Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate.

作者: M. Mamman , G. Gettinby , N. B. Murphy , S. Kemei , A. S. Peregrine

DOI: 10.1128/AAC.39.5.1107

关键词: DiminazeneMicrobiologyDrug resistancePopulationBiologyTrypanosomaTrypanosomiasisDose–response relationshipImmunologyInfectivityPharmacokinetics

摘要: The frequency of trypanosomes resistant to diminazene aceturate at a dose 25 mg/kg body weight was investigated for populations Trypanosoma congolense IL 3274 which reappeared in infected mice after intraperitoneal treatment with the same dosage. At inoculum sizes 10(2), 10(3), 10(4), 10(5), and 10(6) per mouse, relapse were used initiate infections five groups 100 each by intravenous route. Immediately infection, 50 group treated intraperitoneally aforementioned dosage; other functioned as untreated controls. Thereafter, all animals monitored days presence trypanosomes. In group, detected control mice, indicating 100% infectivity sizes. contrast, 10(5) aceturate, 4, 11, 13, 28, 39 respectively. By logistic regression, good fit found between number identified parasitemic Maximum likelihood estimates proportions organisms 8.335 x 10(-4), 2.485 3.02 10(-5), 8.3 10(-6), 1.6 These finding indicate that majority susceptible drug dosage selecting population that, surprisingly, calculated proportion survived exposure varied inversely size. Further experiments indicated inverse relationship did not result from alterations pharmacokinetics different data therefore suggest parasite size are important factors estimating apparent diminazene-resistant T. occurring vivo.

参考文章(48)
M Mamman, D.J.L Williams, N.B Murphy, A.S Peregrine, Apparent rarity of diminazene-resistant trypanosomes in goats infected with a diminazene-resistant population of Trypanosoma congolense Research in Veterinary Science. ,vol. 58, pp. 113- 118 ,(1995) , 10.1016/0034-5288(95)90062-4
I. Stauffert, H. Paulini, U. Steinmann, H. Sippel, C.-J. Estler, Investigations on mutagenicity and genotoxicity of pentamidine and some related trypanocidal diamidines. Mutation Research Letters. ,vol. 245, pp. 93- 98 ,(1990) , 10.1016/0165-7992(90)90006-6
L. D. B. Kinabo, Q. A. McKellar, Current models in pharmacokinetics: Applications in veterinary pharmacology Veterinary Research Communications. ,vol. 13, pp. 141- 157 ,(1989) , 10.1007/BF00346724
Dianne Damper, Curtis L. Patton, Pentamidine transport in Trypanosoma brucei—Kinetics and specificity Biochemical Pharmacology. ,vol. 25, pp. 271- 276 ,(1976) , 10.1016/0006-2952(76)90213-6
DIANNE DAMPER, CURTIS L. PATTON, Pentamidine transport and sensitivity in brucei-group trypanosomes. Journal of Eukaryotic Microbiology. ,vol. 23, pp. 349- 356 ,(1976) , 10.1111/J.1550-7408.1976.TB03787.X
Kiyoshi Yamaoka, Terumichi Nakagawa, Toyozo Uno, Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. Journal of Pharmacokinetics and Biopharmaceutics. ,vol. 6, pp. 165- 175 ,(1978) , 10.1007/BF01117450
Tomas Olsson, Moiz Bakhiet, Conny Edlund, Bo Höjeberg, Peter H. van der Meide, Krister Kristensson, Bidirectional activating signals between Trypanosoma brucei and CD8+ T cells: A trypanosome‐released factor triggers interferon‐γ production that stimulates parasite growth European Journal of Immunology. ,vol. 21, pp. 2447- 2454 ,(1991) , 10.1002/EJI.1830211022
Peter Diffley, James E. Strickler, Curtis L. Patton, Byron H. Waksman, Detection and quantification of variant specific antigen in the plasma of rats and mice infected with Trypanosoma brucei brucei. Journal of Parasitology. ,vol. 66, pp. 185- 191 ,(1980) , 10.2307/3280802