SHIC-Funded Study Examines Emerging Atypical Interstitial Pneumonia-Like Disease in Swine

Submissions to the Iowa State University Veterinary Diagnostic Laboratory have recently included a growing number of pig cases with a severe lung lesion pattern called diffuse alveolar damage (DAD), a syndrome historically rare in swine. To understand what may be driving this change, the Swine Health Information Center funded a study led by Dr. Marcelo Almeida to investigate the etiology of this emergent swine respiratory disease syndrome. A total of 42 DAD cases were reviewed by veterinarians and tested by PCR for common respiratory viruses, including PRRSV, IAV, and PCV2, and next generation sequencing to detect other viruses. While many pigs were infected with common respiratory pathogens, no single virus consistently explained the DAD lesions, suggesting that controlling PRRSV, IAV, and PCV2 through vaccination and sound herd management remains the best strategy available today to help reduce the risk of this severe lung damage in pigs. 

Find the industry summary for SHIC project #24-043 here.  

In veterinary medicine, DAD is most frequently observed as a syndrome in cattle, referred to as atypical interstitial pneumonia, which is associated with ingested pneumotoxins, epitheliotropic viral agents, and noxious gas inhalation (Doster et al., 2010; Carvello et al., 2022; Chien et al., 2022; Haydock et al., 2022). Unlike cattle, diffuse alveolar damage is poorly documented or characterized in pigs, with only rare reports of compatible lesions associated with porcine respiratory coronavirus infection and a historical association with PCV2 (Carvallo et al., 2022; Jung et al., 2007). 

In pigs with respiratory disease complex, expiratory dyspnea – often referred to as “thumping” – is caused by decreased oxygenation and lung compliance due to fluid or cellular expansion of the interstitium. This pattern of interstitial pneumonia occurs as a sequela of systemic insult due to endotoxemia and bacterial or viral infections and is most often associated with PRRSV and PCV2 infections in swine. In contrast, DAD, the focus of this study, is a lesion characterized by synchronous necrosis of respiratory pneumocytes and/or capillary endothelium that compromises diffusion of gases between the alveolar space and circulating red blood cells (Carvallo et al., 2022). 

In the absence of intensive supportive care, DAD progresses to respiratory failure and/or cardiovascular collapse and death in pigs. Surviving pigs typically face a prolonged recovery and sustained clinical signs with adverse production impacts due to the severe and often irreversible damage to lung architecture, leading to interstitial fibrosis and permanently diminished oxygenation capacity. 

The study described herein was a retrospective exploratory study investigating possible causes for an emergent syndrome in pigs presenting with lesions of DAD. The case definition for this retrospective study consisted of porcine accessions submitted to the ISU-VDL for diagnostic investigation, including fresh and fixed lung tissue, a history of severe respiratory disease, and histologic lesions consistent with DAD characterized by necrotizing and lymphohistiocytic pneumonia with hyaline membrane formation.  

Study objectives sought to 1) investigate the etiology of the emergent syndrome of severe necrotizing interstitial pneumonia with DAD in swine, and 2) determine whether the escalating frequency of this syndrome in pigs with respiratory disease complex is a function of enhanced virulence of routine viral agents, or the result of an undetected novel co-infection. In addition, a comprehensive interrogation of samples was performed with whole-genome sequencing (WGS) and in situ imaging techniques. Researchers explored genomic changes in detected viral pathogens and assessed genetic homology of endemic agents, screened tissues for previously undetected or emergent novel viral agents that may contribute to this syndrome, and further characterized the pathology of DAD to confirm in situ localization of known viral pathogens via direct detection methods (immunohistochemistry).  

Forty-two swine cases submitted to the ISU-VDL met the selection criteria and were included in this study. Most cases were diagnosed with PRRSV (71.4%), IAV (35.7%), PCV2 (16.7%), or a combination of two or three of those pathogens (26.2%). PRRSV, IAV, and PCV2 were detected within lesions consistent with those pathogens in 24 (57.1%), 13 (31.0%), and nine (21.4%) cases, respectively. However, none of those pathogens were detected in association with DAD lesions.  

NGS revealed the presence of contemporary PRRSV lineages, IAV subtypes, and PCV2 genotypes in cases associated with DAD. In addition to PRRSV, IAV, and PCV2, 17 other viruses were detected but none were consistently detected in all cases. Parvoviruses were detected in 45% of the cases, with parvovirus 2 and 7 detected in 21.4% and 19% of the cases, respectively. Researchers report that evidence to support the involvement of any of those 17 viruses in the causation of DAD is lacking.  

The literature regarding DAD in pigs is scarce and diagnostic investigations have been limited to PRRSV, IAV, PCV2, and PRV. Therefore, in this retrospective exploratory study, researchers expanded the search for other pathogens. However, the lack of specific lesions or consistency of detection for those pathogens suggests a limited role, if any, in the occurrence of DAD in pigs. 

The recent increase in cases of DAD in pigs observed at the ISU-VDL cannot be explained by the data collected and analyzed for this project; nevertheless, it confirms the involvement of the three main viral etiologies of the porcine respiratory disease complex in association with DAD lesions. It is unknown how PRRSV, IAV, and PCV2 infection results in this severe pattern of histological lesions or the cause of the sharp increase in swine cases of DAD. It is possible that cytokine storms or other immunologic events triggered by unknown factors in cases of severe disease caused by PRRSV, PCV2, and IAV induce DAD lesions; however, why and when that happens remains unclear. 

Researchers conclude that control of related viral infections (PRRSV, PCV2, IAV) through vaccination, management practices, and disease elimination, when possible, is likely the most effective way of preventing the manifestation of DAD in pigs.