In January 2006 a multi-national European research consortium on PCV2 diseases was expanded to include new member states and accession countries of the European Union. Now fully operational, the 6 million project was initiated in December 2004 and involves a consortium from academia and industry with a total of 15 partners from the EU and North America. The following report reviews the main points of current international knowledge of the range of pig diseases attributed to porcine circovirus type 2 (PCV2).
Serologic surveys for the prevalence of PCV2 infection reveal that this virus is found virtually everywhere pigs are raised. Over 90% of young adult swine are seropositive, indicating either active or previous infection. Moreover, sera collected from pigs over 30 years ago show that these animals were also infected, indicating that PCV2 is not a newly acquired pathogen of pigs.
The host range for the virus is restricted exclusively to swine (domestic and feral pigs and wild boar); no evidence for infection has been found in other farm species. Humans in intimate contact with swine and PCV2 are seronegative for the virus. Therefore its source to naïve animals is always infected swine or their premises.
PCV2 infection has now been shown to be associated with a wide spectrum of swine diseases. First recognised as the necessary cause of the post-weaning multisystemic wasting syndrome PMWS, the virus is also an important part of pneumonia and the porcine respiratory disease complex. It is thought to have a role in reproductive failure and is strongly associated with the porcine dermatitis and nephropathy syndrome PDNS. This spectrum of clinically expressed diseases is grouped together as PCV2 diseases or PCVDs.
The last 7 years of research have led to a general acceptance that the PCVDs are a multi-factorial complex, analogous to the shipping fever pneumonia complex of feedlot cattle. After several years of indecision about the importance of PCV2 in swine husbandry, it is now abundantly clear that this virus is a true pathogen of swine as neither PMWS nor the other circovirus-associated diseases occur unless PCV2 is present.
However, PCV2 infection alone is not a significant cause of deaths in pigs. Co-factors seem necessary for the full expression of PCVDs. While the specific co-factors are different in many cases, the general mechanism by which these co-factors potentiate disease is similar each appears to induce a pro-inflammatory state and an activation of the immune response early in the course of PCV2 infection when infected pigs contain infectious virus circulating in the blood (viraemia).
An avirulent mammalian circovirus of swine (PCV1) was discovered over 30 years ago. Only recently, in 1996-7, was a pathogenic circovirus (PCV2) discovered and characterised. The circoviruses are the smallest freely replicating viruses known to occur in vertebrates. The PCV genome is only large enough to accommodate genetic information for 2 viral proteins. The viral DNA replicase which is identical in both PCV1 and PCV2 is a non-structural protein concerned with reproduction of viral DNA. The single structural protein encapsidates newly formed progeny viral DNA and protects it from environmental degradation. However, the nucleocapsid protein of PCV1 and PCV2 differs dramatically and it is this difference that accounts for the disease-causing properties of PCV2.
Moreover, genetic analyses of PCV2 viruses from around the world have shown that all are very closely related to one another and thus form a single viral group. Individual strains may vary in virulence potential, however, and will not behave exactly the same in pigs. Some of these strains cause disease, others may not. A practical note for biosecurity concerns is that the physical characteristics of PCV2 make it highly resistant to temperature and humidity extremes and to many disinfectants.
Piglets receive antibodies for PCV2 from sow colostrums/milk. High titres of these antibodies are protective for expression of disease, but not necessarily for preventing infection. Most piglets seroconvert 3-4 weeks after weaning (6-8 weeks of age), indicating that the infection is acquired as maternal antibody levels in piglets decline. Transmission is undoubtedly accomplished by the faecal-oral and oronasal routes, although the infection may occasionally be acquired in the uterus before birth. Risk factors for infection and ultimately expression as PMWS include acquisition of an early infection (before 4 weeks of age), suckling on sows with moderate or low titres to PCV2 (implying that these piglets will become infected at an early age) and other infectious diseases, particularly scours. Among risk factors for herd outbreaks are the size of unit (the PMWS risk increases for herds with more than 600 sows), introduction of replacement gilts into the breeding herd and recent visits to the unit by outside personnel including attending veterinarians.
Defining the disease
A case definition of PMWS has been developed to provide an accurate diagnosis since there are many other causes of ‘poor doing' in swine and it is a mistake to assume that a wasted pig is always a PMWS pig. Three criteria must be met before a definitive diagnosis of PMWS can be made. Clinical signs and histologic lesions in post-mortem tissues must be compatible with the disease syndrome, also there must be PCV2 protein and/or viral DNA within these lesions. Pigs that have only one or two of these criteria are, by definition, not PMWS.
Herds considered to have the epidemic form of PMWS are those which have confirmed cases of PMWS/PDNS, have an increased mortality versus historical records and have other disease problems that do not respond to ordinary treatment/prevention measures such as the administration of antibiotics. Herds not meeting these strict criteria are either in the early phases of a PMWS outbreak, are stable regarding PMWS or are in the convalescent phase of a PMWS outbreak. Determination of the herd status is important so that the appropriate measures can be taken to prevent further losses associated with the disease.
How can an infectious agent that is always present in herds become responsible, on occasion, for serious and life-threatening clinical disease? We now appreciate that there are other factors in addition to PCV2 which are involved in the genesis of PMWS. Among them are the immunostimulatory effects of other concurrent infections, particularly PRRS and Mycoplasma hyopneumoniae, and the immunostimulation that accompanies vaccinations (see panel).
There is now enough information regarding PCV2 and disease co-factors to construct a general scheme for the pathogenesis of PMWS (see Figure 1). The key viral virulence determinant is the amount of virus which accumulates in virus-infected pigs.
Piglets with low amounts of virus and where the infection is restricted largely to lymphoid tissues will probably not develop PMWS. Those more likely to develop the disease have high amounts of the virus and dissemination of the infection beyond lymphoid tissues, to involve the lungs, liver, kidneys and intestinal tract.
Active PCV2 infection at an early age initiates the process. When the infected piglets are then subjected to the stress of over-crowding and competition for feed, other infectious disease, fluctuating environmental stresses (such as excess heating or chilling and high humidity), early weaning and the immunostimulatory effects of early vaccinations, all of these stimulate increased PCV2 production in the piglets which ultimately is expressed as PMWS. There are also genetic influences but these are not as yet defined.