Browsing by Author "Barkema, Herman W."
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Item Open Access Age and Dose Dependent Susceptibility to Mycobacterium avium subspecies paratuberculosis Infection in Dairy Calves(2014-08-15) Mortier, Rienske Alice Rosa; De Buck, Jeroen; Barkema, Herman W.Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne’s disease (JD), a chronic enteritis in ruminants. Control programs focus on prevention of infection of susceptible individuals: calves < 6 months of age. However, this age-cut-off for susceptibility is not well supported scientifically. Additionally, control programs struggle with low sensitivity of diagnostic tests in the early stages of JD. The main objective of this thesis was to determine age-dependent susceptibility in dairy calves. Additionally, the course of immune responses as well as fecal shedding was assessed. Furthermore, gross lesions, histology and MAP-culture from tissues were used to confirm infection status of each calf, and to investigate age-dependent susceptibility. Fifty calves were inoculated per os on 2 consecutive days at 2 weeks and 3, 6, 9, or 12 months. Within each age group calves received either a high (5 x 109 CFU) or low dose (5 x 107 CFU) of MAP. Six calves served as a negative control group. Serum, whole blood and fecal samples were collected regularly until necropsy at 17 months of age. Macroscopic and histological lesions were assessed and bacterial culture was performed on tissue samples. Calves were successfully infected with MAP up to 1 year of age even with a low dose of MAP. Calves inoculated at 2 weeks, 3, or 6 months of age with a high dose of MAP had more severe necropsy lesions, were shedding MAP in feces more frequently, and had a stronger humoral and cellular immune response, than calves inoculated with a low dose. Shedding and humoral immune responses differed between individual calves and were detected in about half of the calves, which was more than anticipated. A dose-dependent cellular immune response was detected in each inoculated calf soon after inoculation using an interferon-gamma release assay and is therefore a good candidate test for early diagnosis. To conclude, calves are susceptible to MAP infection up to 1 year of age and could be infectious to other calves. Keeping the infection pressure low on-farm could reduce the severity of JD. Early diagnosis of MAP-infection is possible and this could improve the potential to control JD on-farm.Item Open Access Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019–June 2021)(2022-03-07) Kariyawasam, Ruwandi M.; Julien, Danielle A.; Jelinski, Dana C.; Larose, Samantha L.; Rennert-May, Elissa; Conly, John M.; Dingle, Tanis C.; Chen, Justin Z.; Tyrrell, Gregory J.; Ronksley, Paul E.; Barkema, Herman W.Abstract Background Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). Objectives We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. Methods We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. Results Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8–40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1–0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. Conclusions During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.Item Open Access Antimicrobial resistance: Prevalence, genetics and associations with antimicrobial use in food-producing animals(2020-07-27) Borin Nobrega, Diego; Barkema, Herman W.; De Buck, Jeroen M.; Deardon, Rob; Dufour, Simon; Saini, VineetAntimicrobial use (AMU) in livestock has come under growing criticism. There is increasing pressure to optimize AMU in food-producing animals, which will likely entail restrictions and voluntary reductions of their use, as well as implementation of protocols promoting antimicrobial stewardship. In this thesis, 1) methods were compared for obtaining AMU data on dairy farms, 2) factors associated with the prevalence of antimicrobial resistance (AMR) in non-aureus staphylococci (NAS) isolated from intramammary infections were studied, 3) treatment strategies for non-severe clinical mastitis (CM) in dairy cattle were contrasted, and 4) effects of restricted antimicrobial use in food-producing animals towards the prevalence of AMR genes (ARGs) were evaluated. Chapter 2 confirmed that treatment records accurately quantified AMU in well-managed dairy herds. Yet, their widespread adoption into AMU surveillance cannot be recommended, due to an underestimation of AMU in herds with elevated bulk tank somatic cell count. In regard to AMR, Chapter 3 demonstrated that resistance against tetracycline, penicillin and erythromycin in NAS was common in Canadian dairy herds. In Chapter 4, factors associated with AMR were further explored. An association between AMR in NAS and AMU was present when penicillins, 3rd-generation cephalosporins or macrolides were administered systemically, whereas intramammary use of antimicrobials were not associated with AMR. As antimicrobials classified as critically important antimicrobials (CIAs) for humans were associated with AMR, in Chapter 5 a systematic review was done to assess whether CIAs and non-CIAs had comparable efficacy to treat non-severe bovine CM caused by the most prevalent bacteria causing mastitis worldwide. No protocol including the use of CIAs had superior bacteriological cure rates of non-severe CM than protocols relying on non-CIAs. Therefore, no adverse effects in terms of animal health should be expected by ceasing use of CIAs for treating non-severe CM in dairy herds. A second systematic review showed that restricted AMU in food animals was associated with a lower presence of ARGs in bacteria isolated from animals and humans. Reducing use of CIAs to treat non-severe CM in typical dairy herds may reduce load of ARGs without significant impacts on animal health and welfare.Item Open Access Antimicrobial Stewardship: A One Health approach with a focus on antimicrobial reduction in dairy cattle(2023-05-01) McCubbin, Kayley Dawn; Barkema, Herman W.; Orsel, Karin; Sanchez, Javier; Kelton, David Francis; Kastelic, John PatrickAntimicrobial resistance (AMR) is considered one of the greatest threats facing humanity. Without intervention, AMR impacts are expected to be substantial, compromising human, animal, environmental health. The complex interplay of contributing factors highlights the need for a One Health approach in AMR mitigation. Improving antimicrobial stewardship (AMS) is an integral component of AMR mitigation success. Therefore, thesis objectives included: 1) describe the current state of AMR knowledge in Canada available in the literature, and identify the gaps in our understanding; 2) identify perspectives of AMS, including perceived drivers and barriers across the One Health spectrum of relevant Canadian professionals; 3) focus on the dairy industry as an example where AMS efforts are possible through selective dry cow therapy (SDCT); and 4) describe current SDCT uptake and related practices in the Canadian dairy industry. Current limitations in the understanding of AMR in Canada are described through a comprehensive review focussed on: 1) treatment optimization; 2) surveillance of antimicrobial use (AMU) and AMR; and 3) prevention of transmission of AMR. Whereas identified barriers to AMS described by Canadian professionals included: 1) lack of various prescribing and AMU support mechanisms; 2) shift in prescriber attitudes to drive change; and 3) stronger economic considerations to support shifting prescribing practices. Only treating cows who could benefit from antimicrobials at drying off (i.e., SDCT), represents an opportunity to reduce AMU in the dairy industry. A narrative review was conducted summarizing available literature regarding impacts of SDCT on udder health, milk production, economics, AMU motivations, and AMR. An observational study was conducted utilizing 2 in-person questionnaires between July 2019 and September 2021 on 144 dairy farms in 5 Canadian provinces. Overall, 31% reported adopting SDCT, with approximately 50% less intramammary AMU at drying off compared to treating all cows. A slight majority of farms (56%) applied teat sealants (TS) to all cows at drying off, whereas 12% used TS selectively, and 32% did not use TS. Results highlighted the variability in antimicrobial and TS use protocols at drying off on Canadian dairy farms, and the potential for further AMU reduction with increased SDCT adoption.Item Open Access Associations of the COVID-19 pandemic with the reported incidence of important endemic infectious disease agents and syndromes in Pakistan(2022-11-26) Missaghi, Bayan; Malik, Muhammad W.; Shaukat, Waseem; Ranjha, Muazam A.; Ikram, Aamer; Barkema, Herman W.Abstract Background Persons in Pakistan have suffered from various infectious diseases over the years, each impacted by various factors including climate change, seasonality, geopolitics, and resource availability. The COVID-19 pandemic is another complicating factor, with changes in the reported incidence of endemic infectious diseases and related syndromes under surveillance. Methods We assessed the monthly incidence of eight important infectious diseases/syndromes: acute upper respiratory infection (AURI), viral hepatitis, malaria, pneumonia, diarrhea, typhoid fever, measles, and neonatal tetanus (NNT), before and after the onset of the COVID-19 pandemic. Administrative health data of monthly reported cases of these diseases/syndromes from all five provinces/regions of Pakistan for a 3-year interval (March 2018–February 2021) were analyzed using an interrupted time series approach. Reported monthly incidence for each infectious disease agent or syndrome and COVID-19 were subjected to time series visualization. Spearman’s rank correlation coefficient between each infectious disease/syndrome and COVID-19 was calculated and median case numbers of each disease before and after the onset of the COVID-19 pandemic were compared using a Wilcoxon signed-rank test. Subsequently, a generalized linear negative binomial regression model was developed to determine the association between reported cases of each disease and COVID-19. Results In late February 2020, concurrent with the start of COVID-19, in all provinces, there were decreases in the reported incidence of the following diseases: AURI, pneumonia, hepatitis, diarrhea, typhoid, and measles. In contrast, the incidence of COVID was negatively associated with the reported incidence of NNT only in Punjab and Sindh, but not in Khyber Pakhtunkhwa (KPK), Balochistan, or Azad Jammu & Kashmir (AJK) & Gilgit Baltistan (GB). Similarly, COVID-19 was associated with a lowered incidence of malaria in Punjab, Sindh, and AJK & GB, but not in KPK and Balochistan. Conclusions COVID-19 was associated with a decreased reported incidence of most infectious diseases/syndromes studied in most provinces of Pakistan. However, exceptions included NNT in KPK, Balochistan and AJK & GB, and malaria in KPK and Balochistan. This general trend was attributed to a combination of resource diversion, misdiagnosis, misclassification, misinformation, and seasonal patterns of each disease.Item Open Access Bacteriocins of bovine non-aureus staphylococci(2017) Carson, Domonique; Barkema, Herman W.; De Buck, Jeroen; Orsel, Karsina; Cobo, EduardoThe non-aureus staphylococci (NAS) species are among the most prevalent isolated from bovine milk and have been reported to inhibit major mastitis pathogens, likely by producing bacteriocins. This thesis is comprised of two sections, focusing on in vitro inhibition assays and in silico identification of bacteriocin gene clusters and bacteriocin resistance genes in NAS and Staphylococcus aureus, using isolates obtained from the Canadian Bovine Mastitis and Milk Quality Research Network. The first part determined the inhibitory capability of 441 bovine NAS isolates (comprising 25 species) against bovine S. aureus and human methicillin-resistant S. aureus (MRSA) and determined the presence of bacteriocin biosynthetic gene clusters in NAS whole genomes. Overall, 40 isolates from 9 species (S. capitis, S. chromogenes, S. epidermidis, S. pasteuri, S. saprophyticus, S. sciuri, S. simulans, S. warneri, and S. xylosus) inhibited growth of S. aureus in vitro; of which, 23 isolates (from S. capitis, S. chromogenes, S. epidermidis, S. pasteuri, S. simulans, and S. xylosus) also inhibited MRSA. 105 putative bacteriocin gene clusters encompassing 6 different subclasses (lanthipeptides, sactipeptides, lasso peptides, class IIa, class IIc, and class IId) in 95 whole genomes from 16 species were identified. The second part of the thesis determined the susceptibility of 139 bovine S. aureus isolates to a bacteriocin producing S. chromogenes isolate and identified and described the distribution of genes potentially associated with susceptibility and resistance in S. aureus whole genomes. Overall, 90 S. aureus isolates (65%) were resistant to inhibition by the S. chromogenes isolate. We identified 77 genes that were associated with an isolate being resistant. We also identified 76 genes that were associated with an isolate being susceptible to the S. chromogenes. Bacteriocin susceptibility and resistance seems to be linked to a large number of genes, the majority of which are annotated as hypothetical proteins and will need further assessment to determine their role in S. aureus susceptibility. Overall, bacteriocins may be a potential source of novel antimicrobials and this thesis represents the foundation to explore novel NAS bacteriocins.Item Open Access Big data and machine learning tools to understand mastitis epidemiology and other topics(2021-11) Naqvi, Syed Ali; Barkema, Herman W.; Deardon, Rob; Williamson, Tyler; Dufour, SimonIncreased availability of technologies to collect and store individual health data is leading to a growing interest in applying Big Data analytical methodologies to better understand health and disease in both humans and dairy cattle. Data collected through routine observations such as doctor or veterinary visits, milking equipment, or remote sensors can be successfully incorporated to monitor and manage individual and public health, and support operational decision-making on dairy farms. These sources of data also provide an invaluable resource in conducting epidemiological and health research, provided they are appropriately handled during the statistical analysis. In this thesis, 1) data from bacteriological sampling were combined with regularly collected dairy herd improvement (DHI) data to describe udder health in primiparous dairy cattle across Canada; 2) a systematic review and meta-analysis was conducted to synthesize all available research on the effectiveness of pre-calving therapies to improve udder health in primiparous dairy cattle; 3) a model was developed for the detection of clinical mastitis (CM) based on routinely collected data from automated milking systems (AMS); 4) a simulation study assessed the impact of unmeasured heterogeneity in secondary data collected from multiple dairy farms on the performance of a model trained to detect CM onset; 5) the immune fingerprint of children presenting with symptoms of appendicitis are compared by combining emergency department admissions data with results from a multiplex cytokine assay and 6) dietary risk factors for immunological flare-ups in patients with Crohn’s disease are explored by combining patient-reported dietary records with results of a multiplex cytokine assay. Chapter 2 demonstrated that the udder health in Canadian primiparous dairy cows was an issue that needed attention, and chapter 3 demonstrated that pre-calving treatments of different types can be effective at improving udder health in early lactation. Both chapters highlighted the need for routinely collected data to be combined with targeted data collection (monitoring of non-milking dairy cows, culture-based treatment selection) to facilitate targeted management for different parts of a dairy herd. In chapter 5, a deep recurrent neural network (RNN) model was used to detect the onset of CM using regularly collected data from AMS, and chapter 6 demonstrated that predictive performance of deep RNNs is robust to the unmeasured heterogeneity in data collected from multiple farms. Chapter 6 describes how immune response differs between children with abdominal pain symptomatic of appendicitis and provides evidence that data from a multiplex immunoassay conducted on admission may be used to effectively predict disease outcomes. In chapter 7, a similar multiplex immunoassay is used to explore associations between inflammation and diet using food records from patients with Crohn’s disease and demonstrates some of the statistical challenges encountered when working with multiple outcomes and large numbers of explanatory variables.Item Open Access Biosocial Complexities of Antimicrobial Use in Dairy Farming in Alberta, Canada(2020-07-24) Ida, Jennifer A.; Barkema, Herman W.; Wilson, Warren M.; Gerlach, S. Craig; Adams, Cindy L.; Kutz, Susan J.Antimicrobial resistance (AMR), or the ability of a microbe to withstand treatment with antibiotics, is an emerging health issue that has been largely attributed to the inappropriate use of antimicrobial treatments. Many of the current research and policy initiatives focus on knowledge translation and behavioral change mechanisms as ways to achieve absolute reductions in antimicrobial use across all health sectors. However, the current approach fails to address underlying drivers of practice and is narrowly focused on achieving a numeric goal. Given the failure to understand the underlying drivers of decisions made by dairy farmers concerning antimicrobial use (AMU), this study sought to understand one community’s perceptions surrounding AMU, AMR, and regulation in the dairy farming industry in Alberta via the use of ethnography. Specifically, this included participation in on-farm activities (i.e., milking) and observations of relevant interactions (i.e., herd health exams) on dairy farms in Central Alberta for a period of 3.5 months. Interviews were conducted with 25 dairy farmers. Nine of these interviews were analyzed using thematic analysis. Thematic analyses resulted in four key takeaways. Farmers: 1) feel that AMU policies implemented in other contexts are impractical and are concerned that such policies, if implemented in Alberta, would constrain their freedom to make what they perceive to be the best decisions about AMU for their animals; 2) believe that their first-hand knowledge is undervalued by both consumers and policy-makers; 3) do not believe that the public trusts them to make the correct AMU choices and, consequently, worry that AMU policy will be guided by what they believe are misguided consumer concerns; 4) farmers are skeptical of a link between AMU in livestock and AMR in humans. Based on these findings, a better understanding of the sociocultural and political-economic infrastructure that supports such perceptions is warranted and should inform future policy.Item Open Access Characteristics of Escherichia coli Isolated from Bovine Mastitis Exposed to Subminimum Inhibitory Concentrations of Cefalotin or Ceftazidime(2018-11-01) Liu, Gang; Ding, Laidi; Han, Bo; Piepers, Sofie; Naqvi, S. Ali; Barkema, Herman W.; Ali, Tariq; De Vliegher, Sarne; Xu, Siyu; Gao, JianEscherichia coli is a major udder pathogen causing clinical mastitis in dairy cattle and its heat stable endotoxin in powdered infant formula milk is a potential risk factor in neonatal infections. Cephalosporins are frequently used for treatment of mastitis caused by mastitis; however, use of these antimicrobials may induce antimicrobial resistance in E. coli. The objective of this study was to explore the in vitro effect of subminimum inhibitory concentrations (sub-MIC) of cefalotin (CF) and ceftazidime (CAZ) on the morphology, antimicrobial resistance, and endotoxin releasing characteristics of 3 E. coli isolates recovered from bovine clinical mastitis. The parent E. coli isolates, which were susceptible to CF and CAZ, were exposed to CF or CAZ separately at sub-MIC levels to produce 9 generations of induced isolates. Colonies of the CAZ-induced isolates from all 3 parent E. coli were smaller on blood agar and the bacteria became filamentous, whereas the CF-induced isolates did not demonstrate prominent morphological changes. After induction by CF or CAZ, many induced isolates showed resistance to cefoxitin, CAZ, CF, kanamycin, ampicillin, and amoxicillin/clavulanic acid while their parent isolates were susceptible to these antimicrobials. Notably, 5 CAZ-induced isolates from the same parent isolate were found to produce extended-spectrum beta-lactamase (ESBL) though none of the tested ESBL related genes could be detected. All CAZ-induced isolates released more endotoxin with a higher release rate, whereas endotoxin release of CF-induced E. coli isolates was not different from parent isolates. The exposure of cephalosporins at sub-MIC levels induced resistant Escherichia coli. We inferred that cephalosporins, especially CAZ, should be used prudently for treatment of clinical E. coli mastitis.Item Open Access Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators(2019-02-21) Naqvi, S. Ali; Thompson, Graham C.; Joffe, Ari R.; Blackwood, Jaime; Martin, Dori-Ann; Brindle, Mary; Barkema, Herman W.; Jenne, Craig N.Objectives. We aimed to demonstrate the potential of precision medicine to describe the inflammatory landscape present in children with suspected appendicitis. Our primary objective was to determine levels of seven inflammatory protein mediators previously associated with intra-abdominal inflammation (C-reactive protein—CRP, procalcitonin—PCT, interleukin-6 (IL), IL-8, IL-10, monocyte chemoattractant protein-1—MCP-1, and serum amyloid A—SAA) in a cohort of children with suspected appendicitis. Subsequently, using a multiplex proteomics approach, we examined an expansive array of novel candidate cytokine and chemokines within this population. Methods. We performed a secondary analysis of targeted proteomics data from Alberta Sepsis Network studies. Plasma mediator levels, analyzed by Luminex multiplex assays, were evaluated in children aged 5-17 years with nonappendicitis abdominal pain (NAAP), acute appendicitis (AA), and nonappendicitis sepsis (NAS). We used multivariate regression analysis to evaluate the seven target proteins, followed by decision tree and heat mapping analyses for all proteins evaluated. Results. 185 children were included: 83 with NAAP, 79 AA, and 23 NAS. Plasma levels of IL-6, CRP, MCP-1, PCT, and SAA were significantly different in children with AA compared to those with NAAP (). Expansive proteomic analysis demonstrated 6 patterns in inflammatory mediator profiles based on severity of illness. A decision tree incorporating the proteins CRP, ferritin, SAA, regulated on activation normal T-cell expressed and secreted (RANTES), monokine induced by gamma interferon (MIG), and PCT demonstrated excellent specificity (0.920) and negative predictive value (0.882) for children with appendicitis. Conclusions. Multiplex proteomic analyses described the inflammatory landscape of children presenting to the ED with suspected appendicitis. We have demonstrated the feasibility of this approach to identify potential novel candidate cytokines/chemokine patterns associated with a specific illness (appendicitis) amongst those with a broad ED presentation (abdominal pain). This approach can be modelled for future research initiatives in pediatric emergency medicine.Item Open Access Dairy Calf and Heifer (Holstein, Bos taurus) Management Practices in Western Canada: Current Status and Impacts on Animal Welfare(2016) Borges Bond, Guilherme; Pajor, Edmond Anthony; Barkema, Herman W.; Doepel, Lorraine S.; Weary, Daniel M.Calves are the future of the dairy enterprise but their management is often neglected. The objectives of this thesis were: 1) to describe young stock management practices in commercial dairy farms and the compliance of producers with Canadian guidelines and; 2) to analyse the effect of management practices on calf performance, health and welfare. Eighty-two farms were visited in Alberta and British Columbia (BC), Canada. Producers completed a survey about their pre-weaned calf management practices and their awareness and use of the Code of Practice for the Care and Handling of Dairy Cattle (COP, n = 67 farms). Compliance with calf management practices in the COP was moderate and did not change whether producers were aware or not aware of the COP. Few producers changed practices as a result of the COP. The second objective was divided in two sections. The first section, comprised of 2 cross sectional studies, body weight (BW) was estimated for all pre-weaned calves (0 to 8 weeks) and heifers (12 to 15 months, BC farms only). Animals were observed for signs of nasal discharge or diarrhea and assessed for failure of passive transfer of immunity (FPT). Calves fed more than 5L of milk by bottle and introduced to water between 4 and 8 weeks of age had higher BW. Feeding less milk and offering colostrum replacer were associated with increased odds of disease and FPT. Higher heifer BW was associated with higher calf BW in the same farm. In the second section, a study on the effects of milk allowances on water drinking behaviour of dairy calves, animals were fed milk replacer either ad libitum or at 10% BW with free access to water and dry feed. Calves fed restrictively drank more water immediately after weaning. Provision of water was most important during weaning transition and drinking behaviour patterns were compatible with response to stress. The results presented in this thesis demonstrate that different practices chosen by producers can impact calf performance, health and welfare. Therefore, increased producer awareness and use of science-informed practices are needed through additional outreach efforts.Item Open Access Detection of Johne’s Disease on dairy farms using different qPCR target genes for Mycobacterium avium subsp. paratuberculosis in young stock(2023-08) Martins, Larissa; Barkema, Herman W.; Orsel, Karin; De Buck, Jeroen; Pearson, JenniferYoung stock can shed Mycobacterium avium subspecies paratuberculosis (MAP) in feces, present antibody titers and transmit MAP to other young stock. However, most Johne’s disease (JD) control programs do not include young stock in MAP testing strategies, which might be one of the reasons why only a few JD control programs were able to eradicate MAP. This study aimed to include young stock in a JD testing strategy and improve diagnostic tests. A literature review conducted reported that young stock can shed MAP as early as 4 mo of age. However, due to the chronic characteristic of the disease, it was considered important to improve current diagnostic tests and develop new tests, such as phage-based and metabolomics tests. A tentative inclusion of young stock in the MAP testing strategy was evaluated based on direct fecal qPCR and ELISA every 2 mo from animals between 2-12 mo of age. A sudden rise in MAP prevalence was detected at the second sampling, 2 mo after the start of the study. Although the high MAP prevalence was explained in part by the presence of MAP infections in the herd, it was not possible to explain the specificity of the ISMAP02 gene, which raises doubts about different Mycobacterium species being detected by the same assay. Furthermore, an in depth evaluation of the main MAP target genes for qPCR assays was proposed across different sample types and MAP concentrations. Overall, all MAP target genes were able to detect samples with high MAP concentration. IS900 and ISMAP02 consistently identified MAP in all sample types. However, the genes mbtA, hspX and F57 presented issues to detect samples with mid to low MAP concentrations.Item Open Access The Development of a Bovine Leukemia Virus Control Program(2019-12-13) Kuczewski, Alessa Evelyn Traute; van der Meer, Frank; Orsel, Karin; Barkema, Herman W.; Mason, Steve; Erskine, Ronald J.; Fourichon, Christine; Lashewicz, Bonnie M.North American dairy herds are commonly infected with bovine leukemia virus (BLV), with production-limiting effects, reduced animal welfare and consumer concerns. The overall goal of this thesis was the development of an adaptable on-farm BLV control program. To summarize important background knowledge and understand all aspects of BLV control, I performed the following: 1) Available literature concerning BLV transmission and control was reviewed and summarized. 2) Five commercially available ELISA were evaluated and compared, using 160 serum samples from Alberta cattle. 3) Economic impacts of BLV and its control were evaluated by creating an economic model of an average Alberta dairy farm. 4) Motivators and barriers for Alberta dairy farmers to change behavior on farm and implement BLV control measures were investigated by analyzing conversations with farmers as well as veterinarians. 5) In those conversations, dairy farmers’ and veterinarians’ opinions toward various BLV control measures were sought to adjust the BLV control program. 6) Based on findings, a risk assessment tool was designed to identify and weigh on-farm behavior that could cause transmission of BLV between animals. When this risk assessment tool was used on 11 Alberta dairy farms, its results, in combination with serum test results, led to the recommendation of tailored best-management practices aimed at preventing BLV transmission between animals. Implementation, within-herd prevalence, and seroconversions were measured. 7) Finally, all findings were summarized and discussed. In conclusion, recommendations for BLV control have not changed over a long interval, as general principles remain relevant. Additionally, identification of BLV-infected animals is easy and reliable. Although BLV control relies on financial investments, it has an overall economic net benefit. Motivating farmers to implement BLV control is dependent on knowledge and control measures considered feasible by the farmer. Finally, implementation of on-farm BLV control reduced within-herd BLV prevalence for the majority of participating farms.Item Open Access Disease Control on Dairy Farms with a Focus on Johne's Disease and Veterinary Communication(2018-04-19) Ritter, Caroline Manuela Nancy; Barkema, Herman W.; Adams, Cindy L.; Jansen, Jolanda; De Buck, Jeroen M.; Kelton, David F.; Mason, SteveMotivating dairy farmers to implement disease prevention and control strategies can be challenging. The first objective of this thesis was to assess factors that influence farmers’ management decisions. A literature review was conducted focusing on socio-psychological influences and farmers’ preferred information sources. Additionally, surveys and qualitative interviews with Alberta dairy farmers contributed to the current knowledge by assessing farmers’ attitudes, beliefs, and perceptions in regard to the prevention and control of Johne’s disease, an infectious enteritis that is caused by Mycobacterium avium subsp. paratuberculosis (MAP) and is endemic in Canadian dairy cows. Environmental fecal samples were analyzed for MAP to assess whether farm infection status influenced farmers’ decision to enroll in the voluntary Alberta Johne’s Disease Initiative (AJDI). Observed herd prevalence of MAP (i.e., 51%) was similar between AJDI participants and nonparticipants. Results further indicated that farmers have to believe in the importance of the disease and in recommended prevention and control strategies to make changes. In Alberta, the reasons why farmers did not participate in the AJDI or implemented recommended measures included skepticism of the threat and negative effects of Johne’s disease, critique of test sensitivity, required time, and costs. Farmers used a variety of information channels, but herd veterinarians had a major influence on their management. Veterinarians are in an ideal position to communicate and motivate recommended strategies targeted to each farm, and it is well established that effective communication skills can improve adherence with advice and health outcomes. Therefore, the second objective was to assess veterinary communication patterns. First, the suitability of on-farm video recordings for comprehensive communication analysis using the Roter Interaction Analysis System was demonstrated. Then, veterinary communication during 70 dairy farm visits was assessed. Veterinarians spent most of their talk on farmer education and relationship building. Demographics such as gender and length of the professional veterinarian-farmer relationship affected the use of some communication variables, whereas the effect of previous communication training was minimal. Identification of influences on farmers’ management decisions and of veterinary communication patterns can reveal opportunities to enhance communication, thus improving the uptake of prevention and control measures.Item Open Access The economic impact of Johne’s disease (paratuberculosis) in dairy cattle(2021-02-19) Rasmussen, Philip; Hall, David C.; Barkema, Herman W.; Beaulieu, Eugene; Mason, SteveJohne’s disease (JD), or paratuberculosis, is an infectious inflammatory disorder of the intestines primarily associated with domestic and wild ruminants including dairy cattle. The disease, caused by an infection with Mycobacterium avium subspecies paratuberculosis (MAP) bacteria, burdens both animals and producers through reduced milk production, premature culling, and reduced salvage values among MAP-infected animals. The main objectives of this thesis were to estimate the economic impact of MAP infection and potential control practices across a comprehensive selection of dairy-producing regions within a single methodological framework. Additional objectives were to estimate the value of JD control to Canadian dairy producers and to what degree there are economic premiums associated with MAP-negative dairy replacements. Using a combination of Markov Chain Monte Carlo (MCMC) simulation methods, regression analysis, and compensating and equivalent variation analysis, the following results were generated: 1) approximately 1% of gross milk revenue, equivalent to CA$43 (US$33) per cow, is lost annually in MAP-infected dairy herds, with those losses primarily driven by reduced production and being higher in regions characterized by above-average farm-gate milk prices and production per cow; 2) vaccination was the most promising type of JD control practice modelled, with dual-effect vaccines (reducing shedding and providing protective immunity) resulting in BCRs between 1.48 and 2.13 in Canada and a break-even period of between 6.17 and 7.61 years; 3) assuming a within-herd prevalence of 10% and a 50% reduction of that prevalence over 10 years, JD control has an estimated annual value of CA$28 per cow for the average Canadian dairy producer; and 4) MAP-negative replacements are associated with an average benefit of CA$96 per purchase in major dairy-producing regions, equivalent to a premium of 13% of aggregated replacement prices.Item Open Access Enhancing Antimicrobial Stewardship On Dairy Farms With A Focus On Selective Treatment Of Clinical Mastitis(2024-01-16) De Jong, Ellen; Barkema, Herman W.; Orsel, Karin; Kelton, David; Kastelic, John; Sanchez, JavierClinical mastitis (CM) treatment decisions have been the focus of antimicrobial stewardship in the dairy sector, as CM and antimicrobial dry cow treatments account for the majority of antimicrobials used on farms. To improve on-farm antimicrobial stewardship, a selective treatment approach of CM is explored, centering around milk culture-guided decisions. Detailed principles of selective CM treatment and an evidence-based protocol are presented in Chapter 2, alongside an overview of expected cow and farm impacts, impact of proportion of Gram-negative cases on expected reduction in antimicrobial use, adoption rates across the globe, and knowledge and technology gaps. A systematic review and meta-analysis is presented in Chapter 3, evidencing that a selective CM treatment protocol can be adopted without adversely influencing bacteriological and clinical cure, somatic cell count, milk yield, and incidence of recurrence or culling. Chapter 4 presents survey results of 142 farms detailing adoption of various CM protocols among Canadian dairy farmers, demonstrating an association between increased adoption of selective CM protocols and low average cow SCC, as well as a distinction between 3 groups of farmers with similar relative importance of decision factors. Delving further into CM decision-making, Chapter 5 presents considerations of Western Canadian dairy farmers at each decision step from identification of CM to treatment termination, as well as 3 overarching themes impacting each step: Personal attributes, Inter-actor dynamics, and Moving beyond protocols. Chapter 6 describes 4 themes related to perceptions on mastitis-related antimicrobial use: Antibiotic use paradox: Perception vs. reality; Low disease incidence is a badge of honor; In good hands: Veterinarians as safeguards; and “It takes a village to make a change”, alongside 10 proposed interventions designed using the Behavior Change Wheel to mitigate voiced barriers and appeal to facilitators towards milk-culture guided decisions. To advance this research future efforts should be focused on improving selection of CM cases to exclude antimicrobial treatment, discouraging inadequate mastitis-related antimicrobial stewardship practices, enhancing quality and accessibility of milk diagnostic tests, and stimulating and monitoring uptake of selective CM protocols.Item Open Access Evaluation of a risk assessment questionnaire in identifying facility and management factors associated with dairy cattle lameness in Alberta(2019-12-24) van Huyssteen, Michelle; Orsel, Karin; Barkema, Herman W.; Adams, Cindy L.A score-based lameness risk assessment questionnaire (RAQ) was conducted on 65 dairy farms in addition to the assessment of lameness and foot lesion prevalence, both infectious and non-infectious. Within-herd prevalence of lameness was 20%, remaining unchanged since the last assessment of lameness. Accuracy of the RAQ in identifying overall risk on farm was evaluated and determined to be inadequate with weak associations between total RAQ scores and lameness and lesion prevalence. When analyzing each question in the RAQ, 21 questions identified risk factors that were associated with lameness and lesions. After adjustment of the risk scores of categorical answers, the association between herd lameness and lesion prevalence and total RAQ scores improved but remained suboptimal. However, the questions that did identify risk factors can be used to support producers in prioritizing implemented changes for lameness control and mitigation.Item Open Access Evaluation of age-dependent susceptibility in calves infected with two doses of Mycobacterium avium subspecies paratuberculosis using pathology and tissue culture(BioMed Central, 2013-10-07) Mortier, Rienske A. R.; Barkema, Herman W.; Bystrom, Janet M.; Illanes, Oscar; Orsel, Karin; Wolf, Robert; Atkins, Gordon; De Buck, Jeroen; MedicineItem Open Access Exploration of innate immune response during infectious bovine digital dermatitis and the evaluation of topical therapeutic treatment(2018-09-18) Watts, Kaitlyn; Cobo, Eduardo R.; Barkema, Herman W.; De Buck, Jeroen M.; Jenne, Craig N.Digital dermatitis (DD) is a frequently occurring infectious disease amongst dairy cattle associated with ulcerative and necrotizing lesions. Due to the associated pain and lameness, DD is a recognized animal welfare problem and has economic implications associated with decreased milk production, lower reproduction rates, and premature culling. DD is of polymicrobial etiology, with the main causative agent identified as belonging to the Treponema genus. Current treatments include topical application of antibiotics such as oxytetracycline or foot baths containing caustic chemicals; however clinical cure rates remain highly variable. In this thesis cattle with DD were monitored to explore the skin innate immune response. An exhaustive description of the inflammatory response during disease progression and a novel description of bovine host defence peptides (HDPs) and their contribution to disease resolution are found herein. It was observed that active DD was characterized by necrotic tissue populated with neutrophils and elevated Cxcl-8 and Tlr4 expression. Tracheal antimicrobial peptide (Tap) was vastly increased in active lesions and key for the resolution of DD. An in vitro model utilizing human keratinocytes showed pro-inflammatory cytokines are released in the absence of living treponemes through Tlr2 signaling and that secretory treponeme products induced cathelicidins. The ability to manipulate inflammatory reactions via treatment with vitamin D3 in DD was compared to the commonly-used oxytetracycline. A cohort of cattle with M2 were topically treated with vitamin D3 against powdered oxytetracycline for 5 days. Although vitamin D3 did elevated Tap expression, lesions and inflammatory markers remained unchanged. In contrast, oxytetracycline reduced neutrophil chemoattractant Cxcl-8 while Tlr2 remained elevated. Histologic assessment evidenced scab formation. Taken together, this thesis established the skin innate response and role of host defence peptides (Tap) during DD and supported oxytetracycline as a treatment, providing lesion resolution and aiding in bacterial elimination.Item Open Access Exploring the Impact of Bovine Leukemia Virus Proviral Load on Production, and its Potential Use for Control(2024-01-19) Shrestha, Sulav; van der Meer, Franciscus Johannes; Careem, Mohamed Faizal Abdul; Barkema, Herman W.; Orsel, Karsina; van Marle, GuidoThe main aim of this dissertation was to evaluate the efficacy of a bovine leukemia virus (BLV) control program by selective removal of high proviral load (HPL) BLV-infected subsets. Six chapters are included. 1) To be acquainted with the current understanding on BLV infection, transmission routes, diagnosis, control, and most importantly, BLV proviral load, a literature review was conducted. This review explored the applicability of BLV proviral load in disease diagnosis, BLV transmission risk assessment, and BLV control. 2) We implemented a cross-sectional study to evaluate the impact of BLV proviral load on milk production of dairy cows. Data obtained from nine dairy herds in Alberta, Canada demonstrated a significant reduction in milk, fat, and protein production of HPL cows when compared with the BLV-negative counterparts. 3) The effectiveness of HPL-cow focused BLV control program in reducing BLV prevalence and seroconversions within the herd was evaluated by conducting a 3-year study among ten dairy herds. The BLV prevalence decreased in four herds whereas the BLV incidence was reduced in nine herds, which supported the notion that removal of HPL cows can offer a feasible and economical option for BLV control. 4) A 1.5-year longitudinal study was designed by enrolling subset of cows from BLV-seropositive (further classified into various proviral load categories) and BLV-seronegative group to monitor the dynamics of various parameters such as BLV proviral load, lymphocyte, white blood cell (WBC) count, antibody titer, CD3+, CD4+, CD8+, CD21+, and WC1+ cell proportions. A relatively stable pattern of BLV proviral load, WBC, CD3+, and CD4+ cell proportion was observed, indicating frequent testing might not be required for these parameters in monitoring BLV infection. 5) A cross-sectional study was conducted to investigate the hematological and immunological impact of BLV infection which suggested a simpler categorization of HPL and LPL as an appropriate approach. Additionally, a lower proviral load cut-off was identified as an accurate threshold for identifying HPL cows. 6) Lastly, all the results and findings were thoroughly discussed, and future directions for using HPL-focused strategies as a potential tool for BLV control and management were elaborated.