Veterinary Science Collected Works - Theses
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ItemPrednisolone in canine medicine: How and why it is prescribed systemically and the impact of bodyweight on prescriptions and pharmacokinetics( 2022-11)Background: Prednisolone is a commonly used medication in canine medicine, for a variety of indications. It is prescribed for physiologic maintenance, as an anti-inflammatory and as an immunosuppressant. Unfortunately, it also comes with a variety of adverse effects. There is a lack of research describing what conditions prednisolone is prescribed for and what factors influence dose in dogs. Additionally, there is evidence to suggest that canine bodyweight influences risk of side effects, therefore published dosing recommendations for dogs over 25 kg recommend dosing by body surface area. However, there is no research on whether bodyweight influences dose prescribed by veterinarians and little research as to how bodyweight affects prednisolone pharmacokinetics. Objectives: The aims of this thesis were to review the current literature on prednisolone use and pharmacokinetics in dogs (Chapter 1); to describe prednisolone prescribing practices to for dogs in Australia, indication for prescription and to evaluate what factors influence dose prescribed (Chapter 2); to observe prednisolone pharmacokinetics in client-owned dogs and describe any effect of bodyweight (Chapter 3). Method: Chapter 2 was a cross-sectional study using individual canine clinical records acquired from the VetCompass Australia database. Dogs prescribed prednisolone between 1 July 2016 to 31 July 2018 were identified and a random sample of 2,000 dogs from this population were used for data acquisition. Chapter 3 was a prospective, observational study where dogs receiving prednisolone for medical reasons had a series of plasma samples taken after their normal prednisolone dose. Plasma prednisolone concentrations were measured via liquid- chromatography tandem mass spectrometry and the relationship between dog bodyweight, prednisolone dose and prednisolone area-under-the-curve (AUC) was described. Results: Prednisolone was found to be most prescribed for inflammatory conditions, at an anti-inflammatory dose to Australian dogs. Disease of the integument was the most common indication for prescription. Notably, 8% of dogs (n = 152) were prescribed an immunosuppressant dose, for an inflammatory condition, which was considered inappropriate. Bodyweight was found to have a small, independent, negative effect on dose prescribed. The pharmacokinetic study found that dosing by bodyweight (milligrams per kilogram) resulted in AUC being positively associated with bodyweight. Conclusions: This research describes, for the first time, prednisolone prescriptions for dogs in Australia and confirms that bodyweight influences dose prescribed and impacts prednisolone pharmacokinetics. Veterinary clinicians appear to reduce the prednisolone dose prescribed, in milligrams per kilogram, to larger dogs. Regarding pharmacokinetics, when dosed equivalently in milligrams per kilogram, a larger dog has larger plasma prednisolone AUC compared to a smaller dog. This is potentially a cause for the increased adverse effects experienced by larger dogs. This research will improve veterinary clinician awareness to the potential risk to larger dogs prescribed prednisolone and provide groundwork to further research on prednisolone pharmacokinetics in dogs.
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ItemEnvironmental Distribution and Risks Associated with Canine Soil-transmitted Helminths and Canine Lungworms Contaminating Parks in Australia( 2022)In this thesis, 1581 canine faecal samples from 190 parks across Australia were collected and subjected to faecal floatation as well as newly developed qPCR assays to detect a range of canine soil transmitted helminths (cSTHs) and lungworms. In addition, questionnaires were administered to Australian dog owners and veterinarians to establish their knowledge, practices and perceptions with regards to canine endoparasites. In the first research chapter of my PhD project, I set out to develop and optimise Taq-Man based multiplex real-time PCRs (qPCRs) for the detection and characterisation of the species of canine hookworms from faeces. In order to validate these newly developed qPCRs we sourced canine faecal from Vietnam and Queensland (Australia) previously confirmed positive for A. caninum, A. ceylanicum and U. stenocephala by PCR- Restriction Fragment Length Polymorphism (PCR-RFLP). These qPCRs demonstrated a higher diagnostic sensitivity compared to the PCR-RFLP and allowed the detection of additional single and mixed hookworm species infections missed by the PCR-RFLP. In order to validate these tools for A. braziliense (Chapter 3), we sourced hookworm microscopy-positive canine faecal samples from a cross-sectional survey of gastrointestinal parasites of dogs in Nigeria and subjected these to the newly developed qPCRs. The qPCRs were confirmed as a highly sensitive tool for the detection of A. braziliense from field samples and revealed for the first time, the occurrence of this parasites in the country. Further, I updated the occurrence and distribution of hookworm species affecting dogs in Nigeria and highlighted the suitability of the newly developed multiplex qPCR assays as high-throughput tools for the surveillance of zoonotic hookworms, globally. In Chapter 4 extensive fieldwork and sampling of canine faecal samples contaminating parks across seven of the eight states of Australia was performed. Faecal samples collected were subjected to faecal floatation and a set of qPCRs to detect a range of canine soil-transmitted helminths (cSTHs). In total, 44.2% of the parks sampled were contaminated with at least one species of cSTHs, with hookworms being the most prevalent parasites (10.2%) followed by Trichuris spp. (1.3%) and Strongyloides spp. (1.2%). This study revealed a high rate of contamination with cSTHs in dog parks in urban Australia, most of which having proven zoonotic potential. Preventive measures, including awareness-raising educational programs promoting responsible pet ownership, immediate disposal of pet faeces in public areas were encouraged to minimise the health risks associated with cSTHs to both dogs and humans. In Chapter 5, to investigate the faecal prevalence of canine lungworms in Australia, we developed, optimised and validated a multiplex qPCR for the detection of Angiostrongylus vasorum, Crenosoma vulpis, and respiratory species of Eucoleus spp. and subjected canine faecal samples collected in Chapter 4 to the newly developed qPCR. The multiplex qPCR was validated on canine faecal samples from Switzerland and Cambodia previously subjected to Baermann examination and faecal floatation to screen for canine lungworms. The multiplex qPCR was able to detect all the species of canine lungworms targeted with higher diagnostic sensitivity and specificity compared to microscopy-based techniques. This qPCR allows for the simultaneous detection of the main species of canine lungworms from faeces and provides a relatively rapid diagnostic compared to time-consuming traditional techniques such as Baerman, faecal floatation and conventional PCR. Furthermore, qPCR does not require fresh faecal material opposite to Baermann technique hence representing an ideal diagnostic tool for large epidemiological studies. Based on sample size and the diagnostic parameters of the assay, and failure of the multiplex qPCR to detect any samples positive for lungworm DNA, lead to the assumption that the maximum prevalence of canine lungworms in faecal samples contaminating urban parks across Australia is less is than 0.19%. Lastly, Chapter 7 and 8 investigated pet owners and veterinarians’ behaviour, knowledge, and attitudes towards the control of canine intestinal and cardiopulmonary parasites in Australia. Overall, this PhD project found that the majority of dog owners and veterinarians in Australia are not complying with guidelines on the control of canine endoparasites. For instance, although the majority of dog owners dewormed their dogs (89.6%), only the 27.8% followed best practice guidelines, i.e., administered a monthly prophylactic treatment all-year round. A large proportion of respondent dog owners administered prophylactic treatment at an inappropriate frequency (47.8%) or did not treat for canine gastro-intestinal (GI) parasites at all (24.4%). Just over a half of veterinarians (55.9%) recommended prophylactic treatment of nursing or pregnant bitches for canine GI parasites, and recommended puppies to be first dewormed before three weeks of age (55.2%). Furthermore, many veterinarians were also unaware of the most common or significant species of GI parasites occurring in their practice area. This study demonstrates that dog owners and veterinarians in Australia are not complying with best practice regarding the control of canine GI parasites and are exposing themselves and their dogs to the risk of infections. As veterinarians constitute the main source of knowledge to dog owners it is imperative that Australian veterinarians focus on improving their knowledge on companion animal parasitology by accessing up-to-date, reputable online resources and attending continuing professional educational seminars. Furthermore, veterinarians are called to implement dog owner’s education, raise their awareness on the threats canine parasitic diseases pose to both dogs and humans and finally, encourage them to follow a monthly prophylactic treatment for canine GI parasites all year round.
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ItemCoagulation factor activity patterns in venom-induced consumption coagulopathy from naturally occurring tiger snake (Notechis scutatus) envenomation in dogs( 2020)Snake venom-induced consumption coagulopathy (VICC) is an important syndrome resulting from snake envenomation. The prothrombin activator notecarin D is responsible for this coagulopathy in tiger snake (Notechis scutatus) envenomation. In dogs, the presence of this coagulopathy is used to assist with the diagnosis of snake envenomation and, in some cases, can produce clinical signs associated with a coagulopathic envenoming. There are subtle differences in this syndrome between dogs and people, particularly concerning the development of clinical signs. Chapter two reviews tiger snake envenomation and the consequent VICC in Australian dogs with comparisons to human literature. The VICC syndrome between the two species share many clinical similarities; the key difference lies in the significance of clinical haemorrhage in people when compared with dogs. A brief overview of coagulation and coagulometry is provided. Chapter three is a prospective observational cohort study characterising the coagulation factor activity patterns in VICC from naturally occurring tiger snake envenomation in dogs. The changes in coagulation factors in a study cohort of tiger snake envenomed dogs were compared to a healthy control cohort. Fibrinogen, factor V and factor VIII were identified as the most consumed factors and displayed the fastest recovery to control values. Tests of coagulation times (i.e., prothrombin time and activated partial thromboplastin time) were similarly affected. Additionally, higher serum tiger snake venom concentrations were associated with greater reductions in factors II, V and VIII, and greater prolongations in both coagulation times. The elucidation of the consumption and recovery pattern of coagulation factors in dogs, contrasted with that of people, provides insight into the underlying mechanisms of tiger snake VICC and its treatment. This information can be used for further diagnostic and therapeutic endeavours.