Isometamidium Research Articles

Evaluation sur le terrain et sur souris de la résistance des trypanosomes des bovins du plateau de l’Adamaoua au Cameroun à l’acéturate de diminazène et au chlorure d’isométamidium

Suite à une enquête dans quelques villages du département de Faro et Déo, le village de Kontcha, qui a présenté la prévalence de la trypanosomose la plus élevée (32,5 p. 100), a été sélectionné afin d’évaluer la résistance des trypanosomes au diminazène et à l’isométamidium. Deux lots de 40 bovins ont été traités au jour 0, l’un au diminazène, l’autre à l’isométamidium. Le statut parasitologique de ces deux lots a été évalué toutes les deux semaines en utilisant la technique du buffy coat pendant une période de deux mois. Chaque animal diagnostiqué positif a été traité au diminazène. Le pourcentage d’animaux infectés par des trypanosomes a été de 32,5 p. 100 dans le lot traité au diminazène et de 27,5 p. 100 dans le lot traité à l’isométamidium. L’analyse de survie ainsi que l’estimation du risque relatif (1,38) ont suggéré une résistance à l’isométamidium et une diminution de l’activité prophylactique de ce produit. Plusieurs animaux traités au diminazène à 7 mg/kg ont été diagnostiqués positifs deux semaines après le traitement, ce qui indiquait également une forte suspicion de résistance à ce trypanocide. Ces résultats du terrain ont été confirmés par le test standardisé sur souris en utilisant six isolats de Trypanosoma congolense provenant des animaux traités. Ces isolats ont été testés au chlorure d’isométamidium (1 mg/kg) et à l’acéturate de diminazène (20 mg/kg) pour établir leur sensibilité. Tous les isolats ont été résistants à au moins un des produits testés, tandis que quatre isolats ont été résistants aux deux produits. Cette étude montre pour la première fois la présence au Cameroun de souches de trypanosomes résistantes aux trypanocides.

The transmissibility of Trypanosoma congolense seems to be associated with its level of resistance to isometamidium chloride

In large parts of Africa the control of livestock trypanosomiasis relies on the use of trypanocidal drugs. Resistance against the available compounds is developing rapidly in the trypanosome population. The effect of the development of drug resistance on the fitness of the trypanosome is not well known. To determine the effect of the development of resistance to isometamidium chloride on the trypanosome's transmissibility, transmission experiments were conducted. Use was made of three isogenic clones of Trypanosoma congolense with different susceptibility to the drug. The infection rate in Glossina morsitans morsitans differed significantly between clones and was significantly higher in tsetse flies infected with the T. congolense clone with the highest level of drug resistance.

The susceptibility of <i>Trypanosoma congolense</i> isolated in Zambézia Province, Mozambique, to isometamidium chloride, diminazene aceturate and homidium chloride

Resistance to trypanocidal drugs has been detected in various African countries and is a serious impediment to the control of livestock trypanosomosis. To determine whether drug resistant trypanosome strains are present in the Zambézia Province of Mozambique a study was initiated. To assess the effect of the farming system and the drug-use regimen on the development of drug resistance, trypanosome isolates were collected from cattle from subsistence and commercial livestock production systems. The susceptibility of seven isolates against isometamidium chloride, diminazene aceturate and homidium chloride was tested in mice using a multiple-dose test. In four of the seven isolates high levels of drug resistance to diminazene aceturate and isometamidium chloride were detected. In most cases the observed levels of drug resistance correlated with the drug-use practices in the particular livestock production system.

Identification of a genetic marker for isometamidium chloride resistance in Trypanosoma congolense

Isometamidium chloride has remained a very important prophylactic and therapeutic drug against trypanosomosis in cattle since its introduction into the market in the 1950s with, unfortunately, a concomitant development of resistance in trypanosomosis endemic areas. Amplified Fragment Length Polymorphism (AFLP) was used to compare two isogenic clones of Trypanosoma congolense. The parent clone, sensitive to isometamidium, has a CD50 (the curative dose that gives complete cure in 50% of the animals) in the mouse of 0.018 mg/kg and its derivative exposed to increasing doses of isometamidium, has a CD50 that is 94-fold higher. Sixty-four combinations of eight Eco RI and eight Mse I primers were used in comparative AFLP analysis to detect subtle genetic differences between the two clones. Thirty-five polymorphic fragments of DNA that were observed only in the resistant clone were purified and then sequenced. The nucleotide sequences were used in searching the GeneDB T. congolense database to find surrounding sequences upstream of an open reading frame and downstream to a stop codon. The sequences of the open reading frames were subsequently compared to the sequences in the genomic databases. A predicted gene coding for an 854 amino acids protein was thus identified. The protein contains a putative ATP binding site, Walker B and LSGG motifs and eight predicted trans-membrane domains. The gene in the resistant strain of T. congolense has a triplet insertion coding for an extra lysine. Using polymerase chain reaction-restriction fragment length polymorphism, the insertion was sought in the genomes of 35 T. congolense strains isolated from different geographic origins and whose response to isometamidium chloride had been determined through single dose mouse tests. The presence of the insertion, specifying an extra codon was found to always be present in the genomes of T. congolense clones that were resistant to isometamidium chloride.

Evaluation of isometamidium levels in the serum of sheep and goats after prophylactic treatment against trypanosomosis

Isometamidium chloride has been used for the control of trypanosomosis in animals for over 36 years, but recently there have been reports of prophylaxis failure under natural conditions. In this study, use of the drug for prophylactic purpose against trypanosomosis in small ruminants was investigated. Forty-two sheep and 44 goats were divided into four treatment groups. Groups 1 and 2 were treated with isometamidium chloride (Samorin, Rhone Merieux, Lyon, France) at 3-month intervals while groups 3 and 4 were used as controls. All the animals were exposed to natural tsetse challenge and monitored for serum isometamidium levels and anti-trypanosome antibodies. Seven days after drug administration, isometamidium levels were significantly higher in goats 13.7+/-0.07 ng/ml than in sheep 6.2+/-0.06 ng/ml. However, the elimination half-life in the sheep was 14.2+/-0.92 days and was significantly higher (P> 0.05) than that of the goats 12+/-0.5 days. This study established that isometamidium metabolism differs between sheep and goats and this difference may have important implications in high tsetse challenge areas.

Protective efficacy of isometamidium chloride and diminazene aceturate against natural <i>Trypanosoma brucei<i/>, <i>Trypanosoma congolense<i/> and <i>Trypanosoma vivax<i/> infections in cattle under a suppressed tsetse population in Uganda

The protective efficacy of isometamidium chloride (ISMM) and diminazene aceturate (DIM) against Trypanosoma brucei, Trypanosoma congolense and Trypanosoma vivax infections in cattle under a suppressed tsetse population was assessed in southeast Uganda. A total of 66 and 57 trypanosome-infected cattle were treated with ISMM and DIM, respectively together with 177 trypanosome-free animals not treated were followed for 12 months, checked every 4 weeks. There was no statistical difference in the mean time to infection with any trypanosome species in animals treated with ISMM or DIM. However, the mean time to trypanosome infection was significantly longer for treated animals than controls. The mean time to infection with each of the three trypanosome species differed significantly, with the average time to T. vivax infection the lowest, followed by T. congolense and then T. brucei. The protective efficacy of DIM was as good as that of ISMM; implying curative treatments against trypanosomosis are sufficient for combination with tsetse control. Isometamidium chloride or DIM had the highest impact on T. brucei and T. congolense infections in cattle.

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.

Knowledge and attitudes of cattle owners regarding trypanosomosis control in tsetse-infested areas of Uganda

A pilot survey using a structured questionnaire was conducted in Tororo and Busia districts of Uganda on the knowledge and attitudes of cattle owners regarding tsetse fly and trypanosomosis control, in order to understand factors that hindered their full participation. A total of 81 cattle owners was randomly selected and interviewed, of which 92.5% were aware of tsetse flies and trypanosomosis and 87.6% recognised animal trypanosomosis as a problem in the area. Most cattle owners were aware of tsetse fly trapping (76.5%), isometamidium chloride use (55.5%), diminazene aceturate use (48%) and pour-on applications (18.5%). However, knowledge did not coincide with the application of control measures. Despite the widespread awareness, tsetse fly trapping and pour-on applications were used by only a small percentage of cattle owners (7.5% applied tsetse fly trapping while 76.5% were aware of it; 1.2% applied pour-on insecticides while 18.5% were aware of them). Differences between awareness and application were highly significant for tsetse fly trapping (chi2 = 67.8, d.f. = 1, P < 0.001) and pour-on applications (chi2 = 10.8, d.f. = 1, P < 0.05), but not for isometamidium chloride use (chi2 = 0.08, d.f. = 1, P = 0.77) and diminazene aceturate use (chi2 = 0.00, d.f. = 1, P = 1.00). Most cattle owners (97.5%) were willing to participate in future control programmes, but preferred participating on a group basis (85.2%) rather than individually (14.8%). The 4 most favoured control options in order of importance were: fly traps supplied by the government and maintained by cattle owners; contribution of labour by cattle owners for trap deployment; self-financing of trypanocidal drugs and self-financing of pour-on insecticide. The control options that should be selected in order to elicit full participation by cattle owners are discussed.

A comparative study of the pharmacokinetics of isometamidium chloride in sheep and goats

A study was carried out to determine and compare the pharmacokinetics of isometamidium in groups of six animals each of sheep and goats treated by intramuscular injection with isometamidium chloride (Samorin®, Rhone Merieux, Lyon, France) at 0.5 mg/kg body weight. The animals were bled at pre-determined time intervals and serum isometamidium concentrations monitored using isometamidium-ELISA for a period of over 60 days post-treatment. Pharmacokinetic evaluation was carried out using a non-compartment analysis. Mean residence time (MRT) in sheep was higher but not significantly different from that observed in goats. Whereas the mean Cmax values observed in both species were similar, the Tmax value of 12.7 h obtained in goats was significantly longer (P<0.05) suggesting a slower rate of absorption of the drug from injection site. Also, the elimination half-life obtained in goats of 188 h was significantly shorter (P<0.05) than that observed in sheep suggesting rapid elimination rate of the drug in the later. At 60 days no drug was detectable in both sheep and goats.

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).

Trypanocidal drug resistance in eastern province of Zambia

A survey to investigate resistance to drugs used in the treatment of bovine trypanosomosis was conducted in the eastern province of Zambia between 1996 and 1998. A cross-sectional study was conducted in three districts (Petauke, Katete, Lundazi) at 34 village sampling sites selected at random from villages that had shown greater than 6% prevalence of bovine trypanosomosis during an earlier survey. A longitudinal study was conducted in same three districts over a 1-year period. The study sites were chosen from the cross-sectional study and included eight sites showing high trypanosomosis prevalence and where no control activities were recorded. Use was made of parasitological methods, tests of resistance in cattle and mice and isometamidium-ELISA. Overall mean prevalence of trypanosomosis was 14.4, with 96% of infections caused by Trypanosoma congolense. The remainder was caused by Trypanosoma vivax (2%) and Trypanosoma brucei (2%) . Tests in mice showed that of the stabilates collected, 24 (34%) were resistant to only isometamidium chloride, 8 (11.3%) were resistant to only diminazene aceturate, 1 (1.4%) was resistant to both drugs, and 38 (53.5%) were sensitive to both drugs. At least 2 out of 27 stabilates tested in cattle appeared to be resistant to trypanocidal drugs, 1 to isometamidium and 1 to diminazene. Isometamidium could be detected in only 63 (4.1%) of 1526 serum samples from cattle in the study. Only 6 (2.8%) of 212 serum samples from trypanosome-infected cattle had serum levels of the drug above 0.4 ng isometamidium per ml serum which is indicative for drug resistance in the infecting parasite population. Although some drug resistance is apparent, diminazene aceturate and isometamidium chloride can still be expected to be effective as a sanative pair in this area in most cases, since not more than 1 stabilate of 71 investigated showed evidence of resistance to both drugs.

Cryptobia (Trypanoplasma) salmositica and salmonid cryptobiosis.

Salmonid cryptobiosis is caused by Cryptobia (Trypanoplasma) salmositica. The haemoflagellate has been reported from all species of Pacific Oncorhynchus spp. on the west coast of North America. It is normally transmitted by the freshwater leech, Piscicola salmositica, in streams and rivers, and sculpins, Cottus spp., are considered important reservoir hosts. The pathogen can also survive on the body surface of fish because it has a contractile vacuole to osmoregulate when the fish is in fresh water. This allows for direct transmission between fish, especially in aquaculture facilities. The parasite divides rapidly by binary fission in the blood to cause disease, the severity of which is directly related to parasitaemia. Cryptobia salmositica has a mitochondrium and it normally undergoes aerobic respiration; however, if its mitochondrium is damaged it will switch to glycolysis. Its glycolytic enzymes and catalase are contained in glycosomes. Cysteine protease is a metabolic enzyme, and its neutralization inhibits oxygen consumption and multiplication of the parasite. An important virulent factor in cryptobiosis is a secretory metalloprotease. The protective mechanism involves production of complement fixing antibodies, phagocytosis by macrophages, and cell-mediated cytotoxicity. Recovered fish are protected, probably for life as the immunity is non-sterile. Clinical signs of the disease include anaemia, anorexia, splenomegaly, general oedema and abdominal distension with ascites. The metabolism and swimming performance of infected fish are significantly reduced and the bioenergetic cost of the disease is very considerable. Fish are susceptible to hypoxia and their immune system is depressed during acute cryptobiosis. Severity of the disease and mortality rates vary significantly between species and stocks of salmon. Protective strategies include selective breeding of Cryptobia-resistant fish. This is innate resistance to infection and it is controlled by a dominant Mendelian locus. In these fish the parasite is lysed via the alternative pathway of complement activation. In Cryptobia-tolerant fish (infected with the pathogen but which do not suffer from disease) the metalloprotease secreted by the parasite is neutralized by alpha2 macroglobulin. Hence, the production of a transgenic Cryptobia-tolerant salmon is an option. This strategy has the advantage in that human intervention (e.g. vaccination, chemotherapy) is not required once the transgenic fish is produced. Acquired immunity is another option; a single dose of the attenuated live vaccine protects fish for at least 2 years. The protective mechanism in vaccinated fish is similar to that in recovered fish. The trypanocidal drug, isometamidium chloride, is an effective therapeutic and prophylactic agent. It accumulates in the mitochondrium of the parasite and significantly disrupts aerobic respiration by causing lesions in the organelle. Efficacy of the drug is significantly increased after its conjugation to antibodies. This immuno-chemotherapeutic strategy has the advantage in that it will lower the drug dosage and hence side-effects of chemotherapy. It will probably reduce the accumulation of the drug in fish, an important consideration in food fish.

A comparative study of the pharmacokinetics of isometamidium chloride in sheep and goats

A study was carried out to determine and compare the pharmacokinetics of isometamidium in groups of six animals each of sheep and goats treated by intramuscular injection with isometamidium chloride (Samorin ®, Rhone Merieux, Lyon, France) at 0.5 mg/kg body weight. The animals were bled at pre-determined time intervals and serum isometamidium concentrations monitored using isometamidium-ELISA for a period of over 60 days post-treatment. Pharmacokinetic evaluation was carried out using a non-compartment analysis. Mean residence time (MRT) in sheep was higher but not significantly different from that observed in goats. Whereas the mean C max values observed in both species were similar, the T max value of 12.7 h obtained in goats was significantly longer ( P<0.05) suggesting a slower rate of absorption of the drug from injection site. Also, the elimination half-life obtained in goats of 188 h was significantly shorter ( P<0.05) than that observed in sheep suggesting rapid elimination rate of the drug in the later. At 60 days no drug was detectable in both sheep and goats.

Field studies of drug-resistant cattle trypanosomes in Kénédougou Province, Burkina Faso

Field studies were conducted to assess the occurrence of resistance to isometamidium chloride and diminazene aceturate in trypanosomes infecting cattle in Kénédougou Province of Burkina Faso. Forty-five of the 166 villages in Kénédougou were randomly sampled and visited to assess livestock numbers, trypanosomosis risk, and tsetse challenge. The proportion of cattle infections associated with drug-resistant trypanosomes was assessed in the nine villages with the highest trypanosome infection prevalence and one village with a confirmed history of drug-resistant infections. These studies showed that resistance to both isometamidium and diminazene was widespread. However, there was considerable variation between villages in drug-resistance parameters, with the proportion of treated cattle with trypanosome infections 3 months after isometamidium prophylaxis varying from 6.9 to 63.8% and the proportion of cattle having infections 2 weeks after treatment with diminazene varying from 0 to 36.8%. The demonstration of widespread resistance to both isometamidium and diminazene has important implications, as administration of trypanocides is the most commonly employed method to control trypanosomosis in this area.

Trypanosomes résistants aux médicaments : une menace pour la production bovine du sud-ouest éthiopien

La trypanosomose est une maladie importante du bétail dans le sud-ouest de l’Ethiopie. Actuellement la chimiothérapie et la chimioprévention sont les seules méthodes pratiques de lutte contre la trypanosomose animale mais leur efficacité diminue à cause de l’émergence de chimiorésistances. Parmi les médicaments proposés pour le traitement de la trypanosomose animale, Bérénil® (acéturate de diminazène) et Trypamidium® (chlorure d’isométamidium) sont les plus utilisés du fait de leur disponibilité et de leur toxicité relativement faible pour le bétail. La sensibilité à ces médicaments de quatre souches de Trypanosoma congolense isolées à partir de bovins dans le sud-ouest de l’Ethiopie (Ghibe, Bedelle, Sodo et Arbaminch) a été testée sur des souris blanches (Suisses) et sur des zébus indigènes. Les résultats ont montré que, sur ce nombre limité de souches, des souches de T. congolense étaient résistantes aux médicaments. Les isolats de Ghibe, Bedelle et Sodo se sont révélés résistants aux doses thérapeutiques d’acéturate de diminazène (3,5 mg/kg) ainsi qu’aux doses thérapeutiques et prophylactiques standard de chlorure d’isométamidium (0,5 et 1 mg/kg). Ces trois isolats se sont cependant révélés sensibles à l’acéturate de diminazène à la dose de 7 mg/kg. La souche d’Arbaminch a été résistante aux doses recommandées par les fabricants pour les deux médicaments.

Metabolism and distribution of phenanthridine trypanocides in Trypanosoma brucei

Phenanthridine trypanocides (isometamidium chloride hydrochloride, ISM, and Ethidium bromide, EBr) have been widely used to treat African trypanosomiasis in livestock for more than 40 years. Their main action is to inhibit nucleic acid synthesis in trypanosome parasites, by intercalation between the DNA base pairs. They can also linearise selectively kinetoplast DNA minicircles; a form of mitochondrial DNA unique to this group of parasites. However, the metabolism of these compounds by trypanosomes has not been reported. Indeed, it is not known whether or not their metabolism by the parasite contributes to their activity, selective toxicity for these parasites or to the development of chemoresistance. Therefore, we studied the metabolism of EBr and ISM, and their distribution in Trypanosoma brucei (TREU 927) using high performance liquid chromatography (HPLC), liquid chromatography combined with mass spectrometry (LC–MS) and confocal laser scanning microscopy (CLSM). Incubation of EBr with trypanosomes led to the formation of a small amount (0.606±0.191%) of one metabolite (MI). Ion chromatograms extracted from an LC–MS analysis using electrospray ionisation (ESI), showed that the difference in mass between the parent compound and its metabolite was 30. This may correspond to the addition of a hydroxyl and a methyl group. No metabolites could be detected for ISM. The distribution of the two drugs in trypanosomes was investigated by CLSM, using their intrinsic fluorescence. ISM and EBr showed differences in their distribution in trypanosomes. ISM had a greater affinity for the kinetoplast than EBr and it stained other organelles like the flagellum; in contrast the distribution of EBr was more diffuse.

A competitive enzyme-linked immunosorbent assay for diminazene

Diminazene aceturate has remained a very important therapeutic drug for trypanosomosis in cattle, sheep and goats since its introduction into the market in 1955. Despite its continued use, the methods available for its detection in body fluids are lengthy and inefficient for routine monitoring of drug levels in treated animals. A competitive enzyme linked immunosorbent assay (ELISA) has now been developed and optimized for the detection of diminazene in bovine serum. In the assay, diminazene in the test samples and that in a newly developed diminazene–horseradish peroxidase conjugate compete for antibodies to diminazene raised in rabbits and immobilized on a microtitre plate. Tetramethylbenzidine–hydrogen peroxide (TMB/H 2O 2) is used as chromogen–substrate system. The assay has a detection limit of 0.8 ng/ml of serum with a high specificity for diminazene. Cross-reactivity with either homidium bromide and quinapyramine sulphate/chloride of 0.0004% is negligible while that with isometamidium chloride is 0.71%. The assay was able to detect diminazene levels in normal Boran steers for at least two weeks after intramuscular injection with the drug at a dose of 3.5 mg/kg bw. The assay will be useful in monitoring diminazene use, and development of resistance in trypanosomosis endemic areas.

Drug sensitivity of trypanosome populations from cattle in a peri-urban dairy production system in Uganda

Cattle from 50 farms in Mukono County, Uganda, were monitored for trypanosomes every second month over an 18-month period (1995–1996) by mini-anion exchange chromatography and haematocrit centrifugation techniques. Eighteen trypanosome isolates collected from cattle during this period were characterised in cattle, goats and mice for their sensitivity to homidium, isometamidium and diminazene; 10 of the isolates were selected randomly, 8 were from animals that had the highest serum isometamidium concentrations at the time the isolates were collected. All the isolates contained only Trypanosoma brucei and/or T. vivax. In naı̈ve Boran ( Bos indicus) cattle the isolates exhibited low pathogenicity and were sensitive to diminazene aceturate at 3.5 mg/kg body weight (bw) and isometamidium chloride at 0.5 mg/kg bw. In goats, 5 of 8 isolates were highly pathogenic, producing clinical signs indicative of central nervous system involvement within 60 days of infection; all such isolates contained T. brucei. However, all 8 populations were sensitive in goats to diminazene aceturate at 3.5 mg/kg bw. In contrast, 4 populations were refractory to treatment with isometamidium chloride at 0.5 mg/kg bw in at least 1 out of 3 goats each. Furthermore, 5 populations were refractory to treatment with homidium chloride at 1.0 mg/kg bw in a minimum of 2 out of 3 goats each. In mice, the 50% curative dose values for 11 Mukono isolates that contained T. brucei ranged from 0.30 to 1.89 mg/kg bw for diminazene aceturate, from 0.02 to 0.17 mg/kg bw for isometamidium chloride and from 0.90 to 4.57 mg/kg bw for homidium chloride. Thus, by comparison to reference drug-sensitive populations, all the stabilates were highly sensitive to diminazene and isometamidium, while some expressed low levels of resistance to homidium.

Financial implications of rearing sheep and goats under natural trypanosomosis challenge at Galana ranch, Kenya.

A study to compare the profitability of rearing sheep and goats under natural trypanosomosis challenge was carried out on Galana ranch in south-eastern Kenya between July 1996 and October 1997. Seventy-nine male weaner sheep and 79 male weaner goats were monitored monthly for weight changes and fortnightly for trypanosomosis. The animals of each species were divided into two groups. Group 1 was an untreated control, while group 2 was treated with isometamidium chloride (Samorin) at 0.5 mg/kg body weight every 3 months. In both groups, trypanosome infections were detected by microscopy and treated with diminazene aceturate (Veriben), at 3.5 mg/kg body weight, when the packed cell volume reached 17% or below. The profitability of each drug regime was expressed as the marginal revenue over the cost of trypanosomosis (MOT). There were greater losses occasioned by trypanosomosis in sheep than in goats. Animals of both species on chemoprophylaxis gave higher MOT values than those that received chemotherapy on diagnosis. However, the MOT values for the chemoprophylactic regime were higher for sheep than for goats, suggesting that the greater weight gain by sheep more then compensated for the higher cost of maintaining them under high trypanosomosis challenge. Thus, a Galana rancher would be better off keeping sheep rather than goats, other things being equal. The marginal revenue per dose of Samorin was lower than that of Veriben for both species, suggesting that strategic use of Samorin timed to precede the peak incidence of trypanosomosis might be a better option to raise the overall profitability in sheep and goats.

Growth and mortality in sheep and goats under high tsetse challenge in Kenya.

Trypanosomosis is a major impediment to livestock production and economic development in those areas of Africa where it is endemic. Although small ruminants appear to perform better than cattle in various agro-ecological zones, the importance of trypanosomosis has not been extensively investigated in these livestock. This study was designed to investigate the prevalence of trypanosomosis in sheep and goats in an endemic area and to evaluate the performance of different breeds under high tsetse challenge and the potential role of chemoprophylaxis in the control of the disease. The results showed that tsetse flies feed readily on small ruminants, and that these animals are susceptible to trypanosomosis. The Small East African goats acquired fewer infections than the Black Head Persian and Dorper sheep used in the study. In both sheep and goats, chemoprophylaxis with isometamidium chloride (Samorin, Rhone Merieux, Annecy, France) was protective, resulting in fewer infections and higher body weight gain. Trypanosomosis caused anaemia in both sheep and goats, and animals whose PCV fell below 15% rarely recovered, even with trypanocidal drug treatment. The peak transmission period was between 1 and 3 months after the peak tsetse fly density, which raises the possibility of effective strategic prophylaxis.