Observational Study Design in Veterinary Pathology, Part 1: Study Design

Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods

Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species

Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneurnocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. coda from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology. IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunode-pleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs similar to$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.Peer reviewe

Epizootic Hemorrhagic Disease in White-Tailed Deer, Canada

Epizootic hemorrhagic disease affects wild and domestic ruminants and has recently spread northward within the United States. In September 2017, we detected epizootic hemorrhagic disease virus in wild white-tailed deer, Odocoileus virginianus, in east-central Canada. Culicoides spp. midges of the subgenus Avaritia were the most common potential vectors identified on site

Canine Alveolar Echinococcosis: An Emerging and Costly Introduced Problem in North America

Alveolar echinococcosis (AE), caused by the metacestode of Echinococcus multilocularis, is emerging in both dogs and people in North America. Here, we review 27 cases of canine AE opportunistically reported since the index case was described in 2009 in Western Canada. We describe clinical presentation, diagnosis, treatment, outcome, and source of canine infection, based on genetics of the parasite isolated from some canine cases. Diagnosis of AE was by histopathology and/or PCR on DNA extracted from metacestodes. The median age of dogs at diagnosis was 4 years (range 1–12), which is low compared to neoplasia, the most common differential diagnosis. There was no sex predilection and different breeds were involved, but there were a disproportionate number of boxers and beagles relative to their representation in the general canine population. The most common potential risk factors included contact with wildlife and visits to off leash areas. Abdominal distension was the most common clinical sign at presentation, and medical imaging generally revealed an abdominal mass. On histopathology, protoscoleces were observed in 7 out of 14 dogs. In 7 cases, DNA sequences were most similar to European (versus North American) haplotypes, identical to those recently reported in coyotes as definitive hosts in North America, and different between eastern and western North America, implying multiple introduction events. Dogs that were not treated (n = 6) had 16% survival in the first 100 days in comparison with 82% survival of treated dogs (n = 11). Direct costs to the owner of treating canine AE ranged from 1,317 to 12,655 CAD depending on the situation at the onset of treatment. This study provides important clinical, epidemiological, and economic information for veterinary practitioners and regulators for importation of dogs, and for public health, as dogs with AE may serve as indicators of parasite range expansion and risk to humans.Peer Reviewe

An integrative and multi-indicator approach for wildlife health applied to an endangered caribou herd

Abstract Assessing wildlife health in remote regions requires a multi-faceted approach, which commonly involves convenient samplings and the need of identifying and targeting relevant and informative indicators. We applied a novel wildlife health framework and critically assessed the value of different indicators for understanding the health status and trends of an endangered tundra caribou population. Samples and data from the Dolphin and Union caribou herd were obtained between 2015 and 2021, from community-based surveillance programs and from captured animals. We documented and categorized indicators into health determinants (infectious diseases and trace elements), processes (cortisol, pathology), and health outcomes (pregnancy and body condition). During a recent period of steep population decline, our results indicated a relatively good body condition and pregnancy rates, and decreasing levels of stress, along with a low adult cow survival. We detected multiple factors as potential contributors to the reduced survival, including Brucella suis biovar 4, Erysipelothrix rhusiopathiae and lower hair trace minerals. These results remark the need of targeted studies to improve detection and investigations on caribou mortalities. We also identified differences in health indicators between captured and hunter sampled caribou, highlighting the importance of accounting for sampling biases. This integrative approach that drew on multiple data sources has provided unprecedented knowledge on the health in this herd and highlights the value of documenting individual animal health to understand causes of wildlife declines