variabilityandpotentiallyreducesthenumberofanimalsrequiredforstudy[31].
FuturegeneticstudiesusinganimalmodelsThepost-genomiceraofA.fumigatusisextremelyexcitingforthepotentialidentificationofnewdiag-nosticandtherapeutictargetsaswellasfornewinsightsintothepathogenesisandvirulenceoftheorganism.PreliminarystudiesbyZaasetal.[29,32]illustratethepotentialofthesestudies.Theseinvesti-gatorsusedanaerosolchallengeofavarietyofinbredmicetoassesstheroleofhostgeneticbackgroundonsusceptibilitytoAspergillus[32].Interestingly,ingcom-putationalgenetics,achromosomalregionwasthenidentifiedthatcorrelatedwithresistancephenotype.Candidategeneswereidentifiedfromthoseregionandstudiesarecurrentlyongoingtorevealthepotentialsignificanceofthosefindings.Theseresultsdemon-stratethepotentialofcarefullydesignedanimalmodelstoplayanimportantroleinthefutureevaluationintheexperimentalassessmentofinvasivepulmonaryasper-gillosis.
Conclusion
AnimalmodelshavebeenusefulforassessingthepathogenesisandvirulenceofAspergillusandhavesignificantlyaidedthedevelopmentofnewdiagnosticandtherapeuticmodalities.Futuremodelsofexperi-mentalaspergillosisareaimedatassistingintheidentificationanddevelopmentofnewdiagnosticandtherapeutictargetsthatmayresultfromsequencingoftheAspergillusgenome.Thesewillbeofmajorbenefittostudiesaimedultimatelyatimprovingthediagnosisandtreatmentofthisoftenlethalinfection.Acknowledgements
ThisworkhasbeensupportedwithFederalfundsfromtheNationalInstituteofAllergyandInfectiousDis-eases,NationalInstitutesofHealth,underContractNo.N01-AI-30041.
References
1AndrioleVT,MiniterP,GeorgeD,etal.Animalmodels:Usefulnessforstudiesoffungalpathogenesisanddrugef cacyinaspergillosis.ClinInfectDis1992;14(Suppl1):S134ÁS138.2PattersonTF,MiniterP,PattersonJE,etal.Aspergillusantigendetectioninthediagnosisofinvasiveaspergilosis.JInfectDis1995;171:1553Á1558.3GraybillJR.Theroleofmurinemodelsinthedevelopmentofantifungaltherapyforsystemicmycoses.DrugResistUpdate2000;3:364Á383.4NajvarLK,CacciapuotiA,HernandezS,etal.ActivityofposaconazolecombinedwithamphotericinBagainstAspergillus avusinfectioninmice:comparativestudiesintwolaboratories.AntimicrobAgentsChemother2004;48:758Á764.5PattersonT,MiniterP,RyanJ,AndrioleV.EffectofImmuno-suppressionandamphotericinBonaspergillusantigenemiainanexperimentalmodel.JInfectDis1988;158:415Á422.6SabettaJ,MiniterP,AndrioleV.Thediagnosisofinvasiveaspergillosisbyanenzyme-linkedimmunosorbentassayforcirculatingantigen.JInfecDis1985;152:946Á953.7PattersonTF,GeorgeD,IngersollR,etal.Ef cacyofSCH39304intreatmentofexperimentalinvasiveaspergillosis.AntimicrobAgentsChemother1991;35:1985Á1988.8PattersonTF,FothergillAW,RinaldiMG.Ef cacyofitracona-zolesolutioninarabbitmodelofinvasiveaspergillosis.Anti-microbAgentsChemother1993;37:2307Á2310.9PattersonTF,GeorgeD,MiniterP,AndrioleVT.Saperconazoletherapyinarabbitmodelofinvasiveaspergillosis.AntimicrobAgentsChemother1992;36:2681Á2685.10PattersonTF,MiniterP,DijkstraJ,etal.Treatmentofexperi-mentalinvasiveaspergillosiswithnovelamphotericinB/choles-trol-sulfatecomplexes.JInfectDis1989;159:717Á721.11KirkpatrickWR,McAteeRK,FothergillAW,etal.Ef cacyofvoriconazoleinaguineapigmodelofdisseminatedinvasiveaspergillosis.AntimicrobAgentsChemother2000;44:2865Á2868.12PetraitisV,PetraitieneR,SarafandiAA,binationtherapyintreatmentofexperimentalpulmonaryaspergillosis:synergisticinteractionbetweenanantifungaltriazoleandanechinocandin.JInfectDis2003;187:1834Á1843.13PetraitieneR,PetraitisV,GrollAH,etal.Antifungalef cacyofcaspofungin(MK-0991)inexperimentalpulmonaryaspergillosisinpersistentlyneutropenicrabbits:Pharmacokinetics,drugdis-position,andrelationshiptogalactomannanantigenemia.Anti-microbAgentsChemother2002;46:12Á23.14SteinbachWJ,BenjaminDK,Jr,TrasiSA,etal.Valueofaninhalationalmodelofinvasiveaspergillosis.MedMycol2004;42:417Á425.15DixonDM,PolakA,WalshTJ.Fungusdose-dependentprimarypulmonaryaspergillosisinimmunosuppressedmice.InfectImmun1989;57:1452Á1456.16AllendeMC,LeeJW,FrancisP,etal.Dose-dependentantifungalactivityandnephrotoxicityofamphotericinBcolloidaldispersioninexperimentalpulmonaryaspergillosis.AntimicrobAgentsChe-mother1994;38:518Á522.17WarnPA,MorrisseyG,MorrisseyJ,DenningDW.Activityofmicafungin(FK463)againstanitraconazole-resistantstrainofAspergillusfumigatusandastrainofAspergillusterreusdemon-stratinginvivoresistancetoamphotericinB.JAntimicrobChemother2003;51:913Á919.18SteinbachWJ,PerfectJR.Newerantifungaltherapyforemergingfungalpathogens.IntJInfectDis2003;7:5Á20.19PattersonTF,KirkpatrickWR,WhiteM,etal.Invasiveaspergillosis.Diseasespectrum,treatmentpractices,andout-comes.I3AspergillusStudyGroup.Medicine(Baltimore)2000;79:250Á260.20WaldA,LeisenringW,vanBurikJ-A,BowdenRA.EpidemiologyofAspergillusinfectionsinalargecohortofpatientsundergoingbonemarrowtransplantation.JInfectDis1997;175:1459Á1466.21MartyFM,LeeSJ,FaheyMM,etal.In iximabuseinpatientswithseveregraft-versus-hostdiseaseandotheremergingrisk
–2005ISHAM,MedicalMycology,43,S115ÁS119
factorsofnon-Candidainvasivefungalinfectionsinallogeneichematopoieticstemcelltransplantrecipients:acohortstudy.Blood2003;102:2768Á2776.
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