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.     

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.     

Antitheilerial activity of BW720C (buparvaquone): a comparison with parvaquone

A series of hydroxynaphthoquinones, all derivatives of the antitheilerial hydroxynaphthoquinone parvaquone (993C, Clexon; Wellcome) was tested for antitheilerial activity against Theileria parva (Muguga) in vitro. BW720C (buparvaquone) was 20 times more active than parvaquone. When tested in vivo BW720C cured all 13 cattle infected with T parva and all six infected with T annulata treated at a dose rate of 2.5 mg (kg bodyweight)-1 while parvaquone at 20 mg kg-1 cured nine of 10 cattle. All 16 untreated control cattle died of theileriosis.     

Efficacy of parvaquone and long-acting oxytetracycline in Theileria annulata infection

Therapeutic and prophylactic efficacies of parvaquone and long-acting oxytetracycline were tested against Theileria annulata infection, induced by injecting a suspension of infected ground tick tissues (GUTS) into groups of 4 or 5 calves. This infection killed two of four control calves, while all the animals given a single intramuscular dose of 20 mg kg-1 parvaquone or long-acting oxytetracycline on the day of infection underwent mild reactions and recovered. Two separate doses of parvaquone of 10 mg kg-1 administered on the first and second days of fever protected four out of five calves. All the recovered animals from both treated and control groups resisted a homologous challenge with GUTS on Day 45 post-infection which killed three out of four susceptible unimmunized control calves.     

Immunization of neonatal bovines against Theileria annulata by an infection and treatment method

Sixty three cross-bred (Bos taurus X Bos indicus) 4-5-day-old calves were divided into 16 groups (A-P). Each calf in Groups A and B was given ground-up-tick supernate prepared from Theileria annulata-infected or non-infected Hyalomma anatolicum anatolicum (GUTS) equivalent to 5 ticks (50 infected acini). Groups D and E received infected GUTS equivalent to 2 ticks (20 infected acini) and Groups G and H were given infected GUTS equivalent to 1 tick (10 infected acini). Each calf in Groups J, K and L received infected GUTS equivalent to 5 infected acini (0.035 tick), and Group O was inoculated with non-infected GUTS equivalent to 5 ticks. Each calf in Groups A, D, G, J, K and O was also given a single intramuscular injection of long acting oxytetracycline, 20 mg kg-1 body weight just after inoculation of GUTS. Severe reactions resulted in the death of five of eight, three of eight, five of six, one of five and one of five calves in Groups A, D, G, J and K respectively and all of the calves in Groups B, E, H, and L. The surviving calves of Groups A, D, G, J, K and O were challenged on Day 45 post-immunization along with freshly introduced susceptible control calves of Groups C, F, I, M, N and P. All the calves of Groups A, G, J and K withstood the challenge dose; in Group D four of five and in Groups C, F, I, M, N, O, and P all the calves died of theileriosis. It is concluded that though the infection and treatment method of immunization may be used for neonatal bovines, the dose of immunogen should be based on actual counts of infected salivary acini of ticks instead of the number of ticks.     

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.     

Infectivity of ground-up tick supernates prepared from Theilerai annulata infected Hyalomma anatolicum anatolicum.

Groups of Theileria annulata infected Hyalomma anatolicum anatolicum adults prefed on a calf for 1 to 6 days were separately ground in tissue culture medium-199, supplemented with bovine albumin powder, Fraction-V. Supernatant fluid was collected, made up with additional medium, so that each millilitre represented material from 25 ticks, and was injected subcutaneously into groups of cross-bred male calves. The results indicated that ground-up tick supernate (GUTS) prepared from unfed ticks was not infective, whereas that prepared from 1 to 6 days prefed ticks was infective. GUTS prepared from 3 days prefed ticks appeared to contain highest infectivity and 1 ml of it induced fatal theileriosis.     

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.     

Comparison of the efficacy of dermal formulations of ivermectin and levamisole for the treatment and prevention of Dictyocaulus viviparus infection in cattle

Four groups of six parasite-naive calves were infected at seven day intervals with three doses of infective larvae of Dictyocaulus viviparus. Twenty-one days after the first dose three of the groups were treated either with an injectable formulation of ivermectin at a dose rate of 200 micrograms/kg bodyweight, or with pour-on preparations of levamisole at 10 mg/kg or ivermectin at 500 micrograms/kg. On day 28 two calves from each group were slaughtered and their burdens of lungworms counted. On day 35 the remaining calves were reinfected with D viviparus infective larvae at a rate of 80 L3/kg. The levamisole preparation was 94.6 per cent effective and both ivermectin preparations were 100 per cent effective against the initial infections. The ivermectin-treated calves were protected from the reinfection which subsequently became patent in the levamisole-treated and control calves.     

Long-acting oxytetracycline prophylaxis to protect susceptible cattle introduced into an area of Kenya with endemic East Coast fever

Two field trials were carried out in successive years at the Ngong Veterinary Farm, Kenya, in which young cattle, previously unexposed to tick-borne diseases, were introduced into an area with endemic East Coast fever while protected by a series of injections of a long-acting oxytetracycline. In 1984, 12 animals which received injections of 20 mg/kg of the drug on days 0, 7, 14 and 21 after introduction, together with 12 untreated controls, were exposed without tick control until clinical disease occurred. All 12 control animals contracted East Coast fever by day 24 and 10 of them died. Five of the 12 injected animals had detectable parasites, and one of them required antitheilerial treatment. In 1985, four groups of 10 calves were introduced. One group received injections of 20 mg/kg of oxytetracycline on days 7 and 14, one group received injections on days 7, 14 and 21, and a third group received injections on days 7, 12 and 17; the fourth group (controls) had no treatment until clinical disease occurred. By day 35 all the control animals had contracted the disease and one had died despite antitheilerial treatment. Three injections of oxytetracycline suppressed the disease so that mild reactions occurred in only four animals in each group, but two injections failed to prevent severe reactions in two animals and mild reactions in four others.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of ivermectin and levamisole against immature Dictyocaulus viviparus in cattle

Eighteen calves aged approximately three months were each infected with Dictyocaulus viviparus larvae at a rate of 30/kg bodyweight. Seven days later they were randomly allocated to three groups of six animals. Calves of group 1 were controls. Calves of group 2 were given levamisole at a dose rate of 10 mg/kg and calves of group 3 were given ivermectin at a dose rate of 200 micrograms/kg. The anthelmintic activity of these two drugs was compared using clinical, functional, parasitological and pathological parameters. The results showed that the efficacy of ivermectin, given at a therapeutic dose, against immature D viviparus was higher than that of levamisole, given at double the recommended dose.     

Efficacy of long-acting oxytetracycline for the prevention of tick-borne fever in calves

Twenty-six calves which had not previously grazed tick-infested pasture were divided into two equal groups. On May 26, 1988 (day 0) they were turned out into a field of rough grazing where cases of redwater fever had occurred the previous spring. Seven, 14, 21 and 28 days after the start of the trial the animals in one group each received an intramuscular injection of 20 mg/kg bodyweight of long-acting oxytetracycline. During the 60 days of the trial the animals received a severe tick-borne fever challenge, in some cases combined with a redwater fever challenge. An unforeseen complicating factor was the presence of animals persistently infected with bovine viral diarrhoea virus, present in almost equal numbers in both groups. At the end of the trial the treated group weighed on average 16 kg more than the control group, a difference which was attributed to the suppression of tick-borne fever by oxytetracycline.     

Immunization of cattle with nymphal Hyalomma anatolicum anatolicum extracts: effects on tick biology

Antigens derived from partially engorged nymphs of Hyalomma anatolicum anatolicum were used in immunizing crossbred (Bos indicus×Bos taurus) cattle against larval, nymphal and adult H. a. anatolicum and H. dromedarii. The cattle were either infected with Theileria annulata at low parasitaemia or were uninfected. Whole nymphal extract (WNE), nymphal membrane antigens (NMA) and nymphal soluble antigens (NSA) were used for immunization. The group immunized with WNE showed significant and better rejection of H. a. anatolicum ticks as compared to calves immunized with either NMA or NSA. The moulting rates of both engorged larvae and nymphs remained unaffected. Nymphs which engorged on the immunized calves were fully susceptible to infection by T. annulata as indicated by the intensity and abundance of Theileria infections in the resulting adult ticks from immunized and unimmunized Theileria infected cattle. These ticks also transmitted fatal theileriosis to susceptible calves.     

Vaccine potential of recombinant antigens of Theileria annulata and Hyalomma anatolicum anatolicum against vector and parasite

In an attempt to develop vaccine against Hyalomma anatolicum anatolicum and Theileria annulata, three antigens were expressed in prokaryotic expression system and protective potentiality of the antigens was evaluated in cross bred calves. Two groups (grs. 1 and 4) of male cross-bred (Bos indicus × Bos taurus) calves were immunized with rHaa86, a Bm86 ortholog of H. a. anatolicum, while one group of calves (gr. 2) were immunized with cocktails of two antigens viz., surface antigens of T. annulata (rSPAG1, rTaSP). One group each was kept as negative controls (grs. 3 and 5). The animals of groups 1, 2 and 3 were challenged with T. annulata infected H. a. anatolicum adults while the animals of groups 1, 3, 4 and 5 were challenged with uninfected adult ticks. A significantly high (p<0.05) antibody responses to all the three antigens were detected in immunized calves, but the immune response was comparatively higher with rHaa86 followed by rTaSP and rSPAG1. Upon challenge with T. annulata infected ticks, animals of all groups showed symptoms of the disease but there was 50% survival of calves of group 1 while all non immunized control calves (group 3) and rSPAG1+rTaSP immunized calves died. The rHaa86 antigen was found efficacious to protect calves against more than 71.4-75.5% of the challenge infestation. The experiment has given a significant clue towards the development of rHaa86 based vaccine against both H. a. anatolicum and T. annulata.     

Evaluation of infection and treatment methods in immunization of improved cattle against theileriosis in an endemic area of Kenya

Five experiments were carried out to determine the efficacy of immunization against theileriosis in an endemic area of Kenya using artificial infection with a mixture of stabilates of Theileria parva stock or natural infection and treatment with parvaquone or several formulations of oxytetracyclines. For the first four experiments, introduced, susceptible Sahiwal/Friesian crosses were used and in the fifth, calves of Boran/Maasai zebu crosses born on the site. Cattle were infected either artificially with sporozoite stabilates of local isolates of T. parva parva derived from cattle and T. parva lawrencei derived from African buffalo or exposed to natural tick challenge on the ranch mostly derived from buffalo. The cattle were then given various treatment regimens using either parvaquone or long- and short-acting formulations of oxytetracycline. Treatment of natural infections, although it can be effective, was not considered a practical method on a large scale because of the need for intensive monitoring in the case of parvaquone treatment and the possibility of cattle not becoming infected in the case of prolonged application of long-acting formulations of oxytetracycline. Both methods were relatively expensive. Artificial infection treatment proved more practical and methods were developed where the monitoring of cattle was not required during the immunization procedure. Out of a total of 16 drug regimens investigated, one (consisting of two treatments of a short-acting formulation of oxytetracycline at 10 mg kg-1 body weight on Days 0 and 3 or 4 after infection) was found to be the most efficacious and the cheapest, and has now been used on a routine basis. This method can be used successfully on calves greater than 1 month of age.     

Natural infection rates and transmission of Theileria annulata by Hyalomma anatolicum anatolicum ticks in the Sudan

Hyalomma anatolicum anatolicum nymphs were collected from two localities in the Sudan: Eddamer in Northern Sudan and Wad-Medani in Central Sudan. They were allowed to moult to adult ticks, which were assessed for Theileria infection in their salivary glands using Feulgen stain. At Eddamer, 49.6% of 123 ticks examined were infected with Theileria and the mean intensity of infection was 1.3 (i.e. the number of infected acini/number of infected ticks). At Wad-Medani, 8.6% of 162 ticks were infected and the mean intensity of infection was 7.9. The prevalence of infection was higher in female than in male ticks at both localities. When adult H. a. anatolicum were applied onto two susceptible calves, both animals developed the severe form of theileriosis.     

The effect of dose and line on immunisation of cattle with lymphoblastoid cells infected with Theileria annulata

Thirty-one Friesian calves in Morocco susceptible to tropical theileriosis were protected against a lethal sporozoite challenge by prior infection with lymphoblastoid cell lines infected and transformed in vitro by a Moroccan stock of Theileria annulata. The challenge infection of cryopreserved sporozoites killed all four susceptible control calves within 20 days. Four schizont-infected cell cultures at Passage 3 were inoculated at four different doses, 10(8), 10(6), 10(4) and 10(2), into pairs of calves. The recipient animals showed great variation in severity of disease symptoms, which did not show a linear correlation with the cell dose inoculated. The most severe disease symptoms were recorded, prior to challenge, in the 10(2) cell dose recipients; one animal died of acute theileriosis and another had to be treated. One of the four cell lines used was more virulent than the other three. Two years after the completion of this experiment, immunised animals have shown normal productivity traits.     

Efficacy of oxfendazole against inhibited larvae of Ostertagia ostertagi in naturally infected calves in the southern USA

Forty yearling calves were assigned to four equal groups; three of the groups were treated with oxfendazole at dose rates of 6.75 mg/kg, 4.50 mg/kg, or 2.25 mg/kg bodyweight while the fourth group served as an untreated control. The calves were native to north-east Mississippi, USA, and harboured natural infections of gastrointestinal nematodes. The study was conducted during July when inhibited early fourth-stage larvae may be found in large numbers after their acquisition in the spring. The calves were maintained in separate groups on concrete-floored pens for 17 days before the intraruminal administration of oxfendazole. Seven days after treatment, the calves were slaughtered and the gastrointestinal parasites counted. At all the dose rates examined oxfendazole exhibited an efficacy of at least 99.4 per cent against adults of Haemonchus placei, Trichostrongylus axei, Bunostomum phlebotomum, Cooperia species, T colubriformis, Oesophagostomum radiatum, and Trichuris ovis. The efficacy against adult Ostertagia ostertagi was at least 99.4 per cent at dose rates of 6.75 and 4.50 mg/kg bodyweight, but decreased to 93.7 per cent at 2.25 mg/kg. The efficacy of oxfendazole against inhibited larvae of O ostertagi decreased with dose rate from 78.8 per cent at 6.75 mg/kg, to 58.9 per cent at 4.50 mg/kg and 20.3 per cent at 2.25 mg/kg bodyweight.     

A comparison of the clinical field efficacy and safety of florfenicol and tilmicosin for the treatment of undifferentiated bovine respiratory disease of cattle in western Canada.

We compared the field efficacy of a new antibiotic, florfenicol, with tilmicosin in the treatment of naturally occurring undifferentiated bovine respiratory disease. Beef calves with rectal temperatures greater than 40.5 degrees C and signs compatible with undifferentiated bovine respiratory disease were entered into the trial. Calves were randomly assigned to receive either florfenicol (20 mg/kg bodyweight intramuscularly; 2 injections 48 h apart) or tilmicosin (10 mg/kg bodyweight subcutaneously; 1 injection). Clinical measures of efficacy included mortality, rectal temperature, illness index score, assessment of treatment success or failure, and the number of relapses or reinfections. Performance was assessed based on weight gains from day 0 to day 90. Two hundred and twenty calves entered the trial; 112 received florfenicol and 108 received tilmicosin. Seventeen deaths occurred between day 0 and day 90, but only 10 during the 28-day trial period. Seven calves receiving tilmicosin died, compared with 3 receiving florfenicol (P = 0.20). Of the 220 initial treatments, 45 (20%) were categorized as treatment failures; 27 in the tilmicosin group and 18 in the florfenicol group (P = 0.10). The number of calves experiencing a 2nd relapse was significantly different, with 17 of 30 (57%) calves on tilmicosin compared with 7 of 26 (27%) calves on florfenicol relapsing at least twice (P = 0.02). Average daily gains over 90 days were 1.55 kg/day for florfenicol-treated calves and 1.51 kg/day for tilmicosin-treated calves. No significant adverse reactions were noticed with either drug. Results indicate that florfenicol and tilmicosin are comparable in the treatment of undifferentiated bovine respiratory disease in western Canada.     

Eradication of some infectious pig diseases by perinatal tiamulin treatment and early weaning

From 10 days before the expected date of farrowing onwards, 97 sows infected by Mycoplasma hyopneumoniae and Treponema hyodysenteriae were given tiamulin daily at a dosage of 20 mg/kg bodyweight via the feed. Three days before farrowing the sows were washed with a disinfectant and transferred to an isolated farrowing house. The sucking piglets remained with their dams for five days, during which time the sows continued to receive the tiamulin-containing feed. The sucking piglets also received tiamulin daily at a dosage of 30 mg/kg bodyweight. At six days old the weaker piglets of the litter were returned to the original herd, together with their dams. A total of 574 piglets of about 1.5 kg bodyweight each were transferred to an isolated and previously disinfected pig farm and reared there. A total of 13.8 per cent of these pigs died by 50 days old. On the isolated farm, 10.9 per cent of the 829 second generation piglets born to the 101 first generation sows, died up to the age of 50 days. On the isolated farm about 2000 pigs were subjected to repeated clinical, pathological and laboratory examinations for M hyopneumoniae, T hyodysenteriae, Aujeszky's disease virus and Leptospira species during the three year period of study. No evidence of infection with any of these agents was found in the 2000 pigs of the isolation herd, although the original sow herd had been latently infected by these pathogens. No maternally derived antibodies against these pathogens were detectable in sera of three-day-old sucking piglets of the second and third generations.