由圆环病毒2型引起的病毒血症对生产参数的影响

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由圆环病毒2型引起的病毒血症对生产参数的影响

2012年10月10日

作者:Sergio López Soria Joaquim Segalés 译者:刘彩红

圆环病毒2型病理学和它所导致的生产损失已经成为养猪畜牧业的研究目标,因为它们是相连的。1998年，猪圆环，现在由于圆环病毒2型也叫全身性疾病。自从那时，它被认为与不同的病理学相关，还需伴随一种全身性感染，例如，断奶和育肥阶段猪感染圆环病毒2型-猪痢疾和亚临床感染疾病（圆环病毒2型-猪流感），妊娠母猪的生殖疾病(PCV2-RD)等。圆环病毒2型也与显然与疾病感染的特定器官有关，比如说肺或者肠道疾病。当然，直到今天，圆环病毒2型与猪的皮炎和肾病综合征相关，尽管它被认为是由没有明确的表征病因的免疫复合物调节产生的疾病。

当圆环病毒2型扩展到全身，同时通过血液循环传播，个体全身感染明显显示。病毒出现在血液中的现象叫病毒血症。在传统的猪场中，这种疾病常被发现在断奶和育肥阶段的最后时期的患病毒血症的动物身上。这从一个高频，更早爆发PCV2-SD的农场中可以看到，这个农场出现了圆环病毒2型引起的病毒血症动物（图1）。病毒血症的发生（没有发生）与免疫系统抵抗病毒感染的那一刻有关系。这样，产猪的免疫力可以在刚开始的4-12周保护仔猪，尽管之后病毒血症显现直到仔猪发育出积极的免疫应答。然而，这种应答的建议并不意味着病毒血症小时，但是它确实降低了病毒的载量。事实上，不想其他猪的疾病一样，圆环病毒2型具有不同的作用方式（不考虑农场中出现的圆环病毒-猪痢疾），这种作用方式常被发现在大多数比例的携带间歇及（或）持久性病毒的动物身上，它们一直维持到第28周龄。这样，在育肥阶段发现病毒血症和抗体的共同存在抵抗圆环病毒2型就不奇怪了。最近，牧场通过分析唾液进行疾病检测监督由于其经济成本低，已经开展，并且我们使用这种方法能够高效验证疾病，同样使用这种方法，动物身上的病毒在持续病变，甚至在农场中接种疫苗抵抗圆环病毒2型。

由圆环病毒2型引起的病毒血症对生产参数的影响

图1 农场中对圆环病毒2型有应答的病毒血症幼畜的百分比，它们感染或者未感染圆环病毒2型-猪痢疾(来自Sibila 等, 2004动物兽医研究期刊).

PCV2-SD可能是由圆环病毒2型导致的，有很大的经济影响，因为它能导致平均增重和饲料转化率的减少，也因为其能导致死亡率显著增加。在感染疾病以及没感染疾病的农场（都曾经感染过圆环病毒2型）中，不同的经验表现出感染压力对生长动物的生产损失有直观的影响。在实施不同的主要集中于减少疾病的扩展管理措施后，我们已经能够认识到这一事实，这正如2000年20Madc项目组建议的一样。在这条道路上，我们已经看到，许多研究中，有PCV2-SD临床特征的动物血液中病毒的感染率显著高于健康仔猪。事实上，病毒血症水平是建议水平，当其水平高于建议水平时，动物被认为是已经感染了PCV2-SD（变化在>104.7~107.4PCV2基因拷贝子/ml血清，依据实验室进行的分析检测）。这些结果显示血液中高PCV2水平对于疾病表征是关键的。因此，由PCV2导致的损失不仅仅是与病毒血症显现（或者不显现）相关的，而且与大量的病毒相关。在这个意义上，今天我们知道因为平均增重减少，PCV2导致了损失，没有必要在感染PCV2-SD的动物体内发现单个病毒，因为感染病毒载量已经很多了。低到中度的病毒载量已经导致显著的生长损失，这发生在PCV2-SI病例中，这些在没有PCV-SD病例农场接中，能够清楚地看到，接种疫苗的小猪或者某些由接种母猪生下的小猪，它们的日增重为20-51g。这个事实是真的，是毫无疑问的，是了解PCV2病理学知识的步骤，也是解释农场认为接种疫苗后，PCV2不再是一个麻烦，农场也会有盈利。

在成年动物体中，与那些正在生长的动物相比，病毒血症不是很频繁的，因为在断奶和/或育肥阶段他们与病毒接触先于获得免疫能力。这样，母体妊娠阶段，病毒血症能导致PCV2-RD，因为病毒能够通过胎盘，并引起不同的临床特征，这依据于胎盘感染的那一刻，在表1中解释。病毒血症幼畜出生时携带母体的病毒因为它们在妊娠期间被通过胎盘感染，同时它们是一个感染的源头对于周边的动物来说。然而，这些情况主要描述的是阴性母猪，在群体动物中对PCV2很少显高阳性率，这是由于它们先前在断奶和/或育肥阶段与病毒接触，也因为病毒在母猪体内的循环。即便如此，我们必须认识到免疫的事实，然而疫苗或者从之前感染体接种，不能去除病毒血症，像那些通过阴性母猪的胎盘感染病毒的例子。

在妊娠期间胎儿感染的时期	对生殖参数的影响
第1-35天	死胎、定期返情、假妊娠（假孕）、窝产仔数少
第35-70天	木乃伊胎、流产
第70-115天	木乃伊胎、仔猪出生时死亡（死胎）、仔猪出生时体弱、晚产、流产

因此，由于PCV2导致的病毒血症也是全身性基本因为病毒能够导致生长小猪和妊娠母猪的生产损失。积极预防由PCV2导致的生产损失的方法是阻止病毒血症，包括被动或主动免疫，减小病毒在农场种的循环。在这篇报道中，疫苗能够显著减少病毒血症小猪以及血液中病毒感染的百分比（图2）包括病毒的分泌排泄。它们的成功之处在生产参数的显著改善中可以看到。即使如此，我们必须说使用疫苗对抗母体包括小猪的PCV2不能够形成消灭免疫，感染在农场种仍然存在。

图2：对比动力学特征，病毒感染小猪（线）的百分比和感染病毒小猪的平均病毒载量（柱），它们全部用定量PCR ...

图2：对比动力学特征，病毒感染小猪（线）的百分比和感染病毒小猪的平均病毒载量（柱），它们全部用定量PCR检测，在3周龄接种疫苗，以及没有接种对抗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

英文来源：pig333.com