naphthoquinones and parvaquone

Topics: Animals; Cattle; Clinical Trials as Topic; Kenya; Naphthoquinones; Theileriasis

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.

Topics: Animals; Antiprotozoal Agents; Cattle; Cattle Diseases; Diuretics; Drug Combinations; Female; Furosemide; Male; Naphthoquinones; Pulmonary Edema; Theileria parva; Theileriasis; Uganda

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.

Topics: Age Factors; Animals; Antiprotozoal Agents; Body Temperature; Cattle; Cattle Diseases; Diuretics; Drug Combinations; Female; Furosemide; Male; Naphthoquinones; Parasitemia; Sex Factors; Suburban Population; Tanzania; Theileria parva; Theileriasis

Stages obtained from two Asian Babesia gibsoni-isolates cultured in vitro were studied by means of transmission electron microscopy and compared to strains of B. canis cultured in vitro. While the developmental stages of the latter preserved their shape in culture, many of the initially small stages of the B. gibsoni strains grew considerably and often looked rather similar to B. canis.

Topics: Animals; Antiprotozoal Agents; Asia; Babesia; Babesiosis; Dog Diseases; Dogs; Erythrocytes; France; Genotype; Hungary; Imidocarb; Microscopy, Electron; Naphthoquinones

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.

Topics: Administration, Topical; Animals; Antimalarials; Biopsy; Cattle; Female; Fever; Injections, Intramuscular; Insecticides; Kenya; Male; Naphthoquinones; Nitriles; Parasitemia; Pyrethrins; Random Allocation; Theileriasis; Tick Infestations

The horse-parasitizing species Babesia equi Laveran, 1901 was redescribed as Theileria equi Mehlhorn, Schein 1998 and, thus, transferred from one valid genus to another. This transfer was needed since it turned out that this horse parasite showed the relevant characteristics of theilerians with regard to biological data, morphological features, biochemical properties, and molecular biological relationships.

Topics: Animals; Antiprotozoal Agents; Arachnid Vectors; Babesia; Erythrocytes; Horse Diseases; Horses; Life Cycle Stages; Lymphocytes; Naphthoquinones; Piperidines; Quinazolines; Quinazolinones; Theileria; Theileriasis; Ticks

The clinical efficacy of albendazole (ABZ) in the treatment of chronic uncomplicated strongyloidiasis has been reported to be highly variable. In our murine model of strongyloidiasis a single oral dose of 5 and 10 mg kg-1 ABZ reduced (at day 4 post infection) the faecal larval count (FLC) by 54.2 +/- 12.5% and 81.5 +/- 10.2%, respectively. 100 mg kg-1 ABZ reduced the FLC by 100%. Two inhibitors of protozoan and filarial electron transport (720C80 and 993C76) inhibited the endogenous O2 consumption of intact infective (L3) larvae of S. ratti by > 50% at 2 x 10(-5) M in vitro, and reduced the FLC by 72 +/- 9.3% and 62.0 +/- 10.3% respectively in vivo, at a dose of 70 mg kg-1. These results suggest that compounds designed as selective inhibitors of protozoan electron transport have significant efficacy against murine strongyloidiasis and may prove useful in the management of human strongyloidiasis.

Topics: Albendazole; Animals; Antiprotozoal Agents; Female; Naphthoquinones; Rats; Rats, Sprague-Dawley; Strongyloidiasis

Groups of calves were infected by the injection of ground-up-tick supernatant from ticks infected with ODE-Anand stock of Theileria annulata, the causative agent of tropical theileriosis. Treatment with long-acting oxytetracycline, at 20 mg kg-1, injected intramuscularly, had no effect against severe Theileria annulata infection when administered either as a single injection on the day of infection or as three injections given on days 8, 10 and 12 after infection. Halofuginone lactate, given orally at 1.2 mg kg-1 was effective but caused anorexia, diarrhoea and debility. Parvaquone at 20 mg kg-1 intramuscularly given on day 11 after infection, had a marked suppressive effect, while buparvaquone was highly effective. A single treatment with buparvaquone, either at 5 mg kg-1 or 2.5 mg kg-1 intramuscularly, rapidly eliminated schizonts and piroplasms of T annulata. At 5 mg kg-1 it resulted in rapid recovery of all the treated calves.

Topics: Animals; Antiprotozoal Agents; Cattle; Male; Naphthoquinones; Oxytetracycline; Quinazolines; Quinazolinones; Theileria annulata; Theileriasis

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.

Topics: Animals; Antimalarials; Antiprotozoal Agents; Cattle; Iran; Naphthoquinones; Theileriasis

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.

Topics: Animals; Antiprotozoal Agents; Apicomplexa; Cat Diseases; Cats; Female; Male; Naphthoquinones; Protozoan Infections; Protozoan Infections, Animal

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.

Topics: Animals; Anti-Bacterial Agents; Cattle; Chemistry, Pharmaceutical; Delayed-Action Preparations; Immunization; Injections, Intramuscular; Injections, Subcutaneous; Kenya; Male; Naphthoquinones; Oxytetracycline; Theileriasis; Time Factors

Schizont-infected cell lines derived by in vitro infection of bovine T cell clones with the Muguga isolate of Theileria parva were treated for 72 hr with the theileriacidal drug, parvaquone, at a concentration of 10 micrograms/ml. This treatment completely eliminated schizonts from the recovered cells, which failed to undergo further proliferation and died. However, treated cells cultured with either bovine T cell growth factor or human recombinant interleukin 2 remained viable, underwent proliferation, and in many instances, schizonts reappeared. When cultured in the presence of supernatant obtained from an actively growing T. parva-infected cell line, treated cells did not proliferate, but schizonts reappeared. The cells became transformed by the parasite and grew continuously in the absence of exogenous growth factor. The appearance of schizonts was preceded by the development of densely staining intracytoplasmic inclusions, visualized by light and electron microscopy. Electron-dense inclusions were shown to contain DNA. Hybridization of a T. parva-specific DNA probe to Southern blots of restriction enzyme-digested DNA prepared from parvaquone-treated cells which developed inclusions but not schizonts produced a pattern similar to that seen with DNA prepared from schizont-infected cells. We conclude that reorganization of schizonts can occur in T. parva-infected T lymphocytes cured of infection with parvaquone in the presence of interleukin 2 or growth factors produced by T. parva-infected cells. The implications of these results for the establishment of a carrier state following parvaquone therapy are discussed.

Topics: Animals; Apicomplexa; Cattle; Cell Line; Cell Survival; DNA; Interleukin-2; Microscopy, Electron; Naphthoquinones; Nucleic Acid Hybridization; T-Lymphocytes; Theileriasis

Groups of cattle were immunized with 10(-2) dilutions of sporozoite stabilates of Theileria parva lawrencei derived from African buffaloes either alone or in combination with Theileria parva parva derived from cattle and concomitant treatment with either long or short-acting formulations of oxytetracyline. At 90 or 120 days after infection, uninfected Rhipicephalus appendiculatus nymphal ticks were applied to individual immunized cattle and the resultant adults ticks were applied to individual susceptible cattle. Theilerial infection developed from ticks fed on 6 out of 11 animals investigated for evidence of a carrier state. Two additional animals were shown by cell-culture isolation to have persistent theilerial infections. Nine cattle infected with the parasites from carrier animals were treated with paravaquone and 7 recovered. These recovered cattle were then challenged with the original immunizing stabilates at 10 degrees dilution together with the original immunized and carrier cattle. Six out of 7 cattle which had recovered from carrier-derived infection succumbed to this challenge and died but none of the original immunized cattle showed theilerial reactions. When a carrier-derived sporozoite stabilate was used to challenge cattle immune to the original immunizing parasite, they proved to be immune. Cattle immune to the carrier-derived parasites were all immune to challenge with the original parasite. A monoclonal antibody profile against T. parva schizonts isolated by cell culture from samples of the experimental animals did not appear to be sensitive enough to determine the antigenic differences between the carrier-derived parasite and the original immunizing parasite. Indications are that the carrier state is not likely to produce new antigenic strains which would be dangerous to immunized cattle.

Topics: Animals; Antigens, Protozoan; Antimalarials; Apicomplexa; Carrier State; Cattle; Immunization; Naphthoquinones; Oxytetracycline; Theileriasis; Ticks

A high performance liquid chromatographic (HPLC) method for the determination of the antitheilerial drugs parvaquone and buparvaquone in plasma was developed. Both compounds were extracted from plasma with ether. After evaporating the extracts to dryness the residue was dissolved in methanol and an aliquot was injected onto a column (10 cm X 5 mm, i.d.) of ODS-Hypersil (5 mu) with a mobile phase of 0.05 M-Na acetate buffer (pH 3.6)-methanol (15:85, v/v). Detection was at 252 nm. The mean recovery for both compounds was about 92%. This method was used to elucidate their pharmacokinetics in 6 calves after intramuscular administration. The maximum plasma concentration for parvaquone was 6.36 +/- 0.58 micrograms/ml after 0.84 +/- 0.08 h. The corresponding values for buparvaquone were 0.102 +/- 0.030 microgram/ml and 3.17 +/- 0.39 h, respectively. The decay in plasma concentrations for the two drugs was biexponential and the terminal elimination half lives were 11.12 +/- 1.63 h and 26.44 +/- 2.81 h for parvaquone and buparvaquone, respectively.

Topics: Animals; Antiprotozoal Agents; Cattle; Chromatography, High Pressure Liquid; Naphthoquinones

Parvaquone was tested in cattle infected with Theileria annulata when they were presented at clinics in the vicinity of Baghdad. Out of over 200 cases presented with suspected theileriosis between July 1984 and July 1985, the drug was used in 45 cases where theileriosis was confirmed by microscopic examination of blood and lymph node biopsy smears. Twenty seven of the cases were considered mild and 18 cases severe. Weights of the cattle were estimated and parvaquone was administered by intramuscular injection at a nominal dose of 20 mg/kg. A single treatment with parvaquone was used in 25 cases and 20 cases were treated twice but there was no correlation between severity of disease and the number of treatments given. Twelve cases (27%) also received antibacterial therapy. All cases were in exotic cattle or cattle born from exotic (imported) cattle and 64% of the cases were in cattle under six months of age. Temperatures dropped immediately after treatment and the majority were normal (below 39.5 degrees C) by two to three days after the first treatment. Of the 45 cases treated 43 recovered. This compares very favourably with a previously reported mortality of 66% in untreated imported cattle in Iraq.

Topics: Animals; Antiprotozoal Agents; Cattle; Drug Evaluation; Iraq; Naphthoquinones; Theileriasis

Parvaquone was used in 13 cattle naturally infected with Theileria annulata. Blood smears and lymph node biopsy smears were taken, stained and examined for the presence of the piroplasm and schizont stages of the parasite respectively. Smears were examined before and on the third, fifth and seventh day after commencement of therapy. Two doses of parvaquone were injected in the neck intramuscularly at 10 mg/kg bodyweight at 48 hour intervals. Of the 13 cattle treated 11 were discharged in fairly good condition and two died of tropical theileriosis on the sixth day after commencement of treatment.

Topics: Animals; Cattle; Female; Naphthoquinones; Theileriasis

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.

Topics: Animals; Antiprotozoal Agents; Cattle; Male; Naphthoquinones; Theileriasis

Parvaquone (Clexon Cooper) was clinically tested for efficacy as a treatment for East Coast Fever (Theileria parva parva infection) in naturally infected cattle. The drug showed a suppressive effect on Theileria schizonts and piroplasms. A recovery rate of 79% was recorded. Best results were obtained when Clexon treatment was initiated in the early stage of the disease, before many red blood cells were invaded and before respiratory distress was evident. A carrier state in animals recovered from East Coast Fever is suspected.

Topics: Animals; Apicomplexa; Cattle; Female; Naphthoquinones; Pregnancy; Pregnancy Complications, Infectious; Theileriasis

A cat which had recovered from Cytauxzoon felis infection following treatment with the anti-theilerial drug, parvaquone, showed an increase in piroplasm parasitemia after splenectomy and its blood was suitable for the preparation of antigen smears for the indirect fluorescent antibody test. High levels of antibodies were found in this cat after recovery, in two other cats sub-lethally infected with piroplasms and in sera of naturally infected bobcats. Cats recovered from piroplasm infection died from cytauxzoonosis when challenged with organ material containing C. felis schizonts. Tests with piroplasm antigens and positive sera of C. felis, South African Babesia felis and African Theileria taurotragi showed no significant serological relationship between C. felis and the African parasites. C. felis was not shown to be infective for splenectomized sheep.

Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Apicomplexa; Babesia; Babesiosis; Cat Diseases; Cats; Fluorescent Antibody Technique; Naphthoquinones; Protozoan Infections; Protozoan Infections, Animal; Sheep; Sheep Diseases

Topics: Animals; Antiprotozoal Agents; Apicomplexa; Lymphocytes; Naphthoquinones; Quinazolines; Quinazolinones; Theileriasis; Triazines

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.

Topics: Animals; Antiprotozoal Agents; Babesiosis; Carbanilides; Horse Diseases; Horses; Imidocarb; Injections, Intramuscular; Male; Naphthoquinones; Splenectomy

The weight changes, carrier state and nature of chronic disease in cattle following infection with five isolates of Theileria parva and treatment with parvaquone were studied over an 18 month period while the cattle were maintained on normal management under strict tick control. Cattle infected with the T.p. parva Pugu II isolate gained weight similarly to uninfected control cattle and did not develop a detectable carrier state or show chronic disease. The cattle in the 4 other isolate groups regained the weight lost during the initial infection more slowly, then gained weight in parallel to the control cattle. Transmission of infection through ticks was achieved consistently from the T.p. parva Mbita I and Entebbe II isolate infections and intermittently from the T.p. lawrencei Mara II and Manyara infections. Infections were transmitted from cattle which had neither a detectable parasitaemia nor an antitheilerial antibody titre. Persistent macroschizont parasitoses were detected with the T.p. parva Entebbe II and the two T.p. lawrencei infections. The histopathology of the chronic disease lesions is described and the importance of the carrier state discussed.

Topics: Animals; Apicomplexa; Arachnid Vectors; Body Weight; Carrier State; Cattle; Male; Naphthoquinones; Theileriasis; Ticks

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.

Topics: Animals; Antiprotozoal Agents; Cattle; Male; Naphthoquinones; Oxytetracycline; Theileriasis; Ticks

Topics: Animals; Antiprotozoal Agents; Apicomplexa; Cattle; Cell Line; Cells, Cultured; Immune Sera; Naphthoquinones; Theileriasis; Time Factors

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.

Topics: Animals; Antimalarials; Apicomplexa; Cattle; Dose-Response Relationship, Drug; Female; Injections, Intramuscular; Male; Naphthoquinones; Theileriasis; Ticks

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.

Topics: Animals; Antimalarials; Antiprotozoal Agents; Apicomplexa; Cattle; Chemical Phenomena; Chemistry; Kenya; Naphthoquinones; Species Specificity; Theileriasis

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.

Topics: Animals; Antimalarials; Cattle; Female; Male; Naphthoquinones; Theileriasis; Zambia

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.

Topics: Africa, Eastern; Animals; Antiprotozoal Agents; Apicomplexa; Arachnid Vectors; Cattle; Female; Leukopenia; Male; Naphthoquinones; Rabbits; Theileriasis; Ticks

Two groups of five cattle were immunised with a field isolate of Theileria parva as stabilate and simultaneously treated with long acting oxytetracycline or parvaquone in early clinical disease. The oxytetracycline group suffered a marked fall in leucocyte count and one animal died during immunisation. The parvaquone group suffered a less severe fall in leucocyte count and all survived. The surviving immunised cattle were immune to homologous challenge but susceptible to subsequent challenge with T p lawrencei.

Topics: Animals; Antiprotozoal Agents; Apicomplexa; Cattle; Cattle Diseases; Delayed-Action Preparations; Immunization; Leukocyte Count; Leukocytes; Male; Naphthoquinones; Oxytetracycline; Theileriasis

Topics: Animals; Antiprotozoal Agents; Apicomplexa; Cattle; Cell Line; Naphthoquinones; Species Specificity; Theileriasis

The efficacy of halofuginone (DL-trans-7-bromo-6-chloro-3,3-(3-hydroxy-2-piperidyl) acetonyl-4-(3H) quinazolinone), Wellcome 993 C (2-hydroxy-3-cyclohexyl-1,4-naphthoquinone), and oxytetracycline, all of which have been shown to have a schizonticidal effect in the treatment of bovine theileriosis, and the babesicidal drug diminazene diaceturate, were tested against the schizont stages of Babesia equi in cell culture. The in vitro test system measured DNA synthesis in treated and untreated cell lines. Halofuginone (0.02 microgram/ml) and Wellcome 993 C (5 micrograms/ml) suppressed the incorporation of tritiated thymidine by more than 80%. Oxytetracycline was less effective, while diminazene diaceturate showed no notable effect. The insufficient schizonticidal activity may explain the failure of diminazene diaceturate to cure B. equi infections. Schizonticidal drugs either alone, or in combination with known babesicidal drugs, should be tested in the chemotherapy of B. equi infections.

Topics: Amidines; Animals; Antiprotozoal Agents; Babesia; Cell Line; Diminazene; DNA; Lymphocytes; Naphthoquinones; Oxytetracycline; Piperidines; Quinazolines; Quinazolinones; Thymidine

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.

Topics: Animals; Cattle; Injections, Intramuscular; Male; Naphthoquinones; Theileriasis

The efficacy of Wellcome compound 993C and halofuginone was compared using cattle artificially infected with Theileria parva and using in vitro cultures of T parva. At a total dose of 20 mg/kg administered by the intramuscular route, 993C cured all nine cattle of advanced theileriosis and no major recrudescences of the infection occurred. Halofuginone was given by mouth at 1.2 mg/kg and cured five cattle of early clinical theileriosis, but significant recrudescences of infection occurred. Halofuginone at 1.2 mg/kg cured a further five out of six cattle with advanced theileriosis, but four of the five survivors developed moderate to severe resurgences of infection. The dose of 20 mg/kg of 993C was known to be close to its effective level, but 1.2 mg/kg halofuginone, the dose used by earlier workers, may not have been adequate. All 10 untreated control cattle died of acute theileriosis. The in vitro EC50 of both compounds was 0.003 mg per litre but, whereas the dose response curve of 993C was sigmoid, that of halofuginone was bellshaped. This may reflect toxicity to the host lymphoblastoid cells with higher concentrations of halofuginone.

Topics: Animals; Antiprotozoal Agents; Apicomplexa; Cattle; Coccidiostats; Lymph Nodes; Male; Naphthoquinones; Piperidines; Quinazolines; Quinazolinones; Theileriasis

A prominent pathogenic facet of Theileria infections is that the parasite infects lymphocytes and 'transforms' them into parasitized lymphoblastoid cells which are highly proliferative and can be cultured indefinitely in vitro. To analyse the relationship between the intracellular parasite and lymphocyte transformation we have studied the effects of eliminating parasites from these lymphoblastoid cells using the naphthoquinone derivative 993.C. Treatment of Theileria-infected lymphoblastoid cells with 993.C gradually eliminates intracellular parasites but cell proliferation is not inhibited until several days after parasite elimination. The proliferating cells no longer contain schizont particles and are medium-sized lymphocytes and small blast cells. The surface phenotype of these cells, as defined by lectins and monoclonal antibodies, remains unchanged after parasite elimination. The division of non-parasitized cells, under the culture conditions examined, was not indefinite. The compound 993.C itself does not appear to be mitogenic and possible mechanisms for this continued division are discussed. It has been previously reported that co-cultivation of irradiated Theileria-infected lymphoblastoid cells with autologous lymphocytes induces marked DNA synthesis in the latter. We examined further the relevance of this observation for immunity to Theileria by using lymphoblastoid cells treated with 993.C. Elimination of intracellular parasites by this compound does not impair the ability of these cells to stimulate DNA synthesis in autologous lymphocytes. Furthermore, lymphocytes from Theileria-immune or non-immune cattle react similarly. The reaction differs from a classical mixed lymphocyte reaction induced by antigens encoded in the main histocompatibility complex since the stimulator cells are exclusively T lymphocyte-derived cells, the magnitude of response is greater and stimulated lymphocytes are able to act as 'stimulator cells' to fresh autologous lymphocytes. Thus we question the immunological relevance of the observed lymphocyte division. The possibility that Theileria-infected lymphoblastoid cells carry viral genomes or infectious virus particles is discussed. Preliminary electron microscopic studies have not revealed any virus particles.

Topics: Animals; Apicomplexa; Cattle; Cell Division; Cell Line; DNA; Lymphocyte Activation; Lymphocytes; Male; Naphthoquinones; Theileriasis

A tissue culture method was used to screen compounds for activity against Theileria parva, and demonstrated that the hydroxy-alkylated naphthoquinones, 'menoctone' and 993C were highly active, with ED50 values around 0,005 mg/l. When injected into cattle artificially infected the T. parva, menoctone cured all of 7 cattle at a total dosage of 10 mg/kg injected intravenously (i.v.). A further trial showed that injection of menoctone, 10 mg/kg, as a single dose gby the intramuscular (i.m.) route was more effective than when a similar dose was given by the i.v. route. Titration of serum from these cattle in the in vitro system showed that inhibitory levels of drug persisted for three days after i.v. injection and six days when menoctone was injected i.m. The minimum effective dose level of 993C was 20 mg/kg i.m. either as a single dose, or as two doses of 10 mg/kg with an interval of 48 hours.

Topics: Animals; Antimalarials; Cattle; Naphthoquinones; Theileriasis