Treatment of East Coast fever: a comparison of parvaquone and buparvaquone

Two trials were conducted to compare the efficacy of parvaquone and buparvaquone for the treatment of naturally acquired East Coast fever (ECF, Theileria parva infection) which, if untreated, is almost invariably fatal in European breeds of cattle. In the first trial 28 naive cattle were exposed in a paddock infested with ticks carrying a virulent form of the disease. Twelve were treated with each drug when they developed clinical ECF. All 24 cattle were cured. In the second study, 100 cases of ECF occurring naturally on farms in Kenya were treated, 50 with each drug. Parvaquone cured 44 (88%) buparvaquone cured 45 (90%). Intercurrent infections, predominantly anaplasmosis and bacterial pneumonia or scour, were treated specifically. It is concluded that parvaquone and buparvaquone are similarly effective in curing ECF and cure rates are maximised by accurate diagnosis and prompt treatment of both ECF and intercurrent infections.     

Treatment of experimentally induced cytauxzoonosis in cats with parvaquone and buparvaquone

The efficacy of parvaquone (Clexon) and buparvaquone (Butalex) in treating experimentally induced feline cytauxzoonosis was explored. Domestic cats were inoculated subcutaneously with blood from a cat infected with Cytauxzoon felis and treated daily with either 20 or 30 mg kg-1 parvaquone, or 5 or 10 mg kg-1 buparvaquone, beginning on either the first day parasites were detected in peripheral blood, or 2 days after the onset of parasitemia. Fifteen cats were treated and all but one died due to the infection. Unexpectedly, one of two non-treated, infected control cats survived. Although parvaquone and buparvaquone are the treatments of choice for a related hemoprotozoan parasite causing theileriosis in African cattle, wer concluded that at the dosages and regimes tested, these drugs are not effective treatments for feline cytauxzoonosis. Blood from the two surviving cats was inoculated into naive cats and in these animals clinical disease or death were not observed. The latter two naive recipient cats were then inoculated with a lethal dose of viable, frozen C. felis and both died, thereby indicating that blood from surviving cats did not induce an infectious state that resulted in immunity. The two cats that survived the acute infection were subsequently challenged with a lethal inoculum of C. felis; they showed no clinical signs of cytauxzoonosis and were obviously immune to reinfection.     

Chemotherapeutic value of parvaquone and buparvaquone against Theileria annulata infection of cattle

Parvaquone (BW993C), 2-cyclohexyl-3-hydroxy-1,4-naphthoquinone, and buparvaquone (BW720C) 2-(trans-4-t-butylcyclohexyl-methyl)-3-hydroxy-1,4-naphthoquinone, were evaluated to determine their therapeutic efficacy in the treatment of theileriosis caused by Theileria annulata infection in cattle in Iran. One hundred and fifty-nine pure and crossbred Bos taurus cattle, experimentally or naturally infected with T annulata, were treated. Parvaquone was injected into 86 animals with up to three doses of 20 mg kg-1 or 10 mg kg-1 at intervals of 48 hours between doses. Buparvaquone was injected into 73 animals. Up to three doses of 2.5 mg kg-1 were injected with an interval of 48 hours between doses. The recovery rate of animals treated with parvaquone was 60.7 per cent and with buparvaquone it was 88.7 per cent. No significant side effects of relapse of disease were observed following the use of either compound. It is concluded that buparvaquone at a dose of 2.5 mg kg-1 has a satisfactory therapeutic index and is a more effective treatment of T annulata infection than parvaquone. The prophylactic use of schizont tissue culture vaccine and chemotherapy with buparvaquone could be the most promising means of controlling theileriosis in Iran.     

Evaluations of buparvaquone as a treatment for equine babesiosis (Babesia equi)

We evaluated the efficacy of buparvaquone in eliminating Babesia equi of European origin in carrier horses and in experimentally infected splenectomized ponies. When administered at the rate of 2.5 mg/kg of body weight, IM, 4 times at 96-hour intervals, buparvaquone was effective in eliminating B equi carrier infection in 1 horse. Such results could not be repeated at the same dosage or at 3.5 or 5 mg/kg, IM. Buparvaquone given at the rate of 4 to 6 mg/kg IV and/or IM was therapeutically effective in 4 of 5 acute B equi infections in splenectomized ponies. The treated ponies became carriers.     

Activity of 10 naphthoquinones, including parvaquone (993C) and menoctone, in cattle artificially infected with Theileria parva

Ten naphthoquinones, including parvaquone (993C) (Clexon; Wellcome) and menoctone, were tested for activity in cattle artificially infected with Theileria parva, the causative organism of East Coast fever (ECF). Parvaquone cured all 14 cattle treated with a single dose of 20 mg/kg intramuscularly and all five treated twice with 10 mg/kg intramuscularly. Menoctone cured seven of 10 cattle treated with a single dose of 5 mg/kg intramuscularly. Of 25 untreated control cattle, 22 died of ECF. None of the remaining eight naphthoquinones was as active as parvaquone. Three esters of active naphthoquinones, designed as 'prodrugs' of their parent compounds, showed little or no activity in infected cattle despite being highly active in vitro against T parva. These results were instrumental in the selection of parvaquone for development as the first specifically active remedy for ECF.     

Chemoimmunoprophylaxis against bovine tropical theileriosis in young calves: a comparison between buparvaquone and long-acting oxytetracycline

Eighteen seven to 21-day-old crossbred (Bos taurus cross Bos indicus) calves were allocated to four groups (A to D). Groups A and B each consisted of six calves and groups C and D three calves each. Each calf in groups A, B and C was inoculated with ground-up tick supernate (GUTS) equivalent to two infected acini prepared from Theileria annulata-infected Hyalomma anatolicum anatolicum. Each calf in group A was also given a single intramuscular injection of buparvaquone, 2.5 mg kg-1 bodyweight simultaneously with GUTS, whereas each calf in group B was given a single intramuscular injection of long-acting oxytetracycline, 20 mg kg-1 bodyweight following inoculation of GUTS. In calves of group A clinicopathological reactions were negligible, whereas in calves of group B mild to severe reactions were observed resulting in the death of three of the six calves. All the calves of group C (infected, untreated controls) died of acute theileriosis. All the surviving calves of groups A and B withstood a lethal homologous challenge given on day 30 after immunisation, indicating no difference in the immune status of the surviving calves of the two groups. Group D, challenge control, all calves died of theileriosis within 18 days of challenge.     

Treatment of theileriosis with parvaquone in Zambia

Parvaquone was used to treat 126 cattle with theileriosis. Theileria species schizonts were present in their lymph node biopsy smears and the majority of the animals had clinical signs of theileriosis. One hundred and fifteen treated and one untreated cattle survived the infection while 11 treated and 12 untreated animals died of the disease. Despite serological evidence of a parasite challenge during the subsequent rainy season, recovered cattle did not develop clinical signs of theileriosis but untreated cattle in the area continued to die from the disease. An intermittent low piroplasm parasitaemia (less than 1 per cent) was observed in recovered cattle for up to 14 months after detailed monitoring of cattle in the trial; this could be evidence for a carrier status for the Theileria species or strains involved.     

Imidocarb and parvaquone in the treatment of piroplasmosis (Babesia equi) in equids

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.     

Treatment of Theileria annulata infection in calves with parvaquone

Fifteen calves were infected by the injection of stabilate of a suspension of Hyalomma anatolicum anatolicum ticks infected with the Ankara strain of Theileria annulata. Three were kept untreated, as controls, and they all died of theileriosis. Three groups of four calves were treated intramuscularly with parvaquone (Clexon; Wellcome) when early signs of theileriosis were clinically apparent. One group received 20 mg (kg bodyweight)-1 of parvaquone 10 days after infection. Two of these calves were clinically cured and two died of theileriosis. The remaining two groups of four calves received two doses of parvaquone, each of 10 mg (kg bodyweight)-1, either on days 10 and 11 or days 10 and 12. Three calves in each group were clinically cured while one in each group died of theileriosis. Total parasitological cure was not achieved in any of the calves. No symptoms of toxicity due to parvaquone treatment were observed.     

Actions of BW540C in an equine model of acute inflammation: a preliminary study

An equine model of acute non-immune inflammation has been developed to facilitate studies of the inflammatory process and the actions of novel anti-inflammatory drugs. Five polyester sponge strips soaked in sterile 2% carrageenin solution were placed in subcutaneous pouches prepared under local anaesthesia in the necks of conscious ponies. Serial removal of the strips and harvesting of the exudate enabled studies to be made of the cellular, biochemical and mediator aspects of the localised, acute inflammation, and the heat generated by the lesion was monitored by infra-red thermometry. Maximal concentrations of the eicosanoids 6-keto-prostaglandin F1 alpha, thromboxane B2 and leukotriene B4 occurred at 9 h, whereas leukocyte numbers, lactate dehydrogenase (LDH) and total protein concentrations were greatest at 24 h. Lesional skin temperature was increased by approximately 4 degrees C throughout the 24 h period. The novel anti-inflammatory agent BW540C, administered orally at a dose-rate of 20 mg/kg, did not affect leukocyte infiltration or the concentrations of protein, LDH and eicosanoids in exudate but serum thromboxane B2 levels were reduced. Skin temperature rises were greater in drug-treated animals. It is concluded that higher doses of BW540C will be required for a clinically useful anti-inflammatory action in horses.     

Clinical efficacy and plasma concentrations of two formulations of buparvaquone in cattle infected with East Coast fever (Theileria parva infection)

East Coast fever, caused by the protozoan parasite Theileria parva, kills about 600,000 cattle annually in Africa. The hydroxynaphthoquinone compound buparvaquone (BPQ) is curative. Sixteen calves were infected with T. parva. On manifestation of disease symptoms, eight were injected with the original (pioneer) BPQ product and eight with a test product containing BPQ. All 16 calves were cured by one injection of 2.5 mg BPQ/kg bodyweight. The concentration of BPQ in blood plasma was monitored by HPLC. The mean observed C(max) of BPQ was 0.229 and 0.253 microg/mL of plasma, the mean observed time to reach this concentration (T(max)) was 2.62 and 2.12 h and the AUC (area under curve) was 4.785 and 4.156 microg h/mL, respectively, for the pioneer and test product. Considerable variations occurred in the plasma concentration of BPQ within each group. They showed no relationship with either clinical or parasitological parameters following treatment.     

Treatment of experimentally induced Theileria annulata infection in cross-bred calves with buparvaquone

Twenty cross-bred (Bos taurus X Bos indicus) calves, 7-21 days old, were infected by a ground-up tick supernate of Hyalomma anatolicum anatolicum infected with the Hisar isolate of Theileria annulata. Six calves acted as untreated controls and they all died of theileriosis within 17 days of infection. The remaining 14 calves were divided into Group A and B, each consisting of seven calves. All the calves of Groups A and B were treated intramuscularly with buparvaquone (BW 720C) on Day 11 post-infection, when clinical signs of theileriosis were apparent. Each calf received 2.5 mg BW 720 C kg-1 body weight as a single injection. In addition, each calf of Group B was given proprietary haematinics by intramuscular injection, daily for 12 days. In Group A, two calves died of cerebral theileriosis and five were clinically cured. However, four of these five calves later died of anaemia. In Group B, all the calves were clinically cured and none died during the observation period of 1 month. The parasitaemia declined to less than 1% within a fortnight of treatment. The initial declines in haemoglobin concentration and packed cell volume were halted and preinfection values were soon restored. No toxic signs attributable to treatment with buparvaquone were observed.     

Actions of BW540C in an equine model of acute inflammation: A preliminary study

Summary

An equine model of acute non‐immune inflammation has been developed to facilitate studies of the inflammatory process and the actions of novel anti‐inflammatory drugs. Five polyester sponge strips soaked in sterile 2% carrageenin solution were placed in subcutaneous pouches prepared under local anaesthesia in the necks of conscious ponies. Serial removal of the strips and harvesting of the exudate enabled studies to be made of the cellular, biochemical and mediator aspects of the localised, acute inflammation, and the heat generated by the lesion was monitored by infra‐red thermometry. Maximal concentrations of the eicosanoids 6‐keto‐prostaglandin F_1α, thromboxane B₂ and leukotriene B, occurred at 9 h, whereas leukocyte numbers, lactate dehydrogenase (LDH) and total protein concentrations were greatest at 24 h. Lesional skin temperature was increased by approximately 4°C throughout the 24 h period. The novel anti‐inflammatory agent BW540C, administered orally at a dose‐rate of 20 mg/kg, did not affect leukocyte infiltration or the concentrations of protein, LDH and eicosanoids in exudate but serum thromboxane B₂ levels were reduced. Skin temperature rises were greater in drug‐treated animals.

It is concluded that higher doses of BW540C will be required for a clinically useful anti‐inflammatory action in horses.     

Measurement of feline lipase activity using a dry-chemistry assay with a triolein substrate and comparison with pancreas-specific lipase (Spec fPLTM)

Pancreatic lipase immunoreactivity (Spec fPL) is currently considered to be the most accurate blood test for the diagnosis of feline pancreatitis. In this study, we measured lipase activity in cats using a newer catalytic lipase assay of dry-chemistry system (FDC-v-LIP) to determine the reference range and compared the results with those for Spec fPL. Based on the results of healthy cats, the reference range of FDC-v-LIP was determined to be less than 30 U/l. FDC-v-lip did not show a strong correlation with Spec fPL in cats with various diseases, which resulted in the low sensitivity and positive predictive value. However, the relatively high (>90%) specificity and negative predictive value indicated that FDC-v-LIP could be a useful patient-side screening test for the exclusion of feline pancreatitis.     

Comparative studies of the efficacy of parvaquone and parvaquone-plus-frusemide in the treatment of Theileria parva infection (East Coast fever) in cattle

Comparative studies of the efficacy of parvaquone (Parvexon) and parvaquone-plus-frusemide (Fruvexon) Bimeda Chemicals, Ireland, were done on 60 naturally infected cases of East Coast fever (ECF; Theileria parva infection in cattle). Small-scale dairy farmers in the peri-urban of Dar Es Salaam city reported ECF-suspected cases from March to mid-October 2001 and were treated with the two drugs alternately, as were diagnosed positive for ECF. Four sub-groups of 15 cattle each (early stage, 15; advanced stage, 15) were treated with parvaquone and parvaquone-plus-frusemide. Twenty-eight out of 30 (93.3%) cattle treated with parvaquone-plus-frusemide were cured, so do 24 out of 30 (80.0%) cattle treated with parvaquone without frusemide. Early diagnosis and prompt management of pulmonary signs, which accounted for 30.0% of total ECF cases is advised in order to improve cure rates. Unlike parvaquone without frusemide (Parvexon), parvaquone-plus-frusemide (Fruvexon) proved useful in the management of pulmonary signs, hence, a drug of choice in the treatment of ECF cases that are accompanied by or are likely to manifest pulmonary signs.     

Chemotherapy of East Coast fever: parvaquone treatment of Theileria parva parva at intervals after infection

Groups of seven cattle were infected with Theileria parva stabilate and treated with parvaquone (20 mg kg-1 bodyweight) zero, four, eight, 12, 14 or 16 days after infection. Very early treatments resulted in a rapid recovery or no detectable parasitosis and some cattle were subsequently susceptible to homologous challenge. Treatments applied before extensive lymphoid or other organ damage had developed were successful and some cattle treated in advanced disease also recovered. Clinical pathological indications of liver or kidney damage were recorded very late in the disease suggesting that prompt diagnosis and treatment are more important than supportive therapy for survival. Treatment on day 8 after infection allowed the appearance of macroschizonts and a transient pancytopenia but no other disease signs. This group was solidly immune to challenge and this timing and treatment could be recommended for use in an infection and treatment method of immunisation.     

Immunohistochemical detection of chlamydiae in formalin-fixed tissue sections: comparison of a monoclonal antibody with yolk derived antibodies (IgY)

Immunohistological detection of chlamydiae in formalin-fixed and paraffin-embedded sections of various organs from several species is described. In a retrospective study, two antisera, a commercially available monoclonal murine antibody (IgMur) and vitelline immunoglobulins (IgY), extracted from the egg yolk of immunized hens, were compared and tested for their applicability under routine condition. Both antisera were applied to tissues from which chlamydiae had been isolated or in which the presence of chlamydiae had been suspected in specially stained sections. Antigen labelling was optimal with the monoclonal antibody. Vitelline immunoglobulins produced some unspecific reactions, especially in lung tissue sections. Because of the antigenic relationship between the vitelline antibodies and tissues of birds, IgY are not suitable for the detection of psittacosis on avian substrates, when using an indirect immunological method. Staining in other tissues e.g. intestine or placenta was of equal quality as that attained with monoclonal antibodies. Depending on the advantages and disadvantages in every individual case, one of the two antibodies may be chosen for further studies. Vitelline antibodies should be preferred with respect to animal welfare.