Drug Resistance and Drug Action in Trypanosoma congolense

Trypanosomiasis occurs in domestic livestock in 37 countries in sub-Saharan Africa, and within most of these countries appears to be the most important disease constraint to livestock production. The disease is also a significant constraint to livestock production in parts of South America, the Middle East and the Far East In the absence of a vaccine for trypanosomiasis, administration of anti-trypanosomal compounds to livestock and control of the tsetse-fly vector are the primary methods used to control the disease in sub-Saharan Africa. However, because vector control is limited in application, chemotherapy and chemoprophylaxis are the predominant methods used to control the disease in most countries. At present the salts of isometamidium, homidium and diminazene are the only compounds recommended for use in cattle, sheep and goats. All three compounds have been on the market for at least 35 years and drug resistance appears to be an increasing problem. In contrast, the literature reviewed at the beginning of this thesis indicates that drug resistance does not appear to be a problem associated with the compounds recommended for use against the parasites causing theileriosis, babesiosis, anaplasmosis and cowdriosis, even though some of them have been used for as long as the anti-trypanosomal compounds. Drug resistance in trypanosomes appears to be an increasing problem associated with the current anti-trypanosomal compounds recommended for use in domestic livestock. Since it appears unlikely that new compounds will be developed in the near future, the long-term productivity of livestock in trypanosomiasis- endemic areas is dependent, at least in the near future, on maintaining the efficacy of these compounds. In this respect, the research described in this thesis was carried out, firstly, to develop methods to more accurately determine the prevalence and level of drug resistance in the field than is possible with other techniques. Secondly, much of the described research was carried out to characterise aspects of the epidemiology of drug-resistant infections, including definition of the role of various factors in development, maintenance and abrogation of drug-resistant infections in the field. Finally, a number of potential methods for controlling drug-resistant trypanosome infections were evaluated in vivo. In particular, integration of chemotherapy with vector control was shown to be a viable method for controlling multiple-drug resistant infections in cattle. (Abstract shortened by ProQuest.)

Epidemiology of canine heartworm (Dirofilaria immitis) infection in domestic dogs in Ontario, Canada: Geographic distribution, risk factors and effects of climate

Dirofilaria immitis is the causal agent of heartworm, a mosquito-borne parasite that primarily infects domestic and wild canids. The infection is endemic in parts of Canada, and Ontario has been identified as the province where the majority of heartworm infections occur. Test results for blood samples submitted by veterinary clinics for the years 2007-2016 were used to conduct a spatial risk analysis of heartworm among domestic dogs in Ontario. The geographic extent of the apparent heartworm prevalence was examined through smoothed choropleth maps for all 49 census division regions. Furthermore, the regions were assessed for local clusters in apparent prevalence using the flexible spatial scan statistic. Three clusters were found and located in western, southern and eastern Ontario, respectively. A spatial Poisson regression model for heartworm prevalence among pet dog populations in southern Ontario census divisions was fit to determine the association between human population size, heartworm development units (HDUs), climate moisture index (CMI), precipitation and directions, east or north, with heartworm infection. The model identified the spatial distribution of HDUs and CMI as positively associated with heartworm infection and therefore important predictors of the infection. In contrast, human population size, increasing northern latitude and drier areas were negatively associated with heartworm infection. The east direction and precipitation were not significant

Perception of the Importance of Traditional Country Foods to the Physical, Mental, and Spiritual Health of Labrador Inuit

Country foods play an integral role in Inuit life by providing nutrition and a spiritual connection to the land. However, they can harbour foodborne pathogens, such as zoonotic parasites or bacteria, which can cause disease in humans who consume contaminated meat that has been inadequately cooked. Given the heavy reliance of Inuit on subsistence living, it is important to have a clear understanding of the relative safety of these foods and the role that they play in a changing Inuit society. This community-based participatory research project involved Inuit residents of Nain, Nunatsiavut, Canada. Data on Inuit perceptions of the role, importance, and safety of country foods were collected during a series of interviews with focus groups and key informants. Despite the extremely positive views they expressed about country foods and the connections they provide to the land, community, and past, participants had major concerns about human expansion in the North, mining operations, chemical contamination, and the impact of these issues on animals and the food harvested from those animals. Also of concern was a perceived decrease in the importance of country food in their community in general, and specifically among children. These findings provide an understanding of Nunatsiavut residents’ perceptions that is essential to planning effective, culturally appropriate dissemination of public health messages about the safe consumption of country foods.La nourriture de campagne revêt une grande importance dans la vie des Inuits car elle présente à la fois une source de nutrition de même qu’un attachement spirituel à la terre. Cependant, cette nourriture peut être assortie de pathogènes d’origine alimentaire prenant notamment la forme de parasites ou de bactéries zoonotiques qui peuvent entraîner des maladies chez l’être humain qui consomme de la viande contaminée dont la cuisson n’est pas adéquate. Étant donné la grande dépendance des Inuits par rapport à l’alimentation de subsistance, il est important de bien comprendre la salubrité relative de ces aliments et du rôle qu’ils jouent au sein de la société inuite en pleine évolution. Ce projet de recherche communautaire a fait appel à des habitants inuits de Nain, Nunatsiavut, au Canada. Des données relatives aux perceptions des Inuits sur le rôle, l’importance et la salubrité de la nourriture de campagne ont été recueillies dans le cadre d’une série d’entrevues réalisées auprès de groupes de discussion et d’intervenants-clés. Malgré les points de vue extrêmement positifs exprimés au sujet de la nourriture de campagne et de l’attachement qu’elle procure à la terre, à la collectivité et au passé, les participants ont exprimé de grandes préoccupations à propos de l’expansion humaine dans le Nord, de l’exploitation minière, de la contamination chimique et de l’incidence de ces enjeux sur les animaux et les sources de nourriture provenant de ces animaux. Par ailleurs, ils s’inquiétaient de la diminution perçue de l’importance de la nourriture de campagne au sein de leur communauté en général, plus précisément chez les enfants. Ces constatations permettent de comprendre les perceptions des habitants de Nunatsiavut, ce qui est essentiel à une planification efficace et à la dissémination culturellement appropriée des messages de santé publique au sujet de la consommation sécuritaire de la nourriture de campagne

Photometric Accretion Signatures Near the Substellar Boundary

Multi-epoch imaging of the Orion equatorial region by the Sloan Digital Sky Survey has revealed that significant variability in the blue continuum persists into the late-M spectral types, indicating that magnetospheric accretion processes occur below the substellar boundary in the Orion OB1 association. We investigate the strength of the accretion-related continuum veiling by comparing the reddening-invariant colors of the most highly variable stars against those of main sequence M dwarfs and evolutionary models. A gradual decrease in the g band veiling is seen for the cooler and less massive members, as expected for a declining accretion rate with decreasing mass. We also see evidence that the temperature of the accretion shock decreases in the very low mass regime, reflecting a reduction in the energy flux carried by the accretion columns. We find that the near-IR excess attributed to circumstellar disk thermal emission drops rapidly for spectral types later than M4. This is likely due to the decrease in color contrast between the disk and the cooler stellar photosphere. Since accretion, which requires a substantial stellar magnetic field and the presence of a circumstellar disk, is inferred for masses down to 0.05 Msol we surmise that brown dwarfs and low mass stars share a common mode of formation.Comment: 37 pages, 14 figures, accepted by A

Detection of European Strain of \u3ci\u3eEchinococcus multilocularis\u3c/i\u3e in North America

To the Editor: In 2009, an alveolar hydatid cyst, the intermediate stage of the cestode Echinococcus multilocularis, was detected in the liver of a dog from Quesnel, British Columbia (BC), Canada, 600 km west of the nearest known record of this parasite in central North America. Alveolar hydatid cysts normally occur in rodent intermediate hosts. However, humans can serve as aberrant intermediate hosts; cysts generally originate in the liver and, in about one third of cases, metastasize throughout the body. Detection of the larval stage of this pathogen in an unusual host in a new geographic region required application of multiple molecular epidemiologic techniques to determine if this was range expansion of a native strain or introduction of a new strain of veterinary and public health concern. The possible establishment of a European strain in North American wildlife, with spillover into domestic dogs, may have implications for public health and require increased vigilance by medical and veterinary personnel in the newly endemic region. Compared with native North American strains, European strains of E. multilocularis appear to have greater potential to cause alveolar hydatid disease (AHD) in humans. These strains are emerging worldwide (increasing in both prevalence and distribution) as a result of changes in landscape, climate, and wildlife–human interfaces. In Europe, human AHD can be fatal (definite or probable cause of death in 23.5% of 119 recent cases) and has low cure rates (5% of 408 recent cases). As of 2000, in Europe and Asia, the estimated cost per case of AHD was US $100,000–$300,000. Therefore, better understanding of the distribution, genetic diversity, and pathogenicity of strains of E. multilocularis is needed to assess risks and mitigate costs for public and veterinary health, as well as to provide evidence for the regulation and screening of imported domestic animals and translocated wildlife

Clostridium difficile PCR Ribotypes in Calves, Canada

C. difficile, including epidemic PCR ribotypes 017 and 027, were isolated from dairy calves in Canada

Vector-borne and other pathogens of potential relevance disseminated by relocated cats

Large populations of unowned cats constitute an animal welfare, ecological, societal and public health issue worldwide. Their relocation and homing are currently carried out in many parts of the world with the intention of relieving suffering and social problems, while contributing to ethical and humane population control in these cat populations. An understanding of an individual cat’s lifestyle and disease status by veterinary team professionals and those working with cat charities can help to prevent severe cat stress and the spread of feline pathogens, especially vector-borne pathogens, which can be overlooked in cats. In this article, we discuss the issue of relocation and homing of unowned cats from a global perspective. We also review zoonotic and non-zoonotic infectious agents of cats and give a list of practical recommendations for veterinary team professionals dealing with homing cats. Finally, we present a consensus statement consolidated at the 15th Symposium of the Companion Vector-Borne Diseases (CVBD) World Forum in 2020, ultimately to help veterinary team professionals understand the problem and the role they have in helping to prevent and manage vector-borne and other pathogens in relocated cats

The effect of sodium‐glucose co‐transporter 2 inhibitors on outcomes after cardiac resynchronization therapy

Aims: The trials upon which recommendations for the use of cardiac resynchronization therapy (CRT) in heart failure used optimal medical therapy (OMT) before sodium‐glucose co‐transporter 2 inhibitors (SGLT2i). Moreover, the SGLT2i heart failure trials included only a small proportion of participants with CRT, and therefore, it remains uncertain whether SGLT2i should be considered part of OMT prior to CRT. Methods and results: We compared electrocardiogram (ECG) and echocardiographic responses to CRT as well as hospitalization and mortality rates in consecutive patients undergoing implantation at a large tertiary centre between January 2019 to June 2022 with and without SGLT2i treatment. Three hundred seventy‐four participants were included aged 74.0 ± 11.5 years (mean ± standard deviation), with a left ventricular ejection fraction (LVEF) of 31.8 ± 9.9% and QRS duration of 161 ± 29 ms. The majority had non‐ischaemic cardiomyopathy (58%) and were in NYHA Class II/III (83.6%). These characteristics were similar between patients with (n = 66) and without (n = 308) prior SGLT2i treatment. Both groups demonstrated similar evidence of response to CRT in terms of QRS duration shortening, and improvements in LVEF, left ventricular end‐diastolic inner‐dimension (LVIDd) and diastolic function (E/A and e/e′). While there was no difference in rates of hospitalization (for heart failure or overall), mortality was significantly lower in patients treated with SGLT2i compared with those who were not (6.5 vs. 16.6%, P = 0.049). Conclusions: We observed an improvement in mortality in patients undergoing CRT prescribed SGLT2i compared with those not prescribed SGLT2i, despite similar degrees of reverse remodelling. The authors recommend starting SGLT2i prior to CRT implantation, where it does not delay implantation

Sloan Digital Sky Survey Imaging of Low Galactic Latitude Fields: Technical Summary and Data Release

The Sloan Digital Sky Survey (SDSS) mosaic camera and telescope have obtained five-band optical-wavelength imaging near the Galactic plane outside of the nominal survey boundaries. These additional data were obtained during commissioning and subsequent testing of the SDSS observing system, and they provide unique wide-area imaging data in regions of high obscuration and star formation, including numerous young stellar objects, Herbig-Haro objects and young star clusters. Because these data are outside the Survey regions in the Galactic caps, they are not part of the standard SDSS data releases. This paper presents imaging data for 832 square degrees of sky (including repeats), in the star-forming regions of Orion, Taurus, and Cygnus. About 470 square degrees are now released to the public, with the remainder to follow at the time of SDSS Data Release 4. The public data in Orion include the star-forming region NGC 2068/NGC 2071/HH24 and a large part of Barnard's loop.Comment: 31 pages, 9 figures (3 missing to save space), accepted by AJ, in press, see http://photo.astro.princeton.edu/oriondatarelease for data and paper with all figure