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At least 199 records · Page 11Linked to original sources
PubMed1996

Trypanocidal resistance in Trypanosoma evansi in vitro: effects of verapamil, cyproheptidine, desipramine and chlorpromazine alone and in combination with trypanocides.

A study was conducted in vitro to assess the ability of calcium antagonists to reverse trypanocidal resistance in Trypanosoma evansi. Susceptibility patterns of sensitive and resistant parasites were evaluated against calcium antagonists of several chemical classes (verapamil, cyproheptidine, desipramine and chlopromazine), alone and in combination with suramin, diminazene aceturate or melarsen oxide cyteamine. The putative resistance modulators were intrinsically antitrypanosomal, but were unable to reverse resistance to any of the trypanocides tested. It was thus concluded that resistance to these trypanocides in T. evansi may differ from drug resistance mechanisms occurring in cancer cells, malaria or in South American trypanosomosis, where calcium antagonists have successfully reversed resistance.

Animals↗
PubMed2004

Application of field methods to assess isometamidium resistance of trypanosomes in cattle in western Ethiopia.

This study assessed the degree of isometamidium resistance of trypanosomes infecting cattle in the upper Didessa valley of western Ethiopia. An initial prevalence study was conducted to identify sites with a high risk of trypanosmosis in cattle. The trypanosome prevalence varied widely, with two sites, Kone (21.3%) and Village 1 settlement (15%) having a relatively high prevalence based on the phase-contrast buffy-coat technique (BCT). In the highest risk area, the Kone settlement, an isometamidium block treatment study was conducted from April to June 2001. A total of 300 cattle were included in this study, 100 from each of three villages (Cheleleki, Kolu and Burka). At day minus 14 of the study, all 300 cattle were treated with diminazene aceturate at 7 mg/kg body weight. Subsequently, these cattle were ear-tagged and randomly assigned into two groups, 50 controls and 50 for isometamidium treatment in each village. Fourteen days later (day 0), the 50 treatment cattle were given isometamidium chloride at 1 mg/kg body weight. Both groups of cattle were then examined for trypanosome parasites using BCT every 14 days until 84 days. The two indices used in assessing isometamidium resistance, namely the proportion of infections during an 8-week follow-up period and the ratio of mean hazards in an isometamidium treated versus untreated group, provided consistent results across the three villages. In Burka village, both indices demonstrated the presence of isometamidium resistance trypanosome infections while in Cheleleki and Kolu villages, both indices did not indicate significant levels of resistance. There were significant differences between the Kaplan-Meier survival estimates of the control and treatment groups in Cheleleki (P < 0.01) and Kolu (P < 0.05) but not in Burka (P > 0.05).

Animals↗
PubMed2004

Trypanocidal failure suggested by PCR results in cattle field samples.

The aim of this study was to assess, whether polymerase chain reaction (PCR) allows sensitive screening of treatment failure suspicions in areas, where drug resistance against African animal trypanosomosis (AAT) appears to be a problem. PCR was used to detect trypanosome infections prior to, 14 and 28 days after controlled treatment of 738 cattle from 10 villages in Kénédougou, Burkina Faso with isometamidium chloride and diminazene aceturate. Using three sets of primers, PCR was three-four times more sensitive and better at species identification, than standard microscopic examination. The better sensitivity and species specificity of PCR have important advantages for drug resistance studies in the field.

Animals↗
PubMed2005

Leishmania donovani: differential activities of classical topoisomerase inhibitors and antileishmanials against parasite and host cells at the level of DNA topoisomerase I and in cytotoxicity assays.

Different classes of topoisomerase (TOP) inhibitors and antitrypanosomatid agents exhibited variable efficacies against Leishmania donovani parasites and human mononuclear cells both at the level of DNA topoisomerase I (TOPI) catalytic activity and in cytotoxicity assays. Bis-benzimidazoles and the diamidine diminazene aceturate exhibited uniformly high efficacies against parasite and host enzymes as well as against parasite and mononuclear cells, but pentamidine showed around 2 orders of magnitude greater specificity for Leishmania TOPI and amastigote cells (P<0.05). The protoberberine coralyne and the flavonoid quercetin were highly potent, but non-selective, inhibitors in vitro, although the latter showed slight selectivity for parasite TOPI. Camptothecin was selective for mononuclear cells at both levels (P<0.05) and sodium stibogluconate was selective only at the enzyme level displaying 30-fold greater potency against parasite TOPI (P<0.05). These data suggest that at least part of pentamidines' leishmanicidal activity may be mediated through TOPI inhibition, and support the feasibility of exploiting differences between Leishmania and human TOPs to develop modified compounds with improved selectivity.

Acid Phosphatase↗
PubMed2005

Synthesis of a novel PEG-block-poly(aspartic acid-stat-phenylalanine) copolymer shows potential for formation of a micellar drug carrier.

A novel functionalised copolymer with three polymeric components, poly(ethylene glycol)-block-poly(aspartic acid-stat-phenylalanine), PEG-P(asp-phe), was synthesised and investigated for its potential to form micelles via ionic interactions with a model water-soluble drug, diminazene aceturate. Drug-free solutions of structurally related PEG-P(asp-phe) 5:6:4 and PEG-P(asp-phe) 5:4:6 copolymers indicated polymeric aggregation into micellar-type constructs. The size of PEG-P(asp-phe) 5:6:4 micelles was found to be pH and drug content-dependent. The drug-loaded systems existed as discreet units and were fairly uniform in size and shape. More drug could be included in the PEG-P(asp-phe) 5:6:4 micelles as compared to if only interaction with carboxyl groups from aspartic acid units was responsible for micelle formation, indicating the augmentative role of phenylalanine moieties in drug-incorporation. The slower in vitro drug release from PEG-P(asp-phe) 5:6:4 micelles as compared to PEG-Pasp (AB) micelles indicated the role of the phenylalanine moiety in controlling drug release. This study, therefore, confirmed the potential of a novel tri-component copolymer structure, PEG-P(asp-phe), for the formation of polyionic micelles for drug delivery.

Chemical Phenomena↗
PubMed2006

Trypanosomiasis by Trypanosoma vivax in cattle in the Brazilian semiarid: Description of an outbreak and lesions in the nervous system.

An outbreak of trypanosomiasis by Trypanosoma vivax is reported in the semiarid of Paraíba, Northeastern Brazil from May to August 2002. Sixty-four cows out of 130 were affected; 11 died and the other recovered after treatment with diminazene aceturate. Affected animals had fever, anemia, weight loss, hypoglycemia, increased serum levels of aspartate aminotransferase and, in nine cows, nervous signs. All cows with nervous signs died; six of them recovered after treatment, but the disease relapsed. Six cows aborted and one delivered a calf that died immediately after parturition. Thirty-two out of 100 calves were affected and five died. Nervous signs were not observed in the calves. Gross lesions were thickening of the meninges, enlarged lymph nodes and prominent white pulp of the spleen. The main histological lesion was meningoencephalitis and malacia in the brain of cows with nervous signs. No antibodies against trypanosomes were found in 33 blood samples collected before the outbreak in the affected farm and in 29 samples collected at the same time in two other neighbor farms. Until January 2003, all 89 animals tested had antibodies against T. vivax, suggesting the occurrence of sub clinical infections in cattle without clinical signs. Only two out of 85 serum samples collected on April 2004 were positive for T. vivax antibodies. Data obtained suggested that the semiarid region is non-endemic for trypanosomiasis and that disease occurred due to introduction of the parasite in a susceptible population after an apparent rise in the Tabanus spp. population.

Abortion, Veterinary↗
PubMed1997

The influence of supplementation with cotton seed cake on the resistance of Ugandan goats to primary and secondary challenges with Trypanosoma congolense and on their response to treatment.

The present study investigated the influence of supplementation with cotton seed cake on the resistance of the Small East African breed of goats to primary and secondary challenges with Trypanosoma congolense and on their response to chemotherapy with diminazene aceturate. The supplemented group received 300 g of cotton seed cake per day in addition to about 500 g of fresh napier grass which was available to the unsupplemented group. It was observed that the supplemented infected (SI) group tended to sustain higher intensities of parasitaemia than the unsupplemented infected (USI) group particularly during the primary challenge and both groups showed longer prepatent periods to secondary challenge than to primary challenge. Infection caused a significant reduction in the rate of live body weight gain in the USI group compared with the unsupplemented control (USC) group whilst the SI group grew at the same rate as the supplemented control (SC) group. This effect was observed both during primary and secondary challenges. Following primary challenge, both infected groups developed similar degrees of anaemia, but the packed red cell volume (PCV) levels in the SI group improved towards the end of the first challenge and were also significantly higher than those of the USI group during the second challenge. After treatments at 56 and 126 days after infection (DAI), the greatest response was observed in PCV values. The response of the SI group was superior to that of the USI group and by 4 weeks after treatment the PCV values of the SI and SC groups were similar while those of the USI group were significantly lower than those of the USC group. It is concluded that supplementation with cotton seed cake plays an important role in the rate of live weight gain, and rate of recovery from anaemia produced by trypanosome infection in goats.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Cytokines and the acute phase response in post-treatment reactive encephalopathy of Trypanosoma brucei brucei infected mice.

Stimulation of the acute phase response during infection of mice with Trypanosoma brucei brucei (T. b. brucei) was investigated in an experimental model of the post-treatment reactive encephalopathy (PTRE), a common side-effect of anti-trypanosome therapy. Plasma levels of the acute phase proteins (APP), haptoglobin (Hp) and serum amyloid P (SAP) increased by day 7 post-infection, but by day 20 had fallen to an intermediate level. This was accompanied by induction of the cytokines, interleukin (IL)-6 and tumour necrosis factor-alpha (TNFalpha) in both liver and brain. Treatment of mice on day 21 with a subcurative dose of diminazene aceturate (Berenil), a procedure known to induce a mild PTRE, cleared the parasite from the circulation with plasma APP and liver expression of mRNA for IL-6 and TNFalpha returning to the levels in the controls. Cytokine mRNA for both IL-6 and TNFalpha was detected in the brains of animals with developing PTRE although TNFalpha was not significantly greater than in the control group. A further subcurative dose of Berenil, leading to a more severe PTRE, was associated with elevated serum concentrations of Hp and SAP, increased TNFalpha mRNA in the liver and detectable IL-6 and TNFalpha mRNA in the brain. mRNA for IL-1alpha was expressed in brain and liver samples from all animals. A severe PTRE caused a systemic acute phase response which was not apparent with a mild PTRE. The pattern of cytokine mRNA induction was similar following both drug treatments. However, the difference in APP production could be caused by a breakdown in the blood-brain barrier during severe PTRE allowing cytokine synthesised in the brain to enter the circulation and maintain a systemic response.

Acute-Phase Proteins↗
PubMed1995

Inhibition of the proteinase activity in mastitic milk.

The antiproteolytic activity of selected proteinase inhibitors was studied in mastitic bovine milk and urokinase-activated normal milk using a caseolytic agar diffusion assay. The inhibition profiles of mastitic milk and urokinase-activated milk were compared with those of purified proteinases. The proteinase inhibition profile of mastitic milk did not resemble that of any of the pure proteinases, indicating a mixed type of proteinase system in mastitic milk. The trypanocidals diminazene (equivalent to Berenil) and pentamidine (equivalent to Lomidine), together with aprotinin (Trasylol), showed most promise when considering possible applications in mastitis to break up the proteolytic cascade within the inflamed udder.

Animals↗
PubMed1977

Trypanocidal activity of blood and tissue fluid from normal and infected rabbits treated with curative drugs.

A new technique for determining the trypanocidal activity of body fluids has been devised, using very small quantities in the wells of plastic microtest plates. The activities of blood and tissue fluid of rabbits have been measured after the infection of melarsoprol, suramin, diminazene aceturate and isometamidium chloride. Activity against Trypanosoma (Trypanozoon) brucei persisted in body fluids for a shorter time in treated normal rabbits than in treated rabbits infected with the trypanosome. The difference was caused by the participation of the immune response of the infected animals. The new technique was sensitive enough to detect these interactions of chemotherapy and immunology and should be of use in the study of new trypanocidal compounds.

Animals↗
PubMed1988

Attempts to protect goats against challenge with Trypanosoma vivax by initiation of primary infections with large numbers of metacyclic trypanosomes.

Attempts were made to immunize goats by infection with large numbers of metacyclic trypanosomes of a clone of Trypanosoma vivax, followed by chemotherapy. Five groups of 6 goats each were infected intradermally with 5 different doses of cultured metacyclics of T. vivax, ranging from 10(2) to 10(6) trypanosomes/goat. Four weeks after infection, the goats were treated with 10 mg/kg diminazene aceturate (Berenil, Hoechst A.G.). Three weeks after treatment, 3 goats in each group were challenged intradermally with 10(4) homologous metacyclics derived from culture. The remaining 3 goats in each group were challenged by 20 tsetse infected with the homologous clone. Five out of 30 goats were resistant to homologous challenge; 4 of the goats that had been challenged with culture parasites, and 1 that had been challenged by tsetse. In each group 1 goat was protected. Protection was therefore not apparently influenced by the number of trypanosomes used to establish the primary infection. In another experiment, 6 goats were each infected by feeding 100 tsetse on the goats for 15 consecutive days. Three weeks after infection the goats were treated with Berenil and 3 weeks later challenged by 20 tsetse infected with the homologous clone. Three out of the 6 goats resisted challenge. The susceptible goats in both experiments, however, showed a reduction in the peak of parasitaemia following challenge compared with both challenge controls and the initial infections. Lytic antibodies to cultured metacyclics of T. vivax were detected in goats that resisted challenge after a primary infection with cultured metacyclics, and in resistant and susceptible goats after a primary infection by tsetse. All infected goats produced lytic antibodies to live bloodstream forms, as well as antibodies to bloodstream form lysates (demonstrated by ELISA). It is suggested that the immunity that had been induced in some of the experimental animals is due to antibody responses to both metacyclic and bloodstream variable antigen types (VATs) expressed during infection.

Animals↗
PubMed1988

Extravascular foci of Trypanosoma vivax in goats: the central nervous system and aqueous humor of the eye as potential sources of relapse infections after chemotherapy.

Relapse of parasitaemia after drug treatment of trypanosome infection is normally attributed to drug-resistance on the part of the parasite, under-dosage of the drug or reinfection of the host. In addition, inaccessibility of parasites to drug through sequestration in privileged extravascular sites has been shown in the past to occur with Trypanosoma brucei, and we have obtained evidence that extravascular foci of T. vivax can also serve as a source of relapsing infections. Infection of goats with a West African stock of T. vivax resulted in severe illness, which was fatal if untreated. During the terminal stage of an acute infection, clinical signs of central nervous system involvement were apparent. Histologically, the choroid plexus was swollen and oedematous, and in some cases meningitis or meningoencephalitis was seen. Trypanosomes could be detected in the cerebrospinal fluid, and also extravascularly in the choroid plexus and meninges. In three cases they were present in the aqueous humor, associated with corneal cloudiness or opacity. Treatment of 2 goats with the trypanocidal drug diminazene aceturate eliminated parasitaemia, but infections in both relapsed about 6 weeks later, despite trypanosomes being undetectable in the bloodstream during the intervening period. We conclude that the relapse infections were caused by reemergence of trypanosomes from the CNS and/or the eye, where sequestered parasites may have been inaccessible to the trypanocide.

Animals↗
PubMed1988

Susceptibility of goats to tsetse-transmitted challenge with Trypanosoma vivax from East and West Africa.

To determine if, as is the case with Trypanosoma brucei and T. congolense, serodemes of T. vivax could be distinguished on the basis of immunity to the metacyclic stages of the parasite, attempts were made to immunize goats by infection with infected tsetse, followed by chemotherapy or eventual 'self-cure'. Thirty goats were infected by tsetse with either clones or stocks of T. vivax from East or West Africa. Twenty-four goats were treated with diminazene aceturate (Berenil, Hoechst A.G.) 2-6 weeks after infection and 6 goats were allowed to self-cure. Infection, followed by treatment, induced immunity to a first homologous challenge by infected tsetse in only 2 of 24 goats (one immune to the East African stock, and the other to a clone of the West African stock). Immunity to a clone of the East African stock was induced in 3 or 4 animals after a second infection and treatment and in the fourth animal of the group following a third infection and treatment. One of 2 goats infected with the clone of the East African stock was immune to challenge at 16 weeks, following self-cure without treatment, and 1 of 4 goats infected with the parent stock was similarly immune when challenged at 40 weeks post-infection. Goats susceptible to infection with East African T. vivax showed evidence of partial immunity by delayed pre-patent periods and depressed parasitaemias after challenge. Goats infected with the relatively more virulent West African T. vivax were, however, completely susceptible to infection after homologous challenge, and showed only a slight delay in pre-patent period. A similar result was obtained in a further 8 goats primed and challenged by large numbers of tsetse (20 or 100 infected tsetse/goat) with the West African T. vivax. In further experiments using a very short treatment interval, infections following challenge were clearly shown to be the result of a lack of immunity rather than relapse following treatment. Lytic antibody activity to cultured metacyclic trypanosomes could not be detected during infection but such activity against bloodstream forms was detected after 2 weeks of infection. It is suggested that the primary reason for the erratic induction of immunity to T. vivax employing this methodology is the low number of metacyclics transmitted by infected tsetse, and thus poor antigenic stimulus encountered by goats upon tsetse challenge.

Africa, Eastern↗
PubMed1999

Estimating the effects of tsetse control on livestock productivity--a case study in southwest Ethiopia.

A tsetse control campaign was started in January 1991 using a synthetic pyrethroid cypermethrin 'pour-on' applied monthly to cattle exposed to high levels of drug-resistant trypanosomes in the Ghibe valley of southwest Ethiopia. In December 1992, a cost-recovery scheme was introduced, and thereafter farmers paid for treatment. An average of 100 village Ethiopian Highland Zebu cattle were monitored monthly from March 1986 to February 1997. Individual animals in this herd were treated with diminazene aceturate (Berenil, Hoechst, Germany) at 3.5 mg/kg when trypanosomes were detected and their packed cell volume was less than 26%. Superimposed on this systematic trypanocidal chemotherapy, control of tsetse resulted in average reductions from 1992 to 1996 of 95% and 75% in the mean relative densities of tsetse and biting flies, respectively, and of 63% in the prevalence of trypanosomal infections in cattle. Despite these reductions, there was no significant increase in the body weight of the cows, calving rate or the mean body weight of calves at 12 months of age. There was, however, an average decrease of 57% in calf mortality (including still births) by 12 months of age, an increase of 49% in the ratio of live calves under 12 months of age to cows over 36 months of age, and an increase of 8% in the body weight of adult males.

Administration, Topical↗
PubMed2000

The use of trypanocides and antibiotics by Maasai pastoralists.

Information was collected on the use of veterinary drugs by Maasai pastoralists in an area of Kenya where tsetse flies and trypanosomosis occur. Three herds of cattle were followed for between 4 and 5 years and records were kept of every veterinary drug treatment given by the livestock owners. Almost all treatments were either with the trypanocides homidium or diminazene, or with oxytetracycline by intramuscular injection. The rate of trypanocide use varied between 0.66 and 1.56 treatments per animal per year, while oxytetracycline use was between 0.20 and 1.00 treatments per animal per year. Farmers were injecting these drugs in the absence of veterinary supervision, obtaining their supplies mainly from local village shops or informal traders. Underdosing with trypanocides appeared to be uncommon and the indications were that farmers generally gave the drugs at dosage rates above the recommended standard dose. Accurate information on the dose rates of oxytetracycline could not be obtained, but it was noted that in most cases farmers gave a single injection rather than a course of treatment. In a proportion of cases, trypanocides and antibiotics were mixed together before injection. The farmers administered the drugs when disease was recognized and were rarely using trypanocides as prophylactics. Although necessity forces the livestock owners to obtain and use these drugs without veterinary supervision, there are concerns with regard to the possibility of drug misuse and the development of drug resistance.

Animal Husbandry↗
PubMed1990

Selective cleavage of kinetoplast DNA minicircles promoted by antitrypanosomal drugs.

Pentamidine, diminazene aceturate (Berenil), isometamidium chloride (Samorin), and ethidium bromide, which are important antitrypanosomal drugs, promote linearization of Trypanosoma equiperdum minicircle DNA (the principal component of kinetoplast DNA, the mitochondrial DNA in these parasites). This effect occurs at therapeutically relevant concentrations. The linearized minicircles are protease sensitive and are not digested by lambda exonuclease (a 5' to 3' exonuclease), indicating that the break is double stranded and that protein is bound to both 5' ends of the molecule. The cleavage sites map to discrete positions in the minicircle sequence, and the cleavage pattern varies with different drugs. These findings are characteristic for type II topoisomerase inhibitors, and they mimic the effects of the antitumor drug etoposide (VP16-213, a semisynthetic podophyllotoxin analog) on T. equiperdum minicircles. However, the antitrypanosomal drugs differ dramatically from etoposide in that they do not promote detectable formation of nuclear DNA-protein complexes or of strand breaks in nuclear DNA. Selective inhibition of a mitochondrial type II topoisomerase may explain why these antitrypanosomal drugs preferentially disrupt mitochondrial DNA structure and generate dyskinetoplastic trypanosomes (which lack mitochondrial DNA).

Animals↗
PubMed1985

Induction of protective immunity in cattle by tsetse-transmitted cloned isolates of Trypanosoma congolense.

Cattle infected with cyclically (tsetse)-transmitted clones of Trypanosoma congolense were treated with the trypanocidal drug diminazene aceturate ('Berenil') at various intervals during development of local skin reactions (chancres), in order to investigate the role played by trypanosomes in the skin in the induction of protective immunity. Cattle, treated on or before Day 12 after infection and prior to detection of trypanosomes in the blood, showed a range of susceptibility to cyclically-transmitted homologous challenge three weeks later. An animal treated on Day 5, when the skin reaction was first detected, was completely susceptible, whereas of the animals treated on Days 10 to 12 at the peak of the skin reaction, some were immune, others exhibited partial immunity, while the rest were susceptible. The susceptible animals, however, showed evidence of sensitization to trypanosomes, as demonstrated by development of Arthus-type reactions following homologous challenge with tsetse-transmitted parasites or intradermal inoculation with lysed or irradiated homologous trypanosomes. Cattle treated 15 or more days after cyclically-transmitted infection, when chancre reaction was subsiding and trypanosomes were present in the blood, were completely immune to challenge. Immunity was achieved by treating cattle on Day 5 and Day 10 after infection with cyclically-transmitted trypanosomes but only if this procedure was repeated on several occasions, indicating that bloodstream forms of trypanosomes were not essential for the induction of protective immunity. Protective immunity appeared to be effective against the metacyclic trypanosomes at the level of the skin, as animals which were immune to homologous challenge with cyclically-transmitted parasites did not develop detectable skin reactions at the site of the tsetse bite. Furthermore, the time of the appearance in the serum of antibody which completely neutralized the metacyclic population (Day 15) coincided with the time at which cattle had developed immunity against homologous challenge. The immunity produced lasted for five months.

Animals↗
PubMed1992

An enzyme-linked immunosorbent assay (ELISA) for the detection of trypanosomal antigens in goat serum using a monoclonal antibody.

An IgM murine monoclonal antibody (MAb) TEA 1/23.3.4.6 raised against circulating trypanosome antigens was used in a sandwich ELISA to assay trypanosomal antigens in a trypanosome lysate preparation and in sera from goats infected with Trypanosoma brucei evansi. As little as 1.25 ug/ml of trypanosomal antigen could be detected by this assay. Following infection, trypanosomal antigens were first detected in goat serum 24 hours after the intravenous (i/v) or 6 days after the intramuscular (i/m) inoculation of trypanosome parasites. Antigen levels remained detectable during the course of infection. After treatment with diminazene aceturate, antigens dropped to undetectable levels between day 12 to 41, suggesting that this assay offers a promising approach to the diagnosis of African Trypanosomiasis.

Animals↗