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

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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.

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Thereis…• Nolegalextra-labeluseinfeed.Theterm“feed”includes.– Feed– Mineral– Milkreplacer

• Practiceswhichwouldbeillegal– Usingasoybeanmeal/saltcarrierinconjunctionwith50g/lb chlortetracycline(aTypeAfeed)forAnaplasmosiscontrol.

– AddingtheTypeACTCtosupplementamineralwhichdoesnotresultinthelabeledconcentrationof6000g/tonortheproperformulation.

– FeedingaTypeBfeed(asupplement)asaTypeCfeed(thefinalfeedreadyforfeeding.

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Treatment

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HereintheU.S.ouronlyrealoptionis…

• Oxytetracyclineinjectable– Therearemultiplelabeledproducts

• OurbiggesttreatmentchallengeinadultcattleistoimpedethegrowthofAnaplasmamarginalewhilethereareenoughredbloodcellstoallowforrecovery.– Thisiswhyoldercattledomuchworsethancalves.

– Thecalvescanregenerate

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ClearingInfectedCattle

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ClearingAnaplasmosisCarriers

• TherearenodrugslabeledforthispurposeintheUnitedStates– Thismeansthatanyuseinthefeedforthispurposeisillegal.

– InjectableandwaterregimensmaybeusedforthispurposewithintheconfinesoftheAnimalMedicinalDrugUseClarificationAct(AMDUCA)regulations.• ValidVCPR

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Canweevenclearcattle?

• Coetzee,etal.2005ComparisonofthreeoxytetracyclineregimensforthetreatmentofpersistentAnaplasmamarginaleinfectionsinbeefcattle.VeterinaryParasitology127:61-73.

• CrossbredIowasteersweighing470to760lbs (160-230daysold)weresplitinto4groups.Allwereinoculatedwithanoxytetracycline-susceptible isolateofAnaplasmamarginalefromOklahoma.

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Coetzee,etal.

• For62daysafterinitialinoculation,thesteersweremonitoredfor– Percentparasitizederythrocytes(PPE)– cELISA– Packedcellvolume

Whathappens incalves inoculatedwithAnaplasmamarginale

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Coetzee,etal.

• Aftermeetingthecriteriaforbeingcarriers,thetreatmentswereadministered.

• Treatmentswere– Untreatedcontrols– 300mg/mloxytetracyclineat13.6mg/lb IM,once– 300mg/mloxytetracyclineat13.6mg/lb IM,twice,5daysapart

– 200mg/mloxytetracyclineat10mg/lb,IV,oncedailyfor5days.

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Coetzee,etal.

• Noneofthestandardregimensforclearingcarriercattlewereeffective.

• Thiswasconfirmedby– DNAtesting(forA.marginaleDNA)– cELISA testing– Inoculationintosplenectomized calves60daysaftertreatment

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Whydothetextbookssaywecan?

• Magonigle,etal.,(1975)usedthedailyIVtreatmentweusedtoclear11,2-3yearoldserologicallypositivecattle.– Theclearancewasconfirmedinsplenectomizedcalvesbyinoculatingthemwithbloodfromthetreatedcattle4-12monthspost-treatment.

• Roby,etal,(1978),gavetwoinjectionsof200mg/mloxytetracycline,9mg/lb,7daysapart.– Clearanceconfirmedbyinoculatingsplenectomized calves83daysaftertreatment.

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WhatCoetzee,etal.,means

• Noneoftheseshort-terminjectableregimensinthisstudy,includingtheOIEstandardregimenforclearingcarriers(thedailyIVOTC),weresuccessfulinclearingthesedocumentedcarriers.

• Otherstudiesdid,asconfirmedwithinoculationofsplenectomized calves.

• Differencesdueto…– Ageofcarriers?– Timefromcarrierestablishmenttotreatment?– TheAnaplasmamarginaleisolate?

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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.

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Results

• Fivesteerswereselectedforareinfectionstudy.– AntibodiestotheVirginiaisolateweredetectedasearlyas10days.All5steerswerecELISA positiveby24dayspostinoculation.

– RT-PCRdetectionofinfectionoccurredby10daysin4steersandbyday17inthefifthsteer.

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WhatReinbold,etal.,means

• WecanclearcattleinfectedwiththeVirginiaisolateofAnaplasmamarginalebyfeedingCTCat2,5,or10mg/lb bodyweightfor80days– TheywerenegativebyRT-PCRby50days.– Thenegativecontrolsinthestudywerelaterchemosterilizedbyasingleinjectionof300mg/mloxytetracyclinefollowedby2mg/lb BWCTCperdayfor30days.

• Oncecleared,cattlemaybereinfected.

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Extrapolationwarning

• Thesecattlewereallgettingthefulldoseasevidencedbytheplasmaconcentrationmonitoring.– Sporadicandvariable(individualanimalintake)intakemaynotworkthesame(e.g.,mineral)

• ThiswasfortheVirginiaisolate– Itcouldbedifferentforotherisolates

• Couldthisworkthroughthewater?

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Summary• Control?– Yes,buthowmuchisnecessaryconsideringvariationinintake?

• Treatment?– Yes,abalancebetweenRBCregenerativecapabilitiesandshuttingdowninfection

• Clearance?– Yeswecan,but,nolabelforthis– Consistency?