Browsing by Author "Sayer, P.D."
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Item Differential Susceptibility to DL-a-Difluoromethylornithine in Clinical Isolates of Trypanosoma brucei rhodesiense(June 1990) Bacchi, C.J.; Nathan, H.C.; Livingstone, T.; Valladares, G.; Saric, M.; Sayer, P.D.; Njogu, A.R.; Clarkson, A.B. Jr; Kenya Trypanosomiasis Research Institute; Haskins Laboratories, Pace University, New York, New York 10038.PDL-alpha-Difluoromethylornithine is an enzyme-activated inhibitor of ornithine decarboxylase and an antagonist of polyamine metabolism that has been successful in clinical trials against West African sleeping sickness caused by Trypanosoma brucei gambiense. Its potential for use against the more virulent East African form of the disease, caused by T. brucei rhodesiense, is not certain. We examined 14 East African clinical isolates from the Kenya Trypanosomiasis Research Institute strain bank plus 2 established isolates for susceptibility to DL-alpha-difluoromethylornithine and to standard trypanocides. Seven of 16 strains were partially or totally refractory to DL-alpha-difluoromethylornithine in our test system. Four strains were also refractory to arsenical drugs, and five were refractory to diamidines. The results indicate that other novel agents or combinations of established agents may be needed for chemotherapy of East African disease.progressing disease although also invariably fatal if not treated.Item Homidium bromide as a chemoprophylactic for cattle trypanosomiasis in Kenya(1990) Dolan, R.B.; Okech, G.; Alushula, H.; Mutugi, M.; Stevenson, P.; Sayer, P.D.; Njogu, A.R.; Kenya Trypanosomiasis Research Institute; Kenya Trypanosomiasis Research Institute (KETRI), P.O. Box 362, Kikuyu, KenyaHomidium bromide was used in a strategic chemoprophylactic regime to control trypanosomiasis in Boran cattle in Kenya. Trypanosome infection rates in cattle receiving homidium bromide prophylaxis were compared with those in control cattle which received no prophylaxis but were treated with dirninazene aceturate while infected. Homidium bromide was administered twice during the year after which no infections were detected for periods of nineteen weeks and seventeen weeks respectively. The drug sensitivity of the infecting trypanosomes is believed to be a major factor in determining the duration of prophylaxis.Item Pyrethroid Impregnated Ear Tags In Trypanosomiasis control(1988) Dolan, R.B.; Sayer, P.D.; Alushula, H.; Heath, B.R.; Kenya Trypanosomiasis Research InstituteInsecticide impregnated ear tags have been used to control horn flies and face flies in cattle in the United States (Williams, Westby, Hendrix and Haineneser, 1981). In Europe they have proved effective against horn flies and other biting flies (Stomoxys and Tabanus spp., Kunast, Schafer, Schmelz and Schah Zeidi, 1983) while in West Africa impregnated ear tags in N'Dama cattle, resulted in a reduction in the incidence of tsetse-borne trypanosomiasis (Kupper. and Harbers, 1985). Ear' tags impregnated with a synthetic pyrethroid fenfluthrin (Bay Nak 1654, Bayer AG) have now been assessed for trypanosomiasis control in Boran (Bos indicus) steers on Galana Ranch in Kenya; the results are reported here. The wild and domestic animal population of the ranch, its vegetation and tsetse distribution have been described previously (King, Heath and Hill, 1976; Schwartz, Dolan and Wilson, 1983; Njogu, Dolan, Wilson and Sayer, 1985).Item Total Protein and White Cell Changes in the Cerebrospinal Fluid of Vervet Monkeys Infected with Trypanosoma rhodesiense and the Post-treatment Reaction(The Research Centre for Protozoan Molecular Immunology, 1994) Ndungu, J.M.; Ngure, R.M.; Ngotho, J.M.; Sayer, P.D.; Omuse, J.K.; Kenya Trypanosomiasis Research Institute; Kenya Trypanosomiasis Research Institute, P. O. Box 362, Kikuyu, KenyaIn an attempt to elucidate the events leading to the development of post treatment reactve encephalopathy in human Africa trypanosomiasis (HAT),a group of vervet monkeys (ceropithecus aethiops)were experimentally indfected with Trypanosoma rhodesiense. When terminally sick on day 12, they were treated with either diminazene aceturate, suramin or melarsoprol. Trypanosomes appeared in the cerebrospinal fluid(CSF)by day 1 of infection and increased in numbers with progress of the disease. However, only marginal increases in CSF total protein and white cels ocured during the same period. Treatment with Berenil resulted in persistence and increase in numbers of CSF.Trypanosomes, a dramaric increase in proteins and white cells up to 8 weeks after treatment,calminating in clinical encephalitis. Suramin cleared CSF trypanosomes within 4 weeks with marginal increase in proteins and white cells up to 8 weeks after treatment, folowes thereafter by a grasual and prolonged fall to pre-infection levels, Melarsoprol eliminated trypanosomes from the CSF in less than a week but the white cell and protein levels increased for another 4 weeks before finally falling. The pos-treatment increased in white cell numbers and total protein was therefore dependent on the trypanocidal drug, and was highest and most prolonged when Berenil was used and lowest with Suramin. The present studies demonstrate tha trypanocidal treatment of infected animals is followed by a post-treatment reaction in the central nervous system, the severity of which is related to the drug used and the presence of trypanosomes in the CSF.The vervet monkey therefore appears to be a good model for studying the reaction in HAT.Item Treatment of late-stage African trypanosomiasis still relies mainly on one drug, the arsenical melarsoprol (Mel B, Arsobal. Despite its strong antitrypanosomal activity, treatment is hazardous and an arsenical encephalopathy which often ends fatally is the most serious side effect.(1990) Zweygarth, E.; Kaminsky, R.; Sayer, P.D.; Van Nieuwenhove, S.; Kenya Trypanosomiasis Research InstituteTreatment of late-stage African trypanosomiasis still relies mainly on one drug, the arsenical melarsoprol (Mel B, Arsobal). Despite its strong antitrypanosomal activity, treatment is hazardous and an arsenical encephalopathy which often ends fatally is the most serious side effect.Item Trypanosoma brucei rhodesiense:auase of an antigen detection enzyme immunoassay for evaluation of response to chemotherapy in infected vervet monkeys (cercopithecus aesthiops)(1994) Gikhuki, C.W.; Nantulya, V.M.; Sayer, P.D.; Kenya Trypanosomiasis Research Institute; Kenya Trypanosomiasis Research Institute, KikuyuThirty eight Trypanosoma brucei rhodesiense- infected vervet monkeys (Cercopithecus aethiops) in the late (meningoencephalitic) stage of disease, treated with various trypanocidal drugs, were monitored for a period of more than 600 days to assess the rate of clearance of trypanosome antigens from serum and cerebrospinal fluid (CSF). There was a complete but gradual reduction in antigen titres, as assessed by ELISA, in animals treated intravenously with melarsoprol, the standard drug for the late stage disease. In 8 of the 9 monkeys treated with melarsoprol, the antigen titres, as assessed by optical density values, dropped by 50 % within 252 days (mean value 68 days for antigens in CSF and 116 for serum) following treatment. The remaining animal in this group, that displayed persistent antigenaemia, had been treated with a sub-curative drug dosage level. Thus, if time to 50 % reduction in antigen levels were to be taken as an index to predict cure, the follow-up period after melarsoprol treatment could have been reduced from 600 to 252 days for 8 of the 9 animals, leaving only one animal for further follow up. The animals treated with experimental drug combinations displayed a variable picture; Five monkeys showed a persistence of antigens in both serum and CSF throughout the observation period, suggesting failure of the drugs to cure the infection. Parasitologically confirmed relapse of the infection was indeed observed in all the five monkeys. In some monkeys, the parasite antigens eventually cleared from serum and CSF completely, but this took a longer time duration than in the melarsoprol treated animals; others showed persistence of parasite antigens in serum, but the parasites were not detected in blood or CSF throughout the entire follow-up period. These results suggest that the experimental drug combinations used were not effective in clearing the parasites from cryptic foci and hence the persistence of antigens in serum and/or CSF. Antigen ELISA would, thus, appear to be a useful tool for evaluation of response to chemotherapy.Item Use of procyclic trypanosomes for detection of antibodies in sera from vervet monkeys infected with Trypanosoma rhodesiense: an immunodiagnostic test for African sleeping sickness(1986) Pearson, T.W.; Liu, M.; Gardiner, I.C.; Longridge, D.; Beecroft, R.P.; Sayer, P.D.; Gould, S.S.; Waitumbi, J.N.; Njogu, A.R.; Kenya Trypanosomiasis Research Institute; Department of Biochemistry and Microbiology of Victoria, Canada, Kenya Trypanosomiasis Research Institute MugugaUncoated procyclic culture forms of African trypanosomes were used in immunofluorescence and simple agglutination assays to detect antibodies in the sera of vervet monkeys infected with T. b. rhodesiense. Antibodies to procyclic surface antigens were found in sera from animals with active, untreated infections or sera taken soon after treatment with trypanocidal drugs. The antibodies were detectable within 7 days of infection. No specific antibodies were detected in sera prior to infection or long after drug cure. The results indicate that antigens expressed on the surface of pro cyclic culture forms of T. brucei spp. Are useful for the detection of antibodies produced in response to infection with T. b. rhodesiense and may allow the development of a simple immunodiagnostic test for African sleeping sickness. In addition, the use of a form of the trypanosome of a different differentiation state from the infecting organism illustrates the utility of this approach for detection of antibodies to common antigens.Item Use of Procyclic Trypanosomes for Detection of Antibodies in Sera from Vervet Monkeys Infected with Trypanosoma Rhodesiense: an Immunodiagnostic Test for African Sleeping Sickness(veterinary Record, 1986) Pearson, T.W.; Liu, M.; Gardiner, I.C.; Longridge, D.; Beecroft, R.P.; Sayer, P.D.; Gould, S.S.; Waitumbi, J.N.; Njogu, A.R.; Department of Biochemistry and Microbiology, University of Victoria, Canada, Kenya Trypanosomiasis Research Institute, Muguga, KenyaUncoated procyclic culture forms of African trypanosomes were used in immunofluorescence and simple agglutination assays to detect antibodies in the sera of vervet monkeys infected with T. b. rhodesiense. Antibodies to procyclic surface antigens were found in sera from animals with active, untreated infections or sera taken soon after treatment with trypanocidal drugs. The antibodies were detectable within 7 days of infection. No specific antibodies were detected in sera prior to infection or long after drug cure. The results indicate that antigens expressed on the surface of procyclic culture forms of T. brucei spp. Are useful for the detection of antibodies produced in response to infection with T. b. rhodesiense and may allow the development of a simple immunodiagnostic test for African sleeping sickness. In addition, the use of a form of the trypanosome of a different differentiation state from the infecting organism illustrates the utility of this approach for detection of antibodies to common antigens.
