伪狂犬

伪狂犬 , Instructor: HanSoo Joo 人: HanSoo Joo Lecture No. 4, August 17 15:00-16:30 第四讲，8月17日 15:00-16:30 PSEUDORABIES (PRV)/AUJESZKY (ADV) 伪狂犬病(伪狂犬病病毒)/奥叶兹基氏病(奥叶兹基氏病病毒) Referred to as Aujeszky's Disease virus (ADV) in the rest of the world 世界其它地方称之为奥叶兹基氏病病毒(ADV) Etiology 病原学 , Suid herpesvirus type 1; member of alpha herpesviridae subfamily. As a member of this subfamily, PRV/ADV has a restricted host range, relatively short replicative cycle, giant cell formation of infected cells, and establishes latency, primarily in nerve ganglia. 猪疱疹病毒?型;α-疱疹病毒亚科成员，作为本亚科的成员，PRV/ADV有严 格的宿主范围，相对较短的复制周期，感染细胞呈巨细胞样，主要在神经节呈潜 伏感染。 , Latency is extremely common after infection (essentially 100%), reactivation and consequent shedding may occur (usually under stress?). 潜伏期在感染后极为常见(实际上为100%)，重新激活随之排出病毒可能发病 (通常在应激下,) , Important components include lipoprotein envelope, nucleocapsid, DNA coding for several glycoproteins and production of TK enzyme (glycoproteins gI, gX, & gIII are not essential for normal replication; also TK not necessary). 重要结构组份包括脂蛋白囊膜，核蛋白衣壳，用以编码几种糖蛋白的DNA 和 TK酶(胸腺嘧啶激酶)的产物(糖蛋白 gI, gX, 和 gIII不是通常复制所必需的， TK也一样)。 , Not zoonotic (no relation to rabies), 非人畜共患病(同狂犬病没关系)， , No effect on carcass 对胴体质量没影响 History 历史 , Discovered by Dr. Aujeszky in Hungary, 1902. 1902年由奥叶兹基博士发现于匈牙利。 , Referred to as "Mad itch" in U.S. by Shope 1931; described as contagious but subclinical in swine at that time. 1931年美国的Shope称之为“狂痒病”，描述为会感染但在猪当时呈亚临床症 状。 , Clinical outbreaks described in Europe in 1950's and in USA in 60's. 在欧洲的50年代和美国的60年代有过临床爆发的报导。 , Prior to 1977, US had informal control program with no vaccine permitted. In 1977 first vaccine was permitted; MLV BUK strain imported from Czechoslovakia. 1977年之前，由于不准应用疫苗美国已有非正式控制程序。1977年第一次允许 使用疫苗。弱度 BUK株由捷克斯洛伐克进口。 , At present practically eradicated from US 美国目前实际上已经根除了本病 Pathogenesis 发病机理 , Route of infection is oro-nasal virus by contact with secretions. 感染途径是经口鼻途径，通过接触分泌物而感染。 , Invasion of epithelial mucosa in nasal cavity, & oro-pharyngeal area 通过鼻腔和口咽部的粘膜上皮侵入 , Virus shed in secretions for 7-12 days at infectious levels 在排出的在分泌物中病毒感染水平可维持7~12天。 , Predisposition to secondary infections 诱导继发感染 , Detectable viremia may occur but is short-lived 可检测的到病毒血症，但持续时间很短 , In utero infection is relatively uncommon 子宫内感染相对来说并不常见 PRV/ADV in Other Species 其它动物的PRV/ADV , Swine – natural & principle reservoir 猪—天然和主要的储存宿主 , All other species that may be infected are considered as dead end hosts 可能感染的所有其它动物被认为是终末宿主 , Virtually 100% fatal in these species spread between these species is extremely rare; insignificant. Infected non-porcine carcasses may be ingested by swine , infection 事实上，100%致死率使得在这些物种间的传播极其罕见;微不足道。非猪科动 物感染死亡后体尸可能被猪摄食,感染 Transmission Between Herds 猪群间的传播 Major mode of spread between herds = infected swine. Pigs represent the only long-term reservoir. 猪群间的主要传播方式=感染猪。猪是唯一的长期储存宿主。 When controls are not in place on the movement of swine between herds, minor modes include wildlife, fomites, contaminated feed, & airborne. When controls are in place, these apparently minor modes become proportionately more important. 如果猪和猪群的活动管理不当，这些传播模式包括野生动物、污染物、污染的饲料和空气传播是次要的。当管理适当，这些看起来次要的模式相应得变得更加重要。 oEnvironmental survival influenced by humidity and temperature. i.e.: temp; 4C is ideal and can survive up to 4 months in tissue. o环境中的存活受温度和湿度的影响。比如:在组织中，4C是最适温度，可存活4个月。 - clean concrete – hours 干净的混凝土--几个小时 - human skin--4 hours 人体皮肤—4小时 - plastic & steel--3 days 塑料和钢铁—3天 - manure--2 days 粪便—2天 - lagoon water--2 days 2天 污水— - soil--6 days 土壤—6天 o - 35-minute half-life when suspended in mucin and held at 4C & 55% humidity. o在4C 和 相对湿度55%的情况下，混悬在粘蛋白中的半衰期是35分钟。 Clinical Signs 临床症状 Severity of clinical signs depends on: 临床症状的严重程度取决于: , Age of pig; young are most susceptible 猪的年龄;小猪最易感 , Virulence of infecting virus strain 感染病毒株的毒力 , PRV/ADV vaccine history of herd 猪群中PRV/ADV疫苗的使用情况 , Environment (probably influences dose) 外界环境(可影响感染剂量) , Approximately 50% of new herd infections in non-vaccinated herds are subclinical, 35% are moderate, 15% have classical severe signs. 在没有免疫过的新猪群中感染该病，近50%呈亚临床症状，35%呈中度症状，15%呈典型的严重症状。 Preweaning 断奶前仔猪 , High morbidity & mortality (up to 100%) 高发病率和高死亡率(接近100%) , Infection at birth; signs within 1st 2 days with death before 5 days---Fever; oocommonly 105F-108F oo出生时感染;，5天内死亡， 头2天的症状是——发热，通常为105F-108F oo(40.6C-42.2C) , Off feed, vomiting/diarrhea 厌食，呕吐/腹泻 , Central Nervous Signs: 中枢神经症状: - weakness, incoordination, convulsion 虚弱，共济失调，抽搐 - lay on side paddling 侧卧，划游 - shaking & trembling 震颤,发抖 Postweaning 断奶后仔猪 , More resistant than younger pigs 比断奶前仔猪抵抗力强 , High morbidity, variable mortality 高发病率，死亡率不定 , Flu-like sign (sneezing, coughing) 类流感症状(打喷嚏，咳嗽) , General; fever, off feed, listless, vomiting, occasional CNS 通常;发烧，厌食，精神抑郁，呕吐，偶见中枢神经系统症状 Adult and Pregnant Pigs 成年和怀孕猪 , Mild or no clinical sign 轻微或没有临床症状 , Off feed, fever, & mild coughing are most common 厌食，发烧和轻微咳嗽最为常见 , Vomiting, diarrhea, and CNS are less common. 呕吐，腹泻和中枢神经系统症状少见 , Early gest. - Resorption, return to service 怀孕早期—重吸收，返情复配 , Mid gest.- Abortion due to placentitis, mummification 怀孕中期—胎盘炎引起流产、木乃伊化 , Late gest.- Abortion, stillborn, weak & shaker pigs 怀孕后期—流产，死产，产弱仔和先天性震颤仔猪 , Subclinical; detected only by seroconversion 亚临床症状:靠血清学变化才能检出 Post Mortem Lesions 尸体剖检病变 , Gross yellow-gray foci on liver and/or spleen 肝和/或脾肉眼可见的灰黄色坏死灶 , May see interstitial pneumonia 可能见到间质性肺炎 Histopath; Inclusion body 组织病理学:包涵体 Brain: perivascular cuffing 大脑:血管袖套现象 Diagnosis 诊断 , Virus: Virus isolation--tonsil, brain, placenta, aborted fetus, spinal cord 病毒:病毒分离—扁桃体，大脑，胎盘，流产胎儿，脊髓 - Submit refrigerated sample - overnight delivery 递交冷冻样品,隔夜交货 - Fluorescent antibody - tonsil, spleen 荧光抗体,扁桃体，脾 - Lab animal inoculation - rabbit, mice 实验动物接种,兔，小鼠 Serology 血清学 A. Non-differentiating tests cannot distinguish between vacc and nonvacc swine: 非鉴别检测不能区分免疫过和没免疫的猪: 1. Serum Neutralization is considered the official test. It is most specific. However, requires a minimum of 72 hrs, toxic sera cannot be tested. 血清中和反应被认为是法定的检测方法。具有高度特异性;但最少需要72 小时，不能检测含毒素的血清。 2. Screening Enzyme-Linked Immunoassay (ELISA)--commercial kit (only for state labs). Is more sensitive, but will have more false positives. Expensive equipment. 酶联免疫吸附法(ELISA),商业试剂盒(仅在州实验室)更灵敏，但有更 多的假阳性。仪器设备昂贵。 3. Latex agglutination test; Field test, Results within few minutes. 乳胶凝集试验:现场测定，几分钟内出结果。 4. Radial Immunodiffusion Enzyme Assay (RIDEA); In-clinic test, simple and rapid. 放射免疫扩散酶法(RIDEA):门诊检测，简单快速。 B. Differentiating ELISA's have been developed to accompany specific vaccines see below for details. 与各种疫苗配套，已经研发出相应的ELISA以鉴别不同的疫苗，具体见以下: Vaccination接种疫苗 Advantage优点 Disadvantages缺点 - Reduce clinical losses - Does not prevent infection or 减少临床损失 shedding不能防止感染或病毒释放 - Reduces virus shedding - Does not prevent latency 减少病毒释放 development不能防止潜伏病例的 - Reduces cost of eradication 发展 (short-terms) - Complicate serotesting使血清检测 减少扑灭费用(短期内) 变的复杂 - Expensive in long term长期费用高 Safety Concerns with MLV Include 包括减毒疫苗(MLV)的安全相关性 , Recombination with other MLV PRV/ADV vaccines. With wild type? 与其它PRV/ADV的弱毒疫苗(MLV)重组。同野毒型, , Dogs, cats, cattle or sheep , PRV/ADV = death. (Killed vaccine--little protection in other species. 狗，猫，牛或绵羊, PRV/ADV=死亡(灭活疫苗—在其它物种几乎无保护作用) , Immunosuppressive? Some evidence for wild type PRV/ADV. 免疫抑制,一些来自野毒型PRV/ADV的证据 , Safety in pregnant females? Check labels. 对怀孕母猪安全性,检查标签。 Comparison of PRV Elimination Programs for Swine Herds 对比猪群中的PRV消除程序 , Depopulation & Repopulation 清群和复群 - Indicated if herd has high seropositive prevalence (> 80) 假如猪群中有高血清阳性率(> 80) - Genetic strains are of little value 遗传品系的差异意义不大 , Test & Removal (immediate) 检测和淘汰(快速) - No or very slow spread & seropositive prevalence <20% 没有或传播慢及低血清阳性率<20% - Relatively inexpensive & least disruptive 相对便宜和损失最少 , Offspring segregation 隔离后代 - If herd has high genetic value 假如猪群有较高育种价值 - Isolation facilities are available 隔离有价值的设备 , Vaccination (delayed test and removal) 接种疫苗(检测和淘汰被延误时) - Continuous & intensive vaccination to reduce virus shedding and spread. 持续集中接种减少病毒的释放和传播 - Use accompanying differential diagnostic test to detect and eliminate positive individuals. 使用相应的鉴别诊断方法检测并清除阳性个体 Relative Advantages of PRV Elimination Programs PRV扑灭程序的相对优点 Test and Removal Offspring Seg. Depop/Repop Vaccine/Mgmt 检测和淘汰 后代隔离 清群/复群 疫苗/管理 Cost Least Intermediate Most Least 花费 最少 中等 最多 最少 Time to AchieveSlow Intermediate Intermediate Slow 完成时间 慢 中等 中等 慢 Genetics Maintain Maintain Replaced Maintain 遗传学 保留 保留 替代 保留 Disruption to Minor Intermediate Major Minor Management 小 中等 大 小 管理破坏性 Concomitant Same Some Major Medium Diseases Improvement Improvement 类似 中等 伴发病 部分，改善 较大，改善 Likely to Succeed Least Intermediate Most Least 成功性 最小 中等 最大 最小 Summary Aujeszky’s Disease (Pseudorabies) 奥叶兹基氏病(伪狂犬病) , Eradicated from US recently, cases may still occur 最近已经从美国清除，个别病例可能仍会发生 , Affects clinically mostly young pigs 临床上主要侵害幼猪 , No clinical signs evident in adult pigs 成猪无临床迹象 , Can go unrecognized inside a farm 能在猪场内潜伏而不表现迹象 , Diagnostic is achieved by serology 可用血清学诊断 , Regulatory disease, must be reported 受规章限制的疾病，必须上报 , Regular bleeding and certification is required 正规饲养和证明书是必要的 - Stage 1: Preparation 第1步:预备 - Stage II: Herd cleanup – all herds monitored at least once a year 第2步:猪群清除—所有猪群每年至少监控一次 - Stage III: Mandatory Cleanup - <1% herds positive, must test at least 10% of breeding animals 第3步:强制清除-<1%阳性猪群，必须检测至少10%的饲养中的动物 - Stage IV: Disease free for at least 2 years, must test 5% animals 第4步:至少2年无该疾病，必须检测5%的动物 - Stage V: One year at Stage II, some monitoring 第5步:重复第2步，持续一年，并进行监控 , Infected herds are quarantined, can only sell to slaughter 隔离感染的猪群，仅允许卖给屠宰场 , Quarantine is lifted when all animals test negative 当所有动物检测阴性时取消隔离 Control 控制 , Vaccine: MLV g1 deleted (gE modern nomenclature) 疫苗:g1缺失(gE 现代命名)减毒疫苗 , Vaccine has a differential ELISA test that identifies g1 antibodies 疫苗可用ELISA进行鉴别检测，该方法可以确定g1抗体的不同 , Vaccine does not prevent infection but minimizes shedding 疫苗不能防止感染但可以使病毒释放减至最低 , Other control measures: 其它控制措施: - Test and removal 检测和淘汰 - Depopulation/repopulation 清群/复群 - Offspring segregation (SEW) 后代隔离(早期断奶隔离)