Circovirus: Now for the good news
Encouraging results from North America on PCV2 vaccination and valuable European updates on immunity to the virus are reported to a major veterinary meeting held in the USA
Orlando in Florida, USA, is famous as the home of the Disneyland resort. This year the town was the setting for some announcements that should cause pig producers everywhere to celebrate. Orlando gave the backdrop to an exchange between Europe and North America of some highly encouraging information over the costly diseases associated with the PCV2 porcine circovirus.
This exchange formed a major part of the latest annual congress of the American Association of Swine Veterinarians. The visit to Florida in 2007 by the AASV not only brought the unveiling by European experts of valuable updates on circovirus pathogenesis and immunity, but also the presentation by the North Americans of amazingly successful results from vaccinating against PCV2 and its assortment of associated diseases collectively called PCVAD. Among these is the post-weaning multisystemic wasting syndrome otherwise known as PMWS.
Pathogenesis and immunity
Invited lecturer Hans Nauwynck from the University of Ghent in Belgium described how PCV2 is likely to be spread from pig to pig by the faecal and respiratory routes. Pigs, even wild boar, have been infected with the virus for several decades and the various viral strains show a genetic similarity with each other of over 94%. The infection is now worldwide.
At the herd level, piglets are born from naturally infected, immune sows with varying levels of maternally derived antibodies that last for several weeks. When exposed to PCV2, actual infection in piglets occurs during the period between Week 2 and Week 12 of life in the presence of declining antibodies, although the effects vary from herd to herd. Infections in the uterus can also occur, causing reproductive problems in sows.
Contaminated semen is thought to be capable of carrying the virus into high-health herds. Relatively speaking, the virus is slow-growing, taking approximately 36 hours to replicate. Replication in cells can be increased in the laboratory following exposure to interferon-alpha. Normally this is produced by cells as a protective anti-viral cytokine, but it may act as a trigger for PCV2 to replicate when other viral infections such as PRRS occur.
Immuno-stimulation of a pig may also increase virus replication. Following infection, the virus can be found 2-3 weeks later in lymphoid tissue and organs such as lungs, liver and heart. Antibodies are normally produced by 3 weeks after infection and the virus replication is reduced. However, some pigs are not able to produce antibodies due to a damaged immune system and virus replication continues until, finally, clinical PCVAD/PMWS disease is produced.
Another invited lecture, from Ken McCullough of the Institute of Virology at Mittelhausern in Switzerland, described the complexities of the immunological effect of PCV2 infection. Following an infection with PCV2, there is a reduction of white blood cells (this is called leucopoenia) seen in the pigs, which go on to develop PCVAD. The leucopoenia is associated primarily with a depletion of type-B lymphocytes (cells that tell the immune system to produce antibodies) and to a lesser extent the type-T lymphocytes, which stimulate the production of killer cells to kill virus-infected cells and so disable the normal immune response to infection.
However, high levels of virus are found in dendritic cells, which present antigens to the immune system, and also in the macrophages that eat up dying cells and infectious agents. It is thought that the virus does not kill these cells and they continue to function, but it impairs their recognition of danger signals' from other invading organisms. So these infections can come in more easily and cause disease. This would explain some of the additional complications that are seen following enzootic pneumonia and PRRS virus infections and the extensive pneumonias that are caused.
The majority of pigs will respond immunologically and control the PCV2 infection. But PCVAD is more likely to develop if the challenge is high and fast and there is an extra load of additional infections, which may stimulate the replication of the virus.
The Americans and Canadians reported various trials with both a killed PCV2 sow vaccine and 3 versions of killed vaccine for piglets. Their results are summarised in Table 1 and Figure 1.
Plourde and Machell described the response to the sow vaccine (Circovac from Merial) on 77 farms in Canada that had used it over a period of 6 months. The researchers' interviews by telephone with 41 veterinarians compared each unit's total mortality results before vaccination and afterwards. On average, the mortality in the herds that started vaccinating ran at 12.6% (in a range from 11.8% up to 13.3%). After half a year of vaccinations the death losses were down to 5.2% on average, ranging from 5% to 5.4% depending on the unit. So the drop in mortality worked out at 7.4 percentage points.
Desrosiers and others reported on a blinded, controlled study in Canada with using Ingelvac CircoFlex (Boehringer Ingelheim) on a 1300-sow unit where all the nursery pigs were divided into 2 treatment groups. One group was vaccinated while the control pigs were given a placebo instead. The nursery contained 4 multiple-aged groups in which the youngest members had just been weaned at 19-22 days of age while the oldest was 59 days. Vaccinated 3 days before entering the finisher barns, these pigs originated from a herd that was free of both enzootic pneumonia and PRRS. Previously the mortality in the nursery had been low (0.4%), but PCVAD developed later, normally after 3-4 weeks in the finishing house.
The trial involved 3850 pigs and found the combined mortality in the unvaccinated placebo controls averaged 9.5%. Only 2.4% of the vaccinated pigs died, a reduction of 7.1 percentage points. A trend to an improved response to vaccination was noted in younger pigs (see Figure 2), which fits in well with the pathogenesis of the disease we now know the value of stimulating an early immune response before viral damage is caused to the immune system.
Connor and Elsenier described a series of trials with Suvaxyn PCV2 (Fort Dodge Animal Health) in the USA, where the product is now licensed. Two trials were carried out comparing a vaccinated group and an unvaccinated group and a further 4 trials were conducted on a before-and-after-vaccination basis, the mortality in the grower/finisher period being recorded. Four herds were positive for enzootic pneumonia, but none for PRRSV. The average of the 6 trials showed a reduction of mortality from 7.7% to 1.8%, an improvement of 5.9 percentage points. Interestingly, PCV2 viraemia was noted between 8-10 weeks of age and the disease signs started 1-2 weeks later.
De Grau and others carried out a trial in Quebec and Ontario, Canada, using Porcilis PCV2 (Intervet), a 2-shot killed piglet vaccine. The trial was designed as a multi-centred, randomised study involving 21 farms. The pigs were vaccinated initially at 3-5 weeks of age and given a booster 3 weeks later. Over 35 000 pigs were used in the study. The overall mortality in the unvaccinated animals was 9.3%, whereas it was just 2.1% in the ones vaccinated. The investigation team noted that pigs injected after 5 weeks of age had a slightly higher mortality of about 4% compared with 1.5% in farms vaccinating by 3 weeks of age. A local injection-site reaction to the vaccine was noted in 16% of cases.
One central conclusion has been suggested from the depth of the presentations to the AASV meeting. Although the epidemiology and immunology of PCV2 infections are undoubtedly complex, the research work by the European and North American teams has pushed forward our boundaries of knowledge to a considerable extent. The know-how today after 8 years of international problems with PMWS makes exciting news. The results of the vaccine trials in North America may not have come in time to avoid the major losses that cost millions of dollars every year in Europe, but they indicate the tools are here at last with which to control this infection. Despite being carried out to a variety of designs, the trials show clearly that the products work exceptionally well and give real hope for the future. Mortality in finishing pigs has been brought down to the levels that were normal before PCV2 became an issue. PIGI