Effects of a Combination of Artemether and Diminazene Aceturate Therapy on Experimental Trypanosoma Brucei Infection in Rats.
ABSTRACT
This study investigated the effects of a combination of arthemether and diminazene aceturate therapy on experimental Trypanosoma brucei infection in albino rats. Thirty five male albino rats were used for the study. They were randomly assigned to seven groups of five rats each, after acclimatization.
The groupings and their specific treatments were as follows: Group A- infected and treated with diminazene aceturate (DA) at the dose of 7.0 mg/kg body weight (bw) once on day 7 post-infection (pi);
Group B – infected and treated with artemether (AM) at the doses of 3.2 mg/kg bw on day 7pi and 1.6mg/kg bw on days 8,9,10 and 11pi; Group C – infected and treated with DA at the dose of 7.0 mg/kg bw once on day 7pi and AM at the doses of 3.2 mg/kg bw on day 7pi plus 1.6mg/kg bw on days 8,9,10 and 11pi;
Group D – infected and treated with DA at the dose of 3.5mg/kg bw once on day 7pi and AM at the doses of 3.2 mg/kg bw on day 7pi and 1.6mg/kg bw on days 8,9,10 and 11pi;
Group E – infected and treated with DA at the dose of 1.75mg/kg bw once on day 7pi and AM at 3.2mg/kg bw on day 7pi and 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 (CPPT), mortality post infection (MPI), relapse of parasites post clearance (RPPC), rectal temperature (RT), body weight (BW), red blood cell (RBC) counts, haemoglobin concentration (HBC), packed cell volume (PCV).
Total white blood cell (TWBC) counts, serum alanine amino transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine were assayed 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 but not in the blood of rats in group B after treatment.
All the rats in groups B and F (infected, untreated) were dead by day 14pi. No relapse was recorded in rats in groups A and D all through the experimental period whereas infection relapsed in groups C and E.
Infection with trypanosomes led to decrease in erythrocytic parameters and TWBC counts, and elevations in serum ALT, AST, urea and creatinine which were reversed by treatment in rats in groups A and D but not in groups B,C and E. It was concluded that a combination of DA (3.5mg/kg bw once).
AM (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 Trypanosoma brucei in rats and could thus constitute an effective treatment regimen to reduce the occurrence of diminazene toxicity in animals.
TABLE OF CONTENTS
Title ii
Certificationiii
Declarationiv
Dedicationv
Acknowledgementsvi
List of Tables vii
List of figures viii
Table of contentsix
Abstract x
Chapter One: Introduction1
Chapter Two: Review of Related Literature5
2.1 Aetiology and Distribution of Trypanosomosis5
2.2 Animal Hosts of Trypanosomes7
2.3 Life Cycle of Trypanosomes 8
2.4 Transmission of Trypanosomes9
2.5 Insect Vectors of Trypanosomes10
2.6 Clinical Manifestations of Trypanosomosis11
2.7 Pathogenesis and Pathological Lesions12
2.8 Immunity in Trypanosomosis and Trypanotolerance15
2.9 Immunosupressive Effects of Trypanosomosis16
2.10 Haematological and Biochemical changes associated with Trypanosomosis17
2.11 Control of Trypanosomosis21
2.12 Diminazene Aceturate22
2.13 Future Perspectives in Chemotherapy23
2.14 Artemether23
Chapter Three: Materials and Methods25
Chapter Four: Results30
Chapter Five: Discussion and Conclusion53
References57
Appendix
INTRODUCTION
Trypanosomosis is an infection of man and animals caused by parasites of the genus Trypanosoma (Anene et al., 2001). It is a major cause of death in animals in Africa, Asia and Latin America but its geographic distribution is still evolving (Omamegbe and Uche, 1985; Desquesnes et al., 2013).
Trypanosomes found in mammals are blood and sometimes tissue parasites of the order Kinetoplastida, family of Trypanosomatidae, and genus Trypanosoma (Desquesnes et al., 2013).
In humans, trypanosomes cause sleeping sickness, a major human disease affecting about 500,000 people and threatening 60 million others in Africa alone (Rodgers, 2009).
Likewise, trypanosomosis remains a limiting factor to livestock development in sub-Saharan Africa despite attempts at controlling it.
Transmission of trypanosomes can be through cyclical or mechanical mode. Mechanical transmission occurs when the parasite is transferred directly from blood of an infected host to another without undergoing further development in the vector (Foil, 1989; Hall and Wall, 2004).
In cyclical transmission, the parasites develop in either the posterior part of the insect’s digestive tract such as in Trypanosoma cruzi or in the anterior part of the digestive tract such as in the main African Livestock pathogenic trypanosomes like Trypanosoma brucei, Trypanosoma vivax, and Trypanosoma congolense (Desquesnes et al., 2013).
REFERENCES
Abaru, D. E., Liwo, D. A, Isakina, D and Okori. E, E. (1984). Retrospective long – term study of Berenil by follow –up of patients treated since 1965 Tropenmed parasit. 35, 148- 150.
Abimbola A. N., Baba I. A, Yenusa E. Z., Omanibe S. J., and Oladimeji I H (2013). Anti-Trypanosoma effect of peristrophebicalyculata extract on Trypanosoma brucei brucei infected rats. Asian Pac J. Tropi. Biomed 3: 523-531.
Abubakar, A., lliyasu, B, Yusuf, A. B, Igwe A. C., Onyekwelu, N. A. et al (2005) Anti-trypanosomal and haematologic effects of selected Nigerian medicinal plants in Wister rats. Biokemistry 17:95-99.
Adams, E. R., Hamilton, P. B. and Gibson, W.C. (2010). African trypanosomes: celebrating diversity. Trends in Parasitology 26:324-328.
Adamu, U. O. Haruna, M. K., Orbagbedia R. P., Bizi R, Benjamin W., malala U. A., Nwezor F.N.C., and Muhammed M. (2011). Control of African Trypanosomiasis in Nigeria. Time to strengthening Integrated Approches (A Review); International Journal of Animal and Veterinary Advances 3 (3) 138- 143.
Adeyemi O. S., Justine T. E and Faozigat S. (2009) Depletion of parasitaemia by Halotantrine and artemether in rats infected with African Trypanosomosis, African Journal of Pharmacy & Pharmacology, Vol. 3, No 9 pp 432 – 438.