ShapeShapeauthorShapechevroncrossShapeShapeShapeGrouphamburgerhomeGroupmagnifyShapeShapeShaperssShape

Epidemiology and Control of Porcine Circovirus Diseases with Focus on Postweaning Multisystemic Wasting Syndrome

by 5m Editor
24 January 2012, at 12:00am

A review of the epidemiology and control of porcine circovirus (PCV) diseases by Poul Baekbo of the Danish Agriculture & Food Council and co-authors, presented at the International Symposium on Emerging and Re-Emerging Diseases in Pigs in 2011.

Porcine Circovirus Diseases (PCVD) or Porcine Circovirus Associated Diseases (PCVAD) are terms referring to several disease entities, where Porcine Circovirus type 2 (PCV2) plays a significant role. Postweaning Multisystemic Wasting Syndrome (PMWS) is the most important PCVD. Other diseases where PCV2 infection is of importance together with other pathogens include reproductive disorders (64), Porcine respiratory disease complex (PRDC) (29), enteritis (30) and Porcine dermatitis and nephropathy syndrome (PDNS) (63). PMWS will be the focus of this paper.

PCV2 is regarded as a ubiquitous virus infecting most, if not all pig herds. Infection with PCV2 is necessary for PMWS to develop, but most research has shown that PCV2 needs one or more co-factors for PMWS to develop into severe and even fatal disease. Despite extensive laboratory investigations of PMWS affected pigs, no single viral cofactor has yet been identified (36), but several pathogens such as Porcine parvovirus (1), PRRSV (18) and Mycoplasma hyopneumonia (43) have been shown to enhance the severity of PCV2 infections.

PCV2 has been circulating in pigs for many years before being linked to disease (23).

Sequencing of the PCV2 genome has shown several different genotypes. Up till now 5 genotypes have been described and based on a proposal form an EU PCVD Consortium, they are named with letters starting with a, thus as of now a, b, c, d and e (53). Type a and b seem to have a world wide distribution whereas type c-e have only been found in Denmark (8), China (61) and Thailand (24), respectively.

Postweaning Multisystemic Wasting Syndrome (PMWS)

Since its first description in high health herds in Canada in 1991 (17), PMWS has been reported from all major pig producing countries, except in Australia.

PMWS was first described in Europe (France) in 1996 (35), and during the following five to 10 years, most European countries experienced an epidemic-like course of PMWS (58). During this epidemic, most affected herds experienced heavy losses mainly due to a significant increase in post weaning mortality. Presently, the incidences of laboratory confirmed PMWS cases have decreased in most West-European countries (personal reports from UK, France, Spain and Denmark). This probably reflects a true decrease in PMWS incidence as reported from the field but may also reflect an increased confidence in clinical diagnosis among practitioners, reducing the number of requested laboratory diagnostic examinations.

During the present more endemic PMWS situation in Western Europe, reports from the field indicate that the clinical manifestations has shifted from the classical PMWS symptoms with high mortality among weaners in the nursery to a more chronic form among finishers with more unspecific symptoms (unthrifty pigs, some increase in mortality, decreased productivity) and increased incidences of diseases caused by other pathogens. Interestingly, this trend to an older age of PMWS appearance has not been reflected in submissions to a diagnostic lab, at least not in Spain (54).

In North America, the appearance of PMWS is most typically in the grower/finishers phase of the production, comparable to the more endemic situation in Europe now.

Diagnosis of PMWS

It is generally accepted that the PMWS diagnosis on herd level should be based on two conditions: 1) a significant increase in mortality associated to clinical signs compatible with PMWS, and 2) an individual diagnosis in at least one out of three to five necropsied pigs (16). At necropsy, the typical macroscopic findings are wasting, non-collapsed lungs, pulmonary consolidation and enlargement of at least one lymph node. Microscopic findings in lymphatic tissue include lymphocytic depletion, histiocytic infiltration, inclusion bodies and giant cells (52, 56). Together with the microscopic lesions PCV2 antigen should be present in moderate to massive quantity in lymphoid tissues with typical lesions.

Data from a case-control study was used to validate the laboratory diagnostic set-up for PMWS (41). Based on necropsy of three unthrifty pigs from all herds in the case-control study, pigs with PMWS were found in 78 per cent of case herds and in 26 per cent control herd with no obvious clinical signs of PMWS. Thus, the clinical appearance (wasting and excess mortality) should be combined with the laboratory diagnosis to be able to classify a herd as PMWS-affected.

Several studies have assessed the diagnostic value of using serology (antibodies) and PCV2 DNA detection (qPCR) for the diagnosis of PCVDs (14, 57, 66). Even though all studies found significantly higher viral load in PMWS pigs compared to non-PMWS pigs, they concurrently conclude that neither viral load nor antibodies can be used for diagnosing pigs or herds as PMWS affected because the diagnostic sensitivity and specificity are too low (14). Another reason for difficulties in setting up at common threshold for PCV2 DNA is the variance between different labs running qPCR (21).

Significance of PMWS

Post-weaning mortality is one of the most significant losses in PMWS-affected herds but reduction in growth and poor feed utilisation as well as increased consumption of antibiotics add to the cost of the disease.

A study describing the first 43 cases of PMWS in Denmark showed an average post weaning mortality of 11 per cent in the nursery (7-30kg), ranging from a few per cent to more than 30 per cent (19). Other studies comparing affected and non-affected herds showed an increase in mortality among weaners of eight per cent and four per cent, and among finishers of two per cent and 3.7 per cent in Denmark and Spain, respectively (37, 41). These mortality rates reflect the mortality at a given time but do not give information of the total loss during an outbreak of PMWS. However, a Danish study performed in 50 PMWS-affected herds with a laboratory-verified diagnosis, showed that the weaner mortality increased above the average national level (3.8 per cent) already 300 days before the time of diagnosis, peaked at the time of the diagnosis (10.3 per cent) and stayed above the national level until 300 days after the time of diagnosis (2).

In a case-control study, PMWS herds experienced a lower weight gain of 36g per day in weaners and 52g per day in finishers, compared to non-affected herds (41).

The impact of PMWS on feed utilisation has been illustrated in a US vaccine trial (22). In the vaccinated groups of pigs, the daily gain-to-feed ratio increased significantly by 1.5 per cent (396g per kg feed in vaccinates versus 360g per kg feed in controls).

Two Danish studies have illustrated the impact of PMWS on the usage of antibiotics (26, 60). Both studies showed a significant increase in the consumption of antibiotics before and until one year after the time for the diagnosis by the use of register data from a national database (VETSTAT) with information on all antibiotics used on all pig farms each month.

Transmission of PCV2 and PMWS

Several studies have focussed on the infection dynamics and transmissibility of PCV2 and of PMWS.

In a longitudinal study performed in PMWS-affected herds, following cohorts of piglets at certain time points from birth to development of PMWS, showed that the PCV2 viral load in sera, nasal and rectal swabs and in lymphoid tissues were positive and significant correlated (14). These findings are in accordance with a study showing that PCV2 is shed in similar amounts by nasal, oral and faecal routes at least until 209 days post-farrowing (47).

Experimental studies on boars have shown excretion of PCV2 virus in semen continuously until at least 50 days after inoculation of the boars (40). No differences in the shedding patterns were observed between PCV2a and PCV2b strains. A study in boar studs in USA found positive pooled serum samples (qPCR) in 12 out of 17 boar studs (27).

Sampling of colostrum and serum from 125 sows and pre-suckle piglet serum (three to five pigs per sow) in five commercial breeding herds with no PCVD reported, showed high levels of PCV2 virus DNA in colostrum as well as in sow and piglet serum (40 to 47 per cent positive samples) (55). PCV2b was detected at a considerable higher frequency than PCV2a and concurrent PCV2a/PCV2b infections were detected to some extend (six to 12 per cent of samples).

Thus both vertical and horizontal transmission of PCV2 seems likely to occur.

Investigation of the spatial (location of herds) and temporal (time of diagnose) pattern of Danish pig herds diagnosed with PMWS during the first two years after the first herd was diagnosed identified one spatio-temporal cluster between February and May 2002 (58). The identification of a significant spatio-temporal cluster early in the epidemic supports the hypothesis that PMWS is caused by a ‘new’ pathogen initially introduced to one or a few naïve pig herds and subsequently spread to most parts of Denmark during the first two years after the introduction. These findings are supported by study of Dupont et al., 2008 (8) showing a contemporary shift in genotypes from PCV2a to PCV2b in Denmark. This shift in the prevalent genotypes also happened in USA and Canada (12). One case report from two Spanish farms supports, on farm level, this link between simultaneously appearance of PMWS and a genotype shift from a to b (7). Furthermore, some experimental data indicates that different isolates of PCV2 may differ in virulence (45) but no genuine virulence marker of PCV2 has yet been identified.

Transmission of PMWS from diseased pigs to healthy pigs after mingling, have been studied in two transmission experiments (33). Both studies using PMWS affected and non-affected pigs from commercial herds, concluded that PMWS can be transmitted to healthy pigs after mingling with pigs from PMWS affected herds, especially at relatively close contact (pen mates or between pigs in neighbour pens). These results are supported by a similar study in New Zeeland (25). Airborne transmission of PMWS has been shown in an experimental study (32). The conclusions from these transmission studies points at the importance of optimal internal as well as external biosecurity to reduce the prevalence of PMWS.

Risk Factors for PMWS

Epidemiological studies comparing affected herds with non-affected herds have been carried out in UK, France, the Netherlands, Spain and Denmark with the objective to identify factors that either increased or decreased the risk for a herd to be affected by PMWS (6, 9, 37, 49, 50, 59, 63, 65). The most significant factors identified in these studies were:

Factors that INCREASE the risk for a herd to be affected with PMWS Factors that DECREASE the risk for a herd to be affected with PMWS
PRRS:
- Infection or vaccination
- In Denmark only the US strain of PRRS
High level of external biosecurity:
- Quarantine for purchased pigs and gilts
- Change of boots/clothes in entrance room of the farm
- Delivery of finishers through delivery room
Other affected herds in the area Long empty period (weaners and sows)
Purchasing larger amounts of replacement gilts (>500 per year) Dry sows in collective pens
Herd size >400 sows Treatment of external parasites
High seroprevalence of PCV2 antibodies Vaccination of sows against atrophic rhinitis
PPV antibodies among finishers
Active PPV infection in pregnant dams
On-farm semen collection and AI
Visitors without a 3-day pig-free period

Several studies have focussed on risk factors for PMWS at the individual pig level. Pigs with low PCV2 antibody titres at seven weeks of age (and no subsequent seroconversion) and piglets born by sero-negative sows were at higher risk of being affected by PMWS (HR=7.0 and 2.8, respectively) (50). Likewise, active infection of the pregnant sows with parvovirus increased the risk (HR=2.3). Calsamiglia et al, 2007 (4) found that more piglets died from viraemic sows than from non-viraemic sows (OR=2.1) and from sows with low antibody titres (OR=3.0). A longitudinal study in seven PMWS farms showed increased risk of PMWS if piglets were infected early (before seven week of age), whereas reduced risk was found if piglets were weaned after 21 days and if they were born of sero-positive sows (51). The significance of maternal immunity as protective for disease development, as indicated in these studies, is supported by a longitudinal cohort study in 13 Spanish/Danish PMWS farms (15).

Control of PMWS

Concerning control of PMWS, there is a time before and a time after the emerging of commercial PCV2 vaccines in the period 2004-2006. Before the vaccines became available, much focus was on good production practice and on the control of other diseases (38). The timing of other vaccines seemed to play some role in preventing or reducing the problems with PMWS (42, 44). Different reports from the field and one clinical trial indicated that serum from pigs recovered from PMWS by injection could prevent PMWS to some extent (20).

Introduction of the PCV2 vaccines indeed changed the world and a huge number of conference abstracts and peer-reviewed articles have shown great benefit of the vaccines. The success of the vaccines is probably based on activation of both the humeral and cellular immune responses against PCV2 (28). Presently, four commercial PVC2 vaccines are commercial available in most countries; one sow vaccine (Circovac®, Merial) and three piglet vaccines (Ingelvac® CircoFlex, Boehringer Ingelheim; Porcillis® PCV/Circumvent® PCV, Intervet/Merial & Circovac®, Merial). All vaccines are inactivated and based on a genotype PCV2a strain. One vaccine has been withdrawn from the market (Suvaxyn® PCV2, Fort Dodge/Pfizer).

One extensive meta-analysis on the effect of vaccines against PCV2 identified 107 studies from 2007-2008, of which 24 studies of relevant quality were included in the analysis (34). A significant effect of vaccination was seen on average daily gain (ADG). The increase in ADG was 41.5g for finishers, 33.6g for nursery-finishers and 10.6g for nursery pigs. Likewise, a significant effect of vaccination was seen on reduction in mortality. The reduction for finishers were 4.4 per cent and for nursery-finishers, 5.4 per cent. No differences were found in effect on ADG and mortality of the different vaccines.

Even in farms with a subclinical level of PCVD and with acceptable mortality rates, vaccination of piglets has shown to increase ADG by 32g among grower-finishers (from day 41-131) (31).

One vaccine trial (Circumvent® PCV) showed a significant increase in daily gain-to-feed ratio by 1.5 per cent (6g) in vaccinated pigs (22).

The timing of the vaccination of the piglets is often in question due to the possible interaction of maternal derived antibodies (MDA) that in many studies have been shown to protect against development of PMWS (see earlier). In an experimental setup where 3 week old pigs were vaccinated (Porcillis® PCV) and challenged with a PCV2b three weeks after vaccination, high level of MDA at the time of vaccination were found to interfere with the active seroconversion of the piglets, even though the vaccine significantly reduced viremia and shedding of virus (11). One study using Ingelvac® CircoFlex showed no difference in efficacy whether pigs were vaccinated at three or six weeks of age indicating no significant impact of MDA (5). Nevertheless, even though some discrepancies exist on the inhibiting effects of MDA, it is recommended to avoid vaccination of piglets at too early an age.

Concerning the question on using sow and/or piglet vaccination, one clinical field trial in one herd showed similar good efficiency with three different vaccination protocols (Circovac®) – vaccination of sows, vaccination of piglets and vaccination of both (48). An experimental study indicated that sow vaccination and piglet vaccination had similar reducing effect on the viral load in piglets (46). Sow vaccination reduced the prevalence of sows with PCV2 in colostrum compared to non-vaccinated sows (13). One study showed an increase in weaning weight by 0.93kg in piglets born from vaccinated sows (3).

It has been speculated whether the efficacy of the commercial vaccines based on PCV2a might be jeopardised by the fact that most infections are caused by PCV2b strains. Based on an experimental study, this seems not to be the case (10). Based on market research, the piglet vaccination rates on the global marked has been estimated (39). In Europe, examples of countries with a high vaccination rate (>80 per cent) are Germany, UK, Ireland, Austria, and Switzerland whereas Russia, Denmark, and Poland have a low rate (<30 per cent). USA, Canada, Mexico, Brazil and Chile have a very high rate (80 to 98 per cent). In Asia, Korea and Japan has high rates (70 to 90 per cent) whereas China and Viet Nam have low rates (<5 per cent). Interestingly, 34 per cent of the piglets seem to be vaccinated in Australia, where PMWS has not yet been diagnosed.

Whether this extensive use of PCV2 vaccines has changed the epidemiology of PCVDs apart from reducing the losses related to classical PMWS, is still an open question since the data on the prevalence and impact of the various PCVDs are scarce. Thus, more research on the role of PCV2 on enteric, reproductive and respiratory diseases in general should be performed.

References

1. Allan et al. 1991. J Comp Pathol, 121:1
2. Baadsgaard et al., 2006. VSP-report 762 (Danish)
3. Brons et al., 2010. Pig Journal, 64:59-64
4. Calsamiglia et al., 2007. Res in Vet Sci, 82: 299-304
5. Cline et al., 2008. Vet Rec. 163:737-740
6. Cook et al., 2001. Pig Journal, 48:53-60.
7. Cortey et al., 2010. IPVS, P.008, 314
8. Dupont et al., 2008. Vet Micro, 128:56-64
9. Enøe et al., 2006. IPVS, 1:163.
10. Fort et al., 2008. Vaccine, 26:1063-1071
11. Fort et al., 2009. Vaccine, 27:4031-4037
12. Gagnon et al., 2007. Can Vet J, 48:811-819
13. Gerber et al., 2010. Vet Journal, doi:10.1016
14. Grau-Roma et al., 2009. Vet Micro, 135:272-282
15. Grau-Roma et al., 2011a. in preparation
16. Grau-Roma et al., 2011b. in preparation
17. Harding, 1996. AASP, 21
18. Harms et al., 2001. Vet Pathol 38:528
19. Hassing et al., 2003. E & Re-E Pig D. 211
20. Hassing et al., 2006. IPVS, O.25-01
21. Hjulsager et al., 2009. Vet Micro, 133:172-178
22. Jacela et al., 2011. J Sw Health & Prod, 10-18
23. Jacobsen et al., 2009. Vet Micro, 138:27-33
24. Jantafong et al., 2011. Virology J, 8:88
25. Jaros et al., 2006. IPVS, 1:168
26. Jensen et al., 2010. Prev Vet Med. 95:239-247
27. Kauffold et al., 2010, IPVS, O.065, 103
28. Kekarainen et al., 2010. Vet Im & ImPath, 185-193
29. Kim et al., 2003. Vet J, 166:251
30. Kim et al., 2004. Can J Vet Res, 68:218
31. King et al., 2008. AASV, 159-161
32. Kristensen et al., 2007. E & Re-E Pig D, 73
33. Kristensen et al., 2009. Vet Micro, 138:244-250
34. Kristensen et al., 2011. Prev Vet Med, 98:250-258
35. LeCann et al., 1997. Vet Rec, 141:660
36. Lohse et al., 2008. Vet Micro, 129:97-107
37. López-Soria et al., 2005. Prev Vet Med, 69:97-107
38. Madec et al., 2000. Livest Prod Sci, 63:223-233
39. Maass, 2011. personal communication
40. Madson et al., 2008. J Vet Diag Invest, 20:725-734
41. Nielsen et al., 2008. Vet Rec, 162:505-508
42. Opriessnig et al., 2003. Vet Pathol, 40:521-529
43. Opriessnig et al., 2004. Vet Pathol, 41:624
44. Opriessnig et al., 2006. Vet Rec, 158:149-154
45. Opriessnig et al., 2006. J Gen Virol, 87:2923
46. Opriessnig et al., 2010. Vet Micro, 142:177-183
47. Patterson et al., 2011. Vet Micro, 149: 225-229
48. Pejsak et al., 2010. ComImmMicro&InfD, 33/6, e1-e5
49. Rose et al., 2003. Prev Vet Med, 61:209-225.
50. Rose et al., 2005. Livest Prod Science, 95: 177-186.
51. Rose et al., 2009. Prev Vet Med, 90:168-179
52. Segalés et al., 2004. Vet Micro, 98:137-149
53. Segalés et al., 2008. Vet Rec, 867-868
54. Segalés et al., 2010. Vet Rec, 167:940-941
55. Shen et al., 2010. Prev Vet Med, 97:228-236
56. Sorden, 2000. Sw Health & Prod, 8:133-136
57. Turner et al., 2009. Prev Vet Med, 88:213-219
58. Vigre et al., 2005. Vet Micro, 110:17-26.
59. Vigre et al., 2006. IPVS, 1:174.
60. Vigre et al., 2010. Prev Vet Med, 93:98-109
61. Wang et al., 2009. Virus Res, 145:151-156
62. Wellenberg et al., 2004. Res in Vet Sci, 77:177-84.
63. Wellenberg et al., 2004. Vet Microbiol, 99:203
64. West et al., 1999. J Vet Diagn Invest 11:530
65. Woodbine et al., 2007. Vet. Rec, 160:751-762
66. Woodbine et al., 2010. Prev Vet Med, 97:100-106

Reference

Baekbo P., C. Sonne Kristensen and L.E. Larsen. 2011. Epidemiology and Control of Porcine Circovirus Diseases with Focus on Postweaning Multisystemic Wasting Syndrome. International Symposium on Emerging and Re-Emerging Diseases in Pigs, Barcelona, Spain.

Further Reading

- You can view the Proceedings of the 6th International Symposium on Emerging and Re-Emerging Pig Diseases by clicking here.


Further Reading

- Find out more information on PMWS by clicking here.


January 2012