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.     

Evaluation of buparvaquone (BUTA-Kel KELA, Belgium) as a treatment of East Coast fever in cattle, in the peri-urban of Dar Es Salaam city, Tanzania

Evaluation trials of the efficacy of buparvaquone (BUTA-kel KELA Laboratoria, N.V. Belgium), as a treatment of field cases of Theileria parva infection (East Coast fever - ECF) were carried out on 63 cattle in the peri-urban of Dar Es Salaam city, Tanzania, during the period November 2004 to August 2005. Thirty-two cattle (56%) received single-dose treatment (2.5 mg buparvaquone per kg body weight), while two and three-dose treatment with interval(s) of 48 h was given to 33% and 11% of total treated cattle, respectively; 38 cattle (60.3%) were treated at an early stage of the disease, while 25 cattle (39.7%) were treated at an advanced stage of the disease. The rectal body temperature of 90.5% of buparvaquone-treated cattle dropped to normal values (37.5-39.5 degrees C) by day 7 of treatment, and by day 15 of treatment 96.8% of treated cattle showed normal values. Pulmonary signs were observed in 8/68 (11.8%) of total ECF diagnosed cattle and were successfully treated, albeit with parvaquone plus frusemide (Fruvexon); were not included in final evaluation of the efficacy of BUTA-kel. The present evaluation trials record a recovery rate of 95.2%. Buparvaquone (BUTA-kel KELA Laboratoria, N.V. Belgium), therefore, records another efficacious and valuable alternative treatment against East Coast fever in Tanzania.     

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.     

Treatment of East Coast Fever of Cattle with a Combination of Parvaquone and Frusemide

Pulmonary oedema is a common sign of East Coast fever (ECF, Theileria parva infection) of cattle. A trial was conducted on farms in Uganda to compare a product containing both the antitheilerial compound parvaquone and the diuretic compound frusemide with one containing only parvaquone, in the treatment of ECF. The trial involved 40 clinical cases of ECF, some of them complicated by other infections, in cattle of all ages and on several farms. Confirmed cases were treated with either parvaquone+frusemide (P+F) or parvaquone alone (P). Survival after treatment with P+F was 77% compared with 71% with P. Five of the 10 fatalities were complicated cases. The cure rate for severe but uncomplicated ECF was 89% with P+F and 40% with P. Pulmonary signs were resolved within 24-48 h after treatment with P+F and clinical recovery was noticeably more rapid than with P. The antiparasitic effect of the two treatments was similar. P+F could be particularly useful when reporting, diagnosis or laboratory confirmation of ECF is delayed, because advanced cases are more likely to be encountered under these circumstances.     

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.     

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.     

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.     

Further evaluation of the use of buparvaquone in the infection and treatment method of immunizing cattle against Theileria parva derived from African buffalo (Syncerus caffer).

Three experiments were undertaken to determine the efficacy of different doses of buparvaquone in the infection and treatment immunization of cattle against Theileria parva derived from African buffalo (Syncerus caffer). Two of these experiments also compared buparvaquone with standard doses of long- and short-acting formulations of oxytetracycline. In addition, different dilutions of stabilates were used in the experiments. In the first experiment, a 10(-1.0) dilution of stabilate was used to infect groups of cattle treated with buparvaquone at doses of between 5 and 0.625 mg kg-1 body weight (bwt) on Day 0 after infection. All control cattle developed severe theileriosis and none of the treatment regimes (including those utilizing long-acting oxytetracycline) prevented the development of theileriosis. Treatment with buparvaquone at 2.5 mg kg-1 bwt or oxytetracycline gave the most satisfactory results. In the second experiment when the sporozoite dose was reduced to 10(-2.0) dilution, buparvaquone treatment at 5 and 2.5 mg kg-1 bwt and short- and long-acting formulations of oxytetracycline reduced reactions greatly. While all the oxytetracycline treated animals produced a serological response and were immune to a 50-fold higher challenge with the immunizing stabilate, several animals in the buparvaquone groups did not show a serological response and were not immune to challenge. In the third experiment, groups of cattle were infected with 10(-1.2), 10(-1.4) and 10(-1.6) dilutions of stabilate and were treated with 2.5 mg kg-1 bwt of buparvaquone. No animals developed severe theileriosis and all seroconverted. On homologous challenge, however, two out of 14 cattle showed severe reactions. It was concluded that further work on immunization using buparvaquone treatment at 2.5 mg kg-1 bwt and 10(-1.6) dilution of the stabilate would have to be carried out before such a system could be used in the field.     

The effect of buparvaquone treatment on the levels of some antioxidant vitamins, lipid peroxidation and glutathione peroxidase in cattle with theileriosis.

Plasma levels of vitamins A, E, beta carotene, both plasma and erythrocyte glutathione peroxidase (GSHPx), lipid peroxidation (LPO) and reduced glutathione (GSH) were investigated in cattle naturally infected with Theileria annulata and treated with buparvaquone. There were two groups each containing 30 cattle. Naturally infected cattle were used in the second group. Buparvaquone (2.5 mg/kg body weight) was administered to animals in the second group. Blood samples were taken from control animals, and immediately before treatment, and from animals 10 days after the injection of buparvaquone. Detection of the infected animals was carried out by blood smears. Plasma vitamins A, E, beta carotene, both plasma and erythrocyte GSHPx, LPO and GSH levels were determined. The levels of LPO in plasma and erythrocyte samples were significantly (P < 0.05, P < 0.01) higher after treatment than in either control animals or before treatment. Plasma levels of antioxidant vitamins, vitamin E and beta carotene were significantly (P < 0.05, P < 0.01) lower after treatment than in either control animals or before treatment, while the vitamin E level was found to be higher before treatment than in either the control group or animals after treatment (P < 0.05, P < 0.01). The levels of vitamin A in plasma and the activity of GSHPx and GSH in both plasma and erythrocytes in control animals after and before treatment did not differ significantly. In conclusion, we observed that there was a decreased plasma level of vitamin E and beta carotene and an increased level of LPO in cattle treated with buparvaquone. Buparvaquone might function in the treatment of Theileria annulata by forming free radicals.     

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.     

Chemotherapy of East Coast fever: parvaquone treatment of clinical disease induced by isolates of Theileria parva

Two experiments were carried out in which parvaquone was used to treat experimentally-induced acute clinical East Coast fever infections. In the first experiment, infections with Theileria parva parva (Kiambu 5) were induced by applying infected Rhipicephalus appendiculatus ticks or by inoculation of triturated infected-tick stabilate. The character of the disease was similar with both methods of infection and following a single treatment with parvaquone at 20 mg kg-1, 5 of 7 cattle in each group recovered. All untreated control cattle died. In the second experiment, 5 stabilate isolates from different locations within East Africa, and representative of the challenge likely to be met in the field, were used. Treatment was administered in 2 X 10 mg kg-1 doses 48 h apart. The isolates used were T. p. parva (Mbita), T. p. parva (Pugu), T. p. parva (Entebbe), T. p. lawrencei (Mara) and T. p. lawrencei/(Manyara); following treatment 3/7, 6/6, 6/7, 5/7 and 6/7 animals recovered, respectively. All untreated control cattle died. There was evidence of a difference in susceptibility of isolates to treatment, and some animals showed prolonged disease episodes. The nature of the response to treatment and the problems in treating a lympho-destructive disease are discussed.     

Elimination ofTheileria buffeli infections from cattle by concurrent treatment with buparvaquone and primaquine phosphate

Attempts (some successful) were made to eliminate Theileria buffeli infections from 23 naturally or experimentally infected, splenectomised calves. The anti-theilerial hydroxynaphthoquinone derivative buparvaquone was used either alone or in combination with primaquine phosphate. After treatment the calves were monitored for infection for up to 26 weeks. Blood films were examined for piroplasms and serum antibody levels were measured using an immunofluorescence technique. Buparvaquone alone failed to eliminate infections. Infections were eliminated from 11 of 16 calves treated twice with buparvaquone and three or six times with primaquine phosphate. Theilerial parasites were not subsequently seen in these 11 calves nor were antibodies detected beyond the eighth week after treatment.     

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.     

Point mutations in the Theileria annulata cytochrome b gene is associated with buparvaquone treatment failure

Theileriosis is an economically important haemoprotozoal disease with high morbidity and mortality in cattle. Buparvaquone is very effective in the treatment of Theileria infections in cattle. The present study reported an outbreak of bovine tropical theileriosis in Fars Province, southern Iran with buparvaquone treatment failure associated with mutations in drug-binding sites of its causative agent. The infected animals (n=8) exhibited poor condition, fever, anemia, rough coat and superficial lymph node enlargement. Both blood smears and lymph nodes punctures were positive and further molecular examination revealed that these animals were infected with Theileria annulata. Death occurred in seven of the eight infected animals in spite of the buparvaquone treatment. At molecular study, two types of important single-base mutations were observed in the cytochrome b gene of the parasite. These changes resulted in amino acid mutations in the parasite cytochrome b from serine (AGT) 109 to glycine (GGT) for the six dead cases and proline (CCT) 233 to serine (TCT) for one dead case within strongly Q(o) drug-binding sites. In contrast, neither of these mutations was found in the parasite cytochrome b for the buvarvaquone-treated animal. It seems that these mutation sites are associated with resistance to buparvaquone, a hydroxynaphthoquinone compound.     

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.     

Concentrations of buparvaquone in milk and tissue of dairy cows

AIM: To determine the concentration of the anti-theilerial drug buparvaquone in the milk and tissue of dairy cattle following treatment with two different formulations, and to assess the effect of clinical theileriosis on the concentration of buparvaquone in milk.

METHODS: Healthy lactating dairy cows (n=25) were injected once (Day 0) I/M with 2.5?mg/kg of one of two formulations of buparvaquone (Butalex; n=12 or Bupaject; n=13). Milk samples were collected from all cows daily until Day 35. Five cows were slaughtered on each of Days 56, 119, 147, 203 and 328, and samples of liver, muscle and injection site tissue collected. Milk samples were also collected from cows (n=14) clinically affected with theileriosis for up to 21 days after treatment with buparvaquone. Milk and tissue samples were analysed by liquid chromatography-mass spectrometry; limits of detection (LOD) were 0.00018?mg/kg for muscle and 0.00023?mg/L for milk. Concentrations of buparvaquone in milk and tissues were log₁₀-transformed for analysis using multivariate models.

RESULTS: In healthy cows, concentrations of buparvaquone in milk declined with time post-treatment (p<0.001), but were above the LOD in 11 of 25 cows at Day 35. Concentration in milk was higher one day after treatment in cows treated with Butalex than in cows treated with Bupaject, but not different thereafter (p=0.007). Concentrations of buparvaquone in muscle were below the LOD for four of five animals at Day 119 and for all animals by Day 147, but were above the LOD at the injection site of one cow, and in the liver of three cows at Day 328. Tissue concentrations did not differ with formulation nor was there a formulation by time interaction (p>0.3).

Concentrations of buparvaquone in the milk of clinically affected animals were not different from those of healthy animals at 1 and 21 days post-treatment (p=0.72). Between 21 and 25 days post-treatment concentrations were below the LOD in 9/14 milk samples from clinically affected cows.

CONCLUSIONS: Detectable concentrations of buparvaquone were found in the milk of some cows for at least 35 days and in the liver and injection site of some cows until at least 328 days after injection. There were no biologically meaningful differences in milk or tissue concentrations between the formulations, or in the milk concentrations for cows that were clinically affected compared with those that were healthy at the time of treatment.     

Anthelmintic treatment of dairy cows and its effect on milk production.

The results of more than 80 experiments on gastrointestinal parasitism and the impact of anthelmintic treatment on milk production in dairy cattle were reviewed. Abattoir surveys of culled dairy cows, faecal egg counts in milking cows, and serological tests and worm counts in cull cows in milk production studies were collated to assess the level of parasitism in dairy herds. The studies were divided into four general categories: induced infections in previously uninfected cattle; naturally infected cattle treated in mid-lactation; naturally infected cattle treated one to three times during the dry period and/or just before or just after parturition; and naturally infected cattle treated repeatedly from early lactation or given strategic treatments throughout the year. In most studies, the milk production of anthelmintic-treated cattle was compared with that of untreated controls. The anthelmintics investigated included members of the organophosphate, benzimidazole, imidazothiazole and macrocyclic lactone groups. The number of experiments in which the medicated (or uninfected) group had a higher milk yield was compared with the number of experiments in which the control (or infected) group had a higher yield. Overall, the studies demonstrated that grazing dairy cattle are likely to be infected with gastrointestinal nematode parasites, usually Ostertagia ostertagi and Cooperia species. These infections may be present as inhibited larvae, and a periparturient or spring rise is associated with their emergence. There is, at present, no reliable means of determining whether a cow or a herd may be parasitised subclinically at a level sufficient to interfere with milk production. In 70 of 87 experiments (80 per cent) there was an increase in milk production (P < 0.001) after anthelmintic treatment, with a median increase of 0.63 kg/day. In each of the four trial categories, a majority of the studies showed that anthelmintic treatment increased milk production. The yield of milk fat by the medicated cows was greater than by the controls in 26 of the 35 experiments in which that variable was studied (P < 0.01).     

Epidemiological observations on theileriosis following field immunisation using infection and treatment

Thirty-seven high grade cattle were immunised against Corridor disease (Theileria parva lawrencei infection) on a farm with a history of heavy and often lethal theilerial challenge. Nineteen cattle were immunised by treating with two doses of long-acting oxytetracyclines given at 20 mg/kg on days 0 and 4 after sporozoite stabilate inoculation, while the other 18 were treated with naphthoquinone buparvaquone, given as a single dose of 2.5 mg/kg simultaneously with stabilate inoculation. All the cattle underwent subclinical theilerial reactions with all but two developing high antibody titres on the IFAT test against T. parva schizont antigen by day 35 after the immunisation. Both buparvaquone and long-acting oxytetracycline appeared equally effective in the immunisation. To date, 26 months later, only two cases of theileriosis parasitologically characteristic of T. p. parva have been reported in the immunised cattle. Following the two cases, investigations showed that when uninfected Rhipicephalus appendiculatus nymphal ticks were deliberately fed on healthy resident cattle on the farm, the resultant adult ticks transmitted acute and lethal theilerial infections to five out of five susceptible cattle. The resultant infections were parasitologically characteristic of T. p. parva infections. Furthermore, the monoclonal antibody profiles of schizont infected cell lines from these infections appeared to be characteristic of T. p. parva. It was thus concluded that resident cattle on the farm could be a potential source of T.p. parva infection which had broken through the immunity of T.p. lawrencei immunised cattle and could constitute a reservoir of theilerial infection for ticks and hence to susceptible stock on the farm.     

In-vivo therapeutic efficacy trial with artemisinin derivative, buparvaquone and imidocarb dipropionate against Babesia equi infection in donkeys

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.     

The effect of dexamethasone and promethazine in combination with buparvaquone in the management of East Coast fever

The effects of dexamethasone and promethazine on the amelioration of pulmonary oedema in East Coast fever were investigated. The clinical effects of these drugs were further investigated when used in conjunction with the antitheilerial drug, buparvaquone. In the first experiment, 15 crossbred (Friesian x Zebu) steers were divided into four groups. With the exception of the animals in group IV, that served as a control group all the others were infected with Theileria parva sporozoites. On the second day of the febrile reaction, the steers in groups I and II were treated with dexamethasone (0.1 mg/kg) and promethazine (1 mg/kg), respectively. Group III steers served as the infected untreated controls. On the fifth day of the febrile reaction the animals in groups I, II and III were infused intravenously with tattoo ink suspension and 1 h later sacrificed for post-mortem examination and tissue sampling. The clinical picture indicated that both drugs significantly mitigated dyspnoea and the post mortem examination revealed a significant reduction in morphological changes. Tattoo ink particle count reflected a significant (P< 0.01) reduction in vascular leakage in the treated animals, with promethazine being significantly (P < 0.05) more effective than dexamethasone in this respect. In the second experiment, 18 steers were infected with T. parva sporozoites, and then were randomly allotted into three groups each of which contained six animals. After the onset of ECF clinical signs, the animals in the first two groups were treated with buparvaquone in combination with either dexamethasone (group I) or promethazine (group II), and the third group was treated with buparvaquone alone. The results indicated that all the animals in groups I, II and III recovered well and no significant differences were observed in clinical disposition between the groups. Two months later, serum samples were collected from the refractory animals and demonstrated the presence of antibodies against T. parva. When the animals were subsequently artificially challenged with T. parva, none of them succumbed to clinical disease. The same T. parva stabilate stock was used in both experiments and it proved to be infective in a separate batch of steers.