豬流感的免疫控制

1、豬流感的流行情況和免疫控制,張淵魁 13332868393,大北農(nóng)集團(tuán)動(dòng)物保健事業(yè)部,豬流感病毒感染,世界上最常見的豬呼吸道疾病，特征為發(fā)熱（39 ?C -42?C）持續(xù) 5-10 天，反應(yīng)遲鈍、卷縮、扎堆、昏睡呼吸困難、咳嗽、流鼻液、打噴嚏采食下降、增重降低、推遲2周上市母豬繁殖障礙：流產(chǎn)H1N1亞型病毒感染豬只很少發(fā)生死亡慢性疾病由豬肺炎引起的高死亡率肺臟有實(shí)變區(qū)，有支氣管肺炎病變,SIV造成的損失Dr.

2、Seehusen,對育肥豬：與藍(lán)耳病 PRRS 和鏈球菌混合感染，死亡率高個(gè)別達(dá)到20%, 特別是農(nóng)場主拒絕使用抗生素控制繼發(fā)感染時(shí)。 90~100kg豬：感染H1N1或H3N2，到出欄時(shí)每頭豬可導(dǎo)致$7.50 ~ $20.00的損失，包括淘汰豬，死亡，治療，飼料轉(zhuǎn)換等。25~50kg豬：可導(dǎo)致$5.00 ~ $6.00的損失。 當(dāng)豬流感在育肥豬場流行時(shí)，開始進(jìn)行H3N2疫苗免疫時(shí)已經(jīng)損失$5.00 ~$10.00。如果加上治療費(fèi)

3、用損失$15.00 。,SIV造成的損失Dr. Mohr,治療費(fèi)用：豬感染時(shí)應(yīng)提供支持性療法在保育舍需要額外增加治療費(fèi) $0.50/頭生長育肥階段要$0.25~$0.40/頭。PRDC問題：其他疾病加重豬流感有時(shí)豬流感加重其他疾病,SIV造成的損失Dr. Mohr,母豬流產(chǎn)死亡：大多數(shù)情況下分娩率下降5%~10%。產(chǎn)房母豬死亡率增加到4%~5% 。豬流感損失的最大組成部分感染較大豬群而又不能控制，且病毒仍將繼續(xù)

4、危害豬群,豬流感病毒是PRDC最常見的分離物,1. 藍(lán)耳病病毒PRRSV2. 霉形體M.hyopneumoniae3. 豬流感病毒SIV對生產(chǎn)導(dǎo)致巨大經(jīng)濟(jì)影響,豬流感病毒是PRDC最主要原發(fā)病原體,破壞黏膜纖毛系統(tǒng)為休眠狀態(tài)的病原體打開門戶為繼發(fā)感染搭起舞臺霉形體，放線桿菌, 巴士桿菌副豬嗜血桿菌，波氏桿菌與偽狂犬病病毒，霉形體并發(fā)感染與PRRS有協(xié)同作用,豬流感病毒,豬流感不是一種溫和型疾病破壞黏膜纖毛系統(tǒng)為

5、休眠狀態(tài)的病原體打開門戶為繼發(fā)感染搭起舞臺霉形體 放線桿菌, 副豬嗜血桿菌，波氏桿菌, 巴士桿菌常與偽狂犬病病毒，霉形體并發(fā)感染與PRRS有協(xié)同作用,豬流感病毒,流感病毒A型Type A (主要感染人和動(dòng)物)B型Type B (主要感染人)C型Type C (主要感染人)病毒蛋白血凝素( Hemagglutinin, HA or H)14 種亞型 神經(jīng)氨酸酶( Neuraminidase, NA or N)

6、9 種亞型,豬流感病毒,分離株的命名型/動(dòng)物種類/分離地點(diǎn)/分離年代例如. A型/豬/Wisconsin/4754/94,豬流感病毒感染的歷史,至今豬流感已發(fā)現(xiàn)有60多年古典型豬流感病毒H1N1 亞型在世界各地存在H3N2 在歐洲發(fā)現(xiàn)已有10年1998年美國證實(shí)了H3N2,水禽在豬流感病毒流行病學(xué)中的作用,水禽在豬流感病毒流行病學(xué)中的作用,水禽在A型禽流感病毒的流行病學(xué)中起到中心作用（從歷史看來）。所有A型禽流感病毒起

7、源于禽類（遺傳學(xué)研究表明）。在水禽可以見到所有15種HA和所有9種NA各種組合的亞型。水禽常呈廣泛、亞臨床感染，是該病毒的自然貯存宿主。自從1979年以來，禽流感病毒在歐洲和北美洲豬流感病毒流行病學(xué)中的作用。,水禽在豬流感病毒流行病學(xué)中的作用,A型禽流感病毒還是其他多種動(dòng)物病原對馬和家禽（特別是雞和火雞）有極其重要經(jīng)濟(jì)影響的疫病可引起人工飼養(yǎng)的水貂、自由生活的海洋哺乳動(dòng)物嚴(yán)重的疾病可引起奶牛奶產(chǎn)量下降、呼吸道疾病也是人呼吸

8、道疾病的重要病因歷史上，豬流感與人的流感有密切聯(lián)系,1918年世界流感大流行,又稱作西班牙流感這次流感并不是起源于西班牙西班牙死了近500萬人美國死了50多萬人，僅在10月份就死了 19.6 萬人全球死了2千多萬人1918年夏天首次在臨床上認(rèn)識了豬流感早期雜志專門探討豬流感和人流感的相似性?，F(xiàn)已知豬流感和人流感是由密切相關(guān)的病毒所引起,人流感病毒和豬流感病毒,從血清學(xué)實(shí)驗(yàn)證明，1918年人的流感大流行是由與1930’S從豬

9、體內(nèi)所分離的H1N1毒株相關(guān)的病毒所引起的。從福爾馬林固定的舊病理樣品、以及從被北極凍土所埋藏的人所采取的樣品中，已經(jīng)分離到1918年人流感病毒的部分基因片段。研究步表明，這些人流感病毒和豬流感病毒有密切聯(lián)系。是豬流感病毒先傳染給人，還是人流感病毒先傳染給豬？,人流感病毒和豬流感病毒,從此流感病毒在人和豬之間相互傳播豬流感病毒傳播給人自1974年以來，在美國、歐洲、新西蘭發(fā)生過多次豬流感病毒傳播給人事件，包括6起人被感染致死事件

10、。人流感病毒也可傳染給豬這是1998年在美國出現(xiàn)的重組流感病毒H3N2的主要起因。,流感病毒在人和豬之間傳播,豬流感病毒傳播給人自1974年以來，在美國、歐洲、新西蘭發(fā)生過多次豬流感病毒傳播給人事件，包括6起人被感染致死事件。人流感病毒也可傳染給豬這是1998年在美國出現(xiàn)的重組流感病毒H3N2的主要起因。,抗原變異&遺傳進(jìn)化,抗原漂移：HA亞型未變化，但抗原變異HA基因的點(diǎn)突變抗原轉(zhuǎn)變：HA亞型發(fā)生改變所致抗原

11、變異基因重排種間傳播而無基因重排也可導(dǎo)致抗原轉(zhuǎn)變,抗原漂移,抗原漂移發(fā)生于，早先感染所產(chǎn)生的抗體致使動(dòng)物群中現(xiàn)在流行的病毒發(fā)生變異，以逃脫所感染免疫動(dòng)物體內(nèi)抗體的中和作用。盡管抗原漂移是動(dòng)物群體免疫壓力所致，但是，抗原改變的基礎(chǔ)是基因突變。這種突變是逐漸進(jìn)行的，并沒有發(fā)生亞型的改變。,,Swine influenza in the United States used to be a relatively predictabl

12、e disease. It struck in the fall and winter, when temperatures dropped. The cause was a strain of swine influenza virus (SIV) known as H1N1. It spread through a barn like wildfire. Pigs ran a high fever and had a barking

13、 cough. But unless secondary bacterial infections developed, pigs recovered quickly and the swine producer had minimal production losses.,,Today, swine flu is not as predictable. There is still a flu season and the tradi

14、tional acute form of disease, but outbreaks can and often do occur at other times year. In most herds, SIV now manifests not as an acute outbreak, but as a chronic illness that leads to production losses.,,SIV is more of

15、ten seen in conjunction with other viral as well as bacterial infections. In fact, SIV, in addition to Mycoplasma hyopneumoniae and PRRS (porcine reproductive and respiratory syndrome) virus, is one of the three primary

16、pathogens contributing to porcine respiratory disease complex, one of the most costly health problems affecting U.S. swine producers. And when infections such as SIV coexist with other viruses and bacteria, the severity

17、of illness is often worse, escalating losses for the swine producer.,New Viral Strain,最近出現(xiàn)了一種新的更復(fù)雜病原H3N2，它是首先于1998年秋天，在美國北卡州一個(gè)2400頭母豬的豬場中發(fā)現(xiàn)。該豬場豬免疫了H1N1疫苗。不久H3N2在依阿華、More recently, another complicating factor has emerged

18、- a new viral strain called H3N2. It was first seen in the fall of 1998 in a 2,400-sow herd in North Carolina that had been vaccinated for H1N1. Subsequently, cases of H3N2 flu occurred in states including Iowa, Texas, M

19、innesota and Illinois.,,Compared with H1N1, H3N2 seems to cause more severe disease, possibly because herds have not yet developed any immunity to H3N2.,,A practitioner from Iowa who has treated several herds for H3N2 ou

20、tbreaks says this new SIV strain does not seem to affect pigs as seriously as swine flu due to H1N1, but the severity of illness in sows has been particularly notable. Some animals have temperatures up to 105 degrees F,

21、a large percentage go off feed for four or five days and respiratory rates are increased. Coughing has been significant, but it is not the deep cough characteristic of H1N1. H3N2 outbreaks also have resulted in abortions

22、, sow deaths and production losses.,,Exact figures on the economic losses that SIV outbreaks cause are not available, but anecdotal experience indicates two sources. One is for medication costs, particularly if SIV occur

23、s in association with bacterial infections and antibiotic treatment is required. The other and probably larger economic toll comes from the resulting production losses. H3N2 outbreaks in some herds, for instance, have le

24、d to increased mortality in the farrowing house and drops in farrowing rates from 5% to 10%.,,Lingering Questions No one knows why the character of traditional H1N1 swine flu has changed, but it is probably related to t

25、he production systems used in the modern swine industry and the large number of animals moving in and out of swine farms.,,How the H3N2 strain got into U.S. herds is also a mystery. An H3N2 strain has been present in Eur

26、opean swine herds for over 10 years, but research to date indicates it is not exactly the same H3N2 strain now affecting U.S. herds. What is known with certainty is that outbreaks of SIV due to H3N2 has increased faster

27、than anyone imagined possible. Today, the new H3N2 strain is reported to be nearly as prevalent as H1N1.,,At one North Carolina diagnostic lab, the distribution of H1N1 and H3N2 in isolates sent for testing is running ab

28、out 50/50. At the National Veterinary Services Laboratories in Ames, Iowa, 54% of isolates have been H1N1 and 46% H3N2 since the fall of 1998.,,Just a few years ago, the prevalence of the H3N2 based on blood testing of s

29、amples was less then 3%.,,Diagnosing SIVIf a herd vaccinated against H1N1 has a flu outbreak, H3N2 should be suspected, particularly if sows develop high fevers. Otherwise, H2N2 and H1N1 cannot be differentiated based o

30、n clinical signs alone. Diagnosis at a lab is required so that producers can implement appropriate control measures.,,The most widely available method of diagnosing SIV is with a blood test, or serology, known as hemaggl

31、utination inhibition (HI). It takes a few days to perform these types of tests, which can differentiate between H1N1 and H3N2 antibodies.,,A positive HI test indicates exposure to swine influenza through natural exposure

32、 and, in young pigs, it may reflect maternal antibody to SIV. A positive result can also result from vaccination.,,Other types of tests detect antigens to SIV in tissues or secretions. One is the fluorescent antibody ass

33、ay (FA); another is the immunohistochemistry test (IHC). Both FA and IHC can yield results within 24-48 hours. Producers and veterinarians need to ask the lab for additional testing to distinguish H1N1 from H3N2.,,Sample

34、 collection and handling is important to assure accurate results. It is best to ask the lab how it wants samples collected and sent. Generally, however, samples should be taken from acutely ill pigs with an elevated temp

35、erature. If too much time elapses between the time the flu erupts and samples are taken, the virus might not be present and the results could be erroneously negative.,,Managing SIVWhen an SIV outbreak occurs, the only t

36、reatment available is control of fever with aspirin or antipyretic drugs. If secondary bacterial infections develop, antibiotic treatment may be necessary. It also helps to reduce stress by keeping sick animals as comfor

37、table as possible.,,Because treatment options are limited and because SIV is more likely than before to occur in association with other diseases, leading to more severe illness and economic losses, the best approach to S

38、IV management is prevention through biosecurity and vaccination.,,Good biosecurity requires that new stock be negative for SIV exposure. New stock also should be quarantined. Traffic onto swine farms should be limited an

39、d any equipment used around stock disinfected.,,Vaccines for SIV are effective, but it is imperative that accurate diagnosis be made of the SIV strain affecting a given herd. In other words, if H3N2 is causing a problem,

40、 vaccination with the H1N1 vaccine will not help. In some herds, H1N1 may be the cause of flu outbreaks, and the H1N1 vaccine is appropriate. In other cases, herds may need vaccinated against both SIV strains.,,Vaccines

41、for H1N1 have long been available. A conditionally licensed vaccine for H3N2 was developed and produced by Schering-Plough Animal Health Corp. within months of the first H3N2 outbreak in North Carolina. The vaccine, whic

42、h has since been updated to include a U.S. H3N2 isolate found in U.S. herds., has already been administered to thousands of animals and is proving to be both safe and effective. A combination vaccine offering protection

43、against both H3N2 and the older H1N1 strain is in development and should become available later this year.,,Schering-Plough Animal Health has and will continue to keep in close touch with swine veterinarians and diagnost

44、ic labs and plans to further update the vaccine as needed. Likewise, swine producers need to work closely with their veterinarians to plan their vaccine program. In some herds affected by H3N2, producers started by vacci

45、nating just gilts, but found they also needed to vaccinate sows prefarrowing to prevent H3N2 outbreaks.,,When it is necessary to vaccinate pigs in sow-vaccinated herds, waiting until maternal antibodies to SIV have dropp

46、ed helps assure vaccine efficacy. If the vaccine is administered before then, maternal antibody may prevent the vaccine from working.,,In the United States, SIV is clearly a changing disease and management has become mor

47、e complicated. But with good biosecurity, accurate diagnosis of the SIV strain and administration of the appropriate vaccine, good control can be achieved and associated losses minimized.,豬是流感病毒重組的基地,SIV1997-1998的抗原轉(zhuǎn)變,美國

48、1976~1977年、1988~1999年的血清學(xué)檢測結(jié)果表明，H1N1是豬流感的最常見病原在這段時(shí)間，約50%的豬H1亞型抗體陽性，而只有1%的豬H3亞型抗體陽性1997~1998年的一項(xiàng)研究結(jié)果表明H3亞型抗體陽性率上升為以前的8倍1998年在美國豬體內(nèi)分離到H3N2毒株就證實(shí)發(fā)生了抗原轉(zhuǎn)變。,豬流感病毒H3N2的出現(xiàn),1998年8月在美國的北卡羅來那州的一個(gè) 2400頭母豬豬場中分離到H3N2毒株。該豬場豬免疫了H1N1

49、疫苗。感染豬發(fā)生了流感樣呼吸道疾病，種母豬流產(chǎn)，成年母豬死亡2%（典型豬流感豬只死亡很少）。之后又從美國德克薩斯州、明尼蘇達(dá)州 、衣阿華州和依利諾斯州的豬只中分離到H3N2毒株。,豬流感病毒H3N2的出現(xiàn),各病毒分離株分析結(jié)果表明1998年3月在美國的衣阿華、明尼蘇達(dá)、內(nèi)布拉斯加州的豬已感染了 H3N2，1997 年1月在加拿大安大略的豬已感染了 H3N2 。此次流行前，北美分離到H3N2僅有2次1977年在科羅拉多199

50、1年在加拿大,北卡羅來納1998年H3N2豬流感病毒,H3HA=人N2NA=人PB1多聚酶=人基質(zhì)蛋白（M1，M2）=豬核衣殼蛋白=豬非結(jié)構(gòu)蛋白=豬,H3N2豬流感病毒1998~2000,H3HA=人N2NA=人PB1多聚酶=人基質(zhì)蛋白（M1，M2）=豬核蛋白=豬非結(jié)構(gòu)蛋白=豬PA，PB2多聚酶=禽,安大略1997年H3N2豬流感病毒,H3HA=人N2NA=人PB1多聚酶=人基質(zhì)蛋白（M1，M2）=人核

51、衣殼蛋白=人非結(jié)構(gòu)蛋白=人PB2，PA多聚酶=人,美國當(dāng)今豬流感流行情況,美國只有11%左右豬群可能無豬流感Dr. Gene Erickson（Rollins Animal Disease Lab, North Carolina Department of Agriculture, Raleigh）H3N2和H1N1各占50%Dr. Sabrina Swenson（National Veterinary Service Lab

52、oratories, Ames, Iowa）從1998.8 ~ 1999.9.30日，約H1 占50% H3占50% 從1999.10.1 ~ 2000.2.21，H1占 62% H3 占38% 從H3發(fā)現(xiàn)以來，54%為 H1， 46%為 H3.,美國豬流感現(xiàn)狀,H1N1：H1HA=豬N1NA=豬PB1多聚酶=豬基質(zhì)蛋白（M1，M2）=豬核衣殼蛋白=豬非結(jié)構(gòu)蛋白=豬PB2，PA多聚酶=豬,美國豬流感現(xiàn)狀,H3N2：

53、H3HA=人N2NA=人PB1多聚酶=人基質(zhì)蛋白（M1，M2）=豬核衣殼蛋白=豬非結(jié)構(gòu)蛋白=豬PB2，PA多聚酶=禽,A/豬/安大略/01911—1,2/99（H4N6）,1999年10月，3周的病程：咳嗽、呼吸困難、體重下降2600頭生長肥育豬、青年公豬有5%被感染12頭死亡（可分離到鏈球菌、多殺性巴氏桿菌、化膿放線桿菌）PRRSV、PRCV、胸膜肺炎陰性免疫過霉形體和嗜血桿菌菌苗以前沒發(fā)生過流感，也沒有進(jìn)行

54、免疫附近湖泊水禽可分離到流感病毒,豬流感的流行病學(xué),傳播:通過鼻腔分泌物通過空氣無季節(jié)性 春、夏、秋、冬 大霧，低溫，高濕加速疾病的傳播,H3N2 豬流感,臨床癥狀許多情況下與H1N1豬流感相似 發(fā)燒(>39C)High fevers 精神沉郁流產(chǎn)與死亡咳嗽,H3N2 豬流感,嚴(yán)重病例特征一些豬場感染發(fā)病嚴(yán)重發(fā)病率接近100%成年豬死亡率超過4%。與PRRS和鏈球菌Strep.混合感染，育肥豬死亡率高

55、個(gè)別達(dá)到20%（Dr. Seehusen）流產(chǎn)率超過10%,診斷建議,臨床癥狀流行病學(xué)病理解剖血清學(xué)檢測選擇發(fā)燒病豬 至少從5頭豬采集10個(gè)鼻咽拭子，并將其放入合適病毒運(yùn)輸媒介，送往診斷室作病毒鑒定提供肺組織作為鼻咽拭子的后選樣品需要在病前和病后樣品，2次采樣間隔2-3 周血清學(xué)轉(zhuǎn)變明顯,,豬流感的控制方法,作好生物安全工作，嚴(yán)格控制豬群的轉(zhuǎn)移加強(qiáng)通風(fēng)爆發(fā)時(shí)的支持療法解熱：阿司匹林鎮(zhèn)痛：安乃近減少應(yīng)激抗繼發(fā)感

56、染：氟甲砜霉素戰(zhàn)略性使用豬流感疫苗,疫苗的使用,流行期免疫接種可縮短發(fā)病病程可控制疾病的擴(kuò)散非流行時(shí)免疫接種使豬群的免疫水平趨于一致提高機(jī)體的免疫力（豬群的健康狀況）預(yù)防疾病的發(fā)生減少豬群中病毒的排放,免疫計(jì)劃簡單,小豬每頭份2ml，兩次免疫間隔3周種豬免疫配種前，或配種時(shí)，或分娩前首次免疫每頭份2ml，兩次間隔3周以后每年2次,SIV Significant Reduction in Viral Shedd