由圓環病毒2型引起的病毒血癥對生產參數的影響

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由圓環病毒2型引起的病毒血癥對生產參數的影響

2012年10月10日

作者:Sergio López Soria Joaquim Segalés 譯者:劉彩紅

圓環病毒2型病理學和它所導致的生產損失已經成為養豬畜牧業的研究目標,因為它們是相連的。1998年，豬圓環，現在由于圓環病毒2型也叫全身性疾病。自從那時，它被認為與不同的病理學相關，還需伴隨一種全身性感染，例如，斷奶和育肥階段豬感染圓環病毒2型-豬痢疾和亞臨床感染疾病（圓環病毒2型-豬流感），妊娠母豬的生殖疾病(PCV2-RD)等。圓環病毒2型也與顯然與疾病感染的特定器官有關，比如說肺或者腸道疾病。當然，直到今天，圓環病毒2型與豬的皮炎和腎病綜合征相關，盡管它被認為是由沒有明確的表征病因的免疫復合物調節產生的疾病。

當圓環病毒2型擴展到全身，同時通過血液循環傳播，個體全身感染明顯顯示。病毒出現在血液中的現象叫病毒血癥。在傳統的豬場中，這種疾病常被發現在斷奶和育肥階段的最后時期的患病毒血癥的動物身上。這從一個高頻，更早爆發PCV2-SD的農場中可以看到，這個農場出現了圓環病毒2型引起的病毒血癥動物（圖1）。病毒血癥的發生（沒有發生）與免疫系統抵抗病毒感染的那一刻有關系。這樣，產豬的免疫力可以在剛開始的4-12周保護仔豬，盡管之后病毒血癥顯現直到仔豬發育出積極的免疫應答。然而，這種應答的建議并不意味著病毒血癥小時，但是它確實降低了病毒的載量。事實上，不想其他豬的疾病一樣，圓環病毒2型具有不同的作用方式（不考慮農場中出現的圓環病毒-豬痢疾），這種作用方式常被發現在大多數比例的攜帶間歇及（或）持久性病毒的動物身上，它們一直維持到第28周齡。這樣，在育肥階段發現病毒血癥和抗體的共同存在抵抗圓環病毒2型就不奇怪了。最近，牧場通過分析唾液進行疾病檢測監督由于其經濟成本低，已經開展，并且我們使用這種方法能夠高效驗證疾病，同樣使用這種方法，動物身上的病毒在持續病變，甚至在農場中接種疫苗抵抗圓環病毒2型。

圖1 農場中對圓環病毒2型有應答的病毒血癥幼畜的百分比，它們感染或者未感染圓環病毒2型-豬痢疾(來自Sibila 等, 2004動物獸醫研究期刊).

PCV2-SD可能是由圓環病毒2型導致的，有很大的經濟影響，因為它能導致平均增重和飼料轉化率的減少，也因為其能導致死亡率顯著增加。在感染疾病以及沒感染疾病的農場（都曾經感染過圓環病毒2型）中，不同的經驗表現出感染壓力對生長動物的生產損失有直觀的影響。在實施不同的主要集中于減少疾病的擴展管理措施后，我們已經能夠認識到這一事實，這正如2000年20Madc項目組建議的一樣。在這條道路上，我們已經看到，許多研究中，有PCV2-SD臨床特征的動物血液中病毒的感染率顯著高于健康仔豬。事實上，病毒血癥水平是建議水平，當其水平高于建議水平時，動物被認為是已經感染了PCV2-SD（變化在>104.7~107.4PCV2基因拷貝子/ml血清，依據實驗室進行的分析檢測）。這些結果顯示血液中高PCV2水平對于疾病表征是關鍵的。因此，由PCV2導致的損失不僅僅是與病毒血癥顯現（或者不顯現）相關的，而且與大量的病毒相關。在這個意義上，今天我們知道因為平均增重減少，PCV2導致了損失，沒有必要在感染PCV2-SD的動物體內發現單個病毒，因為感染病毒載量已經很多了。低到中度的病毒載量已經導致顯著的生長損失，這發生在PCV2-SI病例中，這些在沒有PCV-SD病例農場接中，能夠清楚地看到，接種疫苗的小豬或者某些由接種母豬生下的小豬，它們的日增重為20-51g。這個事實是真的，是毫無疑問的，是了解PCV2病理學知識的步驟，也是解釋農場認為接種疫苗后，PCV2不再是一個麻煩，農場也會有盈利。

在成年動物體中，與那些正在生長的動物相比，病毒血癥不是很頻繁的，因為在斷奶和/或育肥階段他們與病毒接觸先于獲得免疫能力。這樣，母體妊娠階段，病毒血癥能導致PCV2-RD，因為病毒能夠通過胎盤，并引起不同的臨床特征，這依據于胎盤感染的那一刻，在表1中解釋。病毒血癥幼畜出生時攜帶母體的病毒因為它們在妊娠期間被通過胎盤感染，同時它們是一個感染的源頭對于周邊的動物來說。然而，這些情況主要描述的是陰性母豬，在群體動物中對PCV2很少顯高陽性率，這是由于它們先前在斷奶和/或育肥階段與病毒接觸，也因為病毒在母豬體內的循環。即便如此，我們必須認識到免疫的事實，然而疫苗或者從之前感染體接種，不能去除病毒血癥，像那些通過陰性母豬的胎盤感染病毒的例子。

在妊娠期間胎兒感染的時期	對生殖參數的影響
第1-35天	死胎、定期返情、假妊娠（假孕）、窩產仔數少
第35-70天	木乃伊胎、流產
第70-115天	木乃伊胎、仔豬出生時死亡（死胎）、仔豬出生時體弱、晚產、流產

因此，由于PCV2導致的病毒血癥也是全身性基本因為病毒能夠導致生長小豬和妊娠母豬的生產損失。積極預防由PCV2導致的生產損失的方法是阻止病毒血癥，包括被動或主動免疫，減小病毒在農場種的循環。在這篇報道中，疫苗能夠顯著減少病毒血癥小豬以及血液中病毒感染的百分比（圖2）包括病毒的分泌排泄。它們的成功之處在生產參數的顯著改善中可以看到。即使如此，我們必須說使用疫苗對抗母體包括小豬的PCV2不能夠形成消滅免疫，感染在農場種仍然存在。

圖2：對比動力學特征，病毒感染小豬（線）的百分比和感染病毒小豬的平均病毒載量（柱），它們全部用定量PCR檢測，在3周齡接種疫苗，以及沒有接種對抗PCV2疫苗的。

英文原文

Effect of the viraemia due to the porcine circovirus type 2 (PCV2) on production parameters
10-Oct-2012
Sergio López SoriaJoaquim Segalés
The pathology associated to the porcine circovirus type 2 (PCV2) and its resulting production losses in the swine livestock has been the object of study since it was associated, in 1998, with the porcine circovirosis, also called, currently, systemic disease due to PCV2 (PCV2-SD). Since then, it has been related to different pathologies that need a systemic infection as, for instance, the PCV2-SD and the subclinical infection (PCV2-SI) in animals in the weaners and the fattening stages, as well as a reproductive disease (PCV2-RD) in pregnant sows. The PCV2 has also been associated to diseases that affect, apparently, specific organs, as in the case of the lung or the enteric disease. Also, even today, the PCV2 is associated to the porcine dermatitis and nephropaty syndrome, although being considered as a disease mediated by immunocomplexes without a definitely demonstrated etiology.
The systemic infection of an individual appears when the PCV2 spreads through the body, being the blood circulation the vehicle for its dissemination. This phenomenon in which the virus is found in the blood is called viraemia. In conventional farms, it is frequent to find viraemic animals during the end of the weaners stage and the fattening stage. It has been seen that the presence of viraemic animals due to the PCV2 occurs with a higher frequency and earlier in farms with PCV2-SD (Figure 1). The establishment (or not) of a viraemia is associated to the presence of immunity against the virus at the moment of the infection. So, the maternal immunity can protect the piglet during its first 4-12 weeks of age, although subsequently a viraemia normally appears until the piglet develops an active response. Nevertheless, the establishment of this response not always implies the elimination of the viraemia, but it does reduce the viral load. In fact, unlike other porcine viruses, the viraemias due to PCV2 have a variable way of working (regardless of the presence or not of PCV2-SD in the farm), in which it is frequent to find an important proportion of the animals with intermittent and/or long lasting viraemias that can go on until the 28th week of age. So, it is not strange to find the coexistence of viremia and antibodies against the PCV2 during all the fattening stage. Recently, the implementation of the monitoring of the infection in the farms through the analysis of oral fluids due to its lower financial cost has started, and we have been able to verify efficiently, also with this method, the long-lasting persistence of the virus in the animals that are growing, even in farms that vaccinate against the PCV2.

Fig. 1. Percentage of viraemic piglets with respect to the PCV2 in farms with and without PCV2-SD (adapted from Sibila et al., 2004 Am J Vet Res).
The PCV2-SD is, probably, the disease caused by the PCV2 with a higher financial impact because it causes losses in the average weight gain and the feed conversion ratio, and because it increases the mortality remarkably. The different experiences in farms with and without the disease (although infected by the PCV2 in both cases) have shown that the infection pressure has a direct impact on the production losses of the animals that are growing. We have been able to check this fact after applying different management measures focused on limiting the spreading of the disease, as can be the case with the 20 Madec items suggested in year 2000. In the same way, we have seen, in many studies, that the animals with clinical signs of PCV2-SD have a viral load in the blood significantly higher in comparison with healthy piglets. In fact, viremia levels were suggested, and when the levels found where higher than the suggested ones, it could be considered that an animal suffered PCV2-SD (varying from > 104.7 to 107.4 copies of PCV2 genome/ml of blood serum, depending on the laboratory that performed the analysis). These results tell that high PCV2 levels in the blood are critical for the expression of the disease. So, the losses associated with the PCV2 are not only related to the presence (or not) of viremia, but also to the amount of viruses. In this sense, nowadays we know that in order for the PCV2 to cause losses due to the reduction of the average weight gain, it is not necessary for the viral load to be so high as the one found in the animals affected by the PCV2-SD. Low to moderate viral loads already cause significant growth losses, as it happens in the case of the PCV2-SI, and this has been clearly seen by means of vaccines in farms without PCV2-SD in which the vaccinated piglets or those born to vaccinated sows had a daily weight gain of + 20-51 g. This fact has been, without a doubt, a step forward into the knowledge of the pathology associated to the PCV2, and it is the one that explains that farms that considered that the PCV2 was not a problem have decided to vaccinate and have had profitable results.
In adult animals the viremia is less frequent than in animals that are growing, because the previous contact with the virus during the weaners and/or the fattening stages grants them immunity. So, the viremia during the pregnancy stage can give a result PCV2-RD, because the virus can go through the placenta and cause different clinical manifestations according to the moment of the infection during the pregnancy, as it is explained in Table 1. There is also the possibility that viremic piglets are born to viremic sows beceuse they have been infected through the placenta during the gestation, being then a source if infection of the animals that are in their surroundings. Nevertheless, these situations have been mainly described in seronegative sows, being this a rare fact given the high seroprevalence against PCV2 in this group of animals due to the previous contact with the virus during the weaner and/or the fattening stages, and due to the recirculation of the virus in the sows. Even so, we must comment that the fact of having immunity, whereas vaccinal or derived from a previous infection, does not exclude the viremia, so the infection through the placenta is also possible in seropositive sows.

Moment of the infection of the foetus during the gestation	Consequence on the reproductive parameters
1st-35th day	Embryo death Regular return to oestrus Pseudogestation (false pregnancy) Small litters
35th-70th day	Mummified foetuses Abortions
70th-115th day	Mummified foetuses Piglets born dead (stillbirths) Piglets born being weak Late births Abortions

Table 1. Reproductive problems associated with the PCV2 according to the moment of the infection of the foetus during the gestation (adapted from Opriessnig and Langohr, 2012 Vet Pathol).
So, the viraemia due to the PCV2 is the indicator of a systemic infection due to the virus that is able to cause production losses in growing piglets and in pregnant sows. The most effective way to avoid the production losses related to the PCV2 is to avoid the viremia, inducing a passive or an active immunity that minimizes the circulation of the virus in the farm. In this sense, the vaccines have proven that they reduce significantly the percentage of viraemic piglets, as well as the viral load in the blood (Figure 2) and the virus excretion, and it is here where the key of their success seems to be: in the remarkable improvement of the production parameters. Even so, we must say that the vaccines against the PCV2 in sows, as well as in piglets do not cause a sterilizing immunity, so the infection go on in the farm.

Figure 2. Comparative figure of the dynamics of the percentage of viraemic piglets (lines) and the average viral load in the viraemic piglets (bars), both of them measured with quantitative PCR, in animals vaccinated at 3 weeks of age and not vaccinated against the PCV2

英文來源：pig333.com