Malignant catarrhal fever (MCF) is a sporadic, generally fatal disease caused by gammaherpesviruses in susceptible dead-end hosts. A key pathological process is systemic vasculitis in which productively infected cytotoxic T cells play a major role. Nonetheless, the pathogenesis of MCF vasculitis is not yet clear. We hypothesized that it develops due to an interaction between virus-infected cells and immune cells, and we undertook a retrospective in situ study on the rete mirabile arteries of confirmed ovine gammaherpesvirus-2 (OvHV-2)-associated MCF cases in cattle, buffalo, and bison. Our results suggest that the arteritis develops from an adventitial infiltration of inflammatory cells from the vasa vasorum, and recruitment of leukocytes from the arterial lumen that leads to a superimposed infiltration of the intima and media that can result in chronic changes including neointimal proliferation. We found macrophages and T cells to be the dominant infiltrating cells, and both could proliferate locally. Using RNA in situ hybridization and immunohistology, we showed that the process is accompanied by widespread viral infection, not only in infiltrating leukocytes but also in vascular endothelial cells, medial smooth muscle cells, and adventitial fibroblasts. Our results suggest that OvHV-2-infected T cells, monocytes, and locally proliferating macrophages contribute to the vasculitis in MCF. The initial trigger or insult that leads to leukocyte recruitment and activation is not yet known, but there is evidence that latently infected, activated endothelial cells play a role in this. Activated macrophages might then release the necessary pro-inflammatory mediators and, eventually, induce the characteristic vascular changes.
Post-mortem diagnostics are an important tool for disease diagnosis and therefore early detection of (re-)emerging animal diseases and zoonoses as well as nationwide disease surveillance programs. To counteract the decline of porcine necropsies in Switzerland over the last ten years, the Federal Food Safety and Veterinary Office (FSVO) launched a national project in 2014 called PathoPig. Post-mortem examinations of pigs from herds with health problems were financially supported by the FSVO. During the first 3 years of the project, the number of pig necropsies increased by 195% (mean). An underlying cause of disease was identified in 74% of the cases. These findings resulted in specific recommendations by the attending veterinarians or by the Swiss Porcine Health Service. A follow-up survey revealed that herd health had improved in 90% of the farms implementing the recommendations.
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