Imizol overview (meo athens mtg) msd antiparasitarios finca productiva


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  • Called white piroplasmosis (hemoglobinuria), seasonal, infests adult cattle. Red cells destroyed by RES.
  • Acute phase: hyperthermia, asthenia, anorexia, weight loss, or limited symptoms. Sub-clinical form evolves towards free carrying or severe symptomatic form (hemorrhages, epistaxis, retinal hemorrhages,…) and sometimes death. Necropsy: chronic forms = hemorrhages in numerous organs, lymphadenopathy, oedema of limbs and medular hypoplasia. Destruction of thrombocytes (immune origin) Leucocytosis =  of lymphocytes and plasmocytes
  • The sporozoite invades a red cell (directly?) of the host, multiplies and differentiates into merozoites, infected erythrocytes are ingested by a tick during a blood meal. Pyroplasms differentiate in gametes in the gut lumen of the tick. Fecundation gives a zygote invade gut cells and liberates a free sporokinete. Sporokinetes invades and multiply in various organs of the tick and most importantly in ovaries. By infesting eggs they are transmitted to the next generation of ticks and eventually penetrates the salivary glands of the progeny. They differentiate into sporozoites (sporognies), and infest cattle during a blood meal. For B. bigemina nymphal and imagine stages are infesting, for B. bovis larvae stage is infesting. Les babesia les plus frequentes sur la zone sont B. bigemina, bovis et major (Algerie). Leurs vecteurs sont respectivement Boophilus (1 seul hote) (mais aussi possible par Rhipicephalus et Haemaphysalis) pour les 2 premiere espece et haemaphysalis pour la derniere. Les babesiose des petits ruminants sont B. motasi et B. ovis
  • The sheep and goat species are predominently, B. motas i (large) and B. ovis (small, Middle East). They are not highly pathogenic. Transmitted by Rhipicephalus, haemaphysalis, Ixodes and Dermacentor. Same symptoms as B. Bigemina. The horse species are B. caballi (large) and B. equi (ameboid/pear shape, transstadial transmission, part of the cycle in the lymphocytes) same pathogeny and features as cattle babesiosis.
  • Destruction of red cells: anemia, anoxia Secretion of proteases/esterases: -activation of complement: liberation of anaphylatoxins (vasodilation) -activation of coagulation and liberation of thromboplastin by red cells  disseminated thrombosis (no fibrinolysis, not a real disseminated intravascular coagulation) -activation of kinin system (kallicreine, bradykinine): vaso dilation and inflammation (acute phase proteins,…) Modification of red cells membrane: hemagglutination, capillary adherence, extra-Vascular hemolysis (spleen) Formation of immune-complexes: tissular lesions (kidney, lungs, liver, red cells  extra-vascular hemolysis,…) straining of the immune system ! Liberation of various toxins and debris from red cells (depression of RES) (B. bovis: hypotensive choc with limited number of circulating parasites but a lot of infected red cells in the brain, kidney and muscles capillaries.)
  • Peracute forms: hemoglobinuria and icterus are nearly simultaneous. Acute forms, digestive symptoms:characteristic diarrhea, the animal expels with efforts long spurs of liquid faeces through a tight anus; episodes of constipation. Urine: port-coffee color Attenuated forms: limited symptoms (hyperthermia, loss of appetite, anemia, altered general health state)and severe necropsy lesions.
  • Withdrawal period: milk =21 days ; meat = 90 days (cattle), 60 days (horses) Side effects: (increased vascular permeability) at 5-10mg/kg IM salivation,sweating, muscular fasciculation, hyperventilation, lacrimation, frequent micturition/defaecation; at 20mg/kg IM it kills. With 6 mg/kg IM, peak concentration 20-30 min. after injection, less than 1/2 dose excreted after 7 days, mainly in urine. After SC injection, peak concentration after 1 hour 53% of the dose excreted in 10 days (3 mg/kg SC) Shelf life extended from 2 to 3years Storage: 2-25°C, protect from light Contra-indication: Sterilization or treatment of mixed infections with B. equi should not be attempted in donkeys and mules. Precautions: No injection IV, do not associate with other piroplasmicids Horse: no injection in pectorals, (5 ml max. /site) Side effects of cholinergic nature may occur, salivation, lachrymation, defaecation, and urination (give 0.1-0.2 mg/kg atropine sulphate)
  • 1ml/100 kg = 1.2 mg/kg 2.5 ml/100 kg = 3 mg/kg Immunity (sterilization with 2 mg/kg imidocarb at different times after infection) holds against challenge up to ~6 month (more than 200 days) and depends mainly on the degree of antigenic exposure (2-4 days of parasitemia before sterilization gives intermediate reaction between susceptible controls and untreated groups). Of 16 animals infected with B. bigemina, 9 (56%) were self cured (uninfected) after 32 weeks  elimination of parasite for more than half of the animals in 7 months Of 12 animals sterilised (2mg/kg of imidocarb) 4 weeks after infection with B. bigemina, 9 (75%) resisted to challenge 28 weeks later without need for treatment  sterile immunity lasts ~ 6 month
  • 52 animals followed until 8 months for B. divergens
  • Imizol overview (meo athens mtg) msd antiparasitarios finca productiva

    1. 1. IMIZOL Treatment of: Bovine Babesiosis & Anaplasmosis
    2. 2. ANAPLASMOSIS ( A. marginale , caudatum, centrale , ovis ) <ul><li>Rickettsia, parasite of ruminants’ red cells, </li></ul><ul><li>transmitted by a tick or mechanically by a horsefly (inter-stadial) </li></ul><ul><li>Fever, anaemia, dark yellow urine, icterus, polypnea </li></ul><ul><li> appetite, constipation (greenish faeces), </li></ul><ul><li> milk yield, abortion/dystocia </li></ul><ul><li>Destruction of red cells by the spleen, </li></ul><ul><li>anaemia  hypoxia/anoxia  death </li></ul>
    3. 3. ANAPLASMOSIS Pack Cell Volume % Parasitaemia % Effective treatment period Death Convalescence Immune clearance 21days 29 days <ul><li>Losses: $100 million/year </li></ul><ul><li>Incubation: 21d.-convalescence: 3 mths-carrier state </li></ul>1 16 26 36 46 20 40 60 80 0
    4. 4. EHRLICHIOSIS ( E.canis ) <ul><li>Rickettsia, infests lymphocytes (& thrombocytes?) Transmitted mostly by Rhipicephalus s. tick </li></ul><ul><li>Leucocytosis, thrombocytopenia, peri-vascular infiltration of lymphocytes and plasmocytes </li></ul><ul><li>Incubation: 8-20 days  acute phase (2-3weeks) </li></ul><ul><li> sub-clinic. form (2-3 mths)  asympt. chronic form </li></ul><ul><li>  or acute evolution </li></ul><ul><li>Hyperthermia (39.5-41.5°C), anorexia,  weight, asthenia, (hemorrhages/epistaxis),... </li></ul>
    5. 5. BABESIA SPP. CYCLE merozoites BIPARTITION gametes zygote kinet kinet sporozoites sporogony Female 2, 3,... red cells Female 1 digest. t. eggs Boophilus Cattle . salivary gl Transovarially transmitted
    6. 6. BOVINE SPECIES <ul><li>The most frequent in Africa & Middle East : </li></ul><ul><li>B. bovis (very pathogenic: predominance of shock, small B .)  Boophilus </li></ul><ul><li>B. bigemina (variable pathogenic action, large B .)  Boophilus </li></ul><ul><li>B. major (less pathogenic: predominance of haemolysis, large B. , North Africa) </li></ul><ul><li> Haemaphysalis </li></ul>
    7. 7. PATHOGENIC ACTION <ul><li>Destruction of erythrocytes (intra et extra-vascular) </li></ul><ul><li>Secretion of toxins (proteases) </li></ul><ul><li> activation: compliment, kinins, coagulation </li></ul><ul><li>Antigenic action : </li></ul><ul><li> modification of red cell membrane </li></ul><ul><li> formation of immune -complexes </li></ul>
    8. 8. SYMPTOMS (incubation: 3-15 days) <ul><li>Peracute forms : </li></ul><ul><li>High hyperthermia, acute prostration, rapid haemoglobinuria/icterus, cerebral manifestations-sometimes predominant, death </li></ul><ul><li>Acute forms : </li></ul><ul><li>Fever (40-41°C),  appetite & milk yield, anaemia, red-coffee urine (+ 24-36h), characteristic diarrhea /constipation, [(sub)icterus, pulmonary oedema, cerebral manifestations] </li></ul>
    9. 9. DIAGNOSIS <ul><li>Clinical symptoms </li></ul><ul><li>Stained blood smears (peripheral blood) </li></ul><ul><li>Antibody detection (ELISA, fixation of complement,…) </li></ul><ul><li>Necropsy (spleen, kidney, bladder, samples,…) </li></ul>
    10. 10. IMIZOL Mode of action : Competitive inhibition for inositol red cell membrane receptors. Inositol = essential compound for Babesia metabolism . Destruction of parasites without erythrocytes lysis.
    11. 11. IMIZOL <ul><li>Carbanilid family (derived from urea) </li></ul><ul><li>Peak concentration in blood: 20-30 minutes </li></ul><ul><li>Not metabolized </li></ul><ul><li>Eliminated mostly through urine (3x faeces) </li></ul><ul><li>Dosage, cattle: </li></ul><ul><ul><li>Babesiosis: 1 ml/100kg or, </li></ul></ul><ul><ul><li> prophylaxis: 2.5 ml/100 kg IM (SC ) </li></ul></ul><ul><ul><li>Anaplasmosis: 2.5 ml/100 kg IM (SC) </li></ul></ul>
    13. 13. IMIZOL PREMUNITION = type of immunity depending on the presence of infection. Ends with the end of infection. Protection (animals bitten by ticks during chemoprotection period with 2.5ml/100kg of Imidocarb) has been shown to last at least 8 months with B. Divergens. (1 treatment with 2.5ml/100kg per year during tick season for renewal of protection). Protection against B bigemina could be a mix of premunition (~6months) and sterile immunity (immunity in the absence of parasite, ~6 months).
    14. 14. IMIZOL Molecule ED50 B. rodhaini mg/kg Imidocarb 0,22 Amicarbalide 0,93 Diminazine 7,37 Quinuronium 0,33 Molecule LD50 ED50 mice rat Imidocarb 485 2 727 Amicarbalide 172 620 Diminazine 70 121 Quinuronium 25 226
    15. 15. IMIZOL Babesia Type & no. Treatment Dose no. cured B. argentina 12 splenect. calves imidocarb 5mg/kg sc 11 (= B. bovis ) 12 splenect. calves amicarbalid 5mg/kg sc 7 11 splenect. calves imidocarb 1mg/kg iv/sc 11 6 steers imidocarb 1 mg/kg sc 6 5 steers imidocarb 0,75 mg/kg sc 5 B. bigemina 10 splenect. calves imidocarb 0,4-2mg/kg sc 10 Total 32 32 (100%)
    16. 16. IMIZOL Babesia Steers Dose of imidocarb Protection after (+3-5j) challenge with B. bigemina B. argentina 2 4mg/kg 9 wks=+, 13 wks + 2 2mg/kg 8 wks=+, 12 wks= + 2 1mg/kg 7 wks=+, 11 wks= + 2 0,5mg/kg 7 wks=+, 11 wks= -
    17. 17. IMIZOL ( B. divergens ) Moment of -7d 0d control mean (+7d, treatment: +14d, +21d) Sp. calves 3 3 3 9 Parasites 4.6 - 33.1 20.6 per ml x10 -8 max. t°C 39.9 39.7 41.1 41.2 Reaction 3NR 1D2SR 1VMR 5MR3VMR after challenge 2NR 1NR B.divergens : Cure rate after treatment (1 mg/kg)  105/111 Prophylaxis success rate (2mg/kg)  97.5% (682 animals, followed 4 to 8 months) (12/17 infected during the first month)
    18. 18. IMIZOL A UNIQUE PRODUCT FOR THE TREATMENT OF : - Babesiosis  cattle , horses, dogs - Anaplasmosis  cattle - Ehrlichiosis  dogs
    19. 19. IMIZOL - Babesiosis  horses: 2ml/100kg IM ( B. caballi ) ( B. equi = often 2 inj. at 48h. interval)  dogs: 0.25/10kg IM/SC 0.5ml/10kg = 4-6 weeks protection - Ehrlichiosis  dogs: 2 x 0.5 ml/10kg IM, [14d.]
    20. 20. IMIZOL - Sterilisation of babesiosis  horses: B. caballi = 2 x 2ml/100kg IM[72h.] B. equi = 4 x 4ml/100kg [72h.] (60% success, others = new course 6 weeks later)