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1、PSEUDORABIES Control and Eradication 伪狂犬病的控制和清除,朱稳森 美国谷物协会 广州,Pseudorabies伪狂犬病 PRV 伪狂犬病病毒 Aujeskys Disease (AD)奥叶斯基病 Infectious Bulbar Paralysis感染性延髓麻痹 Historical Records report disease in Cattle in early 1800s 早在1800年有报道该病发生于牛 All species of mammals susceptible.哺乳动物易感 Cats, Dogs, Sheep, Cattle, Hor
2、ses, Rats, Monkeys. Man is resistant. Rare reports in Humans (Skin rash). 人有抵抗性,人感染的报道很少见(皮疹) PRV was often confused with swine fever. 常与猪瘟相混,急性: 流产,木乃伊,死胎,不孕 腹泻,中枢神经症状 High mortality in small pigs 仔猪高死亡率 Pre-wean can be almost 100%断奶前几乎100 5 - 9 weeks less than 10%59周龄低于10 Less than 2% in older pig
3、s稍大猪低于2 Coughing, sneezing咳嗽,喷嚏 Skin lesions/Itching (not common) 皮肤病变/痒(不多见) Varying pathogenicity, sometimes acute form not seen 病毒的致病性不同,有时未见急性型,慢性: Pneumonia in Grow-finish 生长肥育阶段肺炎 Immunity from sow lasts for up to 15 weeks, protective 6 to 12 weeks 母体免疫力可持续到 15 周龄,但保护性只到 612 周龄 Immunosuppressi
4、on, Secondary Infection 免疫抑制,继发感染 APP, Strep, Mycoplasma Interactions Sow herd fairly stable, G/F is virus factory 母猪群很稳定,生长肥育猪产生病毒 Immunity can be cyclic in sow herd 母猪群免疫力可循环,Pseudorabies Spread伪狂犬病的传播 Infected Pigs - 病猪 Lifetime Latent infection 潜伏感染 Virus Shedding when stressed 应激状态下产生病毒 Fomites
5、污染物 Trucks, Boots, Premises 卡车,靴子,环境 Aerosol空气传播 Spreads 3 km very easily 很容易就能传播 3 公里 Circle/Area Vaccination Essential 环形/区域免疫是必需的,PRV - Route of Infection感染途径 Intranasal/oral route鼻腔/口腔途径 Nasal Epithelial cells鼻腔上皮细胞 Nerve Cells - - - up nerves to CNS 神经细胞向上至中枢神经系统 Tonsil扁桃体 Respiratory Tract呼吸道
6、Lymphoid Tissues淋巴组织 Semen/Uterine route possible 可能的精液/子宫途径,After Infection:感染后 The Pig sheds virus for 10 to 14 days. 1014天期间产生病毒 Virus becomes Latent in Nerve Tissue. 病毒在神经组织潜伏 Pig is infected for its Lifetime. 终生感染 Periodic recrudescence occurs. 周期性复发 Latent Infection is detectable by PCR. PCR技术
7、可检测潜伏感染,Gross Lesions总体病变 Sometimes No Gross Lesions are visible 有时见不到总体病变 Multiple White Foci on Liver & Spleen 肝脏和脾脏多个白色病灶 Intranasal/tonsillar Necrosis (not common) 鼻腔/扁桃体坏死(不常见) Pulmonary Edema 肺水肿 Pneumonia 肺炎 Facial Skin Lesions are rare. 面部皮肤病变少见,Microscopic Lesions镜检病变 Meningitis脑膜炎 Encephal
8、itis(大)脑炎 Perivascular Cuffing血管周成套现象 Bronchitis支气管炎 Interstitial Pneumonia间质性肺炎 Necrotic Foci in Liver & Spleen 肝脏和脾脏的坏死性病灶 Enteric Lesions 肠道病变,Differential Diagnosis鉴别诊断 Swine Influenza猪流感 Parvovirus细小病毒 Circoviral “Shaker Pig Disease” 环状病毒性猪震颤病 Classical Swine Fever经典型猪瘟 PRRS蓝耳病 Enterovirus肠病毒,C
9、onfirmed Diagnosis明确诊断 Virus Isolation病毒分离 Fluorescent Antibody Tissue Section 荧光抗体组织切片 Serology血清学 Serum Neutralization (SN)- Reliable, gives serum titer 血清中和反应(SN)可靠,给出滴度 ELISA - Sensitive, specific, Differential ELISA灵敏,特异性强,区别明显 Latex Agglutination (LAT) -Very sensitive, can give false positive
10、(dilute 1:40 may help) 胶乳凝集反应灵敏,可能假阳性(稀释40倍好些) PCR, In-Situ Hybridization, Etc. PCR,原位杂交,等,6 8 10 12 14 16 18 20 22 24 周,伪狂犬病免疫模型,x,x,x,x,x,0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,2 4 6 8 10 12 14 16 18 20 22 24,抗 体 水 平,周龄,伪狂犬病 gE (gI) ELISA,gE (gI),Economic Loss due to Pseudorabies伪狂犬病带来的经济损失,Losses due to Acu
11、te Outbreaks急性爆发的损失 Reproduction Problems繁殖障碍 Piglet Mortality仔猪死亡率 Chronic Form慢性型 Pneumonia肺炎 Immunosuppression 免疫抑制 Losses in Growing/Finishing up to $12 USD/pig 生长肥育阶段的损失可达12美元/头猪 Cost of Vaccination疫苗成本 Lost Access to Markets市场的损失,Percent Lung Damage,支原体,支原体 + 伪狂犬病,Interaction of PRV and Mycopl
12、asma Infection 支原体与伪狂犬病的互作,0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,2 4 6 8 10 12 14 16 18 20 22 24,抗 体 水 平,周龄,伪狂犬病 gE (gI) ELISA,gE (gI),Major Genes of Pseudorabies Virus 伪狂犬病病毒的主要基因,gE (gI) Deletion renders virus avirulent. 缺失后失去毒力 Reliable ELISA, PCR differential testing. ELISA,PCR可用于鉴别检测 gG (gX) Common delet
13、ion in vaccine. 疫苗中通常缺失 Differential ELISA less distinct than for gE ELISA的鉴别检测结果不如对gE效果好,Major Genes of Pseudorabies Virus,TK (thymidine kinase)胸腺嘧啶激酶 Popular safety deletion常见安全缺失 Deletion inhibits virus replication 缺失抑制病毒复制 gI (gp63) Sometimes deleted to reduce virulence 缺失可减弱毒力 Not very importan
14、t in immunization. 在免疫作用中不重要,Major Genes of Pseudorabies Virus,gB (gII) Useful in induction of protective immunity 益于产生保护性免疫力 gC (gIII) Sometimes deleted. Differential Elisa Available 有时缺失,可用ELISA鉴别 gD (gp50) gD controls ability of virus to penetrate cells. gD important in Immunization. 控制病毒对细胞的穿透能力
15、,对免疫重要 Antibody against gB, gC or gD can protect pigs 对 gB, gC 或 gD 抗体可保护猪,Immunity to Pseudorabies Local Immunity 局部免疫 Humoral Immunity激素免疫 Cellular Immunity细胞免疫 Interferon干扰素 Prevention of Latency (occupy sites) 预防潜伏感染 Antibody titers are no measure of protection (Kit, et al. 1994, Boersma et al.
16、1998) 抗体滴度不能衡量保护能力,Pseudorabies Vaccination伪狂犬病的免疫 Vaccination Does Not Produce Absolute Protection 免疫不能提供绝对的保护 Vaccinated Pigs can still get the Infection 免疫后的猪仍可感染 Vaccinated Pigs can still Produce Virus 免疫后的猪可产生病毒 Vaccinated Pigs can still Get Sick 免疫后的猪可发病 Vaccination is Useful, and is Cost-Effe
17、ctive 免疫有用,且合算,Pseudorabies Vaccination Can:免疫能: Reduce Likelyhood of Infection 减少感染可能性 Reduce Severity and Length of Illness if pig is infected 万一猪感染,可缩短病程,减弱病情 Reduce Length of Time that Virus is Produced (4x) 缩短病毒产生时间 Reduce Amount of Virus that is Produced (1000 x) 减少产生的病毒量 Reduce Likelyhood of
18、Latent Infection 减少潜伏感染机会 Reduce Likelyhood of Recrudescence 减少反复感染机会,6 8 10 12 14 16 周,伪狂犬病免疫模型,Maternal Antibody母源抗体 Piglets very well protected at least until after weaning. 至少可为仔猪提供到断奶前的保护 Generally protection is weak by week 8 - 12, and piglet may become infected. 812周龄前保护力减弱,猪可能感染 Significant
19、Potential Interference with Immunization. 对疫苗有明显潜在干扰 Late vaccination (10-16 weeks) gives highest Ab response, but may be too late for protection. 1016周龄免疫可产生高抗体反应,但来不及提供保护 Intranasal vaccination circumvents maternal Ab. 鼻腔免疫接种避开母源抗体,All maternal PRV Ab disappears by 16 weeks of age. 母源抗体到16周龄前消失 Pi
20、gs receiving colostrum from infected sows will be gE - Positive for up to 16 weeks of age. 吃到感染母猪初乳的仔猪16周龄前是gE阳性 Maternal Antibody has a half-life of about 10 days. 母源抗体的半衰期大约10天 Maternal Ab for diseases like Strep, Mycoplasma, APP only lasts 3 -4 weeks. Parvovirus maternal Ab may last as long as 6
21、months. PRRS Ab lasts up to 8 weeks but only protective for about 3 weeks or less. 对链球菌,支原体,猪放线杆菌的母源抗体可持续34周,细小病毒母源抗体持续6个月,蓝耳病的母源抗体可持续8周,但只能保护到3周龄或更小。,6 8 10 12 14 16 周,伪狂犬病免疫模型,Route of Vaccination免疫途径 Intranasal 鼻腔 Rapid Induction of Local Immunity 很快产生局部免疫 Can Immunize Piglets in presence of Mate
22、rnal Ab 有母源抗体存在时可免疫仔猪 Can Block Latency阻断潜伏感染 Intramuscular肌肉 Convenient方便 Practical for Large Swine对大猪可行 Use Long Needle需要长针头 Intradermal - Experimentally used皮内用于试验,未接种,肌肉注射,鼻腔免疫,Intranasal Vaccination Reduces Virus Shedding after Severe Experimental Challenge 试验性严重感染后鼻腔接种可减少病毒产生,Percentage of Pig
23、s Shedding Virus,Choosing a Pseudorabies Vaccine选择伪狂犬病疫苗,Use a vaccine with a gE (g1) deletion.用 gE缺失苗 You will want to be able to differentiate infected and uninfected pigs. 可能想区别感染和未感染猪 Modified Live Virus should be used for initial vaccinations.初次免疫应使用弱毒苗 Modified Live Virus or Killed virus can b
24、e used for repeat vaccinations.重复免疫时可用弱毒苗或灭活苗 Killed virus may produce higher Ab levels on repeat vaccination.重复免疫时灭活苗可产生较高抗体水平,Selecting Appropriate Time for Vaccination 正确选择免疫时机,Sows:母猪 Conventional thinking is to vaccinate before farrowing to make sure piglets are protected. 一般认为产前免疫可保护仔猪 Problem
25、- Some sows do not farrow, thus are not vaccinated, and their immune level can decline below the protection level. 问题一些母猪不分娩,未被免疫,其免疫水平 低于能提供保护的水平 If immune levels fall too low, infected sows will begin to shed virus, and uninfected sows will become susceptible. 免疫水平过低,感染母猪产生病毒,未感染母猪易感,Vaccinating s
26、ows 3 to 4 times each year will stabilize sow herd immunity and prevent shedding. 每年免疫母猪34次,可稳定群体免疫水平,防止产生病毒 Preferable program is to vaccinate sow herd en masse at 3 to 4 month intervals by the calendar. 最好根据日历定期给母猪群体免疫,间隔34月 Sows should be vaccinated regardless of stage of reproduction, pregnancy
27、or lactation. 不考虑繁殖阶段,妊娠或泌乳,母猪全部免疫 When sows are vaccinated in this way, they will shed very little virus and can resist infection. 如此,母猪很少产生病毒,可抵抗感染 Immunity levels are adequate to protect piglets. 其免疫力足可保护仔猪,Replacement Boars and Gilts后备公母猪,Replacement animals should be vaccinated twice at 3 week
28、intervals with MLV vaccine before entry into the herd. 后备猪在进群前应以弱毒苗免疫2次,间隔3周 If negative boars and gilts enter the herd and the herd is vaccinated 3 to 4 times per year, and infected animals are gradually culled with respect given to their status, the herd will become negative in 3 to 4 years. 阴性猪转入
29、定期免疫的群体,感染猪逐渐被淘汰,群体可望在 34年后转为阴性,Piglet vaccination仔猪免疫,A serologic survey of the herd with animals at different ages tested will yield valuable information. 对群体各年龄段作血清学调查可提供有价值信息 The time of infection and decay of maternal antibody will dictate the time of vaccination. 根据感染时间和母体免疫力的消退可决定免疫时间 The tra
30、ditional times of vaccination are to 10 and 14 weeks of age. 传统免疫时间是10和14周龄 When infection is occurring at a relatively young age, earlier vaccination may be indicated. 一旦感染发生在早期,意味着应提早免疫,Presence of maternal antibody may interfere with early intramuscular vaccination. 早期肌肉免疫可能受到母源抗体干扰 Pigs may be s
31、uccessfully vaccinated intranasally even at birth in the presence of maternal antibody, but the immunity may be relatively shortlived. 出生时的鼻腔接种可不受母源抗体干扰,但免疫力时间短 Very early (at birth) vaccination should be followed with a intranasal booster at 3- 4 weeks of age, and an intramuscular booster at 7 to 9
32、 weeks of age. 出生免疫后应在34周龄时鼻腔接种和79周龄时 肌肉免疫进行强化 When vaccinating at 3-4 weeks of age, a single IM booster at 7 to 9 weeks of age should be sufficient. 首次免疫在34周龄时,79周龄时肌肉免疫强化一次足够,6 8 10 12 14 16 周,伪狂犬病免疫模型,0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,2 4 6 8 10 12 14 16 18 20 22 24,抗 体 水 平,周龄,伪狂犬病 gE (gI) ELISA,gE (gI),0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,2 4 6 8 10 12 14 16 18 20 22 24,抗 体 水 平,什么时候感染?,?,+,感染,gE (gI),0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,2 4 6 8 10 12 14 16 18 20 22 24,抗 体 水 平,周龄,什么时候打疫苗?,打疫苗,gE (gI),In the Face of an Outbreak爆发时,An accurate diagnosis is essential. 必需进行急性诊断 The mo
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