1、偽狂犬病的控制和清除Pseudorabies偽狂犬病PRV 偽狂犬病病毒Aujeskys Disease (AD)奧葉斯基病Infectious Bulbar Paralysis感染性延髓麻痹Historical Records report disease in Cattle in early 1800s早在1800年有報道該病發(fā)生于牛All species of mammals susceptible.哺乳動物易感Cats, Dogs, Sheep, Cattle, Horses, Rats, Monkeys.Man is resistant. Rare reports in Humans

2、 (Skin rash).人有抵抗性，人感染的報道很少見（皮疹）PRV was often confused with swine fever.常與豬瘟相混急性：流產(chǎn)，木乃伊，死胎，不孕腹瀉，中樞神經(jīng)癥狀High mortality in small pigs 仔豬高死亡率Pre-wean can be almost 100%斷奶前幾乎1005 - 9 weeks less than 10%59周齡低于10Less than 2% in older pigs稍大豬低于2Coughing, sneezing咳嗽，噴嚏Skin lesions/Itching (not common) 皮膚病變/癢

3、（不多見）Varying pathogenicity, sometimes acute form not seen病毒的致病性不同，有時未見急性型慢性：Pneumonia in Grow-finish 生長肥育階段肺炎Immunity from sow lasts forup to 15 weeks, protective 6 to 12 weeks母體免疫力可持續(xù)到 15 周齡，但保護性只到 612 周齡Immunosuppression, Secondary Infection 免疫抑制，繼發(fā)感染APP, Strep, Mycoplasma InteractionsSow herd fai

4、rly stable, G/F is virus factory母豬群很穩(wěn)定，生長肥育豬產(chǎn)生病毒Immunity can be cyclic in sow herd 母豬群免疫力可循環(huán)Pseudorabies Spread偽狂犬病的傳播Infected Pigs - 病豬Lifetime Latent infection 潛伏感染Virus Shedding when stressed應(yīng)激狀態(tài)下產(chǎn)生病毒Fomites污染物Trucks, Boots, Premises卡車，靴子，環(huán)境Aerosol空氣傳播Spreads 3 km very easily很容易就能傳播 3 公里Circle/Ar

5、ea Vaccination Essential環(huán)形/區(qū)域免疫是必需的PRV - Route of Infection感染途徑Intranasal/oral route鼻腔/口腔途徑Nasal Epithelial cells鼻腔上皮細胞Nerve Cells - - - up nerves to CNS神經(jīng)細胞向上至中樞神經(jīng)系統(tǒng)Tonsil扁桃體Respiratory Tract呼吸道Lymphoid Tissues淋巴組織Semen/Uterine route possible可能的精液/子宮途徑After Infection:感染后The Pig sheds virus for 10 t

6、o 14 days.1014天期間產(chǎn)生病毒Virus becomes Latent in Nerve Tissue.病毒在神經(jīng)組織潛伏Pig is infected for its Lifetime.終生感染Periodic recrudescence occurs.周期性復(fù)發(fā)Latent Infection is detectable by PCR.PCR技術(shù)可檢測潛伏感染Gross Lesions總體病變Sometimes No Gross Lesions are visible有時見不到總體病變Multiple White Foci on Liver & Spleen肝臟和脾臟多個白色病

7、灶I(lǐng)ntranasal/tonsillar Necrosis (not common)鼻腔/扁桃體壞死（不常見）Pulmonary Edema肺水腫Pneumonia肺炎Facial Skin Lesions are rare.面部皮膚病變少見Microscopic Lesions鏡檢病變Meningitis腦膜炎Encephalitis（大）腦炎Perivascular Cuffing血管周成套現(xiàn)象Bronchitis支氣管炎Interstitial Pneumonia間質(zhì)性肺炎Necrotic Foci in Liver & Spleen肝臟和脾臟的壞死性病灶Enteric Lesions

8、 腸道病變Differential Diagnosis鑒別診斷Swine Influenza豬流感Parvovirus細小病毒Circoviral “Shaker Pig Disease”環(huán)狀病毒性豬震顫病Classical Swine Fever經(jīng)典型豬瘟PRRS藍耳病Enterovirus腸病毒Confirmed Diagnosis明確診斷Virus Isolation病毒分離Fluorescent Antibody Tissue Section 熒光抗體組織切片Serology血清學(xué)Serum Neutralization (SN)- Reliable, gives serum tite

9、r血清中和反應(yīng)（SN）可靠，給出滴度ELISA - Sensitive, specific, DifferentialELISA靈敏，特異性強，區(qū)別明顯Latex Agglutination (LAT) -Very sensitive, can give false positive (dilute 1:40 may help)膠乳凝集反應(yīng)靈敏，可能假陽性（稀釋40倍好些）PCR, In-Situ Hybridization, Etc.PCR，原位雜交，等6 8 10 12 14 16 18 20 22 24 周偽狂犬病免疫模型xxxxx010.30.4感染母豬感染仔豬陽性陰性 2 4 6 8

10、 10 12 14 16 18 20 22 24 抗 體 水 平周齡偽狂犬病 gE (gI) ELISAgE (gI)Economic Loss due to Pseudorabies偽狂犬病帶來的經(jīng)濟損失Losses due to Acute Outbreaks急性爆發(fā)的損失Reproduction Problems繁殖障礙Piglet Mortality仔豬死亡率Chronic Form慢性型Pneumonia肺炎Immunosuppression 免疫抑制Losses in Growing/Finishing up to $12 USD/pig生長肥育階段的損失可達12美元/頭豬Cost

11、 of Vaccination疫苗成本Lost Access to Markets市場的損失Percent Lung Damage 支原體支原體 + 偽狂犬病Interaction of PRV and Mycoplasma Infection支原體與偽狂犬病的互作010.30.4感染母豬感染仔豬陽性陰性 2 4 6 8 10 12 14 16 18 20 22 24 抗 體 水 平周齡偽狂犬病 gE (gI) ELISAgE (gI)Major Genes of Pseudorabies Virus偽狂犬病病毒的主要基因gE (gI)Deletion renders virus avirul

12、ent.缺失后失去毒力Reliable ELISA, PCR differential testing.ELISA，PCR可用于鑒別檢測gG (gX)Common deletion in vaccine.疫苗中通常缺失Differential ELISA less distinct than for gEELISA的鑒別檢測結(jié)果不如對gE效果好Major Genes of Pseudorabies VirusTK (thymidine kinase)胸腺嘧啶激酶Popular safety deletion常見安全缺失Deletion inhibits virus replication缺失抑

13、制病毒復(fù)制gI (gp63)Sometimes deleted to reduce virulence缺失可減弱毒力Not very important in immunization.在免疫作用中不重要Major Genes of Pseudorabies VirusgB (gII)Useful in induction of protective immunity益于產(chǎn)生保護性免疫力gC (gIII)Sometimes deleted. Differential Elisa Available有時缺失，可用ELISA鑒別gD (gp50)gD controls ability of vir

14、us to penetrate cells.gD important in Immunization.控制病毒對細胞的穿透能力，對免疫重要Antibody against gB, gC or gD can protect pigs對 gB, gC 或 gD 抗體可保護豬Immunity to PseudorabiesLocal Immunity 局部免疫Humoral Immunity激素免疫Cellular Immunity細胞免疫Interferon干擾素Prevention of Latency (occupy sites) 預(yù)防潛伏感染Antibody titers are no me

15、asure of protection(Kit, et al. 1994, Boersma et al. 1998)抗體滴度不能衡量保護能力Pseudorabies Vaccination偽狂犬病的免疫Vaccination Does Not Produce Absolute Protection免疫不能提供絕對的保護Vaccinated Pigs can still get the Infection免疫后的豬仍可感染Vaccinated Pigs can still Produce Virus免疫后的豬可產(chǎn)生病毒Vaccinated Pigs can still Get Sick免疫后的豬

16、可發(fā)病Vaccination is Useful, and is Cost-Effective免疫有用，且合算Pseudorabies Vaccination Can:免疫能：Reduce Likelyhood of Infection減少感染可能性Reduce Severity and Length of Illness if pig is infected萬一豬感染，可縮短病程，減弱病情Reduce Length of Time that Virus is Produced (4x)縮短病毒產(chǎn)生時間Reduce Amount of Virus that is Produced (1000

17、x)減少產(chǎn)生的病毒量Reduce Likelyhood of Latent Infection減少潛伏感染機會Reduce Likelyhood of Recrudescence減少反復(fù)感染機會6 8 10 12 14 16 周偽狂犬病免疫模型Maternal Antibody母源抗體Piglets very well protected at least until after weaning.至少可為仔豬提供到斷奶前的保護Generally protection is weak by week 8 - 12,and piglet may become infected.812周齡前保護力減

18、弱，豬可能感染Significant Potential Interference with Immunization.對疫苗有明顯潛在干擾Late vaccination (10-16 weeks) gives highest Abresponse, but may be too late for protection.1016周齡免疫可產(chǎn)生高抗體反應(yīng)，但來不及提供保護 Intranasal vaccination circumvents maternal Ab.鼻腔免疫接種避開母源抗體All maternal PRV Ab disappears by 16 weeks of age.母源抗

19、體到16周齡前消失Pigs receiving colostrum from infected sowswill be gE - Positive for up to 16 weeks of age.吃到感染母豬初乳的仔豬16周齡前是gE陽性Maternal Antibody has a half-life of about 10 days.母源抗體的半衰期大約10天Maternal Ab for diseases like Strep, Mycoplasma, APPonly lasts 3 -4 weeks. Parvovirus maternal Ab maylast as long a

20、s 6 months. PRRS Ab lasts up to 8 weeksbut only protective for about 3 weeks or less.對鏈球菌，支原體，豬放線桿菌的母源抗體可持續(xù)34周，細小病毒母源抗體持續(xù)6個月，藍耳病的母源抗體可持續(xù)8周，但只能保護到3周齡或更小。6 8 10 12 14 16 周偽狂犬病免疫模型Route of Vaccination免疫途徑Intranasal 鼻腔Rapid Induction of Local Immunity 很快產(chǎn)生局部免疫Can Immunize Piglets in presence of Maternal

21、 Ab有母源抗體存在時可免疫仔豬Can Block Latency阻斷潛伏感染Intramuscular肌肉Convenient方便Practical for Large Swine對大豬可行Use Long Needle需要長針頭Intradermal - Experimentally used皮內(nèi)用于試驗未接種肌肉注射鼻腔免疫Intranasal Vaccination Reduces Virus Sheddingafter Severe Experimental Challenge試驗性嚴重感染后鼻腔接種可減少病毒產(chǎn)生Percentage of Pigs Shedding Virus C

22、hoosing a Pseudorabies Vaccine選擇偽狂犬病疫苗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?yún)^(qū)別感染和未感染豬Modified Live Virus should be used for initial vaccinations.初次免疫應(yīng)使用弱毒苗Modified Live Virus or Killed virus can be usedfor repeat vacci

23、nations.重復(fù)免疫時可用弱毒苗或滅活苗Killed virus may produce higher Ab levels onrepeat vaccination.重復(fù)免疫時滅活苗可產(chǎn)生較高抗體水平Selecting Appropriate Time for Vaccination正確選擇免疫時機Sows:母豬Conventional thinking is to vaccinate before farrowing to make sure piglets are protected.一般認為產(chǎn)前免疫可保護仔豬Problem- Some sows do not farrow, thus

24、 arenot vaccinated, and their immune level can declinebelow the protection level.問題一些母豬不分娩，未被免疫，其免疫水平低于能提供保護的水平If immune levels fall too low, infected sows will beginto shed virus, and uninfected sows will become susceptible.免疫水平過低，感染母豬產(chǎn)生病毒，未感染母豬易感Vaccinating sows 3 to 4 times each year willstabiliz

25、e sow herd immunity and prevent shedding. 每年免疫母豬34次，可穩(wěn)定群體免疫水平，防止產(chǎn)生病毒Preferable program is to vaccinate sow herden masse at 3 to 4 month intervals by the calendar. 最好根據(jù)日歷定期給母豬群體免疫，間隔34月Sows should be vaccinated regardless of stage ofreproduction, pregnancy or lactation. 不考慮繁殖階段，妊娠或泌乳，母豬全部免疫When sows

26、are vaccinated in this way, they will shed very little virus and can resist infection. 如此，母豬很少產(chǎn)生病毒，可抵抗感染Immunity levels are adequate to protect piglets. 其免疫力足可保護仔豬Replacement Boars and Gilts后備公母豬Replacement animals should be vaccinated twiceat 3 week intervals with MLV vaccine before entry intothe h

27、erd. 后備豬在進群前應(yīng)以弱毒苗免疫2次，間隔3周If negative boars and gilts enter the herd and the herdis vaccinated 3 to 4 times per year, and infected animalsare gradually culled with respect given to their status,the herd will become negative in 3 to 4 years. 陰性豬轉(zhuǎn)入定期免疫的群體，感染豬逐漸被淘汰，群體可望在 34年后轉(zhuǎn)為陰性Piglet vaccination仔豬免疫A

28、 serologic survey of the herd with animals at differentages tested will yield valuable information.對群體各年齡段作血清學(xué)調(diào)查可提供有價值信息The time of infection and decay of maternal antibodywill dictate the time of vaccination.根據(jù)感染時間和母體免疫力的消退可決定免疫時間The traditional times of vaccination are to 10 and 14 weeks of age.傳統(tǒng)

29、免疫時間是10和14周齡When infection is occurring at a relatively young age,earlier vaccination may be indicated.一旦感染發(fā)生在早期，意味著應(yīng)提早免疫Presence of maternal antibody may interfere withearly intramuscular vaccination.早期肌肉免疫可能受到母源抗體干擾Pigs may be successfully vaccinated intranasally even at birth in the presence of m

30、aternal antibody,but the immunity may be relatively shortlived.出生時的鼻腔接種可不受母源抗體干擾，但免疫力時間短Very early (at birth) vaccination should be followedwith a intranasal booster at 3- 4 weeks of age,and an intramuscular booster at 7 to 9 weeks of age.出生免疫后應(yīng)在34周齡時鼻腔接種和79周齡時肌肉免疫進行強化When vaccinating at 3-4 weeks o

31、f age, a single IMbooster at 7 to 9 weeks of age should be sufficient.首次免疫在34周齡時，79周齡時肌肉免疫強化一次足夠6 8 10 12 14 16 周偽狂犬病免疫模型010.30.4感染母豬感染仔豬陽性陰性 2 4 6 8 10 12 14 16 18 20 22 24 抗 體 水 平周齡偽狂犬病 gE (gI) ELISAgE (gI)010.30.4感染母豬感染仔豬陽性陰性 2 4 6 8 10 12 14 16 18 20 22 24 抗 體 水 平什么時候感染？?+感染gE (gI)010.30.4感染母豬感染仔豬陽性陰性 2 4 6 8 10 12 14 16 18 20 22 24 抗 體 水 平周齡什么時候打疫苗？打疫苗gE (gI)In the Face of an Outbreak爆發(fā)時An accurate diagnosis is essential.必需進行急性診斷The most rapid onset of