PCV II - available
Control ToolsDiagnostics availabilityLargely available now. Variety of qPCR tests for viral material in samples. Virus neutralisation tests for detection of antibodies (no commercial and only used in research – unlikely commercial use). IPMA and ELISAS are the standard tests in most laboratories. PCV2 IHC or PCV2 ISH available in most laboratories worldwide. GAPS:
Largely available now. Variety of qPCR tests for viral material in samples. Virus neutralisation tests for detection of antibodies (no commercial and only used in research – unlikely commercial use). IPMA and ELISAS are the standard tests in most laboratories. PCV2 IHC or PCV2 ISH available in most laboratories worldwide. GAPS:
Most of the kits are validated by state diagnostic labs. Probably not easy to establish as yet. The existing tests are probably adequate. GAP: Consider pen-side test that assess need and/or impact of vaccination. Not required and of little value yet if agent is ubiquitous. The vaccines works, however improved vaccines and vaccination schedules would be of value. GAP: Efficient vaccination schedules and criteria for start of vaccination taking into account maternal interference/ protection and cost-benefit. Bedside (e.g. micro-array) tests for diagnosis and estimate of viral load would be helpful if clear cut-offs are established. Need for predictive tools. Vaccines availabilityThe four major companies providing vaccines appear to be able to provide the necessary supplies worldwide. Vaccines now freely available in Europe. No vaccines sold as marker vaccines are available, however, the subunit vaccines could be regarded as marker vaccines if diagnostic tests were developed targeting virus subunits not present in the vaccines. GAP: DIVA capability of sub-unit vaccines needs to be assessed. None. All the vaccines appear to be successful in reducing losses due to PMWS and are capable of producing raised levels of colostral protection and to protect young piglets prior to acquisition of infection in the growing phase. GAPS: Mass vaccination by the intra-muscular route of the pig population is needed; possible improvements would be to reduce the number of injections or replace them with other easier routes and consider combinations. Impossible to say but it is likely that as more knowledge of the pathogenesis of PCV2 infections is generated it may be possible to develop new vaccines based on molecular advances. GAPS: Mass vaccination by the intra-muscular route of the pig population is needed; possible improvements would be to reduce the number of injections or replace them with other easier routes and consider combinations. None. Depends on demand for other vaccines eg new swine flu etc and priorities but PCV2 is the second major threat to pigs behind PRRSV. GAPS: Mass vaccination by the intra-muscular route of the pig population is needed; possible improvements would be to reduce the number of injections or replace them with other easier routes and consider combinations. Very limited due to ubiquitous and resistant nature of the virus. GAPS:
Pharmaceutical availabilityNone. None predicted. GAP: Maybe new generations of T-cell stimulants will be developed or intermediary metabolism modulators. At the moment probably slight. Probably none necessary at the moment. For such a huge disease with no obvious worldwide differences in virus it will be possible to produce vaccines for worldwide use and not have to consider drug therapy. As molecular understanding of viral pathogenicity raises, new developments may take place. GAP: The effect of existing antiviral drugs against PCV2 is not known; this might have bearings on similar small “circular” human viruses which roles are not yet clearly understood. New developments for diagnostic tests
Impossible to say as will be based on elucidating pathogenicity and immunological characteristics yet unknown. GAP: This sort of test would enable vaccination to precede active infection so the sooner the better, as well as managements of vaccination at the herd level and cost control. Classical of similar tests. Continuing EU wide support for multidisciplinary approaches to PCV2 research. GAP: particularly, surveillance of PCV2 populations and elucidating pathogenicity and immunological Unlikely to be made possible unless there is a great reduction in the level of this naturally occurring virus. New developments for vaccinesMass vaccination by the intra-muscular route of the pig population is needed for effective control. Continual search for easier administration eg in the water or in the aerosol form is necessary for farmer co-operation in reducing the incidence of pig disease. GAPS: Possible improvements would be to reduce the number of injections or replace them with other easier routes and consider combinations. This process is already continuing in those companies associated with pig vaccine production. Classical for similar products. GAP: An accepted challenge model for animal of various ages in non infected and infected situations is not clearly available. Any challenge model to assess PCV2 effect on reproductive parameters is not available. Continuing research on the fundamental immunology of the pig and its relation to PCV2 infection (Pathogenicity, immunology). New developments for pharmaceuticalsProbably not applicable until new antivirals become effective in farm animals. Unknown, as no pharmaceuticals exists yet. Unknown, as no pharmaceuticals exists yet. Unknown, as yet no pharmaceuticals available. Disease detailsDescription and characteristics.Porcine circovirus type 1 is a non-pathogenic virus found as a contaminant of porcine cell lines and in pigs. Porcine circovirus type 2 (PCV2) is associated with several disease manifestations in pigs. No pathotypes of type 2 have been found although the isolated strains of type 2 are now called 2a (older or 422 like pattern), 2b (newer or 321 like pattern), and 2c (recently identified in archived tissues in Denmark). Most of the strains or isolates of the virus appear to have >93% homogeneity at the nucleotide level. PCV2 is the necessary but not usually self-sufficient cause of a variety of manifestations of what have come known as Porcine circovirus diseases (PVCD). GAPS:
There are some evidences that the severity of the disease are linked to the emergence of specific genotypes (genotype 2b). The variability of disease may, however, also be related to many other factors such as immune status to PCV2, time of infection, pig genetics, standards of management in the widest sense, and in particular to the health of the herd and the other concurrent diseases. GAPS:
The virus is the smallest of the porcine viruses (together with Porcine parvovirus, with which occasionally occurs) and it is one of the most ubiquitous and resistant. It is stable, resistant to pH 3.0, chloroform and to temperatures of 70 degrees C for 15 minutes. On the farm, only heat or steam in combination with Virkon S at the maximum strength is effective disinfectant. If there is any organic matter PCV2 will survive. In farrowing accommodation this is usually the case and PCV2 is readily available to infect newborn piglets. GAP: There is little information obtained specifically with PCV2 on survival in biological products (meat and meat products, pig sera and/or semen, etc…). Species involvedAll species of pigs appear to be affected including wild boar and feral animals. Many pigs are infected without displaying clinical symptoms of disease and some of these animals act for certain as carriers. GAPS: Identification of infected animals that is likely to spread PCV2 and thereby contribute to the spread and development of PCVD. No evidence of human infection. No evidence of vectors. Probably most pigs are infected. GAP: This aspect has not been explored, but should be addressed if herds are to be declared free of the disease. There has not been found to be any reservoirs. It is closely related to other circoviruses, in particular, Psittacine beak and feather disease virus, Canary circovirus, Goose circovirus, and Pigeon circovirus. This group of viruses are distant related to plant viruses but there has not been any evidence to suggest that these may be a reservoir. Description of infection & disease in natural hostsTransmission is easy because of the ubiquitous nature in the environment but in experiments PCV2 in-contacts are not always infected and certainly does not always produce disease. It depends also on the levels of immunity against the virus and the dosis. GAPS: We miss bio-assays to assess transmissibility from semen in parallel to PCR counts and transmissibility to pregnant gilts and sows is not clarified. Pig to pig transmission either direct or indirect has been identified as the only cycle. There a wide variety of clinical syndromes produced or associated with this virus. Known collectively as PCVD, the first to be identified was the Postweaning Multi-Systemic Wasting Syndrome (PMWS) in which disease in young pigs was characterised by wasting, fever, lethargy, weight loss, dyspnoea, jaundice, lymphadenopathy (lymphoid depletion, necrosis, histiocytosis, viral inclusions and syncytia) and the presence of detectable PCV2 antigen in the tissues (ISH or IHC detection). In many pigs, thymic atrophy and granulomatous enteritis were also identified. Not all the pigs with PCV2 infection develop PMWS. When there is co-infection with parvovirus and/or PRRSV, the disease is much worse. In the early cases in the UK there was also a severe skin /kidney syndrome called Porcine Dermatitis and Nephropathy Syndrome (PDNS) which was extremely difficult to differentiate from ASF/CSF but which was later shown to be associated with PCV2, but has been also associated with secondary bacterial disease with a hypersensitivity reaction usually to gram negative bacteria eg Pasteruella and Mannheimia. It is characterised by red-purple discolouration in the skin marking vasculitis and the deposition of immune complexes which also cause a severe necrotising glomerulonephritis. Another reported syndrome is the Reproductive failure which is manifested as mid-late term abortions or farrowings with increased numbers of stillborns and mummies. In many cases the piglets have enlarged flaccid hearts with myocarditis with demonstration of moderate to high amount of virus in the lesions. One publication has suggested that PCV2 may be associated with congenital tremor but there has not yet been universally accepted and experimental proof is lacking to date. Sporadically, Encephalitis has been reported with PCV2, but also linked to PMWS status. GAPS:
Varies considerably, probably 14-28 days. GAP: Pure effect of possible pathotypes has not been elucidated. Very variable, may be from 1-40%. GAP: Pure effect of possible pathotypes has not been elucidated. As far as one can tell the virus can be shed from all available surfaces, orifices and secretions including blood, colostrum faecal material and semen. GAP: Kinetics and circumstances of shedding are mostly unknown and should be studied in details. The exact cell types involved in the replication/spread and pathogenicity of PCV2 infections has still not been definitively determined, even it is known that epithelial and endothelial cells play a major role (together with a low proportion of macrophages and even some subsets of lymphocytes). There is a high involvement of other pathogens. PRRSV may concurrently occur in 40% of the cases, M. hyo in 27%, and other bacterial species in >10%. In a few cases swine influenza virus is involved. There is a strong association between PCV2 and PRRSV in PDNS cases. PCV2 as a single causative occurrence is a rare event. Certainly PCV2 reduces PRRSV vaccination efficiency. Some of the worst cases are seen in conjunction with parvovirus. This combination of the two smallest viruses requiring cell structures to replicate them occurs in approximately 15% of the cases. The occurrence of enzootic pneumonia is also an exacerbating factor and some authorities have thought that the immune stimulation associated with M. hyo vaccination may potentiate PMWS. The mechanism of pathogenicity is still largely unknown. The virus is so small it does not possess a virally encoded DNA polymerase and therefore relies on the host cell enzymes. It replicates best in the cells in the S phase of the cell cycle, eg myocardiocytes in late gestation, kidney around birth and the 2 weeks after and then in epithelial and endothelial cells and cells of the macrophage/monocyte system. It probably attaches to receptors through heparin sulphate and glycos-aminoglycans and is then replicated in the cell and released in huge amounts from the cells. It is probably stored in the dendritic cells. The virus or parts of the virus (nuclic acid) is found in a non-replicative form in dendritic cells and are belived to modify the cytokine profile of these antigenpresenting cells. The degree of severity of clinical signs and the severity of the lymphoid depletion may have a direct correlation with the amount of circulating virus detected in the blood. GAPS:
Zoonotic potentialNever reported. Not likely to have occurred. None. None. Not likely to occur. Impact on animal welfare and biodiversityThe ubiquitous nature of the virus, its resistance in the environment and as yet not understood effects on the host make it very difficult to control. It is a great blessing that the vaccines available appear to exert such a good degree of control. GAP: Clarifying the circumstances of PCV2 emergence as a pathogen could help understand the evolution of viral populations in changing environments and may be of interest for the study of microbial biodiversity in general. Probably not as vaccination will protect although wild boar can be affected. GAP: situation unknown in Africa. Only as a welfare case. Geographical distribution and spreadWorldwide. Endemic. GAP: The possible trend of cyclical smaller epidemics in a globally endemic situation should be explored. Not yet identified. Progressive spread through a unit over 3-6 months. Virus has been around years before been associated to any pathogenicity despite that typical PMWS lesions has been described years before the big outbreaks. This is one of the big puzzles of the PMWS “epidemic”. GAP: Identification of factor(s) that contribute to the pathogenicity of PCV2 infection. Will cross a border if pigs or pig related products cross. Not noticed so far. GAPS: Resistance and/or sensitivity to climate variations are not clearly known, although the virus is very resistant. Not linked to climate at all. No linkage yet identified. None noted. Route of TransmissionPCV2 is usually introduced from infected pigs directly or indirectly. PMWS always behaves like an infectious disease. GAPS: Most pigs are seropositive to PCV2, how to identify those that contributes to the spread of PCVD. The dynamics over time within herds are also unknown at present and so is the reason for the apparent shift in age preference over time. Probably through semen from boars or AI. Possibly blood or needles or aerosol spread. GAPS: Most pigs are seropositive to PCV2, how to identify those that contributes to the spread of PCVD. The dynamics over time within herds are also unknown at present and so is the reason for the apparent shift in age preference over time. Need for bio-assays. Only one- lack of cleaning with complete removal of organic material and disinfection using approved disinfectant such as Virkon S at full strength. GAP: Most pigs are seropositive to PCV2, how to identify those that contributes to the spread of PCVD. The dynamics over time within herds are also unknown at present and so is the reason for the apparent shift in age preference over time. Detection and Immune response to infectionNeutralising antibodies and cellular immune response (measured as IFN-gamma producing cells) are considered the major immunological components in order to control infection. In PDNS there is a hypersensitivity type 3 reaction triggered and then pro-inflammatory stimulation predisposes to secondary bacterial infection. PCV2 is immunosuppressive however; on the contrary immunostimulation has been shown to promote PMWS development. GAPS:
Pigs with PCV2 infections appear to mount a strong PCV2 specific antibody response. The maternal antibodies appear to decrease during the period 3-11 weeks depending on the sows’ antibody levels and then increase to around 15 weeks in PMWS affected herds or later in subclinically infected herds. Experimentally, antibodies appear about 14 days after infection whereas neutralising antibodies appear about 21 days post-infection. In pigs with PMWS compared with pigs with PCV2 infection but no PMWS there are lower levels of neutralising antibody and IgM isotype antibodies. IgM antibodies indicate active infection. In sub-clinical pigs increased IL-10 leads to a higher ratio of IgG to IgM. High neutralising antibody titres do not necessarily mean there is protection. It may be that PCV2 employs a decoy mechanism to avoid the defences. Interleukin IL-10 is responsible for the suppression of TH1 cells. Generally, IL-10 and pro-inflammatory cytokines are increased in PCV2 infections and there is a decrease in general antiviral responses. The role of interferons is not understood, but a significant IFN-alfa and IFN-gamma responses are related to protection. Complex and multifactorial mechanisms occur in PCV2 induced PMWS. In an infected, but asymptomatic animal, PCV2 may co-exist with the host by undergoing minimal replication and inducing a limited host, balanced TH1/TH2 response. There are many triggering factors of the disease process eg stress, exposure to other pathogens, host genetics and at the molecular level these probably induce increased viral replication. GAPS: The mode of action has only begun to be delineated. Serological tests are not helpful for diagnosis as most pigs are seropositives; we lack any predictive test that would identify pigs that will indeed progress to severe disease. Main means of prevention, detection and controlEffectiveness is only complete with all in/ all out, cleaning and disinfection with recognised disinfectant, use of hospital units for sick animals and reduction of stock density. None, except implementation of tender loving care for piglets ie proper management with minimum disruption ( Francois Madec’s 20 points plan). Clinical signs, gross post-mortem, particularly enlarged inguinal lymph nodes, histopathology with demonstration of PCV2 material by IHC or ISH. Quantification of virus load has been used for diagnosis in some countries but the results are doubtful as a diagnostic tool to predict clinical impact. GAP: Reliable diagnostic parameters for diagnosis of PCVD on live animals should be established, especially if they have some predictive value. Vaccines for control of PCV2 infections in sows and piglets are available both Baculovirus expressed and inactivated full-virus vaccines. GAP: Conditions in which maternal immunity interference occurs should be defined. Not available. No real control except general biosecurity. Herd closure and eradication may be possible, but is not widely used. GAP: It is not clear if herds can be declared and remain free of PCV2 – projects should be performed. No real effective possibilities as PCV2 are ubiquitous. GAP: Methods for identification of carrier/shedding animals are needed. None except thorough cleaning and disinfection to reduce the level of virus uptake. GAP: Vaccination as a tool to avoid introduction of PCV2 in free herds should be examined. Sequencing is necessary to plot changes in the virus over time and identification of genetic changes that may indicate sites of virulence in the genome and any new viruses. GAP: Reliable diagnostic parameters for diagnosis of PCVD on live animals should be established, especially if they have some predictive value. Vaccine provision and serious improvements in care of young piglets is highly successful. Impossible to estimate. GAP: Refinements of economical tools to assess the impact of such endemic diseases are needed; they would be useful for most other similar diseases as PRRSV, M. hyo etc. Disease information from the OIENo. None. None. None. Socio-economic impactComplete loss of profitability due to variation in growth rate increased morbidity and mortality and reproductive failure together with increased veterinary charges. GAP: Refinements of economical tools to assess the impact of such endemic diseases are needed; they would be useful for most other similar diseases as PRRSV, M. hyo etc. None. Huge, but not now vaccines are widely used. Huge decrease in number of finishing pigs per sow per year. GAP: Refinements of economical tools to assess the impact of such endemic diseases are needed; they would be useful for most other similar diseases as PRRSV, M. hyo etc. Impossible to say but huge prior to vaccination. GAP: Refinements of economical tools to assess the impact of such endemic diseases are needed; they would be useful for most other similar diseases as PRRSV, M. hyo etc. Indirect impact was on provision of supply of finishing pigs at the correct grade at the time required. GAP: Refinements of economical tools to assess the impact of such endemic diseases are needed; they would be useful for most other similar diseases as PRRSV, M. hyo etc. Trade implicationsNone probably except for exports to Australia. Probably few apart from some regulation from some countries on import of semen from other member states. GAP: need for bio-assays with semen samples. Unknown. GAP: Refinements of economical tools to assess the impact of such endemic diseases are needed; they would be useful for most other similar diseases as PRRSV, M. hyo etc. Main perceived obstacles for effective prevention and controlNone, now that there is effective vaccination. GAP: Need to control PRRS, mycoplama and swine influenza infections as well. Main perceived facilitators for effective prevention and controlPrivate veterinary surgeons instituting health control programmes based on vaccination schemes and biosecurity controls. GAP: Need to maintain surveillance of the viral populations under vaccination pressure. RiskVirus changes suddenly that present vaccines do not work and we are back to the original scenario. GAP: Continue to monitor PCV populations under vaccination pressure. ConclusionWe need to know why this virus existed in the pig population for a long time and then in the mid to late 1980s suddenly started to cause disease. This can only have happened due to a change in the virus (not yet shown); a change in the environment of the pig (increased production, loss of labour and therefore disappearance of care, Madec’s 20 point plan); or changes in the genetic makeup of the pig (Loss of genes or selection of wrong criteria) and/or a combination of those. GAPS: The availability of effective vaccines might prevent funding more research as the threat is no so acute any more; however we do need to continue viral population monitoring, and to study pathogenicity and immunology especially for diagnostic improvements. A repeatable, reproducible model of experimental disease is still missing. Reliable economical tools for fine costs/benefits assessments are also needed. |
