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Background: Piroplasmosis caused by the Babesia microti-like piroplasm (Bml) is increasingly being detected in dogs in Europe. Sick dogs show acute disease with severe anaemia associated with thrombocytopenia with a poor response to current available drugs. This study assesses the safety and tolerance of three treatments and compares their efficacy over a full year of follow up in dogs naturally infected with Bml., Methods: Fifty-nine dogs naturally infected with Bml were randomly assigned to a treatment group: imidocarb dipropionate (5 mg/kg SC, 2 doses 14 d apart) (IMI); atovaquone (13.3 mg/kg PO q 8 h, 10 d)/azithromycin (10 mg/kg PO q 24 h, 10 d) (ATO); or buparvaquone (5 mg/kg IM, 2 d apart)/azithromycin (same dosage) (BUP). Before and after treatment (days 15, 45, 90 and 360), all dogs underwent a physical exam, blood tests and parasite detection (blood cytology and PCR). Clinical efficacy was assessed by grading 24 clinical and 8 clinicopathological signs from low to high severity., Results: Before treatment, most dogs had severe regenerative anaemia (88.13%) and thrombocytopenia (71.4%). On treatment Day 45, clinical signs were mostly reduced in all dogs, and by Day 90, practically all dogs under the ATO or BUP regimen were clinically healthy (76.4 and 88%, respectively). Highest percentage reductions in laboratory abnormalities (82.04%) were detected in animals treated with ATO. Over the year, clinical relapse of Bml was observed in 8 dogs (8/17) treated with IMI. However, on Day 360, these animals had recovered clinically, though clinicopathological abnormalities were still present in some of them. Parasitaemia was PCR-confirmed on Days 90 and 360 in 47.05 and 50% of dogs treated with ATO, 68 and 60.08% with BUP, and 94.1 and 73.3% with IMI, respectively. Even after 360 days, 13.3% of the dogs treated with IMI returned a positive blood cytology result., Conclusions: IMI showed the worse clinical and parasitological, efficacy such that its use to treat Bml infection in dogs is not recommended. The treatments ATO and BUP showed better efficacy, though they were still incapable to completely eliminate PCR-proven infection at the recommended dose. All three treatments showed good tolerance and safety with scarce adverse events observed.

Anaplasmosis is a worldwide hemolytic disease in cattle caused by a gram-negative obligatory intracellular bacterium, characterized by anemia and jaundice. Among the treatments used for anaplasmosis is a drug called imidocarb dipropionate, also indicated as an immunomodulator agent. However, it causes side effects associated with increased levels of acetylcholine. In view of this, the effects of imidocarb dipropionate on the purinergic system, and antioxidant enzymes in animals naturally infected by Anaplasma marginale were evaluated. Young cattle (n = 22) infected by A. marginale were divided into two groups: the Group A consisted of 11 animals used as controls; and the Group B composed of 11 animals. Imidocarb dipropionate (5 mg/kg) was used subcutaneously to treat both groups (the Group A on day 6 and the Group B on day 0). The treatment reduced acetylcholinesterase (AChE), and adenosine deaminase (ADA) activities, and increased the dismutase superoxide and catalase activities. No changes on lipid peroxidation (TBARS levels) and BChE activities were noticed. These results suggest that imidocarb dipropionate used to treat A. marginale infection in cattle has effect on antioxidant enzymes, and significantly inhibits the enzymatic activities of ADA and AChE., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of this study was to determine the safety of imidocarb dipropionate in sheep. Imidocarb dipropionate (IMDP) was administered (2.4 mg/kg, intramuscular; i.m.) to 10 sheep, and blood samples were obtained 0, 1, 6, and 9 days after treatment. Hemacell counts, serum biochemical values, coagulation values, and serum oxidative status were measured. IMDP caused transient decreases in pH, actual bicarbonate, standard bicarbonate, total carbon dioxide, base excess in vivo, base excess in vitro, oxygen saturation, lactate dehydrogenase, and retinol levels and transient increases in serum creatine kinase-MB, blood urea nitrogen, and creatinine levels. IMDP decreased adenosine deaminase activity, antithrombin III, and superoxide dismutase activity and increased white blood cell counts. In conclusion, IMDP may change serum oxidative status and cause coagulation disorders during treatment in sheep.

Current treatments with imidocarb dipropionate for infected dogs with Hepatozoon canis do not always provide parasitological cure. The objective of this study is to determine whether concomitant use of toltrazuril may potentiate the effect of imidocarb dipropionate in the management of H. canis infection (HCI). Twelve dogs were determined to have naturally HCI based on clinical signs, identification of the parasite in blood smears, and serologic assay. The animals were allocated randomly to one of two groups (n = 6 in each group). Dogs in Imi group were given imidocarb dipropionate at a dose of 6 mg/kg body weight subcutaneously in two injections 14 days apart. Imi plus Toltra group was given imidocarb dipropionate as dose mentioned above and toltrazuril at 10 mg/kg/day orally for the first five treatment days. Clinical findings, blood counts and parasitaemia levels in blood before and 14, 28 and 56 days after the initial treatment were performed to evaluate treatment response. The overall clinical efficacy of imidocarb dipropionate with and without toltrazuril was 83.3% and 66.7%, respectively; with a mean recovery time of 21.0 and 25.6 days, respectively. A substantial main effect of time on mean PCV, Hb, WBC, neutrophil and PLT and gradual reduction of parasitaemia were significantly observed in both groups (P < 0.05), whereas no significant difference was noticed between the studied protocols. The parasitologic cure rate at the end of eight weekly observation period was 16.6% and 33.3% in Imi and Imi plus Toltra groups, respectively. Similar clinicopathologic and parasitologic responses were observed in both treated groups; thus, it was concluded that toltrazuril does not reveal additional benefit to imidocarb therapy in dogs with HCI.

The efficacy of imidocarb dipropionate for the treatment of Hepatozoon canis infection was studied in three naturally infected asymptomatic dogs followed longitudinally over 8 months. Response to treatment was followed by monitoring blood counts, parasitemia levels in blood, parasite in concentrated buffy-coat smears and by PCR. The dogs were initially treated with a low dose of 3 mg/kg imidocarb dipropionate twice a month and when parasitemia persisted after five treatments, with the regular dose of 6 mg/kg. In one dog, H. canis gamonts were no longer detectable by blood and buffy-coat microscopy after 2 months of therapy with 6 mg/kg while in the two other dogs gamonts were intermittently found in blood but persistently detectable in buffy-coat smears during the whole study period. Furthermore, combined therapy with doxycycline monohydrate administered at 10 mg/kg/day PO for 4 weeks also failed to eliminate H. canis. PCR revealed that parasite DNA was present in the blood of all dogs at all sampling dates regardless of treatment refuting the effectiveness of treatment suggested by negative blood microscopy. Detection of H. canis in buffy coat was found to be twice as sensitive than by blood smear and detection by PCR was even more sensitive revealing infection in eight samples (16% of total samples) negative by blood and buffy-coat microscopy. In conclusion, imidocarb dipropionate was not effective in eliminating H. canis from dogs treated repeatedly over 8 months. Microscopical detection is not sufficient for the evaluation of treatment response in H. canis infection and follow up by molecular techniques is recommended., (Copyright 2010 Elsevier B.V. All rights reserved.)

A residue depletion study was performed with high-performance liquid chromatography (HPLC) to determine a withdrawal period of imidocarb (IMD) in swine tissues. The drug was administered intramuscularly (im) at the dose of 2.0 mg kg(-1) of body weight (bw) once a day for 3 days. Samples of muscle, fat, liver, kidney, and injection site muscle from 5 pigs were collected on 7, 14, 28, and 56 days after the last administration. Quantitative analysis of IMD was conducted by HPLC-UV at 260 nm after liquid-liquid extraction. The limit of detection (LOD) of the method was 0.1 microg g(-1) for liver and kidney and 0.05 microg g(-1) for muscle and fat, respectively. Mean recoveries of IMD in all fortified samples at a concentration range of 0.1-25 microg g(-1) were 69.5-89.3%, with a coefficient of variation (CV) below 13.3%. In swine, the highest drug levels occurred in liver and kidney during the whole study period, suggesting that these tissues are targets for residues. IMD concentrations in all examined tissues were below the accepted maximum residue limits (MRLs) recommended by the Committee for Veterinary Medical Products (CVMP) of the European Medical Evaluation Agency (EMEA) at 54 days post-treatment.

Sixteen shorthorn cows from Xiazhuang farm were admitted to the Veterinary Teaching Hospital at the College of Animal Science and Veterinary Medicine, Shandong Agricultural University for evaluation of poor appetite, listlessness, fever, tachycardia, tachypnea, lethargy, positive jugular venous pulse and anemia. Blood smear examination and polymerase chain reaction analysis in these cows revealed an infection with Mycoplasma wenyonii. The subjects were divided into two groups: control group (three cows) treated with intramuscular injection with imidocarb dipropionate (3 mg/kg/day for 2 days) and the experimental group (13 cows), treated with injection-acupuncture (Imidocarb Dipropionate, 1 mg/kg, once every 3 days for 6 days) at BL17, BL18, BL20, BL25, ST36, SP06 and CV04. At day 15, negative results were found using blood smear examination in all control and experimental groups.

A two-way crossover study was performed in eight healthy young pigs to determine the pharmacokinetics of imidocarb dipropionate (IMDP) following intravenous (2 mg/kg b.w.) and intramuscular (2 mg/kg b.w.) administrations. Each animal received one intravenous and one intramuscular injection with a 30-day washout period between the two-treatments. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) assay with UV detector at regular intervals for up to 24 h post-injection. Intravenous plasma concentration profiles best fit a three-compartmental model yielding a mean system clearance (Cl((s))) of 558 mL/kg.h and a mean half-life of 13.91 h. Mean imidocarb AUC((0-infinity)) (microg.h/mL), V(c) (L/kg), V(d(area))(L/kg) and MRT((0-t)) (h) values were 3.58, 0.11, 14.36 and 1.46, respectively. Compartmental modeling of imidocarb, after intramuscular administration produced best fit for two-compartmental model yielding mean Kalpha (h(-1)), Cmax (microg/mL), tmax (h), and bioavailability (%) of 3.89, 2.02, 0.54, and 86.57 for the 2 mg/kg dose level. The present studies showed that IMDP was rapidly absorbed, widely distributed, and slowly eliminated. No adverse effects were observed in any of the pigs after i.v. and i.m. administrations of IMDP. The favorable PK behavior, such as the long half-life, acceptable bioavailability indicated that it is likely to be effective in pigs.

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.

The pharmacokinetics and mammary excretion of imidocarb dipropionate, a therapeutic/prophylactic agent against a variety of tick-borne hemoparasitic diseases in domestic animals, have been investigated in sheep and goats. A commercial formulation of imidocarb di-propionate was injected i.m. at a single dose of 3 mg/kg of body weight in 7 mature lactating ewes and 8 lactating does in good health. Blood samples were collected for 48 h after administration and milk samples were collected every 12 h for 10 d. A weak cation-exchange solid-phase procedure was used to remove imidocarb from plasma. A hexane/isoamyl alcohol liquid-liquid procedure was adopted to extract the drug from the milk of sheep. The same method was used for goat milk after exposing the matrices to enzymatic digestion. The extracted samples were analyzed by HPLC. The i.m. disposition kinetics of imidocarb in the 2 species showed significant differences in the rate of elimination (0.0075 +/- 0.002 and 0.025 +/- 0.004 L/h in sheep and goats, respectively), being faster in ewes than in does. Nevertheless, a smaller area under the concentration-time curve (12.21 +/- 0.76 and 9.49 +/- 0.54 microg/mL per h in sheep and goats, respectively), a larger volume of distribution (4.18 +/- 0.44 and 7.68 +/- 0.57 L/kg in sheep and goats, respectively), and a longer mean residence time (9.07 +/- 0.77 and 14.75 +/- 2.20 h in sheep and goats, respectively) were found in goats, suggesting a more rapid and effective drug storage in tissues during the first 48 h after the injection. The concentrations of imidocarb in milk of both species were higher than in plasma. However, a fast passage through the blood-milk barrier and a high storage of imidocarb were observed in the milk of ewes, whereas the drug concentrations were not as high nor was the extent of drug penetration from blood to milk as great in the milk of goats (AUC(milk 0-48)/AUC(plasma 0-48) = 2.5 +/- 0.45 and 1.26 +/- 0.27 in sheep and goat, respectively). Despite the differences in pharmacokinetic behavior, and considering the sensitivity of pathogens to imidocarb, the same dosage regimen can be used for clinical efficacy against Babesia spp. infection in both species. In contrast, the differences in depletion of imidocarb residue in milk and the large variability in mammary drug elimination found in goats suggests that great care should be taken in defining the withdrawal time in small ruminant dairy species.

The tick-borne rickettsia, Anaplasma marginale, causes the economically important cattle disease anaplasmosis. Once infected, cattle remain lifelong carriers. Herein, we used flow cytometry to test the efficacy of three antimicrobials; oxytetracycline, imidocarb and enrofloxacin against Virginia (VGN) or Oklahoma (OK) A. marginale isolates in short-term erythrocyte cultures. Parasite viability was assessed using the vital dye hydroethidine (HE), which is detectable when living organisms convert HE to ethidium bromide. Viability of A. marginale in selected cultures was determined by subinoculation into susceptible calves. Data were analyzed by MANOVA, Tukey-Kramer honest significant difference and Wilcoxon rank sum tests. Receiver operating characteristic (ROC) analysis was used to correlate results with culture infectivity. Enrofloxacin inhibited A. marginale in a dose dependent manner. Surprisingly, higher concentrations of imidocarb were less effective than lower concentrations against A. marginale with significant differences (P < 0.05) observed between the two isolates. Oxytetracycline was the least active drug tested. Cultures infected with the OK isolate exposed to 4.0 microg/mL enrofloxacin and those of the VGN and OK isolates exposed to 1.0 microg/mL imidocarb were sterilized. This is the first in vitro study demonstrating the efficacy of enrofloxacin against A. marginale. Furthermore, these data indicate that flow cytometry is a useful assay for screening antimicrobials against A. marginale.

Canine babesiosis has a high prevalence in France and continues to constitute a diagnostic challenge. This paper presents essential data derived from epidemiological surveys in order to define the main features of this disease. Atypical forms are frequent, the diagnosis must be confirmed by blood smears and treatment is based on the use of imidocarb. Prophylaxis currently remains insufficient.

In this study one spleen-intact dog (A) and two splenectomised dogs (BSE, CSE) were infected with Babesia canis. All animals developed an acute disease characterised by fever, haemoglobinuria and anaemia, the latter being more severe in the splenectomised dogs. Fever and parasitised red blood cells were detected for three days after imidocarb treatment in the splenectomised animals. Haematological abnormalities included regenerative anaemia, thrombocytopenia and leukopenia (due to neutropenia and lymphopenia) in the acute phase, soon followed by leukocytosis, neutrophilia and left shift a few days later. Acute hepatopathy was detected in all dogs with elevated ALT activity, which was more seriously altered in the splenectomised dogs. Diffuse changes in liver structure and hepatomegaly were seen by ultrasonography. Liver biopsy and histology revealed acute, non-purulent hepatitis in the splenectomised dogs. Both splenectomised dogs were successfully cured after collection of 400 ml highly parasitised blood, proving that large-amount antigen production is possible with rescuing the experimental animals. Whole blood transfusion, imidocarb and supportive care with infusions, antipyretics, glucocorticoids and diuretics were applied. The spleen-intact dog clinically recovered after receiving supportive treatment, with no imidocarb therapy. Microbial infections developed in both splenectomised animals (BSE: haemobartonellosis, CSE: osteomyelitis caused by Escherichia coli), probably as a consequence of immunosuppression after splenectomy and glucocorticoid therapy.

Haematological variables and selected serum indices, particularly those affected by changes in renal and hepatic function, were examined in 6 healthy ponies following 4 intramuscular doses of 4 mg/kg imidocarb dipropionate administered every 72 hours. This treatment regime has been reported to sterilise experimental Babesia equi infections in horses and may have value in preventing the spread of this disease during exportation of possible carrier horses to non-endemic countries. Serum bile acids and serum gamma glutamyltransferase activity were measured to evaluate the effect of this treatment regime on hepatic function. Owing to the absence of any increase in these variables it was concluded that this treatment regime had no clinically detectable deleterious effect on hepatic function in healthy ponies. Urinary gamma glutamyltransferase : creatinine ratios (IU/g), serum creatinine and fractional clearance of sodium, potassium and phosphate (%) were calculated as a measure of renal function. Urinary GGT and urinary GGT : creatinine ratios were significantly elevated on Day 5 of the trial, with 2 of the trial animals also exhibiting mild azotaemia indicative of changes in renal function. The changes in urine GGT : urine creatinine ratios observed in this study also provides evidence of the value of this ratio for the early detection of renal toxicity, following exposure to nephrotoxic agents.

The therapeutic efficacy of imidocarb, artesunate, arteether, buparvaquone and arteether+buparvaquone combination was evaluated against Babesia equi of Indian origin in splenectomised donkeys with experimentally induced acute infection. Efficacies of these drugs were tested by administering each drug or drug combination to groups of donkeys (having three donkeys each group). One group of donkey was kept as untreated control for comparing the results. Parasitaemia, haematology (WBC, RBC, PCV, granulocytes and haemoglobin), biochemical parameters (SAST, SALT, alkaline phosphatase, albumin/globulin ratio) were monitored at regular intervals. Individually, arteether and buparvaquone were found to have no parasite clearing efficacy and the treated animals died within 5-6 days after showing high parasitaemia and clinical symptoms of the disease. However, artesunate treated animals were able to restrict the parasite multiplication but only during the treatment period. Animals treated with imidocarb and arteether+buparvaquone combination were able to clear the parasite from the blood circulation after 2-5 days post-treatment (PT). After 55-58 days PT, recrudescence of B. equi parasite was observed in both these groups and a mean survival period of 66 days and 69 days, respectively, was recorded in these groups. Results of haemato-biochemical parameters had shown that imidocarb had deleterious effect on the liver function while on the other hand arteether+buparvaquone combination was found to be safe. This limited study indicates that arteether+buparvaquone combination could be a better choice than imidocarb for treating B. equi infection, but further trials are required in detail.

It has been demonstrated that the attenuated organisms used in the unfrozen South African Babesia bovis and B. bigemina (redwater) vaccines are susceptible for longer periods to the residual effect of the anti-babesial drugs diminazene and imidocarb dipropionate than the virulent field strains. Reports of vaccine failures in some animals vaccinated with the frozen South African redwater vaccines after prophylactic treatment with imidocarb dipropionate have led us to reinvestigate the validity of the recommended prescribed waiting periods. Results indicated that waiting periods before administration of the frozen B. bovis and B. bigemina vaccines in animals that have been treated with diminazene at 3.5 mg/kg live weight, compare favorably with results initially obtained for the unfrozen vaccines at 4 and 8 weeks, respectively. However, the inhibitory effect of imidocarb dipropionate at 3.0 mg/kg live weight on the infectivity of both frozen B. bovis and B. bigemina vaccines is longer than previously anticipated and necessitated changing the minimum waiting periods before administration of these vaccines from 8 to 12 weeks and 16 to 24 weeks, respectively.

The objective of this study was to determine the pharmacokinetic behaviour of imidocarb in horses following a single i.m. injection at the dose commonly administered to treat Babesia caballi infections or to prevent babesiosis. Eight horses were injected i.m. with a single dose of 2.4 mg imidocarb dipropionate/kg bwt and blood, faecal, urine and milk samples were collected. For imidocarb determination, a high-performance liquid chromatographic method (HPLC) was used after weak cation-exchange solid phase, or liquid-liquid, extraction procedures. Twelve hours after treatment, no detectable plasma concentrations were recorded in any of the treated animals. The distribution and elimination patterns of the drug suggested that it is quickly sequestrated in some storage tissues and remains in the body for a long time. Its prolonged presence in the body may confer a reservoir effect to imidocarb in some tissues, therefore making it undetectable in the plasma of animals but sufficient to produce its described therapeutic and prophylactic activities.

Bobcats (Lynx rufus) are the reservoir hosts for Cytauxzoon felis, the causative agent of cytauxzoonosis. Cytauxzoonosis is a highly fatal tickborne blood protozoal disease of domestic and exotic cats. Treatment of clinically affected cats has generally been unrewarding. In our report, 6 of 7 cats had signs of illness and laboratory findings indicative of cytauxzoonosis and were successfully treated with 2 i.m. injections of diminazene aceturate or imidocarb dipropionate (2 mg/kg [0.9 mg/lb] of body weight, each). One cat died after the first injection of diminazene. Additional treatment with isotonic fluids i.v. and heparin s.c. were used as supportive care for dehydration and disseminated intravascular coagulation that were detected by laboratory testing between diminazene or imidocarb treatments. Atropine was effective in recovery and preventing adverse reactions associated with imidocarb treatment of 1 cat.

Treatment of pregnant mares to prevent abortions due to equine piroplasmosis is a novel idea practised empirically at some Thoroughbred studs in South Africa. This paper presents the results of an investigation to ascertain whether imidocarb dipropionate crosses the equine placenta. Three pregnant mares were injected intramuscularly with imidocarb and their foetuses were mechanically aborted at varying time intervals thereafter. Imidocarb was found in foetal blood at a level similar to that in the dam's blood, suggesting that imidocarb administered to the dam would be available for anti-parasitic activity in the foetal circulation. Uncertainty concerning the time of treatment to achieve the desired effect currently makes this a questionable exercise.

A single subcutaneous injection of imidocarb at 6 mg kg-1 gave 2 weeks protection against experimental inoculation of Babesia canis merozoites in Beagle dogs. The prophylactic effect was evaluated by daily measurements of parasitaemia, rectal temperature, haematological values and specific antibodies.

Intramuscular injections of a vitamin B preparation, imidocarb, imidocarb+lidocaine, and a preparation of salts of fatty acids produced significant increases in plasma creatine kinase activity in groups of five to six dogs. Activities peaked between 3 and 8 h, and were as high as 23 times base values with the fatty acid salts preparation. Quantification of the equivalent muscle damage gave means of 0.04, 0.25, 0.23 and 0.30 g kg-1 body weight, respectively, for each of the above preparations.

Diamidine (imidocarb, 3,3'-di-imidasolin-2-yl carbonylide dihydrochloride), a babesicidal drug, was encapsulated in liposomes to reduce the toxicity of the drug and to increase its therapeutic index. Liposomes were prepared from the mixture of egg yolk phosphatidyl choline and cholesterol (1:1 molar ratio) by a reverse-phase evaporation technique. Liposomes used in the study were of diameter 1.5-2.5 microns and contained 53 mg/ml (0.125 M) of diamidine. Animal tests were performed in three animal species. The LD50 values of the liposome-encapsulated diamidine administered intravenously and intramuscularly in inbred white mice were 52 and 6000 mg/kg, respectively. The overall decrease in acute toxicity compared to that for free drug amounted to 50-fold. At a dose of 30-80 mg/kg the loposomal diamidine was satisfactorily tolerated by sheep and horses, while free diamidine is lethal to these animals at 10 mg/kg. The liposome-encapsulated diamidine had no effect on metabolic functions of the liver. After four i.m. injections of the liposomal diamidine at a dose of 30 mg/kg we observed a 10% increase in haemoglobin content and an elevation in erythrocyte count in the blood of Babesia equi-infected horses. This indicates a therapeutic effect of the liposomal form of the drug.

A comparison of the efficacy of imidocarb dipropionate solution and tetracycline hydrochloride in the treatment of naturally occurring ehrlichiosis of dogs presented at the University of Nairobi small animal clinic was carried out. Five to 7 mg per kg imidocarb dipropionate given intramuscularly twice at an interval of 14 days was as effective as 14 daily, oral doses of 66 mg per kg tetracycline hydrochloride in alleviating the clinical signs of disease. Imidocarb eliminated the infection in 81 per cent of the cases whereas tetracyclines cleared only 25 per cent as judged by cell culture isolation. Imidocarb had the further advantage of controlling concurrent babesiosis. The majority of dogs showed some transient side-effects after administration of imidocarb, while a small proportion of dogs dosed with tetracycline reacted adversely and dosage had to be reduced or stopped.

The efficacy of a standard tetracycline, imidocarb and a new experimental long-acting tetracycline (T-200) in the treatment of anaplasmosis was examined in 5 groups of 9 nonsplenectomised, adult, 4-year-old, speyed cattle. The efficacy of T-200 was further examined using 9 splenectomised calves. One treatment of imidocarb (3.5 mg/kg) or T-200 (20 mg/kg) or 2 treatments (10 mg/kg) of a standard tetracycline were very effective in controlling the infection in the intact cattle. On inoculation of T-200 (20 mg/kg) controlled infection in 5 splenectomized calves, whereas all 4 untreated control calves died. T-200 did not sterilise either intact or splenectomised cattle.

The seasonal pattern of tick load on Bunaji cattle under traditional management in northern Nigeria was observed over 12 months to investigate the possibilities of strategic use of acaricide. Ticks were removed 2-3 times weekly by hand from 16 animals, counted and the species determined. Tick load was low in the dry season (2-5 ticks per animal per week), increased after the onset of the first scattered rains, reached a peak (40 ticks per animal per week) 1 month after the beginning of the heavy rains, and declined thereafter. The dominant tick species was Amblyomma variegatum; other species found were Boophilus spp., Rhipicephalus spp. and Hyalomma spp. The low level of tick load compared with data from literature and from crossbred (Friesian-Bunaji) cattle kept in the study area suggests high tick resistance in Bunaji cattle. A biologically feasible method of controlling ticks in indigenous cattle would be twice weekly spraying with acaricide during only 2 months of the year in the early wet season to break the pronounced peak in the tick load. However, hand spraying offers no advantage over hand removal of ticks in terms of saving labour. The main advantage of strategic spraying lies in more thorough removal of ticks and possibly prevention of dermatophilosis at a lower cost than year-round use of acaricide. Knowledge of the seasonal pattern of tick load is also valuable for planning the introduction of selected stock with higher genetic potential, but higher susceptibility to tick-borne diseases than exhibited by Bunaji cattle.

Eight dogs, given imidocarb dipropionate subcutaneously at a dose of 6 mg/kg, were challenged with a sporozoite stabilate of a French strain of Babesia canis, prepared from infected Dermacentor reticulatus ticks, 2, 3, 4 or 5 weeks after treatment. Three control dogs were similarly infected but not preventively treated. One of the controls and one of the dogs treated 5 weeks prior to challenge died of babesiosis. Prepatent and incubation periods were similar in treated and control dogs, and all dogs showed important reductions in the packed cell volume. Relapses were commonly seen after recovery from the initial reaction. Although further work is needed before a final conclusion can be drawn to whether imidocarb is suitable as a chemoprophylactic against B. canis infection, it can be used as a curative drug.

The therapeutic efficacies of imidocarb and parvaquone were tested against Babesia equi of European origin in carrier horses and for induced acute infections in splenectomized ponies. Imidocarb, at a dosage of 4 mg/kg of body weight, given IM at 72-hour intervals 4 times, was ineffective in eliminating B equi-carrier infection in 9 mature geldings. A single IM administration of 4 mg/kg was not therapeutic in acutely infected splenectomized ponies. When given at 3 different dosages and treatment schedules, parvaquone was ineffective in clearing carrier infection. Parvaquone given IM once at a dosage of 20 mg/kg was effective for acute B equi infections in splenectomized ponies; parasitemia began to decrease within 24 hours after treatment. Infections were not eliminated however, and within 4 weeks, secondary parasitemia and anemia developed. Of 4 ponies, 3 died of acute piroplasmosis.

Imidocarb was used by three different methods to control reactions in cattle induced by a Babesia blood vaccine produced in South Africa. Simultaneous administration of 0,15 mg/kg imidocarb and Babesia bovis vaccine gave satisfactory control. When the vaccine was given seven days prior to the imidocarb treatment a dose between 0,15 mg/kg and 0,6 mg/kg imidocarb was required for effective control. A combined B. bovis and Babesia bigemina vaccine given at 21 and again 61 days after a 3 mg/kg imidocarb treatment allowed the development of an adequate premunity to both these parasites.

The babesicides imidocarb and amicarbalide, which have structural similarities to the antitrypanosomatid diamidines, proved active against Trypanosoma brucei mouse infections: both cured infections when doses were administered daily for 3 days 24 h post-inoculation (curative dose imidocarb, 10 mg/kg; amicarbalide, 25 mg/kg). Mice were considered cured after survival 30 days longer than untreated infected controls, with no trypanosomes present in blood or cerebrospinal fluid smears. Both agents also cured when administered 48 and 72 h after challenge with T. brucei and prolonged the lives of animals 94 h after challenge. The results are discussed in respect to the potential of these carbanilides and their precursors, the antitumor phthalanilides, as lead compounds in chemotherapy of mammalian trypanosomiases.

Treatment of calves with 5 mg/kg Imidocarb (3,3-1-bis-(2 - imidazolin - 2 - yl)carbanilide dipropionate) given intramuscularly 14 days before and 14 days after exposure to Babesia infected Boophilus microplus larvae rendered the next generation of larvae incapable of transmitting Babesia infection. When administered to calves 14 or 28 days before tick exposure, the drug prevented the development of clinical babesiosis; the larval progeny of ticks reared on the calf which was treated 28 days before infestation were infective. Treatment of a calf 42 days before exposure to infective larvae did not prevent the development of a Babesia parasitaemia but appeared to reduce the severity of infection.

The toxic effects of imidocarb dipropionate (3,3'-bis[2-imidazolin-2-yl] carbanilide dipropionate) were studied in calves injected twice intramuscularly with 0, 5, 10 or 20 mg/kg dosages. Transient, dosage dependent signs of toxicosis consisted of excessive salivation, serous nasal discharge, diarrhoea and dyspnoea. Elevations in blood urea nitrogen concentrations and serum glutamic oxalacetic transaminase activities were related to dosage and markedly increased at the high dosage. Renal hyperaemia, hepatomegaly, pulmonary congestion and oedema, hydrothorax, hydroperitoneum, hydropericardium and mortality occurred at the 20 mg/kg dosage. Microscopic lesions observed at the high dosage included acute severe renal tubular necrosis and focal hepatocellular necrosis. Injection site reactions varied from microscopic areas of necrotising myositis at the 5 mg/kg dosage to focal grossly visible areas of necrosis, encapsulated by granulation tissue and surrounded by fascial oedema at the 20 mg/kg dosage.