06-4. Respiratory disease 呼吸系统疾病及其它细菌性疾病– Swi.ppt

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1、Respiratory Disease Swine Influenza Virus 呼吸系统疾病猪流感病毒Bob Morrison DVM, MBA, PhDMarie Gramer, DVMKurt Rossow DVM, PhDEtiology 病原学nSIV used to be straightforward 猪流感过去被认为并不重要nSIV diagnostics and disease control has become more challenging after the introduction of new types 在新类型病毒被报道后，猪流感的诊断和控制变得更富挑战性

2、。 nType A Influenza virus belongs to the Orthomyxoviridae family. A型流感病毒属于整粘病毒科Enveloped, RNA virus 有囊膜、RNA病毒Lipid envelope 脂质囊膜Helical nucleocapsid. 螺旋状的病毒粒子Swine Influenza Virus Structure猪流感病毒结构Fields Virology, Fourth EditionRNA gene segments脂质双分子层神经氨酸酶血凝素M2离子通道M1基质蛋白感染细胞蛋白RNA基因片断核衣壳转录酶复合体2 struct

3、ural proteins present on the virus.病毒表面存在的两种结构蛋白nHemagglutinin (13 types) 血凝素（13种类型）responsible for the attachment of the virus to the host-cell and for fusion of the viral envelope to the host-cell membrane 负责病毒附着到宿主细胞和让病毒囊膜与宿主细胞膜融合Antibodies to the hemagglutinin are responsible for preventing infe

4、ction with an influenza virus containing the same hemagglutinin protein. 血凝素的抗体可以起到阻止包含有相同血凝素蛋白的流感病毒感染的作用。nNeuraminidase protein (9 types) 神经氨酸酶（9种类型）responsible for elution of virus from erythrocytes. It may play a role in the release of virus from infected cells. 负责病毒从红细胞上脱离。它可能在病毒从感染细胞上释放过程中起重要作用

5、antibodies against the neuraminidase restrict the spread of virus from infected cells. 神经氨酸酶的抗体限制了病毒由感染细胞的扩散。These 2 surface glycoproteins are the basis for naming subtypes这两种表面糖蛋白是命名亚型的基础nFour main subtypes in swine 感染猪的四个主要亚型Most common in US 在美国最常见的nH1N1, H3N2Also 以及nH1N2, H1N7 Viral Change/Evolu

6、tion 病毒的改变/进化H1N1 and H3N2nEmerged in 2000 出现于2000年n7 genes from the H3N2 viruses 7个基因来自H3N2病毒H1N1HAH3N2NAPAPB2H1N2H1N1HANAH3N2PAPB2H1N1nEmerged in 2002 出现于2002年nSurface of the H1N1 viruses 表面蛋白来自H1N1病毒 nInternal gene components derived from the H3N2 viruses. 内部基因组件源于H3N2病毒Pathogenesis 发病机理nThe viru

7、s is inhaled and deposited on the surface of the lower respiratory tract. 病毒被吸入并沉积于下呼吸道表面。nIncubation period from 1 - 3 days. 潜伏期从1-3天不等。nWidespread interstitial pneumonia for up to 21 days after infection and hemorrhagic lymph nodes may be seen. 弥漫性间质性肺炎在感染后21天出现，也可能出现出血性淋巴结。 nUncomplicated infecti

8、ons have changes in the cranial ventral lung lobes. There is generally a sharp line of demarcation between normal and affected lung tissue. 单纯性感染时病变出现于肺的尖叶。一般在正常和病变肺组织间有明显的界线。nThe involved areas are often purple and firm. Some interlobular edema may also be evident. 感染病变区域常呈紫色硬结。一些小叶间质水肿明显。nThe airw

9、ays are likely to be filled with blood-tinged fibrinous exudate. Often the bronchial and mediastinal lymph nodes are enlarged. 通气道可能充满淡红色纤维素性渗出物。支气管和纵隔淋巴结常常肿大。Clinical signs 临床症状nVery fast spread and affects high prevalence - aerosol spread probably occurs 非常快速的传播和可能出现以高感染力气溶胶形式传播的情形nDyspnea, loud,

10、nonproductive cough (bark), 呼吸困难、大声的无痰干咳（吠咳）nNasal and eye discharge, 鼻和眼有分泌物流出nHigh fevers (42.0 C) with lethargy and anorexia. 伴有高热（ 42.0 C ）的嗜睡和食欲不振nMost pigs recover spontaneously and quickly, 大部分猪可以自然快速痊愈，nOften complicated by secondary infections 病情常因继发感染而变得复杂Lesions 病变Interstitial edema; wet

11、heavy Lung 肺脏间质水肿；湿润，重量增加Diagnosis 诊断nclinical signs with lung lesions, 临床症状及肺部病变nhistopathological confirmation of lesions, 通过组织病理学确认的病变npaired sera, and （取）成对血清（样品），nantigen detection 抗原检定Histopathology Necrotizing bronchiolitis. Airways filled with exudate. Widespread alveolar atelectasis, inters

12、titial pneumonia and emphysema. Peribronchial and perivascular cellular infiltration. 组织病理学坏死性细支气管炎。通气道充满渗出物。广泛的肺泡性肺不组织病理学坏死性细支气管炎。通气道充满渗出物。广泛的肺泡性肺不张、间质性肺炎和间质水肿。支气管周围和血管周围细胞浸润。张、间质性肺炎和间质水肿。支气管周围和血管周围细胞浸润。Severe necrotizing bronchiolitis in the lung of a pig with swine influenza infection 猪流感感染猪肺部严重的

13、坏死性猪流感感染猪肺部严重的坏死性细支气管炎细支气管炎Necrotizing bronchiolitis associated with antigen (brown staining).坏死性坏死性细支气管炎相关抗原（棕色染色细支气管炎相关抗原（棕色染色部位）部位）Diagnosis 诊断nVirus shedding is early and of relatively short duration 病毒扩散出现在疾病早期且其扩散持续的时间相对较短shedding is highest in the first few days of infection and is associated

14、 with fever 病毒扩散的高峰出现在感染的头几天而且与发热相关Pigs may develop a second febrile episode after the influenza infection due to secondary infections 猪在感染流感后由于继发感染可能出现第二发热期。Lung lesions may take 4 weeks to resolve 肺部病变可以持续4周才结束Samples for virus detection病毒检验的样品采集nSamples for collection 样品的收集Nasal swabs sample many

15、 pigs 鼻拭子在多头猪身上取样Lung early 肺病变早期Lung lavage acceptable sample, if the lavage is positive 肺部灌洗物如灌洗物是阳性的，灌洗物是可接受的样品nSend packed with plenty of refrigerant 样品和大量冷却剂一同打包邮寄Virus detection techniques病毒检验技术nPCR sensitive, specific, rapid, sample can also be used for subtyping or sequencing 聚合酶链式反应敏感、特异性、快

16、速，样品可被用于亚型确定或测序nVirus isolation sensitive ,specific, sample can be used for subtyping or sequencing 病毒分离敏感、特异性、快速，样品可被用于亚型确定或测序nImmunohistochemistry specific, “dead end” results 免疫组织化学特异性、“终端”结果nDirectigenR Flu A test DirectigenR 的A型流感检测 nHistopathology 组织病理学Serology 血清学nHI test 血凝抑制实验pigs seroconve

17、rt approximately 3 weeks post infection. Detection of antibody and the resultant titer may depend on the virus used in the test. 猪血清学变化出现在感染后约3周。检验抗体和产生抗体的滴度将依赖于在实验中使用的病毒。nSIV H1 Elisa test 猪流感H1酶联免疫吸附实验picks up most but not all H1 antibodies. 选择最普遍种类而非所有种类的抗体。 Correlation of Elisa values to titers.

18、 酶联免疫吸附的结果值与抗体滴度相关 Best read as a positive or negative result. 用于了解结果阳性或阴性的最好方法Control 控制nBiosecurity to prevent new introductions, 生物安全措施以阻止新类型的产生nDistance to other pig farms, 远离其他猪场nVaccinate 接种疫苗Sows 母猪nmaternally derived antibody protected 5 week old pigs from clinical disease, virus infection i

19、n the lung, and lung pathology. Maternal antibody did not prevent nasal viral shedding. 母源分泌抗体保护5周龄内的猪免于出现临床疾病、病毒感染肺脏和肺部病状。母源抗体不能阻止病毒经鼻腔扩散。Pigs 其他猪nmarkedly reduced nasal shedding, virus infection in lung tissue, and lung pathology than nonvaccinated animals. 经免猪较未免疫猪可显著减少病毒经鼻腔扩散、病毒对肺脏组织的感染和肺部病状。SIV

20、 outbreaks 猪流感的爆发nDetermine if SIV losses are due to 决定猪流感是否导致损失的因素Virus variation or new virus introduction 病毒毒力或新型病毒的传入Vaccination compliance issues 免疫未遵从要求进行Vaccination failure 疫苗接种失效Antigenic change and cross-protection? 抗原改变和交叉保护？nStrains of antigenic and genetic differences, lack of cross-reac

21、tivity 病毒毒株和遗传的差异，缺乏交叉反应性nVaccination with one influenza subtypeProtection against subtype variants if sufficiently high titers 一种亚型的流感疫苗免疫如果有足够高的抗体滴度可以起到对抗该亚型变异株的保护作用nHA and NA changes escape from vaccinal immunity 血凝素和神经氨酸酶的改变病原可以逃避疫苗免疫作用nTiming, dose, maternal antibody decay, co-infections 时间安排、剂

22、量、母源抗体衰竭、混合感染Genetic Sequencing 基因测序nSurveillance 监测GenBank 基因库Influenza Sequence Database 流感序列数据库nMulti-lab Collaboration 多实验室协作收集nGenetic differences in specific regions 特异区域的遗传差异Cleavage sites, epitope sites, glycosylation sites 裂解位点、抗原决定簇位置、糖基化部位nAntigenic changes, immune system escape, virulenc

23、e 病原改变、免疫系统逃避、毒力nOrigin and Evolution 起源和进化Epidemiology 流行病学SW/IA/30SW/IL/63SW/WI/61SW/NJ/76SW/NE/92SW/IN/88NE/45891/00SW/WI/98NC/44173/00IN/28086/00AR/2976/02MN/1192s/01MN/40318/00MN/25447/00IN/6771/01NC/48600/00MN/7002/01MN/37866/99KS/6577/01NE/8397/01MN/29404/00MN/2525/01MN/17211/01MN/26194/01MN/

24、222/02MN/11695/01NC/36883/00NC/27117/00NC/52225/00NC/47834/00NC/45444/01NC/46470/01NC/35354/01NC/33006/01H1N1HANAH3N2PAPB2H1N1H1N1 Classical古典型古典型H1N1HAH3N2NAPAPB2H1N2Genetic Sequencing 基因测序Future 未来nChanges will continue 病毒改变将继续下去nNational, Regional, State monitoring 国家、地区、州（省）监控机制nVaccination and Challenge Studies 疫苗接种和攻毒试验nMonitoring and characterization to stay on top 病毒监控和鉴定保持高度警觉。