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Abstract
This study evaluated the efficacy of a combination of artemether and diminazene aceturate therapy in experimental Trypanosoma brucei infection in rats. Thirty five male albino rats used for the study were randomly assigned to seven groups of five rats each as follows: Group A- infected and treated with diminazene aceturate (DA) at 7.0 mg/kg body weight (bw), intramuscular (IM) once on day 7 post-infection (pi); Group B – infected and treated with artemether (ART) at 3.2 mg/kg bw IM on day 7pi and 1.6mg/kg bw IM on days 8,9,10 and 11pi; Groups C,D and E, – infected and treated with DA at 7.0 mg/kg bw IM, 3.5 mg/kg bw IM, and 1.75 mg/kg bw IM respectively, once on day 7pi and ART at 3.2 mg/kg bw IM on day 7pi plus 1.6mg/kg bw on days 8,9,10 and 11pi; Group F –infected, untreated and Group G – uninfected, untreated. Onset of parasitaemia (OP), level of parasitaemia (LOP), clearance of parasites post treatment, mortality post infection, relapse of parasitaemia post clearance, rectal temperature, and body weight, were determined at specified intervals during the 70-day experimental period. Results showed that there were no significant (p>0.05) variations in the OP and LOP between the infected groups. Trypanosomes were cleared from the blood of rats in group A, C, D, and E after treatment. All the rats in groups B and F were dead by day 14pi. The infection relapsed in groups C and E. It was concluded that a combination of DA (3.5mg/kg bw once) and ART (3.2 mg/kg bw on day 1 of treatment and 1.6 mg/kg bw for 4 consecutive days) exhibited efficacy comparable to the standard dose of DA at 7mg/kg in the treatment of trypanosome brucei in rats and could thus possibly constitute an effective treatment regimen to reduce the dose of DA and avoid toxicity.
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References
- Abimbola A. N., Baba I. A, Yenusa E. Z., Omanibe S. J., and Oladimeji I H (2013). Anti-Trypanosoma effect of peristrophebicalyculata extract on Trypanosomabruceibrucei infected rats. Asian Pac J. Tropi. Biomed 3: 523-531.
- Adams, E. R., Hamilton, P. B. and Gibson, W.C. (2010). African trypanosomes: celebrating diversity. Trends Parasitol; 26 (7):324-328.
- Adeyemi O. S., Justine T. E., and Faozigat S. (2009). Depletion of parasitaemia by halofantrin and artemether in rats infected with African Trypanosomosis. Afr J. Pharm.Pharmacol; 3(9): 432-438.
- Anene, B. M., Onah, D. N and Nawa Y. (2001). Drug resistance in Pathogenic African trypanosomes. What hopes for the future? Vet.Parasitol., 96(2):83-100.
- Anosa V. O. (1988a). Haematological and Biochemical changes in human and animal trypanosomiasis. Part 1. Rev. Elev. Med. Vet. Pays Trop., 41: 45-78.
- Apted F. I. C. (1980) Present status of chemotherapy and chemoprophylaxis of human trypanosomiasis in the Eastern Hemisphere. Pharmacol. Ther 11(2): 391-413.
- Akande, F. A and Fagbemi, B. O. (2011). In vivo and in vitro effects of Artemisinin group of Drugs on Trypanosomosis in Mice. J. Nat. Sci.Engr.Tech; 10 (1): 73-80.
- Bacchi, C. J. Nathan, H. C., YarleH, N., Goldberg, B., McCann P. P., Sjoerdsma, A. Saric M., and Clarkson A. B. Jr (1994) Combination Chemotherapy of drug resistant Trypanosomabruceirhodesiense infections in mice using D. L-&-Difluoromethyl Ornithine and standard Trypanocides. Antimicrob Agents Chemother; 38(3); 563-569.
- Classen W, Altmann B, Cretener P. Souppart C., Skelton- Stroud P, Krinke G. (1999) Differential effects of orally versus parenterally administered Qinghaosuderivative artemether in dogs, Exp. Toxicol. Pathol., 51 (6):507-516.
- Egbe-Nwiyi T. N. and Yakubu C. (2015). Therapeutic efficacy of Cotecxin alone and its combination with Diminazeneaceturate (Berenil) in the treatment of experimental Trypanosomabruceibrucei infection of rats.Afr J. Biomed. Res. Vol 18, no1 (43-47).
- Ekanem J. T., and Yusuf O. K. (2008), Some biochemical and haematological effects of black seed (Nigella sativa) oil on Trypanosomabrucei infected rats. Afr. J. Biomed. Res. 11:79-85.
- Herbert W. J, and Lumsden W. H (1976)Trypanosomabrucei: a rapid “matching” method for estimating the hosts parasitemia. Exp. Parasitol . 40 (3); 427-31.
- Holmes, P. H., Eisler, M. C., and Geevts, S. (2004) Current chemotherapy of animal trypanosomiasis in Maudin T., Holmes P. H., and Miles. M. A. (Eds). The Trypanosomiasis, C. A. B International, U. K. pp 583- 593.
- Ilemobade A. A. and Balogun T. F. (1981). Pig Trypanosomiasis: effects of feed intake, liveweight gain and carcass traits. Tropical Animal Health and Production. Feb. 1981, Vol 13, issue 1: 128-136.
- Losos, G. J and Crockett, E. (1969). Toxicity of berenil in the dog. Vet. Rec. 85,196.
- Mbaya A. W., Ahmed M. I., Adamu G., Gyang S. N. (2009). Toxicity and combined therapeutic activity of artemether and lumefantrin in Trypanosoma infected rats. Nig. J.Parasitol. Vol 30, no 1.
- Mishina Y. V., Krishna S., Haynes R. K. and Mead J. C. (2007). Artemisinins inhibit Trypanosomacruzi and Trypanosomabruceirhodesiense in vitro growth. Antimicrobial Agents and Chemotherapy, 51:50, 1852-1854.
- Muller (1988). Diminazene diaceturate (Berenil) micronucleus test in male and female NMRI mice after oral administration. Unpublished report no 88.0248 from Pharma Research Toxicology and Pathology, Hoechst, Aktiengesellschalt, Frankfurt, Germany.
- Soulsby, E. J. I. (1986). Helminths, Arthropods and Protozoa of Domesticated Animals, 8th Edition London. Bailliere Tindall, pp 203-206.
- Sulaiman, F. A., and Adeyemi, O. S., (2010) changes in Haematological indices and protein concentration in Trypanosomabrucei infected rats treated with Homidium Chloride and Diminazeneaceturate. E. X. C. L. I Journal 9: 39-45.
- Swallow B. M.(2000), Impact of trypanosomiasis on African agriculture. ILRI. Nairobi, Kenya, pp 1-46.
- Woodrow, C. J., Haynes R, K, and Krishna S. (2005) Artemisinin. Postgrad. Med. J. 81: 71-78.
References
Abimbola A. N., Baba I. A, Yenusa E. Z., Omanibe S. J., and Oladimeji I H (2013). Anti-Trypanosoma effect of peristrophebicalyculata extract on Trypanosomabruceibrucei infected rats. Asian Pac J. Tropi. Biomed 3: 523-531.
Adams, E. R., Hamilton, P. B. and Gibson, W.C. (2010). African trypanosomes: celebrating diversity. Trends Parasitol; 26 (7):324-328.
Adeyemi O. S., Justine T. E., and Faozigat S. (2009). Depletion of parasitaemia by halofantrin and artemether in rats infected with African Trypanosomosis. Afr J. Pharm.Pharmacol; 3(9): 432-438.
Anene, B. M., Onah, D. N and Nawa Y. (2001). Drug resistance in Pathogenic African trypanosomes. What hopes for the future? Vet.Parasitol., 96(2):83-100.
Anosa V. O. (1988a). Haematological and Biochemical changes in human and animal trypanosomiasis. Part 1. Rev. Elev. Med. Vet. Pays Trop., 41: 45-78.
Apted F. I. C. (1980) Present status of chemotherapy and chemoprophylaxis of human trypanosomiasis in the Eastern Hemisphere. Pharmacol. Ther 11(2): 391-413.
Akande, F. A and Fagbemi, B. O. (2011). In vivo and in vitro effects of Artemisinin group of Drugs on Trypanosomosis in Mice. J. Nat. Sci.Engr.Tech; 10 (1): 73-80.
Bacchi, C. J. Nathan, H. C., YarleH, N., Goldberg, B., McCann P. P., Sjoerdsma, A. Saric M., and Clarkson A. B. Jr (1994) Combination Chemotherapy of drug resistant Trypanosomabruceirhodesiense infections in mice using D. L-&-Difluoromethyl Ornithine and standard Trypanocides. Antimicrob Agents Chemother; 38(3); 563-569.
Classen W, Altmann B, Cretener P. Souppart C., Skelton- Stroud P, Krinke G. (1999) Differential effects of orally versus parenterally administered Qinghaosuderivative artemether in dogs, Exp. Toxicol. Pathol., 51 (6):507-516.
Egbe-Nwiyi T. N. and Yakubu C. (2015). Therapeutic efficacy of Cotecxin alone and its combination with Diminazeneaceturate (Berenil) in the treatment of experimental Trypanosomabruceibrucei infection of rats.Afr J. Biomed. Res. Vol 18, no1 (43-47).
Ekanem J. T., and Yusuf O. K. (2008), Some biochemical and haematological effects of black seed (Nigella sativa) oil on Trypanosomabrucei infected rats. Afr. J. Biomed. Res. 11:79-85.
Herbert W. J, and Lumsden W. H (1976)Trypanosomabrucei: a rapid “matching” method for estimating the hosts parasitemia. Exp. Parasitol . 40 (3); 427-31.
Holmes, P. H., Eisler, M. C., and Geevts, S. (2004) Current chemotherapy of animal trypanosomiasis in Maudin T., Holmes P. H., and Miles. M. A. (Eds). The Trypanosomiasis, C. A. B International, U. K. pp 583- 593.
Ilemobade A. A. and Balogun T. F. (1981). Pig Trypanosomiasis: effects of feed intake, liveweight gain and carcass traits. Tropical Animal Health and Production. Feb. 1981, Vol 13, issue 1: 128-136.
Losos, G. J and Crockett, E. (1969). Toxicity of berenil in the dog. Vet. Rec. 85,196.
Mbaya A. W., Ahmed M. I., Adamu G., Gyang S. N. (2009). Toxicity and combined therapeutic activity of artemether and lumefantrin in Trypanosoma infected rats. Nig. J.Parasitol. Vol 30, no 1.
Mishina Y. V., Krishna S., Haynes R. K. and Mead J. C. (2007). Artemisinins inhibit Trypanosomacruzi and Trypanosomabruceirhodesiense in vitro growth. Antimicrobial Agents and Chemotherapy, 51:50, 1852-1854.
Muller (1988). Diminazene diaceturate (Berenil) micronucleus test in male and female NMRI mice after oral administration. Unpublished report no 88.0248 from Pharma Research Toxicology and Pathology, Hoechst, Aktiengesellschalt, Frankfurt, Germany.
Soulsby, E. J. I. (1986). Helminths, Arthropods and Protozoa of Domesticated Animals, 8th Edition London. Bailliere Tindall, pp 203-206.
Sulaiman, F. A., and Adeyemi, O. S., (2010) changes in Haematological indices and protein concentration in Trypanosomabrucei infected rats treated with Homidium Chloride and Diminazeneaceturate. E. X. C. L. I Journal 9: 39-45.
Swallow B. M.(2000), Impact of trypanosomiasis on African agriculture. ILRI. Nairobi, Kenya, pp 1-46.
Woodrow, C. J., Haynes R, K, and Krishna S. (2005) Artemisinin. Postgrad. Med. J. 81: 71-78.