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PubMed1988

Development of a radioimmunoassay for isometamidium.

A radioimmunoassay for the trypanocidal drug isometamidium (ISMM) has been developed using antibodies produced in sheep immunized against the drug cross-linked to human serum albumin. With 14C-ISMM as a radioligand, cross-reactivity of the antibodies was determined and found to be less than 3% with pyrithidium, diminazene and quinapyramine and about 13% with homidium. The limit of detection of ISMM in serum without prior extraction was 5.8 pmol/tube and within-assay and between-assay coefficients of variation were four and 14% respectively.

Animals↗
PubMed1989

Efficacy of experimental trypanocidal compounds against a multiple drug-resistant Trypanosoma brucei brucei stock in mice.

Several experimental trypanocidal compounds, 6-amidino-2-(4-amidinophenyl)indole dilactate (DAPI), DL-alpha-difluoromethylornithine (DFMO), 2-(dimethylamino)-4'-[(1-methyl-2-nitroimidazole-5-yl) methoxy] aceto-anilide (Ro 15-0216), sinefungin, and triacetylbenzene-tris(guanylhydrazone)trimethanesulfonate hydrate (TBG-MS) were tested to evaluate their ability to cure mouse infections with a multiple drug-resistant Trypanosoma brucei brucei stock (CP 547). This stock proved to be drug-resistant against diminazene aceturate, homidium chloride, isometamidium, quinapyramine sulfate, Mel B, and pentamidine isethionate but fully sensitive to suramin. Compared with the sensitive stock CP 462, the drug-resistant stock CP 547 was completely resistant to 16-fold the curative dose of sinefungin and partially resistant to 4-fold the curative dose of DAPI and to 13-fold the curative dose of TBG-MS, a dose that killed 25% of the animals due to its toxicity. Ro 15-0216 cured all mice when 18 times the usual curative dose level was given. DFMO was equally effective against both stocks.

Animals↗
PubMed1978

Evaluation of an indirect fluorescent antibody test, enzyme-linked immunosorbent assay and quantification of immunoglobulins in the diagnosis of bovine trypanosomiasis.

An indirect fluorescent antibody test (IFAT), a microscale version of the enzyme-linked immunosorbent assay (microELISA) and determination of IgM levels in serum were assessed for their comparative diagnostic value in the detection of bovine trypanosomiasis. Serum samples from drug-treated N'dama cattle and untreated N'dama and Zebu cattle from Liberia were examined for the presence fo antibodies to trypanosomes. In the untreated Zebu cattle, infections with T. vivax predominated and the prevalence of infection was higher than that found in untreated N'damas in which infections with T. congolense predominated. The proportion of animals which showed serological evidence of trypanosomiasis in the untreated Zebus was slightly higher than that found in the untreated N'damas. The prevalence of infection was low in N'dama cattle which had been treated with diminazene aceturate and homidium chloride but 50% of the animals showed serological evidence of trypanosomiasis. More serologically positive animals were detected by microELISA than IFAT, but both tests were equally sensitive in detecting antibodies in cattle in which trypanosomes were demonstrated by examination of peripheral blood. With both IFAT and microELISA it was necessary to carry out tests using antigens prepared from T. brucei, T. vivax and T. congolense in order to detect all serologically positive animals. Increases in serum IgM occurred in both N'dama and Zebu cattle but the levels were raised in only approximately half of the known infected animals. Overall, more animals gave positive reactions with IFAT and microELISA than showed raised IgM levels.

Animals↗
PubMed1988

Prevalence of anaplasmosis and babesiosis in N'Dama cattle of the Gambia.

Sera from 184 N'Dama cattle randomly selected and averaging 2-7 years of age were tested for the presence of specific antibodies to Anaplasma marginale, Babesia bovis and B. bigemina, using one or more serological tests including complement fixation, rapid card agglutination and indirect fluorescent antibody (IFA). Tests for A. marginale and B. bovis were essentially negative. Utilising the IFA test 65% of the sera tested were positive for B. bigemina. Three randomly selected two-year-old N'Dama bulls were splenectomised. All three showed an acute recurrence of a B. bigemina parasitaemia. Two died following typical signs of acute babesiosis and a third recovered following diminazene therapy. No evidence of either B. bovis or A. marginale recrudescence was observed in the single surviving bull. Babesia bigemina appears endemic in the N'Dama cattle of The Gambia but no confirmed serological or clinical evidence of B. bovis or A. marginale was observed.

Agglutination Tests↗
PubMed1994

Trypanosomosis and reproduction: I. Effect of Trypanosoma vivax infection on the oestrous cycle and fertility in the ewe.

Ten West African Dwarf ewes were inoculated with Trypanosoma vivax and, at varying intervals, treated subcuratively with diminazene aceturate to maintain the infection. Soon after infection all ewes had anoestrus for 40 to 96 days and 5 died by day 110 post infection. Compared to control animals, infected ewes had prolonged low levels of plasma progesterone until recovery or death. However, no gross or histological lesions were detected in the endocrine or reproductive organs. Of the survivors, the 5 that were aparasitaemic subsequently became pregnant and had normal gestations.

Anestrus↗
PubMed1991

Porcine cerebral Trypanosoma brucei brucei trypanosomiasis.

This paper describes the investigation of a disease outbreak among 10 adult pigs in Nsukka, Anambra State, Nigeria. Prior to the investigation one sow died of the disease. Trypanosomes were later detected in the blood of two of the nine pigs subsequently investigated. All the pigs were then treated with deep intramuscular injection of 8 mg/kg diminazene aceturate (Berenil). Thirty six days after treatment a boar and a sow relapsed with signs similar to the ones shown previously. Further examination of their blood and faeces revealed nothing of parasitological significance. Following deteriorating condition and development of nervous signs the boar was salvaged while the sow died of the infection. Brain impression smears taken from both animals during postmortem examination revealed numerous trypanosome parasites identified by morphology and blood incubation infectivity test (BIIT) as Trypanosoma brucei brucei. The clinical and economic significance of the outbreak are discussed.

Animals↗
PubMed1997

Observations on the treatment of natural haemosporidia infections by total alkaloid of Peganum harmala L. in cattle.

Eighty two cattle naturally infected with haemosporidians were treated with total alkaloid hydrochloride of Peganum harmale L. (0.5 mg/kg/day). Fifty eight cases with Theileria sergenti showed a cure rate of 86%; thirteen cases with Theileria annulata showed a cure rate of 85%; eight cattle infected with Babesia bigemina showed a cure rate of 88% and three cases of Anaplasma marginale were completely cured. The results suggested that the curative effect of total alkaloid of P. harmale was better than that of diminazene aceturate and produced minimal side effects. The alkaloid could also be administered to pregnant animals. It was concluded that the total alkaloid of P. harmale showed a marked effect as a treatment for haemosporidican infections in cattle.

Alkaloids↗
PubMed1992

Failure of chemoprophylaxis against bovine trypanosomiasis on Galana Ranch in Kenya.

The duration of prophylaxis provided by 1 mg kg-1 bodyweight of homidium bromide was compared with that provided by 1 mg kg-1 bodyweight of isometamidium chloride in a 12 month field trial involving 90 Boran cattle exposed to trypanosome challenge on Galana Ranch in Kenya. Weekly trypanosome prevalences of over 30% were observed during 4 of the 12 months. During these periods of heavy challenge, parasites were detected 2-3 weeks after administration of both homidium bromide and isometamidium chloride. Both prophylactic drugs were administered, on a group basis, eight times over the 12 month trial and in addition individual infections were also treated with diminazene aceturate. Isometamidium chloride provided slightly longer periods of prophylaxis than homidium bromide, 28.4 days compared with 25.4 days. There was a highly significant difference in the productivity of the two groups during a period of poor grazing. 27% of the isometamidium chloride herd died from a severe wasting condition with substantial liver damage evident on post mortem. The condition was not observed in the homidium bromide herd. The surviving animals in the isometamidium chloride herd had a mean annual weight gain of 24 kg less than that recorded in the homidium bromide herd.

Animals↗
PubMed1993

Inhibition of topoisomerases in African trypanosomes.

African trypanosomiasis continues to pose a challenge for the development of new chemotherapy. Type II topoisomerases, essential enzymes in nucleic acid metabolism, have proven highly suitable as targets for antibacterial and antitumor therapy. Well-characterized topoisomerase II inhibitors affect the cognate nuclear and mitochondrial enzymes in Trypanosoma equiperdum. Inhibition is accompanied by extensive fragmentation and structural alteration in nuclear and mitochondrial DNA. Some clinically important antitrypanosomal drugs bind to DNA (i.e., pentamidine, isometamidium, diminazene). These agents inhibit the mitochondrial, but not nuclear, topoisomerase II of trypanosomes. These studies suggest that type II topoisomerase inhibitors may prove to be effective and safe new antitrypanosomal drugs.

Animals↗
PubMed1994

Induction of resistance to melarsenoxide cysteamine (Mel Cy) in Trypanosoma brucei brucei.

A population of Trypanosoma brucei brucei with reduced sensitivity to melarsenoxide cysteamine (Mel Cy) was produced in immunosuppresed mice using subcurative drug treatment. Melarsenoxide cysteamine resistance was stable after cyclical transmission through Glossina morsitans centralis. In vitro, the blood-stream forms showed 15-fold higher values for the minimal inhibitory concentration as compared with the parental clone. Cross-resistance could be determined with another arsenical drug, melarsoprol (14-fold) and to two different diamidines (diminazene aceturate: 47-fold; pentamidine methanesulphonate: 34-fold), but not to suramin. When cells were transformed to procyclic forms and tested in vitro, the sensitivity of the resistant population to melarsenoxide cysteamine was only 6-fold lower than that of the parent, but comparatively high cross-resistance could be shown to other drugs (melarsoprol; 85-fold; pentamidine methanesulphonate: 17-fold; quinapyramine sulphate: 40-fold). Selection of the resistant trypanosomes from non-resistant ones was possible under pentamidine methanesulphonate pressure in cell culture.

Animals↗
PubMed1991

Development of an enzyme-linked immunosorbent assay for the detection and measurement of the trypanocidal drug isometamidium chloride in cattle.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure accurately levels of the trypanocidal drug isometamidium in the serum of treated cattle. The assay requires only 5 microliters of test serum, is sensitive to a level of 0.5 pg ml-1 and is highly specific. Cross reactivity does not occur with the two other widely used trypanocidal drugs diminazene aceturate and homidium bromide. Serum drug levels are detectable for up to six months in cattle after a single dose of 1 mg kg-1 intramuscularly, the maximum period under field conditions for which effective prophylaxis can be maintained against tsetse challenge. Application of the assay will aid the rationalisation of treatment campaigns and assist in assessing the occurrence of drug-resistant trypanosome populations.

Animals↗
PubMed1982

Effects of exogenous polyamine and trypanocides on the DNA polymerase activities from Trypanosoma brucei brucei, mouse thymus and murine leukemia virus.

The effects of exogenously added spermine on activated (gapped) DNA-directed and poly(dC) . (dG)12-18-directed DNA synthesis were tested on the chromatographically separated DNA polymerase activities of Trypanosoma brucei brucei. Activated DNA-directed DNA synthesis by the Peak I (eluting from DNA-agarose at 0.15 M KCl) and Peak II (eluting at 0.3 M KCl) polymerase was consistently inhibited or stimulated, respectively, by exogenous spermine. Kinetic analysis revealed that inhibition of the Peak I enzyme with respect to template DNA occurred by a mixed mechanism, while a major factor in the stimulation of the Peak II enzyme by spermine appeared to be the polyamine-mediated reversal of "substrate inhibition' by DNA at concentrations above 10 micrograms/ml. The apparent Km values of Peak I and Peak II DNA polymerase for activated DNA were determined to be 5 and 0.5 microgram/ml, respectively. In contrast to the results observed with activated DNA, activation of Peak II-enzyme-catalyzed poly(dC)-directed DNA synthesis was similar at all template-primer concentrations. Peak I enzyme-catalyzed poly(dG) synthesis was either inhibited or slightly stimulated by spermine, depending upon the presence or absence of heteropolymeric DNA, respectively. Dose-dependent inhibition of DNA-directed DNA synthesis catalyzed by T. b. brucei DNA polymerases, murine thymus DNA polymerase alpha, and Rauscher murine leukemia virus reverse transcriptase by trypanocides was examined to determine a possible mechanism of selective toxicity by such agents. The drugs Antrycide (quinapyramine), pentamidine, imidocarb, Berenil (diminazene aceturate), WR-199-385-[2,5-bis(4-guanylphenyl)furan . 2HCl] and isometamidium inhibited DNA polymerases of the eucaryotic cells at approximately the same degree, and at similar concentrations. The presence of spermine in reaction mixtures did not spare any drug inhibition. Stimulation of reverse transcriptase activity was observed in the presence of Antrycide and imidocarb, however, this could be negated by stimulatory amounts of spermine present in the reaction mixture. The results, obtained using an activated DNA-directed assay system, suggest that trypanosomal DNA polymerases are not the selective target of trypanocidal drugs currently available.

Animals↗
PubMed1989

Detection of parasite peptidase in the plasma of heifers infected with Trypanosoma congolense.

Plasma samples from heifers infected with Trypanosoma congolense were shown to contain a parasite peptidase. In some instances, trypanosome peptidase was detected in plasma samples taken from heifers for up to 14 days after infections had been successfully treated with diminazene aceturate (Berenil). Trypanosome peptidase was detected in plasma using starch gel electrophoresis and also by a dot blot assay in which a McAb, raised against the enzyme, was spotted onto nitrocellulose filters which were then used to absorb enzyme from the samples. The molecular weight of the enzyme was approximately 60,000. The possible role that a trypanosome peptidase may play in inducing pathology and its use in the diagnosis of infection and disease are discussed.

Animals↗
PubMed1990

Serum haemolytic complement activity and C3 levels in bovine trypanosomosis under natural conditions of challenge--early indications of individual susceptibility to disease.

Twenty-five Baoule (Bos taurus) and 12 Zebu (Bos indicus) cattle, which were part of an experiment aimed at characterizing cattle for resistance to trypanosomosis under natural challenge in Burkina Faso, were monitored for complement levels. Total haemolytic activity of the alternative complement pathway and C3 in sera taken weekly were estimated. The results were analysed in relation to the course of the disease, parasitological data, packed red cell volume (PCV) and body weight. All the animals became infected with Trypanosoma vivax and/or T. congolense. The Zebu had to be treated with Berenil (Diminazene aceturate, Hoechst, W. Germany) after a mean period of 5 weeks of infection, whereas 7 of the 25 Baoule remained in good condition throughout the experiment. The remaining 18 Baoule required treatment after a variable period of infection. There was a decrease in haemolytic complement activity (HC') as well as in C3 levels, which coincided with the first detection of parasites in the blood. The titres in the Zebu fell to 10-20% of pre-infection level within 2-3 weeks and they showed no tendency towards regaining normal levels. The drop in complement in the Baoule was less pronounced and was in most cases followed by an increase approaching normal values. In these animals, the complement level in early infection was found to depend on the intensity of parasite load and on the control potential of each individual. There was a significant correlation between minimum complement activity (min. HC'), minimum C3 (min C3) and minimum PCV (min.PCV) in early infection. These three parameters correlated with individual resistance and might, therefore, be useful criteria for the identification of the most resistant individuals within a trypanotolerant breed.

Animals↗
PubMed1992

The pathophysiology of ovine trypanosomosis: haematological and blood biochemical changes.

The course of Trypanosoma congolense infection in sheep was followed for 96 days. Infected animals developed fluctuating parasitaemia, macrocytic normochromic anaemia and leucocytosis which was principally a lymphocytosis. Following treatment with the trypanocidal drug, diminazene aceturate at 84 days after infection, the haematological values returned to normal within 12 days. Infected sheep developed hypocholesterolaemia and hypophospholipidaemia leading to a reduction in total serum lipids. This study has shown that sheep infected with T. congolense develop anaemia, the onset of which follows the first wave of parasitaemia. The changes in blood lipids observed in infected sheep appeared to be related to the intensity and duration of parasitaemia.

Animals↗
PubMed2006

Trypanosoma brucei: composition, organisation, plasticity, and differential transcription of NlaIII repeat elements in drug-resistant and sensitive isolates.

A Trypanosoma brucei brucei DNA repeat sequence termed NlaIII repeat (NR) was originally isolated from a multidrug-resistant field isolate CP547 [Jamnadass, R., 1995. Identification and characterisation of an extrachromosomal element from a multidrug-resistant isolate of T. brucei brucei, Ph.D. thesis, Brunel University, UK]. Subsequently studied in a laboratory strain (Tb427) [Alsford, N.S., Navarro, M., Jamnadass, H.R., Dunbar, H., Ackroyd, M., Murphy, N.B., Gull, K., Ersfeld,K., 2003. The identification of circular extrachromosomal DNA in the nuclear genome of T. brucei. Molecular Microbiology 47, 277-288], NRs were exclusively episomal. Here we show that NR sequences in CP547 are present on linear chromosomes as well as on episomal circular elements. Sequence analysis shows that NRs are composed of three classes of sub-repeat arranged in a specific order. Heterogeneity in size and sequence of an episomal 6.6kbp element was shown in successive passages of the original CP547 isolate and derived clones in mice. Its copy number was unstable and was affected by selective pressure with the trypanocide diminazene aceturate. Some of the extrachromosomal elements appear to be composed of RNA-DNA hybrids. NR sequences were transcribed in a developmentally regulated manner but transcripts did not contain the spliced-leader sequence found on all trypanosome mRNAs.

Animals↗
PubMed2006

Epidemiology of Trypanosoma vivax infection in cattle in the tse-tse free area of Lake Chad.

A study was conducted in Chad to estimate the prevalence and the incidence of Trypanosoma vivax infection in herds of cattle from the Lake Chad area. The risk factors associated with disease were also identified. A random sample of 933 cattle from 17 herds was initially selected (January 1999, cold dry season). Cattle were identified by ear-tags and sampled in the rainy season (July 1999) and the cold dry season (January 2000). Each animal sampled was treated with diminazene aceturate (3.5mg/kg). Samples were examined for the presence of T. vivax using an antibody (indirect ELISA) and a parasite detection test (buffy-coat technique, BCT). Standardized questionnaires with information about the host and management practices were collected and evaluated for their association with seroprevalence (model 1) and parasitological prevalence (model 2) as indicator of host susceptibility to T. vivax infection. Risk factors were selected using two approaches: ordinary logistic regression (OLR) and generalized estimating equations (GEE) to account for within-herd correlation. The apparent prevalence was 1.6% using BCT and 42.3% with indirect ELISA. The true prevalence in the sample was estimated to (2.0%-8.0%) with two assumptions of BCT sensitivity. Overall, 58.8% (BCT) and 100.0% (ELISA) of the herds had a least one-positive animal. In January-July 1999, apparent monthly incidence was calculated at 0.24% in comparison with 0.76% for August 1999-January 2000. The true monthly incidence was estimated at 0.36%-1.43% for the first period and at 0.94%-3.78% for the second period. Risk factors associated with seroprevalence were age, race, a great number of small ruminants in the herd, and latitude and longitude of pasture area in the rainy season. Risk factors associated with BCT prevalence were duration of seasonal migration and longitude of pasture area in the rainy season. In conclusion, T. vivax is present and widely disseminated in the cattle herds of tse-tse free area of Lake Chad. Farm-level factors, particularly seasonal migration, should be considered as the main risk factors for infection and to host susceptibility to the parasite.

Animals↗
PubMed2006

Equine trypanosomosis in the Central River Division of The Gambia: a study of veterinary gate-clinic consultation records.

The objective of this study was to provide epidemiological information of equine trypanosomosis in the Central River Division (CRD) of The Gambia. Therefore, 2285 consultations records of equines, admitted in a gate-clinic at Sololo in CRD, were studied retrospectively. The data were recorded in the period between September 1995 and July 2002 and comprised consultations of 2113 horses and 172 donkeys. 'Trypanosome infection' was the most frequently diagnosed condition and accounted for 61% of the cases. Horses were more frequently diagnosed with trypanosome infections than donkeys (p<0.001), with an occurrence of 63% compared to 43% in donkeys. In both horses and donkeys, trypanosome infections were mainly due to Trypanosoma congolense (64%) and T. vivax (32%). There was no difference observed in the occurrence of trypanosome infections in male or female donkeys (p=0.585), but there were more female (67.8%) horses observed with trypanosome infections than male horses (60.7%; p=0.003). There was no difference observed in the occurrence of trypanosome infections in donkeys older or younger than 1 year (p=0.130), but more older horses (63.2% >1 year) were observed with trypanosome infections than young horses (54.5% <1 year; p=0.033). The number of donkeys and horses with trypanosome infections decreased during the rainy season (June-September). The majority of equines that were admitted with trypanosome infections were severely anaemic. The average packed cell volume (PCV) declined with increasing parasitaemia (p=0.006). Seventy-four percent of the farmers' predictions of trypanosome infections in their equines were confirmed by darkground-microscopy. That proved that farmers had a fairly accurate knowledge of the diseases affecting their equines. The treatments executed at the gate-clinic were generally effective. The few (0.4%) relapses of the T. vivax infections that were previously treated with diminazene aceturate in this study were not sufficient to prove drug resistance. The study showed that the analysis of consultation records at a gate-clinic can provide complementary information to conventional epidemiological studies in the same research area.

Age Factors↗