Pharmacokinetics of ampicillin and pentobarbital in the course of subclinical fascioliasis in sheep

Pharmacokinetics of two common veterinary drugs, ampicillin and pentobarbital, were determined in sheep before and four, eight, 12, 17 and 21 weeks after infestation of animals by an oral administration of 150 metacercariae of Fasciola hepatica. The parasite infestation was ascertained by clinical observation of the animals. The pharmacokinetics of ampicillin were not significantly affected by the liver parasitism but the disposition of pentobarbital changed. A significant increase in elimination half-life (around 180 per cent), volume of distribution (130 per cent) and mean residence time (154 to 170 per cent) was observed in sheep infected by the parasite for four to 12 weeks. In these animals, duration of narcosis caused by pentobarbital was prolonged 1.8-fold. The results suggested that both reduced elimination of pentobarbital and impaired distribution of the drug would be responsible for the prolonged duration of narcosis in infected animals.     

The serum glucose and beta-hydroxybutyrate levels in sheep with experimental Fasciola hepatica and Fasciola gigantica infection

The influence of Fasciola hepatica and Fasciola gigantica infection on serum glucose and beta-hydroxybutyrate (beta-HOB) in sheep was evaluated. This was done by setting up two groups of sheep. The first group (n=13) was split in two sub-groups, one experimentally infected with F. hepatica (n=9) and the other (n=4) as uninfected control. A second group consisting of a sub-group experimentally infected with F. gigantica (n=9) the other sub-group (n=6) left as uninfected control was also set up. The results of weight gain, parasitological and serum liver enzymes activity (glutamate dehydrogenase [GLDH] and gamma glutamyltransferase [gamma-GT]) used in monitoring the infection showed that all infected animals developed fasciolosis. It was observed that a reduction in serum glucose levels was significantly lower (p<0.05) in F. hepatica infected sheep than in uninfected control sheep starting from 5 weeks post-infection (wpi) to the end of the experiment. Similar reduction was recorded in F. gigantica infected sheep between 8 and 19 wpi. In contrast, serum beta-HOB levels were elevated in F. hepatica infected sheep between 6 and 16 wpi and in F. gigantica infected sheep between 7 and 15 wpi. It would appear from these serum glucose and beta-HOB levels that fasciolosis does lead to energy deficiency (low glucose) and ketosis (increased beta-HOB). The decrease in serum glucose and increase in serum beta-HOB levels in infected sheep may help in understanding the interaction between fasciolosis and nutritional status of infected ruminants especially in young growing animals.     

Chemotherapy and pharmacokinetics of some antimicrobial agents in healthy dwarf goats and those infected with Ehrlichia phagocytophila (tick-borne fever)

The therapeutic efficacy and pharmacokinetics of oxytetracycline (10 mg kg-1), ampicillin (20 mg kg-1) and a combination (TSS) of trimethoprim (20 mg kg-1), sulphadimidine (50 mg kg-1) and sulphamethylphenazole (50 mg kg-1) were investigated in normal dwarf goats and in those infected with Ehrlichia phagocytophila. Goats given oxytetracycline or TSS intravenously showed improvement, whereas ampicillin was ineffective. The infected goats had significantly prolonged elimination half-life values for sulphadimidine and oxytetracycline. The disposition kinetics of ampicillin and sulphamethylphenazole showed no marked differences between the healthy and infected animals. The tick-borne fever model used in the present study can be of value in testing the therapeutic efficacy and pharmacokinetics of chemotherapeutic agents in rickettsial infections.     

Preliminary observations on the use of the capillary flocculation test for the diagnosis of heartwater (Cowdria ruminantium infection).

A capillary flocculation test was developed to diagnose heartwater disease of ruminants. Antigen was prepared from the brains of cattle and goats highly infected with Cowdria ruminantium. Sera were obtained from experimentally infected ruminants which either recovered naturally or with the aid of oxytetracycline treatment. Antibodies were first detected one to two weeks after clinical recovery or after treatment, and persisted for periods varying between one and four weeks. Control sera collected from cattle (sheep) and goats in the Netherlands where heartwater does not occur, or from animals serologically positive for Anaplasma marginale or Eperythrozoon ovis infections, did not react to the test.     

Antipyrine disposition in calves. I. Effects of some drugs

The influence of four drugs on antipyrine pharmacokinetic parameters was studied after 3 h, 2 and 6 days in 32 Friesian calves. Dexamethasone phosphate and griseofulvin led to increased antipyrine elimination. The effect of dexamethasone remained significant 2 and 6 days later. The rate of antipyrine elimination was markedly but transiently depressed by chloramphenicol and oxytetracycline. The apparent volume of antipyrine distribution remained unaltered during treatment.     

Comparison of three oxytetracycline regimes for the treatment of persistent Anaplasma marginale infections in beef cattle

Anaplasmosis, caused by the tick-borne rickettsia, Anaplasma marginale, is an economically important disease of cattle in the United States and worldwide. Cattle that recover from acute infection become carriers in which low or microscopically undetectable A. marginale rickettsemia persists. Tetracycline antimicrobials are currently the only drug used in the US for treatment of acute anaplasmosis. There are currently no drugs specifically licensed for elimination of persistent infections. This study tested the efficacy of three oxytetracycline treatment regimens to clear A. marginale from cattle that were persistently infected. Forty Angus x Simmental steers, aged 6-12 months were experimentally infected with A. marginale. After the steers recovered from acute infection, seroconverted, and were confirmed infected using nested PCR followed by DNA hybridization, the carrier status of each animal was ascertained by sub-inoculation of blood into a separate, splenectomized Holstein calf. The steers were then blocked by bodyweight and randomly assigned as follows to four treatment groups: Treatment A, 300 mg/ml solution of oxytetracycline (Tetradure LA-300, Merial Canada Inc.) administered at 30 mg/kg, by intramuscular (i.m.) injection on day 0; Treatment B, the same 300 mg/ml solution of oxytetracycline administered at 30 mg/kg, i.m. on day 0 and again on day 5; Treatment C, a 200 mg/ml solution of oxytetracycline (Liquamycin LA-200, Pfizer Animal Health) administered at 22 mg/kg, intravenously (i.v.), q 24 h for 5 days (a treatment dose that corresponds with current Office International des Epizooties (OIE) recommendations for treatment prior to export). The fourth group consisted of untreated infected control cattle. All steers were still nested PCR and cELISA positive at 60 days after treatment. Infection was confirmed by subinoculation of blood into a splenectomized Holstein calf. These results demonstrated that the treatment regimens tested failed to clear A. marginale infections in carrier cattle.     

Evaluation of cercarial antigen for the serodiagnosis of fasciolosis in experimentally and naturally infected sheep

The value of cercarial antigen for diagnosis of experimental and natural sheep fasciolosis was studied by enzyme linked immunosorbent assay (ELISA) and enzyme linked immunotransfer blot (EITB). In ELISA, the antibody levels of experimentally infected sheep with Fasciola gigantica appeared at 2 weeks post infection (PI), gradually increased till 7 weeks PI and nearly remained at the same level from 7 to 13 weeks PI (the end of experiment). Also, the sensitivity and specificity of cercarial antigen for diagnosis of naturally sheep fasciolosis were 100 and 90%, respectively.In EITB, in the sheep experimentally infected with F. gigantica, the band of 32.5kDa molecular weight polypeptide appeared at 2 weeks PI and continued till the end of experiment. Also, the cercarial antigen recognized 32.5kDa molecular weight band with all sera from naturally infected sheep with fasciolosis (n = 25). This band did not cross-react when tested with sera from infected sheep with Cysticercus tenuicollus (n = 20). This study suggests that, the 32.5kDa molecular weight polypeptide could be used as sensitive and specific epitope for the serodiagnosis of sheep fasciolosis.     

Effects of experimentally induced Theileria annulata infection on the pharmacokinetics of oxytetracycline in cross-bred calves

The effects of an experimental Theileria annulata infection on the intravenous (10 mg kg-1) pharmacokinetics of oxytetracycline (OTC) were investigated in crossbred calves. The serum concentration-time curve of oxytetracycline before and after the experimental infection was best described by an open two-compartment model. The experimental infection was induced by a subcutaneous administration of ground-up tick supernate (GUTS) equivalent to 30 Hyalomma anatolicum anatolicum ticks infected with Theileria annulata. It produced a definite temperature rise and symptoms of clinical disease in the calves. The haemoglobin, packed cell volume (PCV), white blood cell (WBC) counts and serum Cu, Fe and Zn concentrations decreased after onset of the infection. The distribution and elimination half-lives (t1/2 alpha and t1/2 beta), volume of the central compartment (Vc), AUC0-infinity, AUMC and mean residence time (MRT), were significantly reduced (P < or = 0.05) and the hybrid rate constants K12, Kel, K12/K21 ratio and total body clearance (ClB) of oxytetracycline were significantly (P < or = 0.05) increased after infection. The infection, however, had no effect on the C0, K21, apparent and steady-state volumes of distribution (Vd(area) and Vdss) of the drug. The above changes may necessitate changes in the dosage regimen of oxytetracycline used to treat Theileria infections in cattle under field conditions.     

Bovine fasciolosis: coprological, abattoir survey and its economic impact due to liver condemnation at Soddo municipal abattoir, Southern Ethiopia

A study was carried out to determine the prevalence and the species of liver flukes in indigenous adult cattle, to compare the diagnostic efficiency of fecal and post mortem examination and to assess the economic significance of bovine fasciolosis due to liver condemnation in the abattoir. Of the 406 livers and fecal samples examined, 57 (14.0%) and 20 (4.9%) were positive for fasciolosis. The most common liver fluke species affecting the cattle was Fasciola gigantica, 9.1% of cattle were infected with F. gigantica while, Fasciola. hepatica, mixed infections and unidentified or immature forms of Fasciola spp. were present in 3.2 %, 0.7% and 1 % of cattle, respectively. A retrospective abattoir survey revealed that the prevalence of fasciolosis was 12.7%. The prevalence of fasciolosis recorded in this study was lower than that reported by other researchers in this country. There was a strong relationship between fecal examination and postmortem findings of liver lesions, (K?=?0.23) but under local conditions, postmortem examination was considered a better diagnostic tool for fasciolosis. Fasciolosis is of significant economic importance as the resultant liver condemnations caused an average loss of 4000 USD per annum. Hence, this disease deserves serious attention by the various stakeholders in order to promote the beef industry in the study area in particular and in the country in general.     

Plasma and tear concentrations of antibiotics administered parenterally to cattle

Chloramphenicol, erythromycin, gentamicin, oxytetracycline, penethamate and procaine benzyl penicillin were administered parenterally to cattle and the concentrations of these antibiotics in plasma and tears were assayed microbiologically. Concentrations in plasma and tears were significantly correlated for all antibiotics tested but the concentration of antibiotic in tears and the tear flow rate were not correlated. Lipophilic drugs diffused into the tears in higher concentrations than did drugs which were not lipophilic. Concentrations of lipophilic but not hydrophilic antibiotics in tears could be predicted from the Henderson-Hasselbach equation. In cattle, it is possible through parenteral administration of chloramphenicol, erythromycin, gentamicin or oxytetracycline to achieve antibiotic concentrations in the tears which are bacteriostatic to Moraxella bovis, a primary aetiological agent of infectious bovine keratoconjunctivitis.     

Performance characteristics of an enzyme-linked immunosorbent assay for the detection of liver fluke (Fasciola hepatica) infection in sheep and cattle

AIM: To validate an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against liver fluke (Fasciola hepatica) in sheep and cattle sera. METHODS: Gold-standard sera from sheep and cattle of known infection status, i.e. sera from non-infected animals and from animals known to be infected with F. hepatica were assayed with a commercially available ELISA and results analysed by ROC analysis. RESULTS: The ROC analysis suggested cut-offs that were considerably lower than those suggested by the manufacturer, yet the ELISA performed with high sensitivity and specificity, 98 to 100%, respectively for sheep and cattle sera. For bovine sera, particularly good discrimination between positive and negative sera was observed. Infection in experimentally infested animals could be demonstrated 7-8 weeks earlier than with classical parasitological techniques. CONCLUSIONS: The analysis of the ELISA's performance demonstrated high sensitivity and specificity. ROC analyses optimised the cut-off point suggested by the manufacturer of the commercial diagnostic assay. Diagnosis of infection with F. hepatica was achieved much earlier than is possible with current parasitological techniques. This could help with the control of fasciolosis, enabling treatment before clinical manifestation of the disease.     

Comparison of the efficacy of enrofloxacin, imidocarb, and oxytetracycline for clearance of persistent Anaplasma marginale infections in cattle

This study compared enrofloxacin and imidocarb dipropionate treatments with an oxytetracycline regimen proposed by the World Organization for Animal Health for elimination of persistent Anaplasma marginale infections in cattle. The effect of therapy on competitive ELISA and polymerase chain reaction (PCR) reactivity was also assessed. Twelve A. marginale-infected carrier calves were randomly assigned to groups receiving either enrofloxacin (5 mg/kg IV q24h for 5 days), imidocarb (5 mg/kg IM twice, 7 days apart), or oxytetracycline (22 mg/kg IV q24h for 5 days). One calf infected with an Oklahoma isolate in the imidocarb group and one infected with a Virginia isolate in the oxytetracycline group failed to infect a splenectomized calf following blood subinoculation. Both became competitive ELISA negative by 44 days after treatment, but the imidocarb-treated calf remained PCR positive. None of the tested treatments reliably eliminated persistent A. marginale infections in all cattle. Furthermore, PCR was not a reliable means of determining the success of chemosterilization in calves.     

Influence of experimentally induced theileriosis (Theileria annulata) on the pharmacokinetics of a long-acting formulation of oxytetracycline (OTC-LA) in calves

The effects of experimental Theileria annulata infection on the i.m. (20 mg/kg) pharmacokinetics of oxytetracycline were investigated in crossbred calves. The serum concentration-time curves of oxytetracycline (OTC-LA), before and after experimental infection, were best described by a one-compartment open model. The experimental infection by subcutaneous administration of ground-up tick supernate (GUTS), equivalent to 30 Hyalomma anatolicum anatolicum ticks infected with Theileria annulata, produced a clear temperature rise and signs of clinical disease in calves. Subsequently, haemoglobin, packed cell volume, total leucocyte count and serum Cu, Fe and Zn concentrations decreased after infection. The absorption and elimination half-lives (t1/2 Ka and t1/2 Ke), mean absorbance time (MAT), time to peak concentration (Tmax), mean residence time (MRT), area under the serum concentration time curve (AUC infinity) and the bioavailability (F) were significantly (P < 0.05) decreased. The peak serum concentration (Cmax), however, remained unchanged after infection. These changes may necessitate alterations in the dosage regimen of oxytetracycline used to treat Theileria annulata infections in cattle under field conditions.     

The prevalence and economic importance of bovine fasciolosis in Kenya--an analysis of abattoir data

A retrospective study covering a period of 10 years (1990-1999) was carried out using post mortem meat inspection records at the Veterinary Department Headquarters at Kabete to determine the prevalence and economic importance of bovine fasciolosis in Kenya. Meat inspection records from abattoirs in 38 districts distributed over seven out of the eight provinces of Kenya were examined. Prevalence of fasciolosis was calculated as the number of cattle found to be infected with Fasciola, expressed as a percentage of the total number of cattle slaughtered. Using the average weight and market price of a bovine liver, the monetary loss occasioned by condemnation of Fasciola infected livers was calculated. A survey was also carried out at Dagoretti slaughterhouse complex in Nairobi to determine the relative occurrence of F. gigantica and F. hepatica in slaughtered cattle. Cattle slaughtered at Dagoretti slaughterhouse originate from all parts of the country. A total of 5,421,188 cattle were slaughtered in the seven provinces of Kenya during the 10-year period and 427,931 (8%) of these cattle were infected with Fasciola. The region with the highest prevalence of fasciolosis was Western Province (16%) followed, in descending order, by Eastem Province (11%), Nyanza Province (9%), Rift Valley Province (8%), Central Province (6%), Nairobi Province (4%) and Coast Province (3.5%). The total economic loss incurred by the country during the 10-year period as a result of condemnation of the infected livers was approximately US$2.6 million. The total annual economic losses during this period ranged from approximately US$0.2-0.3 million. The highest total economic losses for the 10-year period were recorded in Western Province (US$0.8 million) and Central Province (US$0.7 million). A total of 1584 cattle originating from five provinces of Kenya were slaughtered at Dagoretti slaughterhouse over a period of two months of which 147 (9.3%) were infected with liver flukes. All the liver flukes obtained from the infected livers were identified as F. gigantica. It is concluded that fasciolosis is prevalent in cattle in all provinces of Kenya, that it causes great economic losses as a result of condemnation of infected livers, and that F. gigantica is the main species of liver flukes affecting cattle in Kenya. Local climatic factors, cattle trade, rustling and population numbers, and the presence of the snail intermediate hosts are probably the main factors influencing the incidence of the disease in the various regions of the country.     

Human and animal fasciolosis: Coprological survey in Narok,Baringo and Kisumu counties,Kenya

Fasciolosis is caused by digenean trematodes of the genus Fasciola. The principal definitive hosts are cattle, sheep and goats. Humans are infected as accidental hosts. Fasciolosis is one of the major neglected tropical diseases and is considered an emerging zoonotic infection. This study was aimed at determining the prevalence of human and domestic animal fasciolosis in selected counties in Kenya. Stool samples for Fasciola diagnosis were collected from humans and domestic animals and transported to the laboratory at Egerton University and processed using sedimentation technique and examined for the presence of eggs. A total of 272 human samples collected were all negative for Fasciola eggs. A total of 582 domestic animals (cattle [46.0%], sheep [29.9%] and goats [24.1%]) samples collected had overall prevalence of 30.9% for Fasciola infection. There was no significant differences (p > 0.05) between the prevalence of fasciolosis and origin of the animals, sex and season. There was a significant difference (p < 0.05) between the prevalence of fasciolosis and domestic animals, age and body condition. The prevalence of fasciolosis was high in two irrigation schemes which favour the breeding of intermediate host snail and grazing of animals along the irrigation canals where metacercaria of Fasciola parasites could be present on the vegetation. Although human fasciolosis was not detected in this study, the presence of animal fasciolosis can pose public health risk because of its zoonotic nature. Therefore, it is important to introduce measures which would help to reduce the exposure of animals to Fasciola infection.     

A retrospective study of the prevalence and seasonal variation of Fasciola gigantica in cattle slaughtered in the major abattoirs of Zimbabwe between 1990 and 1999

A retrospective study covering a period of 10 years (1990--1999) was conducted using post mortem meat inspection records of the Veterinary Department Information Management Unit at Harare to determine the prevalence and seasonal variation of bovine fasciolosis in Zimbabwe. Records of monthly and annual returns from five major abattoirs were examined in regard to total cattle slaughtered and the corresponding number of livers condemned due to Fasciola gigantica infection. Prevalence of fasciolosis was calculated as the number of cattle found to be infected with F gigantica, expressed as a percentage of the number of cattle slaughtered. Seasonal variations in the prevalence were examined by pooling respective monthly condemnation data over a 10-year (1990--1999) period. A total of 2,474,232 cattle were slaughtered during this period and 917,565 (37.1%) of these cattle were infected with F. gigantica. The pattern of distribution of F. gigantica was significantly higher in cattle originating from catchment areas of high rainfall than in those of relatively low rainfall, and in those slaughtered during the wet season than those slaughtered during the dry season (P< 0.05). Based on the study findings a control programme for the disease in Zimbabwe is suggested.     

The in vitro effect of six antimicrobials against Mycoplasma putrefaciens, Mycoplasma mycoides subsp. mycoides LC and Mycoplasma capricolum subsp. capricolum isolated from sheep and goats in jordan

Respiratory disease in sheep and goats is a major problem in Jordan and is often associated with Mycoplasma species. Without effective vaccines, control is mainly by chemotherapy, but the uncontrolled use of antimicrobials has led to concerns about the potential development of antimicrobial resistance. The in vitro effect of chloramphenicol, florfenicol, enrofloxacin, tylosin, erythromycin and oxytetracycline was determined against 32 isolates of Mycoplasma species-M. mycoides subsp. mycoides LC (6), M. capricolum subsp. capricolum (8) and M. putrefaciens (18), all isolated from either nasal swabs or milk, from sheep and goats in different regions of Jordan. The antimicrobial susceptibility showed some Mycoplasma species-specific differences, with M. capricolum subsp. capricolum being more susceptible to tylosin and erythromycin. Chloramphenicol and florfenicol were the least effective for all three Mycoplasma species. No trends or significant differences in antimicrobial susceptibilities were observed between sheep and goat isolates, between milk or nasal swab isolates, or between isolates from different regions of Jordan. Some isolates of M. capricolum subsp. capricolum and M. putrefaciens showed higher MIC levels with oxytetracycline, as did two isolates of M. mycoides subsp. mycoides LC with tylosin, possibly indicating signs of development of antimicrobial resistance.     

An outbreak of subacute fasciolosis in Soay sheep: ultrasonographic biochemical and histological studies

A naturally occurring outbreak of subacute fasciolosis in a group of 17 seven-month-old Soay ram lambs was studied following the sudden death of two sheep. In addition to standard biochemical investigations, ultrasound examination of the liver and cranial abdominal cavity was undertaken. There was a significant positive linear correlation between liver weight and ultrasonographic determination of liver size (R=0.72, P<0.05). Ultrasonographic examination of the liver revealed multiple hyperechoic dots in the parenchyma giving a granular appearance to the hepatic texture in three sheep corresponding to the most advanced histopathological changes as determined by the size of the abscesses and their relatively mature fibrous capsules, and areas of hepatic necrosis. No distension of the bile duct system was noted nor was the gall bladder imaged. While serum concentrations of albumin, globulin and certain liver enzymes assisted in the diagnosis of subacute fasciolosis in sheep, only glutamate dehydrogenase, and gammaglutamyl transferase remained elevated four weeks after triclabendazole treatment.     

The awareness of farmers with regard to bovine fascioliasis

The owners of 54 cattle herds with bovine fasciolosis, as a livestock problem in Switzerland, were surveyed on their farm, on their education and knowledge on Fasciola hepatica. The aim of the survey was to assess the awareness of the farmers concerning this economically important parasitosis. The analysis of the questionnaires revealed that 72.2% of the farmers were unaware of the fasciolosis in their animals. The knowledge of 51 out of 54 (94.4%) respondents was classified as low to moderate, only four farmers (7.4%) had knowledge of control strategies in addition to the parasite cycle. The knowledge on fasciolosis did not correlate with farm data or year of graduation from school for agriculture. Furthermore, the results were compared to the answers of 33 farmers whose animals were not infected with Fasciola hepatica. Of this group of respondents 12.1% believed that their cattle suffered from fasciolosis.     

Pharmacokinetics of oxytetracycline after intramuscular administration with lidocaine in sheep, comparison with a conventional formulation

The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep after intravenous and intramuscular administration at a single dosage of 20 mg kg⁻¹ bodyweight. A conventional formulation was injected by the intravenous route and two different preparations were administered by the intramuscular route: a conventional formulation (T-100) and an aqueous solution of OTC with lidocaine (1 per cent) (OTC-Q. The objective was to determine whether there are differences between both formulations in the disposition kinetics of OTC after intramuscular administration to sheep. After intravenous administration of the conventional formulation, plasma oxytetracycline concentrations were best fitted to an open two-compartment model. Mean apparent volume of distribution was 0·77±0·02 litre kg⁻¹ and the harmonic mean half-life was three hours. The OTC transfer process between central and peripheral compartments was fast and that did not influence the elimination process. After intramuscular administrations of both formulations, half-lives were longer than after intravenous administration (mean values of 14·1 and 58·2 hours for T-100 and OTC-L respectively). In both cases, a biphasic absorption, a ‘flip-flop’ model and a complete bioavailability were found. OTC-L provided therapeutic plasma concentrations over 0·5 μg ml⁻¹ (the minimum inhibitory concentration for most susceptible pathogens) for a longer period of time than T-100 (72 hours compared with 36 or 48 hours).