High Prevalence of Drug Resistance in Animal Trypanosomes without a History of Drug Exposure 英文参考文献.docVIP

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High Prevalence of Drug Resistance in Animal Trypanosomes without a History of Drug Exposure 英文参考文献.doc

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High Prevalence of Drug Resistance in Animal Trypanosomes without a History of Drug Exposure 英文参考文献

HighPrevalenceofDrugResistanceinAnimal TrypanosomeswithoutaHistoryofDrugExposure SimbarasheChitanga1,2,TanguyMarcotty1,3,BonifaceNamangala2,PeterVandenBossche1,3{,JanVan DenAbbeele1,VincentDelespaux1* 1InstituteofTropicalMedicineAntwerp,Antwerp,Belgium,2DepartmentofParaclinicalStudies,SchoolofVeterinaryMedicine,UniversityofZambia,Lusaka,Zambia, 3DepartmentofVeterinaryTropicalDiseases,UniversityofPretoria,Onderstepoort,SouthAfrica Abstract Background: Trypanosomosis caused by Trypanosoma congolense is a major constraint to animal health in sub-Saharan Africa.Unfortunately,thetreatmentofthediseaseisimpairedbythespreadofdrugresistance.Resistancetodiminazene aceturate(DA)inT.congolenseislinkedtoamutationmodifyingthefunctioningofaP2-typepurine-transporterresponsible fortheuptakeofthedrug.Ourobjectivewastoverifyifthemutationwaslinkedornottodrugpressure. Methodology/PrincipalFindings:Thirty-fourT.congolenseisolatessampledfromtsetseorwildlifewerescreenedforthe DA-resistancelinkedmutationusingDpnII-PCR-RFLP.Theresultsshowed1sensitive,12resistantand21mixedDpnII-PCR- RFLPprofiles.Thissuggeststhatthemutationispresentonatleastonealleleofeachofthe33isolates.Fortwelveofthe isolates,astandardscreeningmethodinmicewasusedby(i)microscopicexamination,(ii)trypanosome-specific18S-PCR after2monthsofobservationand(iii)weeklytrypanosome-specific18S-PCRfor8weeks.Theresultsshowedthatallmice remainedmicroscopicallytrypanosome-positiveaftertreatmentwith5mg/kgDA.With10and20mg/kg,8.3%(n=72)and 0%(n=72)ofthemicebecameparasitologicallypositiveaftertreatment.However,intheselattergroupsthetrypanosome- specific 18S-PCR indicated a higher degree of trypanosome-positivity, i.e., with a unique test, 51.4% (n=72) and 38.9% (n=72)andwiththeweeklytests79.2%(n=24)and66.7%(n=24)for10and20mg/kgrespectively. Conclusion/Significance: The widespread presence of the DA-resistance linked mutation in T. congolense isolated from wildlife suggests that this mutation is favourable to parasite survival and/or its diss