Swine respiratory disease

PRESENTATION

BROCHURE

Swine Respiratory Disease Paolo Martelli · Joaquim Segalés

Montserrat Torremorell · Elena Canelli Dominiek Maes · Heiko Nathues

Swine Respiratory Disease

Susan Brockmeier · Marcelo Gottschalk Virginia Aragón

Swine Respiratory Disease Paolo Martelli · Joaquim Segalés

Montserrat Torremorell · Elena Canelli Dominiek Maes · Heiko Nathues

Susan Brockmeier · Marcelo Gottschalk

Swine Respiratory Disease

Swine Respiratory Disease

Virginia Aragón

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AUTHORS: Paolo Martelli, Joaquim Segalés, Montserrat Torremorell,

Elena Canelli, Dominiek Maes, Heiko Nathues, Susan Brockmeier, Marcelo Gottschalk, Virginia Aragón.

FORMAT: 17 x 24 cm.

NUMBER OF PAGES: 144.

NUMBER OF IMAGES: 62.

BINDING: hardcover.

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€55 This book aims at providing an updated overview on the most

eBook included

frequent pathogens responsible for Porcine Respiratory Disease Complex (PRDC), viruses and bacteria, acting in association and mainly potentiating their anatomical and functional effects and worsening the clinical outcome and economic impact. The authors, prestigious and rewarded experts with a wide experience in respiratory diseases in pigs, have focused their efforts on preparing chapters that illustrate the latest information and data on the treated topics, while making them as readable as possible. The book inspires to facilitate comprehension and educational enrichment to the preparation of a well-designed, practical approach.

Presentation of the book Respiratory diseases, together with enteric disorders, are the most frequently diagnosed clinical entities in pigs. The high incidence of the infectious agents responsible for pneumonia, in association with frequent, sub-optimal environmental conditions and management practices, lead to a vicious cycle of respiratory disorder persistence in the herd, at times with an increase in severity of clinical signs and mortality and economic losses.

Indeed, the interest of veterinarians and farmers is often focused only on the infectious agents, rather than on the more important, non-infectious conditioning factors. However, the quality of the microenvironment as a whole (temperature, humidity, dust, ventilation, air speed, etc.) is a pivotal player as a predisposing factor and must be considered first when developing strategies to control respiratory distress today. Vaccines and antibiotic treatment cannot counteract poor environmental conditions. In particular, the need to reduce and prudently use antimicrobials requires a revisiting of the approach of the respiratory diseases as a whole. Erroneously, in the past, it was believed that clinical problems could be mainly solved with drugs. This approach must be inverted and the order of priority of the actions to be taken for the prevention of respiratory disorders has changed to environment, management, vaccines and antimicrobials.

The complexity of the approach to respiratory disease in pigs cannot, of course, leave aside the role of infectious agents and their interaction. For this reason, the most extensively used definition of this “never-ending” problem is Porcine Respiratory Disease Complex (PRDC). The term “Complex” is both an adjective and a noun, sustaining the complexity of the approach and the complex features of the clinical signs and economic losses it causes. Morbidity, poor growth performance in growing and finishing pigs and mortality limit the profitability of the herd.

In order to address a successful approach to the control of PRDC, all components generating the pathological entity must be carefully considered.

This book aims at providing an updated overview on the most frequent pathogens responsible for PRDC, viruses and bacteria, acting in association and mainly potentiating their anatomical and functional effects and worsening the clinical outcome and economic impact. In fact, the efforts of the authors have been focused on preparing chapters that illustrate the latest information and data on the treated topics, while making them as readable as possible. The book inspires to facilitate comprehension and educational enrichment to the preparation of a well-designed, practical approach.

The authors wish to dedicate this book to all those people involved in porcine health management and particularly to the students, at all the different levels of their educational program.

Enjoy the reading and make use of the many concepts for controlling PRDC. On behalf of the authors: Paolo Martelli

Swine Respiratory Disease

The authors Paolo Martelli Paolo Martelli graduated (DVM) in Veterinary Medicine (with Honours) from the University of Parma (Italy) in 1984. Veterinary practitioner for 4 years, he started his career as a researcher in 1992. In 1998, he became Associate Professor and since 2002 he is Full Professor of Internal Medicine (Veterinary Clinical Medicine) at the University of Parma, Department of Veterinary Sciences. Paolo Martelli was Head of the Department for 7 years (2002–2008) and Vice Rector of the University of Parma for 3 years. He is a founding member (2004) and Diplomate of the European College of Porcine Health Management (ECPHM). He was coordinator of the PhD course in Animal Health and Veterinary Science at the University of Parma. Currently, Paolo Martelli is President of the ECPHM (2016–2019). He was President of the International Symposium on Emerging and Re-emerging Pig Diseases (Rome, Italy, 2003) and the 6th European Symposium of Porcine Health Management (ESPHM) (Sorrento, Italy, 2014). He was chair of the Scientific Committee of the 24th International Pig Veterinary Society Congress (IPVS)/8th ESPHM (Dublin, 2016). He also acted as President of the Italian Pig Veterinary Society (1995– 2001 and 2007–2013). He has in charge the teaching of Physical examination and Internal Medicine - Clinics of Large Animals. His research activity focuses on porcine health management (porcine reproductive and respiratory syndrome virus [PRRSV], porcine circovirus type 2 [PCV2], Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae) and clinical and experimental immunology (vaccinology). He has been invited as speaker in more than 400 national and international conferences.

Joaquim Segalés Joaquim Segalés obtained his DVM from the Universitat Autònoma de Barcelona (UAB, Spain) in 1991. After completing a 15-month research period at the University of Minnesota (USA), he defended his PhD at the UAB. He obtained his Dipl. European College of Veterinary Pathologists (ECVP) in 2000, and the Dipl. European College of Porcine Health Management (ECPHM) in 2004. Dr. Segalés was a founding member of the ECPHM and President of this College between 2013 and 2016. He is Associate Professor at the Veterinary School of the UAB (Department of Animal Health and Anatomy). He is also a researcher of the Centre de Recerca en Sanitat Animal (CReSA, Spain) and was its Director during the period 2012–2017. He also serves as a diagnostician at the Department of Pathology of the School of Veterinary Medicine of the UAB since 1996 where he was the responsible for the pathological diagnostic activity in swine for the period 1996–2012. Dr. Segalés has been involved in research of swine diseases since 1993, mainly infectious diseases (including infections caused by porcine reproductive and respiratory syndrome virus [PRRSV], Aujeszky’s disease virus, porcine circovirus type 2 [PCV-2], swine hepatitis E virus, swine Torque teno sus viruses [TTSuV], Actinobacillus pleuropneumoniae, Haemophilus parasuis and Mycoplasma hyopneumoniae). He has co-authored more than 250 articles in international peer-reviewed journals, and has recently started working on MERS (Middle East Respiratory Syndrome)-coronavirus infection animal models.

Montserrat Torremorell Montserrat Torremorell is Associate Professor in the Department of Veterinary Population Medicine at the College of Veterinary Medicine of the University of Minnesota (USA).

She obtained her DVM from the Universitat Autònoma de Barcelona (UAB, Spain) in 1994 and her PhD from the University of Minnesota in 1999. Dr. Torremorell joined the University of Minnesota as the Leman Chair in Swine Health and Productivity in May 2009. Prior to that, she was employed at Genus PIC, the largest swine breeding company in the world, in a range of roles related to health assurance and health research. Dr. Torremorell led the efforts in porcine reproductive and respiratory syndrome virus (PRRSV) elimination where PIC USA was able to move from 12 % to 100 % PRRSV-negative status in 5 years. She also participated in the National PRRSV Elimination program in Chile and more recently has worked in the control of other diseases such as swine influenza. Dr. Torremorell has an extensive background in swine health, research, and production systems, including health improvement strategies, disease eradication, diagnostics, biosecurity programs, and health genomics. She currently conducts research in influenza transmission and control to understand influenza dynamics in swine farms. She also researches biosecurity technologies with applicability to prevent and mitigate airborne infections in pigs. She teaches Veterinary Medicine to both DVM and graduate students and is passionate about helping producers and veterinarians to apply science to control diseases. She is also the director of the Swine Disease Eradication Center at the College of Veterinary Medicine of the University of Minnesota. Dr. Torremorell is the author of more than 70 peer-reviewed journal articles and more than 200 abstracts and articles in conference proceedings. She was awarded with the Allen D. Leman Science in Practice Award from the University of Minnesota in 2003 for her work on PRRS elimination. Her research interests include infectious diseases of swine focusing on influenza, PRRS and Haemophilus parasuis, and other swine diseases of economic significance as well research on biosecurity approaches to mitigate pathogen transmission.

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Swine Respiratory Disease

Elena Canelli Elena Canelli graduated (DVM) from the University of Parma (Italy) in 2006, and obtained a Specialist degree in Animal Health and Livestock Productions from the same university in 2009. In 2015, she obtained the PhD in Biotechnology applied to Veterinary Sciences from the University of Milan, discussing a thesis on the development of new diagnostic protocols to be applied to the study of avian rotaviruses. She also holds a second-level master’s degree in Molecular Virology in 2016 from the Faculty of Medicine and Pharmacology at La Sapienza University (Rome, Italy). In 2015, she started her residency program of the European College of Porcine Health Management (ECPHM) at the Department of Veterinary Sciences of the University of Parma. She has been working from 2006 at the Specialized Virology Laboratory of the Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna (IZSLER, Brescia, Italy), focusing in particular on laboratory diagnostics. In 2010, she moved to the Virology Laboratory of the Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana (IZSLT, Rome), where she was concerned on molecular virology. She came back to the Specialized Virology Laboratory of the IZSLER from 2011 to 2014, continuing to work on virology, and also adding to her experience the electron microscopy expertise; she was also involved in different National and European research projects. Nowadays, she works at the University of Parma, Department of Veterinary Sciences, with a post-doctoral fellowship. She also works in the sanitary technical service, for swine farms, of an Italian feed company. Her professional activity focuses on virology, and particularly on viral diseases of livestock, laboratory diagnosis of viral infection, and molecular virology. Her current research concerns primarily swine immunity and vaccinology, and porcine health management. She is the author and co-author of several publications about virology on peer-reviewed journals, congress proceedings and textbooks.

Dominiek Maes Dominiek Maes is Full Professor and Head of the Unit of Porcine Health Management at the Faculty of Veterinary Medicine of Ghent University (Belgium). He is a specialist of the European College of Porcine Health Management (ECPHM). His main research areas include respiratory disease, sow reproduction and production, Salmonella in pigs and antimicrobial use and resistance. The research group has performed lots of studies on Mycoplasma hyopneumoniae and has focused mainly on the pathogenesis and transmission of the pathogen, differences between mycoplasma strains, interaction of the pathogen with the animal host, antimicrobial treatment and resistance of M. hyopneumoniae field strains, and control measures, with emphasis on vaccination. He is Chair of the porcine section of the International Research Programme on Comparative Mycoplasmology (IRPCM), Standing Committee of the International Organization of Mycoplasmology (IOM). He has published over 260 papers in international peer-reviewed journals, from which over 50 on swine mycoplasmas. He has supervised 30 completed PhDs, and made more than 260 contributions to national and international conferences. He is Past President of the International Pig Veterinary Society Congress (IPVS) Belgian branch, the ECPHM, the European Board of Veterinary Specialisation (EBVS) and Past Director of the Institute for Continuing Professional Development at the Faculty of Veterinary Medicine of Ghent University. He is currently Chair of the Committee for Internationalization in the same faculty, section editor of Livestock Science, and editor-in-chief of the journal Porcine Health Management.

Heiko Nathues Prof. Dr. med. vet. Heiko Nathues graduated from the University of Veterinary Medicine in Hannover (Germany) in 2004. He spent some month in a specialised pig and poultry practice in Northern Germany. From late 2004 until 2011 he was employed at the Field Station for Epidemiology of the University of Veterinary Medicine Hannover (Bakum, Germany), where he also obtained his Dr. med. vet. in 2007 and his PhD in 2011. The latter one was assigned with the “Konrad Boegel Young Talent Award for veterinary epidemiology and veterinary public health”. During his time in Bakum, he built up from the scratch a laboratory for molecular biology, serology and genetic engineering. Awarded with a Marie Curie Intra-European Fellowship, he joined the Veterinary Epidemiology, Economics and Public Health Group of the Royal Veterinary College (London, UK), from 2011 to 2013. He was involved in the development of within-herd transmission models for pig diseases and contributed to various research projects dedicated to porcine health management.

He also obtained a Postgraduate Certificate in Veterinary Education. In 2013, he finalized his habilitation and received the venia legendi for “Pig diseases and population medicine” from the University of Veterinary Medicine Hannover. Since then, he is Professor at the Vetsuisse Faculty of the University of Bern (Switzerland), where he is heading the clinic for swine. Prof. Nathues is Diplomate of the European College of Porcine Health Management (ECPHM) and currently the Vice-President of the ECPHM. He is also Honorary Professor at the Jiangsu Academy of Agricultural Sciences (Nanjing, China). His primary areas of interest include diagnosis, epidemiology and control of porcine virus and mycoplasma diseases. His current research is focused on modelling diseases in pig herds, the improvement of diagnostic methods and the determination of the efficacy of methods to control the disease.

Susan Brockmeier Susan Brockmeier received her DVM from the University of Missouri (Columbia, Missouri, USA), and a PhD in Veterinary Microbiology from Iowa State University (Ames, Iowa, USA).

She is currently a Research Veterinary Medical Officer with the United States Department of Agriculture (USDA), Agricultural Research Service (ARS), at the National Animal Disease Center (Ames, Iowa, USA), where she has conducted swine infectious disease research for the past 25 years. Dr. Brockmeier has extensive experience working on polymicrobial infections and her work is centered around how bacterial pathogens establish infection and cause disease alone and in combination with other common viral and bacterial respiratory pathogens to produce the swine respiratory disease complex (PRDC). The disease models she has developed have been used to analyze pathogenesis, transmission, innate and adaptive immune responses, biotherapeutic interventions, and vaccine efficacy.

Swine Respiratory Disease

Marcelo Gottschalk Marcelo Gottschalk received his DVM from the Faculty of Veterinary Medicine of the University of Buenos Aires (Argentina). He moved to Canada in 1987 where he completed a PhD at the University of Montreal. Since 2001, he is Full Professor at the Faculty of Veterinary Medicine of the University of Montreal, where he is the Director of the reference laboratory for the diagnosis of Actinobacillus pleuropneumoniae (App, aetiological agent of swine pleuropneumonia).

He is also the Director of the international reference laboratory for Streptococcus suis. He founded the Swine Infectious Diseases Research Center at the Quebec province (Canada) and he was also the Director of the Research Group of Swine Infectious Diseases at the University of Montreal. He received the Degree of Doctor Honoris Causa from Ghent University (Belgium) in 2018. He has published more than 300 papers in international peer-reviewed journals and more than 150 papers in professional journals. He is also the author of two chapters of the reference book Diseases of Swine (Actinobacillosis and Streptococcus). He has been invited as speaker in more than 200 occasions from more than 35 countries by different universities, research centers, associations of swine practitioners, associations of swine producers and pharmaceutical companies. He has participated in more than 400 studies presented in different international meetings. His research is highly focused on App and S. suis.

Virginia Aragón Virginia Aragón completed her PhD at the University of Navarra (Pamplona, Spain) working with virulent strains of Brucella, mainly B. melitensis and B. abortus. Her work provided her with the opportunity to continue her scientific career as postdoctoral fellow at three different universities in the USA. Dr. Aragón joined the Centre de Recerca en Sanitat Animal (CReSA, Spain) in 2003 and established herself as a leading scientist in the research line of respiratory bacterial infections of swine. Dr. Aragón has been involved in the genomic and functional characterization of the swine pathogen Haemophilus parasuis, with especial research interest in unravelling the molecular mechanisms and components responsible for H. parasuis pathogenesis. Currently, her research focus extends to understand the role of the nasal microbiota in controlling respiratory disease in swine. Her scientific achievements are published in peer-reviewed international journals in the areas of Microbiology and Veterinary Medicine and are also divulged to clinicians and producers in technical talks. Her research on H. parasuis has produced articles in international journals, one book chapter in the book Diseases of Swine, several doctoral thesis, divulgative publications and several communications in national and international congresses. She has been the principal investigator in five national projects on H. parasuis and nasal microbiota, and has collaborated in other projects since she joined CReSA. Dr. Aragón also participates in educational programs, teaching for Master students and supervising high schoolers through the Argó program (Autonomous University of Barcelona, UAB, Spain). In the last 5 years, she has participated in six research projects, has published 24 peer-reviewed articles (including one review), an invited editorial, one book chapter in Diseases of Swine, and she has supervised three PhD thesis and eight Master thesis.

Swine Respiratory Disease Paolo Martelli · Joaquim Segalés

Montserrat Torremorell · Elena Canelli Dominiek Maes · Heiko Nathues

Swine Respiratory Disease

Susan Brockmeier · Marcelo Gottschalk Virginia Aragón

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Table of contents 1. Porcine respiratory disease complex: A combination of factors (Paolo Martelli and Joaquim Segalés)

2. Porcine reproductive and respiratory syndrome virus (Paolo Martelli)

3. Swine influenza virus (Montserrat Torremorell)

4. Aujeszky’s disease virus (Elena Canelli)

5. Porcine circovirus type 2 (Joaquim Segalés)

6. Mycoplasma hyopneumoniae (Dominiek Maes, Filip Boyen and Freddy Haesebrouck)

7. Mycoplasma hyorhinis (Heiko Nathues)

8. Bordetella bronchiseptica (Susan Brockmeier and Samantha Hau)

9. Actinobacillus pleuropneumoniae (Marcelo Gottschalk)

10. Haemophilus parasuis (Virginia Aragón)

Recommended literature

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PORCINE RESPIRATORY DISEASE COMPLEX: A COMBINATION OF FACTORS Porcine Respiratory Disease Complex (PRDC) is a multifactorial syndrome characterized by respiratory clinical signs caused by the interaction of infectious viral and bacterial pathogens (multiple microorganisms are usually involved), as well as environmental stressors, management practices and genetic factors. Indeed, the term “complex” emphasizes the complexity of the interactions. Moreover, PRDC is extensively used to define a disease complex featuring clinical signs of respiratory disease and causing economic losses due to morbidity ranging from 10 % to 40 %, mortality varying from 2 % to 20 %, and poor growth performance in growing and finishing pigs, limiting herd profitability. The economic losses are enhanced by the increased use of antimicrobials and control measures, namely vaccination.

In light of the current limitation on the use of antibiotics to reduce the risk of antimicrobial resistance and the changes in the husbandry practices, it is particularly important to review today’s approach to PRDC.

It is commonly accepted that the primary pathogens involved in swine respiratory disease are viruses and/or Mycoplasma hyopneumoniae, which predispose infected pigs to concomitant bacterial infections through a decrease in host defense.

Porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Aujeszky’s disease virus (ADV), porcine circovirus type 2 (PCV-2) and classical swine fever virus (CSFV) may all play a role in PRDC. M. hyopneumoniae is frequently documented as a primary respiratory pathogen in PRDC, both for its effects on the defense mechanism of the respiratory tract and the high incidence of the infection in the pig population worldwide.

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The interaction among pathogens and the related clinical and productive consequences can vary based on the specific herd epidemiology of these infections (sequential or concurrent). Moreover, within the same herd, circulation and the transmission pattern of a given infectious agent may be different over time.

PRRSV infection in nursery pigs can change significantly over time according to the unstable or stable status of the herd and the type of production (one-site, three-site production). M. hyopneumoniae infection dynamics depends on the status of the replacement gilts and their proportion within the inventory of the farm. It is therefore necessary to recurrently monitor the disease by appropriate diagnostic investigations.

The most common bacteria isolated from pneumonic lungs include Pasteurella spp., Streptococcus spp., Bordetella bronchiseptica, Haemophilus parasuis and Actinobacillus pleuropneumoniae. They can act as concomitant invaders of the respiratory tract and cause worsening of lesions and functions already compromised by the effects of viruses or mycoplasma or as primary agents causing a given disease, such as Glässer’s disease for H. parasuis and porcine pleuropneumonia for A. pleuropneumoniae.

The pathology associated with PRDC varies depending on the specific pathogens involved in each case, and it is common to observe a combination of lesions of viral and bacterial origin. Importantly, the contribution of multiple infectious agents also causes variability on the observed lesions when several pigs from the same outbreak are necropsied. It is therefore highly recommended to necropsy several animals to avoid missing lesions potentially indicative of certain pathogens or diseases.

The most evident pathological expression of PRDC is pneumonia.

Pigs can display all types of pneumonia, including catarrhal-purulent (suppurative) bronchopneumonia, fibrino-(haemorrhagic)-necrotizing pleuropneumonia, interstitial pneumonia, broncho-interstitial pneumonia and embolic pneumonia (Table 1 and Fig. 1).

As mentioned above, pigs affected by PRDC outbreaks will probably have a combination of these lesions (in different pigs and/or the same pig), thus the veterinarian should be able to discriminate among them to establish their likely

PORCINE RESPIRATORY DISEASE COMPLEX: A COMBINATION OF FACTORS

causes. Although lung lesions are rarely specific of one infectious agent, the type of lesion is certainly indicative of broad groups of pathogens (i.e., interstitial pneumonia is generally caused by viruses, while suppurative bronchopneumonia is caused by bacteria). Examples of the different types of pneumonia patterns can be observed in Figure 1.

Table 1. Major types of pneumonia in pigs, most usual gross findings and major infectious causes.

Type of pneumonia

Lesion distribution

Pleural involvement

Major causes

Suppurative bronchopneumonia

Cranio-ventral, full consolidation

No

Pasteurella multocida Bordetella bronchiseptica Streptococcus suis Haemophilus parasuis

Fibrino-necrotizing pleuropneumonia

Cranio-ventral to caudodorsal consolidation, including necrosis; eventual haemorrhages

Yes (presence of fibrin)

Actinobacillus pleuropneumoniae Actinobacillus suis Pasteurella multocida

Interstitial pneumonia

Tan-mottled, multifocal, generalized; lack of pulmonary collapse; eventual interstitial oedema

No

PRRSV PCV-2 Porcine respiratory coronavirus (PRCV) Salmonella choleraesuis

Broncho-interstitial pneumonia

Multifocal, mainly cranioventral consolidation

No

Mycoplasma hyopneumoniae SIV

Embolic pneumonia

Multifocal abscesses, generalized

Yes (in abscesses affecting the pleura)

Pyogenic bacteria circulating systemically (emboli) (Trueperella pyogenes is one of the most usual agents)

Given that PRDC is a multifactorial syndrome caused by several infectious agents in combination with non-infectious influences, it is necessary to understand the interactions among all these factors.

Pathogens can influence each other and their combined effects on the respiratory tract worsen the severity of the disease. Moreover, vaccination is widespread, still being the most cost-effective approach in controlling the infectious agents involved in PRDC, and the interaction between vaccines and infection is particularly important.

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a

b

c

Figure 1. Different pneumonia patterns. (a) Normal lung within the thoracic cavity. Note the well-collapsed parenchyma and lack of colour alterations. (b) Suppurative bronchopneumonia: diffuse pulmonary cranio-ventral consolidation affecting apical, middle and cranial part of diaphragmatic lobes. (c) Fibrinohaemorrhagic-necrotizing pleuropneumonia: marked pulmonary dorso-caudal consolidation with necrosis and haemorrhages (dark areas). The amount of fibrin is scarce, providing a frosted aspect of the pleura. (d) Interstitial pneumonia: tan-mottled, non-collapsed lung usually described as “chessboard pattern”. (e) Broncho-interstitial pneumonia: multifocal to coalescent pulmonary cranio-ventral consolidation, mainly in cranial and middle lobes, but also extended multifocally towards the cranial part of the left diaphragmatic lobe. (f) Embolic pneumonia: presence of multifocally distributed abscesses through all lung parenchyma, most of them with relatively small diameter.

PORCINE RESPIRATORY DISEASE COMPLEX: A COMBINATION OFÂ FACTORS

d

e

f

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Interactions among pathogens and between pathogens and PRDC vaccines Interaction between PCV-2 and PRRSV PCV-2 and PRRSV are widespread in the pig population, so it is likely that the majority of the farms are dually infected and both vaccines are being used. The interaction between PRRSV and PCV-2 infections is well documented. In fact, PRRSV infection potentiates PCV-2-associated lesions, viral load in sera of coinfected pigs as well as the levels of PCV-2 antigens in tissues. Conversely, PCV-2 does not significantly influence PRRSV replication or associated lesions.

In farms with dual PCV-2/PRRSV infection status, vaccination against PRRSV can minimize the effect of the PRRSV-associated enhancement of PCV-2 replication. Unexpectedly, PRRSV vaccine in conjunction with PCV-2 infection was found to enhance PCV-2 replication. This is attributable to the fact that attenuated PRRSV vaccine replication is similar to what happens with a natural PRRSV/ PCV-2 co-infection.

Under field conditions, PRRSV vaccination is applied around weaning, many weeks before PCV-2 infection most frequently manifests, i.e., from 10 to 16 weeks of age. In any case, it is advisable to determine the PCV-2 infection status in pigs prior to PRRSV vaccination.

The efficacy of PCV-2 vaccination does not seem to be affected by PRRSV infection. However, in PRRSV-viraemic piglets, PCV-2 vaccination induces a weak or absent cell-mediated immune response.

Concurrent vaccination against PRRSV and PCV-2 does not negatively influence the immune response and the clinical efficacy in comparison to single administrations.

Interaction between PCV-2 and M. hyopneumoniae Under field conditions, M. hyopneumoniae infection occurs most frequently following, rather than concurrently to, PCV-2 infection. However, this is not always the case and concurrent infections must be considered.

In pigs firstly infected with M. hyopneumoniae and subsequently with PCV-2, there can be an increase in the severity of PCV-2-associated lung and lymphoid lesions, PCV-2 viraemia and the incidence of porcine circovirus diseases (PCVD). Therefore, mycoplasma vaccination alone should reduce

PORCINE RESPIRATORY DISEASE COMPLEX: A COMBINATION OF FACTORS

M. hyopneumoniae enhancement of PCVD, but does not reduce the proportion of pigs with PCV-2 viraemia or PCV-2-associated lung and lymphoid lesions in dually infected pigs. Conversely, PCV-2 does not increase the levels of nasal shedding of M. hyopneumoniae. PCV-2 vaccination alone reduces PCV-2 viraemia and its associated lung and lymphoid lesions, but does not decrease M. hyopneumoniaeinduced lung lesions.

Infections caused by these agents are highly prevalent and commercial M. hyopneumoniae and PCV-2 vaccines are widely used in pig production. It is necessary to vaccinate pigs with both pathogens to control co-infection with M. hyopneumoniae and PCV-2.

Interaction between PRRSV and M. hyopneumoniae The relationship between M. hyopneumoniae and PRRSV is very well known.

M. hyopneumoniae infection potentiates pneumonia induced by PRRSV and enhances viraemia, whereas PRRSV neither increase pneumonia lesions induced

by M. hyopneumoniae nor its nasal shedding.

Based on the relationship between PRRSV and M. hyopneumoniae, pneumonia reduction can be achieved by M. hyopneumoniae vaccination with positive effects also on PRRSV replication. Therefore, at least theoretically, mycoplasma vaccination can help in controlling the effects of PRRSV infection in dually infected farms suffering from PRDC. An appropriate design of a vaccination schedule can significantly contribute to the control of PRDC. The success of a vaccination plan is first related to the intrinsic efficacy of the vaccine itself and how it is applied in pigs in terms of timing, route of administration, potential residual interference of maternally-derived antibodies, health status of the animals at vaccination, etc. Currently, the optimization of the vaccination strategies is a mainstay of the PRDC prevention. In particular, vaccination efficacy can also be complicated by the interaction between the vaccine and concomitant infections. In fact, it is already well known that incomplete protection expected from an attenuated PRRSV vaccine (reduction of PRRSV viraemia, clinical signs and pathological lesions) can be additionally compromised by M. hyopneumoniae infection that negatively modulates the cell-mediated response to the virus. Therefore, the monitoring of M. hyopneumoniae infection status before PRRSV vaccination seems to be important. It has been reported that the efficacy of two doses of mycoplasma vaccine are not affected by prior PRRSV vaccination,

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but a first dose of mycoplasma vaccination followed by PRRSV vaccination and a second dose of mycoplasma vaccination can compromise the protection of the double administration. Conversely, in the case of a one-dose mycoplasma vaccine, the efficacy is not decreased by prior administration of a PRRSV vaccine.

In order to effectively improve the control of PRDC, it is necessary to understand the dynamics of the epidemiology of the infectious agents in the farm and know the interactions between them and the vaccines available.

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