Data generated by five years of FAMACHA© clinical evaluation trials on one farm, and two years of trials on a second farm in South Africa, where targeted selective treatment was applied to treat haemonchosis in sheep, was used as a basis to explore new computational epidemiological methods to analyse the results of the trials. The research flowed from the earlier work of Dr. J.A. van Wyk and co-workers at the Faculty of Veterinary Science, University of Pretoria, who did much to develop, introduce, and validate the FAMACHA©system in South Africa and elsewhere in the world. Clinical haemonchosis was common during the summer rainfall season, and was found to increase in severity during January and February of each year. Sensitivity analysis of FAMACHA© data indicated that on the first farm (Farm 1) investigated, many of the animals that were clinically non-diseased were in fact anaemic, but due to misclassification, these animals were not detected. This was not the case on the second farm (Farm 2), where most animals that were clinically diseased according to FAMACHA© were found to be truly anaemic. The high prevalence of misclassification on Farm 1 has important implications for monitoring and chemotherapy of haemonchosis. The results indicated that under the conditions where the data were generated, the FAMACHA© system is sensitive enough, and adequately specific, to detect anaemic sheep despite misclassification. The application of Receiver Operating Characteristic curve analysis to the FAMACHA© method to select FAMACHA© categories for treatment, was in agreement with the findings that misclassification on Farm 1 would of necessity require that different treatment thresholds would need to be implemented to achieve the same test sensitivity as on Farm 2.Although the use of the Receiver Operating Characteristic method requires the use of dedicated software to generate results, especially if large data sets are analysed, it was found to be an accurate and valid way of indicating FAMACHA© threshold categories for treatment on both farms, for a desired sensitivity. A previously published multiple regression model was modified to incorporate stochasticity in the FAMACHA© proportions and the body mass of sheep, in order to simulate probable worm count. The fluctuations in simulated worm count adequately reflected the changing epidemiological situation of haemonchosis as indicated by temporal histograms of differential FAMACHA© proportions in flocks. The model was most sensitive to changes in FAMACHA© proportions in the sample, followed by increasing variability in body mass as a worm season progressed. Furthermore, for a given class of animal, a range of probable haemoglobin values could be associated with a preselected threshold worm burden. Themodel was sensitive to blanket drenching events, as a lower intensity of infection was predicted immediately after blanket drenching in all samples. It followed that model indications could be used probabilistically, to indicate minimum haemoglobin levels that would need to be sustained in order to prevent overwhelming worm burdens in a given classof animal. The penultimate chapter of the thesis is concerned with alternative methods of evaluation of rainfall as a risk factor for haemonchosis. Three different periods of rainfall, in relation to FAMACHA© sampling events, were evaluated in terms of entropy, or spread, and tested for strength of association with simulated flock haemoglobin values by regression analysis. Shannon’s entropy was used as an indicator of rainfall variability. Findings indicated a negative, and significant, correlation between rainfall entropy and flock haemoglobin level. On the strength of the association, a simulation model was proposed, which could theoretically indicate a probable range for expected flock haemoglobin level in a subsequent two-week period following FAMACHA© evaluation, provided that rainfall entropy is known. This work attempts to bridge the gap between implementation of the FAMACHA© system, and the investigation of several vital issues that would need to be addressed in the development of a wider ranging anthelmintic treatment decision-support system to delay anthelmintic resistance. The application of important quantitative methods, such as two-graph Receiver Operating Characteristic analysis, Monte Carlo simulation, and Shannon’s entropy to the FAMACHA© system, have provided new perspectives from which to develop an integrated computerized decision-support system. The thesis strongly supports the continued use of the FAMACHA© system in its present form, but the work has emphasised several key issues, such as misclassification, the need to develop decision-support systems that are useable in real time at farm level as opposed to regional level, and that the FAMACHA© system can and should be used as a basis for further development of decision-support software. / Thesis (PhD (Veterinary Tropical Diseases))--University of Pretoria, 2007. / Veterinary Tropical Diseases / unrestricted

The gastrointestinal parasite, Haemonchus contortus, is of major concern in the sheep and goat industry as well as in zoological settings. Over the years this parasite has developed resistance to the three classes of anthelmintics, benzimidazoles, imidazothiazoles and macrocyclic lactones, that are currently used for treatment. One of the mechanisms proposed to be involved in this resistance is the efflux transporter P-glycoprotein (Pgp). In this study, the resistance status of several strains of H. contortus was evaluated using the larval development assay DrenchRite®. After documenting the resistance status of these strains, transcription of Pgp in L3 larvae after exposure to anthelmintics was quantitated using polymerase chain reaction (PCR). Of the strains analyzed, only one was determined to be susceptible to all of the anthelmintics tested, while the others showed variable levels of resistance to one or more. A Haemonchus strain acquired from a giraffe at a zoo in Florida was the most resistant, showing extremely high levels of resistance to benzimidazoles and levamisole. Molecular characterization of the 18S rRNA gene and the internal transcriber spacer region (ITS) were performed on the giraffe strain to identify the species. Although there were variations in the isolate sequences, the most likely species for the giraffe strain was H. contortus. No transcription of Pgp was identified in H. contortus L3 larvae under the conditions of this study. Thus, increased Pgp does not appear to be a primary mechanism of drug resistance in this stage of the worm.

The data herein described is a compilation of retrospective and prospective studies of diseases in goats diagnosed at the Laboratório de Anatomia Patologica at the Universidade Federal de Mato Grosso do Sul. This investigation examined 74 necropsy reports of goats obtained for the period between January 2012 and August 2015. The results yielded 72 conclusive diagnoses (in 6 cases there was more than one diagnosis by necropsy), and 16 it was not possible to conclude for a diagnosis.. Of the 72 conclusive diagnoses, 65.3% were infectious and parasitic diseases, 25.0% were intoxications and toxinfections, and 8.3% were metabolic and nutritional diseases. Other disorders were diagnosed on one occasion only (1.4%). Haemonchosis was the most prevalent condition in all diagnoses (27.8%), followed by bilateral bronchopneumonia (20.8%) and poisoning by Brachiaria decumbens (18.1%). Four scientific papers resulted from this study: (1) Spontaneous poisoning by Brachiaria decumbens in goats; (2) Renal encephalopathy due to acute renal failure in a goat; (3) Granulomatous leptomeningitis in a goat associated with infection by Cryptococcus neoformans and (4) Hepatogenous chronic copper toxicosis associated with grazing Brachiaria decumbens in a goat. These four papers are already published and attached to this thesis. / Esta tese envolveu o estudo retrospectivo e prospectivo de doenças de caprinos diagnosticadas no Laboratório de Anatomia Patológica da Universidade Federal de Mato Grosso do Sul. Para isso, foram examinados os laudos de necropsias de caprinos realizadas de Janeiro de 2012 a Agosto de 2015. Durante o período estudado foram realizadas necropsias de 74 caprinos, que resultaram em 72 diagnósticos conclusivos (em 6 necropsias houve mais de um diagnóstico) e em 16 não foi possível concluir por um diagnóstico. Do total de 72 diagnósticos conclusivos, 65,3% eram de doenças infecciosas e parasitárias, 25,0% eram de intoxicações e toxinfecções e 8,3% eram de doenças metabólicas e nutricionais. Outros distúrbios foram diagnosticados em menor proporção (1,4%). Hemoncose foi a condição mais prevalente sobre o total de diagnósticos (27,8%), seguida de broncopneumonia bilateral (20,8%) e de intoxicacao por Brachiaria decumbens (18,1%). Este estudo resultou em quatro trabalhos científicos: (1) Spontaneous poisoning by Brachiaria decumbens in goats; (2) Renal encephalopathy due to acute renal failure in a goat; (3) Granulomatous leptomeningitis in a goat associated with infection by Cryptococcus neoformans e (4) Hepatogenous chronic copper toxicosis associated with grazing Brachiaria decumbens in a goat. Esses quatros trabalhos já estão publicados e estão anexados a esta tese.