Post-weaning multi-systemic wasting syndrome in pigs: why did it emerge?

Within a few years, post-weaning multi-systemic wasting syndrome (PMWS) has become a worldwide animal health concern to the pig industry and a real challenge to the veterinary science community. A small single-stranded DNA virus, Porcine Circovirus type 2 (PCV2), was rapidly found in the damaged tissues of affected pigs.

However as soon as the laboratory tools adequately tailored to PCV2 detection on a large scale were available, it became evident that the virus was widespread and found in PMWS-affected as well as in non-affected farms. Additionally, retrospective studies consistently showed that it had been present for decades, long before PMWS was recognized and reported. Since the first descriptions in North America in the mid 1990s (Harding, 1996), a huge research effort has been directed at the disease.

At present our understanding of the disease is far from complete, but the damage caused on commercial farms remains considerable in some areas. After a brief recap of the symptoms and elements of diagnosis, the major part of this paper will attempt to propose scenarios that could have led to the emergence of PMWS and PCV2-associated diseases.


Disease syndromes and their diagnosis

Typically when PMWS strikes, the post-weaned growing pig (7-15 weeks of age) is the favourite if not exclusive target. The pigs show ill thrift and low feed intake; and in more advanced stages they become pale and exhibit laboured breathing. Fever is a common clinical sign (up to 41°C) as well as diarrhoea.

In individual pigs, the disease progresses rapidly, and within 3-7 days weight loss can be considerable and affected pigs soon look miserable. Wasting is often fatal whereas poor-doing pigs require euthanasia. In severe cases, total mortality can easily reach 20-30%. The severity and type of disease expression vary among pigs, with respiratory and/or digestive (diarrhoea) syndromes being the most frequent.

In a given group of pigs, whilst several are strongly depressed, the majority do not display any obvious sign of sickness throughout weaning and fattening phases. In addition to wasting, on PMWS-affected farms a number of pigs (much less than 1% on average but up to 5-8 % in groups of contemporaries on some farms) show dermatitis. Irregular red-to-purple macules appear mainly on the hind legs and the perineal and rump area but also the ears and belly. They tend to coalesce and can cover a significant area of the body.

Due to simultaneous severe kidney lesions, the condition was named PDNS (Porcine Dermatitis and Nephropathy Syndrome). Case fatality is rather high with PDNS, even in grow-finish pigs. Surprisingly, in farrow-to-finish operations no obvious consequences of PMWS are seen in the sow herd: sow productivity is maintained. The severity of PMWS varies among farms. A litter (sow) effect was also found; and the duration of clinical disease also varies.

When adequate hygiene measures were strictly applied, severe disease was stopped within 3 to 6 months whereas in farms reluctant to change sanitation practices the disease could remain for more than two years (Madec et al., 2000). In individual pigs, at necropsy, the most frequent anomalies are enlarged lymph nodes with a number of other lesions widely reported in the literature. Similarly, numerous histological lesions have been recorded such as lymphocyte depletion and histiocytic and multinucleate giant cell infiltration in the lymphoid tissues.

Establishing the diagnosis of PMWS at the herd level is still debated despite interesting inputs (Sorden, 2000). A general definition has been proposed by an EU multidisciplinary consortium (Allan and McNeilly, 2006): ‘The occurrence of PMWS is characterised by an excessive increase in mortality and wasting post-weaning compared with the historical level in the herd.’ The most recommended option is thus to refer to periods of time. The current time period is one or two months whereas the historical reference period should be at least three months.

A diagnosis of PMWS is highly suggested when current losses (associated with wasting) significantly exceed the historical levels (χ² tests). The authors insist on the necessity for good on-farm records and the need to submit several affected pigs to the laboratory to properly establish the diagnosis. In order to establish the diagnosis, in addition to the clinical signs, histological lesions are depletion of lymphoid organs/tissues and/or lymphohistiocytic to granulamatous inflammation in any organ (typically lungs and lymphoid tissues). Finally, PCV2 should be detected within the lesions.


What may have caused emergence of PMWS?

The following hypotheses as regards PMWS emergence throughout the world are backed by the authors’ experience both from the field and from experimental trials. They can be ranked into five points:

1. The PCV2 changed (i.e., PMWS is induced by a new specific virulent strain).

2. PCV2 did not change but there is another new or presently unknown pathogen involved (e.g., virus X) or an already known PCV2-interacting virus changed (e.g., PPV, retrovirus).

3. The pigs were exposed to something new of a non-infectious nature but which facilitated/triggered PCV2 replication through immunomodulation (e.g., vaccines, ingredients in diets) and/or modification of the virus environment within the target cells. The new factor has been spreading through normal international and national trade.

4. Management and husbandry have been changing (e.g., collateral consequences of increased litter size like more cross fostering, less attention paid to colostrum intake, to vaccination schemes, to mixing and overstocking). Those management and husbandry changes in breeding herds may also have interfered with the routes of PCV2 spread (e.g., semen as ‘new’ route for PCV2 or increased PCV2 pressure in semen).

5. The genetic background of the pigs changed (reduced variability through targeted breeding programmes and increased susceptibility of certain lines).

These five hypotheses are not all mutually exclusive versus PMWS and obviously they do not necessarily evolve independently. Hence hypothesis 3 is part of 4 and the genetic background (5) to a certain extent as well.

At the region/country level, the PMWS problem abruptly appeared with a progressive increase in reported cases. When the disease occurred on a specific farm, the suddenness of the break was a common feature. In other words, in nicely and quietly performing farrow-to-finish units, high losses suddenly occurred due to wasting in growing pigs without any perceivable premonitory clinical signs at any other stage of the herds. In respect to suddenness at the individual farm level, all five hypotheses are more or less plausible. But when the geographical spectrum is widened while considering the same period of time (i.e., Europe and North America, 1995-1996), some of them can hardly be valid (e.g., 4 and 5) and even 1.

Hypothesis 1 (change of PCV2 virulence) would suppose that either the same mutation occurred in the PCV genome simultaneously in different countries/continents or the change occurred in one place but the new mutant spread rapidly throughout the other countries. Both hypotheses 1 and 2 would suppose that the pathogen only spread in selected countries, those where PMWS struck. Two amino acids in the capsid gene were found involved in PCV 2 attenuation (Fenaux et al., 2004) and a total of nine amino acid changes in ORF2 and two amino acid changes in ORF1 were found between two strains isolated in the USA (Opriessnig et al., 2006).

When the virulence of two isolates was compared experimentally, differences were noted. Those differences related to microscopic lesions and to PCV2 genomic copy numbers in the tissues. However no clinical disease could be obtained in the trial. On the other hand no agent ‘x’ has yet been found by the scientific community. Sudden onset is more compatible with hypothesis 3. Such an exposure would be supposed to break the pre-existing more or less fragile balance involving the PCV2.

The quantitative clinical expression of PMWS depending on the farm and also on the batch in farrow-to-finish systems is most in favour of hypothesis D. The immune system is affected in this disease and logically poor hygiene and shortcomings in housing and husbandry contribute to the burden of secondary pathogens. Hypothesis 3 is also valid as the exposure to the triggering factor can vary in a more or a less quantitative way.

The epidemiological pattern of PMWS did not look typical of epidemics leading to waves of disorders in a region. A former example of such a devastating wave could be PRRS in The Netherlands in early 1990s where 400,000 piglets were lost within two months. Nothing like this was seen with PMWS.

However with PMWS some geographical clusters were occasionally seen. Both experimental and field trials told us that the disease (not only PCV2 infection) is clearly horizontally transmissible. This major point strongly suggests an infectious cause, i.e., hypothesis 1 and 2 and hardly 3, 4 or 5. However when not only PCV2 transmission is considered but also the viral load (PCV2 pressure) presumed necessary to launch clinical signs in susceptible contact pigs, the conditions sustained by hypothesis 3, 4 and 5 should not be ignored.

PCV2 is widespread, and was so for a long time before PMWS clearly emerged. If the virus did not change and in the absence of other infectious alternatives, it would mean that the reasons for emergence are to be found in 3, 4 or 5 and in their combinations/interactions.

The actions behind hypothesis 4 have been proven to determine disease severity in field conditions. When hypothesis 3 and 4 are combined, the most important epidemiological traits and the outcome of the trials can be adequately explained. This would mean that when clusters formed in regions it was not due to pathogen spread but to the changing environment of the pigs, especially their exposure to commercial products and/or dietary factors that could trigger massive PCV2 replication at critical stages in the piglet’s life regarding susceptibility to PCV2 invasion. In other words, under normal initial farming conditions the pig could resist PCV2 infection and the virus remained silent until exposure to triggering factors that spread according to normal local, national or international conditions.

The possible trigger compounds are numerous and varied (feed with multiple ingredients of all sorts, drugs, pigs, semen) and might enter a farm even when it is said to be closed and when high biosecurity measures are taken. Among these, adjuvanted vaccines are highly suspect, especially when administered to young piglets.

Both experimental trials and field observations are found in the literature that provide converging results. In short, a plausible hypothesis could be that in PCV2 infected herds, early sharp and subtle stimulation of the immune system through certain vaccinations could result in an abundant production of cells that provide PCV2 the required specific cellular environment to replicate massively.

The problem is that clearly-defined PMWS only concerned a limited number of farms, whereas early vaccination is widespread. Reciprocally, the disease was also seen in farms where the young piglets were not vaccinated. The question of vaccine use in sows can also be raised as there is no experimental evidence of a direct causative role. Other compounds capable of initiating the required response by the immune system might also be mentioned (e.g., an ingredient or combinations of ingredients in the diet, the feed-related microflora, etc.).

To our knowledge, nothing on this point was noted by the veterinary research community. Veterinary research tends to be confined to investigations of viral and immunopathogenic aspects; and unfortunately no collaborative efforts with other branches of animal science have appeared on this issue.

Recently the implication of retroviruses was investigated, which opened a new field in relation to PMWS (Tucker et al., 2006) whereas no link could be established between PMWS and lymphotropic γ-herpesvirus (McMahon et al., 2006).

The most probable scenario resulting in PMWS emergence still remains to be established, despite most of the pieces of the puzzle now being in place. The allegation that PCV2 plays a pivotal role can easily be agreed. The crucial question still unanswered is why PCV2 suddenly became so influential on health. Obviously the scenario not yet found, of existing subtle changes in PCV2 when pathogenic, would be enlightening.

Only the question of how it could rapidly pass through biosecurity measures would have no answer. The same question would emerge if another, presently undetected pathogen (virus ‘x’) is finally found to work in concert with PCV2.

Additionally, it seems that PMWS clinical disease at a herd (and at the individual pig) level is not a yes-or-no phenomenon. PCV2 is a necessary condition but there are other factors important at different stages. The pregnant sow has a major role. The immune challenge she faces (e.g., parvovirus) and her immune status at farrowing are reflected in the piglet at birth and long after birth.

At birth, colostrum composition and intake is a critical step regarding piglet resistance to PMWS (Moll, 2004). The point is easily overlooked. Recent studies show that colostrum is rapidly modified with respect to certain components, the alteration taking place soon after farrowing (Devillers et al., 2004). Not enough attention is paid to colostrum intake, especially in highly prolific sows and when cross-fostering is intense. As regard PMWS clinical expression, as early as 12 hrs post-partum, important determinants of the susceptibility to the disease are in place.

Additional challenges may appear that launch the triggering process. Among such challenges are vaccination, mixing, and exposure to infectious challenges. Disease expression will depend on the nature and strength of the immune response to the latter and on the degree of susceptibility of the individual pig at the moment these challenges appear. In that, the dynamics of PCV2 in herds should be a key indicator of susceptibility to PMWS.

Such a scenario shows a cascade (a sequence) of events taking place early in the piglet’s life, despite disease expression being delayed to the growing or even the finishing phase (PDNS). Bringing together the required determinants of the triggering process in due time leads to emergence. This implies the need for both the required conditions and proper timing of intervention. The intensity of the chain reaction will depend the severity of clinical expression, the latter ranging from nothing perceivable (only PCV2 infection) to fatal disease.

References

Allan, G. and F. Mc Neilly. 2006. PMWS/PCVD: diagnosis, disease and control: what do we know? Proceedings 19th IPVS Congress, Vol. 1, Copenhagen, July, pp. 1-9.

Devillers N., C. Farmer, A.M. Mounier, J. Le Dividich and A. Prunier. 2004. Hormones, IgG and lactose changes around parturition in plasma, and colostrum or saliva of multiparous sows. Reproduction, Nutrition and Development 44: 381-396.

Fenaux, M.T., P.G. Opriessnig, P. Halbur, F. Elvinger and X.J. Meng. 2004. Two amino acid mutations in the capsid protein of type 2 porcine circovirus (PCV 2) enhanced PCV 2 replication in vitro and attenuated the virus in vivo. J. Virol. 78:13440-13446.

Harding, J.C. 1996. Post-weaning multisystemic wasting syndrome: preliminary epidemiology and clinical findings. In: Proceedings West Canadian Association of Swine Practitioners, p. 21.

Madec F., E. Eveno, P. Morvan, L. Hamon, P. Blanchard, R. Cariolet, N. Amenna, H. Morvan, C. Truong, D. Mahé, E. Albina and A. Jestin. 2000. Postweaning Multisystemic Wasting Syndrome (PMWS) in pigs in France: Clinical observations from follow-up studies on affected farms. Livestock Production Science 63: 223- 233.

McMahon K.J., D. Minihan, E.M. Campion, S.T. Loughran, G. Allan, F. McNeilly and D. Walls. 2006. Infection of pigs in Ireland with lymphotropic γ-herpesvirus and relationship to Postweaning Multisystemic Wasting Syndrome. Vet. Microbiol. 116: 60-68.

Moll A. 2004. The effect of passive colostral transfer on the subsequent viability and development of post-weaning multisystemic wasting syndrome (PMWS) in pigs. Pig Journal 54: 206-225.

Opriessnig, T., N.E. Mc Keown, E.M. Zhou, X.J. Meng and P.G. Halbur. 2006. Genetic and experimental comparison of porcine circovirus type 2 (PCV2) isolates from cases with and without PCV2-associated lesions provides evidence for differences in virulence. J. Gen. Virol. 87:2923-2932.

Sorden, S.D. 2000. Update on porcine circovirus and post-weaning multisystemic wasting syndrome (PMWS). Swine Health Prod. 8:133-136.

Tucker A.W., L. Scobie, M. Donadeu, M. Torremorell and M. Mellencamp. 2006. Retroviraemia in commercial pigs and its preliminary association with low health status. Proceedings 19th IPVS Congress, Copenhagen, Vol. 1, p. 217.