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從古典豬瘟的存在看非洲豬瘟的防控

點擊次數(shù)：
日期： 2019-03-11
來源： TK康博士曾容愚

1.古典豬瘟和非洲豬瘟的臨床癥狀最相似，是早發(fā)現(xiàn)ASF疑似豬群，早隔離處理措施的最大干擾項。凈化豬瘟，就可以更好地感知ASF的入侵。

1.1 在豬群非洲豬瘟已經(jīng)呈現(xiàn)地方性流行的地區(qū)，其特征已從死亡率接近100%的特急性疾病轉(zhuǎn)變?yōu)樗劳雎瘦^低的疾病，但是，急性、亞急性或慢性的感染率會增加（SanchezBotija和Polo Jover，1964年；Scott，1965a）。通常不可能根據(jù)臨床癥狀和病變來區(qū)分這些形式的非洲豬瘟和古典豬瘟。更令人擔(dān)憂的是，帶毒豬只在家豬中維持和傳播非洲豬瘟的作用變得越來越重要(W.R.Hess,1971）

In areas where ASF has become enzootic in domestic swine, its character has changed from a peracute disease with mortality approaching 100 per cent to a disease of lesser mortality with an increased incidence of acute, subacute, and chronic infections (SANCHEZ BoTIJA and PoLo JovER, 1964; ScoTT, 1965a). It is often impossible on the basis of clinical signs and gross lesions to distinguish these forms of ASF from classical swine fever. Of even greater concern is the fact that carriers have become increasingly important in the maintenance and spread of the disease in domestic swine (W.R.Hess,1971).

1.2 ASF和CSF感染的細胞亞群高度一致

非洲豬瘟病毒和豬瘟病毒都對免疫系統(tǒng)的細胞，主要是那些來自單核巨噬細胞譜系（屬于白細胞），有感染嗜性。利用這些細胞特有在全身的游走能力，實現(xiàn)病毒的擴散和持續(xù)感染，是這兩個病毒在體內(nèi)得以復(fù)制和產(chǎn)生致病性的重要手段。非洲豬瘟感染出現(xiàn)發(fā)熱反應(yīng)，在此期間，白細胞總數(shù)可能降至正常值的40%左右（Detrayand Scott，1957年）。此外，ASF感染的豬血小板降低30倍（臨床發(fā)現(xiàn)ASF感染豬血凝不良）（Hovakim Zakaryan，2014）

Both ASFV and CSFV sharea tropism for immune system cells, mainly those that are derived from themonocytemacrophage lineage.It is assumed that theinfection of these cells plays an important role in virus replication andpathogenesis by exploiting their migratory ability, which promotes viral spreadand persistence in the host for both ASFV and CSFV. During this period thetotal leukocyte count may fall to about 40 per cent of normal (DETRAYand ScoTT,1957). By the last day of infection the number of platelets in the peripheral blood was 30-fold reduced compared with control (Hovakim Zakaryan，2014).

1.3 ASF和CSF感染破壞的組織和器官高度一致

如CSF一樣，ASF幾乎專門侵害網(wǎng)狀內(nèi)皮組織。事實上，每個器官和組織都可能顯示出一些由血管損傷引起的變化。

The virus acts almostexclusively on reticuloendothelial tissues. In fact, every organ and tissue mayshow some changes that are attributable to vascular damage.

2. 在非洲豬瘟疫苗上市之前，豬體健全強大的免疫系統(tǒng)是豬感染ASF后減少排毒，減少擴散，實現(xiàn)“早發(fā)現(xiàn)，早處理,'拔牙式'”定點清除策略的唯一武器。豬瘟是破壞免疫系統(tǒng)的頭號疾病，導(dǎo)致豬體最廣泛的免疫抑制。所以，非瘟面前，做好古典豬瘟的深度防控和場內(nèi)凈化，尤其重要。

2.1 豬瘟病毒感染加劇非洲豬瘟病毒感染損失的免疫學(xué)機理

2.1.1 從ASFV感染中康復(fù)的豬通�？梢缘钟N病毒下一次的感染，但一般情況下沒有對異種病毒的交叉保護能力。總的來說，是否存在抗體介導(dǎo)的保護，即中和抗體，仍有爭議。注射高免血清可能有一定的緩解作用。然而，好幾個報道認為根本不存在中和抗體，其他報道在體外實驗時發(fā)現(xiàn)抗體可以降低病毒滴度或在一定程度上中和ASF病毒。

雖然抗體的作用仍存爭議，細胞毒性T細胞似乎是抗病毒免疫保護的主力軍。有報道證明，CD8+T細胞的減少將會導(dǎo)致保護作用的消失（Schulz et al,2017, Vet Res）。

2.1.1 Pigs recoveringfrom ASFV infection are usually protected against homologues challenge, butcross-protection against heterologous strains is often missing. Generally,theexistence of an antibody-mediated protection, i.e. virus neutralization, iscontroversially discussed. It is possible to confer a certain level ofprotection by passive transfer of hyperimmune sera [23]. However, severalauthors suggest the complete absence of neutralizing antibodies [24], others foundthat antibodies could reduce virus titers or neutralize ASF virus to a certainextent in vitro [25–27]. While the role of antibodies is controversiallydiscussed, cytotoxic T-cell responses seem to play a major role in mediatingantiviral protection. It was demonstrated that depletion of CD8+ cells leads toabrogation of protection [31].

2.1.2 豬瘟病毒導(dǎo)致的各個白細胞亞群的數(shù)量減少程度不同，其中B淋巴細胞，輔助性T細胞和細胞毒性T細胞的數(shù)量減少最明顯，這會導(dǎo)致豬體出現(xiàn)廣泛性的免疫抑制，這種免疫抑制不僅僅是針對豬瘟病毒感染本身，而且針對與豬瘟病毒同時出現(xiàn)的混合感染或者隨后出現(xiàn)的繼發(fā)感染（Summerfield等，2001）。

2.1.2 CSF leukopeniaaffects leukocyte subpopulations unequally, with B-lymphocytes, helper T cells,and cytotoxic T cells the most affected. This would have consequences in termsof the immuno-compromisation of the animals,not only in the face of CSFV, butalso with respect to other concomitant or secondary infections（Summerfield et al,2001）.

綜上所述，豬瘟感染會導(dǎo)致豬體白細胞的減少，尤其是細胞毒性T細胞的減少，而細胞毒性T細胞又是目前知道的豬體對非洲豬瘟產(chǎn)生保護的主要力量，因此，小編推測，豬瘟感染豬只一旦繼發(fā)非洲豬瘟感染，其原本低下的免疫保護力將會變得更加不堪一擊，臨床損失會加劇。也就是說豬瘟病毒感染可能會加劇非洲豬瘟病毒感染的損失（下面試驗剛好證這推測）。

2.2 雙重感染的案例

亞臨床感染經(jīng)典豬瘟的野豬再感染非洲豬瘟的研究

African swine fevervirus infection in Classical swine fever subclinically infectedwild boars Cabezón et al. 2017,BMCVeterinary Research

2.2.1 有趣的是，感染豬瘟的野豬（A組）表現(xiàn)為典型的漸進性急性出血性疾病。然而，沒有感染豬瘟病毒的野豬（B組）沒有一頭表現(xiàn)出血性疾病的臨床特點。就臨床癥狀的嚴重性而言，兩組在感染非洲豬瘟后4天和7天之間差異達到統(tǒng)計學(xué)意義上顯著的水平（p<0.05）。

2.2.1 Interestingly, theanimals infected with a CSF persistent form (Group A) showed a progressiveacute haemorrhagic disease after ASFV infection. However, none of thepestivirus-free-ASFV infected wild boars (Group B) developed the haemorrhagicclinical form of the disease. Statistical significant differences (p < 0.05)in terms of clinical signs between both experimental groups were found from 4dpi to 7 dpi.

2.2.2 IFN-α是豬先天性免疫應(yīng)答的支柱力量，豬瘟病毒持續(xù)感染的豬一直保持IFN-α陰性，這也就是為什么豬瘟病毒亞臨床感染的豬一直能夠在體內(nèi)維持高而恒定的豬瘟病毒載量[28，42]。本試驗再次令人吃驚地發(fā)現(xiàn)在豬瘟亞臨床感染的野豬中，IFN-α的應(yīng)答受到了抑制，即使這些豬后來感染了非洲豬瘟病毒，這樣一個能對先天性免疫系統(tǒng)產(chǎn)生強烈刺激的病毒，IFN-α的應(yīng)答一直沒有增強。

2.2.2 The CSFV PIanimals remained IFN-α negative, a cornerstone in the innate immunemechanisms; this fact might promote the maintenance of a high and constant CSFV load [28, 42]. Strikingly, once again, the IFN-α response seemed to beimpaired in CSFV PI animals,even after infection with the ASFV virus, whichinduces a potent effect on the innate immune system.

在兩種疾病都流行的國家，考慮到ASF傳播的增加和CSF亞臨床形式的長期共存，不能排除豬同時感染ASFV和CSFV的可能性，需要更深入地研究。本試驗提示豬瘟亞臨床感染可能會使豬只更易感非洲豬瘟病毒，并加重其病程（國內(nèi)臨床已有雙重感染的發(fā)現(xiàn)，私人通訊）。

Considering theco-existence of the increasing spread of ASF and the presence of CSF subclinical forms in endemic countries for both diseases, the possibility of ASFV and CSFV co-infection in swine cannot be ruled out and needs to be studiedin greater depth. The CSFV subclinical infection may also predispose animals toASF disease and aggravate its progression.

3. ASF面前，減少免疫次數(shù)就是減少豬群里面ASF傳播的風(fēng)險。2018年天康豬瘟E2疫苗大量使用數(shù)據(jù)證明，母豬一年只需免疫2針，仔豬只需免疫一針就能上市；進一步減少豬群的應(yīng)激和人和豬的接觸，降低豬群感染ASF的風(fēng)險。過去的2018年，我們成功地解放了豬瘟超免用戶，2019年我們將繼續(xù)解放豬瘟首免用戶。

感染基因II型ASF毒株后第三天出現(xiàn)臨床癥狀，第二天就出現(xiàn)毒血癥。這個信息提示我們，對外表健康的豬免疫疫苗，也有散毒風(fēng)險（針頭散毒是必然的）。

Although the firstclinical signs of infection appeared at 3 dpi,viremia was observed after the 1st day of infection.

3.1 母豬連續(xù)免疫2次E2后，抗體持續(xù)280天。