The Intriguing Pathology of Infectious Diseases

This special issue seeks to blend the border between pathology and microbiology, exploring recent developments in the understanding and recognition of infectious diseases of domestic animals. The pathology and pathogenesis of animal infectious diseases is a fascinating world, and veterinary pathologists encounter the breadth of these conditions in the course of their routine activities. Pathogens of domestic animals are important: they lead to suffering and death, are responsible for lost production and performance, underlie the widespread use of antibiotics in veterinary medicine, and cause disease in humans. Pathology is a key tool in the diagnosis, understanding, and control of these diseases. From a more selfish perspective, the lesions and pathogenesis of infectious diseases hold an intrinsic fascination and were a defining motivation for many of us to have focused our careers on veterinary pathology or veterinary infectious diseases. That moment on the microscope when we notice syncytia and intracytoplasmic inclusions in a calf’s lung arouses our natural curiosity of how bovine respiratory syncytial virus incites these lesions and how these lesions incite clinical disease. ¹⁶ Seeing is not only believing but also a stimulus for further exploration.

The evolutionary adaptations of microbes to their hosts, and of hosts to their microbes, have created a spectacular diversity of disease mechanisms. Fact really is better than fiction. Who could have dreamt a story of a virus that infects a fetus before its immune system develops, allowing persistence of the infection and then viral mutation to a form that kills the host (bovine viral diarrhea virus and mucosal disease)? ¹ Or a bacterium that triggers widespread cancer-like proliferation of epithelial cells in the intestine by mechanisms that still await discovery (Lawsonia intracellularis and porcine adenomatosis)? ¹⁷ Or the ways that multiple pathogens, environmental influences, and host factors converge to precipitate disease from a highly host-adapted opportunist that cannot quite cause disease on its own (Mannheimia haemolytica)? ³ Or a parasite that corrupts our methods of detecting and eradicating bovine tuberculosis (Fasciola hepatica)? ⁶ Or a bacterium that rarely causes illness unless a disease-causing superantigen in its plasmid is activated by enrofloxacin, thus triggering bacterial disease by the very drug that was intended to cure (Streptococcus canis)? ⁸ Or germ warfare as an evolutionary strategy, where otherwise-placid sheep carry a virus that does them no harm but causes fatal disease in neighboring species with which they compete for resources (ovine herpesvirus 2 and malignant catarrhal fever)? ¹³ The stories written by animal pathogens and their hosts are unmatched in modern literature.

See the lesions and understand the disease. Understanding morphology is a basis for veterinary education and reveals pathogenesis. ^10,11 Nonetheless, morphologic changes do not reveal the full picture of how or why disease develops. Conversely, data generated by the “omics” technologies, while exciting and rewarding, can remain meaningless without a solid understanding of underlying morphological changes. Molecular methods and proteomics are now well-established tools for uncovering disease mechanisms and for diagnosis; examples of their use are included in this issue. ^2,4 Many bacterial pathogens appear to have eschewed the hard evolutionary work of developing new virulence factors and instead have acquired the necessary genes from other organisms. The recognition of these mobile genetic elements is changing our thinking of how bacteria evolve as pathogens, and the virulence factors they encode have a major impact on how these pathogens cause disease. ⁷

Research and diagnostic investigation are making real progress in understanding and controlling infectious diseases of animals. Perhaps the most striking example is postweaning multisystemic wasting syndrome of swine. Its first recognition—only 20 years ago—led directly to identification of a novel pathogen, the difficult work of proving causality for a disease that scorns Koch’s postulates, the unexpected role of immunostimulation in its pathogenesis, and finally the development of a vaccine with remarkable effect on this formerly widespread and devastating disease. ⁵ Other examples have less economic impact but are nonetheless startling. AA amyloidosis has for over a century been considered secondary to inflammation, where fragments of inflammation-induced host proteins deposit and persist in tissue. The recent findings that AA amyloid particles may be transmissible shakes our comfortable understanding of this disease, suggesting novel ways to control its occurrence in susceptible populations but also raising the specter of a new threat to humans from consumption of amyloid fibrils in meat. ¹²

As old infectious diseases are controlled, new ones emerge. Investigators who study previously ignored animal populations usually find something novel, and investigations of animal shelters have revealed a rich diversity of new or emerging pathogens: canine circovirus, hypervirulent feline calicivirus, canine respiratory coronavirus, and Streptococcus zooepidemicus. ^14,15 The emerging role of equine herpesvirus 5 in equine multinodular pulmonary fibrosis affects not only our understanding of this pathologically satisfying disease but other important and enigmatic fibrotic lung diseases that afflict humans and other animals. ¹⁸ And no story of veterinary infectious disease would be complete without a mind to swine influenza virus, for which unprecedented levels of gene trading create looming threats to both swine production and public health. ⁹ Infectious diseases of animals are changing, both in the nature of the diseases and how we understand them, and this special issue tells a few of their stories of relevance to veterinary pathology.