Naturally occurring genetic diseases caused by de novo variants in domestic animals.

With the advent of next-generation sequencing, an increasing number of cases of de novo variants in domestic animals have been reported in scientific literature primarily associated with clinically severe phenotypes. The emergence of new variants at each generation is a crucial aspect in understanding the pathology of early-onset diseases in animals and can provide valuable insights into similar diseases in humans. With the aim of collecting deleterious de novo variants in domestic animals, we searched the scientific literature and compiled reports on 42 de novo variants in 31 genes in domestic animals. No clear disease-associated phenotype has been established in humans for three of these genes (NUMB, ANKRD28 and KCNG1). For the remaining 28 genes, a strong similarity between animal and human phenotypes was recognized from available information in OMIM and OMIA, revealing the importance of comparative studies and supporting the use of domestic animals as natural models for human diseases, in line with the One Health approach.

Comparative epidemiological study of breast cancer in humans and canine mammary tumors: insights from Portugal.

Dogs spontaneously develop mammary gland tumors (MGT) and exhibit striking similarities in clinical and epidemiological characteristics to human breast cancer (HBC). Descriptive and comparative analysis of HBC and canine MGT with a focus on evaluating similarities and geographical distribution were the aims of this study. HBC cases were obtained from North Regional Oncological Registry (RORENO) (2010-2015) and canine MGT cases from Vet-OncoNet (2019-2022). Analyses were performed based on published and well accepted classification systems (ICD-O-3.2 for humans and Vet-ICD-O-canine-1). Age-standardized incidence risks (ASIR) of Porto district municipalities were calculated using 2021 Portuguese census (INE) and data from the Portuguese animal registration system (SIAC). Among 7,674 HBC cases and 1,140 MGT cases, a similar age and sex distribution pattern was observed. Approximately 69.2% of HBC cases were between 40 and 69 years old, while 66.9% of MGT cases were diagnosed between 7 and 12 years old (mean age of 9.6 years, SD = 2.6). In women, Invasive breast carcinoma (8500/3) was the most common histological type (n = 5,679, 74%) while in dogs it was the Complex Carcinoma (8983.1/3) (n = 205, 39%). Cocker and Yorkshire Terriers exhibited the highest relative risks (3.2 and 1.6, p < 0.05, respectively) when compared to cross breed dogs. The municipalities' ASIR of the two species exhibited a high correlation (R = 0.85, p < 0.01) and the spatial cluster analysis revealed similar geographic hotspots. Also, higher ASIR values both in women and dogs were more frequently found in urbanized areas compared to rural areas. This research sheds light on the shared features and geographical correlation between HBC and canine MGT, highlighting the potential of cross-species environmental oncology studies.

A retrospective histopathological survey on canine lymphomas subtypes of Porto District.

Background: Lymphomas are dogs' most common hematopoietic neoplasms and represent a heterogeneous group, as occurs in humans. Considering the role of dogs as models of human lymphomas and the geographical correlation of the cases of canine and human lymphoma, it is important to continuously assess the epidemiological distribution of lymphoma subtypes in dogs. Aim: This study aimed to provide a survey of canine lymphoma subtypes diagnosed from 2005 to 2016 in the academic veterinary pathology laboratory of the University of Porto. Methods: A total of 75 canine lymphomas diagnosed by histopathology in the Porto district were included. All cases were immunophenotyped by CD3 and PAX5, classified according to the current classification WHO and coded with Vet-ICD-O-canine-1. Results: Mixed breed dogs were most common (28%), followed by Cocker Spaniels (12%), Boxers (9%), and Labrador Retrievers (6%). The mean age was 9.2 years (SD = 3.3) (10.7 years for small, 8.9 years for medium and large, and 5.7 years for giant breed dogs, p < 0.05). Regarding sex, there was no difference in frequencies or mean age. B-cell lymphomas were more common (57.4%) than T-cell lymphomas (37.3%), and 5.3% were classified as non-B/non-T-cell lymphomas. Of the cases, 49% had a multicentric distribution, followed by splenic (22%), cutaneous (12%), alimentary (12%), and extranodal (3%) forms. The most common B-cell subtypes were diffuse large B-cell lymphoma (DLBCL) (16.3%) and large immunoblastic lymphoma (14%), while T-zone lymphoma (21.4%) and intestinal lymphoma (18%) were the most common T-cell lymphoma subtypes. Conclusion: Our study shows that the Porto district follows the international trend of higher prevalence of B-cell lymphomas in dogs, especially of the DLBCL subtype.

Characterisation of antimicrobial usage in Danish pigs in 2020.

Introduction: Denmark is one of the world's largest exporters of pigs and pig meat, so the sector plays an important role in the national antimicrobial use (AMU). The Danish government has run antimicrobial stewardship programs in collaboration with the pig industry for more than 25 years. These have resulted in substantial overall reductions in total AMU and limiting the use of fluoroquinolones, the 3rd and 4th generation cephalosporines and the polymyxin colistin. To understand where further reductions in AMU could take place, it is necessary to investigate which antimicrobials are being used, how, and for which reasons. Materials and methods: We characterized the AMU in the Danish pig sector in 2020, providing new analytical insights based on data retrieved from the VetStat database. The AMU data were segmented into classes, routes of administration, treatment indications and age groups, and interpreted as an outcome of the interventions taken. We evaluated the current AMU regarding choice of antimicrobial class. Moreover, we discussed how to further improve the antimicrobial stewardship in Danish pig production to achieve additional reductions without jeopardizing animal welfare. Where relevant, two pig veterinary specialists were consulted. Results: In 2020, 43.3 mg antimicrobials per population correction unit (PCU) were ascribed to the Danish pig sector. There was practically no use of fluoroquinolones, 3rd and 4th generation cephalosporins and polymyxins. Weaners related to 45% of the total AMU in pigs when measured in tonnes and 81% when measured in defined animal daily doses, of these 76% were ascribed to gastrointestinal indications and overall, 83% were administered perorally. Conclusion: To enable further reductions in AMU, it should be investigated how and when to replace group treatments (e.g., all animals in section or a pen) with individual treatments. Moreover, prevention of disease and promotion of animal health should be prioritized, e.g., through focus on feed, vaccination, biosecurity, and disease eradication.

Vet-OncoNet: Malignancy Analysis of Neoplasms in Dogs and Cats.

Analysis of canine and feline tumor malignancy data can help clinicians identify high-risk patients and make more accurate decisions. Based on a sample of 16,272 cancer records, including 3266 cats and 13,006 dogs, collected from January 2019 to December 2021 in the Vet-OncoNet Network database, this study aimed to compare the tumor malignancy profile between cats and dogs, considering animal-related factors (sex, age, and breed), topography, and geographic location using a mixed-effects logistic regression model. Cats had a higher proportion of malignant tumors (78.7%) than dogs (46.2%), and the malignancy profile was very different regarding tumors' topographies. The mean age of malignant tumors occurred eight months later than benign ones (9.1, SD = 3.4; 9.8, SD = 3.2), in general. Species (OR = 3.96, 95%CI 3.57: 4.39) and topography (MOR = 4.10) were the two most important determinants of malignancy risk. Female dogs had a higher risk than male dogs (OR = 1.19, 95%CI 1.08: 1.31), which does not appear to be the case in cats (OR = 0.98, 95%CI 0.77: 1.23). Breed contributed significantly to differences in malignancy risk in dogs (MOR = 1.56), particularly in pit bulls and boxers. District of residence was not so relevant in predicting malignancy risk (MOR = 1.14). In both species, the risk of malignancy increased by approximately 20% every three years. It could be hypothesized that species differences in genetic structure may contribute to tumor malignancy.

Cross Species Analysis and Comparison of Tumors in Dogs and Cats, by Age, Sex, Topography and Main Morphologies. Data from Vet-OncoNet.

The animal cancer burden is essential for the translational value of companion animals in comparative oncology. The present work aims to describe, analyze, and compare frequencies and associations of tumors in dogs and cats based on the Animal Cancer Registry created by Vet-OncoNet. With 9079 registries, regarding 2019 and 2020, 81% (n = 7355) belonged to dogs. In comparison, cats have a general one-year right advance in the mean age of cancer diagnosis compared to dogs. The multivariate topography group analysis shows a distinct pattern between the two species: dogs have higher odds of cancer in the genito-urinary system, spleen, soft tissue tumors and skin, while cats show higher odds for tumors in the eyes, digestive organs, nasal cavity, lymph nodes, bones and mammary glands. Regarding morphologies, dogs are overrepresented in mast cell tumors (MCT), melanomas, and hemangiosarcomas. While cats are overrepresented in fibrosarcomas, lymphomas (T and B-cell), in malignant mammary tumors, and squamous cell carcinoma (SCC). Females have greater odds only in the mammary gland, with males having greater odds in six of twelve topographies. This study is the first outcome of continuous animal cancer registration studies in Portugal.

Vet-ICD-O-Canine-1, a System for Coding Canine Neoplasms Based on the Human ICD-O-3.2.

Cancer registries are fundamental tools for collecting epidemiological cancer data and developing cancer prevention and control strategies. While cancer registration is common in the human medical field, many attempts to develop animal cancer registries have been launched over time, but most have been discontinued. A pivotal aspect of cancer registration is the availability of cancer coding systems, as provided by the International Classification of Diseases for Oncology (ICD-O). Within the Global Initiative for Veterinary Cancer Surveillance (GIVCS), established to foster and coordinate animal cancer registration worldwide, a group of veterinary pathologists and epidemiologists developed a comparative coding system for canine neoplasms. Vet-ICD-O-canine-1 is compatible with the human ICD-O-3.2 and is consistent with the currently recognized classification schemes for canine tumors. It comprises 335 topography codes and 534 morphology codes. The same code as in ICD-O-3.2 was used for the majority of canine tumors showing a high level of similarity to their human counterparts (n = 408). De novo codes (n = 152) were created for specific canine tumor entities (n = 126) and topographic sites (n = 26). The Vet-ICD-O-canine-1 coding system represents a user-friendly, easily accessible, and comprehensive resource for developing a canine cancer registration system that will enable studies within the One Health space.

Vet-OncoNet: Developing a Network of Veterinary Oncology and Reporting a Pioneering Portuguese Experience.

Vet-OncoNet is a replicable tripartite animal cancer database with the scientific and academic purposes of collecting data and producing evidence-based knowledge for cancer science in general. Inspired by the One Health vision, Vet-OncoNet uses business intelligence tools to optimize the process of capturing, treating, and reporting animal cancer data to a national level in three interfaces: ACR (animal cancer registry, pathology-based), COR (clinical oncology registry, vet practice-based) and RFR (risk factor registry, owner-based). The first results show that skin and mammary gland are by far the most affected systems. Mast cell tumors and complex adenoma of the mammary gland are the most frequent histologic type in dogs, while in cats they are squamous cell carcinomas, tubular adenocarcinoma of the mammary gland and lymphomas. Regarding COR, it provides valuable information on the landscape of veterinary oncology practices, therapeutics options, outcomes and owners' drivers' adherence towards therapies, which range from 30% up to 80% upon vet practices. Furthermore, being aware of the role of animals within the family and as possible sentinels of environmental risks to cancer in humans, the network built an interface (Pet-OncoNet) dedicated to owners and a database (RFR) that receives information regarding pets and owners' daily habits.

Use of a new antimicrobial consumption monitoring system (Vet-AMNet): Application to Dutch dairy sector over a 9-year period.

Introduction: The urgency of preventing the increase of antimicrobial resistance has been emphasized by international authorities such as the World Health Organization, European Medicines Agency, and World Organization for Animal Health. Monitoring systems capable of reporting antimicrobial consumption data are regarded as a crucial pillar of this fight. The Vet-AMNet system was developed to collect and analyze national antimicrobial consumption data in Portuguese dairy farms to support the veterinary authority in stewardship actions and to assist both veterinarians and farmers in daily decisions related to antimicrobials. Methods: To evaluate the robustness of the system and other identified critical success factors, it was used to analyze antimicrobial consumption data available from the Dutch dairy cow sector over the period from 2012 to 2020. The data previously used for publications by the Netherlands Veterinary Medicines Institute (SDa) were imported and pre-processed by the Vet-AMNet system according to the SDa's standard operating procedure and the Dutch metrics to measure antimicrobial consumption were calculated. Results: By comparing the outputs with the figures generated by the system established in the Netherlands, the Portuguese system was validated. Antimicrobial consumption data from the Dutch dairy sector during the 9-year period will be presented in unpublished graphs and tables, where each molecule's pharmaceutical formulation, pharmacotherapeutic group and line of choice will be related and discussed, illustrating the evolution of sectorial antimicrobial consumption against a background of a strong national antimicrobial policy initiated by public-private cooperation and supported by legislation.

A multilevel study of the environmental determinants of swine ascariasis in England.

Ascariasis is considered a common parasitosis of swine worldwide. The disease causes significant economic losses due to its effect on feed conversion ratio and liver condemnations at slaughter (liver milk spots). This study aimed to characterise the between-farm and spatial variance in porcine ascariasis in England and to assess the association between the percentage of infected animals and potential environmental risk factors, including production system, socioeconomic deprivation, soil characteristics (pH, topsoil bulk density, topsoil organic matter, topsoil texture class, soil water regime, topsoil available water capacity, and elevation), and climatic conditions (relative humidity, air temperature, and rainfall) before slaughter. Post-mortem inspection results were provided by the Food Standards Agency and comprised information about the number of rejected livers, the number of animals sent to slaughter and the production system. All farms were georeferenced based on the postcode, which allowed the assessment of the area index of socioeconomic deprivation and the extraction of soil and climatic characteristics available in different online databases. Under a multilevel framework with adjustment for spatial autocorrelation, a standard linear mixed model was fitted to estimate the association between these determinants and the percentage of infected animals. From 2,513,973 English farmed pigs included in the study, 4.3% had their livers rejected due to milk spots. The percentage of infected pigs per batch ranged from 0% to 100%. The highest percentages were found in Surrey, East and West Sussex (8.9%) and lowest in Leicestershire, Rutland and Northamptonshire (2.0%). Significant associations were found at multivariable analysis between the proportion of infection and the number of animals sent to slaughter (ß=-0.005; 95%CI=-0.005, -0.004), soil texture (peat compared to coarse textured soils; ß=-0.516; 95%CI=-1.010, -0.063), relative humidity (ß=0.011; 95%CI=0.006, 0.015), mean temperature (ß=0.007; 95%CI=0.003, 0.012), and rainfall (ß=0.022; 95%CI=0.004, 0.037). In conclusion, our findings suggest that ascariasis can be influenced by a complex network of environmental factors. Future research needs to acknowledge these intermingled relationships to guide the development and application of control measures by the industry.

Limited Knowledge About Hydatidosis Among Farmers in Northwest Portugal: A Pressing Need for a One Health Approach.

Hydatidosis is a re-emerging disease. Farmers are a vulnerable population; however, little is known about their awareness of this disease. The purpose of this study was two-fold: (1) to assess sheep and goat farmers' awareness of, perceptions of, and attitudes towards parasitic zoonoses and hydatidosis and (2) to identify the preferred means for promotion of information about hydatidosis. A cross-sectional study was conducted. An in-person questionnaire was constructed and administered to 279 individuals. A coprological survey in shepherd dogs was performed using 88 faecal samples. SPSS version 18.0 was used for statistical analysis. Farmers reported several risk practices (69% practice home slaughtering, 46% do not deworm the dogs, 58% of these dogs have contact with other animals) and very little knowledge about hydatidosis (97% have never heard about it). Nevertheless, 75% of the farmers demonstrated interest in receiving information, mainly from a veterinarian. A wide diversity of potentially zoonotic parasites (Trichuris spp., Ancylostomatidae, Toxocara spp., Taeniidae) was found in 61% of the dogs. This survey revealed farmers' lack of knowledge in relation to hydatidosis and a high prevalence of potentially zoonotic parasites in dogs, thus pointing to the need for health education and a closer collaboration between veterinarian and public health professionals.

Prevalence of antimicrobial resistance in enteric Escherichia coli from domestic pets and assessment of associated risk markers using a generalized linear mixed model.

Antimicrobial resistance (AMR) is a growing global public health problem, which is caused by the use of antimicrobials in both human and animal medical practice. The objectives of the present cross-sectional study were as follows: (1) to determine the prevalence of resistance in Escherichia coli isolated from the feces of pets from the Porto region of Portugal against 19 antimicrobial agents and (2) to assess the individual, clinical and environmental characteristics associated with each pet as risk markers for the AMR of the E. coli isolates. From September 2009 to May 2012, rectal swabs were collected from pets selected using a systematic random procedure from the ordinary population of animals attending the Veterinary Hospital of Porto University. A total of 78 dogs and 22 cats were sampled with the objective of isolating E. coli. The animals' owners, who allowed the collection of fecal samples from their pets, answered a questionnaire to collect information about the markers that could influence the AMR of the enteric E. coli. Chromocult tryptone bile X-glucuronide agar was used for E. coli isolation, and the disk diffusion method was used to determine the antimicrobial susceptibility. The data were analyzed using a multilevel, univariable and multivariable generalized linear mixed model (GLMM). Several (49.7%) of the 396 isolates obtained in this study were multidrug-resistant. The E. coli isolates exhibited resistance to the antimicrobial agent's ampicillin (51.3%), cephalothin (46.7%), tetracycline (45.2%) and streptomycin (43.4%). Previous quinolone treatment was the main risk marker for the presence of AMR for 12 (ampicillin, cephalothin, ceftazidime, cefotaxime, nalidixic acid, ciprofloxacin, gentamicin, tetracycline, streptomycin, chloramphenicol, trimethoprim-sulfamethoxazole and aztreonam) of the 15 antimicrobials assessed. Coprophagic habits were also positively associated with an increased risk of AMR for six drugs, ampicillin, amoxicillin-clavulanic acid, cephamycin, ciprofloxacin, streptomycin, and trimethoprim-sulfamethoxazole. In summary, pets with a record of one or more previous quinolone treatments and exhibiting coprophagic habits were at an increased risk of harboring multidrug-resistant E. coli strains in their feces compared to pets without these characteristics. AMR is a serious global problem, and assessing the risk markers for the presence of drug-resistant bacteria in pets, a very close source of resistance determinants to humans, is essential for the implementation of safe handling procedures for companion animals and for the prudent selection of antimicrobial compounds in veterinary practice.

Transmission parameters estimated for Salmonella typhimurium in swine using susceptible-infectious-resistant models and a Bayesian approach.

BACKGROUND: Transmission models can aid understanding of disease dynamics and are useful in testing the efficiency of control measures. The aim of this study was to formulate an appropriate stochastic Susceptible-Infectious-Resistant/Carrier (SIR) model for Salmonella Typhimurium in pigs and thus estimate the transmission parameters between states. RESULTS: The transmission parameters were estimated using data from a longitudinal study of three Danish farrow-to-finish pig herds known to be infected. A Bayesian model framework was proposed, which comprised Binomial components for the transition from susceptible to infectious and from infectious to carrier; and a Poisson component for carrier to infectious. Cohort random effects were incorporated into these models to allow for unobserved cohort-specific variables as well as unobserved sources of transmission, thus enabling a more realistic estimation of the transmission parameters. In the case of the transition from susceptible to infectious, the cohort random effects were also time varying. The number of infectious pigs not detected by the parallel testing was treated as unknown, and the probability of non-detection was estimated using information about the sensitivity and specificity of the bacteriological and serological tests. The estimate of the transmission rate from susceptible to infectious was 0.33 [0.06, 1.52], from infectious to carrier was 0.18 [0.14, 0.23] and from carrier to infectious was 0.01 [0.0001, 0.04]. The estimate for the basic reproduction ration (R0) was 1.91 [0.78, 5.24]. The probability of non-detection was estimated to be 0.18 [0.12, 0.25]. CONCLUSIONS: The proposed framework for stochastic SIR models was successfully implemented to estimate transmission rate parameters for Salmonella Typhimurium in swine field data. R0 was 1.91, implying that there was dissemination of the infection within pigs of the same cohort. There was significant temporal-cohort variability, especially at the susceptible to infectious stage. The model adequately fitted the data, allowing for both observed and unobserved sources of uncertainty (cohort effects, diagnostic test sensitivity), so leading to more reliable estimates of transmission parameters.

Assessing risk profiles for Salmonella serotypes in breeding pig operations in Portugal using a Bayesian hierarchical model.

BACKGROUND: The EU Regulation No 2160/2003 imposes a reduction in the prevalence of Salmonella in pigs. The efficiency of control programmes for Salmonella in pigs, reported among the EU Member States, varies and definitive eradication seems very difficult. Control measures currently recommended for Salmonella are not serotype-specific. Is it possible that the risk factors for different Salmonella serotypes are different? The aim of this study was to investigate potential risk factors for two groups of Salmonella sp serotypes using pen faecal samples from breeding pig holdings representative of the Portuguese pig sector. METHODS: The data used come from the Baseline Survey for the Prevalence of Salmonella in breeding pigs in Portugal. A total of 1670 pen faecal samples from 167 herds were tested, and 170 samples were positive for Salmonella. The presence of Salmonella in each sample (outcome variable) was classified in three categories: i) no Salmonella, ii) Salmonella Typhimurium or S. Typhimurium-like strains with the antigenic formula: 1,4,5,12:i:-, , and iii) other serotypes. Along with the sample collection, a questionnaire concerning herd management and potential risk factors was utilised. The data have a "natural" hierarchical structure so a categorical multilevel analysis of the dataset was carried out using a Bayesian hierarchical model. The model was estimated using Markov Chain Monte Carlo methods, implemented in the software WinBUGS. RESULTS: The significant associations found (when compared to category "no Salmonella"), for category "serotype Typhimurium or S. Typhimurium-like strains with the antigenic formula: 1,4,5,12:i:-" were: age of breeding sows, size of the herd, number of pigs/pen and source of semen. For the category "other serotypes" the significant associations found were: control of rodents, region of the country, source of semen, breeding sector room and source of feed. CONCLUSIONS: The risk factors significantly associated with Salmonella shedding from the category "serotype Typhimurium or serotype 1,4,5,12:i:-" were more related to animal factors, whereas those associated with "other serotypes" were more related to environmental factors. Our findings suggest that different control measures could be used to control different Salmonella serotypes in breeding pigs.