Pharmacokinetics of Chloramphenicol in Sheep after Intramuscular Administration

This study was carried out to determine the pharmacokinetics of chloramphenicol in eight sheep injected intramuscularly with chloramphenicol sodium succinate (25 mg/kg body weight). The animals were bled at pre-determined time intervals and serum chloramphenicol concentrations monitored using chloramphenicol-ELISA for a period of 30 days post drug administration. Pharmacokinetic evaluation was carried out using a non-compartment analysis. The mean Cmax values obtained in the eight sheep was 134±34 mg/ml and the time required to reach Cmax (tmax) was 10±0.05 minutes. The mean elimination half-life obtained was 36.37±3.7 h and the mean residence time was 2.83±0.27 h. These findings show that chloramphenicol was absorbed and distributed rapidly from the injection site. At two weeks post drug administration, the drug levels had declined to below the limit of detection of the assay (0.1 ng/ml).Keywords: Chloramphenicol, pharmacokinetics, sheep, ELISAEast and Central African Journal of Pharmaceutical Sciences Vol. 12 (2009) 3-

Validation of a competitive chloramphenicol enzyme linked immunosorbent assay for determination of residues in Ovine tissues

Chloramphenicol is a broad-spectrum antibiotic, which has been used for treatment of animals. However, in humans it leads to hematoxic side effects particularly aplastic anaemia for which a dosage-effect relationship has not yet been established. The objective of this study was to validate a developed chloramphenicol enzyme linked immunosorbent assay for the determination of chloramphenicol residues in ovine tissues. Two groups (n=5) of sheep were injected with chloramphenicol sodium succinate at 25-mg/kg bodyweight and slaughtered one and four weeks post drug administration. Overall, the mean percentage recoveries in muscle, liver and kidney were 92 %, 70% and 78% respectively. The limits of detection were 1.2 ng/g, 0.6 ng/g and 0.8 ng/g while the detection capability was 2.5 ng/g, 1 ng/g and 1 ng/g in muscle, kidney and liver respectively. This enables the method to be used effectively as a screening tool for chloramphenicol residues in livestock products especially in the liver, muscle and kidney.Keywords: Chloramphenicol, enzyme linked immunosorbent assay, ovine, muscle, liver, kidneyEast and Central African Journal of Pharmaceutical Sciences Vol. 13 (2010) 12-1

Multiple evolutionary origins of Trypanosoma evansi in Kenya

Trypanosoma evansi is the parasite causing surra, a form of trypanosomiasis in camels and other livestock, and a serious economic burden in Kenya and many other parts of the world. Trypanosoma evansi transmission can be sustained mechanically by tabanid and Stomoxys biting flies, whereas the closely related African trypanosomes T. brucei brucei and T. b. rhodesiense require cyclical development in tsetse flies (genus Glossina) for transmission. In this study, we investigated the evolutionary origins of T. evansi. We used 15 polymorphic microsatellites to quantify levels and patterns of genetic diversity among 41 T. evansi isolates and 66 isolates of T. b. brucei (n = 51) and T. b. rhodesiense (n = 15), including many from Kenya, a region where T. evansi may have evolved from T. brucei. We found that T. evansi strains belong to at least two distinct T. brucei genetic units and contain genetic diversity that is similar to that in T. brucei strains. Results indicated that the 41 T. evansi isolates originated from multiple T. brucei strains from different genetic backgrounds, implying independent origins of T. evansi from T. brucei strains. This surprising finding further suggested that the acquisition of the ability of T. evansi to be transmitted mechanically, and thus the ability to escape the obligate link with the African tsetse fly vector, has occurred repeatedly. These findings, if confirmed, have epidemiological implications, as T. brucei strains from different genetic backgrounds can become either causative agents of a dangerous, cosmopolitan livestock disease or of a lethal human disease, like for T. b. rhodesiense

Reduced Mitochondrial Membrane Potential is a Late Adaptation of Trypanosoma brucei brucei to Isometamidium Preceded by Mutations in the γ Subunit of the F1Fo- ATPase

Background: Isometamidium is the main prophylactic drug used to prevent the infection of livestock with trypanosomes that cause Animal African Trypanosomiasis. As well as the animal infective trypanosome species, livestock can also harbor the closely related human infective subspecies T. b. gambiense and T. b. rhodesiense. Resistance to isometamidium is a growing concern, as is cross-resistance to the diamidine drugs diminazene and pentamidine. Methodology/Principal Findings: Two isometamidium resistant Trypanosoma brucei clones were generated (ISMR1 and ISMR15), being 7270- and 16,000-fold resistant to isometamidium, respectively, which retained their ability to grow in vitro and establish an infection in mice. Considerable cross-resistance was shown to ethidium bromide and diminazene, with minor cross-resistance to pentamidine. The mitochondrial membrane potentials of both resistant cell lines were significantly reduced compared to the wild type. The net uptake rate of isometamidium was reduced 2-3-fold but isometamidium efflux was similar in wild-type and resistant lines. Fluorescence microscopy and PCR analysis revealed that ISMR1 and ISMR15 had completely lost their kinetoplast DNA (kDNA) and both lines carried a mutation in the nuclearly encoded γ subunit gene of F1 ATPase, truncating the protein by 22 amino acids. The mutation compensated for the loss of the kinetoplast in bloodstream forms, allowing near-normal growth, and conferred considerable resistance to isometamidium and ethidium as well as significant resistance to diminazene and pentamidine, when expressed in wild type trypanosomes. Subsequent exposure to either isometamidium or ethidium led to rapid loss of kDNA and a further increase in isometamidium resistance. Conclusions/Significance: Sub-lethal exposure to isometamidium gives rise to viable but highly resistant trypanosomes that, depending on sub-species, are infective to humans and cross-resistant to at least some diamidine drugs. The crucial mutation is in the F1 ATPase γ subunit, which allows loss of kDNA and results in a reduction of the mitochondrial membrane potential

The effects of drug-sensitive and drug-resistant Trypanosoma congolense infections on the pharmacokinetics of homidium in Boran cattle

Two groups of five Boran (Bos indicus) cattle were infected with one of two populations of Trypanosoma congolense; one drug-sensitive (IL1180), and one drug-resistant (IL3330). The animals were then treated intramuscularly with homidium bromide at a dose rate of 1.0 mg kg−1 bodyweight 7 days after trypanosomes were detected in the peripheral blood of all the five animals in each group. Following treatment of cattle infected with drug-sensitive trypanosomes, parasites could no longer be detected in the bloodstream of four out of five cattle after 24 h, and after 48 h for the fifth animal. The animals remained aparasitaemic up to the end of the observation period of 90 days and serum drug concentrations determined by enzyme-linked immunosorbent assay (ELISA) remained above the detection limit of 0.1 ng ml−1 for the entire period. Following treatment of cattle infected with drug-resistant trypanosomes, parasites did not disappear from the bloodstream in any of the five animals. The rate of drug elimination was greater in cattle infected with drug-resistant trypanosomes and the drug was no longer detectable approximately 3 weeks after treatment. Non-compartmental pharmacokinetic analysis showed that the values for tView the MathML sourceβ of 75.5±16.9 h, the area under the curve (AUC0−∞) of 1.33±0.156 μg h ml−1 and the MRT0−∞ of 32.8±4.45 h obtained in cattle infected with the drug-resistant trypanosome population were significantly lower than the values of 424±146 h for tView the MathML sourceβ, 1.67±0.233 μg h ml−1 for AUC0−∞ and 297±159 h for MRT0−∞ obtained in cattle infected with the drug-sensitive population. The persistence of drug-resistant infections in cattle following homidium treatment was associated with more rapid drug elimination than in those in which infections with drug-sensitive parasites were cleared by the drug

Evidence Of Improper Usage Of Veterinary Drugs In Cattle In Maasailand, Kenya

Cent treize éleveurs dans les localités d\'Olkiramatian et Siana au Kenya étaient interrogés entre octobre 2005 et février 2006. L\'objet de l\'entretien était de collecter des informations sur l\'usage de médicament vétérinaire à la ferme. La technique de statistique descriptive et la technique de régression étaient utilisées pour analyser les données. Les éleveurs utilisaient des doses plus faibles que celles recommandées pour tous les trypanocides disponibles chez tous les groupes d\'âge de bétail, à l\'exception des taureaux adultes à qui on a administré une surdose d\'acéturate de diminazène (Veriben®, Ceva Santé Animale, Libourne, France), de chlorure d\'homidium (Novidium®, Merial, Lyon, France) et de diacéturate de diminazène (Tryzan®, Cooper, Nairobi, Kenya). L\'hydrochlorure d\'oxytétracycline (Adamycine®, Assia, Nairobi, Kenya), l\'antibiotique le plus largement utilisé dans les deux sites d\'études, était sous-dosé dans toutes les concentrations chez tous les groupes d\'âge de bétail, sauf pour l\'hydrochlorure d\'oxytétracycline à 20% utilisé pour les taureaux adultes. A part le chlorure d\'homidium, que les éleveurs ont dissous correctement, ils ont mis moins d\'eau que ce qui est recommandé pour préparer les trypanocides. De même, la concentration d\'acaricides était plus faible que celle recommandée pour le contrôle des tiques, sauf pour l\'alphacyperméthrine (Dominex®, FMC, Philadelphie, Etats-Unis) ; et les éleveurs pulvérisaient plus de bétail que ce qui a été recommandé à chaque concentration. La tendance à utiliser correctement les médicaments vétérinaires était positivement associée à l\'âge de l\'éleveur et à son lieu d\'origine (

Prevalence of parasitic infections in small ruminants in a pastoral community in Narok district, KenyaPrevalence des infections parasitaires chez les petits ruminants dans une communaute pastorale du district de Narok au Kenya

A cross-sectional study was carried out in two villages (Emorijoi and Ngoswani) in Lemek group ranch and one village (Enkoje) situated in Koyaki group ranch in Narok District to investigate parasitic infections in small ruminants. Blood and faecal samples were collected from 150 sheep and an equal number of goats during wet season (May-June) and dry season (August-September) and analyzed using different parasitological methods. The findings showed that parasites infecting small ruminants in the area were helminthes, Cowdria ruminantium, ticks and trypanosomes. The most prevalent genera of nematodes identified were Strongyles, which usually occurred concurrently in most animals. The percentage of animals with at least one or more helminth eggs detected during the wet season in sheep and goats was 36% (54) and 52% (78) respectively before deworming with Nilzan plus (1.5% levamisole plus refoxanide hydrochloride). Approximately two months after deworming the animals, this percentage of animals declined to 18% (27) and 24.6% (37) in sheep and goats respectively during the dry season. During the wet season the overall trypanosome prevalence in sheep and goats was 1.3% (2) and 4.6% (7) respectively and decreased significantly to 0% (0, goats) (P0,05). Le taux de prvalence globale de la cowdriose tait beaucoup plus lev (