PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL CORRELATIONS RELATING TO THE THERAPY OF COLONIC INFECTIONS IN THE PIG AND BREAKPOINT DETERMINATIONS
D.G.S. Burch

Abstract
The colonic contents concentrations (CCCs) of valnemulin, tiamulin, lincomycin, tylosin and acetylisovaleryl tylosin were related to their pharmacodynamic effect on Brachyspira hyodysenteriae and B. pilosicoli from a variety of published minimum inhibitory concentration (MIC) surveys and, where possible, these findings were correlated with clinical data to determine suitable clinical breakpoints. There were limited data available for CCC determinations and some results had to be estimated. Determinations of MICs also varied, depending on the method. The micro-broth method gave figures, on average, one dilution lower than agar plate tests; but doubling dilutions of antibiotic used in the tests also limit precision. Tests on large numbers of isolates of B. hyodysenteriae with the micro-broth test demonstrated MIC patterns where possible mutations occurred and reduced susceptibility or tolerance occurred. In the case of tylosin, there was a large jump in MICs to complete resistance development. The other antibiotics seemed to develop resistance in a more gradual stepwise way and these dips were thought to demonstrate where the effective bio-concentrations of the antibiotics reached in the colon to stimulate the mutations. When these results were compared with clinical challenge study results, with isolates of known MICs, or field experience reports, in general, a confirmatory picture evolved.

Breakpoints for the antibiotics at their normal upper usage levels were derived for brachyspiras. Valnemulin at 75ppm had an estimated breakpoint at >0.125 and >0.25?g/ml for micro-broth test and agar plate test respectively and similarly for 100ppm tiamulin >0.5 and >1.0?/ml, lincomycin 110ppm >50 and >100?/ml, tylosin 100ppm >16 and >32?/ml and 100ppm acetylisovaleryltylosin >16 and >32?/ml.

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PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL CORRELATIONS RELATING TO THE THERAPY OF LAWSONIA INTRACELLULARIS INFECTIONS, THE CAUSE OF PORCINE PROLIFERATIVE ENTEROPATHY ('ILEITIS') IN THE PIG
D.G.S. Burch

Abstract
Porcine proliferative enteropathy, commonly referred to as 'ileitis,' caused by Lawsonia intracellularis, is a common and widespread intestinal infection of pigs. In its acute form, it can cause mortality in finishing pigs and young breeding stock and in its chronic form, depression and unevenness of growth in growers and finishers.
In the United Kingdom, 67% of antimicrobials are delivered via the feed and at least a similar proportion is administered to pigs. Several important families of antibiotics are used to treat and prevent ileitis, including the tetracyclines, macrolides, lincosamides and pleuromutilins. Surprisingly, there is little published information on the pharmacokinetics of these products in the intestines of pigs and especially in the ileum.
The purpose of this paper was to establish a baseline model for antibiotic concentrations that are likely to be achieved in the ileal contents. These could then be related to the pharmacodynamic activity of the antibiotics, in particular to the intracellular minimum inhibitory concentrations (MICs) against L. intracellularis, which were established in the 1990s and correlate these with clinical studies. Pharmacokinetic/pharmacodynamic relationship analysis is a powerful tool, not only to predict dose rates and intervals, but also, as in this case, how antimicrobials are likely to work against target pathogenic bacteria and treat infectious disease.
In the paper, the ileal contents concentration (ICCs) for a number of antibiotics are estimated, but deficiencies in the determination of the intracellular MICs are highlighted. The ICCs do appear to correlate with the inhibitory activity of the antibiotics against L. intracellularis in the intracellular cell culture system, but due to the deficiencies in the data, more precise correlations cannot be mad

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PHARMACOKINETICS AND TOXICITY ASSESSMENT OF HIGH DOSES OF AMIKACIN IN PIGS
H. Sumano, L. Gutierrez, L. Ocampo and C. Velazquez

Abstract
The pharmacokinetic variables for amikacin in pigs were determined after administration of amikacine sulphate either intravenously (IV) or intramuscularly (IM) at a dose of 25 mg/kg/day for three days. Amikacin concentrations at time zero and maximum serum concentrations were 166.3 ? 1.3 ?/mL and 135.4 ? 0.4 ?/mL, respectively. The elimination half-life remained unchanged during the three days of administration (T_?? = 1.58 ? 0.05 h for the IV route and T_?? = 1.89 ? 0.05 h for the IM route). Apparent volumes of distribution suggest limited distribution out of the central compartment (Vd_AUC = 0.460 L/kg; Vd_c = 3.0 L; and Vd_ss = 0.120 L/kg), but a high plasma concentration gradient to tissue may facilitate greater tissue concentrations. Bioavailability after IM administration was 115%, a convenient feature for the treatment of pigs. Serum profiles of urea, creatinine, albumin, electrolytes and pH, as well as macroscopic and histopathologic analysis, after 3-day treatment with amikacin at a dose of 25 mg/kg/day IM, revealed no detectable changes. Considering that amikacin has an important antibacterial effect vs Gram-negative bacteria and that pneumonic diseases in pigs tend to be caused by these type of bacteria, these results suggest a single-daily large dose of amikacin for future clinical trials in outbreaks of bacterial diseases caused by Gram-negative micro-organisms in pigs.

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THE EFFECT OF WEIGHT LOSS DURING LACTATION ON WEANING TO FIRST SERVICE INTERVAL, FARROWING RATE TO FIRST SERVICE AND SUBSEQUENT LITTER SIZE IN SOWS
C.M.P. Weldon and G. Bilkei

Abstract
The objective of the study was to determine the relationship of weight loss during lactation on subsequent reproductive performance of sows. The reproductive data on seven indoor European pig breeding units of similar climate, similar genetics, health status and under identical reproductive management and feeding were evaluated. Sows were categorised according to lactation weight losses of <5%, 5-10%, 11-15%, 16-20% and >20%. Weaning to service intervals, farrowing rates and total-born litter sizes were compared. Lactation weight losses exerted a quadratic effect (P>0.01) on weaning to service intervals. When analysed across parity categories, with parity category included as a fixed effect, the weaning to service intervals appeared to be minimised at lactation weight losses of >5%. Weaning to service intervals increased (P>0.05) when lactation weight losses increased above >11% for parity 1 sows, but not until lactation weight losses exceeded 20% for parity 2 and above. There was a parity effect observed (lactation weight losses of >10%, P>0.05; and lactation weight losses of >10 %, P=0.01). Lactation weight losses >10% had P>0.05 that of >20%, a P> 0.01 negative effect on subsequent farrowing rates to first service. Lactation weight losses >10% resulted in a significant reduction in litter size.
Implication: The sows' reproductive performance can be improved by reducing their lactation weight losses.

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CLINICAL REPORT - CLOSTRIDIUM DIFFICILE AND POST-WEANING PIGLET LOSSES IN OUTDOOR PRODUCTION
N. Blasko and G. Bilkei

Abstract
Clostridium difficile has not been reported as a cause of losses in outdoor raised weaned pigs. In an outdoor production unit, 4-11 days after weaning, the piglets suffered a sudden increase of diarrhoea, respiratory distress and mortality. Enrofloxacin, ceftiofur and gentamycin (sensitivity tested and effective against the E. coli, present on the unit) showed no therapeutic effects. Necropsy revealed meso-colonic oedema, hydrothorax and ascites. Microscopic examination showed scattered foci of suppuration in the lamina propria of the colon and accumulation of neutrophils and fibrin on the colonic mucosa. Anaerobic cultures of the colon yielded heavy growth of Clostridium difficile. Hygienic and weather/stress improvements decreased post-weaning morbidity from 51% (January to March 2004) to 11% (March to June) and mortality from 12% to 2% during the same period of time.

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SHORT COMMUNICATION - PERI-PARTURIENT DISEASE ASSOCIATED WITH PSEUDOMONAS AERUGINOSA AND ESCHERICHIA COLI IN SOWS FARROWING OUTDOORS
C. Dial and G. Bilkei

Abstract
A total of 145 late-pregnant sows reared outdoors were randomly divided into three groups. One group continued to be reared and farrowed outdoors and was medicated with in-feed enrofloxacin for three weeks prior to farrowing. Two other groups were moved to individual farrowing crates indoors, and one group was medicated similarly to the outdoor group. The other group was given no medication. The incidence of peri-parturient diseases, sow mortality, early post-natal piglet mortality and the number of sows culled with vulval discharge post-weaning and/or chronic mastitis was evaluated. The incidence of peri-parturient disease was significantly higher (p>0.05) in the outdoor medicated sows compared with indoor sows. Similarly, piglet mortality and the number of sows culled was greater (p>0.05) in outdoor medicated sows compared with the indoor sows, regardless of treatment.

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POST-WEANING MULTISYSTEMIC WASTING SYNDROME (PMWS) IN DENMARK - THE SITUATION TO DATE
P. Baekbo

Abstract
Post-wasting Multisystemic Wasting Syndrome (PMWS) was first diagnosed in Denmark in 2000. In April 2005, Denmark had 541 confirmed cases of PMWS. This corresponds to a prevalence of approximately 10 per cent of all sow herds. However, the estimated real prevalence is 17 per cent. The PMWS-affected herds are widespread, with the highest prevalence in the most pig dense areas. Recorded PMWS cases are based on clinical signs in the herd and on laboratory tests (histopathology). Post-wasting Multisystemic Wasting Syndrome is mainly seen among weaners and gives high mortality and reduced growth rate. The productivity of finishers in affected herds also seems to be reduced. The options for controlling PMWS are based on changes in management aimed at reducing stress on pigs, reducing potential transmission of pathogens between pigs and of ensuring a high level of hygiene. Research on the aetiology and control of PMWS has had high priority during the last five years.

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POST-WEANING MULTISYSTEMIC WASTING SYNDROME (PMWS) RESEARCH IN DENMARK
P. Baekbo

Abstract
In Denmark, much research on PMWS takes place in co-operation between the pig industry and public research institutes. Completed studies indicate that PMWS can be transmitted from pig to pig and that low levels of Vitamin E at weaning increase the risk of dying during the post-weaning period. Total depopulation/repopulation and autogeneous serum are options for controlling PMWS, whereas feed supplement with so-called immune stimulation substances seem to be of no effect. Ongoing studies focus on detecting possible risk factors for the development of PMWS and possible differences in virulence of PCV2 isolates. The studies also search for possible unknown infectious trigger agents for PCV2. Future research to be started in Denmark is mainly concentrated on a big EU project. Focus will be on epidemiology of PMWS, on genetic susceptibility and on control measures for PMWS. Furthermore, a small field study will be performed on the efficacy of Acetylsalicylic acid for reduction of post-weaning mortality in PMWS-affected herds.

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POST-WEANING MULTISYSTEMIC WASTING SYNDROME (PMWS) IN PUREBRED WILD BOAR (SUS SCROFA) ON A FARM IN EAST ANGLIA
N.G.A. Woodger

Abstract
Post-weaning multisystemic wasting syndrome (PMWS) was diagnosed in farmed Wild Boar in East Anglia. This involved an overstocked unit, resulting from movement restrictions following the 2001 Foot-and-Mouth disease epidemic.
A severe wasting disease with scouring, coughing and anorexia was first noticed in growing pigs from 3-4 months of age, in April 2003. There was a marked increase in mortality, which approached 50 per cent of all growing pigs. This paper describes the background, laboratory findings and conclusions leading to the diagnosis of PMWS and other diseases after post-mortems on seven affected pigs. Possible sources and the impact of management changes are discussed.
Several reports of PMWS in Eurasian Wild Boar in Canada, Spain and Germany are recorded; but this would appear to be the first report of PMWS in farmed purebred Wild Boar in the UK.

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POST-WEANING MULTISYSTEMIC WASTING SYNDROME (PMWS) IN FARMS: DEFINING DISEASE AND THE ROLE OF PORCINE CIRCOVIRUS 2 (PCV2)
M. Turner, C. Schnier, K. Woodbine, L. Green, G. Medley and J. Slevin

Abstract
The cause of PMWS is as yet undetermined. There has been great controversy over the role of PCV2 in the disease. Current case definitions for the disease vary, but all include the presence of PCV2 antigen or nucleic acid. In a cross-sectional study of 116 farms, there was little difference in the PCV2 serological profiles of PMWS positive, negative and recovered farms. However, PCV2 antigen levels were more raised in sick pigs on all farms. There were also high levels on farms where the farmers had not reported PMWS and some positive farms where no antigen was detected. Antigen levels were correlated with current mortality with PMWS on the farms. Porcine circovirus 2 was not included in the proposed case definition due to the uncertainty of its role in the disease.
There were 28 significant differences between the post-mortem examination (PME) of sick and healthy pigs, ignoring farm of origin. These differences were mainly enteric and respiratory. There were three significant differences between the histology results from sick and healthy pigs. These differences were significant in the ileoceacocolic lymph node. A case definition has been proposed using these significantly different signs.

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THE USE OF PRACETAM (PARACETAMOL) PREMIX IN POST-WEANING MULTISYSTEMIC WASTING SYNDROME (PMWS) AND POST-WEANING DIETS
L. Glattleider and N. Capdevielle

Abstract
Controlled clinical trials were performed to evaluate the effect of PRACETAM in either PMWS or in a post-weaning diet.
The efficacy of PRACETAM was demonstrated by a controlled clinical trial under blind conditions in a pig herd chronically infected with PMWS. The therapeutic dose in the treated group was 30 milligrams of Paracetamol per kilograms body weight (1000 milligrams per kilogram of feed) for ten consecutive days and no concomitant antibiotic treatment was used. During the first period of the trial (between day 0 and day fourteen), only a small number of pigs died or lost weight. The difference between the treated and control group was not significant. During the second period of the trial, a statistically significant difference in the number of dead or wasting pigs was observed between the treated and control group and treatment with PRACETAM was concluded to have helped in reducing the mortality rate and the number of wasting piglets.
A controlled trial was carried out to evaluate the effect of PRACETAM on growth rate during the post-weaning period. Three hundred and fifty-one piglets were involved in this study, from the day of weaning (day zero) to the end of the post- weaning period (day 35), randomly divided into a control and a treated group and reared under different conditions. Under favourable conditions (5 piglets per box and completely slatted floor), a significant effect of PRACETAM was observed on growth performance with daily weight gain 55g higher than in the control group). Under unfavourable conditions (10 piglets per box, partially slatted floor and stimulation of the immune system by vaccination against Mycoplasma), an even greater effect of PRACETAM was seen throughout the growth period, despite the immune stimulation.

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EPIDEMIOLOGY OF SWINE INFLUENZA IN GREAT BRITAIN AND EMERGING GLOBAL ISSUES
I.H. Brown

Abstract
Pigs serve as a major reservoir of H1N1, H3N2 and H1N2 influenza viruses that are endemic in pig populations worldwide and are responsible for one of the most prevalent respiratory diseases in pigs. The maintenance of these viruses in pigs and the frequent exchange of viruses between pigs and other species are facilitated directly by swine husbandry practices which provide for a continual supply of susceptible pigs that have regular contact with other species, particularly humans. Surveillance studies in the UK since 1991 have revealed a changing epidemiology through emergence, variation and disappearance of virus strains. Currently, avian-like swine H1N1 and swine H1N2 viruses co-circulate; but continual exchange of genes between viruses provides a heterogenous population of virus genotypes. Increasingly, farming of mixed species, including pigs, has been shown to present an increased risk for the transmission of novel viruses for pigs. Recent reports of infection of pigs with emerging avian subtypes such as H9, H7 and H5 emphasise the importance of ongoing surveillance programmes to enable early detection of these viruses should they acquire the ability to spread readily between pigs and become significant disease-causing pathogens.

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PORCINE RESPIRATORY DISEASE COMPLEX (PRDC) IN ITALY
M. Terrini

Abstract
The author describes the main characteristic of the Italian swine industry as the production of heavy pigs. In 2004, the total number of pigs raised in Italy was 8, 972, 000, which represented 5.9% of EU production. The porcine respiratory disease complex (PRDC) has been described in Italy. Updated data, resulting from analyses carried out in the pathology Departments located in the most pig-populated areas of Northern Italy, Lombardia and Emilia-Romagna, confirm the presence of porcine reproductive respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2), swine influenza viruses (SIV), Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae (APP), Pasteurella multocida (PM), Streptococcus suis and Bordetella bronchiseptica. Specific figures about the most important aetiological agents are reported in this paper, as well as an update about M. hyopneumoniae epidemiology.

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AN UNEXPECTED SEROLOGY PROFILE AFTER SWINE INFLUENZA VIRUS (SIV) INFECTION IN A PORCINE RESPIRATORY DISEASE COMPLEX (PRDC) OUTBREAK
M. Terrini

Abstract
Swine Influenza has been recognised in Italy since 1980. It has a well known role in PRDC and its presence on farms nationwide has been confirmed over the last few years. All three subtypes H1N1, H3N2 and H1N2 are present and, in some situations, can co-exist on the same farm. The author reports a case of PRDC, with SIV, that was experienced on a 400 farrow-to-finish unit. The outbreak began with most of the growers affected and presenting the typical clinical picture of SIV. About 10 days later, the mortality rate increased. The analyses made confirmed the presence of H1N2, as well as some secondary bacterial infections. The serological profile showed an unexpected lack of seroconversion for H1N2 in the paired samples. When a homologous strain was substituted for the original routine virus used in the HI test, seroconversion was then evident. Serology is more appropriate for monitoring programmes, while virus identification is recommended for diagnosis in new outbreaks.

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FINISHING PIGS SYSTEMS RESEARCH:PRODUCTION, MICROBIAL AND MEAT QUALITY RESULTS OVER FOUR FEEDING TRIALS UNDER TWO CONTRASTING HOUSING SYSTEMS, FULLY-SLATTED VERSUS STRAW-BASED ACCOMMODATION
B.P. Gill, K.R. Matthews, L. Taylor and K. Hillman

Abstract
In this paper, results relating to pig performance, cost of production, environmental impact and meat quality from large-scale production studies under a three-year ?1.8m multidisciplinary research programme on finishing pigs, co-ordinated by the Meat and Livestock Commission, are presented. The main conclusion is that liquid feeding technology offers considerable potential for improving growth performance and feed conversion in the production of finishing pigs. These improvements translate into a net economic benefit of around 14p/kg dead weight in reduced cost of production. Liquid feeding also holds the potential for reducing salmonella carriage at slaughter, thereby improving consumer confidence in pork and pig meat products.

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FINISHING PIG SYSTEMS: HEALTH AND WELFARE IN STRAW-BEDDED OR SLATTED HOUSING
S. Edwards, K. Scott, D.J. Chennells, F. Campbell, B. Hunt, D. Armstrong, L. Taylor and B.P. Gill

Abstract
Whilst current pig welfare legislation encourages provision of straw, many factors must be taken into consideration when selecting the type of housing for finishing pigs. A comparison of straw-bedded and fully-slatted housing, designed to minimise other confounding factors associated with site, building design and management, has been carried out in four consecutive experiments over a three-year period. This has highlighted the relative advantages and disadvantages of each system for animal health and welfare.

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FEEDING THE MODERN GENOTYPE - TRACE ELEMENTS
J.A. Taylor-Pickard

Abstract
Trace mineral nutrition has until recently been a neglected area in pig nutrition. There is scant and incomplete information concerning the mineral requirements of modern genotypes with high levels of productivity. Consequently, many minerals are used at higher inclusion levels, such as zinc and copper in weaner rations to improve growth and reduce digestive disturbances post-weaning. Traditionally, inorganic minerals have been added to pig rations. Recently, there has been increased interest in the role of organic minerals which are more bioavailable and better meet the requirements of the modern genotype. In many circumstances, inclusion levels can be reduced through the use of organic minerals further reducing excretion levels. Not only does this improve efficiency, but also the health and welfare of the animal whilst better meeting environment requirements.

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MULTIFOCAL CYSTIC ENDOMETRIUM WITH HYDROMETRA (WITH FOLLICULAR CYSTIC OVARIES) IN A GLOUCESTER OLD SPOT GILT
S.H. Done and E. Cabell

Abstract
Four semi-domesticated eight month old gilts, in apparent good health, were killed and examined by the authors. Post-mortems revealed no significant lesions in three of the pigs. The remaining gilt presented a large cystic uterus upon examination. This seemingly rare finding is described in the following paper.

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BIOFILMS
A.E.J. Waddilove

Abstract
A biofilm is a collection of bacteria and/or fungi that exists in a multicellular or community form, encased in an extracellular polysaccharide matrix that they themselves synthesise. They require the presence of water, and form on a solid substrate, on soft tissue surfaces within living organisms and at liquid-air interfaces. Formation of a biofilm starts with adherence of bacteria followed by production of the polysaccharide matrix. Other bacteria, other micro-organisms and debris become incorporated in the biofilm. Bacteria within a biofilm communicate by quorum sensing leading to phenotypic modifications and changes in gene expression. Bacteria within the biofilm are protected from disinfectants and have a fundamentally reduced antibacterial sensitivity compared with planktonic, free living, bacteria. Biofilms are highly important in human medicine. In the pig industry, they are important in reducing antibacterial and disinfectant efficacy, causing the persistence of infections in houses and systems, in blocking water systems and probably have a direct role in pig disease. Control of biofilms is difficult and addresses preventing initial formation and removing existing biofilms. Biofilms are best removed by oxidative disinfectants.

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THE DISEASE STATUS OF THE UNITED KINGDOM PIG INDUSTRY
W.D. Strachan

Abstract
(MEMBERS' PAPERS) While statutory measures allow accurate knowledge of the notifiable disease status of the United Kingdom pig industry, the status of the industry with respect to enzootic diseases is less well characterized. There have been few recent published estimates of the herd and animal prevalences of the more important production-limiting diseases. The problems of enzootic disease surveillance are outlined. In addition, the status of the UK pig herd with regard to porcine reproductive and respiratory syndrome, Aujeszky's disease, swine influenza, transmissible gastroenteritis, enzootic pneumonia, progressive atrophic rhinitis, Streptococcus suis, Actinobacillus pleuropneumoniae, swine dysentery, porcine colonic spirochaetosis, proliferative enteropathy and sarcoptic mange is reviewed.

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BIOSECURITY: REDUCING THE SPREAD
S.F. Amass

Abstract
Many of the same biosecurity principles used to minimize introduction of new pathogens to a herd can be used to minimize the spread of pathogens within a herd. Producers and veterinarians are encouraged to take a scientific and herd-specific approach to biosecurity programme development. Risk assessment is recommended so that protocols can be based on actual risk instead of fear. Then, biosecurity procedures can be strategically implemented, based on effectiveness, compliance and economic benefit. One should expect variability in the effectiveness of procedures due to differences in herds, personnel and facilities. Once implemented, protocols should be regularly monitored for compliance and efficacy. Practices should be modified as scientific advances are made in the field and as new pathogens emerge. Practices that are not effective or not cost-effective should be eliminated.

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LABORATORY DIAGNOSIS OF PORCINE INFERTILITY IN THE UK
C. Bidewell, S. Williamson and S.H. Done

Abstract
Investigation of any of the so-called infectious causes of reproductive failure calls for a complete history of the problem. Detailed records must be compiled and should include all clinical signs, their chronological sequence, together with their magnitude. A proper combination of appropriate diagnostic tests must be undertaken, requiring the submission of the right material to the laboratory. Help with the correct interpretation of such results is often necessary. All these factors are looked at in detail in this paper, together with useful advice from the authors to the practising veterinarian.

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