SEARCH · PubMed Health

Results for “Diminazene”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1994

Response of diminazene-resistant and diminazene-susceptible Trypanosoma congolense to treatment with diminazene when occurring as a mixed infection in goats.

A study was carried out to determine whether a drug-resistant trypanosome population could influence the survival of a drug-sensitive population in mixed infections in goats. To identify both populations during the course of a mixed infection, a system for distinguishing them was developed; using a nucleotide sequence of a cDNA that was derived from Trypanosoma congolense ILNat 3.3 (IL 1616), a pair of 20-mer primers was designed which, in a PCR, amplified a 900-bp sequence from the diminazene-sensitive trypanosome, T. congolense IL 1180, but not the diminazene-resistant trypanosome, T. congolense IL 3247. The PCR technique detected 100 pg of IL 1180 DNA when mixed with 25 ng of total genomic DNA of IL 3274, as determined by gel electrophoresis and ethidium bromide-staining of the PCR products. Using the 900-bp PCR product as a 32P-labelled probe on Southern blots, the sensitivity was increased 100-fold. Three groups of five goats each were infected with IL 1180 (group A), IL 3274 (group B) or both clones simultaneously (group C), and treated with diminazene aceturate at a dose of 7.0 mg/kg body weight following detection of trypanosomes. Three other groups of three goats each were similarly infected and kept as untreated controls. All group A animals were cured, while all in group B and four animals in group C relapsed. Trypanosomes were harvested from all animals at regular intervals up to 60 days post treatment. Using the PCR techniques, IL 1180 DNA could not be detected in any post-treatment trypanosome DNA sample. It therefore appeared, on the basis of the sensitivity of the DNA detection systems used, that IL 1180 is unable to survive treatment with diminazene aceturate when mixed with IL 3274 in goats.

Animals↗

PubMed1995

Apparent rarity of diminazene-resistant trypanosomes in goats infected with a diminazene-resistant population of Trypanosoma congolense.

Experiments were carried out in goats to determine the frequency with which diminazene-resistant trypanosomes occur in parasite populations before and after the intramuscular treatment of the goats with diminazene aceturate. Trypanosoma congolense IL 3274, a diminazene-resistant clone, was used to initiate infections in three groups of five goats. The goats in the first group were treated with diminazene aceturate at a dose of 7.0 mg kg-1 bodyweight within 10 seconds of infection; one of the goats was cured. All of the second group, which received no treatment, became parasitaemic. The third group of goats received the same dose of drug as the first group but three days after all of them were first detected parasitaemic; trypanosomes reappeared in all the five goats. When this third group was treated, the frequency of trypanosomes resistant to the drug dosage was estimated to be less than 1 in 10(3). The parasites which reappeared after the treatment of these animals were used to infect two additional groups of five goats intravenously. The goats in one group were treated with the same dose of drug as before, within 10 seconds of infection and were all cured. In contrast, the five goats in the second, untreated, group became parasitaemic. Finally, when the goats in which the infections had relapsed were retreated with diminazene aceturate at the same dose rate, the level of parasitaemia temporarily decreased by at least 10(3) trypanosomes ml-1. These findings suggest that diminazene-resistant T congolense occur at low levels in trypanosome populations despite attempts to select for a population resistant to the dose of drug used.

Animals↗

PubMed1995

Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate.

The frequency of trypanosomes resistant to diminazene aceturate at a dose of 25 mg/kg of body weight was investigated for populations of Trypanosoma congolense IL 3274 which reappeared in infected mice after intraperitoneal treatment with diminazene aceturate at the same dosage. At inoculum sizes of 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes per mouse, the relapse populations were used to initiate infections in five groups of 100 mice each by the intravenous route. Immediately after infection, 50 mice in each group were treated intraperitoneally with diminazene aceturate at the aforementioned dosage; the other 50 mice functioned as untreated controls. Thereafter, all animals were monitored for 100 days for the presence of trypanosomes. In each group, trypanosomes were detected in 50 of 50 control mice, indicating 100% infectivity for all five inoculum sizes. In contrast, in the groups of 50 mice infected with 10(2), 10(3), 10(4), 10(5) and 10(6) trypanosomes and treated with diminazene aceturate, trypanosomes were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic regression, a good fit was found between the number of mice identified as parasitemic and the inoculum sizes. Maximum likelihood estimates for the proportions of trypanosomes resistant to diminazene aceturate at 25 mg/kg of body weight for the inoculum of 10(2), 10(3), 10(4), 10(5), and 10(6) organisms were 8.335 x 10(-4), 2.485 x 10(-4), 3.02 x 10(-5), 8.3 x 10(-6), and 1.6 x 10(-6), respectively. These finding indicate that the majority of the relapse trypanosomes were susceptible the the drug dosage used for selecting the population and that, surprisingly, the calculated proportion of organisms which survived drug exposure varied inversely with the inoculum size. Further experiments with mice indicated that the inverse relationship did not result from alterations in the pharmacokinetics of the drug with different inoculum sizes. The data therefore suggest that parasite inoculum size and drug dosage are important factors in estimating the apparent frequency of diminazene-resistant trypanosomes in populations of T. congolense occurring in vivo.

Animals↗

PubMed1995

The chemotherapeutic efficacy of diminazene aceturate and lithium chloride against relapse infection of Trypanosoma brucei brucei in rats.

The chemotherapeutic efficacy of diminazene aceturate (Berenil) and lithium chloride (LiCl) in relapse infection of trypanosomiasis was investigated in rats experimentally infected with Trypanosoma brucei brucei. The study showed that the combination of diminazene aceturate at (7 mg/kg) and LiCl (10 micrograms/kg) appeared more effective therapeutically than diminazene aceturate, or diminazene aceturate and LiCl and dexamethasone group, as more of the rats in the diminazene aceturate and LiCl treated-group remained aparasitaemic for longer days (60 days). Relapse parasitaemia occurred on days 10 and 12 in diminazene aceturate (7 mg/kg); diminazene aceturate (7 mg/kg) and LiCl (10 micrograms/kg) plus dexamethasone (1 mg/kg) treated group respectively, while relapse parasitaemia did not occur in the diminazene aceturate and LiCl treated group until day 20. Histopathological examination of the brain did not show any signs of inflammatory reaction in the diminazene aceturate and LiCl and dexamethasone treated group. However lesions associated with meningoencephalitis, such as cellular infiltration of mononuclear cells, perivascular cuffings and perivascular congestion and oedema were observed in the diminazene aceturate; diminazene aceturate and LiCl treated groups.

Animals↗

PubMed1996

Pharmacokinetics of diminazene in plasma and lymph of goats.

OBJECTIVE: To characterize the pharmacokinetics of diminazene in plasma and pseudo-afferent lymph of East Africa X Galla goats. DESIGN: The efferent prescapular lymphatic duct of 3 goats was cannulated 8 weeks after surgical removal of the lymph node. Thereafter, 3.5 mg of diminazene base/ kg of body weight was administered to these goats and to 3 noncannulated goats. PROCEDURE: Using high-performance liquid chromatography, concentration of diminazene was determined in plasma and lymph collected up to 96 hours after treatment. RESULTS: Maximal concentrations of diminazene in plasma of noncannulated goats (median [range], 4.30 [4.28 to 5.01] micrograms/ml), plasma of cannulated goats (3.94 [2.94 to 4.06] micrograms/ml), and lymph (1.06¿0.73 to 1.86] micrograms/ml) were significantly different (P < 0.05); values in lymph were considerably lower than those in plasma from noncannulated and cannulated animals. Time to reach maximal concentration did not differ significantly between lymph and plasma of noncannulated and cannulated goats. Over the first 24 hours after drug administration, concentration of diminazene in plasma of noncannulated goats was generally higher than that in lymph, but thereafter was similar. Apparent volume of distribution of diminazene in the plasma of noncannulated (2.57 [1.93 to 2.60] L/kg) and cannulated (2.30 [1.04 to 2.40] L/kg goats did not differ significantly. Penetration ratio of diminazene into lymph, compared with plasma, of cannulated goats was 1.69:1. CONCLUSIONS: Disposition of diminazene in goats is characterized by higher concentration in plasma than in lymph. However, the drug persists longer in lymph than in plasma. CLINICAL RELEVANCE: The longer persistence of diminazene in lymph than in plasma may account for the enhanced therapeutic efficacy of diminazene in the early stage, compared with later stages, of a tsetse fly-transmitted trypanosome infection.

Animals↗

PubMed1993

Pharmacology of diminazene: a review.

Chemotherapy for trypanosomiasis in domestic livestock depends on only a few compounds, of which several are chemically closely related. Of these compounds, the most widely used therapeutic agent in cattle, sheep and goats is diminazene aceturate. Diminazene was first described in 1955. Subsequently, a substantial body of data has been generated on various pharmacological aspects of the compound. In this review, we consider the current status of knowledge concerning the therapeutic spectrum of diminazene, resistance to diminazene in trypanosomes, and combination therapeutic regimens in which diminazene has been administered together with other compounds. Analytical techniques for diminazene, the pharmacokinetics of diminazene, data concerning diminazene's toxicity, and the different molecular mechanisms by which diminazene may exhibit trypanocidal action are also considered.

Animals↗

PubMed1992

Metabolic N-hydroxylation of diminazene in vitro.

The two N-hydroxylated derivatives (amide oximes) and the corresponding amides of the trypanocidal diamidine diminazene (Berenil, CAS 536-71-0) have been synthesized. These reference compounds made it possible to investigate the in vitro metabolism of the amidine functionalities of diminazene. Diminazene metabolites were detected for the first time, in the form of the corresponding mono- and di(amide oxime), after incubation with 12000 g supernatants from rabbit liver homogenates and careful workup (freeze drying). The identification was based on the behavior in thin-layer chromatography and on comparison of the mass spectral data for the metabolites with those for synthetic material. The N-hydroxylation of diminazene showed the properties typical of a reaction catalyzed by a microsomal monoxygenase. Diminazene amides did not occur as metabolites. The di(amide oxime) of diminazene was tested for its trypanocidal and leishmanicidal activity on various laboratory strains of trypanosomes in mice and on Leishmania donovani in hamsters. The studies showed that the di(amide oxime) has a trypanocidal effect on various strains of trypanosomes (T. brucei, T. vivax, T. congolense and T. evansi), but this is distinctly weaker than that of diminazene. A diminazene-resistant strain of T. rhodesiense is also unaffected by the di(amide oxime). The di(amide oxime) also has a leishmanicidal effect, but this again is distinctly less than that of diminazene.

Animals↗

PubMed1999

Comparative pharmacokinetics of diminazene in lactating goats and sheep.

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.

Animals↗

PubMed1993

Comparative pharmacokinetics of diminazene in noninfected Boran (Bos indicus) cattle and Boran cattle infected with Trypanosoma congolense.

The pharmacokinetics of diminazene in five female Boran (Bos indicus) cattle before and then during acute and chronic phases of experimental infections with Trypanosoma congolense were investigated. A 7.0% (wt/vol) solution of diminazene aceturate (Berenil) was used in all three phases of the study and administered as a single intramuscular dose of 3.5 mg of diminazene base per kg of body weight. There were no significant differences between the values of pharmacokinetic parameters for the noninfected cattle and the values for cattle with a chronic T. congolense infection. However, the maximum concentration of the drug in plasma during the acute phase of infection (8.25 +/- 1.72 micrograms/ml) was significantly (P < 0.01) greater than that during chronic infection (5.04 +/- 0.26 micrograms/ml) and that in the noninfected state (4.76 +/- 0.76 micrograms/ml). Similarly, the time to maximum concentration of the drug in plasma when diminazene was administered during the acute phase of infection (18.00 +/- 6.71 min) was significantly (P < 0.02) shorter than that for noninfected cattle (36.00 +/- 8.22 min) and that during chronic infection (33.75 +/- 7.50 min). The volume of distribution at steady state during acute infection (1.01 +/- 0.31 liter/kg) was significantly (P < 0.01) smaller than that in the noninfected state (1.37 +/- 0.17 liter/kg) and that in chronic infection (1.51 +/- 0.24 liter/kg). Eight hours after the drug had been administered, the concentration-time data profiles for each of the three study phases were very similar. Mean concentrations of diminazene in plasma 48 h after administration of the drug were 0.43 +/- 0.07 microgram/ml in noninfected cattle, 0.43 +/- 0.11 microgram/ml during the acute phase of trypanosome infection, and 0.44 +/- 0.09 microgram/ml during the chronic phase of the infection. Results of the present study indicate that the area under the concentration-time curve for diminazene in trypanosome-infected cattle did not differ significantly for noninfected cattle. It, therefore, appears that the total amount of diminazene attained and maintained in the plasma of cattle is not significantly altered during infection with T. congolense.

Acute Disease↗

PubMed1987

Effect of tetracycline administration on the efficacy of diminazene aceturate therapy and prophylaxis in Trypanosoma brucei infections of mice.

The simultaneous administration, to Trypanosoma brucei infected mice, of rolitetracycline or oxytetracycline and diminazene aceturate appeared to have no effect on the initial trypanocidal action of the diminazene aceturate in that trypanosomes were cleared from the circulation. It also had no effect on the duration of the aparasitaemic period which follows diminazene aceturate treatment and the mice remained free of circulating trypanosomes for some time. However, if used prophylactically, relatively large amounts of tetracyclines (4 x 10 mg kg-1) administered with 40 mg kg-1 diminazene aceturate caused a reduction of the prophylactic period compared with those mice given only diminazene aceturate. This reduction in the prophylactic period is unlikely to have any practical significance in the combination diminazene aceturate/tetracycline treatment of domestic animals as diminazene aceturate is used therapeutically and not prophylactically in the control of trypanosomiasis.

Amidines↗

PubMed1991

In vivo and in vitro sensitivity of Trypanosoma evansi and T. equiperdum to diminazene, suramin, MelCy, quinapyramine and isometamidium.

The sensitivity of three Trypanosoma equiperdum clones and thirteen Trypanosoma evansi clones originating from the People's Republic of China, the Philippines, Ethiopia and elsewhere to a series of drugs was determined in vivo and in vitro. The drugs tested were diminazene aceturate (Berenil), suramin (Naganol), MelCy (Cymelarsan), quinapyramine sulfate (Trypacide) and isometamidium chloride (Samorin). The activity of each drug was expressed as: 1) in vitro: the minimal effective concentration which killed trypanosome population by 100% within 24 h of drug exposure (MEC100); the maximum tolerated concentration in which trypanosomes could propagate at the same rate as the controls during 48 h of drug exposure (MTC100); 2) in vivo: the curative dosage in 100% of infected mice (CD100); the highest ineffective dosage: 100% of infected mice remain infected (ID100). MEC100 values of diminazene aceturate ranged from 0.0556 microgram/ml to 14.24 micrograms/ml for the eleven tested clones (differed by 256-fold); CD100 values of this drug ranged from 2.25 mg/kg to greater than 89 mg/kg (differed by greater than 40-fold). Diminazene aceturate at up to 89 mg/kg had no effect on T. evansi SHBR, T. equiperdum PBR (Berenil resistant organisms selected by continual passage of the organisms through mice treated with increasing concentrations of drug), or T. evansi AH (strain isolated in the field). Comparable MEC100 values for other trypanocides tested were 1-8 micrograms/ml for suramin, 0.005-0.04 microgram/ml for MelCy, 1-16 micrograms/ml for quinapyramine sulfate and 1-4 micrograms/ml for isometamidium chloride. Clones selected for resistance to diminazene aceturate were not cross-resistant to suramin and isometamidium chloride. In contrast, the clones resistant to diminazene were shown to be more sensitive to quinapyramine sulfate than the normal strains in in vivo tests. The results indicate that resistance to diminazene aceturate by T. evansi and T. equiperdum clones in vivo also occurred in vitro. Resistance to isometamidium chloride in the clones tested in vivo was not observed in vitro, except for T. equiperdum SA. It therefore appears that drug bioavailability is altered or drug biotransformation occurs during the in vivo test. We conclude that the in vitro assay procedure may be of potential use for screening new trypanocides and also for the rapid detection of drug resistant isolates of T. evansi and T. equiperdum.

Animals↗

PubMed1995

The effects of hyperosmolar agents lithium chloride and sucrose on the brain concentration of diminazene aceturate in rats.

The concentrations of diminazene aceturate in the brain of Trypanosoma brucei brucei infected and uninfected rats treated with diminazene aceturate (3.1 mg/kg, im) and either LiCl (2.5, 5.0 and 10 micrograms/kg) or sucrose (0.25, 0.5 and 1.0 g/kg) were determined. When diminazene aceturate was administered at a standard dose of 3.1 mg/kg (im), the addition of LiCl (10 micrograms/kg, im) increased significantly (P < 0.05) the concentration of the drug in the brains of both trypanosome infected and normal infected rats. The addition of sucrose (1.0 g/kg, im) instead of LiCl failed to give any significant increase in diminazene aceturate levels in the brain. The diminazene aceturate levels were significantly (P < 0.05) higher in the organs (brain, kidney, liver and spleen) of trypanosome infected compared to uninfected rats. The concentration of diminazene aceturate in the organs increased significantly (P < 0.05) with increasing concentrations of LiCl.

Animals↗

PubMed1997

Susceptibility of Ugandan Trypanosoma brucei rhodesiense isolated from man and animal reservoirs to diminazene, isometamidium and melarsoprol.

Thirty-six Trypanosoma brucei spp. stocks isolated from man and domestic animals in south-east Uganda were studied for susceptibility to diminazene, isometamidium and melarsoprol in vitro. All stocks were susceptible to melarsoprol. One T.b. rhodesiense stock isolated from a sleeping sickness patient showed reduced susceptibility to the veterinary drugs diminazene and isometamidium. More than 100 ng/ml diminazene or 0.78 ng/ml isometamidium were required to eliminate that stock during 10 days drug exposure. In contrast, the remaining stocks were eliminated by 0.8-6.3 ng/ml diminazene and 0.01-0.20 ng/ml isometamidium. Clones derived from the resistant T. b. rhodesiense stock showed reduced susceptibility to isometamidium and diminazene comparable to the parental population. Control of sleeping sickness by treatment of the animal reservoir could, therefore, face serious problems since drug-resistant stocks as reported here would most likely not be eliminated by recommended doses of diminazene and isometamidium.

Animals↗

PubMed1993

Pharmacokinetics of diminazene in female Boran (Bos indicus) cattle.

The disposition kinetics and bioavailability of diminazene in five healthy heifers were determined after single intravenous (i.v.) and intramuscular (i.m.) administration of the drug in sequence with a wash-out period between administrations of 6 weeks. Intact diminazene in plasma, whole blood and urine samples was analysed using high-performance liquid chromatography. Nonlinear regression analysis of the i.v. and i.m. data indicated that, for either route, the plasma disappearance curves of diminazene were best described by triexponential equations. The i.v. bolus was followed by rapid and biphasic distribution with half-life values of 0.04 h and 0.58 h, Vd(ss) was 1.91 +/- 0.42 l/kg, elimination half-life was 31.7 h while Cl averaged 1.74 +/- 0.40 ml/min/kg. Within 30 min of the i.v. dose, the erythrocyte/plasma partition ratio of diminazene was 0.30 +/- 0.15. Diminazene was rapidly absorbed following i.m. administration; t1/2ka was 0.60 h. Cmax, 4.68 +/- 1.12 micrograms/ml, was attained in 10-15 min and systemic availability was 102.42 +/- 7.25%. The half-life of the terminal disappearance phase was 145.48 h. About 8.26% of the i.m. dose was excreted intact in the urine within the first 24 h of treatment. In vitro, diminazene was bound to bovine plasma albumin to the extent of 38.01-91.10%.

Absorption↗

PubMed1993

Time-dose-response of Trypanosoma brucei brucei to diminazene aceturate (Berenil) and in vitro simulation of drug-concentration-time profiles in cattle plasma.

Bloodstream form Trypanosoma brucei brucei of axenically growing populations were incubated in the presence of 10.0, 1.0 or 0.1 micrograms/ml diminazene aceturate (Berenil) at 37 degrees C for various periods and, subsequently, either inoculated into mice or further propagated in vitro in drug-free medium. Growth was monitored for 10 days. The ability of trypanosomes of drug-sensitive CP 2137 (clone 1) to grow in vitro was irreversibly damaged after short incubation (< 1 min) with 10.0 micrograms/ml or after 15 min with 1.0 micrograms/ml diminazene aceturate. In contrast, drug-resistant CP 2469 (clone 1) trypanosomes tolerated incubation with 10 micrograms/ml of drug for up to 6 h and 1.0 micrograms/ml of drug for up to 24 h. Differences in drug susceptibility were also detected regarding infectivity to mice and changes in trypanosome cell volume. The results demonstrated that less than 1 min exposure to diminazene aceturate at concentrations as seen in bovine plasma at the initial peak after diminazene aceturate treatment is enough to irreversibly damage drug-sensitive trypanosomes. However, these concentrations were not sufficient to completely eliminate drug-resistant trypanosomes after exposure for 1-6 h; trypanosomes continued to grow for 48 h before the majority of them died and only a few organisms survived to revive the cultures. When drug-sensitive trypanosomes were exposed in vitro for 24 h to diminazene aceturate at the level of concentrations found in cattle after treatment with 3.5 mg/kg, most of the trypanosomes died and none of the surviving parasites could be propagated in vitro in the absence of drug for more than 2 days. However, a small population of drug-resistant trypanosomes was not irreversibly damaged and a few surviving trypanosomes were able to establish growing cultures. The addition of feeder layer cells did not change the outcome of these experiments.

Animals↗

PubMed1992

Response of Trypanosoma congolense in goats to single and double treatment with diminazene aceturate.

Diminazene aceturate is one of a limited number of compounds currently marketed for treatment of trypanosomiasis in cattle, sheep and goats. The pharmacokinetics of the compound in goats suggest that double treatment with diminazene aceturate might enhance the compound's therapeutic activity. A study was therefore conducted in goats using two clones of Trypanosoma congolense, IL 3274 and IL 1180, which were previously shown to be resistant and sensitive, respectively, to single treatment with diminazene aceturate. The results indicated that, as compared to single treatment, double treatment with diminazene aceturate at a dose of 7.2 mg kg-1 bodyweight, at either eight or 24 hour intervals, did not greatly enhance the therapeutic activity of the drug. Furthermore, treatment with the same drug dose eliminated infections with T congolense IL 3274 when treatment was administered 24 hours after infected Glossina morsitans centralis had fed, but failed to do so if treatment was delayed until after goats were detected to be parasitaemic. This suggests that failure of T congolense IL 3274 to respond to treatment with diminazene may not be due to drug resistance per se.

Animals↗

PubMed1993

Variation in sensitivity of Trypanosoma congolense to diminazene during the early phase of tsetse-transmitted infection in goats.

Twenty-five goats were randomly allocated to five groups of five animals each and infected with Trypanosoma congolense IL 3274 via the bites of infected Glossina morsitans centralis. At intervals of 1, 4, 8, 12 or 19 days following infection, each group of five animals was treated intramuscularly with diminazene aceturate at a dose of 7.0 mg kg-1 body weight (b.w.). While treatment on Day 1 eliminated infections in all five goats, treatment on Day 19 did not cure any of the animals; in groups treated 4, 8 or 12 days following infection, two of five goats in each group were cured. Since the alteration in apparent resistance of T. congolense IL 3274 between Day 1 and Day 19 could have been due to alteration in expression of drug resistance by trypanosomes as the population expanded, the experiment was repeated using trypanosomes that reappeared in the animals that had been treated with diminazene aceturate on Day 19. On Day 36, when all five animals were parasitaemic, five groups of teneral G. m. centralis, each containing 160 flies, were fed on one occasion on each of the five goats (one group of testse flies per goat). Thereafter, each group of tsetse flies was maintained on clean rabbits. When infective, five flies from each group were allowed to feed on two naive goats each (i.e. two goats per group of tsetse flies). One animal in each pair was treated 24 h after infection with diminazene aceturate at a dose of 7.0 mg kg-1 b.w., the other was treated on Day 19, when parasitaemic, with the same drug dosage. As before, treatment 24 h following infection eliminated infections in all animals, but when treatment was delayed until Day 19, trypanosomes in all animals were refractory to treatment. Thus, although tsetse flies were infected with trypanosomes that had arisen in infected goats following treatment with diminazene aceturate at a dose of 7.0 mg kg-1 b.w., when the same flies were allowed to feed on clean goats, the resultant infections were sensitive to treatment with the same drug dosage when administered 24 h following infection. These data therefore indicate that there is a significant alteration in diminazene sensitivity of IL 3274 between Day 1 and Day 19 and that this is associated with an alteration in the resistance phenotype of the trypanosomes.

Animals↗

PubMed1996

Trypanocidal value of liposomal diminazene in experimental Trypanosoma brucei evansi infection in mice.

The trypanocidal value of liposomal diminazene was examined. Three hundred mice were divided randomly into six groups of 50 mice each. Groups 1, 2 and 3 were pretreated 2 h before Trypanosoma brucei evansi challenge with 0.2 ml saline solution, 0.2 ml diminazene solution (5 mg ml-1) and 0.2 ml liposomal solution (5 mg diminazene per ml), respectively. Mice in Group 1 all died within 6 days, 33 in Group 2 and four in Group 3 died within 15 days after challenge, respectively. Groups 4, 5, and 6 were treated 4 days after T. b. evansi challenge with 0.2 ml saline solution 0.2 ml diminazene solution (5 mg ml-1) and 0.2 ml liposomal solution (5 mg diminazene per ml), respectively. Mice in Group 4 all died within 6 days, 19 in Group 5 and two in group 6 died within 15 days after challenge, respectively. The remaining mice survived for more than 30 days, were symptom-free and behaved normally. No adverse effects associated with treatment were noted.

Animals↗