JPC SYSTEMIC PATHOLOGY
RESPIRATORY SYSTEM
October 2023
P-V25
Signalment (JPC #92-21908): Piglet.
HISTORY: This one-week-old crossbred piglet was from a litter that was born weak and within a few days exhibited respiratory distress (“thumping”). The producer had farrowed six sows thus far in this grouping, and all six had litters with the above problems. Most sows would eventually have one or two survivors per litter.
HISTOPATHOLOGIC DESCRIPTION: Lung: Diffusely alveolar septa are expanded up to 10X normal by numerous macrophages, lymphocytes, fewer viable and necrotic neutrophils and plasma cells, fibrin, and edema. Multifocally, alveolar lumina are variably filled and expanded by an exudate composed of previously described inflammatory cells, necrotic cellular debris, fibrin, and edema that minimally extends into adjacent terminal bronchiolar lumina. Multifocally affecting alveolar septa, there is necrosis and loss of type I pneumocytes with replacement by cuboidal pneumocytes (type II pneumocyte hyperplasia). Interlobular septa and perivascular connective tissue are mildly expanded by edema, fibrin, and few macrophages, lymphocytes, and plasma cells.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, lymphohistiocytic, diffuse, subacute, moderate, with type II pneumocyte hyperplasia, crossbreed, porcine.
ETIOLOGIC DIAGNOSIS: Arteriviral pneumonia
CAUSE: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)
CONDITION: Porcine Reproductive and Respiratory Syndrome
SYNONYMS: Swine infertility and abortion syndrome; Porcine epidemic abortion and respiratory syndrome; Blue ear disease
GENERAL DISCUSSION:
- Positive-sense, single-stranded, enveloped RNA virus in the family Arteriviridae that causes a syndrome of late-term reproductive failure and interstitial pneumonia in pigs
- May persist and circulate within the herd indefinitely
- Two predominant genotypes, type 1 mainly in Europe and type 2 in North America; type 2 isolates reported to be more virulent
- Highly pathogenic PRRS has emerged and now endemic in Asia (type 2)
- Genome has 8 open reading frames (ORF)
- ORFs 1a, 1b: Encode RNA replicase required for virus replication
- ORFs 2-4 encode structural proteins with unknown functions
- ORF 5: GP5 envelope protein is also involved in receptor recognition and induces apoptosis
- ORF 6: M envelope protein is important in virus assembly, budding and infectivity; complexes with gene product 5 of ORF 5 (GP5) to contribute to attachment to heparin-like receptors on porcine alveolar marcrophages
- ORF 7: N protein plays a role in assembly of infectious particles; its abundant expression makes it a good target for diagnostic assays
- Genomic variability: High mutation rate due to error-prone RNA polymerase and frequent recombination
- Major primary pathogen in the porcine respiratory disease complex (PRDC); secondary bacterial infections are common
- Includes PRRSV, swine influenza A, porcine circovirus 2, Pasturella multocida, and Mycoplasma hyopneumoniae
- PRRSV and porcine circovirus-2 are implicated in porcine dermatitis and nephropathy syndrome (I-M33), a fatal disease characterized by vasculitis in the skin and kidneys and other organs
- Opportunistic infections common: Pneumocystis carinii sp.f. suis, Strep. suis, Salmonella Cholerasuis, Glaesserella parasuis (plus Pasteurella multocida and Mycoplasama hyopneumoniae)
PATHOGENESIS:
- Transmission is by direct contact, ingestion, inhalation, coitus, bite wounds, and transplacentally during last trimester of pregnancy
- Feedstuffs may harbor virus and are a potential way to introduce virus on a farm
- Vaccine derived strains may also cause disease
- Virus has tropism for nasal, tonsillar, or pulmonary macrophages with resultant spread to regional lymph nodes, viremia, and systemic spread via macrophages
- Infection of monocyte-macrophage system cells may be determined by ligand-receptor interactions and presence of sialoadhesin glycoprotein (macrophage-specific receptor)
- Lesions and disease are due to apoptosis of infected macrophages and adjacent non-infected macrophages and lymphocytes and induction of cytokines; apoptosis due to GP5 and substances released from infected macrophages (p25, cytokines, reactive oxygen species, nitric oxide)
- Destruction of macrophages and damage to mucociliary apparatus make host susceptible to other infections
- Surviving pigs can develop chronic persistent infection that is the most significant epidemiologic feature of PRRSV infection
- Mycoplasma hyopneumoniae may exacerbate disease due to macrophage proliferation and activation, enhancing the replication and persistence of PRRSV
- Highly virulent strains have different replication capacity within tissues and higher levels of inflammatory cytokines which may lead to more severe lesions and systemic disease
- PRRSV infection may alter angiogenesis in submucosal tissues at maternal-fetal interface
- Resistance to fetal infection may be related to homeostasis of angiogenesis in the endometrium
TYPICAL CLINICAL FINDINGS:
- Litters will contain variable numbers of normal, weak, or dead piglets that may be stillborn, autolytic, or partially/completely mummified with a hemorrhagic umbilical cord
- High preweaning mortality; young growing pigs most likely to show clinical signs: sneezing, fever, listlessness, anorexia/emaciation, splayleg, cough, dyspnea (thumps), and chemosis
- Some piglets develop cyanosis on the ears or abdomen (i.e., “blue ear disease”)
TYPICAL GROSS FINDINGS:
- Post-natal:
- The most consistent gross lesion is markedly enlarged tan lymph nodes throughout the body, most notably the bronchial, mediastinal, cervical, and inguinal are tan white and solid
- Lungs are diffusely mottled tan and red, and fail to collapse (interstitial pneumonia), often with rib impressions; parenchyma is resilient, firm (resembling texture of thymus), and moist
- Secondary bacterial infections: lesions of cranioventral consolidation superimposed on diffuse interstitial pneumonia
- Gross lesions are not evident in boars, sows, and usually aborted fetuses; most severe lesions in younger age groups
- Fetal lesions:
- The most consistent fetal lesion is segmental to diffuse umbilical cord hemorrhage; perirenal and colonic mesenteric edema is common
- Live, stillborn, and mummified fetuses may be born in same litter
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Moderate to severe multifocal interstitial pneumonia with type II pneumocyte hyperplasia, septal infiltration by mononuclear cells, and accumulation of necrotic macrophages and alveolar exudate; +/- vasculitis
- Presence of aggregates of free chromatin and necrotic alveolar macrophages is highly suggestive of PRRSV infection
- Secondary bronchopneumonia is common (PRRSV does not directly affect bronchiole epithelium)
- Generalized lymphadenopathy: Lymphoid tissues are reactive with marked follicular and paracortical hyperplasia and/ or apoptotic lymphocytes
- Perivascular infiltrates of multiple organs: Nasal mucosa, heart, kidney, and brain most commonly
- Other lesions include lymphocytic infiltrates in multiple organs, including lymphoplasmacytic rhinitis, myocarditis, endometritis and myometritis, and lymphohistiocytic meningoencephalitis and choroiditis, characterized by perivascular cuffs, vasculitis, gliosis and glial nodules
- Vasculitis, fibrin thrombi, and rarely fibrinoid necrosis may occur in any organ
- Aborted fetus: Segmental hemorrhagic enlargement of umbilical cord caused by segmental necrosuppurative lymphohistiocytic vasculitis
ULTRASTRUCTURAL FINDINGS:
- Virions are enveloped viral particles 45-65nm in diameter with a smooth surface and a central isometric core about 25-30nm in diameter
- Budding of viral particles is through intracytoplasmic membranes
- Intracytoplasmic enveloped viral particles accumulate in cytoplasmic vesicles
ADDITIONAL DIAGNOSTIC TESTS:
- PCR and IHC are mainstays for diagnosis
- PCR àTissue (e.g. docked tails), processing fluids (serosanguinous exudate from tail docking and castration), serum, oral fluids, or semen
- Subsequent molecular analysis to differentiate field versus vaccine strains
- Pooled or aggregated samples used to monitor herd prevalence
- IFA
- Virus Isolation
- ELISA à Useful to determine prior exposure in unvaccinated herds
DIFFERENTIAL DIAGNOSIS:
- Porcine Respiratory Disease Complex is often due to synergy of both viral and bacterial pathogens
- Respiratory Viruses:
- Postweaning Multisystemic Wasting Syndrome (H-V11, Porcine circovirus 2): Granulomatous to lymphohistiocytic interstitial pneumonia with BALT depletion, with or without intracytoplasmic inclusion bodies and bronchiolar epithelial necrosis
- Swine Influenza virus (P-V18, Orthomyxovirus): Acute necrotizing bronchitis/bronchiolitis
- Porcine respiratory coronavirus
- Pseudorabies virus (E-V01, N-V07): Diffuse lymphohistiocytic interstitial pneumonia with coagulative necrosis, necrotizing bronchitis, and intranuclear inclusion bodies
- Proliferative and necrotizing pneumonia; cause may be multifactorial
- Respiratory Bacteria:
- Mycoplasma hyopneumoniae (P-B03): Lymphoplasmacytic bronchointerstitial pneumonia with hyperplasia of bronchus associated lymphoid tissue
- Actinobacillus pleuropneumoniae (P-B04): Severe fibrinous and necrotizing pleuropneumonia with oat cells and numerous intralesional bacteria
- Actinobacillus suis: Severe fibrinous and necrotizing pleuropneumonia with oat cells and numerous intralesional bacteria
- Haemophilus parasuis, Mycoplasma hyorhinus, and Streptococcus suis: Severe suppurative bronchopneumonia with fibrinopurulent pleuritis/polyserositis
- Pasteurella multocida: Suppurative bronchopneumonia usually without pleuritis
- Salmonella cholerasuis: Thrombosis and vasculitis; septal infiltrate; alveolar exudate, fibrinous inflammation
COMPARATIVE PATHOLOGY:
Other Arteriviruses of veterinary importance:
- Equine arterivirus (equine viral arteritis) - targets macrophages, endothelium and mesothelium in many tissues; lesions include congestion, edema and hemorrhage in many tissues; up to 80% of mares may abort (abortion storms) often without premonitory clinical signs
- Simian hemorrhagic fever virus (H-V04) - causes a highly contagious fatal disease of rhesus macaques characterized by bleeding diathesis, extensive congestion, hemorrhage, and necrosis; distinguished from Ebola viruses by absence of hepatic/adrenal necrosis and absence of typical filoviral intracytoplasmic inclusions
- Lactate Dehydrogenase-elevating virus (LDV) - arterivirus of mice with tropism for macrophages and neural tissue; no clinical signs or other than elevations of LDH enzyme due to reduced clearance of the enzyme by the monocyte-macrophage system
- Frequent contaminant of murine transplantable tumors
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