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.     

牛环形泰勒焦虫裂殖体胶冻细胞苗应用效果观察

河南省桐柏县是牛环形泰勒虫病流行的多发区,对养牛业危害十分严重,1985年该县从宁夏农林科学院畜牧兽医研究所引进“虫苗”2万头份,在区域试验的基础上在全县16个乡（镇）进行了大面积防疫注射,经年终统计表明：虫苗安全性100%,注苗15000头（其中有水牛45000头）,发病3头,发病率0.02%;未注苗36000头,发病2060头,发病率5.7%,实际有效保护率达99.98%,取得了明显的社会经济效益。     

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.     

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 sheep against Theileria hirci infection with schizonts propagated in tissue culture

Two experiments were carried out. In the first, three groups of lambs were inoculated subcutaneously with 3 X 10(6) schizonts of different passages (3, 30 and 63) of Theileria hirci propagated in tissue culture. Severe reactions were observed in lambs inoculated with organisms derived from the 3rd passage. In the second experiment, four groups were inoculated with 5 X 10(5), 3 X 10(6), 1 X 10(7) and 5 X 10(8) schizonts of the 63rd passage. No clinical reactions or parasites were detected in lambs inoculated with 5 X 10(5) schizonts. Mild reactions were observed in lambs inoculated with 3 X 10(6), 1 X 10(7), and 5 X 10(7) schizonts. Lambs inoculated with 3 X 10(6) schizonts were resistant to challenge with a virulent strain. The indirect fluorescent antibody (IFA) test was used to determine the antibody titre.     

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.     

Haematological and biochemical studies on experimental Theileria annulata infection in crossbred calves

Administration of ground-up tick tissue stabilate (0.75 tick equivalent) by the subcutaneous route to crossbred calves aged 1 week to 1 month led to the development of acute theileriosis. Haematological studies revealed significant progressive decreases in haemoglobin concentration, packed cell volume and red blood cell count, whereas the total leukocyte count showed an initial non-significant leukocytosis followed by a significant leukopenia. Analysis of serum revealed significant increases in levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine kinase and -glutamyltransferase, and in the concentrations of uric acid, blood urea nitrogen and bilirubin. The concentrations of total protein, albumin, glucose, cholesterol and calcium showed non-significant decreases, while phosphorus decreased significantly during the terminal stages of the disease.     

Immunoprophylaxis against Theileria annulata with protein from plasma membrane of infected lymphoblasts

Cross-bred (Bos taurus male x Bos indicus female) calves were protected against the homologous sporozoite-induced challenge of Theileria annulata when immunised with protein from the plasma membrane of macroschizont-infected lymphoblasts of allogeneic origin. However, such protection was parasite-strain specific with the plasma membrane originating from lymphoblasts infected and transformed by the same isolate of T. annulata sporozoites. No protection ensued when the infected lymphoblasts and sporozoites were from immunologically different isolates of T. annulata. There was enhanced proliferation of cells and evidence for lymphokine, originating from antigen-sensitised lymphocytes, demonstrable as macrophage migration inhibition factor in peripheral blood lymphocytes of the calves immunised by plasma membrane protein and challenged by sporozoites of homologous origin.     

Antigenic diversity of Theileria annulata macroschizonts

A series of monoclonal antibodies has been produced which reacts with the intracellular macroschizont of Theileria annulata, and this series has been used to examine the level of antigenic diversity between and within stocks of the parasite in addition to species specificity within the genus. The majority of the monoclonal antibodies (six of eight) reacted with all stocks tested and four were species-specific. Two monoclonal antibodies detected variation between stocks and within stocks. The variation within a stock was manifest as only a proportion of the macroschizonts reacting with the monoclonal antibody. This was demonstrated as being due to the strain containing more than one antigenic type of parasite by cloning the infected lymphocyte cell line and showing that the resulting cloned cell lines were antigenically homogeneous. The variation between stocks allowed them to be divided into three groups on the basis of antigenic profile.     

Presence of Theileria annulata in Mauritania

A fatal case of bovine theileriosis by Theileria annulata is reported from Mauritania in a Friesian cow born in a dairy farm in Nouakchott. The farm was originally established with cattle imported from France. Specific diagnosis was based on piroplasm morphology and on high specific antibody titres in some of the animals. The only tick found in the herd was Hyalomma dromedarii. Four of 49 local zebus sampled at random in the south of the country had high specific antibody titres to T. annulata, while 14 had lower or doubtful titres. The infection therefore appears to be autochthonous.     

新疆托克逊部分地区牛环形泰勒虫感染情况调查

为了解2014-2016年托克逊县部分地区牛环形泰勒虫病的感染情况,采用血液涂片法对托克逊县4个乡疑似牛环形泰勒虫的835例进行病原学检测,并分析各年龄段和不同地区牛环形泰勒虫的感染情况。结果表明,该疫区2014-2016年牛环形泰勒虫阳性率为49.46%(413835);4个乡均不同程度感染牛环形泰勒虫,其中伊拉湖乡牛环形泰勒虫阳性率最高,为53.80%(99/184)。不同年龄段牛环形泰勒虫感染无显著性差异。调查结果为托克逊地区环形泰勒虫病的防控提供了参考。     

Comparative pathogenicity of Theileria annulata strains

Twenty three susceptible crossbred calves were inoculated with five Indian strains of Theileria annulata, collected from natural cases of tropical theileriosis at Ludhiana, Hissar, Jaipur, Uruli-Kanchan and Bangalore. All the strains produced clinical disease with typical symptoms and lesions of acute theileriosis. The strains were considered highly virulent and equally pathogenic.     

Comparative pathogenicity of Theileria annulata strains

Summary

Twenty three susceptible crossbred calves were inoculated with five Indian strains of Theileria annulata, collected from natural cases of tropical theileriosis at Ludhiana, Hissar, Jaipur, Uruli‐Kanchan and Bangalore. All the strains produced clinical disease with typical symptoms and lesions of acute theileriosis. The strains were considered highly virulent and equally pathogenic.     

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.     

Prophylactic efficacy of buparvaquone in experimentally induced Theileria annulata infection in calves

The antitheilerial activity of buparvaquone (BW 720C) was evaluated in experimentally induced Theileria annulata infections in cross-bred male calves. T. annulata infections were induced by injecting a suspension of infected ground tick tissue suspension (GUTTS) equivalent to two ticks subcutaneously into each calf. Buparvaquone at a dose of 2.5 mg kg-1 body weight was given as a single injection (intramuscularly) on Day 0 (Group 1), Day 8 (Group 2) and Day 12 (Group 3) post-infection. The animals in Groups 4 and 5 were untreated and challenged controls, respectively. All of the recovered animals from Groups 1-4 were challenged with a lethal dose of T. annulata at 6 weeks post-infection. The immunized animals were resistant to the homologous challenge, which killed three of four control animals (Group 5); the controls showed typical antemortem and post-mortem lesions of theileriosis.     

Immunization against bovine tropical theileriosis, using 60Co-irradiated infective particles of Theileria annulata (Dschunkowsky and Luhs 1904) derived from ticks.

Portions of ground supernate material from Theileria annulata-infected and prefed adults of the Hyalomma anatolicum anatolicum were irridiated by 60Co source at 0, 3, 5, 6, 7, or 9 krads. These portions were injected subcutaneously into different groups of cross-bred calves. The calves injected with 0-, 3-, or 5-krad irradiated tick supernate had severe reactions (rectal temperature 39.8 to 41.6 C, two- to fourfold enlargement of prescapular lymph gland, mean peak parasitemia 27.3% to 32.5% infected erythrocytes, decreased PCV 41.7% to 60.7%, and hemoglobin concentration 37.5% to 50.8%), and many died, whereas those injected with 6- or 7-krad irradiated tick supernate had minimal reactions (rectal temperature 39.2 to 39.8 C, slight enlargement of prescapular lymph gland, parasitemia less than 1%, decrease packed cell volume 15.1%, and hemoglobin concentration 20.1%), with no mortality. All surviving calves injected with nonirradiated (0-) or 3-, 5-, 6-, or 7-krad irradiated tick supernate developed comparable indirect fluorescent antibody titers and were resistant to challenge exposure with infective material from 30 ticks. The calves injected with 9-krad irradiated tick supernate showed no reactions and did not develop indirect fluorescent antibody titers; they were also susceptible to challenge exposure with infective tick material.     

Common and stage-specific antigens of Theileria annulata.

Western blot analysis of Theileria annulata antigens was carried out using sera collected from cattle which had been immunised and challenged with either T. annulata sporozoites or schizont-infected cells. Three antigens between 71 and 73 kDa proved to be common to the three stages of parasite studied: sporozoites, schizonts and piroplasms. An antigen was found at 32 kDa which was specific to T. annulata piroplasms. Results were reproducible using sera from Morocco and the UK. At least one of the proteins at 71-73 kDa, but not that at 32 kDa were also recognised by sera from animals infected with Babesia species.