RESUMO
Four Trypanosoma evansi stocks with sensitivity to suramin in mice ranging from 0.05 to 160 mg kg-1 were cloned and sub-cloned and the sensitivity of the clones determined. The results suggest that it is easier to clone and sub-clone trypanosome stocks which are sensitive to suramin than those that are resistant to the action of the drug. The clones obtained from the four stocks had sensitivities to suramin which were similar to or different from the parent stocks. These results are important in view of the development of resistance for, in the presence of suramin, these resistant yet heterogeneous populations would provide the material from which selective processes could operate. These observations also suggest that the maintenance and spread of suramin-resistant trypanosomes might be curtailed by their comparative inability to establish themselves in a new host.
Assuntos
Suramina/toxicidade , Tripanossomicidas/toxicidade , Trypanosoma/crescimento & desenvolvimento , Animais , Camelus/parasitologia , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos , Especificidade da Espécie , Trypanosoma/efeitos dos fármacos , Trypanosoma/isolamento & purificação , Tripanossomíase/veterináriaRESUMO
A total of 183 camels from Kenya were examined for circulating trypanosomal antigens by four methods: (1) a monoclonal antigen-detection enzyme-linked immunosorbent assay (Ag-ELISA) and circulating anti-trypanosomal antibodies; (2) antibody-detection enzyme-linked immunosorbent assay (Ab-ELISA); (3) buffy-coat examination (BCE); (4) mouse subinoculation (MI). Thirty-seven camels (20%) were parasite-positive by BCE and 60 camels (33%) were parasite-positive by MI. Sixty-three camels (34%) tested positive on Ag-ELISA. Of the 24 camels which could not be detected by BCE, Ag-ELISA detected 18 (75%). Ab-ELISA detected 90 (49%) positive camels. Of all the parasite-positive camels (61), Ag-ELISA detected 93% and Ab-ELISA 95%. Based on the results of 55 camels, there was a significant statistical difference (P < 0.0001) in Ag-ELISA optical density (OD) values (of either serum or plasma antigen analysis) between parasite-positive and parasite-negative camels. No significant difference was observed in Ab-ELISA OD values between parasite-positive and parasite-negative camels. Diagnosis of T. evansi infection in camels by the use of Ag-ELISA alone or in combination with BCE could therefore be a more preferred approach in assessing patient infection than the use of Ab-ELISA.
Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/sangue , Camelus/parasitologia , Trypanosoma/imunologia , Tripanossomíase Africana/veterinária , Animais , Ensaio de Imunoadsorção Enzimática , Tripanossomíase Africana/diagnósticoRESUMO
Suramin-resistance was experimentally induced in cloned or uncloned T. evansi populations using both immunosuppressed and immunocompetent mice by administration of subcurative doses of the drug. The highest level of resistance achieved was 3,000 fold using cloned trypanosomes in immunosuppressed mice. In the absence of suramin, suramin-resistance in T. evansi was observed to be stable for ten passages in mice. The results obtained in this study imply that induction of suramin resistance is by a mutational event followed by selection of resistant mutants by the presence of the drug. Immunosuppression of animals by heavy parasite burden or stressful conditions in conjunction with underdosing may therefore play an important role in the development of drug resistance under field conditions.
Assuntos
Suramina/farmacologia , Trypanosoma/efeitos dos fármacos , Animais , Resistência a Medicamentos/genética , Resistência a Medicamentos/imunologia , Tolerância Imunológica , Imunocompetência , Camundongos , Trypanosoma/genéticaRESUMO
The efficacy of treatment in 61 naturally trypanosome-infected camels was evaluated by antigen and antibody detection. Following treatment of 14 infected field camels with an arsenical drug (RM110) no trypanosomal antigens could be detected in the animals which were treated with 0.6 mg/kg body weight and 1.2 mg/kg body weight, 90 days thereafter. In two out of three camels treated with 0.4 mg/kg body weight no trypanosomal antigens could be detected by day 90 post-treatment. However, there was evidence of trypanosomal antigens in camels treated with 0.2 mg/kg body weight and untreated positive controls. Antibody levels were still high in all the 14 camels, 90 days post-treatment. In another group of 55 field camels, of which 47 camels were parasite-positive and eight parasite-negative, trypanosomal antigens could not be detected in 42 camels, 28 and 48 days post-treatment with Quinapyramine Prosalt. However, antigen levels were still high in five parasite-positive camels, 48 days post-treatment. In all the parasite-positive camels, antibody levels were still high 48 days after treatment. In the eight parasite-negative camels, antigens were detected in four camels before treatment. By day 48 post-treatment, all the four camels were antigen-negative. However, four of the eight parasite-negative camels were still antibody-positive by day 48 post-treatment. These observations indicated that antigen-detection could be used to evaluate the success of therapeutic trials where trypanosome detection tests may fail to pick low patent infections.