EVALUATION OF SOME NATURAL AND SYNTHETIC PRODUCTS AGAINST AFRICAN TRYPANOSOMIASIS
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- NGN 3000
ABSTRACT
The chemotherapy of African trypanosomiasis, a fatal protozoal disease of man and animals is beset with many problems including a limited repertoire of expensive compounds, drug toxicity and resistance and protracted treatment protocols. In order to improve chemotherapy, some natural and synthetic products were evaluated against African trypanosomiasis using in vitro and in vivo assays. Honey, extracts of Brassica oleracea and of frog and snakes (viper and cobra) skins were assessed. Cymelarsan was evaluated in Trypanosoma brucei brucei and Trypanosoma evansi infections of albino rats and rabbits; and verapamil in the reversal of T. evansi resistance to cymelarsan, using parasitaemia and antigen and antibody enzyme linked immunosorbent assay. Five products were assessed for tsetse fly repellent activity. Oral combination administration of difluoromethylornithine (300 mg/kg), chloroquine (50 mg/kg) and honey (50 mg/kg) was evaluated in trypanosome infected albino rats. Topical application of melarsoprol, ethidium bromide and diminazene aceturate singly and combined with cattle butter (ghee) and shea butter was evaluated in infected mice and rats. Three groups of sleeping sickness patients were diagnosed and treated at Ethiope East, Delta State, Nigeria as follows: first group (pentamidine i.m. 4 mg/kg body weight for 10 days), second group (melarsoprol i.v. 1.8 – 3.6 mg/kg for 3 weeks plus prednisolone orally 1.0, 0.7 and 0.5 mg/kg daily for the first, second and third weeks respectively; third group (a single i.m. injection of 4mg/kg pentamidine plus melarsoprol and prednisolone as in second group). Questionnaires were used to assess the social, economic, cultural and behavioural factors which adversely affect treatment. The honey sample PBMH1 exhibited bactericidal and antitrypanosomal activities in vitro and transient in vivo antitrypanosomal activity. Brassica oleracea aqueous extract exhibited in vitro antitrypanosomal activity. 10 mg/kg of the aqueous extracts of frog and snake skins potentiated the activity of subcurative dose (2.5 mg/kg) of diminazene aceturate in T. brucei brucei infection. T. brucei brucei was sensitive to cymelarsan but T. evansi resisted it. Verapamil prolonged the lives of T. evansi infected rabbits but could not reverse the trypanosomal resistance. Lantana camara leaf extract and macerated tsetse fly fluid (but not Tapinanthus) as well as mosquito repellents (“OFF” and “ANTIMOS”) were shown to repel tsetse flies. Combined oral administration of difluoromethylornithine, chloroquine and honey was effective in either T. brucei brucei or T. gambiense infection. Melarsoprol, ethidium bromide/ghee combination; and diminazene aceturate/ghee combination were effective topically; but not ethidium bromide and diminazene aceturate singly or their combination with shea butter. In treated human groups, pentamidine alone cured the early stage cases, melarsoprol and prednisolone combination cured the early and late stages, and combination of pentamidine, melarsoprol and prednisolone cured the late stages. Prednisolone was effective against melarsoprol–induced encephalopathy. The evaluated serum biochemical parameters, body weight and temperature, blood pressure and pulse rate were normal in some of the patients. Abnormalities recorded in a few patients normalized after treatment. Results of polymerase chain reaction on patients’ blood samples showed therapeutic efficiency. Limited awareness of the disease, treatment seeking behaviour, some cultural and superstitious beliefs are the major factors which adversely affect treatment. The medicinal plants and animal parts used by the respondents in treatment can form important base for drug discovery. These findings are important for improved, safe and efficient chemotherapy and for the overall control of African trypanosomiasis.
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