College of Veterinary Medicine
Prevention,Treatment,andClearanceofAnaplasmosisUsing
Drugs
MikeApleyDVM,PhDDepartmentofClinicalSciences
KansasStateUniversityCollegeofVeterinaryMedicine
College of Veterinary Medicine
Prevention
College of Veterinary Medicine
Wethinkofitasprevention,but…
• Theactuallabelindicationis…– Forbeefandnon-lactatingdairycattle:asanaidinthecontrol ofactiveinfectionofanaplasmosiscausedbyAnaplasmamarginalesusceptibletochlortetracycline.
6,000g/tonChlortetracycline
College of Veterinary Medicine
Thismeans…
• 1500lb cow– 6000g/tonisequivalentto3gramsofchlortetracyclineperpoundofmineral
– A1500lb cowat2mg/lb perdaywouldneed3grams.– Therefore,a1500lb cowwouldneedtoeatapoundofmineraladaytoget2mgCTC/lb ofbodyweightperday.
– 4ouncesofmineralwouldgiveher¼ofapoundofmineral,whichwouldbe750mg.• 750mgdividedby1500lbs equals0.5mgCTC/lb ofbodyweightperday.
• Abull?
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In–feedControl
• Cattle(beef,under700pounds)– Amount:350milligramsperheadperday.– Indications:Forthecontrolofactiveinfectionofanaplasmosis caused
byAnaplasmamarginale susceptible tochlortetracycline.– Limitations:Awithdrawalperiodhasnotbeenestablished forthis
productinpreruminating calves.Donotuseincalves tobeprocessedforveal.
• Cattle(beef,over700pounds)– Amount:0.5milligramsperpoundofbodyweightperdayinfeed.– Indications:Forthecontrolofactiveinfectionofanaplasmosis caused
byAnaplasmamarginalesusceptible tochlortetracycline inbeefcattleover700pounds.
– Limitations:Nolimitationsareincluded intheCFRforthisspecieswhenusingthisproduct inthisamount.
College of Veterinary Medicine
Thereis…• Nolegalextra-labeluseinfeed.Theterm“feed”includes.– Feed– Mineral– Milkreplacer
• Practiceswhichwouldbeillegal– Usingasoybeanmeal/saltcarrierinconjunctionwith50g/lb chlortetracycline(aTypeAfeed)forAnaplasmosiscontrol.
– AddingtheTypeACTCtosupplementamineralwhichdoesnotresultinthelabeledconcentrationof6000g/tonortheproperformulation.
– FeedingaTypeBfeed(asupplement)asaTypeCfeed(thefinalfeedreadyforfeeding.
College of Veterinary Medicine
Treatment
College of Veterinary Medicine
HereintheU.S.ouronlyrealoptionis…
• Oxytetracyclineinjectable– Therearemultiplelabeledproducts
• OurbiggesttreatmentchallengeinadultcattleistoimpedethegrowthofAnaplasmamarginalewhilethereareenoughredbloodcellstoallowforrecovery.– Thisiswhyoldercattledomuchworsethancalves.
– Thecalvescanregenerate
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ClearingInfectedCattle
College of Veterinary Medicine
ClearingAnaplasmosisCarriers
• TherearenodrugslabeledforthispurposeintheUnitedStates– Thismeansthatanyuseinthefeedforthispurposeisillegal.
– InjectableandwaterregimensmaybeusedforthispurposewithintheconfinesoftheAnimalMedicinalDrugUseClarificationAct(AMDUCA)regulations.• ValidVCPR
College of Veterinary Medicine
Canweevenclearcattle?
• Coetzee,etal.2005ComparisonofthreeoxytetracyclineregimensforthetreatmentofpersistentAnaplasmamarginaleinfectionsinbeefcattle.VeterinaryParasitology127:61-73.
• CrossbredIowasteersweighing470to760lbs (160-230daysold)weresplitinto4groups.Allwereinoculatedwithanoxytetracycline-susceptible isolateofAnaplasmamarginalefromOklahoma.
College of Veterinary Medicine
Coetzee,etal.
• For62daysafterinitialinoculation,thesteersweremonitoredfor– Percentparasitizederythrocytes(PPE)– cELISA– Packedcellvolume
Whathappens incalves inoculatedwithAnaplasmamarginale
College of Veterinary Medicine
Coetzee,etal.
• Aftermeetingthecriteriaforbeingcarriers,thetreatmentswereadministered.
• Treatmentswere– Untreatedcontrols– 300mg/mloxytetracyclineat13.6mg/lb IM,once– 300mg/mloxytetracyclineat13.6mg/lb IM,twice,5daysapart
– 200mg/mloxytetracyclineat10mg/lb,IV,oncedailyfor5days.
College of Veterinary Medicine
Coetzee,etal.
• Noneofthestandardregimensforclearingcarriercattlewereeffective.
• Thiswasconfirmedby– DNAtesting(forA.marginaleDNA)– cELISA testing– Inoculationintosplenectomized calves60daysaftertreatment
College of Veterinary Medicine
Whydothetextbookssaywecan?
• Magonigle,etal.,(1975)usedthedailyIVtreatmentweusedtoclear11,2-3yearoldserologicallypositivecattle.– Theclearancewasconfirmedinsplenectomizedcalvesbyinoculatingthemwithbloodfromthetreatedcattle4-12monthspost-treatment.
• Roby,etal,(1978),gavetwoinjectionsof200mg/mloxytetracycline,9mg/lb,7daysapart.– Clearanceconfirmedbyinoculatingsplenectomized calves83daysaftertreatment.
College of Veterinary Medicine
WhatCoetzee,etal.,means
• Noneoftheseshort-terminjectableregimensinthisstudy,includingtheOIEstandardregimenforclearingcarriers(thedailyIVOTC),weresuccessfulinclearingthesedocumentedcarriers.
• Otherstudiesdid,asconfirmedwithinoculationofsplenectomized calves.
• Differencesdueto…– Ageofcarriers?– Timefromcarrierestablishmenttotreatment?– TheAnaplasmamarginaleisolate?
College of Veterinary Medicine
Canweevenclearcattle?
• Reinbold,etal.2010Theefficacyofthreechlortetracycline regimensinthetreatmentofpersistentAnaplasmamarginaleinfection.VetMicro145:69-75.
• AnaplasmamarginaleinfectedHolsteinsteers,confirmedbybothcELISA andRT-PCR.– Virginiaisolate
• Thesteersreceivedeither2,5,or10mgCTC/lb BWperdayfor80days– 5infected steersand1splenectomized controlsteerper
treatmentgroup– Also6infected steersandIsplenectomized steerinthecontrol
group
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Results• AllsteerswerenegativebyRT-PCRat46,46,and49daysforthe2,5,and10mg/lb groupsrespectively.
• ThecELISA resultsdidnotbecomenegativeuntil18,54,and18daysafterthe80dayfeedingperiodforthe2,5,and10mg/lb groupsrespectively.
• Chemosterilizationwasconfirmedbyinoculatingsplenectomized calveswithpooledbloodsamplescollectedfromchemosterilized steersat50dayspasttheendofthe80dayfeedingperiod.– Noneofthe3splenectomized calvesdevelopedanaplasmosis overa6weekmonitoringperiod.
College of Veterinary Medicine
Results
• Fivesteerswereselectedforareinfectionstudy.– AntibodiestotheVirginiaisolateweredetectedasearlyas10days.All5steerswerecELISA positiveby24dayspostinoculation.
– RT-PCRdetectionofinfectionoccurredby10daysin4steersandbyday17inthefifthsteer.
College of Veterinary Medicine
WhatReinbold,etal.,means
• WecanclearcattleinfectedwiththeVirginiaisolateofAnaplasmamarginalebyfeedingCTCat2,5,or10mg/lb bodyweightfor80days– TheywerenegativebyRT-PCRby50days.– Thenegativecontrolsinthestudywerelaterchemosterilizedbyasingleinjectionof300mg/mloxytetracyclinefollowedby2mg/lb BWCTCperdayfor30days.
• Oncecleared,cattlemaybereinfected.
College of Veterinary Medicine
Extrapolationwarning
• Thesecattlewereallgettingthefulldoseasevidencedbytheplasmaconcentrationmonitoring.– Sporadicandvariable(individualanimalintake)intakemaynotworkthesame(e.g.,mineral)
• ThiswasfortheVirginiaisolate– Itcouldbedifferentforotherisolates
• Couldthisworkthroughthewater?
College of Veterinary Medicine
Summary• Control?– Yes,buthowmuchisnecessaryconsideringvariationinintake?
• Treatment?– Yes,abalancebetweenRBCregenerativecapabilitiesandshuttingdowninfection
• Clearance?– Yeswecan,but,nolabelforthis– Consistency?
