Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Several antibodies and genome detection kits are available commercially. At least three different commercially produced ELISAs to detect IgG or IgM antibodies against PCV-2 are available. These kits are presumable able to detect antibodies against all PCV-2 genopypes.

  In addition at least two real time quantitative PCR (qPCR) kits are available on a commercial basis. These kits are presumably able to detect the genome of all genotypes. A number of in-house qPCR methods have already been developed as well.

  List of commercial diagnostic kits (Diagnostics for Animals).

  GAPS :

  The efficiency of detection of PCV-2 antibodies or DNA from different genotypes has not been compared within and among diagnostic kits. The results, especially quantitative ones, are poorly standardized and can differ among kits and laboratories.The analytic and diagnostic performances of some kits developed by emerging companies are not clearly evaluated and stated. Selection of the most appropriate assay can be challenging.The interpretation of antibody detection is difficult, especially in vaccinated populations, and used alone (without qPCR) may lead to incorrect diagnosis.

• Diagnostic kits validated by International, European or National Standards

  Diagnostic kits are following the standards of quality and control at international level, following the different agencies over the world. They have been internally validated mainly for serum (ELISA) and for serum, plasma, and tissues (qPCR).Most kits are validated by state diagnostic labs.

  GAPS :

  There are no international standards based on OIE (currently WOAH) since PCVDs are not notifiable diseases.The kits have not been validated for non-common samples such as oral or processing fluids.

• Diagnostic method(s) described by International, European or National standards

  Diagnostic criteria for PCVDs were established several decades ago (late 90s), based on three main observations: presence of clinical signs, presence of specific histological lesions in target organs such as lymphoid tissues and others and presence of PCV-2 in tissues with characteristic lesions. Therefore, four major disease outcomes have been described:

  1. PCV-2 systemic disease (PCV-2-SD, formerly known as postweaning multisystemic wasting syndrome, PMWS)
  2. PCV-2 reproductive disease (PCV-2-RD)
  3. PCV-2-subclinical infection (PCV-2-SI)
  4. Porcine dermatitis and nephropathy syndrome (PDNS).

  The latter one is an immunocomplex disease, and the evidence of PCV-2 causality is still circumstantial, so, for the final diagnosis of PDNS, detection of PCV-2 is not compulsory. These classical diagnostic criteria include the detection in characteristic microscopic lsesions and PCV2 demonstration mainly by immunohistochemistry (IHC) and in situ hybridization (ISH). qPCR can be considered as well if accompanied by histopathological assessment.

  GAPS :

  Although PCVD diagnostic criteria are very clear-cut, the availability of histopathological expertise and techniques able to detect the virus within the lesions is still limited in many parts of the world, also including Europe.

  Standardization of the diagnostic criteria must be considered difficult due to their subjective nature, since the clinical and pathological assessment depends on the observer (clinician/pathologist).The relationship between viral titre and disease is a source of confusion among field veterinarians. The variability in quantification can be due to biological factors, selected diagnostic kit (different standards for quantification, variability in the primers/probe and their interaction with genotype/strain- specific genome sequence, etc), sample processing etc. The veterinarian should be made aware of these limitations.

• Commercial potential for diagnostic kits in Europe

  The commercial kits for PCV-2 DNA or antibody detection are widely used by field veterinarians.

  GAPS :

  The potential use of histopathology and detection of PCV-2 by means of IHC or ISH in damaged tissues is still of limited use in many parts of the world.

• DIVA tests required and/or available

  Detection of viral DNA in a tissue or other samples means that natural infection is going on (or at least the DNA has been generated by natural infection, corresponding to infectious virus or not), since all vaccines on the market today are inactivated, vectored or subunit ones.

  GAPS :

  No DIVA tests are available for PCV-2 differentiation between antibodies raised against vaccination and infection. Field veterinarians would like to have this type of DIVA tests, since nowadays there is no clue to ascertain whether antibodies against PCV-2 have been elicited by vaccination, maternal transfer, or natural infection.Diagnostic assay based on cell-mediated response that correlate with protective immune response derived from vaccines or natural infection (i.e. interferon TB test in humans) are missing for a routinaly screening.

• Vaccines availability

• Commercial vaccines availability (globally)

  A significant number of PCV-2 vaccines do exist all over the world. This number is very high in some Asian countries, while more limited in Europe. There are five major vaccines against PCV-2 in Europe, which are inactivated, sub-unit or vectored.

• Marker vaccines available worldwide

  No marker vaccines are available in the global market, since they cannot differentiate antibodies elicited from vaccination, maternal immunity, or natural infection.

  GAPS :

  Detection of antibodies anti-Rep would differentiate immune responses since they cannot be elicited by currently existing vaccines (non-replicative). However, this positive marker would not allow establishing if the animals have been vaccinated or not in case of positivity; only negativity against Rep and positivity against Cap would establish that animals have been vaccinated. However, without a negative marker, it would not be possible to get a DIVA outcome.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  All the vaccines currently on the market, independently of the PCV-2 genotype which all are based on the PCV-2a genotype in Europe (but one, based on both PCV-2a and PCV-2b) appear to be successful in reducing losses due to PCV-2-SD and can produce increased levels of colostral protection and protect young piglets before acquisition of infection in the nursery-growing phase.Most vaccines are applied intramuscularly, and some of them can be applied intradermally.Vaccination protocols are sometimes developed by veterinarians based on the serological and virological status of pig herds which often prove to be more efficacious than the standard protocols.

  GAPS :

  It is not known if the combination of different genotypes within a vaccine may increase the level of protection against PCV-2 circulating genotypes. High difficulty in assessing vaccines with combined genotypes against mono-genotype based vaccines considering that the latter ones have already high efficacy. Immunity is not sterilizing and the knowledge of the role of vaccination in shaping viral evolution is limited.Limited/absent experimental information on the protection conferred against emerging genotypes.There is a great potential for increasing intradermal vaccination due to animal welfare reasons.A better understanding of PCV2 vaccines induced immunity mechanisms is needed to enable better foundation for the development of a herd specific vaccination protocol.The definition of success or failure of a a given vaccination program needed to be better clarified.

• Commercial potential for vaccines in Europe

  PCV-2 vaccines are the most used vaccines in the pig industry worldwide and are considered highly efficient.

  GAPS :

  There is a potential of developing new products based on life vaccine virus and mixing new antigens/genotypes. In addition there is also a great potential to explore alternative administration routes.

• Regulatory and/or policy challenges to approval

  The most feasible way to demonstrate the effects of the vaccine is based on clinical trials, since pre-clinical ones are poorly demonstrative of efficacy on productive parameters.

  GAPS :

  The lack of uniform challenge model is an obstacle to regulatory and policy approval.

• Commercial feasibility (e.g manufacturing)

  Highly effective to produce subunit vaccines.

  GAPS :

  Certain shortcomings of producing viral seed stocks, due to the limited replication of PCV-2.However, some companies have overcome this by using genetically modified cell lines which support PCV-2 growth much better.

• Opportunity for barrier protection

  Very limited due to the ubiquitous and resistant nature of the virus.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  None.

• Future therapy

  None predicted.

  GAPS :

  Maybe new generations of T-cell stimulants will be developed or intermediary metabolism modulators.

• Commercial potential for pharmaceuticals in Europe

  Not foreseen at the moment.

• Regulatory and/or policy challenges to approval

  Non-expected due to the lack of apparent need of pharmaceutical products.

• Commercial feasibility (e.g manufacturing)

  Since there are no major differences in virus genotypes, it seems feasible to produce vaccines for worldwide usage without the need to consider drug therapy.

• New developments for diagnostic tests

• Requirements for diagnostics development

  Current tests to detect PCV-2 antibodies and DNA are considered of high standard, and there is no clear evidence of lack of detection (or underperformance) of antibodies or DNA against certain genotypes.

  GAPS :

  Pen-side tests to facilitate an estimate of viral load. However, better understanding of how to interpret the obtained results/viral loads is needed and such tests should be carefully positioned in the decision-making process, regarding the steps to better control the disease.The effect of PCV-2 genetic heterogenicity at genotype/strain level on individual assay performances has never been formally assessed through a standardized panel of well-characterized strains.

• Time to develop new or improved diagnostics

  Impossible to say as will be based on elucidating pathogenicity and immunological characteristics yet unknown. Thanks to advancements in sequencing technologies, the development of new, updated PCR-based assays can be expected to occur extremely fast.

  GAPS :

  A farm based quick-performing test would enable vaccination to precede active infection so the sooner the better, as well as management of vaccination at the herd level and cost control.

• Cost of developing new or improved diagnostics and their validation

  The cost of developing new or improved diagnostics will be similar to most other assays including available PCV2 tools.

• Research requirements for new or improved diagnostics

  Continuing EU wide support for multidisciplinary approaches to PCV-2 research.

  GAPS :

  Especially, surveillance of PCV2 genotypes and elucidating pathogenicity and immunological markers.Regular organization of ring/proficiency test.

• Technology to determine virus freedom in animals

  Unlikely to feasible unless there is a great reduction in the level of this ubiquitous viral pathogen of pigs. Nevertheless, current tools can be considered adequate if applied based on a proper and statistically supported study design.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  Piglet mass vaccination is needed for effective control of PCVDs; the potential of mass vaccination of gilts/sows may reduce the overall infectious pressure.Continuous search for easier administration (i.e., in the water or in the aerosol form is necessary for farmer co-operation in reducing the incidence of this pig disease).

  GAPS :

  Possible improvements would be to reduce the number of injections or replace them with other easier routes and (i.e., intradermal vaccination is nowadays a reality). In addition, combinations with other non-PCV-2 vaccines commonly administered to pigs could also be considered of great interest (some are already in place, especially together with Mycoplasma hyopneumoniae).

• Time to develop new or improved vaccines

  This process is already continuing in those companies associated with pig vaccine production.

• Cost of developing new or improved vaccines and their validation

  Classical for similar products.

  GAPS :

  An accepted challenge model for animal of various ages in non-infected and infected situations is not clearly availableAny challenge model to assess PCV-2 effect on reproductive parameters is not available. There are difficulties in assessing the effect of co-factors on vaccine efficacy (immunity development and effectiveness upon challenge).

• Research requirements for new or improved vaccines

  Continuing research on the fundamental immunology of the pig and its relation to PCV-2 infection (pathogenesis, immunology).

  Further exploring combination of PCV-2 vaccines including other antigens (nowadays several combinations do exist of vaccines containing PCV-2 and Mycoplasma hyopneumoniae antigens).

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  Probably not applicable until new effective antivirals become eavailable for usage in farm animals

• Time to develop new or improved pharmaceuticals

  Unknown, no pharmaceuticals exist yet.

• Cost of developing new or improved pharmaceuticals and their validation

  Unknown, no pharmaceuticals exist yet.

• Research requirements for new or improved pharmaceuticals

  Unknown, no pharmaceuticals exist yet.

Disease details

• Description and characteristics

• Pathogen

  PCV-2 is associated with several disease manifestations in pigs. Up to nine different genotypes have been described (PCV-2a to PCV-2i), being PCV-2d, PCV-2b and PCV-2a the most usually found worldwide, in decreasing frequency. PCV-2 is the necessary but not usually self-sufficient cause of a variety of manifestations of what have come known as PCVD; the most economically important PCVDs are PCV2-SD and PCV-2-SI.So far, four different porcine circoviruses have been described, namely PCV-1, PCV-2, PCV-3 and PCV-4. A certain degree of cross-reaction does exist between PCV-1 and PCV-2, but none for the others PCVs.

  GAPS :

  The molecular characterization of PCV-2 has largely been used in phylogenetic analysis but the impact of the overall diversity and of specific mutations on vaccine cross-protection and virulence has not been assessed.There is a need to continue surveillance and monitoring the evolution of the PCV-2 populations, as vaccination pressure increases.There is a need to investigate the biological impact of genotype diversity.There is need to better understand the interplay between PCV-2 and other emerging and re-emerging endemic pathogens.

• Variability of the disease

  Besides differences in genotypes, which have been lately classified based on 1) maximum intra-genotype p-distance of 13% (calculated on the ORF2 gene), 2) bootstrap support at the corresponding internal node higher than 70% and 3) at least 15 available sequences, recombination among genotypes has been described. As indicated, up to nine PCV-2 genotypes have been described, and although their definition is based on nucleotide sequencing, the putative differential biological effects of genotypes are considered low based on disease outcomes on farms.

  GAPS :

  The knowledge of the relationship between genotype and phenotype is largely linked to field/anecdotical experiences and specifically designed experimental/epidemiological studies aimed to objectively demonstrate such a relationship are lacking. The role of co-factors in PCV-2 pathogenesis further confounds such association. The deteriminants of epidemiological fluctuation (e.g. waves of different genotpes over time and differential geographical distribution) are still poorly understood.

• Stability of the agent/pathogen in the environment

  The virus is the smallest of the porcine viruses (together with porcine parvovirus) and it is one of the most ubiquitous and resistant viruses. It is stable, resistant to pH 3.0, chloroform and to temperatures of 70ºC for 15 minutes. On the farm, only heat or steam in combination with Virkon S at the maximum strength is effective. If there is any organic matter PCV-2 will survive. In farrowing accommodation, this is usually the case and PCV-2 is readily available to infect newborn piglets. Few other disinfectants are effective against PCV-2.

  GAPS :

  There is little information obtained specifically with PCV-2 on survival in biological products (meat and meat products, pig sera and/or semen, etc…).

• Species involved

• Animal infected/carrier/disease

  All suidae species of pigs appear to be susceptible to PCV-2 infection. Many pigs are infected without displaying clinical signs of disease (PCV-2-SI).

  GAPS :

  Identification of infected animals that is likely to harbor PCV-2 and thereby contribute to the spread and development of PCVD. PCV-2 has been sporadically detected in non-Suidae species. The reliability of such reports and the epidemiological relevance of these species are difficult to be established.

• Human infected/disease

  No evidence of human infection.n be infected with PCV1 or PCV2.

  GAPS :

  Some vaccines used for humans have been found to contain PCV-2 and other small DNA viruses, but studies have not shown any impact on human health to date.Some human cell lines can be infected with PCV-1 or PCV-2.

• Vector cyclical/non-cyclical

  No evidence of vectors. Probably most pigs are infected along their productive life (ubiquitous virus).

  GAPS :

  This aspect has not been significantly explored, but it should be addressed if herds are to be declared free of the virus.

• Reservoir (animal, environment)

  No reservoirs have been identified.

  GAPS :

  This aspect has not been significantly explored, but it should be addressed if herds are to be declared free of the virus.

• Description of infection & disease in natural hosts

• Transmissibility

  PCV-2 transmits easily because of its ubiquitous nature in the herds and environment. However, in experiments, PCV-2 contacts are not always infected and certainly do not always develop clinical disease. This depends also on the levels of immunity against the virus and the dosage of the virus.

• Pathogenic life cycle stages

  Pig-to-pig transmission either directly or indirectly has been identified as the only cycle; There is no apparent need for any intermediate host or vector.

  GAPS :

  The role of piglets persistently infected at birth needs to be clarified.

• Signs/Morbidity

  PCVD clinical scope is wide depending on the specific disease considered:

  - PCV-2-SD: wasting is the major sign, but it can be accompanied by respiratory distress, diarrhea, jaundice, and high lethality; morbidity variable but can reach 40-50% in the worst case-scenarios

  - PCV-2-RD: late-term abortions or delivery of mummified piglets with different crown-to-rump length are the main outcomes; morbidity is considered high in start-up herds but very occasional in commercial farms

  - PCV-2-SI: it is probably the most frequent PCVD; no evident clinical signs but loss of weight when average daily weight gain (ADWG) is calculated; low to high morbidity in vaccinated farms, very variable

  PDNS: presence of characteristic red-to-purple skin macules and papules, mainly in the hind limbs, even it can be generalized; very low morbidity, usually lower than 0.5%, and almost disappeared with the mass vaccination against PCV-2.

  GAPS :

  The role of PCV-2 in PDNS has not been clarified; this syndrome is still mostly a mystery and we do not know its pathogenesis, besides lesions point out to an immunocomplex disorder.

  The role of PCV-2 on reproductive disorders has been relatively poorly investigated under field conditions since clinical cases of the overt disease are scarce; the subclinical impact of PCV-2 on reproductive performance is poorly understood; moreover, its potential association with embryo death and return-to-oestrus deserves much more investigation.

• Incubation period

  Varies considerably, probably 7-28 days.

  GAPS :

  Variable effect of possible genotypes has not been elucidated.

• Mortality

  Very variable, may be from 1-40%.

  GAPS :

  Variable effect of possible genotypes has not been elucidated; severity of disease depending on the genotype has not been demonstrated, but a variable severity in co-infection has not been almost investigated.

• Shedding kinetic patterns

  PCV-2 can be shed from all available surfaces, orifices and secretions including blood, colostrum, faecal material, semen, urine, and other excretions/secretions (respiratory, vaginal, etc). Shedding with feces can be observed in pigs with viremia undetectable in qPCR.

  GAPS :

  Kinetics and circumstances of shedding are mostly unknown and should be studied in detail.The role of environmental contamination on kinetics of infection in pigs has not been elucidated.

• Mechanism of pathogenicity

  Epithelial and endothelial cells play a major role (together with a low proportion of macrophages and even some subsets of lymphocytes) in PCV-2 replication.There is a high involvement of other pathogens as potential triggers (PRRSV, PPV, M. hyopneumoniae and probably others) of PCVD in PCV-2 infected animals.PRRSV infection reduces PCV-2 vaccination efficiency, mainly by impairing the cellular immune response.The most important lesion outcome is lymphocyte depletion and granulomatous inflammation of lymphoid tissues, which suggest that severely affected animals are immunosuppressed; macrophages and dendritic cells harbour a huge amount of PCV-2 genome/antigen in these cases, but they accumulate the virus rather than support their replication.The degree of severity of clinical signs and the severity of the lymphoid depletion/granulomatous inflammation of lymphoid tissues have a direct correlation with the amount of circulating virus detected in the blood.

  GAPS :

  The exact mechanisms of pathogenicity are still largely unknown.The potential immune modulatory role of PCV-2, especially its effect on professional antigen presenting cells needs to be clarified.Factors that activate the replication of PCV2 need to be identified, especially in PCV-2-SD phases when all tissues seem to be suddenly involved.The effect of the virus in PCV-2-SI is poorly understood, and no clue on the cause of ADWG decrease in such scenario.

• Zoonotic potential

• Reported incidence in humans

  Never reported.

• Risk of occurence in humans, populations at risk, specific risk factors

  None.

• Symptoms described in humans

  None.

• Likelihood of spread in humans

  Not likely to have occurred; detection in nasal cavity of humans are considered as environmental contamination of professional workers in the swine sector.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  The ubiquitous nature of the virus, its resistance in the environment and the not completely understood effects on the host make it very difficult to control. Disease prevention is nowadays based almost exclusively on vaccination.

  GAPS :

  Once the pig suffers from clinical PCVDs, it can be supported by various therapies and possibly also by urgent vaccination; however, those aspects have been minimally explored.

• Endangered wild species affected or not (estimation for Europe / worldwide)

  Appearently, PCV-2 infection has minimal impact on wild Suidae based on information to date.

  GAPS :

  The PCV-2 infection scenario is poorly understood in Africa and other parts of the world, with small farms structures and backyard pigs including in forests and jungles. Minor genotypes have been demonstrated in these areas, whose epidemiological relevance or role in PCV-2 evolution is unknown. A similar conclusion can be applied to as of now undetected genotypes.

• Slaughter necessity according to EU rules or other regions

  Only as a welfare case as human endopoint.

• Geographical distribution and spread

• Current occurence/distribution

  Worldwide.

• Epizootic/endemic- if epidemic frequency of outbreaks

  Endemic infection, although infection pressure is usually lower in vaccinated animals.

  GAPS :

  Vaccination pressure has implied a decrease in infection pressure, and the possibility of infections occurring during gestation and early in life; in those cases, epidemic outbreaks may occasionally occur. Vaccination of sows/gilts as a systematic approach may solve this issue.

• Speed of spatial spread during an outbreak

  Progressive spread through a unit over 3-6 months. Virus has been around for decades before being identified and associated to any pathogenicity despite that classical PCV-2-SD lesions have been described years before the big outbreaks. This is one of the big puzzles of this “epidemic” disease before the advent of vaccines.Risk factors including external (co-infections, nutrition, etc.), viral (maybe genotype) and host (immunity, age, genetic background) ones may modify the clinical outcome of PCVDs.

  GAPS :

  Identification and full characterization of factor(s) that contribute to the pathogenicity of PCV-2 infection.

• Transboundary potential of the disease

  PCV-2 is a ubiquitous, worldwide spread virus, so, transboundary trading of alive pigs implies the transboundary transmission of the virus.

  GAPS :

  So far, no demand of freedom from PCV-2 is claimed internationally; otherwise, it would be almost impossible to find truly negative (serologically and by qPCR) pigs.

• Route of Transmission

• Usual mode of transmission (introduction, means of spread)

  PCV-2 is usually introduced from infected pigs directly or indirectly. PCV-2-SD always behaves like an infectious disease, although it can be modulated by the presence or absence of disease triggering factors in PCV-2 infected pigs.

  GAPS :

  Most pigs are seropositive to PCV2. The determinants of individual subject viral spreading capability and effectiveness are unknown. The presence of super-spreaders and their relevance are debated.. 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.

• Occasional mode of transmission

  Spread possibly by blood, needles, aerosol, and environmental contact.Semen does not look to be a way of spreading, since the amount of PCV-2 in naturally infected boars is not sufficient to infect gilts/sows.

  GAPS :

  The minimum amount of PCV-2 loads for ensuring viral transmission horizontally or vertically is not specifically known.

• Conditions that favour spread

  Lack of proper cleaning, disinfecting, and drying of the facilities.Mixing up pigs from different ages and origins.

  GAPS :

  The massive use of vaccination has significantly diminished the infectious pressure with PCV-2. This implies a change in the epidemiology of the virus, creating subpopulations of animals (including those to be used as gilts) that are seronegative and susceptible to the viral infection. That is the reason for increasing rates of vaccinating gilts and sows.

• Detection and Immune response to infection

• Mechanism of host response

  Neutralising antibodies and cellular immune response (measured as IFN-gamma producing cells) are considered the major immunological correlates of protection.In PDNS there is a hypersensitivity type 3 reaction triggered and then pro-inflammatory stimulation predisposes to secondary bacterial infection.PCV-2-SD affected animals are immunosuppressed; however, immunostimulation has been shown to promote PCV-2-SD development.

  GAPS :

  Clarification of the immune modulatory role of PCV2.The role of cell-mediated immunity to PCV2 is not completely known and should be investigated; it is not known the duration of cell immunity provided by vaccines.Lack of understanding of PDNS, which seems to be related to hypersensitivity.

• Immunological basis of diagnosis

  Pigs with PCV-2 infection appear to mount a strong PCV-2 specific antibody response, mostly directed against the capsid protein, but not exclusively (also against Rep protein). The maternal antibodies appear to decrease during the period 3-11 weeks depending on the sows’ antibody levels and then increase once natural infection occurs in absence of vaccination.Experimentally, antibodies appear about 14 days after infection whereas neutralising antibodies appear about 21 days post-infection.Pigs experiencing PCV-2-SD tend to develop lower levels of neutralizing antibodies compared to those suffering from a PCV-2-SI.IgM antibodies are relative surrogates of active infection, and ELISA tests have been developed to detect such Ig subclass.The role of interferons is not properly understood, but a significant IFN-alfa and IFN-gamma responses are related to protection.Complex and multifactorial immune mechanisms occur in PCV-2-SD affected animals. ELISA tests have been designed to mainly determine the level of total IgG in serum, but do not discriminate among neutralizing and non-neutralizing antibodies.

  GAPS :

  The mode of action has only begun to be delineated; kinetics of responses are as important as the responses themselves and should be documented; we could benefit from acquiring more information about responses directed against ORF1 protein.Serological tests are not helpful for diagnosis as most pigs are seropositive; we lack any predictive test that would identify pigs that will indeed progress to severe disease; these tests are used as a non-DIVA monitoring tool.

  No commercial diagnostic tests have been yet developed to measure cell immune responses against PCV-2.

• Main means of prevention, detection and control

• Sanitary measures

  Effectiveness 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.Proper nutrition, zootechnical measures and biosecurity are considered pivotal as well.

• Mechanical and biological control

  None, except implementation of tender loving care for piglets (i.e., François Madec’s 20 point plan).

• Prevention through breeding

  Transmission through semen of naturally PCV-2 infected boars is not considered a risk, so, breeding is not expected to be a favouring or detrimental effect for the infection.

  GAPS :

  Although a pig breed effect has been reported, the actual magnitude and potential of genetic selection as a control strategy is poorly understood.

• Diagnostic tools

  Clinical signs, gross post-mortem (particularly enlarged inguinal lymph nodes), histopathology of lymphoid tissues and demonstration of PCV-2 material (by IHC or ISH in damaged tissues) are the key elements for the diagnosis of PCV-2-SD.Diagnostic criteria are also available for PCV-2-RD (clinical signs, histopathology mainly of fetal heart and demonstration of PCV-2 material in tissues) and PDNS (gross and histopathological findings; PCV-2 detection is not a key factor for its diagnosis).Quantification of virus load has been used as an aid for the diagnosis; in some cases, it is used as the unique way of diagnosis, which may be misleading if not evaluated together with other clinical and pathological approaches.

  GAPS :

  Reliable diagnostic parameters for diagnosis of PCVD on live animals should be established, especially if they have some predictive value; viral load measured by qPCR is an aid to the diagnosis, but it is not sufficient.There is no precise information regarding the viral load needed to exert a significant effect on ADWG in subclinically infected pigs.

• Vaccines

  Vaccines to control PCV-2 infections in sows and piglets are available, and are very efficient (see Section “Vaccine availability”).

  GAPS :

  Some studies have shown that maternally derived immunity does interfere with vaccine induced seroconversion, but not on clinical outcome (measured as ADWG); however, this has been tested only with few vaccines currently on the market.Impact of viral diversity on vaccine cross-protection should be assessed in more detail, and side-by-side comparisons among vaccine types would be needed. The effect of multiple heterologous vaccinations in eliciting a broad cross-protection should also be assessed.

• Therapeutics

  Not available.

• Biosecurity measures effective as a preventive measure

  No real control except general biosecurity. Herd closure and eradication may be possible, but it is hardly used.

  GAPS :

  It is not clear if herds can be declared and remain free of PCV-2; few projects have shown that PCV-2 reintroduction into negative herds occurs frequently, but more studies are needed.Eradication by means of mass vaccination of sows (three times a year) and piglets (twice at the nursery period) might be feasible as demonstrated by one study, but cost-effectiveness has not been calculated.

• Border/trade/movement control sufficient for control

  No real effective possibilities as PCV-2 are ubiquitous.

  GAPS :

  Methods for identification of carrier/shedding animals are needed.

• Prevention tools

  None, except thorough cleaning and disinfection to reduce the level of virus uptake.

  GAPS :

  Vaccination as a tool to avoid the establishment of PCV-2 in free herds should be examined; however, the number of PCV-2 free herds is extremely low if any.

• Surveillance

  Sequencing is necessary to plot changes in the virus over time and identify the emergence of variants with potentially new virulence, epidemiological or immunological features.

  GAPS :

  Mapping of genetic changes over time and geographic location could be useful.The genotype variation of PCV-2 is getting wider, so, systematic surveillance over the world would be needed, especially in the eventuality of finding potential vaccine-escape mutant viruses.

• Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

  Vaccine provision and serious improvements in the care of young piglets is highly successful to control PCVDs.

  GAPS :

  An eradication protocol was applied in a farm in Spain by means of mass vaccination (indicated above, section 16.7). While vaccinating, the virus was not able to be found. More insights on mass vaccination programs at a regional level may help on assessing the real feasibility of eradication.

• Costs of above measures

  Impossible to estimate globally, although several tools or systems exist to monitor vaccination impact at farm or production sites levels.

  GAPS :

  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. hyopneumoniae, etc.Difficulties of a proper evaluation of the cost considering that PCVDs are usually present together with other diseases, which complicates the discrimination of the effect of each particular pathogen. The effect of non-infectious factors is also difficult to be quantified and accounted.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  No.

• WOAH disease card available

  Yes, technical disease card available for all circoviruses affecting multiple species here.

• WOAH Terrestrial Animal Health Code

  No.

• WOAH Terrestrial Manual

  No.

• Socio-economic impact

• Zoonosis: impact on affected individuals and/or aggregated DALY figures

  It does not apply, no zoonosis.

• Zoonosis: cost of treatment and control of the disease in humans

  It does not apply, no zoonosis.

• Direct impact (a) on production

  Complete loss of profitability due to variation in growth rate increased morbidity and mortality and reproductive failure.

  GAPS :

  Not known the precise impact of PCV-2 subclinical infections on the ADWG of growing pigs and reproductive parameters in gestating and lactating sows.

• Direct impact (b) cost of private and public control measures

  Increased veterinary charges.In some instances, before vaccination, brought pig farmers into or to the brink of bankruptcy and despair; in the early days was the direct cause of pig farms being closed.Probably little effect now with access to vaccination, except if affected for a long time become bankrupt and give up pigs.

• Indirect impact

  Shortage of pigs into the market before the advent of vaccines. Increase use of antimicrobials and associated risk of antimicrobial resistance due to PCV-2 induced immunosuppression. Once vaccines were widely used, higher numbers of pig carcasses became available on the market.

  GAPS :

  Effect of PCV-2-subclinical infection on pig immunocompetency and thus effectiveness of other vaccination protocols, disease susceptibility and antimicrobial usage.

• Trade implications

• Impact on international trade/exports from the EU

  None, probably except for exports to certain countries, and mainly due to other concomitant diseases; for PCV-2 itself trade restriction does not make sense since it has been detected in all pig producing countries.

• Impact on EU intra-community trade

  Probably few to none, apart from some regulation from some countries on import of semen from other member states.

• Impact on national trade

  Probably negligible if any.

• Links to climate

• Seasonal cycle linked to climate

  Not apparently.

  GAPS :

  Resistance and/or sensitivity to climate variations are not clearly known, although the virus is very resistant.

• Distribution of disease or vector linked to climate

  Not apparently.

• Outbreaks linked to extreme weather

  No, the disease is present in all countries with a significant pig production.

• Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

  Not apparently.

• Main perceived obstacles for effective prevention and control

  So far, PCVDs are considered controllable diseases based on well established diagnostic criteria and very effective vaccine products that can be applied to piglets and/or breeding stock.

  GAPS :

  The knowledge on PCV-2 infection pathogenesis is still incomplete.Genetic resistance/susceptibility of the pig is still a major gap of knowledge.Although no consistent evidence exists in this sense, the differential cross-protection conferred by currently available vaccines against different genotypes is perceived as a weakness point by some field veterinarians, decreasing the trust in vaccination efficacy.

• Main perceived facilitators for effective prevention and control

  Field veterinarians and farmers are cornerstones as facilitators for preventing PCVDs in the farms.The pharmaceutical industry played a major role in PCV-2 vaccine development during 2000s; without these developments, the diseases would have not been able to be contained.

  GAPS :

  Further developments including novel vaccines with multiple genotypes or combined with other pathogens are already in the pipeline of pharmaceutical industry.

Global challenges

• Antimicrobial resistance (AMR)

• Mechanism of action

  Not applicable since PCV-2 is a virus.

• Conditions that reduce need for antimicrobials

  Although PCVDs are caused by a virus, they are immunosuppressive/immunomodulating diseases, which implies that concomitant bacterial infections can happen frequently. One of the major concerns of farmers and veterinarians before the availability of PCV-2 vaccines was the fact that antibiotic treatments did not work properly; such a situation was reverted once vaccines were applied widely, and the use of antimicrobials was substantially reduced due to PCVDs.

  GAPS :

  Effect of PCV-2-subclinical infection on pig immunocompetency and thus effectiveness of other vaccination protocols, disease susceptibility and antimicrobial usage.

• Alternatives to antimicrobials

  Not applicable since PCV-2 is a virus.

• Impact of AMR on disease control

  The wide use of PCV-2 vaccines prompted a significant reduction of antimicrobial use, therefore, diminishing the potential induction of AMR.

• Established links with AMR in humans

  Not applicable since PCV-2 is a virus.

• Digital health

• Precision technologies available/needed

  Precision technologies are increasing in their use, but none of them are specific to monitor PCVDs.

  GAPS :

  Since PCV-2 has an impact on growth and causes fever and inflammation in the nursery-growing pig, it would be ideal to have available precision tools that can monitor growth and fever at the individual level.

• Data requirements

  No specific data is required regarding digital health on PCVDs.

• Data availability

  No specific data is available regarding digital health on PCVDs.

• Data standardisation

  It does not apply.

• Climate change

• Role of disease control for climate adaptation

  Not applicable.

• Effect of disease (control) on resource use

  Not applicable.

• Effect of disease (control) on emissions and pollution (greenhouse gases, phosphate, nitrate, …)

  The effectiveness of PCV-2 vaccines implied to have a higher number of pigs reaching slaughter due to disease prevention.

• Preparedness

• Syndromic surveillance

  Mortality was the most important syndromic surveillance parameter being monitored before the advent of vaccines, together with the number of runts or sacrificed animals because human endpoint.Once vaccines were available and losses mostly controlled, no syndrome surveillance would be appliable.

• Diagnostic platforms

  Diagnostic criteria are well established as noted above (see Part 1, Section 1).Monitoring tools such as antibody detection by ELISA tests and PCR/qPCR methodologies are also widely available and used by field veterinarians.

  GAPS :

  Pen side diagnostic and monitoring tools would be desirable.Data sharing and summary would be desirable to monitor the infection/disease occurrence in different regions and evaluate potential variation in the historical patterns.

• Mathematical modelling

  Not needed for preparedness reasons, since PCVDs are endemic diseases worldwide.

• Intervention platforms

  Not needed for preparedness reasons, since PCVDs are endemic diseases worldwide.

  GAPS :

  PCV-2 genomic surveillance should be considered important, as long as the possibility of vaccine-escape mutant variants may change the current epidemiological scenario at a worldwide level.

• Communication strategies

  Not needed for preparedness reasons, since PCVDs are endemic diseases worldwide.

  GAPS :

  Information or alert systems could be desirable to promptly report variations in PCV-2 epidemiology.

Main critical gaps

• Complete comprehension of the multifactorial pathogenesis of PCV-2 infections and how disease triggering factors act.Diagnostic tools able to monitor disease (not infection) in real-time and in alive pigs.Determination of the correlation between a given viral load and the loss of productivity (ADWG for growers, reproductive parameters for gilts/sows).Novel vaccine developments (needle free, multiple genotypes, multiple pathogens).Understanding of genetic determinants of PCV-2 biology.

Conclusion

• PCVDs are nowadays considered fairly well-controlled diseases by means of vaccination of piglets and/or gilts/sows, so, they do not pose a major challenge for the swine industry. However, in the last few years, an increase in the numbers of PCVDs occurred in different parts of the world, probably due to the change in PCV-2 epidemiology caused by the very high vaccination (immunological) pressure exerted. This situation must imply to keep an eye (surveillance) on the current circulating PCV-2 genotypes and recombinants, since the appearance of genetic forms able to escape vaccine-induced immunity is not impossible.

Sources of information

• Expert group composition

  Joaquim Segalés, Universitat Autònoma de Barcelona and IRTA-CReSA, Spain – [Leader]

  Giovanni Franzo, University of Padua, Italy

  Lars L. Larsen, University of Copenhagen, Denmark

  Tomasz Stadejek, Warsaw University of Life Sciences, Poland

  Fabio Vannucci, University of Minnesota, USA

  Tanja Opriessnig, Roslin Institute, UK, and Iowa State University, USA

• Date of submission by expert group

  December 2022

• References

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