scholarly journals Chemotherapeutic efficacy of secnidazole-diminazene aceturate combination therapy in experimental Trypanosoma brucei brucei infection in rats

2017 ◽  
Vol 11 (30) ◽  
pp. 349-354 ◽  
Author(s):  
G. Eke Ifeanyi ◽  
O. Ezeh Ikenna ◽  
A. Ezeudu Terry ◽  
U. Ezeh Ukamaka ◽  
O. Anaga Aruh ◽  
...  
2020 ◽  
Vol 282 ◽  
pp. 109138
Author(s):  
Chukwunonso Francis Obi ◽  
Ikenna Onyema Ezeh ◽  
Michael Ikenna Okpala ◽  
Idika Kalu Idika ◽  
Nnamdi Mbe ◽  
...  

2014 ◽  
Vol 7 (6) ◽  
pp. 438-445 ◽  
Author(s):  
Adieme Ijeoma Chekwube ◽  
Ezeh Ikenna Onyema ◽  
Ugochukwu Emmanuel Ikenna ◽  
Romanus Chukwuduruo Ezeokonkwo

Author(s):  
Ifeanyi Gabriel Eke ◽  
Ikenna Onyema Ezeh ◽  
Terry Adaeze Ezeudu ◽  
Ukamaka Uchenna Eze ◽  
Aruh Ottah Anaga ◽  
...  

2020 ◽  
Vol 65 (No. 12) ◽  
pp. 543-552
Author(s):  
IG Eke ◽  
UU Eze ◽  
IO Ezeh ◽  
TA Nzeakor ◽  
AO Anaga ◽  
...  

Relapse parasitaemia is a major setback in the chemotherapy of a late stage Trypanosoma brucei brucei infection. An aberrant serum biochemical profile resulting from a T. b. brucei infection in dogs has been attributed to multiple organ injuries resulting from the invasive nature of the organism. Therapy with diminazene aceturate alone has not been satisfactory. This study evaluated the effects of a secnidazole-diminazine aceturate (SEC-DA) combination therapy on parasitaemia and the serum biochemical profile after the late treatment of a T. b. brucei infection in dogs. Eighteen dogs were randomly assigned to 6 groups (n = 3) as follows: Group A: uninfected nor treated; group B: infected without treatment; group C: infected and treated with DA (3.5 mg/kg) (DA-monotherapy) intramuscularly (i.m.) once; group D: infected and treated with SEC (100 mg/kg) and DA (3.5 mg/kg); group E: in-fected and treated with SEC (200 mg/kg) and DA (3.5 mg/kg) and group F: infected and treated with SEC (400 mg/kg) and DA (3.5 mg/kg). Secnidazole was administered orally for 5 days while DA was given i.m. once in groups D–F. The dogs were infected with 5 × 10<sup>5</sup> trypanosomes intraperitoneally and treatment started 14 days post-infection. The parasitaemia was monitored daily while the serum biochemical indicators were monitored 14, 21, and 28 days post-infection. The total aparasitaemia was achieved in the SEC-DA treated dogs 72 h post-treatment and in 86 h in the DA-monotherapy dogs. A relapse parasitaemia occurred in the DA-monotherapy dogs 17 days post-treatment. The SEC-DA combination therapy caused a significant (P &lt; 0.05) decline in the hitherto elevated urea and creatinine concentrations, and the ALP, ALT, AST activities. Also, there was a significant (P &lt; 0.05) increase in the previously decreased serum albumin in the SEC-DA treated dogs. In conclusion, secnidazole-diminazene aceturate combination therapy prevented the relapse parasitaemia and ameliorated aberrant serum biochemical profiles of T. b. brucei infected dogs after late treatment.


Synergy ◽  
2017 ◽  
Vol 4 ◽  
pp. 19-22
Author(s):  
Mohammed Auwal Ibrahim ◽  
Aliyu Muhammad Musa ◽  
Hassanat Taye Tairu ◽  
Maryam Kassim ◽  
Abubakar Babando Aliyu ◽  
...  

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 ◽  
...  

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.


2020 ◽  
Vol 17 (4) ◽  
pp. 37-45
Author(s):  
I. C. Chukwudi ◽  
O. C. Omemgboji ◽  
B. M. Anene

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.


2019 ◽  
Vol 9 (4-s) ◽  
pp. 273-279
Author(s):  
Zongo André ◽  
Vitouley Sèna Hervé ◽  
Bengaly Zakaria ◽  
Kaboré Adama ◽  
Traoré Aristide ◽  
...  

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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