Use of register data to assess the association between use of antimicrobials and outbreak of Postweaning Multisystemic Wasting Syndrome (PMWS) in Danish pig herds

In 2001, the first case of Postweaning Multisystemic Wasting Syndrome (PMWS) was reported in the Danish pig population. During subsequent years, the number of affected farms increased exponentially. The aim of this study was to determine how this increase influenced the use of antimicrobials between 2002 and 2004. We used national register data of herd characteristics, antimicrobial usage and disease occurrence. The analysis included data on antimicrobial usage in 3371 pig herds with weaners and 7434 pig herds with finishers, which accounted for 56 and 82% of the national amount of antimicrobials prescribed to weaners (prescribed by 347 practitioners) and finishers (prescribed by 522 practitioners), respectively.The estimation of the effect of PMWS was done by comparing the amount of antimicrobials (measured as Animal Defined Daily Doses (ADDkg) used per pig-day at risk each month in each herd) used in herds before and after an outbreak of PMWS, and by comparing the amount of antimicrobials used in herds experiencing PMWS with the amount of antimicrobials used in herds not experiencing PMWS. The effects were estimated in a three-level (veterinarian/herd/study-month) linear mixed regression model with an autoregressive correlation of order 1 (AR1).We found that after a herd had experienced an outbreak of PMWS, the antimicrobial usage in weaners was increased for a year. During the first 3 months post outbreak the usage increased by 22%, followed by an increase of 7% during the next 4th to 12th month when compared to the pre-outbreak usage. There was a significant variation between herds in this effect. Additionally, in herds experiencing an outbreak of PMWS, the usage of antimicrobials before the outbreak was 37 and 19% higher in herds with weaners and finishers, respectively, compared to herds not experiencing PMWS.Generalisation of the results to the entire Danish pig population indicated that the increase of PMWS infected herds from almost zero to about 20% during a 4-year period resulted in a national increase of 4–5% in antimicrobials usage in weaners. The effect of PMWS on usage of antimicrobials in finishers was unclear.     

免疫刺激商品断奶仔猪复制多系统衰竭综合征(PMWS)

猪圆环病毒2型（PCV2）是引起PMWS的必需病原,与其他病原混合感染或受到外界刺激时表现PMWS临床症状。本试验将16头商品化断奶仔猪（32日龄）随机分为4组（每组4头）,即对照组、钥匙孔血蓝蛋白刺激组、PCV2攻毒组和PCV2攻毒后钥匙孔血蓝蛋白刺激组,用上海某猪场分离株PCV2-SH、钥匙孔血蓝蛋白（KLH）反复刺激断奶仔猪以复制PMWS。其中对照组、钥匙孔血蓝蛋白刺激组未出现症状;PCV2攻毒组症状较轻,出现增重缓慢,伴有短暂的体温升高;而PCV2攻毒后钥匙孔血蓝蛋白刺激组出现明显的临床症状,2头猪在攻毒后第11天濒临死亡,其中1头在第12天死亡,攻毒猪宰杀后脏器出现明显的病理变化。PCV2攻毒组和PCV2攻毒后钥匙孔血蓝蛋白刺激组于攻毒后第4天出现病毒血症,宰杀后肺脏、淋巴结均检测到PCV2的DNA。以上结果说明,PCV2-SH感染结合免疫刺激可以引起商品化仔猪发生PMWS,为PCV2致病机理和免疫学研究提供了动物发病模型。     

断奶后多系统衰竭综合征病猪中存在沙门氏菌和猪繁殖与呼吸系统综合征病毒共感染

调查了曾经暴发沙门氏菌病的四个猪场的14头病猪,发现在这些猪的肿胀淋巴结中出现带有淋巴细胞排空的肉芽肿性炎症。应用免疫标记和PCR方法在病变部位检测到猪圆环病毒2(PCV2)抗原和PCV2DNA。此外,在这些病猪的肺脏中检测出猪繁殖与呼吸综合征病毒(PRRSV),分离到猪霍乱沙门氏菌。在9头沙门氏菌感染猪中,有5头为沙门氏菌、PMWS与PRRSV并发感染,其数量(55.6%)远远高于沙门氏菌与PMWS感染猪(22.2%)或沙门氏菌与PRRSV感染猪(22.2%)。     

猪圆环病毒2型在PMWS患猪体内分布的初步研究

利用建立的PCR方法对发生PMWS自然患猪的内脏组织中存在的PCV2病毒DNA进行检测,结果发现PCV2病毒主要存在于病猪的淋巴结、肾脏和脾脏中,在肝脏、肺脏中少量存在,心脏中最少。本研究对PCV2临床诊断和致病机理研究具有一定指导意义。     

华东地区PMWS患病猪群PCV-2的检测及其基因特征

用 PCR方法 ,对江苏、上海、山东、江西、安徽和浙江等省市 6 5家猪场 99例断奶仔猪多系统衰弱综合征(PMWS)肺脏和淋巴结病料 ,进行了猪圆环病毒 - 2 (PCV- 2 )基因检测 ,发现其中 18家猪场 2 1例病料为 PCV- 2阳性。源自安徽和上海的 PCV- 2分离株经基因序列分析显示 ,2个分离株部分 ORF2 与国外分离毒株同源性为 92 %～99%。安徽分离株 AHHF6与韩国分离株 KSY- 1同源性为 99% ,而上海分离株 SHHT1与加拿大分离株 Imp.114 7同源性为 98%。上述结果表明 ,我国 PMWS患病猪群广泛存在 PCV- 2 ,不同地区 PCV- 2存在一定基因差异 ,它们可能来源于不同国家或地区     

Individual risk factors for Post-weaning Multisystemic Wasting Syndrome (PMWS) in pigs: A hierarchical Bayesian survival analysis

Risk factors for Post-weaning Multisystemic Wasting Syndrome (PMWS) at the pig level were identified using data from a longitudinal study in seven PMWS-affected farms in France. In each farm, a representative sample of 120 pigs (180 in one farm) was randomly selected after farrowing and followed from birth to slaughter. Individual information included serological status for Porcine Circovirus type 2 (PCV-2), Porcine Reproductive and Respiratory Syndrome (PRRS) virus, and Porcine Parvovirus (PPV), individual weight, rearing conditions, and clinical observations recorded at 7, 13, 16 and 21 weeks of age and at slaughter. Two different Bayesian frailty models were used to identify variables related to time-to-PMWS: (i) a logistic-survival model and (ii) an accelerated failure time model (different survival time distributions) both with two levels of clustering (litter and farm). Similar results in terms of variables related to time-to-PMWS were obtained with both models. However, information provided by the different approaches were complementary. Piglets were more likely to exhibit PMWS after early infection by PCV-2 (i.e. before 7 weeks old) and if they were weaned early (before 21 days). Piglets born to PCV-2 seronegative sows and/or to sows with neck injuries due to poorly performed injections were also more at risk. With the accelerated failure time model, time ratios were obtained giving an estimation of the expected survival time (increased or decreased) after exposure to the factor. The logistic-survival model showed that the majority of the risk factors were mostly related to the odds of PMWS whereas the PCV-2 passive immunity derived from the dam also tended to postpone PMWS appearance later.     

上海PMWS并发PRRS自然病例的病理组织学观察

对上海5例5～13周龄断奶仔猪多器官衰竭综合征（PMWS）并发猪繁殖与呼吸综合征（PRRS）自然病例进行了病理组织学观察。结果：5例病猪均出现坏死性淋巴结炎、间质性肺炎以及不同程度的坏死性脾炎、间质性肾炎和肝炎。2例病猪出现心肌炎，表现为心肌纤维断裂、溶解和心肌间质中淋巴细胞局灶性浸润。2例病猪出现脑炎，在大脑白质区出现神经胶质细胞结节。     

Effect of the Pietrain breed used as terminal boar on Post-weaning Multisystemic Wasting Syndrome (PMWS) in the offspring in four PMWS-affected farms

The aim of this study was to determine the potential risk factors for PMWS at the individual pig level and assess the effect of the Pietrain paternal genetic background of the animals in a cohort study. The survey was set up in four PMWS-affected farms with 2 repetitions (batches) per farm. A representative sample of 60 pigs per batch, stratified according to the paternal genetic background (Pietrain: yes vs. no), was randomly selected after farrowing. The representative cohort was divided into 8 batches and the pigs were individually monitored from birth to slaughter. Survival analysis was used to determine the factors related to the time to PMWS. The litter-cluster effect was taken into account using the marginal Cox model (robust estimation of the covariance matrix) and the gamma shared frailty model which were compared.No protective effect of the Pietrain breed on the time to PMWS and the proportion of affected pigs in the offspring was found in this study. Piglets showing low circovirus type 2 (PCV2) titres at 7 weeks-old with no subsequent seroconversion and piglets from PCV2 negative sows were most likely to be affected by PMWS (HR=7.0 and 2.8, respectively). Active infection of the pregnant dams with parvovirus was related to an increased risk of PMWS in the offspring (HR=2.3). Neck injuries due to poorly performed injections in the dams were associated with an increased risk of PMWS with the marginal model (HR=2.1). Oxytocin injection (dams) during farrowing was protective against PMWS in the offspring (HR=0.6).     

Detection of Porcine Circovirus Type 2, Porcine Parvovirus and Porcine Pseudorabies Virus from Pigs with Postweaning Multisystemic Wasting Syndrome by Multiplex PCR

Multiplex PCR was established to detect porcine circovirus type 2 (PCV-2), porcine parvovirus (PPV) and porcine pseudorabies virus (PRV) and applied to samples from 137 piglets exhibiting clinical signs of postweaning multisystemic wasting syndrome (PMWS). PCV-2 DNA was detected from all samples. Moreover, 43 samples were positive for PPV but negative for PRV; 11 samples were positive for PRV but negative for PPV; and 35 samples were positive both for PPV and PRV. These results suggests that PCV-2 co-infection with PRV and PPV may play an important role in PMWS. Also, multiplex PCR is an appropriate candidate method for diagnosis of PCV-2, PRV and PPV simultaneously in field cases.     

Induction of porcine post-weaning multisystemic wasting syndrome (PMWS) in pigs from PMWS unaffected herds following mingling with pigs from PMWS-affected herds

In this paper we present the results from two experimental studies (I and II) investigating whether post-weaning multisystemic wasting syndrome (PMWS) can be induced in pigs from PMWS unaffected herds by mingling with pigs from PMWS-affected herds and to observe whether transportation and/or mingling of healthy pigs from unaffected herds could induce PMWS.The studies comprised pigs from 12 different herds. Eight herds had PMWS while four were unaffected. All 12 herds were found to be infected with PCV2. Pigs from PMWS-affected herds were mingled with pigs from unaffected herds in four separate compartments in both study I and study II. In addition, in study II, four groups of pigs from unaffected herds were included. Two groups with pigs transported and mingled from unaffected herds and two groups with pigs which were only transported. The PMWS diagnoses on the individual pigs were based on lymphoid depletion, histiocytic proliferation and the presence of giant cells or inclusion bodies together with the demonstration of PCV2 in lymphoid tissue.Healthy pigs, in both studies, developed PMWS 4–5 weeks after mingling with pigs clinically affected with PMWS. None of the pigs from unaffected herds which had no contact with pigs from PMWS-affected herds developed clinical signs of PMWS. Transportation and mingling of pigs from PMWS unaffected herds in combination or alone was insufficient to provoke PMWS.     

Postweaning multisystemic wasting syndrome (PMWS) in pigs in Croatia: detection and characterisation of porcine circovirus type 2 (PCV2)

The objective of this study was to characterise porcine circovirus type 2 (PCV2) from pigs with naturally occurring postweaning multisystemic wasting syndrome (PMWS) in Croatia, and to determine the epizootiological, clinical and pathomorphological features of the disease. During a systematic health monitoring programme conducted in the period from January 2002 to June 2003, PMWS was suspected on eight different pig-producing farms in Croatia. The diagnosis of PMWS met all three key criteria: the presence of compatible clinical signs, the presence of the characteristic microscopic lymphoid lesions, and the detection of PCV2 within the lesions by polymerase chain reaction (PCR) and by in situ hybridisation (ISH). Moreover, PCV2 DNA from swine tissues was extracted and sequenced. The phylogenetic analysis of 4 Croatian PCV2 strains showed close relationship to PCV2 strains isolated in Slovenia, France, the Netherlands, the United Kingdom, China and Hungary. PCV2 was also demonstrated by electron microscopy in the lymph node of an affected animal. This is the first demonstration of PMWS in Croatia based on all scientifically accepted diagnostic criteria.     

Immunohistochemical characterisation of the lymph node reaction in pig post-weaning multisystemic wasting syndrome (PMWS)

The goal of this study was to identify a strain of feline immunodeficiency virus (FIV) that would be more virulent for adult cats than the prototype FIV-APetaluma and, thereby, enhance the FIV infection model for HIV-1 related research. Diehl et al. reported that one clade C strain of FIV, FIV-CPGammar, was more virulent than other known FIV isolates. Mortalities from 58 to 100% were reported for kittens 12 weeks of age and less following intravenous inoculation. A more variable and somewhat less virulent disease course was observed in neonatal to 8-10-week-old kittens infected orally, intravaginally or intrarectally with this same isolate (Obert and Hoover, 2000). However, no studies have been done with FIV-CPGammar in adult cats. Therefore, the virulence of FIV-CPGammar for young adult cats was compared to that of FIV-APetalulma, the original FIV isolate. One group of five cats were inoculated intraperitoneally with 470 TCID(50) of FIV-CPGammar in the form of pooled plasma from acutely infected cats, while a second group was infected with plasma containing the 750 TCID50 of FIV-APetaluma. The cats were observed for 20 weeks for gross signs of disease, hematologic abnormalities, time of antibody appearance, and plasma and peripheral blood mononuclear cell (PBMC) associated virus levels. Viral RNA and proviral DNA were measured by a real-time PCR, sensitive to 50 copies per milliliter. The only outward sign of disease was lymphadenopathy, which occurred at a similar time and intensity in both groups of cats. Cats infected with FIV-CPGammar were more likely to be neutropenic and lymphopenic during the first 10-12 weeks of infection than cats infected with FIV-APetaluma. Both groups of cats showed similar overall declines in absolute mean CD4 cell counts and identical concomitant increases in CD8 cells. CD4/CD8 cell ratios were also similar. Antibody, as measured by an ELISA against recombinant FIV-TM antigen, appeared in all cats by 4 weeks post-infection. The most significant differences were in plasma viral RNA and PBMC proviral DNA levels. Cats infected with FIV-CPGammar had up to 100 times higher mean levels of viral RNA during the first few weeks of infection than cats infected with FIV-APetaluma. This difference was also mirrored in levels of proviral DNA in PBMC, which were significantly higher in the FIV-CPGammar infected cats. Plasma viral RNA and PBMC proviral DNA levels were virtually identical in both groups of cats at 20 weeks post-infection. However, proviral DNA in tissues such as thymus and popliteal lymph nodes was 10-fold or so higher in FIV-CPGammar infected cats at 20 weeks and histopathologic lesions were more severe. Based on these various parameters, we concluded that FIV-CPGammar was more virulent than FIV-APetaluma in young adult cats during the 20-week study period. However, we were not able to recreate the severe and rapidly progressive disease previously reported for kittens, suggesting an age-related resistance similar to that observed previously for FIV-APetaluma (George et al., 1993).     

Bovine viral diarrhea (BVD) eradication in Switzerland--experiences of the first two years

A national eradication programme was designed with the aim of achieving total freedom from bovine viral diarrhea virus (BVDV) infection in the Swiss cattle population. The eradication programme consisted of testing every Swiss bovine for antigen, culling virus-positive animals and applying movement restrictions. Starting in 2008, the campaign achieved the goal of reducing the proportion of newborn calves that were virus-positive from 1.8% to under 0.2% within two years (situation in September 2010). Both good data flow between the parties involved as well as speed and efficiency (e.g. concerning the application of tests, movement restrictions and slaughter) are central to the success of the programme. Since the beginning of the programme 2.85 million cattle have been tested for bovine viral diarrhea virus (BVDV). The BVD-prevalence in cattle at the individual and herd levels following the implementation of the eradication programme was assessed. Using data collected during this campaign a risk factor analysis was conducted in order to identify factors associated with the appearance of virus positive newborn calves in herds where BVD had not previously been detected; these risk factors would allow targeting of future surveillance. Herd size, early death rate (i.e. the number of animals that either die before 15 days of age or are stillborn per number of newborns per year), buying in stock, using communal summer grazing, production type, age structure and management strategy were factors associated with the appearance of new cases of infection. Testing of newborn calves for antigen will continue to be conducted until the end of 2011, this is combined with outbreak investigation of newly infected herds (consisting of re-testing dams of virus-positive calves and if necessary all cattle on or that recently left the farm). This process is done to identify infected animals that may have been missed during prior testing (false negatives), it also serves to identify other factors that may be responsible for the introduction of BVDV onto the farm. Since October 2009, testing of calves for antigen combined with outbreak investigation has led to the detection of 55 infected animals that had tested negative (presumably false negative) during previous rounds of testing.     

Simulating the spread of classical swine fever virus between a hypothetical wild-boar population and domestic pig herds in Denmark

Denmark has no free-range wild-boar population. However, Danish wildlife organizations have suggested that wild boar should be reintroduced into the wild to broaden national biodiversity. Danish pig farmers fear that this would lead to a higher risk of introduction of classical swine fever virus (CSFV), which could have enormous consequences in terms of loss of pork exports. We conducted a risk assessment to address the additional risk of introducing and spreading CSFV due to the reintroduction of wild boar. In this paper, we present the part of the risk assessment that deals with the spread of CSFV between the hypothetical wild-boar population and the domestic population. Furthermore, the economic impact is assessed taking the perspective of the Danish national budget and the Danish pig industry. We used InterSpreadPlus to model the differential classical swine fever (CSF) risk due to wild boar. Nine scenarios were run to elucidate the effect of: (a) presence of wild boar (yes/no), (b) locations for the index case (domestic pig herd/wild-boar group), (c) type of control strategy for wild boar (hunting/vaccination) and (d) presence of free-range domestic pigs. The presence of free-range wild boar was simulated in two large forests using data from wildlife studies and Danish habitat data. For each scenario, we estimated (1) the control costs borne by the veterinary authorities, (2) the control-related costs to farmers and (3) the loss of exports associated with an epidemic. Our simulations predict that CSFV will be transmitted from the domestic pig population to wild boar if the infected domestic pig herd is located close to an area with wild boar (<5 km). If an outbreak begins in the wild-boar population, the epidemic will last longer and will occasionally lead to several epidemics because of periodic transfer of virus from groups of infected wild boar to domestic pig herds. The size and duration of the epidemic will be reduced if there are no free-range domestic pig herds in the area with CSF-infected wild boar. The economic calculations showed that the total national costs for Denmark (i.e. the direct costs to the national budget and the costs to the pig industry) related to an outbreak of CSF in Denmark will be highly driven by the reactions of the export markets and in particular of the non-EU markets. Unfortunately, there is a substantial amount of uncertainty surrounding this issue. If hunting is used as a control measure, the average expenses related to a CSF outbreak will be 40% higher if wild boar are present compared with not present. However, a vaccination strategy for wild boar will double the total costs compared with a hunting strategy.     

Postweaning multisystemic wasting syndrome (PMWS) in pigs with particular emphasis on the causative agent, the mode of transmission, the diagnostic tools and the control measures. A review

Postweaning multisystemic wasting syndrome (PMWS) is a worldwide emerging disease of weaned piglets. The objective of this review is to summarize the current knowledge regarding PMWS, its causative agent, mode of transmission, diagnostic techniques to detect PCV-2, the possible control measures, and the association of PMWS and PCV-2 with porcine dermatitis and nephropathy syndrome (PDNS). The causative agent of PMWS is porcine circovirus type 2 (PCV-2), however, not all pigs infected with PCV-2 develop the syndrome. PCV-2 is consistently associated with PMWS and PMWS is considered not to occur without it. Both the syndrome and the virus are not regarded as new. Co-factors that could activate PCV-2 to cause PMWS are considered. This enigmatic nature of both the syndrome and the virus is triggering a concern towards uncertainties of the viral transmission, its introduction in to the herd, effective tools of diagnosis, and control strategies.     

Prevalence of lungworm D. arnfieldi (Cobbold 1884) in donkeys in Denmark and in horses in herds together with donkeys (author's transl)

During a 5 months' period from January to May 1981 faecal samples of 176 donkeys from 59 herds all over the country were examined at the Institute of internal medicine, The Royal Veterinary and Agricultural University, Copenhagen. In addition, the investigation also included 106 horses from 30 of the donkey herds and 34 horses hospitalized with symptoms of dyspnoea and chronic coughing. In all, 87.5% of the donkeys were shown to excrete D. arnfieldi larvae, often in very high numbers, and the larval excretion was the only symptom of lungworm infection. There was no significant correlation between larval excretion and age, sex or herd size. In horses, the frequency of D. arnfieldi infection was approximately the same in the horses from donkey herds and in horses hospitalized due to chronic cough (10.4% and 8.8% resp.). In contrast to the donkeys, the infection in horses was always accompanied by dyspnoea and coughing.