A diminazene-resistant strain of Trypanosoma brucei brucei isolated from a dog is cross-resistant to pentamidine in experimentally infected albino rats

Parasitology ◽  
2005 ◽  
Vol 132 (1) ◽  
pp. 127-133 ◽  
Author(s):  
B. M. ANENE ◽  
R. C. EZEOKONKWO ◽  
T. I. MMESIRIONYE ◽  
J. N. A. TETTEY ◽  
J. M. BROCK ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Trypanosoma Brucei ◽  
Active Compound ◽  
Careful Consideration ◽  
Albino Rats ◽  
Trypanosoma Brucei Brucei ◽  
Diminazene Aceturate ◽  
Pentamidine Isethionate ◽  
Relapse Rates

Trypanosomosis is a major cause of mortality for dogs in Nigeria and treatment with diminazene aceturate has steadily become less effective, either as a result of low quality of the locally available diminazene preparations or of drug resistance. To investigate these alternatives, samples of locally obtained drugs were analysed for diminazene aceturate content and a strain of Trypanosoma brucei brucei was isolated from a diminazene-refractory dog in Nsukka, south-eastern Nigeria, and used to infect albino rats. The quality of diminazene aceturate-based preparations was variable, with two preparations containing less than 95% of the stated active compound. Rats infected with T. brucei isolated from the dog were treated 7 and 10 days after infection either with 7 mg/kg diminazene aceturate (intraperitoneally, once) or with 4 mg/kg pentamidine isethionate (intramuscularly, 7 consecutive days). Relapse rates were 100% for both trypanocides in the groups of rat treated 10 days post-infection, and 83% and 50% of rats treated 7 days after infection relapsed to diminazene aceturate and pentamidine isethionate, respectively. Careful consideration of physiological parameters showed that pentamidine was only marginally superior to diminazene aceturate as applied in this study. It was concluded that dogs in Nigeria are infected with genuinely diminazene aceturate-resistant trypanosomes that appear to be cross-resistant to pentamidine isethionate.

Azithromycin and Diminazene Aceturate Combination Therapy in Experimental Multidrug-resistant Trypanosoma brucei brucei Infection in Albino Rats

2020 ◽  
Vol 282 ◽  
pp. 109138
Author(s):  
Chukwunonso Francis Obi ◽  
Ikenna Onyema Ezeh ◽  
Michael Ikenna Okpala ◽  
Idika Kalu Idika ◽  
Nnamdi Mbe ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Trypanosoma Brucei ◽  
Multidrug Resistant ◽  
Albino Rats ◽  
Trypanosoma Brucei Brucei ◽  
Diminazene Aceturate

Effects of Trypanosoma brucei brucei infection and diminazene aceturate administration on the blood pressure, heart rate, and temperature of Wistar albino rats

2018 ◽  
Vol 29 (3) ◽  
pp. 265-269
Author(s):  
Olushola Emmanuel Adeleye ◽  
Jude Makinde Ale ◽  
Emmanuella Olubanke Amope Sogebi ◽  
Ladoke A. Durotoye ◽  
Adenike Iyabo Adeleye ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Trypanosoma Brucei ◽  
Treated Group ◽  
Control Group ◽  
Albino Rats ◽  
Trypanosoma Brucei Brucei ◽  
Blood Pressure Monitor ◽  
Diminazene Aceturate ◽  
Wistar Albino Rats

Abstract Background: This study was carried out to determine the blood pressure changes in experimentally Trypanosoma brucei brucei-infected Wistar albino rats and diminazene aceturate-treated rats. Methods: Twenty-four rats were purchased and divided into four groups consisting of six rats each. Control group (CON) received 0.5 mL of distilled water, i.m., infected but not treated group (INF) received 2×106 trypanosome/mL i.m., infected but diminazene aceturate-treated group (INFDIM) received 2×106 trypanosome/mL, 3.5 mg/kg, i.m.) and non-infected but diminazene aceturate-treated group (DIM) received 3.5 mg/kg, i.m. and served as negative control. The blood pressures were measured using a CODA 2® non-invasive blood pressure monitor (Kent Scientific, USA). The results were compiled and statistical analysis was done with significance set at p≥0.05. Results: The values of the blood pressure readings of the Trypanosoma-infected INF (137.0±2.0 mmHg) and diminazene-treated rats INFDIM (125.0±7.5 mmHg) when compared to the control group (168.0±3.0 mmHg) were significantly lower (p≤0.05) at the end of day 7. The heart rate was also significantly reduced in the INF (403.5±1.5 beats/min) and DIM (445.0±24 beats/min) groups of rats when compared with the control group (613.0±2.0 beats/min) at the end of day 8. Conclusion: The findings indicate the significant reduction in blood pressure and heart rates during Trypanosoma brucei brucei infection and with diminazene aceturate administration. Hence, caution should be exercised when treating trypanosome-infected patients with diminazene aceturate.

scholarly journals The Trypanocide Diminazene Aceturate Is Accumulated Predominantly through the TbAT1 Purine Transporter: Additional Insights on Diamidine Resistance in African Trypanosomes

2004 ◽  
Vol 48 (5) ◽  
pp. 1515-1519 ◽  
Author(s):  
Harry P. de Koning ◽  
Laura F. Anderson ◽  
Mhairi Stewart ◽  
Richard J. S. Burchmore ◽  
Lynsey J. M. Wallace ◽  
...  
Keyword(s):  
Cell Line ◽  
Trypanosoma Brucei ◽  
Domestic Animals ◽  
Trypanosoma Brucei Brucei ◽  
Diminazene Aceturate ◽  
Severe Problem ◽  
African Trypanosomes ◽  
Detectable Rate ◽  
Almost All ◽  
Null Mutants

ABSTRACT Resistance to diminazene aceturate (Berenil) is a severe problem in the control of African trypanosomiasis in domestic animals. It has been speculated that resistance may be the result of reduced diminazene uptake by the parasite. We describe here the mechanisms by which [3H]diminazene is transported by Trypanosoma brucei brucei bloodstream forms. Diminazene was rapidly accumulated through a single transporter, with a Km of 0.45 ± 0.11 μM, which was dose dependently inhibited by pentamidine and adenosine. The Ki values for these inhibitors were consistent with this transporter being the P2/TbAT1 adenosine transporter. Yeast expressing TbAT1 acquired the ability to take up [3H]diminazene and [3H]pentamidine. TbAT1-null mutants had lost almost all capacity for [3H]diminazene transport. However, this cell line still displayed a small but detectable rate of [3H]diminazene accumulation, in a nonsaturable manner. We conclude that TbAT1 mediates [3H]diminazene transport almost exclusively and that this explains the observed diminazene resistance phenotypes of TbAT1-null mutants and field isolates.

scholarly journals Efficacy of Isometamidiumin Combination with Verapamil, Chlorpromazine ‎or Sodium-ethylenediaminetetra-acetic Acid in Treatment of Experimental ‎Diminazene Aceturate-resistant Strain of Trypanosoma brucei brucei ‎Infection in Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 37-45
Author(s):  
I. C. Chukwudi ◽  
O. C. Omemgboji ◽  
B. M. Anene
Keyword(s):  
Acetic Acid ◽  
Trypanosoma Brucei ◽  
Resistant Strain ◽  
Parasite Clearance ◽  
Negative Control ◽  
Male Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Trypanosoma Brucei Brucei ◽  
Diminazene Aceturate

This study investigated the efficacy of different chemotherapeutic regimes in the treatment of rats experimentally infected with diminazene aceturate-resistant strain Trypanosoma brucei brucei. Thirty Sprague Dawley male rats used for the study were randomly assigned to six groups of five rats eachas follows: group A-uninfected untreated (negative control), group B-infected and untreated (positive control), groups C-F were infected and treated with 1.0 mg/kg isometamidum chloride, administered intramuscularly on day 11 post-infection. However, rats in groups D, E and F received further treatments with 700 mg/kg sodium-ethylenediamine tetra-acetic acid, 0.4 mg/kg verapamil and 3 mg/kg chlorpromazine, respectively, administered orally for four days. Clearance of parasite post-treatment (PT), mortality PT, relapse parasitaemia post-clearance, body weight change, rectal temperature, packed cell volume (PCV), haemoglobin (HB) concentration and red blood cell count (RBC) were determined during the experiment. Result showed parasite clearance PT of 100% in groups D and E, 80% in group F and 20% in group C by 24 hours PT. The infection relapsed on day 35 PT in 40% of rats in group C, on day 37 PT in 20% of rats in group F and lastly 20% of rats in groups D and E on day 39 PT. Rats that received drug combination showed marginal improvement in erythrocytic parameters analysed when compared with those treatment with isometamidium alone. Combination therapy showed faster clearance of parasite from the blood and also prolonged relapse post-clearance, thus had a better promising efficacy when compared to using isometamiduim chloride alone.

scholarly journals Anti-Trypanosomal Activity of Guiera senegalensis on Trypanosoma brucei Infected Mice

2019 ◽  
Vol 9 (4-s) ◽  
pp. 273-279
Author(s):  
Zongo André ◽  
Vitouley Sèna Hervé ◽  
Bengaly Zakaria ◽  
Kaboré Adama ◽  
Traoré Aristide ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Survival Time ◽  
Trypanosoma Brucei ◽  
Oral Route ◽  
Phytochemical Screening ◽  
Trypanosoma Brucei Brucei ◽  
Diminazene Aceturate ◽  
Mean Survival Time ◽  
Guiera Senegalensis

Aqueous decoction of Guiera senegalensis leaves was studied orally and intraperitoneally for its antitrypanosomal activity on mice infected experimentally with Trypanosoma brucei brucei. After a phytochemical screening followed by an acute toxicity study on mice, the extract of plant was administered once daily for 2 days at doses of 60, 120 and 240 mg / kg orally and 15, 30 and 60 mg / kg intraperitoneally after infection. Then, parameters of parasitaemia, packed cell volume (PCV), mean survival time and body weight of the mice treated with the extract were measured and compared with positive (diminazene aceturate) and negative (distilled water) controls for 7 days in a row. Results indicate that the aqueous extract of G. senegalensis leaves contains tannins, flavonoids, saponosides, reducing compounds and anthocyanosides, alkaloids and coumarins. LD50 of the extract are 1264.49 mg / kg by oral route and 316.22 mg / kg by intraperitoneal route. The doses of 240 mg / kg by oral route and 15 and 60 mg / kg by intraperitoneal route of aqueous extract showed a mean survival time (5 days) comparable to the positive control. Parasitaemia level increased in all mice tested except in mice treated with diminazene aceturate during the post-infestation period. During this period, PCV and body weight of all mice decreased by both routes of administration. These results of the study show the pharmacological utility of G. senegalensis leaves in the control of TAA by herders / pastoralists and suggest continuing further bio-guided studies to isolate the active components of the plant in order to improve their efficiency. Keywords: In vivo test; Trypanosoma brucei brucei; Guiera senegalensis leaves; phytochemical screening; acute toxicity.

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