Introduction

Veterinarians and researchers continue to discover and add new pathogens (i.e. respiratory coronavirus, PRRSV, and circovirus) to the list of contributors to the porcine respiratory disease complex (PRDC). The etiology of PRDC is multifactorial and varies from farm-to-farm. Improved diagnostic tools (i.e. immunohistochemistry, PCR) have increased the speed and accuracy of finding out exactly what agents are involved in each respiratory disease outbreak. Once the pathogens involved are confirmed and prioritized, progressive veterinarians and producers quickly move towards minimizing losses and driving the disease subclinical or eliminating it from the production system with appropriate medication, vaccination, and production changes. Cost-effective management of PRDC begins with the proper diagnosis.

Respiratory Pathogen Trends

Table 1 summarizes 1993-1996 field case data from the Iowa State University Veterinary Diagnostic Laboratory. A clear trend towards increasing case numbers of pneumonia due to porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), and Mycoplasma hyopneumoniae (MH) is demonstrated. The number of cases of pneumonia due to the other primary pathogens (pseudorabies virus, Actinobacillus pleuropneumoniae , Salmonella choleraesuis) is steady or decreasing. The increased incidence (six-fold) of PRRSV-induced pneumonia is most remarkable. The three-fold increase in SIV and MH is also of interest and concern.

Nursery Disease Reflects Sow Herd Stability

The dynamics of respiratory disease in nursery pigs are a lot less predictable today. This is likely due to increasing sow herd size, high gilt replacement rates, multisourcing of gilts, earlier weaning of pigs, wide weaning age range, and multisourcing of nurseries. Bigger sow herds and high gilt replacement rates result in variable exposure to infectious agents across the breeding barn. This translates into variable levels of passive antibody passed on to the pigs via the colostrum. The end result is subpopulations of young pigs susceptible to diseases that in the past were not observed until much later in the production system.

Swine influenza is a good example of disease that in the past was primarily manifest in grow-finish pigs. Most sows and sow herds were solidly immune to SIV resulting in passive antibody protection for pigs that lasted for 10 or more weeks. Now, SIV has become a very common pathogen in nursery age and even suckling pigs. It is not at all uncommon to have nurseries endemically-infected with SIV similar to what we expect with PRRSV or TGEV. To address this, a lot of SIV vaccine is used in sow herds to build passive antibody levels and protect pigs until they are older and less severely affected by SIV. Mycoplasmal pneumonia in the past was also very uncommon before 12-14 weeks; however, now it is common to diagnose Mycoplasma hyopneumoniae and opportunistic bacteria resulting in enzootic pneumonia in 5-8 week old nursery pigs. Focus for control of early-onset mycoplasmal pneumonia has also moved to immunization of the sow herd.

One thing that has not changed is that PRRS virus continues to be a major problem in nursery pigs. This is due in large part to the fact that passive antibody protection acquired from the sows wanes by 2-5 weeks of age so that pigs become susceptible to PRRSV during the period of weaning, mixing, and moving to the nurseries. The reasons for increasing incidence of inclusion body rhinitis due to porcine cytomegalovirus in nursery age pigs is less clear. Many people believe that the pigs suffering from inclusion body rhinitis are from naive gilts that somehow got all the way through gestation without being exposed to porcine cytomegalovirus.

Porcine circovirus is a newly discovered pathogen that has become a major player in nursery pig respiratory disease in Canada. We are anxious to see how widespread circovirus is or becomes in the U.S. and what role it will play in the nursery pig respiratory disease complex.

Mid to Late Finishing Phase Complex

The so-called "18-20 week wall" has received a lot of attention in the last two years. The clinical problem is first characterized as a severe acute respiratory disease outbreak which becomes chronic in some pigs and endemic in the barn resulting in increased mortality and high numbers of cull pigs. Morbidity has been reported to range from 30-70% and mortality 4-6%. Diagnosticians most often detect porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (MH) in these pigs. Pasteurella multocida (PM), Streptococcus suis (SS), swine influenza virus (SIV), or porcine respiratory coronavirus (PRCV) are sometimes also involved in the syndrome. In most cases, treatment and prevention programs which focus primarily on the mycoplasma and PRRSV have been successful in controlling this costly problem in subsequent groups of pigs.

Recent evidence suggests that the inability to stabilize sow herds infected with PRRSV in many cases may be due to subpopulations. Clinical researchers demonstrated that subpopulations of seronegative animals and acutely infected animals existed within the endemically infected population resulting in ongoing spread of the virus and clinical disease in the sow herds. This same concept has also been proposed to be applicable in the grow-finish phase respiratory disease complex. Cross sectional serology and necropsies have been used to substantiate this theory. In typical grow-finish units, the seroprevalence of PRRSV generally gradually increases to nearly 100% by the end of the finishing phase, however, 30-40% of the population is often seronegative to Mycoplasma hyopneumoniae by the late grow-finish phase which is when they typically hit the "18-20 week wall". PRRSV-infected and mycoplasma-susceptible pigs continue to be infected with mycoplasma and opportunistic bacteria such as Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis resulting in severely enhanced enzootic pneumonia. In some cases, SIV is the primary pathogen or a synergist with PRRSV.

Primary Swine Viral Respiratory Pathogens

In order to investigate and understand these complexes or syndromes, it is important to have a clear idea of how to diagnosis and what to expect clinically and pathologically from the primary viral and bacterial pathogens. It is also important to understand what the more common opportunistic pathogens are and to be able to prioritize which pathogens in the complex are most cost-effective to control. Primary swine viral respiratory pathogens include porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), porcine respiratory coronavirus (PRCV), and pseudorabies virus (PRV).

Porcine Reproductive and Respiratory Syndrome (PRRSV)

PRRSV is a member of the Arteriviridae family of the order Nidovirales. In swine dense areas, 50-80% of the herds are infected with PRRS. Considerable genetic, antigenic, and pathogenic variation exists among European and U.S. isolates. Severe abortion storms, neonatal respiratory disease, and nursery pig pneumonia problems were prevalent from 1987-1991 and have had a resurgence in 1996-1997. Reproductive failure (abortions, stillborns, weakborn pigs) can persist for 2-3 months but usually does not reoccur unless naive females are added to the population. Sows may experience anorexia, lethargy, and pyrexia. European researchers have reported blue discoloration of ears (thus the term "blue-ear disease"). Severe respiratory distress, abdominal respiration, and general failure-to-thrive is observed in neonatal pigs. Pneumonia, rhinitis, and increased incidence of secondary bacterial diseases (Streptococcus. suis, Haemophilus parasuis, Actinobacillus suis, H. E.coli) is observed in nursery pigs. The virus may persist in continuous-flow nursery pig populations indefinitely causing pneumonia and predisposing pigs to other viral, bacterial, and/or mycoplasmal infections. Coughing is NOT a feature of PRRSV infection. If coughing is present, there must be concurrent infection with other pathogens. Inapparent to mild to moderate transient respiratory disease is observed in grow-finish pigs infected with PRRSV. The concurrent infections are what make PRRSV a problem in finishers. It must be remembered that many seropositive herds have had no clinical reproductive or respiratory problems whatsoever.

We have a lot to learn about the unusual pathogenesis of PRRSV. There clearly are marked differences in the virulence of PRRSV isolates. Some isolates induce severe respiratory disease and lesions, whereas, others induce inapparent disease and lesions. Previous infection with the homologous strain seems to be protective, as does colostrum from immune sows. Protective colostral antibody wanes in 3-6 weeks. Cross protection between strains of PRRSV ranges from excellent to poor.

Infection has been established by oronasal, intramuscular, intravenous, intrauterine, and intraperitoneal routes experimentally. Oronasal route of exposure seems most likely. The virus then replicates in macrophages and dendritic cells in tonsils, upper respiratory tract, and lungs resulting in viremia by 6-12 hours which may persist for several weeks. Further replication occurs in lymph nodes, spleen, thymus, bone marrow, and lungs. PRRSV is shed via respiratory tract, saliva, feces, urine, and semen. PRRSV may persist in tonsils and lungs for 3 weeks to 1 year. Recovered pigs may be a source of infection of other pigs for 3-6 months or more. An area of great interest is persistent infection with PRRSV. Recent research indicates that some pigs born to sows that were infected in the third trimester may be viremic for over 200 days. These pigs have been called Long Term Viremic Pigs (LTVP’s) and may be a very important source of virus dissemination and persistence in herds.

Gross lesions of PRRS are very characteristic. Neonatal and nursery pigs may have mild-to-severe, multifocal-to-diffuse, tan-mottled discoloration and consolidation of the lung. Pneumonia is evident by 3 DPI, most severe at 7-10 DPI, and if uncomplicated, resolves by 14-21 DPI. Lymphadenopathy is the most consistent lesion and is characterized by 3-10 times enlarged tan lymph nodes which sometimes contain multiple fluid-filled spaces. Microscopic lesions are also quite characteristic. Interstitial pneumonia in neonatal and nursery pigs is characterized by (i) septal infiltration with mononuclear cells, (ii) type II pneumocyte hypertrophy and hyperplasia, and (iii) alveolar exudate consisting of mixed inflammatory and necrotic cells. Airway epithelium is generally unaffected at the light microscope level. Lymphadenopathy is characterized by marked follicular hypertrophy with focal follicular necrosis, and less often by the presence of subcapsular fluid-filled spaces and multinucleated cells. Lymphomononuclear perivascular encephalitis, myocarditis, and rhinitis with epithelial metaplasia may be observed with some strains.

PRRSV infection results in destruction of alveolar and intravascular macrophages decreased alveolar and lymphoid macrophage function, damage to the mucociliary apparatus, and decreased function of antigen presenting cells such as dendritic cells and macrophages. This accounts for PRRSV-induced disease and the increased secondary infections in PRRSV positive pigs. PRRSV-induced lysis of macrophages likely results in systemic release of cytokines which are important systemic mediators of inflammation. Nonregenerative anemia and transient leukopenia have been experimentally induced by PRRSV infection and are common observations in the field.

Definitive diagnosis of PRRS is based on antigen detection by fluorescent antibody (FA) examination of frozen tissue sections or immunohistochemical (IHC) examination of formalin-fixed tissue sections. Virus isolation from serum, lung, lymphoid tissues, and alveolar macrophages (lung lavages) is quite successful. Several good quality serologic tests (IFA, IPMA, SVN, and ELISA) are available. The ELISA test is the preferred test at this time. Serum antibody is detected by the ELISA by 7-10 days post infection and persists for 4-7 months.

Swine Influenza Virus (classical SIV)

Swine influenza is caused by Influenza type A, subtype H1N1 of the Family Orthomyxoviridae. Nucleoprotein and matrix proteins determine the "type". "Subtype" classification is by antigenic properties of surface glycoproteins hemagglutinin (H) and neuraminidase (N). There are variants within subtypes based on amino acid sequence of the H and N. Most swine influenza in the U.S. is caused by H1N1. Infection with subtype H1N1 is common in the Midwestern U.S., 25-50% of slaughter pigs are seropositive. H1N1 is widespread in Europe. H3N2 has been associated with disease outbreaks in Europe since 1984. Several commercially available vaccines in Europe contain both H1N1 and H3N2 virus types.

Clinical signs consistent with SI include sudden onset of respiratory disease with high morbidity and low mortality if uncomplicated. Dyspnea, abdominal respiration ("thumping"), paroxysmal "barking cough", prostration, and fever are characteristic. Rapid recovery occurs in 2-6 days if uncomplicated. SI is Most common in 60-200 lb. pigs and is less common, but quite severe when it occurs in nursery and neonatal pigs. Classically SI is seen in fall and winter months but it is now commonly seen all times of the year. Passive antibody is generally protective and decays by 8-12 weeks.

Swine influenza virus is probably spread pig-to-pig via nasopharyngeal secretions. Carrier animals may allow for persistence of SIV in the herd. Virus attaches to the cilia and viral replication begins in the epithelium of the nasal and tracheal epithelium by 2 hrs post inoculation. Infection spreads to bronchi and bronchioles and by 8 hours there is loss of cilia, extrusion of mucus and vacuolar degeneration of epithelial cells, By 24 hours the airway epithelium is necrotic and sloughing. Emigration of leukocytes into airway lumens occurs and there are plugs of exudate that cause atelectasis. Extension of virus infection to alveolar epithelium, endothelium, and alveolar macrophages results in flooding of alveoli with serofibrinous exudate. Pigs are predisposed to bacterial pneumonia due to damage to the mucociliary apparatus and decreased macrophage function. Resolution occurs in 4-6 days if uncomplicated by bacterial pathogens.

Swine influenza virus-infected pigs may have cranioventral, multifocal or diffuse, dark red-tan mottling or checker-board pattern of consolidation affecting 20-100% of the lung tissue. Blood-tinged foam in airways and diffuse congestion of the lungs may be observed. Lungs are very heavy. Enlargement and hyperemia of mediastinal and tracheobronchial lymph nodes is common. Severe necrotizing bronchiolitis is typical. In mild cases of SIV, viral replication is limited to the upper respiratory tract, in severe cases replication extends down to the alveoli.

Diagnosis of SI is based on observation of very characteristic clinical signs as described above. Antigen detection by fluorescent antibody examination (FA) of frozen sections or immunohistochemical (IHC) examination of formalin-fixed sections is successful in the early stages of disease. Antigen capture kits for rapid diagnosis from nasal or bronchial swabs have also become available recently. Virus isolation (VI) from nasal swabs or lung tissue is quite successful in the early stages of disease. Multiple nasal swabs for pooling are the preferred herd specimen for VI. Paired serology (HI, ELISA, IFA) is needed due to the persistence of passive antibody for 8-12 weeks and because it common takes 3-4 weeks to detect seroconversion. Hemagglutination inhibition test is most commonly used for serology. This test is specific for the serotype (type A, H1N1) used in the test itself. Antibodies against some H1N1 variants (antigenic variants) may not be detected by this test. The IFA test will detect antibodies against all serotypes (H1N1 and H3N2) because it detects antibodies directed against the viral envelope and nucleocapsid protein.

Swine Influenza Variants

There is still a lot of confusion regarding the recently described swine influenza antigenic variants in North America. These variants are also Type A, subtype H1N1, but they are antigenically and genetically distinguishable from North American and European reference strains. These variants were first reported in Canada in 1988. The disease has been referred to as Proliferative and Necrotizing Pneumonia (PNP) because of the unique histopath lesions. Now it appears that some of the original outbreaks of "PNP" were probably caused by a combination of SIV and PRRSV or possibly SIV and circovirus. The disease also has been referred to as "atypical influenza".

The swine influenza situation is Europe is also changing. The more common swine influenza isolates in Europe since 1979 are similar to, but distinguishable from, the classical H1N1 strains. Since 1979 the isolates have been antigenically and genetically more similar to H1N1 viruses isolated from birds. In January 1992 there was a sudden increase in respiratory disease in the swine population of England. The isolate A/swine/England/195852/92 was typical of the isolates from this outbreak. Convalescent sera from this outbreak tested negative in hemagglutination inhibition tests with the classical UK- prototype H1N1 and H3N2 swine influenza viruses. By comparison of H1N1 serotypes in hemagglutination inhibition tests using monoclonal antibodies to the H1 hemagglutinin, A/swine/England/195852/92 is distinguishable from classical and European swine viruses.

Clinical signs are similar to that of classical SI. Severe abdominal respiration (thumping), lethargy, anorexia, and pyrexia in neonatal, nursery and grow-finish pigs is observed. Some Canadian farms report concurrent reproductive failure. Respiratory disease outbreaks may last for 10-14 days or become an endemic problem particularly in nursery and grower age pigs.

Diagnosis is based in part on observation of typical clinical disease, gross lesions, and "PNP" microscopic lesions. Gross lesions essentially are the same as observed for classical SI. Microscopic lesions are characterized as Proliferative and Necrotizing interstitial Pneumonia ("PNP") with necrotizing bronchiolitis, marked type II pneumocyte proliferation, alveolar exudate and fibrin deposits along alveolar septa. Virus isolation and antigen detection (FA, IHC) are done using the same procedures as for classical SI. Once the virus is isolated, antigenic characterization can be done by comparative hemagglutination inhibition tests using monoclonal antibodies to the H1 hemagglutinin. Conventional hemagglutination (HI) inhibition serology may not be of much value depending on the strain used in the test. Expect low or negative titers using a classical strain in the HI.

Porcine Respiratory Coronavirus (PRCV)

PRCV belongs to the family Coronaviridae and is closely related to TGEV. PRCV was first isolated in Belgium in 1986. A large percentage of the Belgian swine herds became seropositive to TGEV but exhibited no signs of enteric or respiratory disease. The incidence of clinical TGE has greatly decreased since the introduction of PRCV into the European swine population. This has stimulated interest in the use of PRCV as an immunogen for TGEV. PRCV was first isolated in the U.S. in 1986. The significance of PRCV is threefold; (i) some strains may induce respiratory disease alone or synergistically with other viruses, bacteria, or mycoplasmas, (ii) it is difficult to distinguish PRCV serologically from TGEV, (iii) PRCV may immunize a herd against TGE.

European and U.S. researchers have reported a wide range of clinical respiratory signs in experimentally inoculated pigs. Most isolates are felt to be nonpathogenic, others mildly pathogenic. PRCV-induced experimental disease is characterized by lethargy, dyspnea, and polypnea for 3-10 days duration. Several recent isolations have been made from U.S. nursery pigs exhibiting moderate endemic respiratory disease. Increasing reports of respiratory disease in grow-finish pigs during the period of time where seroconversion to TGEV/PRCV is observed may suggest a role for PRCV in the grow-finish respiratory disease complex. Recent reports from Canada suggest that more virulent isolates may exist in the Canadian swine population.

PRCV replicates primarily in the epithelium of the upper respiratory tract and subsequently invades the bronchi and bronchiolar epithelium with extension to the peribronchiolar and alveolar regions. PRCV is shed in nasal secretions for up to 10 days. In stressed or naive pigs, PRCV may predispose pigs to other respiratory pathogens by damaging the mucociliary apparatus. Decreased pulmonary alveolar macrophage function by PRCV-infected macrophages may also play a role in decreased defense. Most pigs appear to become naturally infected at 5-8 weeks of age despite having some passive antibody protection at this time.

Gross lesions vary from no gross lesions to nearly 50% multifocal tan mottling or consolidation of the lung. Experimentally-induced gross lesions are observed from 4-10 days post inoculation. Uncomplicated cases resolve by 14 days. Microscopic lesions of bronchointerstitial pneumonia characterized by necrosis, metaplasia, and proliferation of bronchiolar epithelium and mild interstitial infiltration by mononuclear cells, mild type II pneumocyte proliferation, and the presence of alveolar exudate consisting of mixed mononuclear cells and sloughed pneumocytes. At 7-10 days post inoculation, the microscopic lesions may resemble mycoplasmal pneumonia with marked peribronchiolar lymphomacrophagic nodule formation.

Diagnosis may be difficult because disease is often subclinical. Diagnosis is based on recognition of respiratory disease in growing pigs that have high antibody titers (SVN) to TGEV but have had no clinical enteric disease or lesions of atrophic enteritis. Titers of ³ 1:512 are highly suspicious. The SN test for TGE detects, but cannot differentiate, antibodies to PRCV. After screening with the TGE SN test, positive samples can be sent to the National Veterinary Services Laboratory in Ames, Iowa where a competition blocking ELISA can be used to differentiate TGEV from PRCV antibodies. Antigen detection for PRCV can be done by FA or immunohistochemistry (IHC). Nasal swabs from acutely infected pigs are the ideal samples for virus isolation. Identification of a coronavirus, either PRCV or TGEV, can be done by polymerase chain reaction (PCR) amplification of the S gene and detection by a cDNA probe. Specific sites and sizes of deletions have been associated with virulence characteristics of PRCV and is an area of great interest and current research.

Pseudorabies Virus (PRV)

Pseudorabies virus (PRV) is in the family Herpesviridae. Clinical signs depend on the strain of PRV, the challenge dose, and the age of pig infected. Maternal antibody persists for 8-12 weeks and vaccines are quite effective so it is unusual to have clinical respiratory disease in pigs less than 8 weeks in a herd that vaccinates for PRV. Overwhelming virus challenge may overcome low maternal antibody titers in some cases. The incubation period is 3-6 days. Shedding via nasal secretions begins by 2 days and continues for 2 weeks plus. All infected pigs should be considered potential carriers due to viral latency.

Pseudorabies virus has an affinity for both nervous and respiratory systems. Young pigs are primarily affected neurologically. Nursery pigs often have both neurologic and respiratory disease. Respiratory symptoms are most common in grow-finish pigs. "Flu-like symptoms with a few CNS signs" in grow-finish pigs is a classical description. Infected pigs may exhibit lethargy, prostration, sneezing, coughing, "thumping" and nasal discharge. Outbreaks often have a 6-10 day duration if uncomplicated. Decreased weight gain in grow-finish pigs may be the only sign. PRV-infected growing pigs often are predisposed to various bacterial respiratory pathogens such as Actinobacillus pleuropneumoniae or Salmonella choleraesuis.

Gross lesions in growing pigs are often absent or overlooked. There may be fibrinonecrotic rhinitis, tonsillitis, laryngitis, tracheitis, and swollen and hemorrhagic lymph nodes of the upper respiratory tract. Suppurative and necrotic tonsils and pharynx may be observed. Patchy pulmonary hemorrhage and firm darkened areas may be observed. Microscopic lesions in growing pigs are characterized by pulmonary congestion with patchy-to-diffuse septal thickening. Multifocal necrosis and hemorrhage involving the septa and airways may be observed. Eosinophilic intranuclear inclusion bodies in focal necrotic areas may also be observed. Mild-to-severe nonsuppurative encephalitis is common.

Diagnosis of PR is based on typical clinical signs and microscopic evidence of a viral encephalitis along with multifocal necrotizing interstitial pneumonia. Antigen detection by FA of tonsil, brainstem, lung, or trachea is often successful. Virus isolation from brain, spleen, and lung is routinely done. Many serology tests (SVN, ELISA, Latex agglutination) exist for detection of PRV-induced antibodies. Interpretation may be confounded by passive antibody or vaccination.

Porcine Cytomegalovirus (PCMV/Inclusion Body Rhinitis)

Incidence and severity of porcine cytomegalovirus (PCMV)-induced disease seems to have increased dramatically in the last few years. New production schemes such as multiple site production and "mega-nurseries" supplied from multiple sow herds may have created a more susceptible population of animals. PCMV is also a member of the family Herpesviridae. Serologic evidence from the United Kingdom indicates over 90% of the herds have been exposed to infection. Infection is common but clinical disease and mortality are uncommon.

Severity of disease depends on the age and immune status of the pig, and immunity of the dam. Transmission is by aerosolized droplet or transplacental. PCMV directly invades cells of the nasal mucosa and tubulo-alveolar glands. Replication and spread can occur in macrophages throughout the body. In most pigs it is an inapparent infection. In pigs under 10 days; sneezing, thick white nasal exudate, inability to nurse, paresis, and death may occur in 4-5 days (naive herd). In pigs over 2 weeks; snuffles, mucopurulent nasal exudate, low morbidity and mortality, anemia, and stunting. PCMV may predispose pigs to colonization by B. bronchiseptica or P. multocida. A synergistic interaction of PCMV and PRRSV has been suspected in nurseries with problem rhinitis and pneumonia.

Gross lesions are characterized by mucopurulent nasal exudate that may plug the nares. Petechial hemorrhages may be observed on the kidneys. There may also be mild multifocal consolidation of the lung and interlobular edema in a naive pig. Typical large basophilic intranuclear inclusion bodies in cytomegalic cells of the tubulo-alveolar glands are observed in the turbinates. Occasionally similar inclusions are present in other organs, especially renal tubular epithelium and pulmonary endothelial cells. Atrophic rhinitis due to secondary invaders often occurs.

Diagnosis of PCMV-induced inclusion body rhinitis is based on histopathological observation of the characteristic basophilic intranuclear inclusion bodies in the tubulo-alveolar glands in the turbinates. Virus isolation is difficult and few labs attempt it at this time. More research is needed on this "old" but potentially emerging pathogen in todays production systems.

Porcine Circovirus

Post Weaning Multisystemic Wasting Syndrome (PMWS) is a recently described syndrome of nursery and early grower pigs that has become a significant problem in western Canada in the last 2 years. Sporadic cases of PMWS have been seen in Iowa as well. Clinicals signs of PMWS include wasting, dyspnea, and less often jaundice. Gross lesions included enlarged tan lymph nodes, firm lungs that fail to collapse, and sometimes enlarged waxy kidneys. PMWS is confirmed by microscopic examination of tissues. Characteristic microscopic lesions are depletion of B-cell dependent regions of lymphoid tissues and granulomatous inflammation of the lymphoid tissues, liver, lung, and a variety of other tissues. Porcine circoviral inclusion bodies (collections of viral particles) are present in lymphoid tissues. It is currently unknown whether porcine circovirus (PCV) is the primary cause of PMWS. Diagnostic tools such as immunohistochemistry and in situ hybridization are now available and have proven to be very useful in detecting PCV in field cases.

Diagnostic Workup of a Potential Viral Pneumonia Case

Fresh tissues for virus isolation and antigen detection should include; turbinate, tonsil, lung, lymph nodes, brain, heart, spleen, and pooled sera for PRRS virus isolation. Lung lavages are also useful for isolation of PRRSV from alveolar macrophages. Formalin-fixed tissues should include; turbinate, lung, tonsil, lymph nodes, brain, heart, and liver. Nasal swabs collected from 10-30 or more acutely infected pigs are the preferred sample for PRCV and SIV isolation. Paired sera should be collected from 10-30 or more pigs for SIV, TGEV, PRRSV, M. hyo., and possibly PRV serology. If several cycles of respiratory disease are observed in the production system, it may be most cost effective to submit several live pigs from different age groups throughout the system to detect and follow the introduction and progression of pathogens in the production system.

Swine Bacterial Respiratory Pathogens

Bacterial Pneumonia must be thought of in terms of management + environment + pathogens. The branch design of airways causes bacteria to impact the mucous layer in airways. Bacteria are propelled up the mucociliary apparatus or are phagocytized by macrophages or neutrophils. Virulence factors of the bacteria and dose of the inoculum determine if there will be effective clearance of the pathogens. Damage to mucociliary apparatus by viruses (SIV, PRV, PRCV) or mycoplasmas will enhance bacteria-induced respiratory disease.

Primary swine bacterial respiratory pathogens include Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae and Bordetella bronchiseptica. Opportunistic bacterial respiratory pathogens include Pasteurella multocida, Streptococcus suis, and Haemophilus parasuis. Septicemic causes of bacterial pneumonia include Salmonella choleraesuis, Actinobacillus suis, and Actinomyces pyogenes.

Actinobacillus pleuropneumoniae (APP)

APP is a small, g(-) coccobacillus. There are 12 capsular serotypes. North American seroprevalence is 60-70%, however, clinical disease is much lower. Serotypes 1, 5, and 7 are the most common in the U.S. APP is spread by direct contact or aerosol over short distances. APP recovered carriers are common. The organism resides in tonsils, necrotic lung tissue, and the nasal cavity.

There is a marked difference in virulence between serotypes and strains within serotypes. Virulence factors include a hemolysin/cytolysin (ApX) which results in characteristic necrosis and hemorrhage. LPS release results in profound endotoxemia with induction of coagulation and inflammatory pathways. The capsule of APP also inhibits phagocytosis.

Outbreaks of APP are usually precipitated by stress and are characterized by fever, lethargy, dyspnea, cyanosis, recumbency, and froth from the nose. Gross lesions are characterized by fibrinohemorrhagic pleuropneumonia that is firm, dark red, friable, necrotic and often in dorsocaudal portions. Microscopic examination reveals the presence of fibrin and neutrophils filling airways and alveoli, fibrinosuppurative pleuritis and lymphatic plugs, necrosuppurative vasculitis and thrombosis, and the presence of degenerate or "streaming" neutrophils associated with areas of necrosis and bacterial colonization. Definitive diagnosis is made by culture or direct coagglutination. Serotyping can be done by coagglutination as well. Serologic tests based on bacterial structural antigens and those based on neutralization of toxins are available. Enzyme-linked immunosorbent assay (ELISA), tube agglutination, and complement fixation tests are available depending on the laboratory used. Neutralization tests are complicated and more expensive and used mostly in research at this stage. The ELISA tests are considered to have good potential to be the serologic test of choice for APP in the future.

Mycoplasma hyopneumoniae (MH)

It has been demonstrated that 30-80% of slaughter swine have lesions of enzootic pneumonia due to MH. Mycoplasma hyopneumoniae has been demonstrated to induce a reduction in gain proportional to the size of lesion. Transmission occurs primarily through direct contact with respiratory secretions and less so by aerosolization. Chronic, sporadic, nonproductive cough, with high morbidity is very characteristic of MH. Enzootic pneumonia results when MH is combined with opportunistic bacteria (Pasteurella multocida, Bordetella bronchiseptica, Streptococcus suis, Haemophilus parasuis, Actinomyces pyogenes).

Inhalation of MH results in infection of trachea and bronchi and bronchioles. MH attaches to the cilia and surface of epithelium by adhesin proteins. There is clumping and loss of cilia, epithelial cell death, and reduced function of the mucociliary apparatus. This results in decreased clearance of normal lung secretions, inhaled particles, and pathogens. Mycoplasma hyopneumoniae also induces suppression of macrophages and the immune system.

Diagnosis of mycoplasmal pneumonia is based on observation of the characteristic chronic non-productive cough with poor performance and a spread in weights of the pigs. Gross lesions are characterized by the presence of well-demarcated, purple-to-tan, depressed areas of cranioventral lung that exude viscous fluid. Microscopic examination reveals bronchopneumonia with suppurative and histiocytic alveolitis and the presence of characteristic peribronchiolar and perivascular cuffs and nodules. Confirmation is most often by histopathological observation of characteristic lesions and antigen detection by FA examination of frozen lung sections or immunohistochemical examination of formalin-fixed lung sections. Isolation of MH can also be done if necessary but it is difficult. Serology has become more widely used since the development of the Tween 20 ELISA. CF and latex agglutination tests also are used. Seroconversion may take 4-8 weeks or more.

Bordetella bronchiseptica (Bb)

Bordetella bronchiseptica colonizes ciliated epithelium of the respiratory tract resulting in decreased mucociliary apparatus function and pneumonia. Typical gross lesions are a necrohemorrhagic pleuropneumonia in young pigs or a tan, firm bronchopneumonia in older pigs. The acute form in neonates grossly resembles APP with a cranioventral distribution. The more chronic form seen in nursery and grower pigs is very firm and tan with fibrosis. Diagnosis is by isolation of the organism from nasal swabs, trachea, or lung.

Opportunistic Bacterial Pathogens

Pasteurella multocida (PM). Most lung isolates of PM are capsular serotye A and a few are type D. PM is considered an opportunistic invader of lung that is rapidly cleared from the lungs of normal pigs. Virulence factors of PM are poorly recognized. A polysaccharide capsule helps to resist phagocytosis. The role of PM dermatonecrotoxin in pneumonia is still in question. Gross lesions typical of PM-induced pneumonia are red-grey cranioventral pneumonia with pus in airways. Focal dry, translucent pleuritis may also be observed. Lobular purulent bronchopneumonia is observed microscopically. Diagnosis is by isolation of the organism from nasal swabs, trachea, or lung.

Streptococcus suis (SS). There are 29+ capsular serotypes of Streptococcus suis. Type 2 is more commonly isolated than 1/2, 3, and then type 8. Streptococcus suis invades tonsils and reaches the lymph nodes via lymphatics. Infected monocytes may distribute the organism throughout the body and to the brain. Virulence factors are not well characterized. The capsule inhibits phagocytosis and antigens associated with virulence include muramidase-release protein (MRP) and extra-cellular factor (EF). Streptococcus suis persists in tonsils and nasal cavities of carrier pigs. Clinical signs are characterized by sudden deaths, fever, depression, dyspnea, arthritis, +/- central nervous system signs. Gross and microscopic lesions of purulent bronchopneumonia with pleuritis or polyserositis and meningitis are characteristic of SS infection. Definitive diagnosis is by isolation and serotyping of the organism.

Haemophilus parasuis (HPS). There are 15+ serotypes of HPS. Clear association of certain serotypes with virulence is still in question. Clinical signs associated with HPS include fever, depression, cyanosis, dyspnea, CNS signs, and arthritis. HPS infects the nasopharynx which is followed by entrance to blood stream via tonsils or turbinates and then septicemic dissemination. Characteristic gross and microscopic lesions are fibrinosuppurative polyserositis, arthritis, meningitis, and suppurative bronchopneumonia. Definitive diagnosis is based on characteristic lesions and isolation of HPS.

Septicemic Causes of Pneumonia

Salmonella choleraesuis (variant Kuzendorf). Clinical signs typical of salmonellosis include lethargy, fever, anorexia, cyanosis, dyspnea, cough, and yellow-brown diarrhea. Gross lesions include cyanosis, enlarged, edematous, hemorrhagic lymph nodes, splenomegaly, diffuse or cranioventral bronchointerstitial pneumonia with interlobular edema, +/- ulcerative or necrotic enterocolitis. Microscopic lesions of "paratyphoid nodules" in liver, suppurative and histiocytic interstitial pneumonia, and necrosuppurative enterocolitis are highly suggestive of salmonellosis. Salmonella choleraesuis invades the gastrointestinal mucosa and multiplies in phagocytic cells. There is dissemination of the organism via the circulation. Endotoxemia results in cytokine release, inflammation, fever, and complement fixation. Definitive diagnosis is based on observation of characteristic clinical signs and lesions and isolation of Salmonella choleraesuis from the tissues.

Actinobacillus suis (AS). Actinobacillus suis is still relatively uncommon, however, it may well be an emerging pathogen particularly in high-health status herds. Clinical signs are characterized by sudden death, fever, tachypnea, cyanosis, swollen extremeties, widespread hemorrhages, and skin lesions resembling erysipelas. AS-induced gross lung lesions of fibrinohemorrhagic pleuropneumonia can easily be confused with those of APP. Polyarthritis and polyserositis are also commonly observed with AS.

Microscopic examination reveals septic embolism, hemorrhage, and pleuropneumonia with characteristic streaming neutrophils. Definitive diagnosis is by isolation and identification of the organism from tissues.

Control Through Diagnostics, Management, Medication, and Vaccination

Cost-effective management of PRDC begins with the proper diagnosis. Diagnostic laboratories today have greatly improved the diagnostic tools such as virus isolation procedures and have adopted exciting new technologies such as immunohistochemistry, in situ hybridization, and polymerase chain reaction (PCR). With proper submissions and serological herd profiling, the cause(s) of particular respiratory disease outbreaks need not go undiagnosed. Veterinarians and producers can then make a sound decision about which pathogens are important to address and where in the production system to most appropriately do so. In some cases this may involve the sow herd, or it may involve pig flow changes, weaning age changes, ventilation modifications, pulse medication, and/or vaccination. Cross sectional necropsies and serological profiles allow for defining where in the production system to implement vaccination and medication. Fortunately, quality vaccines are available for the most important primary viral (PRRSV, SIV, PRV) and mycoplasmal pathogens which initiate and/or play a major role in most of the severe respiratory disease outbreaks today. For the long term, management strategies focused on sow herd stabilization and segregated early weaning (SEW) using multiple site production seem most appropriate. SEW is an established way to attain high health status pigs. We likely will rely on strategically administered high quality vaccines to establish uniform immunity and lessen the risk of respiratory disease outbreaks in these highly susceptible populations of pigs.

Suggested Reading

Brown IH, Done SH, Spencer YI et al.: 1993, Pathogenicity of a swine influenza H1N1 virus antigenically distinguishable from classical and European strains. Vet Rec 132:598-602.

Dea S, Bilodeau R, Sauvageau R, Montpetit C, Martineau GP: 1992, Antigenic variant of swine influenza virus causing proliferative and necrotizing pneumonia in pigs. J Vet Diagn Invest 4:380-392.

Dee SA: 1996, The porcine respiratory disease complex: Are subpopulations important? Swine Health and Production 4:147-149.

DesRosiers R: 1997, Diagnosis and control of swine respiratory diseases. In Proceedings of the American Association of Swine Practitioners pp333-344.

Galina L: 1995, Possible mechanisms of viral-bacterial interaction in swine. Swine Health and Production 3:9-14.

Halbur PG, Paul PS, Andrews JJ: 1993, Viral contributors to the porcine respiratory disease complex. In Proc Am Assoc Swine Pract pp343-350.

Halbur PG, Paul PS, Meng X-J et al.: 1996, Comparative pathogenicity of nine U.S. porcine reproductive and respiratory syndrome virus (PRRSV) isolates in a 5-week-old cesarean-derived-colostrum-deprived pig model. J Vet Diagn Invest 7:8:11-20.

Harding JCS, Clark EG. 1997, Recognizing and diagnosing Post-Weaning Multisystemic Wasting Syndrome (PMWS). Swine Health and Production 5(5):201-203.

Paul PS, Halbur PG, Vaughn EM: 1994, Significance of porcine respiratory coronavirus infection. Comp on Cont Educ for the Pract Vet 16:(9)1223-1233.

Rekik MR, Arora DJS, Dea S: 1994, Genetic variation in swine influenza virus A isolate associated with proliferative and necrotizing pneumonia in pigs. J of Clin Microbiol 32:(2)515-518.