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Emerging Threats Quarterly Report – Pig Diseases - October-December 2012

08 May 2013

Among the highlights of the latest report from the AHVLA are the emergence of penicillin resistance in Streptococcus suis and the recent evolution of H1N2 swine influenza virus. There were also seasonal outbreaks of leptospirosis and a growing proportion of salmonellosis due to monophasic Salmonella Typhimurium-like isolates.

Highlights

These reports aim to identify emerging animal disease related threats. Their production is underpinned by a large amount of surveillance data and information compiled as part of the Defra Food and Farming Group animal disease surveillance programme. Some of these data can be viewed on the AHVLA web site.

  • Penicillin resistance in Streptococcus suis from pigs in England
  • Recent evolution of H1N2 swine influenza virus in GB pigs
  • Seasonal occurrence of leptospirosis outbreaks
  • Increased proportion of salmonellosis due to monophasic Salmonella Typhimurium-like isolates

New & Emerging Diseases

Penicillin resistance in Streptococcus Suis isolated from pigs in England

Two clinical isolates of Streptococcus suis from pigs have been found to have raised penicillin Minimum Inhibitory Concentration (MIC) values. This is a newly-confirmed finding and represents a new and emerging antimicrobial resistance threat.

AHVLA provided 100 clinical and 100 non-clinical recent Streptococcus suis isolates to the University of Cambridge and Imperial College who are collaborating on a large BBSRC-funded (Lola) project 'A multivalent vaccine and single platform diagnostic for bacterial respiratory diseases of pigs.' As part of this, Cambridge tested all the isolates for penicillin MICs and found 10 non-clinical and two clinical isolates to have raised penicillin MIC values. The two clinical isolates showed raised penicillin MIC values above the clinical breakpoint for central nervous system (CNS) infection, these isolates date from 2009 and 2010.

Previous surveillance at AHVLA revealed a S. suis isolate apparently resistant to penicillin in screening disc diffusion tests in 2006, although unfortunately the isolate was not retained to allow confirmatory testing. Penicillins are front-line treatment for disease due to S.suis in pigs and humans. Resistance or reduced susceptibility need careful definition, because isolates could potentially be classified in one or other category for clinical purposes, dependent on whether they caused CNS infection or visceral infection.

S. suis was the most commonly diagnosed systemic disease in VIDA 2011 in pigs and approximately 100 clinical isolates of S. suis are made annually by AHVLA from pigs. Up to seven human cases of S. suis have been reported per year in UK between 2002-2011 (HPA, 2011). The penicillin resistance was also found in non-clinical S. suis isolates which indicates that there is potential for more penicillin resistance than is currently detected from diagnostic submissions amongst the S. suis colonising pigs in England and Wales. Penicillin resistance in human and pig S. suis isolates is not a new global finding and both have been recorded previously in other countries (Palmieri and others 2011).

The AHVLA scanning surveillance pig project is funding penicillin MIC tests on all the S. suis isolates from diagnostic cases in 2011 and 2012 (approximately 200) to determine the prevalence of penicillin resistance in more recent isolates in the light of these findings. In January 2011, AHVLA changed from a routine 10 to a 1ug penicillin disc for the disc diffusion antimicrobial sensitivity test used routinely on diagnostic isolates. This would have detected the two clinical isolates with raised MICs from 2009 and 2010 so it is unlikely that penicillin resistance has increased recently in prevalence in the isolates made in AHVLA. The MIC testing results for 2011-12 isolates will indicate the range of MIC values in recent isolates and whether this shows any change, as well as whether the isolates would be classified as resistant or susceptible when applying the CNS breakpoints or the breakpoints applied for visceral infections in man.

The Veterinary Medicines Directorate are aware of these investigations. These findings were included in a presentation to Pig Veterinary Society in November 2012 by Dan Tucker, University of Cambridge and a publication is in preparation.

Ongoing Emerging Disease Investigations

Klebsiella pneumoniae septicaemia in pre-weaned pigs

The most recent outbreak of Klebsiella pneumoniae subspecies pneumoniae (Kpp) septicaemia was diagnosed in August 2012, none was diagnosed during October to December 2012. This confirms the seasonal pattern seen in 2011 with restriction of disease outbreaks to the summer months.

A PCR has been developed allowing rapid detection of the presence of a small plasmid which has, to date, only been found in outbreak-associated Kpp and not in non-outbreak-associated and historic isolates. Kpp isolates have been obtained from nasal cavities and tonsils of pigs submitted to AHVLA for diagnosis of disease unrelated to Kpp septicaemia. So far, none of these has contained the small plasmid. Sequencing of the small plasmid and, if a funding application is successful, of the whole genome of outbreak Kpp is planned. This may provide information to help explain the emergence of Kpp septicaemia outbreaks in 2011. An oral presentation on Kpp septicaemia has been accepted for the joint PVS-ESPHM meeting in May 2013.

The re-emergence of Kpp septicaemia in 2012 was highlighted in monthly reports and an information sheet

Recent evolution of H1N2 swine influenza virus in GB pigs

The majority of H1N2 viruses isolated from pigs submitted to AHVLA in 2012, and a few from 2011, have been sequenced and all are reassortant viruses with a core from pandemic H1N1 2009 virus and outer component from H1N2.

This reassortant H1N2 swine influenza virus has emerged as one of the two dominant endemic strains currently circulating in GB pigs, with pandemic H1N1 2009 virus being the other strain identified. The first detection of this type of reassortant in GB pigs was in April 2010 (Howard and others, 2011). The fact that this reassortant variant of H1N2 has become the dominant H1N2 detected through AHVLA swine influenza surveillance suggests that there has been natural co-selection due to better ‘fitness’ of this genotype. This could be due to more favourable transmission in pigs, for example due to a lower infective dose, or greater viral shedding.

Virus sequencing has also revealed that the H1N2 component of the virus shows significant genetic and antigenic drift away from the reference H1N2 which was isolated in 1994 and is used in the serological panel for the haemagglutination inhibition assay. This has implications for serology and a more recent H1N2 isolate is being evaluated alongside the reference isolate as a potential substitute in the serological panel. It is likely that the anomalous swine influenza serology results described in the July to September Emerging Threats report in part reflect the effect of this antigenic drift in recent H1N2 viruses. Several initiatives are ongoing to further this investigation including funding HAIT serology on swine influenza ELISA-positive sera and genetic analysis of further H1N2 viruses isolated.

There are no additional implications for animal or public health but these findings emphasise the importance of swine influenza surveillance in keeping our knowledge on strains actively circulating and diagnostics up to date. The Health Protection Agency and Human and Animal Interface Risk Surveillance group have been made aware of these findings. A presentation is planned for the joint Pig Veterinary Society (PVS) and European Symposium of Porcine Health Management (ESPHM) meeting in May 2013.

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.

Severe reproductive disease on a newly established outdoor breeding unit

Severe reproductive disease was investigated on an outdoor gilt start-up unit, to be run on a three-weekly batch system. Gilts were vaccinated for parvovirus, erysipelas, porcine reproductive and respiratory syndrome (PRRS) and Mycoplasma hyopneumoniae, but not porcine circovirus 2 (PCV2).

Service, mostly by artificial insemination, appeared to proceed well with gilts clearly manifesting oestrus. No returns were seen at three weeks post-service but conception rates at scanning at five weeks of gestation were poor, ranging from 45 to 65 per cent. Intermittent boar presence at three to five weeks did not improve manifestation of returns to service in non-pregnant gilts. At farrowing, high rates of stillborn and non-viable piglets were seen (20 per cent average but up to 100 per cent in some litters), with low numbers of pigs weaned per sow. Some gilt deaths occurred through complications with endometritis.

Brucella suis infection was ruled out through culture and maternal serology, and foetal testing for pathogenic Leptospira, PRRSv, parvovirus, and bacterial causes of abortion, all proved negative. There was no evidence of myocarditis in stillborn and nonviable piglets to suggest PCV2 or encephalomyocarditis virus (EMCV) involvement. Histological examination of foetuses and uteri from non-pregnant gilts was largely unremarkable. Maternal antibodies were not detected to any of 19 Leptospira serovars or to swine influenza.

Medication with chlortetracycline did not improve reproductive performance at any stage, although some improvement in farrowing performance in one batch was seen in a recent batch when in-feed penicillin was used to combat pyelonephritis, which was found in one gilt which had retained its litter, in combination with endometritis. When poor five-week conception rates were seen in previously affected sows served for their second pregnancies, the possibility of a non-infectious aetiology was suspected.

No other units have been reported to have similar disease which is unusually persistent and severe and is threatening the viability of this unit. Investigations continue and include virus microarray and assessment of potential environmental factors.

Changes in Disease Patterns and Risk Factors

Seasonal occurrence of leptospirosis outbreaks

Two leptospirosis outbreaks were diagnosed in October 2012, serology suggesting involvement of Leptospira Icterohaemorhagiae in both. One involved reproductive disease with sequential foetal death and birth of mummified piglets on a small indoor breeder-rearer unit, the other involved systemic illness and jaundice in sucking pigs born to both gilts and sows on a small outdoor breeding and indoor rearing farrow to finish farm. In both cases, pathogenic Leptospira DNA was detected in the kidneys by PCR.

Subsequent leptospire serology on sow sera from the first case implicated L. Icterohaemorrhagiae, a rodent-associated leptospire which causes Weil’s disease in humans. In the second case, antibody titres were also detected to Icterohaemorrhagiae, together with lower titres to some other serovars.

Antimicrobial treatment was effective in controlling clinical disease in the pigs.

Effective rodent control was also recommended and is also important in reducing the zoonotic risk as urine from infected rodents represents a transmission risk to humans. Further advice was given to reduce the risk of human infection on the farms. The most recent diagnoses of leptospirosis in pigs by AHVLA were also in the autumn to winter months in 2011.

This seasonal occurrence of disease is likely to reflect increased contact of pigs with wild rodents as the rodents’ food supply becomes more scarce. Significant populations of rodents were present on both farms prior to being controlled.

A presentation on diagnosis of leptospirosis in pigs is planned for the joint PVS-ESPHM meeting in May 2013 to raise awareness.

Increased proportion of salmonellosis due to monophasic Salmonella Typhimurium-like isolates

Salmonella Typhimurium and the two variants of monophasic Salmonella Typhimurium-like (mST) strains remain the three most commonly isolated Salmonella serovars in GB pigs.

Syndromic analysis has shown that, although there has been no significant change in the number of diagnoses of salmonellosis in pigs overall during 2012, there was a significant rise in the proportion of systemic and miscellaneous disease incidents due to mST isolates (Salmonella 4,5,12:i:- and 4,12:i) and a significant reduction in the proportion of systemic and miscellaneous disease incidents due to S. Typhimurium.

A significant proportion of mST isolates from pigs exhibit resistance to six or more antimicrobials including resistance to apramycin, neomycin and gentamicin, of which only apramycin is licensed for use in UK pigs. These resistance patterns are not normally seen in mST from other livestock species. Reports of Salmonella 4,12:i:- in particular appear to have been increasing in pigs, with 13 during 2010, 20 during 2011 and 26 during 2012. Loss of the O5 antigen in this strain is thought to be a response of the organism to enhance evasion of the host organism immune response.

This is raised here for awareness. Approaches to the control of mST strains are the same as for other Salmonella serovars in pigs. Information on salmonellosis in pigs has been provided to BPEX for dissemination to producers.

Swine influenza strains actively circulating in GB pigs

During 2012, 37 of 184 diagnostic submissions which were tested by PCR were positive for swine influenza virus. Allowing for repeat submissions from a few farms, swine influenza was diagnosed on 33 pig units in GB during 2012.

Strain identification was possible in 21 of the PCR-positive submissions and revealed 12 positive for H1N2, eight positive for pandemic H1N1 2009 and just one for avian-like H1N1 virus. The avian-like H1N1 strain was predominant before emergence of pandemic H1N1 2009 but now appears to have been largely displaced by pandemic H1N1 2009 virus. No H3N2 viruses have been detected in GB pigs since 1997. It was not possible to isolate virus from 16 submissions, this reflects the fact that the PCR is more sensitive than virus isolation and detects swine influenza virus in samples in which it is no longer viable or is present at very low levels.

Strain identification assists in making decisions regarding use of vaccination for control of swine influenza in pigs and in investigating and understanding the epidemiology of outbreaks and of swine influenza in GB.

Horizon-Scanning

Periweaning Failure to Thrive syndrome

Post-weaning failure to thrive syndrome (PFTS) is a wasting disease of unknown aetiology reported from Northern America and distinct from porcine circovirus-2 associated disease. An invited speaker at the November 2012 Pig Veterinary Society meeting described the emergence of PFTS in Canada.

The syndrome affects previously healthy pigs 60 to 72 hours post-weaning and results in death within two to three weeks. No infectious or other aetiology has been identified to date. Pigs are weaned earlier in Canada at 21 days. Pigs show anorexia and repetitive chomping or licking is a consistent finding. The affected pigs are mentally depressed and often show prolonged standing, abnormal gait, including knuckling, strabismus and nystagmus. Thymic atrophy and bronchopneumonia are more prevalent in affected pigs than unaffected pigs, however both changes could be secondary to debility. A lymphocytic fundic gastritis and perigangliitis, atrophic enteritis of the distal small intestine and a sparse meningoencephalitis are the most common histological findings but not all are seen in all cases and these may also reflect the effects of anorexia rather than being primary lesions. Laboratory testing has shown no association so far with infection with a range of bacterial and viral pathogens.

The condition is now reported in the USA, Canada and Spain. There is a nursery prevalence of around 4 per cent in the USA and Canada with a one per cent to 10 per cent prevalence in pigs on affected farms. An information sheet is available online.

The DNR data for submissions of post-weaned pigs with wasting as a presenting sign were reviewed to see if there was any evidence for emergence of PFTS. The overall DNR rate to Q4 for submissions with wasting as the presenting sign for GB was 7.4 per cent (6/81) compared to 13.4 per cent for the same period in prior years. Fifty of the submissions were from post-weaned pigs of which three submissions were not diagnosed (six per cent) compared to 12.3 per cent in prior years. These three undiagnosed submissions were not suspicious of PFTS.

AHVLA and SAC have no evidence of PFTS cases in GB pigs to date and DNR analysis of undiagnosed submissions with wasting as a presenting sign in postweaned pigs in 2012 did not reveal evidence of a new and emerging syndrome. Information has been circulated to VIOs and practitioners to raise awareness.

High-pathogenicity genotype 2 PRRSv in experimental infections in Pigs

Further useful information on the pathogenesis of genotype 2 highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) was published from the United States (Guo and others 2013). The HP-PRRSV replicated in pigs with at least 100-fold increased kinetics over a reference U.S. strain. The HP-PRRSV caused significant weight loss, exacerbated disease due to bacterial sepsis and caused more severe gross and histopathological lesions, including thymic atrophy. The paper also described rapid transmission of HP-PRRSV to in contact pigs.

Presentations at the November 2012 Pig veterinary Society on epizootic diseases threatening UK pigs raised awareness of HP-PRRSv (Andrew Gresham ‘World-wide distribution of epizootic diseases of pigs of major risk to the UK’ and Susanna Williamson ‘Epizootic diseases threatening UK pigs - What do they look like?’).

No genotype 2 PRRSv have been detected in UK pigs. Incursion of HP-PRRSV would be likely to cause high mortality and may prompt investigation as suspect notifiable disease. The diagnostic PCR for PRRSv at AHVLA detects and differentiates genotype 2 PRRSv.

References

Baoqing Guo, Kelly M. Lager, Jamie N. Henningson, Laura C. Miller, Sarah N. Schlink, Matthew A. Kappes, Marcus E. Kehrli,Jr, Susan L. Brockmeier, Tracy L. Nicholson, Han-Chun Yang, Kay S. Faaberg (2013). Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. Virology 435 372–384

Howard WA, Essen SC, Strugnell BW, Russell C, Barrass L, Reid SM, et al. Reassortant pandemic (H1N1) 2009 virus in pigs, United Kingdom. Emerging Infectious Diseases. 2011 17: no.6 http://dx.doi.org/10.3201/eid1706.101886

HPA, 2011. Appendix 4 page 82 http://www.defra.gov.uk/publications/files/pb13851-zoonoses-2011.pdf

Palmieri, C., Varaldo, P.E. and Facinelli, B. 2011. Streptococcus suis, an Emerging Drug-Resistant Animal and Human Pathogen. Frontiers in Microbiology 2:235

Further Reading

Find out more information on the diseases mentioned in this article by clicking here.

May 2013

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