Emerging Threats Quarterly Report – Pig Diseases – January to March 2012 (Q1)

During February 2012, eight PRRS outbreaks were diagnosed in submissions to Bury St Edmunds Regional Laboratory. This occurred at the same time as anecdotal reports of increased PRRS in the region by veterinary surgeons and producers at an Eastern Pig Health Steering Group meeting.
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Highlights

  • Actinobacillus pleuropneumoniae serotype 9 detected in Scotland
  • PRRS outbreaks in East Anglia
  • Investigations into swine dysentery outbreaks in Yorkshire
  • Ampicillin-resistant Actinobacillus pleuropneumoniae isolated
  • Respiratory disease prominent over winter months

New and Emerging Diseases

Analysis of diagnostic submissions from which no diagnosis was made

This report reviews VIDA data where a diagnosis was not reached (DNR) despite the sample receiving “reasonable” testing. This allows monitoring of this class with the aim of providing information on potential new or emerging diseases or syndromes. ‘Prior years’ refers to pooled data for 2008-2011 for GB VIDA data.

Overall VIDA data: DNR by presenting sign and syndrome

  • The overall percentage of pig diagnostic submissions for GB VIDA data for the first quarter of 2012 where a diagnosis was not reached was 15.4 per cent (37/240). This was similar to the same period in prior years (17.8 per cent). Overall DNR rates for SAC and AHVLA individually were not significantly elevated for this period compared to the same period in prior years.

  • There was no increase in DNR for any individual presenting sign or syndrome in Q1, 2012, for Great Britain (GB), AHVLA or SAC data compared to prior years.

  • To Q1, 2012, there was a significant increase in undiagnosed AHVLA submissions with diarrhoea as a presenting sign in Eastern England; 50 per cent were undiagnosed (5/10) compared to 19 per cent in prior years.

  • The rolling 12-month DNR data was also reviewed and DNR rates were not raised overall or for any individual presenting sign or syndrome.

DNR for diarrhoea as a presenting sign in Eastern England

  • The undiagnosed submissions in Eastern England were reviewed and there was no consistent presentation. They were a mix of inappropriate disease phase, inconclusive testing, suspected dietary change and likely poor milk supply.

DNR for wasting as a presenting sign

  • The DNR data for submissions in Q1, 2012 with wasting as a presenting sign in post-weaned pigs were reviewed as part of scanning surveillance for post-weaning failure to thrive syndrome (PFTS). PFTS is a wasting disease of unknown aetiology reported from Northern America (see under horizon scanning) and distinct from porcine circovirus-2 associated disease.

  • The DNR rate for submissions with wasting as the presenting sign for GB was 5.3 per cent (1/19) compared to 11.1 per cent for prior years. Fifteen of the submissions were of post-weaned pigs. The one undiagnosed submission was a chronic case of ill-thrift in a 13-week-old pig following diarrhoea several weeks earlier, intestinal villus atrophy was present pointing to an earlier enteric insult and submission of a typical case earlier in the course of disease was recommended.

  • There were no submissions suspicious of PFTS in Q1, 2012.

Analysis of undiagnosed submissions in Q1, 2012 does not reveal evidence of a new and emerging syndrome, or of emergence of PFTS, in GB pigs.

Actinobacillus Pleuropneumoniae serotype 9 detected in Scotland

Actinobacillus pleuropneumoniae (APP) serotype 9 was isolated from chronic lesions detected incidentally in the lungs of three pigs sampled during abattoir slaughter checks in a batch of about 200 pigs.

Serotype 9 was last reported in the UK in 1994 (McDowell and Ball, 1994). Serovars isolated between 1995 and 2007 in England and Wales were most recently identified using multiplex PCRs as 2, 3, 6, 7, 8 and 12, of which 8 was predominant (using serotyping, serovar 3 appeared predominant however PCR identified most serovar 3 isolates as being serovar 8 (O’Neill et al., 2010).

Virulence of this APP serotype 9 isolate is not known. Virulence is considered to be multifactorial in APP and is influenced by exotoxin production and other factors. Exotoxin (Apx) production by each serovar has been categorized by Reimer at al. (1985) and serotype 9 produces Apx I,II and IV. In general, serovars producing Apx I are considered to be more virulent and to cause higher mortality in pigs, especially when in combination with Apx II.

This is the first APP isolate producing exotoxin Apx I to have been identified in GB since 1995. The pig that this serotype 9 was isolated from was not imported and the source of infection is not known. It is possible that this serotype has remained present in the pig population at a very low level since 1994. In Europe, serovar 9 is prevalent in the Netherlands, Spain, France and Germany.

Recent APP serotypes isolated in England and Wales will be serotyped and future isolates will be kept under review. No increase in APP diagnoses is evident from VIDA data in GB.

Ongoing Emerging Disease Investigations

Incoordination in growing pigs with unusual peripheral neuropathy 0006/ED1200/2011

No further cases have been diagnosed since August 2011. This investigation was initiated in May 2011 and detailed in Q2, Q3 and Q4 2011 Emerging Threats reports.

Pigs aged 6-11 weeks old from three units were diagnosed with this unusual radiculitis, ganglionitis and peripheral neuritis with myelin deficits.

The pathology has been characterised in more detail; electron microscopy confirmed significant myelin deficits but intact axons and coronin 1a immunohistochemistry revealed intense labeling of inflammatory cells in nerve roots and peripheral nerve. No viruses were detected in nervous tissue from affected pigs when examined using an extended microarray (a 60,000-probe chip covering around 2,500 virus species).

An immune-mediated aetiology is considered most likely based on current findings, similar to that described Guillain-Barré Syndrome in humans. This syndrome is an immune-mediated polyneuropathy for which the initial trigger is not known but for which certain specific infections/vaccinations are recognised as preceding disease in certain individuals, the hypothesis being that immunogens cross-react with epitopes of peripheral myelin due to molecular mimicry. A condition with similar pathological findings is described in White Leghorn chickens with acute paresis (Bader at al, 2010) for which the cause not known but suspected to be an interaction between vaccination and infections with particular genotypes at risk. A sampling protocol is established for future cases.

Details of the condition, including videos of affected pigs, have been shown at meetings of pathologists and pig veterinarians and an oral presentation was made to the European Symposium of Porcine Health Management in Bruges in April 2012 (Williamson et al., 2012); no-one reported having seen similar cases elsewhere in Europe.

Klebsiella pneumoniae subsp. pneumoniae septicaemia 0007/ED1200/2011

No further outbreaks have been diagnosed since September 2011. Six outbreaks of septicaemia due to Klebsiella pneumoniae subsp. pneumoniae infection were diagnosed as the cause of sudden death of preweaned pigs on outdoor breeding units between July and September, all were in East Anglia. Details were included in the Q3 and Q4 Emerging Threats report.

Characterisation of the outbreak isolates and comparison with historic isolates was undertaken by AHVLA Weybridge. Multilocus sequence typing (MLST), which evaluates the relatedness within a bacterial species, revealed very consistent findings for the six outbreak Klebsiella isolates, which all belong to the same sequence type (ST25). They also possess the same virulence gene rmpA and a 4.5kb plasmid.

Analyses indicate that, although some individual characteristics are present in historic isolates, this combination of attributes is not shared by any historical isolates examined to date but is shared by some outbreak-related isolates obtained from live pigs on affected farms. A questionnaire is established for future cases if outbreaks occur again.

Details of the condition have been presented to Pig Veterinary Society and further information is available on the VLA web site and a poster was presented at the European Symposium of Porcine Health Management in Bruges in April 2012 (Bidewell et al., 2012).

Increased PRRS diagnoses in East Anglia

During February 2012, eight outbreaks of PRRS were diagnosed in submissions to Bury St Edmunds Regional Laboratory. This occurred at the same time as anecdotal reports of increased PRRS in the region by veterinary surgeons and producers at an Eastern Pig Health (EPH, part of Pig Health Improvement Project) Steering Group meeting.

The percentage of submissions with PRRS diagnosed by AHVLA for January to March 2012 increased compared to the same quarter in 2011 and the last quarter of 2011 – 11.4 compared to 7.7 per cent and 8.6 per cent, respectively – although the increase was not statistically significant in either case. Whether this perceived upsurge relates to the spread of a particular strain, to disease manifesting on units where it had previously been controlled, or to independent biosecurity breaches was investigated by sequencing of the open reading frame 5 (ORF5) of virus from several outbreaks.

Results so far indicate that the outbreaks involve different viruses and not a novel or particular strain spreading in the region. Figure 2 illustrates the recent strains sequenced.


Figure 2. Phylogenetic tree showing ORF 5 sequences of 2012 PRRSv isolates from East Anglia

One outbreak was on a vaccinated breeding unit and included deaths of breeding sows, one of which was submitted and had died due to likely secondary Pasteurella multocida pneumonia.

Mass vaccination on the unit was reported to have reduced clinical disease, suggesting that vaccinal immunity was still providing some protection. This incident was reported to Veterinary Medicines Directorate.

It is important to note that virus sequencing can indicate the genetic relationship between PRRSv strains and assists epidemiological investigations, provides an insight into the extent of genetic diversity and distinguishes vaccine from field strains. It is not possible, from the results of ORF 5 genetic sequencing alone, to predict the degree of protection that would be afforded by the vaccine to infection by a field isolate, nor can virulence be predicted.

Awareness about the increased diagnoses was raised by presentations at a pharmaceutical company’s Symposium for pig practitioners on porcine respiratory disease in April 2012 and at the Pig Veterinary Society Spring meeting in May 2012. If EPH can secure funding, increased PRRSv testing in the region is planned in response to the concerns.

Swine dysentery outbreaks in North Yorkshire

During the period January to March 2012, swine dysentery (SD) was diagnosed on five new premises in the area of North Yorkshire in which outbreaks were diagnosed in 2011.

Since mid-2011, 10 units have been or are still infected with SD; of these three have undergone total depopulations and are awaiting repopulation, another two have undertaken successful medicated partial depopulations or whole-herd medication programmes using tiamulin. Success with the latter approach has only been possible where tiamulin Minimum Inhibitory Concentrations (MICs) have confirmed sensitivity in isolates. Five infected units remain of various types and sizes. As shown previously, there is evidence in one infected unit that continuing use of tiamulin is leading to resistance in the Brachyspira hyodysenteriae present.

In February 2012, AHVLA was funded by BPEX to undertake multi-locus sequence typing (MLST) on nine strains of B. hyodysenteriae from this area, as well as three control strains. Results showed that all B. hyodysenteriae isolates from the area fell into one of two distinct groups. Control strains (from other parts of the UK) were very different. Interestingly, one group comprised organisms with high tiamulin MICs and some fully sensitive organisms; in one case, two isolates from the same farm, one sensitive to tiamulin (before medication) and one highly resistant (post medication), were in the same MLST group, implying that resistance had been induced in the organism by use of that antimicrobial. It was inferred that organisms also in that same group had potential for developing resistance and appropriate advice was given to producers with those isolates.

The tiamulin MIC findings were supported by clinical findings of reducing efficacy over time.

Epidemiological links between the units in the different clusters were identified at a producer meeting, supporting the relevance of applying MLST methodology which shows promise as a useful epidemiological tool in these outbreaks. The concept of collaborative working among affected producers, to improve pig health and productivity, as championed by BPEX in these regional initiatives, will be an essential part of sustainable improvements in pig health.

Tiamulin MICs continue to be undertaken funded by AHVLA’s ‘Monitoring of Antimicrobial Resistance in Bacteria from Animals and their Environment Project’ on AHVLA B. hyodysenteriae isolates. Any tiamulin-resistant isolates are tested for their sensitivity to other antimicrobials available for treatment of SD. Results are reported to practitioners with a comment that alternative interventions (all-in, all-out management systems; cleaning and disinfection; and partial and total depopulation leading to eradication) are vital to prevent the development of wider antimicrobial resistance.

Unusual Diagnoses or Presentations

There were a number of unusual diagnoses this quarter; details of these have been included in monthly AHVLA reports and AHVLA highlights to BPEX, BPA and Pig Veterinary Society. These will be kept under review to assess whether they justify initiation of emerging disease investigations.

Unusual case of thrombocytopenia in neonatal pigs

A case of thrombocytopenia was diagnosed in neonatal pigs on one indoor breeder-finisher on which half of one litter in each of the previous three farrowing batches developed subcutaneous haemorrhages and half of these affected pigs then faded and died. The farmer had seen alloimmune thrombocytopenia purpura previously and considered these piglets to be clinically similar but was concerned because piglets showed signs within 24 hours of birth and one was from a gilt litter.

Piglets were reported to be unaffected at birth, strong and sucking well. Two live piglets were submitted, both had subcutaneous haemorrhages distributed according to likely local skin trauma and suggestive of a coagulopathy, with no other significant gross lesions.

Haematology confirmed thrombocytopenia and anaemia and histopathology revealed megakaryocyte hyperplasia consistent with a regenerative response to platelet damage and supporting a diagnosis of alloimmune thrombocytopenia purpura, although not pathognomic. All three main lineages were well represented in bone marrow and the pathology did not bear resemblance to bovine neonatal pancytopenia.

Further investigation revealed that the gilt had returned to service five to seven weeks after her initial service and was believed to have been pregnant, this duration of pregnancy would be sufficient for thrombocytes to have developed in the foetus and, as the same boar was used to serve the gilt, thrombocytopenia purpura was therefore possible. Gammaglobulin concentrations indicated that both piglets had received good quantities of colostral antibody, which may help explain the early onset of disease.

Disease tentatively attributed to in utero Mycoplasma suis infection in neonatal pigs

Mycoplasma suis was detected in blood from neonatal pigs by microscopy and DGGE/PCR, and was confirmed by sequencing of the PCR product during an investigation into stillbirths and recumbent piglets on an indoor weaner-producer unit. Approximately 12 per cent of litters from any parity of sow were affected each week and a concurrent increase in diarrhoea in two- to three-day-old pigs was reported.

There had been periodic surges of this presentation on the unit and the incidence had increased in the two weeks prior to submission. No other significant health problems were reported on the unit and no increase in sow mortality. Once pigs reach around two weeks old, they grow well and wean at a good weight.

No diagnosis was established for weakness in live piglets and stillbirths submitted, nor for the diarrhoea in two older pigs from the unit which had moderate to good colostral antibody.

The two live weak piglets and one of the diarrhoeic piglets had a regenerative anaemia and M. suis was detected in all three by PCR and in two by EDTA. Histopathology on bone marrow may suggest an erythroid regenerative response, which supports the anaemia being due to M. suis and does not suggest bone marrow suppression or iron deficiency anaemia. However, interpreting histopathological findings in neonatal bone marrow is problematic without bone marrow from age-matched haematologically normal piglets.

Clinical disease due to M. suis reportedly is often associated with outbreaks of other infectious diseases in the herd. There was no evidence that PRRS was underlying disease but active swine influenza infection is known to be present on the unit and vaccination is being considered.

Given the findings, improvements were made in hygiene, in particular, more frequent changes of needles during sow vaccinations. Clinical disease subsided; however, further investigation is planned if there is an upsurge of similar disease on this unit to include blood sampling sows of affected and unaffected litters and, if possible, examination of age-matched healthy non-anaemic pigs. This involved a single breeding unit.

In utero transmission of M. suis is reported in the literature (Henderson et al., 1997) and tetracycline treatment can be used for treatment but does not eliminate the organism.

Eosinophilic enteritis of unknown aetiology

Two cases of eosiniphilic enteritis were diagnosed this quarter in different regions of England. Both were in growing pigs, one in nine-week-old pigs, the other was seen in 16-week-old finishers. Porcine intestinal adenomatosis due to Lawsonia intracellularis infection was suspected due to visible thickening of the terminal ileum, but was ruled out by histopathology.

Histologically, large numbers of eosinophils were seen within the lamina propria of the affected sections of intestine. This change is unfortunately non-specific and likely to represent a historical event, therefore no definitive diagnosis could be made with regard to the intestinal pathology in either case.

Enteric syndrome submissions will be kept under review and the histopathological sections are being circulated amongst histopathologists in AHVLA and SAC for second opinion and awareness.

Changes in Disease Patterns and Risk Factors

Respiratory disease diagnoses

Disease trend analysis shows a rise in swine influenza diagnoses with seven per cent of submissions diagnosed in the first quarter of 2012 compared to 3.7 per cent in the same period in 2011, and 4.5 per cent in the previous quarter. Syndromic analysis for respiratory disease indicates a significant increase in swine influenza diagnoses in Q1 2012 compared to the same period in 2007-2011, with most of the 15 diagnoses made in Eastern England.

Strains identified in Q1 2012 were four pandemic H1N1 2009; four H1N2 and seven influenza A gene PCR positive but not typable as no virus was isolated. Avian-like H1N1 has not been detected since an outbreak in the Thirsk region in November 2011. Two diagnoses were made from nasal swabs submitted for testing free of charge under Defra’s swine influenza surveillance project, the others were made in pigs submitted for diagnostic investigations and found to have a variety of respiratory and other infections concurrent with swine influenza.

The GB PRRS Q1 2012 diagnoses as a percentage of diagnostic submissions tested is 10.8 per cent (17 cases) and is the highest of any quarter since records began in 2002, although this is not a significant increase and, in part, reflects the outbreaks in East Anglia.

Interestingly, BPHS data has shown a rising trend in enzootic pneumonia-like lesions in pigs at slaughter (George Gunn, SAC, presentation at Pig Veterinary Society, May 2012). Investigation into whether exposure to swine influenza and/or PRRSv is a risk factor, which may explain this trend, would require further investigation including serology from batches of inspected pigs and this should be considered as a component of future surveillance.

Outbreaks of swine influenza are associated with autumn and winter months attributed to the climatic conditions favouring survival of the virus and promoting transmission. PRRSv survival is favoured in similar conditions and survival in vehicles and pig accommodation is also more likely as effective cleaning and disinfection and drying of surfaces is harder to achieve in wet cool conditions.

Intestinal torsions in replacement gilts on outdoor units

There was a significant increase in diagnoses of intestinal torsion accounting for 7/54 (13 per cent) of enteric syndrome submissions in Q1, 2012 compared to five per cent for the same period in prior years (2007-2011). All were AHVLA diagnoses and three were made in East Anglia replacement gilts after their arrival on outdoor units. The other cases showed no pattern.

Clinical signs in replacement gilts varied from found dead to lethargy, reduced appetite and apparent respiratory signs. Significant quantities of stones, grit or sandy material were found in the large intestines and the unbalanced weight due to ingestion of this may have predisposed to torsion.

It was recommended in each case that further gilts dying be submitted to determine whether the problems were sporadic or part of a group problem. Amongst measures recommended by attending veterinarians to reduce the risk of torsion are provision of plentiful straw to provide gut-fill and distract the gilts in the paddocks and feeding more regularly.

Ampicillin-resistant Actinobacillus pleuropneumoniae

Two APP isolates from diseased finisher pigs with typical APP lung lesions submitted to Thirsk and Bury St Edmunds laboratories showed in vitro resistance to ampicillin. In both cases, amoxicillin treatment used on the unit to control disease had, more recently, not resulted in the expected clinical response. On one unit, autogenous vaccine was being used to try and control disease due to APP (serotype 8) with limited success.

Ampicillin (beta-lactam) resistance in APP has been detected by AHVLA in the past but is comparatively rare in England. It is of concern as penicillin/penicillin derivatives are drugs of choice for the control of APP outbreaks. Improving pig flow and ventilation and avoiding other predisposing factors such as viral disease and stresses are important in controlling disease due to APP and reducing reliance on antimicrobial treatment. Routine surveillance for antimicrobial resistance in APP is in place and would detect changing trends in isolates from diagnostic submissions.

Increasing beta-lactam resistance in APP is reported in other countries and, in Italy, ampicillin resistance increased from 11 per cent of isolates in 1994 to 80 per cent in 2009 (Vanni et al,, 2012). This resistance can be plasmid-encoded and transferable and the LOLA project (Imperial College and University of Cambridge) is examining AHVLA APP isolates for plasmid content.

Horizon Scanning

Peri-weaning failure to thrive syndrome (PFTS)

This syndrome, previously only reported from North America, was suspected on three farms in Spain as described in a Veterinary Record letter (Segales et al., 2012). This is the first report of this condition from Europe. The syndrome has been highlighted to pig practitioners as a cause of periweaning ill-thrift of unknown aetiology. An information sheet is available on the VLA web site. AHVLA and SAC have no evidence of PFTS cases in GB to date. Information has been circulated to VIOs to raise awareness.

European Commission action plan on the rising threats from antimicrobial resistance

In November 2011, the European Commission released a communication detailing an action plan to deal with the perceived rising threats to human and animal health from antimicrobial resistance (EC 2011). This comprised 12 suggested actions, of which five relate to veterinary medicine.

It is estimated that pigs account for the highest antimicrobial usage of all livestock species, as measured by amount of active ingredient sold per tonne of liveweight slaughtered, so these proposals may have significant consequences for the industry.

A subgroup of the Defra Antimicrobial Resistance Coordination Group (DARC) met with representatives from Pig Veterinary Society and Pig Expert Group, AHVLA, to obtain information on the use of, and issues surrounding, antimicrobials in pig veterinary medicine.

Accurate diagnosis and disease surveillance, in which AHVLA has a role, underpin responsible use of antimicrobials. One action suggests strengthening surveillance systems on antimicrobial resistance and consumption in veterinary medicine. Presentations at the May 2012 Pig Veterinary Society described national monitoring of on-farm antimicrobial use in the Netherlands and Denmark. Similar surveillance would also provide an indirect measure of health and welfare and should be considered as pig health surveillance strategies are developed by AHVLA and industry.

References

Bader et al. (2010) Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans. Journal of Neuroinflammation 7:7.
Bidewell C.A., Williamson S.M., Rogers J.P., Hunt B.W., Davis N.J., Ellis R., AbuOun M. and Woodward M.J. (2012) Characterisation of Klebsiella species isolates from outbreaks of septicaemia in piglets: an emerging pathogen? Proceedings of 4th European Symposium of Porcine Health Management, Bruges April 2012 P179, p.200.
European Commission (2011) Communication from the Commission to the European Parliament and the Council ‘Action plan against the rising threats from Antimicrobial Resistance’ COM (2011) 748.
Henderson J.P., J. O'Hagan, S.M. Hawe, M.C.H. Pratt (1997) Anaemia and low viability in piglets infected with Eperythrozoon suis. Veterinary Record 140:6 144-146.
O'Neill C,, S.C.P. Jones, J.T. Bossé, C.M. Watson, S.M. Williamson, A.N. Rycroft, J.S. Kroll, H.M. Hartley, P.R. Langford (2010) Prevalence of Actinobacillus pleuropneumoniae serovars in England and Wales. Veterinary Record 167:661-662. doi:10.1136/vr.c5106.
McDowell, S.W. and Ball, H.J. (1994) Serotypes of Actinobacillus pleuropneumoniae isolated in the British Isles. Veterinary Record 134, 522-523.
Reimer D., J. Frey, R. Jansen, H.P. Veit and T.J. Inzana (1995) Molecular investigation of the role of Apxl and Apxll in the virulence of Actinobacillus pleuropneumoniae serotype 5. Microbial Pathogenesis, 18:197-209.
Segalés J., J. Martínez, E. Vidal, et al. (2012) Periweaning failure to thrive in pigs in Spain. Veterinary Record, 170:499.
Vanni M., M. Merenda, G. Barigazzi, C. Garbarino, A. Luppi, R. Tognetti and L. Intorre (2012) Antimicrobial resistance of Actinobacillus pleuropneumoniae isolated from swine. Veterinary Microbiology 156:172–177.
Williamson, S, Scholes, S., Jeffrey, M. and Dastjerdi, A. (2012) Unusual peripheral hypomyelinating neuritis in growing pigs causing incoordination – a novel disease? Proceedings of 4th European Symposium of Porcine Health Management, Bruges, April 2012 O26 p.110.

Further Reading

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June 2012
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