TRYPANOSOMOSIS AND TRYPANOCIDAL DRUGS: DISEASE PREVALENCE, DRUG QUALITY, EFFICACY AND UTILIZATION PRACTICES, IN CATTLE IN SELECTED HOT SPOTS OF SOUTH-WESTERN ETHIOPA

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2017-04

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Ethiopia has the largest livestock population in Africa and livestock accounts 15-17% of total GDP and 35-49% of agricultural GDP. Unfortunately, the development and intensification of livestock production is hampered by diseases such as African animal trypanosomosis (AAT). Drug treatments often complemented with vector control will continue to be the main tool available to smallholder livestock producers to control the disease. However, due to various reasons, the increasing development of trypanocidal resistance is posing a major threat that is seriously undermining control efforts. A number of brands of trypanocidal drugs are on the local market and control over their circulation and use appear to be very loose in rural communities such as the west and south-western part of the country. Therefore, this PhD thesis research work hypothesized that owing to their persistent use and the continued threat posed by the disease; the quality and efficacy of such drugs circulating in the local market is low and hence development of drug resistance is inevitable in the study area. The objective of the study was therefore to assess the prevalence of bovine trypanosomosis, determine extent of the occurrence of trypanocide drug resistance in identified hot spots and assess the utilization practice and quality of trypanocides currently in use in south western Ethiopia. Although extensive studies have been reported on the distribution of the disease in many places of the country, only few indicators are available on prevalence of drug resistant to trypanosomes and attention has not given to assess the quality of trypanocidal brands currently in use and the practice of their utilization. The study has attempted to demonstrate the current situation of bovine trypanosomosis in the study area by using parasitological (woo) and molecular (PCR-RFLP) techniques, assess trypanocidal drug utilization practices of farmers through a structured questionnaire survey, determine the quality of trypanocidal drugs circulating in the local markets and show the prevalence of drug resistant trypanosomes by using a field trial method. For the drug quality testing, a total of 50 samples were collected from different sources (legal and illegal) and the drugs were subjected to high performance liquid chromatography (HPLC) test. For drug susceptibility/resistance trial, 80 parasitaemic animals were selected and studied for a period of xvii 28 days by alternate treatment with Diminazene aceturate and isometamidium chloride. Post-treatment parasitaemia was detected on days 14 and 28. Cross-sectional study to estimate trypanosomosis prevalence was done (December/2013-February2014) on systematically selected 2000 cattle whereas, 100 farmers were randomly selected for the interview on trypanocidal drug utilization practices. The study indicated that the overall prevalence of trypanosome infection by buffy coat was 4.5% (CI = 3.4% to 5.4%) with significant variation between the study districts; being higher in Abeshege and Cheha (p=0.000). T. congolense (61.1%) followed by T. vivax (17.8%) mixed infection of the two (10%) and T. theileri (11.1%) were the species demonstrated by parasitological technique. One hundred fifty one samples that were considered negative by Woo technique were further subjected to PCR-RFLP. The PCR detected 19.2% additional positive cases (76% of them T. congolense) suggesting that parasitologcal techniques are seriously underestimating the magnitude of the problem. The PCR further ascertained that by Woo technique, it was easier to identify T. congolense much better than T. vivax or mixed infection of the two species. T. theileri was often confused with T. vivax under Woo technique. The overall mean PCV was significantly reduced in parasitaemic animals (22.6%= CI: 21.46-23.73) compared to aparasitaemic (25.6%= CI: 25.41-25.78) animals (P=0.000). The questionnaire survey result revealed that trypanosomosis was a significant animal health constraint for all farmers interviewed in the hot spot villages. The majority of respondents of all villages (56%; 95% CI= 46.3-65.7%) get trypanocidal drugs from unauthorized/illegal markets. Significant numbers of farmers in the study villages (59%) administer trypanocidal drugs by themselves or through family members and 85% of the respondents treat their animals with more than six times injections/animal per year. Altogether, this suggests that risk factors for the development of trypanocidal drug resistance to trypanosomes are there. In addition, trypanocidal drug quality assessment by using HPLC has unequivocally demonstrated that 28% of the drugs tested had substandard quality and hence did not comply with the active ingredient content described by the manufacturers. In this regards, clients of authorized and non-authorized markets are at similar risk of purchasing non-compliant trypanocides. This study has also shown that although some European companies are not immune from the problem, most non-compliant drugs were produced in Asian pharmaceutical companies (P< 0.05) suggesting that some of the drugs were defective right from their origin. The observation that trypnocidal drugs are inappropriately utilized and some of the drug types circulating in the local market are reported to have poor quality are the basis to undertake field trial to assess the efficacy of known brands of diminazene aceturate and isometamidium chloride on trypanosome positive cattle selected from the study areas using an abbreviated 28 days field protocol. The overall findings revealed multiple drug resistance to recommended doses of Diminazine aceturate (7.5%) and Isometamidium chloride (6.25%) whereas relapse to single treatment with recommended doses (3.5 mg/kg body weight for DA or 0.5 mg/kg body weight for ISM) was 47.5% in case of DA and 27.5% for ISM. In conclusion, T.congolense and T. vivax are the dominant trypanosome species posing significant losses in the study areas as demonstrated by the drop in PCV. Parasitological techniques seem to undermine the magnitude of the disease problem leading to wrong diagnosis and failure to treat sick animals on time. This is being exacerbated by the inappropriate use of available trypanocidal drugs by untrained farmers and the widespread circulation of fake drugs in the local market altogether facilitating the development of drug resistance. This assumption was validated by the demonstration of single and multiple resistances to recommended doses of both diminazene aceturate and isometamidium chloride. Existence of multiple drug resistance has seriously threatened the use of sanative pair. This necessitates intensification of vector control strategies, rational utilization of the few available trypanocidal drugs, effective implementation of regulatory and legislative frameworks for Veterinary drug supply, distribution and utilization, improving veterinary extension programs and veterinary services to educate livestock owners on development of drug resistance and its economic impacts.

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