全的弱毒疫苗，对各种年龄和品种的猪都没有副作用，并且有良好的免疫效力，它能同时诱导体液免疫和细胞免疫应答，对不同基因型的猪瘟病毒株均能提供有效的免疫保护。免疫母猪通过母乳可对仔猪提供被动免疫保护，但过高水平的母源抗体会影响仔猪对C株疫苗的主动免疫应答。目前已经完成了包括C株及其亲本株在内的几十株猪瘟病毒的全基因组序列测定和注释，建立了猪瘟病毒的反向遗传操作系统，初步解析了猪瘟病毒主要基因的结构与功能，并构建了不同的反向遗传操作标记疫苗，赋予了C株疫苗新的生命和内涵。C株疫苗可以用于猪瘟的控制和根除，借助于C株疫苗密集接种和综合控制措施，有关国家有效地控制了猪瘟，甚至消灭了猪瘟。尽管如此，要在全球范围内根除猪瘟，今后依然有漫长的路要走，这可能有赖于对C株进行进一步改造和利用。
DOI:10.1038/s41598-017-18196-yURLPMID:5738429 [本文引用: 1]
Classical swine fever (CSF) is one of the most important infectious diseases causing significant economic losses. Its causal agent, CSF virus (CSFV), is a member of thePestivirusgenus included into theFlaviviridaefamily. Previous molecular epidemiology studies have revealed the CSFV diversity is divided into three main genotypes and different subgenotypes. However, the classification system for CSFV has not yet been harmonized internationally. Similarly, the phylogeny and evolutionary dynamics of CSFV remain unclear. The current study provides novel and significant insights into the origin, diversification and evolutionary process of CSFV. In addition, the best phylogenetic marker for CSFV capable of reproducing the same phylogenetic and evolutionary information as the complete viral genome is characterized. Also, a reliable cut-off to accurately classify CSFV at genotype and subgenotype levels is established. Based on the time for the most recent common ancestor (tMRCA) reconstruction and cophylogenetic analysis, it was determined that CSFV emerged around 225 years ago when the Tunisian Sheep Virus jumped from its natural host to swine. CSFV emergence was followed by a genetic expansion in three main lineages, driven by the action of positive selection pressure and functional divergence, as main natural forces.
DOI:10.2376/0005-9366-126-468URLPMID:24511821 [本文引用: 1]
Classical swine fever (CSF) is considered to be one of the most important viral diseases in pigs worldwide. In many parts of the world great efforts are being undertaken to reduce economic losses caused by CSF or to eradicate the disease. Among the member states of the European Union (EU) a harmonized strategy for diagnosis, control and eradication of CSF is applied. Success of the common strategy is documented by the decreasing number of outbreaks during the last decade. The present article summarizes the recent situation concerning CSF in Europe with special focus on the situation in the EU member states. In particular, outbreaks in domestic pigs and wild boar, the identified virus isolates, and eradication and monitoring programs actually performed in the EU are described. Despite achieved progress towards eradication, CSF remains a continuous threat to the European pig and wild boar population. After introduction of CSF virus (CSFV) into the domestic pig population rapid spread as a consequence of high frequency of animal movements and intensive trade within Europe can be suspected. Platforms like the CSF sequence database and the CSF in wild boar surveillance database have been implemented as tools to easily exchange information concerning CSF. The improved availability of data about circulating CSFV isolates will help to elucidate possible sources of virus introduction and to better understand routes of virus transmission.
DOI:10.1017/S1466252315000109URLPMID:26050570 [本文引用: 3]
Classical swine fever is a highly contagious disease that affects domestic and wild pigs worldwide. The causative agent of the disease is Classical swine fever virus (CSFV), which belongs to the genusPestiviruswithin the familyFlaviviridae. On the genome level, CSFV can be divided into three genotypes with three to four sub-genotypes. Those genotypes can be assigned to distinct geographical regions. Knowledge about CSFV diversity and distribution is important for the understanding of disease dynamics and evolution, and can thus help to design optimized control strategies. For this reason, the geographical pattern of CSFV diversity and distribution are outlined in the presented review. Moreover, current knowledge with regard to genetic virulence markers or determinants and the role of the quasispecies composition is discussed.
URL [本文引用: 1]
Abstract Classical swine fever (CSF) represents a major health and trade problem for the pig industry. In endemic countries or those with a wild boar reservoir, CSF remains a priority for Veterinary Services. Surveillance as well as stamping out and/or vaccination are the principle tools of prevention and control, depending on the context. In the past decades, marker vaccines and accompanying diagnostic tests allowing the discrimination of infected from vaccinated animals have been developed. In the European Union, an E2 subunit and a chimeric live vaccine have been licensed and are available for the use in future disease outbreak scenarios. The implementation of commonly accepted and globally harmonized concepts could pave the way to replace the ethically questionable stamping out policy by a vaccination-to-live strategy and thereby avoid culling of a large number of healthy animals and save food resources. Although a number of vaccines and diagnostic tests are available worldwide, technological advancement in both domains is desirable. This work provides a summary of an analysis undertaken by the DISCONTOOLS group of experts on CSF. Details of the analysis can be downloaded from the web site at http://www.discontools.eu/.
DOI:10.3321/j.issn:0578-1752.2003.08.017URLMagsci [本文引用: 1]
猪瘟 (classicalswinefever,CSF)仍然是严重危害全球养猪业的重要传染病 ,是我国主要的畜禽疫病之一。目前该病流行于除北美和大洋洲外的世界上各大洲和地区。笔者分析了当前国际上猪瘟的流行态势与流行原因 ,并在此基础上结合我国养猪业的发展现状 ,根据自身多年的研究结果 ,用可靠的试验数据 ,着重阐述了我国猪瘟的流行现状与分子流行病学本底 ,就此提出了一些新的防制对策 ,供同行商榷。
DOI:10.3321/j.issn:0578-1752.2003.08.017URLMagsci [本文引用: 1]
猪瘟 (classicalswinefever,CSF)仍然是严重危害全球养猪业的重要传染病 ,是我国主要的畜禽疫病之一。目前该病流行于除北美和大洋洲外的世界上各大洲和地区。笔者分析了当前国际上猪瘟的流行态势与流行原因 ,并在此基础上结合我国养猪业的发展现状 ,根据自身多年的研究结果 ,用可靠的试验数据 ,着重阐述了我国猪瘟的流行现状与分子流行病学本底 ,就此提出了一些新的防制对策 ,供同行商榷。
URL [本文引用: 1]
DOI:10.1016/S0378-1135(00)00141-3URLPMID:10785324 [本文引用: 1]
Three regions of the classical swine fever virus (CSFV) genome that have been widely sequenced were compared with respect to their ability to discriminate between isolates and to segregate viruses into genetic groups. Sequence data-sets were assembled for 55 CSFVs comprising 150 nucleotides of the 5 non-translated region, 190 nucleotides of the E2 envelope glycoprotein gene and 409 nucleotides of the NS5B polymerase gene. Phylogenetic analysis of each data-set revealed similar groups and subgroups. For closely related viruses, the more variable or larger data-sets gave better discrimination, and the most reliable classification was obtained with sequence data from the NS5B region. No evidence was found for intertypic recombination between CSFVs. A larger data-set was also analysed comprising 190 nucleotides of E2 sequence from 100 CSFVs from different parts of the world, in order to assess the extent and global distribution of CSFV diversity. Additional groups of CSFV are evident from Asia and the nomenclature of Lowings et al. (1996) [Lowings, P., Ibata, G., Needham, J., Paton, D., 1996. J. Gen. Virol. 77, 1311 1321] needs to be updated to accommodate these. A tentative assignment, adapting rather than overturning the previous nomenclature divides CSF viruses into three groups with three or four subgroups: 1.1, 1.2, 1.3; 2.1, 2.2, 2.3; 3.1, 3.2, 3.3, 3.4. The expanding data-base of CSFV sequences should improve the prospects of disease tracing in the future, and provide a basis for a standardised approach to ensure that results from different laboratories are comparable.
DOI:10.1007/s11262-005-3253-0URLPMID:16175340
The 5' non-coding region (5'-NCR) of 27 classical swine fever virus (CSFV) isolates from Lao People's Democratic Republic (Lao PDR) during 1997 and 1999 were amplified by RT-PCR. A 150-bp region of the 5'-NCR amplicons was analysed and compared with reference CSFV of European and Asian origin and a phylogenetic dendrogram constructed. Following analysis, all viruses were determined to belong to genogroup 2. Viruses from Lao PDR grouped on a geographical basis with the majority of northern/central isolates falling into subgroup 2.1 and southern/central isolates falling into subgroup 2.2. These results concur with previous studies of CSF viruses from Lao PDR, although this study recognized the first occurrence of subgroup 2.1 in southern Lao PDR.
DOI:10.1007/s11262-005-0048-2URLPMID:16972026
The genome of a novel classical swine fever virus (CSFV), SWH/CA/2004, isolated from a hog pen in Henan Province, central China, is 12296 nucleotides (nt) in length. It is composed of a 373-nt 5′ terminal non-translated region (NTR), a 11697-nt open reading frame (ORF) encoding a polyprotein of 3898 amino acids (aa), and a 226-nt 3′-NTR. Genome comparison of the SWH/CA/2004 isolate (GenBank Accession: DQ127910) with other known CSFV isolates was performed and analyzed. Corresponding segments from SWH/CA/2004 and other reported strains shared 80.4–99.8% identity at the nucleotide level and 89.5–99.8% identity at the amino acid level. From an evolutionary point of view, isolate SWH/CA/2004 is closely related to the highly virulent isolate cF114/CA/2001, with a pairwise distance of 0.013; and distantly related to the moderately virulent isolate GXWZ02/CA/2003, with pairwise distance 0.170. The phylogenetic trees of the full-length genome and the following region E rns , E1, E2, and NS5B-based neighbor-joining (NJ) method were constructed and approximately divided into different genetic groups according to avirulence, moderate virulence and high virulence, while other region-based NJ trees demonstrated sequence conservation between these groups. The four genomic regions may constitute important criteria for genetic typing of diverse CSFV isolates. Based on these analyses, isolate SWH/CA/2004 was deduced to belong to the highly virulent isolate group. However, SWH/CA/2004 also contains a 14-U deletion in the 3′-NTR that is characteristic of avirulent isolates. These analyses constitute a comprehensive study of the phylogenetics of CSF based on distinct regions of the genome and may provide the basis for future molecular epidemiology research to identify virulent strain outbreaks and trigger implementation of appropriate control measures.
DOI:10.1186/1297-9716-43-50URLPMID:22676246
pAbstract/p pMolecular epidemiology has proven to be an essential tool in the control of classical swine fever (CSF) and its use has significantly increased during the past two decades. Phylogenetic analysis is a prerequisite for virus tracing and thus allows implementing more effective control measures. So far, fragments of the 507NTR (150 nucleotides, nt) and the E2 gene (190 nt) have frequently been used for phylogenetic analyses. The short sequence lengths represent a limiting factor for differentiation of closely related isolates and also for confidence levels of proposed CSFV groups and subgroups. In this study, we used a set of 33 CSFV isolates in order to determine the nucleotide sequences of a 3508–3510 nt region within the 507 terminal third of the viral genome. Including 22 additional sequences from GenBank database different regions of the genome, comprising the formerly used short 507NTR and E2 fragments as well as the genomic regions encoding the individual viral proteins Nsuppro/sup, C, Esuprns/sup, E1, and E2, were compared with respect to variability and suitability for phylogenetic analysis. Full-length E2 encoding sequences (1119 nt) proved to be most suitable for reliable and statistically significant phylogeny and analyses revealed results as good as obtained with the much longer entire 507NTR-E2 sequences. This strategy is therefore recommended by the EU and OIE Reference Laboratory for CSF as it provides a solid and improved basis for CSFV molecular epidemiology. Finally, the power of this method is illustrated by the phylogenetic analysis of closely related CSFV isolates from a recent outbreak in Lithuania./p
DOI:10.1016/j.vetmic.2012.07.045URLPMID:22902191 [本文引用: 2]
Identification and classification of classical swine fever virus (CSFV) on the basis of nucleotide sequencing and phylogenetic analysis have become an important tool to study the epidemiology and to control CSF disease. According to phylogenetic analyses of short sequences from the 5 ontranslated region (150nt) and the E2 (190nt), most CSFV isolates from South and Central America have been assorted to the subgenotypes 1.1 and 1.3, while CSFV isolates from Cuba have been allocated to subgenotype 1.2. Here we demonstrate that determination and comparison of full-length E2 sequences as well as of the sequences encoding for Npro, C, Erns, E1 and E2 (3361nt) do not support segregation of Cuban CSFV isolates to subgenotype 1.2. In fact, our analysis revealed that the Cuban isolates are more divergent from other so far known CSFV subgenotype 1 isolates and form a novel separate subgenotype that is proposed to be designated subgenotype 1.4.
DOI:10.1016/j.vetmic.2017.01.012URL
Classical swine fever(CSF) is a devastating infectious disease of pigs caused by classical swi ne fever virus(CSFV).The disease has been controlled following extensive vaccination with the 1 apinized attenuated vaccine C-strain for decades in China.However,frequent CSF outbreaks occurr ed recently in a large number of C-strain-vaccinated pig farms in China and a new subgenotype 2.1 d of CSFV has been reported to be responsible for the outbreaks.Here we analyzed the molecul ar variations and antigenic differences among the C-strain-based commercial vaccines of different o rigins from different manufacturers in China,and reevaluated the vaccines against the emerging su bgenotype 2.1 d strain of CSFV.The results showed that the C-strain adapted to the continuous ST cell line(C_(ST)) contain a unique M290 K variation on the E2 protein,compared to those of prima ry BT cells(C_(BT)) or rabbit origin(C_(BT)) and the traditional C-strain sequences available in the Ge nBank database.Serum neutralization test revealed the antigenic differences between Cst and Cbt or C_(RT).Notably,the neutralizing titers of porcine anti-C-strain sera against the CSFV isolate of su bgenotype 2.1 d were significantly lower than those against C-strain or Shimen strain.The C-strainvaccinated,subgenotype 2.1 d HLJZZ2014 strain-challenged pigs did not show any clinical signs an d all survived.However,these pigs displayed mild pathological and histological lesions,and the C SFV viral RNA was detected in the various tissue and blood samples.Taken together,the C-strain-based vaccines of different origins showed molecular variations and antigenic differences,and cou1 d provide clinical but not pathological and virological protection against the subgenotype 2.1 d CS FV emerging in China.Further investigation is needed to comprehensively assess the efficacy of C-strain of different doses against the subgenotype 2.1 d CSFV.
DOI:10.1016/j.vetmic.2014.04.004URLPMID:24793098
Classical swine fever (CSF), caused by Classical swine fever virus (CSFV), is an OIE-listed, highly contagious, often fatal disease of swine worldwide. Currently, the disease is controlled by prophylactic vaccination in China and many other countries using the modified live vaccines derived from C-strain, which was developed in China in the mid-1950s. This minireview summarizes the epidemiology, diagnostic assays, control and challenges of CSF in China. Though CSF is essentially under control, complete eradication of CSF in China remains a challenging task and needs long-term, joint efforts of stakeholders.
DOI:10.1016/j.jviromet.2015.08.012URLPMID:26300371
Discrimination between different field and vaccine strains of classical swine fever virus (CSFV) is crucial for meaningful disease diagnosis and epidemiological investigation. In this study, a rapid method for differentiating vaccine strains and outbreak CSFV isolates by combined RT-PCR and high-resolution melt (HRM) analysis has been developed. The assay is based on PCR amplification of short fragments from the most variable region of CSFVgene E2, followed by HRM analysis of amplicons. RT-PCR/HRM for CSFV detection and differentiation analysis has sensitivity comparable to RT-qPCR and genotyping resolution comparable to E2 nucleotide sequencing. This assay in one step enables rapid and sensitive identification and genotype discrimination of CSFV in field samples, and thus will be valuable for CSF outbreak response and disease control.
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DOI:10.1016/j.meegid.2016.04.002URLPMID:27085291
61Genetic diversity of current CSFV subgenotype 2.1 isolates in the world was revealed in this study, which were divided into 10 sub-subgenotypes (2.1a-2.1j).61Sub-subgenotypes 2.1d-2.1j were newly classified.61The newly classified 2.1 sub-subgenotypes were further categorized into three groups: dominant sub-subgenotype (2.1b, 2.1c, 2.1h, 2.1i, and 2.1j), minor sub-subgenotype (2.1d and 2.1g) and silent sub-subgenotype (2.1a, 2.1e, and 2.1f).61Sub-subgenotype 2.1b plays a dominant role in CSF epidemics in China.
DOI:10.1016/j.meegid.2015.05.031URLPMID:26031602 [本文引用: 1]
The lapinized attenuated vaccine against classical swine fever (CSF) has been used in China for over half a century and has generally prevented large-scale outbreaks in recent years. However, since late 2014, a large number of new cases of CSF were detected in many immunized pig farms in China. Several of these CSV viruses were isolated and characterized. Phylogenetic and genomic sequence analyses indicate that these new isolates, as well as some reference isolates, form a new subgenotype named 2.1d, and share several consistent molecular characteristics. Since these new isolates emerged in disparate geographic regions within 5months, this suggests that these isolates may be widespread. Given that current vaccines do not appear to provide effective protection against this new subgenotype, further investigation of these strains is urgently needed.
DOI:10.1016/j.jviromet.2004.03.010URLPMID:15158595 [本文引用: 1]
The diagnostic properties of several assays on live animals were studied using data from different experiments. These experiments involved 128 classical swine fever virus (CSFV) infected pigs (weaner pigs, fatteners and sows). Since all pigs in the study were infected with CSFV, only the proportion of test positive results and the time until a test positive result is obtained were evaluated. The RT-nPCR detected the highest proportion of infected pigs (98.9%), whereas the Antigen ELISA gave the worst detection results (74.7%). Within the group of test positive animals, infection was detected earliest using the leukocyte count and latest using Antigen ELISA. Using the virus neutralisation test, antibodies against CSFV were detectable on average 7.6 days after the onset of viraemia in virus isolation in whole blood. Using survival analysis, the time until the first positive diagnosis and the proportion of detected animals were combined in one test. Results showed that RT-nPCR performed significantly better than either virus isolation in different blood fractions or antigen ELISA. It is concluded that the RT-nPCR technique is the best diagnostic tool available for early detection of a classical swine fever infection.
DOI:10.1371/journal.pone.0125692URLPMID:25938664 [本文引用: 1]
Abstract It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN- -producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN- producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed. In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence.
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DOI:10.1016/j.vaccine.2006.07.033URLPMID:16934915 [本文引用: 1]
Classical swine fever (CSF) is an economically important highly contagious disease of swine worldwide. Classical swine fever virus (CSFV) is its etiological agent, and the only natural hosts are domestic pigs and wild boars. Although field CSFV strains vary in the virulence, they all result in serious losses in pig industry. Highly virulent field strains generally cause acute disease and high mortality; moderately virulent field strains raise subacute or chronic infections; postnatal infection by low virulent field strains produces subclinical infection and mortality in the new-born piglets. CSFV can cross the placental barrier, and this transplacental transmission usually results in mortality of fetuses and birth of congenitally infected pigs with a late-onset disease and death. Two main strategies to control CSF epidemic are systematic prophylactic vaccination with live attenuated vaccines (such as C-strain) and non-vaccination stamping-out policy. But neither of them is satisfying enough. Marker vaccine and companion serological diagnostic test is thought to be a promising strategy for future control and eradication of CSF. During the past 15 years, various candidate marker vaccines were constructed and evaluated in the animal experiments, including recombinant chimeric vaccines, recombinant deletion vaccines, DNA vaccines, subunit vaccines and peptide vaccines. Among them, two subunit vaccines entered the large scale marker vaccine trial of EU in 1999. Although they failed to fulfil all the demands of the Scientific Veterinary Committee, they successfully induced solid immunity against CSFV in the vaccinated pigs. It can be expected that new potent marker vaccines might be commercially available and used in systematic prophylactic vaccination campaign or emergency vaccination in the next 15 years. Here, we summarized current strategies and candidate CSFV marker vaccines. These strategies and methods are also helpful for the development of new-generation vaccines against other diseases.
DOI:10.1016/j.vetmic.2009.09.042URLPMID:19892497 [本文引用: 1]
A new chimeric pestivirus P7_E1E2alf_TLA , based on the infectious cDNA of bovine viral diarrhea virus (BVDV) strain CP7, was constructed. The substitution of BVDV E1 and E2 with the respective proteins of classical swine fever (CSF) strain Alfort 187 allows an optimal heterodimerization of E1 and E2 in the chimeric virus, which is beneficial for efficient and authentic virus assembly and growth. In addition, for implementation of E2-based marker diagnostics, the previously described antigenic CSFV-specific TAVSPTTLR epitope was exchanged with the corresponding E2-epitope of BVDV strain CP7. Recombinant virus CP7_E1E2alf_TLA displayed a growth defect, and was not reacting with monoclonal antibodies used in commercial E2 antibody blocking ELISAs. Therefore, efficacy as well as marker properties of CP7_E1E2alf_TLA were investigated in an animal experiment with both a high dose and a low dose vaccine preparation. All CP7_E1E2alf_TLA-vaccinated animals seroconverted until day 28 post-vaccination with neutralizing antibodies. Furthermore, at the day of challenge infection CP7_E1E2alf_TLA-immunized animals showed distinct lower ELISA values in a commercial CSFV E2 antibody test in comparison to the C-strain vaccinated controls. However, E2-ELISA reactivity as well as neutralizing titers were directly connected to the dosage used for vaccination, and only the low dose group had E2-ELISA values below threshold until challenge infection. Following challenge infection with highly virulent CSFV strain Koslov, all vaccinees were protected, however, short-term fever episodes and very limited CSFV genome detection with very low copy numbers could be observed. In conclusion, manipulation of the TAVSPTTLR-epitope within the tested chimeric virus resulted in an slightly reduced efficacy, but the E2 marker properties unexpectedly did not allow a clear differentiation of infected from vaccinated animals in some cases.
DOI:10.1016/j.virol.2014.09.021URLPMID:25461526 [本文引用: 1]
61Stabilization of a vaccine candidate for CSFV by increasing codon distance to revertant residues.61Development of a genetically stable marker vaccine for Classical Swine Fever Virus.61Nucleotide substitution to increase genetic stability against revertant virus.
DOI:10.20506/rst.18.3.1192URLPMID:10588007 [本文引用: 3]
Classical swine fever (CSF) (hog cholera) virus infection is still of world-wide concern, either because of the direct effects of the disease on swine breeding in areas where the virus is epizootic or enzootic, or as a threat in areas where the virus has been eradicated. The authors provide an overview of the characteristics of the disease. Special emphasis is placed on the chronic form of disease, particularly in the late stages of eradication programmes. In the early 1980s, the European Union (EU) was composed of countries which were officially free of the disease (absence of infection and no vaccination) and countries in which vaccination was either permitted or was compulsory. To ensure free trade between the Member States, an eradication plan was agreed upon and implemented. Initially, the plan consisted of a combination of vaccination with the Chinese strain of the virus and slaughter and removal of infected herds. Consequently, when the number of infected herds was low, vaccination was abandoned and the control of CSF was conducted exclusively by eradication (removal and slaughter). The United Kingdom, Austria, Denmark, Ireland, Luxembourg, Finland and Sweden ceased vaccination before 1980. In the other countries, vaccination was useful in controlling the last epidemics and was finally ceased as follows: France in 1983, the Netherlands in 1986, Belgium, Spain and Greece in 1988, Germany in 1989 and Italy in 1990. From 1990 onwards, no vaccination against CSF has been performed in the EU. New techniques for the diagnosis of CSF (for example, the enzyme-linked immunosorbent assay based on the detection of the p125 antigen of the virus) have been shown to be of value in the early detection of infected animals. In enzootic areas, the use of vaccines based on the Chinese strain has been successful. Vaccines with at least 100 PD50 of virus per dose are able to significantly limit the replication of virulent virus in the tonsils. Consequently, shedding of virus after infection can be reduced considerably. In heavily infected areas, vaccination plays a crucial role. The European experience shows that eradication may be achieved when vaccination with highly effective vaccines is combined with effective identification of swine, movement control, early diagnosis and the rapid elimination of infected herds.
DOI:10.1080/01652176.2004.9695177URLPMID:15663211 [本文引用: 2]
Classical swine fever (CSF) is one of the most important viral pig diseases. Basic measures to control epidemics of CSF comprise eradication of infected herds and preventive emptying of herds at risk. Identification of these herds at risk is based on knowledge of the different transmission routes of the virus. Direct transmission of CSF is undoubtedly the most efficient way of CSF virus transmission. Data on indirect transmission are variable and often equivocal. Various indirect transmission routes like swill feeding, wild boar and artificial insemination are well described, and the importance is beyond discussion. Mechanical transmission via vehicles and persons are categorized as very important based upon epidemiological research, whereas in experiments they can only be reproduced under worst case conditions. The role of arthropods, birds, rodents, and other animals in the spread of CSF virus remains doubtful. Active transmission by these has never been demonstrated and also very sparse indications for mechanical transmission are available. Also the role of airborne transmission remains debated. However epidemiological as well as experimental data indicate that airborne spread over short distances is probable.
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正2016年,乃中国养猪业丰收的一年,持续的能繁母猪总量减少让不少专家预测最近两年将是养猪业较为赚钱的两年,站在阶段性胜利的舞台,笔者觉得我们应该更加理性地思考当前我国养猪业存在的问题,更加深入地思考与探讨养猪业未来的大趋势与新模式。首先,我国养猪业当前存在如下几个显著的问题:1)生猪价格波动大2013—2014年持续低迷的猪价加
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正2016年,乃中国养猪业丰收的一年,持续的能繁母猪总量减少让不少专家预测最近两年将是养猪业较为赚钱的两年,站在阶段性胜利的舞台,笔者觉得我们应该更加理性地思考当前我国养猪业存在的问题,更加深入地思考与探讨养猪业未来的大趋势与新模式。首先,我国养猪业当前存在如下几个显著的问题:1)生猪价格波动大2013—2014年持续低迷的猪价加
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DOI:10.1079/AHR200479URLPMID:15984335 [本文引用: 1]
The risk of foreign animal disease introduction continues to exist despite Canada's strict regulations concerning the importation of animals and animal products. Given the rapidity with which these diseases can spread, especially in areas with dense livestock populations, eradication efforts which rely solely on quarantine and stamping-out measures can present a formidable undertaking. This, combined with growing economic and ethical considerations, has led to renewed interest in the use of vaccination as a tool in controlling foreign animal disease outbreaks. Vaccination has effects at the individual and population levels. Efficacious vaccines reduce or prevent clinical signs without necessarily preventing virus replication. They may also increase the dose of virus needed to establish an infection and/or reduce the level and duration of virus shedding following infection. Vaccine effectiveness within a population is a function of its ability to reduce virus transmission. Transmission is best described by the reproductive ratio, R, which is defined as the average number of new infections caused by one infectious individual. By helping to reduce the R-value below 1, vaccination can be an effective adjunct in abbreviating an outbreak. Nevertheless, vaccination can also complicate serological surveillance activities that follow eradication, if the antibody response induced by vaccination is indistinguishable from that which follows infection. This disadvantage can be overcome by the use of DIVA vaccines and their companion diagnostic tests. The term DIVA (differentiating infected from vaccinated individuals) was coined in 1999 by J. T. van Oirschot of the Central Veterinary Institute, in the Netherlands. It is now generally used as an acronym for differentiating infected from vaccinated animals . The term was originally applied to the use of marker vaccines, which are based on deletion mutants of wild-type microbes, in conjunction with a differentiating diagnostic test. The DIVA strategy has been extended to include subunit and killed whole-virus vaccines. This system makes possible the mass vaccination of a susceptible animal population without compromising the serological identification of convalescent individuals. The DIVA approach has been applied successfully to pseudorabies and avian influenza eradication, and has been proposed for use in foot-and-mouth disease and classical swine fever eradication campaigns. This paper will survey current vaccine technology, the host immune response, and companion diagnostic tests that are available for pseudorabies, foot-and-mouth disease, classical swine fever and avian influenza.
