Browsing by Author "Murilla, G.A."
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Item An Assessment of Tsetse and Trypanosomosis Research Technology Transfer: Gender Considerations in Partnership Projects Involving Rural Communities in Makueni and Kajiado districts, Kenya(Kenya Agricultural Research Institute, 2004) Nyamwaro, S.O..; Murilla, G.A.; Bukachi, S.A.; Wanjala, K.B.; Njogu, A.; Kamanga, J.; Kenya Agricultural Research InstituteFormer Kenya Trypanosomiasis Research Institute (KETRI) now Kenya Agricultural Research Institute - Trypanosomosis Research Centre (KARl - TRC) is mandated by the GoK to carry out research and technology development into all aspects of tsetse and trypanosomosis problems and reclaim tsetse-infested lands in Kenya. Tsetse-transmitted trypanosomosis is one of the most devastating parasitic diseases constraining both livestock and human health and production in sub-Saharan Africa in general, and Kenya in particular. Various developed control technologies are now available targeting either the vector (tsetse fly) or the parasite (trypanosome). Research control technologies developed by the former KETRI are geared toward the control of both the vector and the disease (trypanosomosis). One of the major research technologies KETRI has developed, validated and transferred to target communities for tsetse control is the trapping technology.Item Chemotherapy of Second Stage Human African Trypanosomiasis: Comparison between the Parenteral Oiamidine OB829 and Its Oral Prodrug OB868 in Vervet Monkeys(2015) Thuita, J.K.; Wolf, K.K.; Murilla, G.A.; Bridges, S.A.; Boykin, W.D.; Mutuku, N.J.; Liu, Q.; Jones, K.S.; Gem, O.C.; Ching, S.; Tidwell, R.; Wang, Z.M.; Pain, M.F.; Brun, R.; Kenya Trypanosomiasis Research Institute; Philippe Büscher, Institute of Tropical Medicine, BELGIUM; Kenya Agricultural Research InstituteHuman African trypanosomiasis (HAT, sleeping sickness) ranks among the most neglected tropical diseases based on limited availability of drugs that are safe and efficacious, particularly against the second stage (central nervous system [CNS]) of infection. In response to this largely unmet need for new treatments, the Consortium for Parasitic Drug Development developed novel parenteral diamidines and corresponding oral prodrugs that have shown cure of a murine model of second stage HAT. As a rationale for selection of one of these compounds for further development, the pharmacokinetics and efficacy of intramuscular (IM) active diamidine 2,5-bis(5-amidino-2-pyridyl)furan (DB829; CPD-0802) and oral prodrug2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868) were compared in the vervet monkey model of second stage HAT. Treatment was initiated 28 days post-infection of monkeys with T. b. rhodesiense KETRI 2537. Results showed that IM DB829 at 5 mg/kg/day for 5 consecutive days, 5 mg/kg/day every other day for 5 doses, or 2.5 mg/kg/day for 5 consecutive days cured all monkeys (5/5). Oral DB868 was less successful, with no cures (0/2) at 3 mg/kg/day for 10 days and cure rates of 1/4 at 10 mg/kg/day for 10 days and 20 mg/kg/day for 10 days; in total, only 2/10 monkeys were cured with DB868 dose regimens. The geometric mean plasma Cmax of IM DB829 at 5 mg/kg following the last of 5 doses was 25-fold greater than that after 10 daily oral doses of DB868 at 20 mg/kg. These data suggest that the active diamidine DB829, administered IM, should be considered for further development as a potential new treatmeItem A device for restraining mice and confining tsetse flies during trypanosome infection transmission experiments(2013) Ndung’u, K.; Kibugu, J.K.; Gitonga, P.K.; Thuita, J.K.; Auma, J.E.; Gitonga, S.K.; Murilla, G.A.Chemical (anaesthesia) and manual techniques are commonly used to restrain mice during vector-mediated parasite transmission experiments in the laboratory. Chemical restraint may interfere with natural fly vector–mouse interactions and therefore potentially affect the outcome of transmission experiments. Conversely, manual restraint is labour-intensive and exposes laboratory animals to excessive restraining-related discomfort. We report development of a mouse restraining device (Infectra®-kit) that allows essential transmission studies to be carried out with minimal human manipulation and without the need for anaesthesia. Infectra®-kit can be used as a single unit for restraining one mouse or as eight-assembled units, thus significantly improving efficiency of a single operator in comparison to manual restraint. The kit was validated by comparing feeding success in tsetse flies fed on mice restrained using Infectra®-kit (Group I) to those manually restrained (Group II). The mean ± SE % feeding success was 75.0 ± 8.2% and 82.1 ± 8.2% for tsetse flies in Groups I and II respectively. Statistical analysis using two sample t-test showed no significant difference between the two groups at p ≤ 0.05, indicating that Infectra®-kit as a restraining device was as good as the conventional manual restraint method. The main benefits of using Infectra®-kit for transmission studies therefore include reduction of man-hours and animal restraining-related discomfort. In addition, the risk of accidental injury to laboratory personnel by either mice or tsetse flies is minimized, which is an important consideration when working with zoonotic parasites.Item The effects of drug-sensitive and drug-resistant Trypanosoma congolense infections on the pharmacokinetics of homidium in Boran cattle(Elsiever, 2002) Murilla, G.A.; Peregrine, A.S.; Ndung'u, J.M.; Holmes, P.H.; Eisler, M.C.; Kenya Trypanosomiasis Research Institute; Kenya Trypanosomiasis Research Institute (KETRI), P.O. Box 362, Kikuyu, Kenya, International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi, Kenya, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, UKTwo groups of five Boran (Bas indicus) cattle were infected with one of two populations of Trypanosoma congolense: one drug-sensitive (ILl180), and one drug-resistant (IL3330). The animals were then treated intramuscularly With homidium bromide at a dose rate of 1.0 mg kg - I bodyweight 7 days after trypanosomes were detected in the peripheral blood of all the five animals in each group. Following treatment of cattle infected with drug-sensitive trypanosomes. Parasites could no longer be detected in the bloodstream of four out of five cattle after 24 h. and after 48 h for the fifth animal. The animals remained aparasitaemic up to the end of the observation period of 90 days and Serum drug concentrations determined by enzyme linked immunosorbent assay (ELISA) remained above the detection limit of 0.1 ng ml- I for the entire period. Following treatment of cattle infected with drug-resistant trypanosomes. parasites did not disappear from the bloodstream in any of the five animals. The rate of drug elimination was greater in cattle infected with drug-resistant trypanosomes and the drug was no longer detectable approximately 3 weeks after treatment. Non compartmental pharmacokinetic analysis showed that the values for of 75.5 ± 16.9 h. the area under the curve (AUCo_",) of 1.33 ± 0.156 Ilg h ml- I and the MRTo -f. of 32.8 ± 4.45°h obtained in cattle infected with the drug resistant trypanosome population were significantly lower than the values of 424 ± 146 h for t 1.67 ± 0.233 Ilg h ml-- I for AUCo _ Cf and 297 ± 159 h for MRTo _ J: obtained in cattle infected with the drug-sensitive population. The persistence of drug-resistant infections in cattle following homidium treatment was associated with more rapid drug elimination than in those in which infections with drug-sensitive parasites were cleared by the drug. (g 2002 Elsevier Science B.Y. All rights reserved.Item Factors influencing the prevalence of trypanosomosis in Orma Boran (trypanotolerant) and Teso zebu (trypanosusceptible) cattle crosses in Teso District, western Kenya(2009) Gachohi, J.M.; Bett, B.; Murilla, G.A.; Kenya Trypanosomiasis Research Institute; Kenya Agricultural Research Institute, Trypanosomiasis Research Centre (KARI-TRC), International Research InstituteThe objective of this study was to determine factors associated with occurrence of trypanosomosis in the first generation (F1) crossbreds between trypanotolerant Orma Boran and trypanosusceptible Teso zebu cattle in a trypanosomosis endemic area in Teso District, western Kenya. The offspring were screened for trypanosomosis and other haemoparasites using parasitological methods. Packed cell volume (PCV), body weights and tsetse density (FTD) were also determined. Factors considered in the analysis included sex, age, body weight and season of the year. Generalized linear mixed models (GLMM) were used for multivariable analysis to account for clustering of observations at the animal level and estimate outcome variance parameters.Item Factors influencing the prevalence of trypanosomosis in Orma Boran (trypanotolerant) and Teso zebu (trypanosusceptible) cattle crosses in Teso District, western Kenya(2009) Gachohi, J.M.; Bett, B.; Murilla, G.A.; Kenya Agricultural Research Institute, Trypanosomiasis Research Center (KARI-TRC), International Livestock Research Institute (ILRI)The objective of this study was to determine factors associated with occurrence of try panosomos is in the first generation (F 1) crossbreds between trypanotolerant Orma Boran and trypanosusceptible Teso zebu cattle in a trypanosomosis endemic area in Teso District, western Kenya. The offspring were screened for trypanosomosis and other haemoparasites using parasitological methods. Packed cell volume (PCY), body weights and tsetse density (FTD) were also determined. Factors considered in the analysis included sex, age, body weight and season of the year. Generalized linear mixed models (GLMM) were used for multivariable analysis to account for clustering of observations at the animal level and estimate outcome variance parameters.Item The Socio-Economic Impact of Tsetse and Trypanosomiasis(Kenya Agricultural Research Institute, 1966) Murilla, G.A. ; Kenya Agricultural Research InstituteThis thesis concerns the development, validation and use of enzymelinked immunosorbent assays (ELISA) to determine homidium concentrations in sera of treated cattle. Previously published work with particular emphasis on control and specifically, chemotherapy of animal trypanosomiasis are reviewed in Chapter One. This includes the development and use of trypanocidal drugs detailing previous analytical techniques used in the determination of drug levels in plasma/serum of treated cattle.Item The Socio-Economic Impact of Tsetse and Trypanosomiasis(Kenya Agricultural Research Institute, 1996) Murilla, G.A.; Kenya Agricultural Research InstituteThe African trypanosomiases constitute a group of closely related diseases that affect man and livestock whose causative organism is the haemoprotozoan parasite, the trypanosome. The disease is known as 'nagana' in cattle, 'surra' in camels and 'sleeping sickness' in humans.Item Validation of a competitive chloramphenicol enzyme linked immunosorbent assay for determination of residues in Ovine tissues(2010) Murilla, G.A.; Wesonga, J.O.; Foddey,T.; Crooks, S.; Guantai, A.N.; Karanja, W. M.; Maitho, T.E.; Kenya Trypanosomiasis Research Institute; TRC, Residue Analysis Section, Kenya Agriculture Research Institute, P.O.Box 362, Kikuyu, Kenya, Medical Laboratory Sciences Department, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000-00200, Nairobi, Kenya, Veterinary Sciences Division, Agri-Food Biosciences Institute, Stoney Road, Belfast BT4 3SD, UK, Department of Pharmacology and Pharmacognosy, School of Pharmacy, College of Health Sciences, University of Nairobi, P.O. Box 19676-00202, Nairobi, Kenya,Chloramphenicol is a broad-spectrum antibiotic, which has been used for treatment of animals. However, in humans it leads to hematoxic side effects particularly aplastic anaemia for which a dosage-effect relationship has not yet been established. The objective of this study was to validate a developed chloramphenicol enzyme linked immunosorbent assay for the determination of chloramphenicol residues in ovine tissues. Two groups (n=5) of sheep were injected with chloramphenicol sodium succinate at 25-mg/kg bodyweight and slaughtered one and four weeks post drug administration. Overall, the mean percentage recoveries in muscle, liver and kidney were 92 %, 70% and 78% respectively. The limits of detection were 1.2 Ng/g, 0.6 ng/g and 0.8 ng/g while the detection capability was 2.5 ng/g in muscle, kidney and liver respectively. This enables the method to be used effectively as a screening tool for chloramphenicol residues in livestock products especially in the liver, muscle and kidney.
