Europe meets N. America over PMWS PCVAD

Europe meets N. America over PMWS/PCVAD - The Way Forward
by
David G S Burch
BVetMed DECPHM MRCVS
Veterinarian, Octagon Services Ltd

(Published in "Pig International" May 2007)

The recent American Association of Swine Veterinarians Congress in Orlando, Florida, was the venue for the two continent's latest views and information exchange on Porcine Circovirus type 2 (PCV2) and its associated diseases (PCVAD) or Post-weaning Multisystemic Wasting Syndrome (PMWS). Its pathogenesis and immunity were presented by European experts and the amazingly successful vaccination results by the North Americans.
Pathogenesis and Immunity
Hans Nauwynck from the University of Ghent in Belgium described how PCV2 is likely to be spread from pig to pig by the oro-faecal and respiratory route. Pigs, even wild boar, have been infected with the virus for several decades and the various strains show a >94% genetic similarity and the infection is now worldwide. At the herd level, piglets are born from naturally infected, immune sows, with varying levels of maternally derived antibodies (MDAs), which last for several weeks. When exposed to PCV2, actual infection in piglets occurs from week 2-12 in the presence of declining antibodies and varies from herd to herd. Infections in the uterus can also occur, causing reproductive problems in sows but usually at first exposure to the virus in high health herds and semen is thought also to be a carrier of the virus. 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, which is normally produced as a protective anti-viral cytokine and this may act as a trigger to PCV2 when other infections 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 post infection and the virus replication is reduced. However, some pigs are not able to produce antibodies and virus replication continues and finally clinical PCVAD/PMWS disease is produced.
Ken McCullough, formerly of Belfast, N. Ireland, described the complexities of the immunological effect of PCV2 infection. Following an infection with PCV2, there is a reduction of white blood cells (leucopoenia) seen in the pigs, which go on to develop PCVAD. The leucopoenia is primarily associated with depletion of the B lymphocytes, the cells that tell the immune system to produce antibodies and to a lesser extent the T lymphocytes, which stimulate the production of killer cells to kill virus-infected cells, thus disabling the normal immune response to infection. However, the cells with the high level of virus are the dendritic cells, which present antigens to the immune system and the macrophages, which also eat up dying cells and infectious agents. It is thought that the virus does not kill these cells and they continue to function but the virus impairs their recognition of 'danger signals' from other invading organisms and permits these infections to 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 if the challenge is high and fast and there is an extra load of additional infections, which may stimulate the replication of the virus, then PCVAD is more likely to develop.
Clinical trials
The Americans and Canadians described a variety of trials with both the killed PCV2 sow vaccine and three various killed vaccines for piglets and their results are summarised in Table 1 and Graph 1.
Plourde and Machell described the response to the sow vaccine (Circovac® - Merial) in Canada in 77 farms, which had used the vaccine over a six-month period. They telephone interviewed 41 veterinarians and compared the farm's total mortality results before vaccination and afterwards. On average, the mortality was running at 12.6% (max 13.3 - min 11.8%) before vaccination and 5.2% (max 5.4 - min 5.0%) following vaccination giving a 7.4% drop in mortality.

Table 1. Comparison of the effect on mortality of sow and piglet vaccines against PCV2

Product	Vaccine	Type of trial	Mortality unvaccinated (%)	Mortality vaccinated (%)
Circovac	Sow (2 shot followed by booster 1 shot)	Before and after studies (77 farms) Total mortality	12.6	5.2
CircoFLEX	Piglet (1 shot)	Controlled study; vaccinated & non-vaccinated Finisher mortality	9.5	2.4
Suvaxyn PCV2	Piglet (1 shot)	2 controlled studies & 4 before and after studies. Grower/finisher mortality	7.7	1.8
Porcilis PCV2	Piglet (2 shot)	Multi-centred randomised studies (22 farms), vaccinated and non-vaccinated. Nursery and finisher mortality	9.3	2.1

Graph 1. Comparison of the effect on mortality of sow and piglet vaccines against PCV2

Desrosiers and others reported on a blinded, controlled study in Canada with Ingelvac® CircoFLEX™ (Boehringer Ingelheim) on a 1300 sow unit, where all the nursery pigs were divided into two treatment groups, vaccinated and unvaccinated (given a placebo) control. There were four multiple-aged groups in the nursery, the youngest just weaned at 19-22 days of age to the oldest 59 days, 3 days prior to movement into the first of the four finisher barns. The herd was enzootic pneumonia and PRRS free and there was a low mortality (0.4%) in the nursery but PCVAD developed normally 3-4 weeks into the finishing barn. The trial involved 3850 pigs. The combined mortality in the unvaccinated placebo controls averaged at 9.5% and the vaccinated at 2.4%, a reduction of 7.1%. A trend to improved response to vaccination in younger pigs was noted (see Graph 2), which fits in well with the pathogenesis of the disease i.e. stimulate an early immune response before the viral damage to the immune system is caused.
Connor and Elsenier described a series of trials with Suvaxyn ® PCV2 (Fort Dodge Animal Health) in the US, 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 carried out on a before and after vaccination basis and the mortality in the grower/finisher period was 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%. 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 Canada (Quebec and Ontario) with Porcilis PCV2 (Intervet Inc.) using a two-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 and the overall mortality in the unvaccinated pigs was 9.3% and in the vaccinated pigs 2.1%, a fall of 7.2%. It was 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.

Graph 2. Comparative efficacy of a PCV2 vaccine (Ingelvac CircoFLEX) by age of pig vaccinated

Conclusions
The epidemiology and immunology of PCV2 infections is very complex but the research work has probably pushed forward our boundaries of knowledge substantially, over the last 8 years, while we have had PMWS. Unfortunately, it did not come up with a solution to the problem in Europe, hence the frustration, especially in the UK where PMWS is still a major problem, costing over £42 million ($80 million) a year to the industry.
It is really exciting to see the results of the vaccine trials in N. America and to think that at last we have tools to control this infection. The trial work was carried out to a variety of designs, however, they show one very clear result that the products work exceptionally well and there is clear hope for the future. Mortality in finishing pigs has been brought down to normal levels, before PCV2 was an issue. I am sure without the extensive European research work the rapid American vaccine advances would not have been made, but from a pig industry perspective, we need both to work together in the future.

References:
Connor, J. and Elsener, J. (2007) Field efficacy of Suvaxyn® PCV2 one dose in pigs. Proceedings of the American Association of Swine Veterinarians Conference Orlando, Florida, USA, pp 151-152
De Grau, A.F., Jorgensen, J., Thacker, B. et al (2007) Field performance of a conditionally licensed vaccine: Canadian experience. Proceedings of the American Association of Swine Veterinarians Conference Orlando, Florida, USA, pp 159-161
Desrosiers, R., Clark, E., Tremblay, D. and Tremblay, R. (2007) Preliminary results with Ingelvac® CircoFLEX™ to protect multiple ages of Quebec pigs against PCVAD. Proceedings of the American Association of Swine Practitioners Conference Orlando, USA, pp 143-145
McCullough, K.C. Vincent, I.E., Summerfield, A. et al (2007) The immunology of PCV2 infections. Proceedings of the American Association of Swine Veterinarians Conference Orlando, Florida, USA, pp 497-503
Nauwynck, H., Lefebvre, D., Misinzo, G. et al (2007) PCVAD essentials for survival. Proceedings of the American Association of Swine Veterinarians Conference Orlando, Florida, USA, pp 489-495
Plourde, N and Machell, N. (2007) Evaluation of the changes in total mortality rates observed after a six month use of Circovac ® porcine circovirus vaccine allowed in Canada for emergency use. Proceedings of the American Association of Swine Veterinarians Conference Orlando, Florida, USA, pp 139-140

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