Charactehzed by the presence ofPrPTeS typelin western
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Charactehzed by the presence ofPrPTeS typelin western
/∴「′▲′r/∫∂/どJd//βJOJog血J∫jイ「2β8引2ヱ7−2jノ rtc】し1’J1・ こ】】、已、iくご(C_「1)〕、∴111l一、三川こ1】ユiInsoI¶nia and 〔je】1Jl「Llし⊥S血■Scゝ1L川ke」トn山川−1C・ (j[ト、こ:しL、く=†うい=1S叩〔)「記iご,ご、、=〔こ:C∴ntr口呂亡nicincluding thご「T ハトJC=1ほd、、=こ∫1上しハ‖1e叩「)=岩:!nrl¶enCePha一 明1L ′!てじ・kて∴∩し1S tl三C−−1=ご、;「(−・H豆右三 rOr thlS disease \\こ1ゝこコごし・ 「■1川■’bl▼J−Fし1…=ヱ■IJr〔1さa gI〉′COprOtein 山1し二 †hrドrCSC−1tい1て1こ再二こln;?呂】⊂a】form(PrPC) \、′】11し∴hぺ†〕Lパl−コ‥恒】いS3C、1【lイ∴に)=−rP、〔)Tlle【ransition simofIaC】呈0血1;=〔’:ミこlh)封一恒re‡川ゝいしTP −amroFnOC−Sn己「〔l こビ乙1.けSlr1 しi C\ミ.12Sし\】 rご∴)ーニ「\k∵†l、(c 【101㍉1こ・、二Cこし、L、、′已LT−b血号「し、ししl!−11汀】rゝLコ]PrPCprlmarlly 〇ローlT.L、二1ご1Lゝ、しJrりし▲三JlfJrヱ)\⊂ (∴1=iJハ0= βshcetsinits 山rcい〔1}1し・こ5二し−!1jさ汀l」C【tl:C〔J:「フこ〕】くじ厄r∴Ct亡hzcd by jn− 汀ユ〔ご「じ【、∴・ミし「し∴:11し≡∴こ】nnロr ユ1こLl−;1しつ【11汀OtCin whichis parこ=⊥Z・、iし…二「しさ⊥Stani(Prf)、:C:cLハこg已り「PrP5Cbypro一 こC三[・−Cl∴、し∴=「==+・、、0【)′F)已川iノーノぐ∴・−1じr“こS【cmbloいype ll〔)!−」二,l・Cニし1て∴rl呂t(1r)、1Ⅰご†−1C:∴ゝS】nこat:0!1[5], S∴:しt.∴、〔∴1∵㍉二じ‥】illtl‘tこ】UtlCJ7 Ll;cctltコnli11ユtionfrombio− pllニールゝし川・▲し」1 jしこしゝしVI−1〔ナ∴・J亡 四Pご汀CJFroJ¶human Cdh【しユ\ぐトごe;1Cし=山忙【CJしLトニーうメrl、川(111】tr;lいOn[6−8】.This Jlan(、1▲−「∴− ∫11し1111l、し=1aSl)e…〔什二こ=∵C(T−1−‘川)・Vimses.Al・ bし】rllTl>、」1t 。こ1:じて、、r rldn(〕Illrr∴、1【1!1こ15b已じrlCOnductcd on SCrai、e†L 〉nド「tltCい1【ワ] Tさc r Flいヾい「血s rese己[こJll、巨一封uJ)・抽e efflCaCy Of 【1こ川〔、ミ†しr、 rlぐ)n⊂J[)Ⅰ)rP、こirl〔1【こiごここn川tr山uce thlS me【hod l‖t(−こr−じ=〕皿」1⊥lこtur=1三PIOCCゝSぐ−!こ=忙Ⅰ’‘lrじ==cl】¶1¶unOglob− 1L】t】∩㌧nlし∴ 1∴\=1T)Ilり⊂】obし11川C 丁一)=1「 E】りじし nnll:.rl rl\い、(、しJ tl〔Hllしし C「)」i、L【1し二 >Ⅰい「111rl こ:〔〉Tlヽ tlTし ・し、、L川じちcqし:川Cn=−∴一「∴一=1ユn【hリーーOC〉,leimuno− 1鳥】亡CいCmlr†1」佃叫1;、「亡ゞり、C叩Cn【ac【1ngmainly lh!11血、⊂\ノほS一了【re川ご▼r7CS111nSしぃFthel¶01ecule5 −「ごこ▲1こi〔三corl、−ごC】】こl−い’し11り吊=「川ggrartrqeC− トcel上「し、こCi〕l(甘口Fl(1〔:「〕3、トiL.1ch∬∴molecuIes, r〕、じこ卜re⊂じi㍉い1S,ご(トlこご−ハ∵==川m〔)lecuI巳SOradhe− −lご、1(二Lj二.CD5、コn(1⊂I)こti/iLhetherapcu【icindica− い=Oul!1こS ・こ1 、、:・竹re\、1nn!(汀:F\▼1−爪∩‘PrCヽ7ention and てJ∴∵∴∴∴∵()ーど「ユ!:「ご1e∴」〔)「1 ・tLニ1こ【 〕こL;1】、こ三C r▲:1じtllこa D∴∴=∴=∴∵こ∵けごじ㌧、くり†Ⅰ)LⅢL了∴1〉 rlいいlleC〔トニ川Canti−human th=1「−い【J、し亡;1【−ユrh〕= ‥、いゝこ▲し1dcJFor the viral IntheLymPhoBlobu】ine⑬manufactunngprocess.human thyTn∝yteS,membrane red blood ce11s and p)acenta are USed.These human elements represent a vi爪ualpotential sourceofcontaminationoFLymphoglobu]ine⑬・ 2.2・〃〟爪dれ∫OMrCビげグロJ力∂JクgJc(7/prJ鋤PrOJeJ乃 AfterthehistoIoglCal,invnunohistochemicalandbiochem− icalanaIysesofpostTrnOrtemhumanbrains,OneCaSeOfde負− nite CJD,andone non−CJDwerechosen.The anatomic site chosen was the frontalcortex.The CJD case selected was Charactehzed by the presence ofPrPTeS typelin western blotanalysISaCCOrdingtoParchi’sclassihcationandbysynapT ticdepositsorPrP5Cwithanimmunohistochemicaltechnique・ Thesamehuman cortex wasused assourceofPrPSCforthe rc托renc8SCaIeandforthenano別けationsamples. 2.J.Jd叩Jgク′甲drβrわ〃 2.j・ノ.仇仰〃〃か〃∫〃力∂椚∂gビn〃Jg FrontalcortexofCJDandnon・CJDcases was spikedin PBSbufEer,l:10a【finaldilutjon.Thesehomogenateswereh]・ teredsuccessivelywithneedlesofO・6mmandO・5mmdiam− eterin order to obtain homogenous prepaTation・Af[cr ∝ntd餌g8tlOnatlOOOgねr5min,SupematantSW8陀appli8d ThisrcferencescalewaspreparedwithserleSOfdilutionsof CJDbrainhomogenateinLymphoglobulineQ)froml=10・tO lこ20,000.This reference scale was based on the(echniquc 2.j.j.∧加q仲「(沼0〃∫〃′7pJg∫ ThesesampleswereprepaTedusingCJDbrainhomogenate dilutionsinLymphoglobulinc⑩・ThreediffereJltSampleswere produced;SarnPlesatahighPrPiCdilution(1:500),Samplesat amoderatePrPSCdilution(1:100)ar)dsamplesatalowPrPSC dilution(1:10),Eachdilut10nWaSPreParedforth∫eeSaJnples, on¢nOn−nanOfilt∫ated(COntrOl)弧d twonano別けated,meSe SamPleswer¢preparedasarekrenc¢SCalewithanadapt血on ofthemethodusedbyLceetaI.【11]. 3bars.ThesarnplesuJlderwentnanofiItrationinthefollowlng pI’C、′侶1いrl,:しミtcコて⊂−Ojこ≡川)】5n(ユビSikdeya 1ィ\∵叩Llご)】川e箪】Sここ 川こ1叫r‖1口C〉rしCCqし1】nCimmuno一 Crea、し、r m=叩】▲1Tllnt−nn,lnさ1し二nlこItt)1〔)g),、L)rmPhog】obu− lln㌔1ゝ‘・上、し11.山†tlr【rcaこ】−−C【1t()!申し!Stl亡、1n亡−−1iilandinthe trc‘山l、t,r ;、、:ご川】tircゝjくT.1rlてどJIJ=㌧でl>しJS210S【し1isease. conけOliamPl∈a【1= H・−L〉mPho如b山・n亡丑.×ニ.r い1 JCじし∃】ndupl C拙 droxide(2M)rorlhbe抽eeneaCl川ご1∩川11trlこionoFdlrrerenし PrPSCdilutionsamp】es. 2.J,PrPrど∫dビJビC〃β/王 .じ Thewes【en−blottechniquel仏′aSUS己JIodeし亡CtPrPTC$arlC− cclI(5JP≡し:」、皿ま川1日UF−C‖1山し・鳥jOrl・t】Sai)PrOVed For【he / CJDsamplea【a】ow汁Pd‖皿0∩(1:−0)i止ym.−トーし一己」obJい−】亡恩=抑d(e)rlC占∴いこ us¢dbyLeee【al.【10,11】・ 芸l〔−h吊1 1rlしまし:Cご六i=1Ⅰて1uIlOS叩;1Ⅰ・Ciゝio=辻S a rCSu】t ofT− 2 (c)CJDs肌Plea(am(血ratcPrP“dlluい0∩り一 冊1一叩Ph吋ob油i−㌔十⊥ The nano汽hra【ion materlalwas trじ.itCJ\、rltllSOdium】1ニーー 2.j.2.尺(押re几Ce∫C♂Jg Smalトsizcd(membranediameter:47mm)PallO帥占rs(hy・ drophilic Polyvinyli(kne fhoddeln膵!OpOTOuS membrane) withmeanpor¢SizesforPall⑧DVDofaboutO・1岬l,Pa11◎ DV50ofabou【50nmandPalld)DV200fabout20nmwere usedsuccessivelyinthenanoMtTationprocess・nealtradon mode was conductd at a constant membraれそp一合SSure Of 三,1Ⅰ■Lc【・∴」=1=l11亡抽り(1、 g】ob山】neOこ(b)CJDsmp−巳a【ah】⊆−一打㌣㍉高山「こ∴∴〕1日1一〉叩hD昌lob吊=・ご・ tonano別けationprocess・ 2.4.FJJJr(山0〃 ヽ∴= Fig.1Nano刷皿しionproc亡SS(a)ドega【】V亡COnlrD∼・呵)ぐdtl:】OLnL\nlPllく、 order:negatiYeCOntfOl,CJDsamplesatahighPrPSCdilution (1:500).CmsamplesatamoderaはPrP粥dilu血n(1:100), CJDsamplesatalowPrPSCdilutlOn(1:10)andnegatiYeCOn− け0】(Fig.1). PrOteinase Ktrealment[12]・Thean【卜PIIJn T)rOtein antlboJ〉′ revea】ed three stnps of a molecuiar\、JC上ght bctween30anし! ter nanofiltra【ion. Therererencescal巳SdmPlesandsユ【叩・已Sr(号■na∫0仙ruti州 WerePrOduced and dcve】op巳d b)′thい、′CStこ「【1blo【tcchniqし亡 under the same condi【ions andin theくL.Ⅰ;1こt:I11e. し, て、Cし)し l ユユkDa(Fig・ユ)co汀巳SpOndlれgtOlheb宣拘、coS〉〉latcd,mOnOgり− COSy】atedandung】ycos〉・IatedFoms・T」〇∴、PI:〆⊂5wasrcvcalじ(j by chemilumincscenceThis techniclし一C“′LIS uSed to detcc† PrP‘モSinrererencescユIcsamp】esand=1Sムー叩烏bcroreandこ⊥ト ご\ ト‘_\、、\一 1 ⊂山∴1、、・1,\jrJしll川ご】しこし【亡 tlし1: し11ト亡tユiご5、UCllaS Creutz− し=こ\∵じ、 〔 T)・ \、、r)()し )、r▲)ヽ 1。一 】 、 Iいぃ∴∴1∵\=∵、CJo♪ごhrJ‥、、d tn rlごL汀し〕】02】C8】disorders ) )し 2.∂.伽Jビ′抑厄JJ釧イre血紬0〃♪cro′ヾ t lし ThereductlOnfacしOr5defined asLhc rじ山ccし!tlterVerSUStご〕ご rea】titerprcsentinthcsplkedsamplい\CrCJc一己n†11nedbyco=1− pamngthePrFCSslgnaIorsa汀】ple5bじrOrヱユ・1(1ユrtOrnanOnitr山〔【▲ W山=hePrP「亡旦signaloFreferencescユ】c‘1iこじrtとuscompads〔J= WedeterminedareductjonFactor(log):10rCこ1Cさ1SilmPZe. 3.Res111ts Tberererence5CaIerangcsrroml∴り∴j・二○,000diItj再′Ⅰ−J OfCJDbrainhomogenales FromthelH):0:言〔)00dilし】tio肛 L・:・C 〉 ⊥丁用ぐ/IO/∼J♂J./βl∂わg血J∫jイr2α)dJ227−2J/ 1一丁(−=し’SくじS[14〕E汀cc両い−−Ctl一口Js∴1Cl朕icForcxampleexpo・ ゝしユl亡し∩】1Is口dlunlll)て1「〔−Xlde(宣し1「】nさdし1こOChvlnga【12lOC. plaqu鮎Orr∝aldeposltSOfPげ虻stillremaina托erhomogeniz− 1ngthecerebralcortexandth¢hypothcsiswasmadethatthis Ttlここkind oF−11CtllOJusingchc=−=CaIngc【11s(sodiumhydrox− kindofPrPSCaggregationcouldbetheresultofabiasinthe j〔je,州0「川已aIhl帥COnC亡ntraし10【1S)帥d ph〉・Sicaltreatment methodoJogy,Forthisreason,PrPreStypelassociatedwith b、一・し1tOC】帥1F一三】s、’Cr〉,(irRS†ican(11Sこ1realprob】emtoinac− SynaPtic de匹SltS With animmunohistochemicalte{hnique い′ごlこPrPくCLnblOPna[maCeUtica】productswllhoutmodifying waschoseninordertotesttheLymphoglobuline◎nanohltra− 山cl:thcl‘こ1PじUtにP「OPe「lics・Tl−CrCdしICtionofan〉rhskassoci・ tionprocessun血rworsしCOnditionstot8Stthe仙ers.In山is 11しCし:、、′1しilユPllarm;▲CCUいCa】Ⅰ)rO山c川川be(まependen【onthe study,Lymphog】obuline⑳wasspikedwithbrainhomogenate Ph巨∃cn3rc【l−OValo(1nfcct)VCma加1aldur=一gPrOductmanu− atdifferentdilutions(1:10,l:100,qndl:500),ThesePrPSCdi− 「こ1C乙汀Cト1ユF−)一Iccllniques ror pI‘15maぺien、・e〔5products,SuCh 2−SCtlanロ】行ac【10∩エIion,Jcplhfう1traいロnandchromatographic P了ロしCSS已S,t「ayCO爪「ibし】te【DaS甲−】ficantpa爪【ionlngOrPnOn ilrr〕しl−1し10,15−18】人】tll口ugllCarlyapplicaこionsoFnano触ra− 110「L tこ1r言eled\’iralrc−¶0、′al[7鼠191,nじ“′da【aSuggeSt【hatit mコニーbea叩eCほcremova!s)−StC=1rOrPnOnPrOteinsaswell. rlt】一∵∴=1TST三pathof:enSind=utじdbrこ】n homogenatewerere・ rJUrlこd【n bc re∫−10、′ed b)′Jゝ1】‖リー0re SCreC=−t)・Pe O.025ドm ■T已】’t汀a−−仁 一iltcr e−叩】0〉Cd dし汀1ngl)rOducしioIlOr grOWth IlOrr−(1nC「2()〕rTo“rc、Cr、口nけa5J−−州qし1ar一旬OFdi】utedbrain 1utions can be correl8ted with World Health Organiz&tion (WHO)cla5Si鮎ationororganinたctivity:thelowPrPSedilu一 也onco汀eSpOndingtol:10(brainandspinalcord),mOder叫 PrPSCdilutioncorrespondingtol:100(SPlecn,tOnSil,lymph node,intestine,placenta…)and high PrP父diludon co汀C・ SpOnding tol:500(brain stem,叫mus,liver,p弧Cr組S, 1ungs…). TIleCOmpaポsonofthe鑓爪P】esbefore∽da鮎rnano釦加一 tionshowedarcductionfactorbetwcen3.3andl.6lollnCOm− pad鍾n With the r曲帽nCe SCal¢.me reductioれねctor of トac⑩vonhP3−【ar再心甘厄=せしor山Sa〕idI】しOCビミ⊥1e〇−、川(lF SamplesatalowPrP‘dilution(1:10)wasbetween3and こri(!:−eS“’i止r11ean POrC Sizcs rr(=1175to10nm were used 3・3Iog・Thisdilutioncouldcorrespondtoabrainorasplnal tollite[brnin hozllOgennこe[rorllmiこe‖げec:ed with human cordPrP父concentration(WHO).The reductionfactorsfor ′rSl三[二けドr=nFc(二tiヽ′1ty\VaS(icしじC把din th亡35nm別けate. a v引γhigh PrP火comcentn山on obtaindillus加te a v引γ −11‡1J!−Llt】1(〕さじニ1】C aさCnlⅥ′aS CSll‖1ニ1こCd しO bc approximately goodd瀧cacyorthcnano別けadonprocess. 」in…1inゞ;こe】lo“′C、′cr.SOll−じ「ビSゝ血こ!irl「CC:ivl【y wasround InsampI鮎atamOdcmtemPC鵬Iution(1:100)andsamples 汗1什e】On=15hratいVhcnl%5arkos〉1“aSaddedtotheho− atahighPrP‘Cdi)ution(l:500).thePrPre‘stripswerenotde− Ⅰ¶口ざCna【c「ユニ].Rcc亡n=y,rCnlO、・幻(汗5CraPie agent ME7, tected afternano別汀atiop,山ereducdon factor was s扇cuy こl【11氾Se adaptc〔】sTraln OF scrこ叩jC USC(1as a modelねr the greaterthan2・3andl.61og,reSpeCtively.Thel:100dilution 了iSEnrvCJD agentsbyusing【1a110R】汀a【ionora29らalbumin COuldco汀eSpOndataspI伐れOrtOnSilorlymphnodeorintcs− ゝ0Il):血1SPiked\VithtLbralnhonlOgenalc[23].Thealbuminre− tineorpIacen【aPげ屁conce州∫adon(WHO)and血el:500di・ Cn、叩\\■aSO、Cr90%・Exte=tOrrCnlm′a】“′aSin軋enccdbyth¢ 代目cr L)′PC an(1し)〉・Lhc ad(机10n Oran抑ionic detergen【(Sar− kいゝ〉1)Loしhe[)rOtCin soIu【ion ^n】nfeclivIt〉′0[4,93and l.(−11い昌仙′nS re1110\’じd uslng a35−∩【11帥er“ithout andwi山 〔1cLcrgc咄rCSP亡Ctj\′じ1y・ト′lorcn、′Cr,a rCduc【ion orinfectivlty lutioncouldcorrespondtoabrainstemorthyTnuSOrliveror PanCreaSOrlungsPrPSCconccntration(WHO),Inconclusion, thedataobtain¢donbo血血郎手打PCdiludons訂e¢nCOuraging be00uSモ.a魚ernano別けation,加計P−signal、was not de− t∝ted,akhough山ey訂eOn】yindicativew仙probablyuれder− Or>5,S7ムー1(14,ユ1Iog“′aS OblairlCd us王ng a15−nm別㍑rin estimated reductjon factors.Fina11y.the reduction factor tナー〇しbsc−1Cea=Jprcscnceord巳【crぎ巳nl,rCSPCC【ivcly.Noresid− Obtainedis3・3logandseemtodemonsけatethee錦cacyof し】こ1】11rCCtl\’1〔〉’≠′aS〔まcしec【巳djna【1〉ノril汀aほ“′he■−USlng15nmor thenano負1tTationproccssonhumanCJDPrPSCwithagood =1く1ごrPし)rnSlty仙crs・Stし−(1】CS厄\ノCSl−Cハ、11こ川eFRcacyof35− proteinrecoYeり′. 15【1rこ1鋸tcrs川aCh心‘1ngSOmCrCnlO、alorprlOnSrrOmbioIog− RemoYalmaybモbasedon8SievlngmeCh肌ismordu¢tO adsorptlOnOnthemembranc・Thepotentialtousenano別tra・ 〔三aこLl、n肘10ugh cncouraglng,Should bc ana】yzed moreaccu− tionasadedicatedstepforpnonrernoYalmayhveasignは− rユこC:.Y・山ctothctc【1JcncyoFpt’10【1SPikcstoaggregateunder Can(impactonth¢SafbtyofbiopharmaceutlCaIproductsand 血ご叩erinlC−1talcondItions uscd anJ“・it】−hしエman PnOnprO− rccombinantproteins,WhenproductioninvoIvcstheuseofhu・ te‖1hccaし1SC111isre†110、’alcouldbcdcp亡Ilden10nthe“st∫血” manoranimaldedv由mat¢血Is.ormedicinalp一山uctsdか く11pTl011P10tCln▼ rived from bovine sources【25.26].This technique has the 1Cnj、Olし出Or15仏・出1:hc bes【rcnlO\′aI仏′1Lh n15−nm filteェThe IJ:OUrStし1dy.、、′い㌧・an【edtosこtldytI】亡C汀cac)′Ofnano別けa− abilitytoextendtheconccptofsterili(yofbioIogjcalproducts tionlnhし1manPrPく⊂lnabiopharmaccu:icalpTOduct(Lympho− 加mbacteriato,atleast,SOmCViruses.Ourresultssuggest か両軸㌔).\\′eusじdI−u−−−d−1PrP㌧亡r−○∫−1CJDpa【1en【sasthe じOnl∴皿廿ほn【.1’†=S COntan−】naしion〔Or−diLユ0∩、、raSimponantto that nanofiltration could be also of interest for the removal Ofhumanpath01oglCalprlOnprOteins, rednuqihCeミnoiこlr仙01tan㊤cilubO吋hpmyLこ出二i(uts COn〔∴い0nS aS C】osc as possibk10a POSSibIc con【aminadon Referenct!5 b),l−mlan CCl】sused rorthcprcparat】0n O川1isproducLT鵬 CXにrうt Or rCロー0、・al−nay beln仙cnced byしhe aggregation, 11】PmsincrSB.NovG】prol∈inac印闇p鮎ticI那CauS亡沈mpie・Scienc胃1982; 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Tabl亡500nOr∼(ハ・12引or】3b:l【bl〔)Odco・¶POn亡‖じS岬一に=ハ「、;「−tCr⊂しt。イ(=一 Tra爪irUi10n Cコち⊂ N〔JDSUdatabaseasYCJDcases.Thesear亡th亡donoTSOfth亡 Tw。(】inicalcase50FtransFusion−tranSmittedvCJDr亡femd topreviously(se⊂VCJDcaseswithhistoryoFdonation)・ date F ′】′、J′ ー bhod〔OmpOn亡nblr抑5ト∫∼ぐd 199ユ 1 「1umb〔rOrJonor50「lコ加ic Jご〔・ コ8 F.r r p F3こけVr(〔ゝ伸C甘く】 L。,人 l,†、(J scmcaseswithhlstoryof加nshsion 六oJr、r120∴‘〇 rl−r「、r・1L」∫10ぢ帝1 Fi吋【WOCaSe50Fs⊂JD眈n【伽db亡tWでen1980andゴ∞O ∧b∩、rnん5(′一仁 werereportedtohavere⊂eivedabloodtrans毎sionlOFwhich 1し一1坤、○じJrn 什ナ 28re⊂亡ived a tran血siona触r1980・Tran5Fu5ion re⊂Ord5 「「(ここ畑= qJ ● d5∫二言1亡dつn口汚。「㍑−」てJ】「【亡1、㍍=捏宥1ドりこぐ、: ■1こ、 QJ ﹁J d亡athnotr由t亡dtoUD.Twenりdono円arenOtknownto J「、■.ご〔いlr⊂(ト。。て▼−1−亡∵り し1〔与rT〇∫rr1「’い′二 ■て州己:−1昌kob nJ つ▲ 7〕Tハこ 8 /、「【ト‘==)nlし、1 ﹁▲ wereFoundforsevensCJDcas亡StranSfusedbetwecn1984 and1997.DonoTd亡taiLswere found For24donors who donatedcomponentstran血5edt8thescs亡V亡nSCJDcascS・ oneofth⊂S亡donorsisknowntohav亡diedlWithacaus亡OF Fっ〔[∩▼:( 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Thc polymorphism was also idenlifledin 2rぐC岬1entS Of blood from a preclinic封BSE− HE誉しJtS Cha11engeddonoJ.nCi【hc【Ofwhichshow仁山vi庇nccpfinfection. 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Cr8Ul函IdlJakobd弓s紬Se.pr■OnPrOtO■ngenO・ 2061・2067. 吋P8an叫S180fposltivoappendhtlssu8SamPL8S こ〔HeaトIhProtectlOrIA9en叩Fou「thcas00†varlant fro「【dr8trOSP8Cl・VePreValencosIudy.8MJ. CJDlnfectlon且SSOdalodwLthb100dtTandusion. 2006.332,118t;・‖8乳 He∂1hProIec†旧nA;】OnCy2007.hnp〟〝W〟.h・ 32 MeadS.JornerSD8さb「uslalSM.¢taJ. PaOr9Uk/hp〟∩伊〝釘aバ;cle釘P「8SS_r818aSe5/ Cr8Utヱ†eldlJ8kobdlSやa50.Pr10nP柑tein9モ∩8 2007ノ070118vUD,htm.AccessedJanuaけ18, COdon129冊andanovo‡PrPScけPein8yOu咽 2DO7 Brl侮hwom抑.ArchNou「D】.2007;64.1780・1784. 21 PedenAH.HeきdMW,R」tChねDし,β811」∈. 〇3.GregorlL.McCo爪bieN.P山m即D.8tal.Efloc・ lronsk18JW.PrlらC【佃Cli】vCJD8¶8rbl00dtransfリー tlV8nOSSOfleucoreduct10n†orremova10† S10nlnaPRNPcく〉don129hote相打gOUSPdl■e州. ln†ecIMIYO=ran3mlSSlble叩0ng一†o「menc白・ し8nCel′200ヰ.364:527・529. PhaIopatheSrrOmb10¢d,し抑C0120(】4,ユ64: 22 HoustonEF,Hall■daySL」8付「oyM.G01dmannW. 529・531 HunlerN,NewZealandshe叩Whhsc帽P18−SUS− ∩ 0 1 d u d e R r 之 一 e . 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VoIume491ssue4,Pagcs797r81 Publisht∋d On【ine:2Jan 2〕09 てSave岬 !n…=0= Abstract F 恥†emFL:H Texu HTML 巳[竺、111kl From mad cows to sensible b100d transfusion:い把1−Eこ…く、:: (abife bJoodcomponentsin the United Kirlgdonr dr‘i〔∴ Jean−JacquesLefre「eanc PaしriCaHevJtt FromN;it†on∂】lnstrtuteo†BF00dTransFusO− P3「に ∂nJ:・reし France:and theNatLOnaB〇CコSer\′】Ce」cJニニ∩.し・く Correspondencet〇Pa汗Cla Hel川tt.Nat;〇rla:二〇C√ノS己「;ここeCc1鉦e;1 Pa佃Cra−hewLtt@nbsnhs山 ABSTRACT 日回国固臥・・回 T「ansfusiont「∂nS■¶isslO[ロー川e;)rion.汗〇ポ・∵ユー㌧・arに‖t Cr皇∴ご SubjectsInfected thro=Gh f00d may trn∵S√1tて汁ヒ(5Ca5C■r∵てリコL to date by this threat are【he UnL【cd KrlE;〔】orr(しKj LinC}i二rEirC0 the UKover the past5years.」n Francc,a f巳∴′「∴∵duaS∴′「rO山.∴. Ieading to arlSk of transmts5h3n tO reCドe[1Isエ0、1C Of v/h〇(11CC)し∴ Large−SCale scTeemng teSttほ」mPOSSiLl;e tc r二Stこ1L)Sh t†1e PrCVa∴ ィし andtransfused patjents ThrsacK Of aトニこ!EiLこ〕,)′eVentS叩OCT】C−(,rt transfusion transmisslOrleSSe=圧訓y rer” at r”3SCrl:on cl〔‥ferr告 】nbo†hwhite b100dceLFs己nd p】asma.1c」k〇reこコ〕〇こつ∩Sド「涙雨叫−ニ† 】n†he absence of ascree「llg teSt forヒ1二つd(ハ;:⊇OnS,「己CCr、:)/C Furthermore.whELethe d[elary spread o(vCJこ5Cこ「て13e‖iCer叫C二1 thespread ofp「ト0nSthroLJgh b】00d tra[〇fLiSCrr Li,1C10ther seccrldこLT)′「つ」㌻pノ Received fo「pub】lCar10n M勘・12,2008,rCVrSしrlr∵Ceルed Oこ:cb己r■っ DIGITALOBJECTIDENTIFIER(DOり 10.111111537−2995.2006C2C4くxAbout[ノ〕 ARTFCLETEXT TheflrSt CaSe kr10vVn nthe hStOry Cf rTeJCH’ノaレJlrad−C1、.J/〔;13仁 一亡 ∪=itedK血gdom(UK).11ルheretheepFGこ㌻1CS」rOこ・こ‥1日de【)′†つV2し)ニ by bovine spongfo「m enccprla)opathy(L3S弓 ▲・‘○∴:【k叫′,lEle C;川; livestockwith animalfood p「epared fro∵r r亡Sエ亡ごfrom s;Lし′3rltじr∴ Which djed f「om sc「ap】e and cJ=e af†eこ:⊂Cヒ ∴、、トつこradLC 〇rr7「二一 1n1988in the UKand】n「99‘1【n Francc Crl∵∴∵120,10J5 BSEagent wastransmissLbleto man,A∵け∴ 1Prl;〕ath′:一つT; OeutzfeldトJakob Disease(n〇トtranS・:【シニ/∴′よ∵ノar【Lr∵′J㌻∴∵ Unlike othe「けansfusion・t「a「S「〕沌S【bre http://仰肌り.1nlerS(len〔e.WL】eY.(Omノ〔gl−し叫/「ute入て1こ1G・二三さう′ト汀MLSl∴RT EP(DEM10しOGY OF vC)D arlGニこ〇1TIPCSed〇∪∫叫Ofproternノこ・〕The”r10rmaE”prionorPrPC(Hproteinaceouspa{tlcle”)isaprot8inexpressed O〔tlle CC【し」】己r m・つmi)「3neby anしJT「bcroE hssuesr but thegreatest amountisfound ontheneuronsinthebrain. 回回国屈匠・・・回 Sel「SltりetOtneこCt=3[Of proこeo=y汀CenZymeSIPrPChasaha…feofafewhours・DespitehavinganidenticaI an「:(ぺ〕3CrOSeqUenCE:tOthat c}ftEICnOrrTlal[ormltheBSEagentisaprionofdifferentccnformatEon,designatedby To December2007,aCUrTIUJative totar of166cases of vCJDhひノ〔 accountsforthema)OT.tyOfcaseswo汗か〟ide Mean ageofa=ecこCし VJithasJjght marepredominance・Themeand]rationcfihc synrF〕;c′「 months)・A‖testedpat】en【swerehomozygous VM.Thc most prcこ〔 dietary二nOriskfactorototherk.ndsofCJDv!a50bserve□‘6・17′ ′ −anoitIsropaybnietrlmonh=rfqsiehtmordv.eSlna画印rcsofCS(ミPr[OEtaIVe)・〇ht Strし」C【lraJmod甘C∂t」〇rTandco=VerSOnい⊃a;LChLybeta・PEeat8dsheet・4Theabnorma[prionhasatendencyto agqre〔nte a〔dabov>∃arla「esiSこance(lrom丹什ChESderjveditsotherabbreviation,●‘PrPTeS.■ )toproteolytic e【1Z;(1「ワS(n〇【a叫PrO!ernaseK)resEStanCe)′mginthemajorityconformationinbeta−PJeatedsheets.5Theprion transfusion,and some of these have been=nkec v川h a knov/rlEnF己じ rSeJ![laYSa「0【ec)fco(ac【orHl川SCOnfor汀’attOna[change.lninfectedsubjects,PTP$Cinduces.onnativePrP lnFrance.vCJDincidencewas.asinthe UK.prorort0naとt〇dteiElr\′ COntamina【ed beef血o France一nCreaSed regu[ar】y fromlOa5t010 decreasedintheUKoverthesameperLOd.18Hov/eVer.!heEeveioT{三・:〕C moごC∵leslaCOnfo「r「一a110n tnElt C〇nferson汗ほmtheirpatho)ogiccharacter,andthephenomenonofamp=ficationis Se】トpりPaqaled6Bocal」Set a侮ctslheaccumuはt■OnOfaproteinpresentinitsnaturalstatejnthebody.the,eis no;rnn=JnO】oglC reSPOrlSe′ne侶「e「the produc!On Ofantibodiesnoraspecificce11ular response,Accumulationof aOn(l「†「、融P「CnS gerle「a【esvacu〇厄s mtrle CerebraEtissue.giving eventually aspongiforrn appearanceandhence theこ:es口Cn勺†o「nlenCePllajopalhy beenlO to20times10Wer【hanthat of the Uiく,Wth nⅥreOVer a dr†ニr已 datesofoccu(renCe:the comparison belween the number c)f Frerlこlrし⊂15L; ト⊂ ac ount theyearofthe begin ing ofthe symptomatic pha5e)irld:,1ミ亡5∴J OC Ur 8d5years after the peak of the eplde雨C m the L]K,V/here:一しつ∩し」′ L:ミr l汁几l′\N 門刊ON[)】S〇Rf〕ERS decreasedshce1999・17Thislemporaigap[∩=reepidem】CHltnL?」・<肌 r 瓦E[]宮宮・‥回 maximalexposureofthegeneralpopulatTonlnthe twocoun!r】es ■丁■hehしm己n t「aTISmIS〇】bLespo「1gEfcrillCnCePha:opathies(TSEs)genera”yfol10WaJongincubationperiod,butwith Between1996and2007・23vCJDcaseshavebeenreg】StereCl=lFrこ1C 58years)andanequa!sex「atio(12males,11fema′es)「■he cl】「 tothoseo=he B(itlShvCJDpatients.Themean durationof the5、ノY∴〇 months)・AlitheanaJyzed caseswe(ehomozygous MM,W[け○しt alr StaySinthe UK(lessthanlO・dayperiods)wcrementionedn3p :debircs amofSJLiraVh【od1(l[aI⊃=t山〇ved[parミnCu〔e5bUS TnいdlC)Path=ニ=IこC「OerS.Pr】nCりつaHy the sporadicform o†CJD(SCJD),WhichcontinuestobethecommQneSt †つrETl・Et a;)Pea「5D「edomlnarlily[n the三;亡Nenth decade,Wirhanannualincidence,Ofltol.5casespermillion ;、\つPし」:ati〔⊃r一′〇コ己1h To;10WS、L/”hl「「6m〔「ths・Thisform,Whichisassociatedwithapatho10gicprion,has ‘「 the UK.†orlong periods.between1987and1996 し:1kncl:Yrlelr)1:Cl′t p「Oba叫resuhsfrom aspontaneousconformationaFmodificatjon ofPrPto PrPSC. 1nothercountrjes,VCJDcases remain excep=〇naF Asma‖nunlbe the UK,but thereTemainanumbervvh;chappear to have b已en己ご】) inlrelandltheNetherEandsISaudiATabia.Spanand Port明a[andこ了○ Theqer○:1C[cJn■S:1am:ZlaCJD(fCJC))・〔元rstmann−Strausler.Schehkersyndrome,andfatalfamilialinsomnia. 「㌢1e aC〔くじj ̄CJlこ】「rて1S\‘ヾ′e「Cしj「t11966,〔=「uman o「lgln:ku町†0UndinN8WQ」ineaandlink8d tofuneral [r∂C=ces・こ「ldこhf)伯こ「OSCniC Fo「nlOf⊂JD.seenafteruseofcontaminated neuro$Urg(calinstrumcnts.cornea] Severa[studies have been conducted to estir.1ate the ex〔en【of t 12・674ind仙d=a】swithout c=nica■∨αD‥22什烏rareapp(:(▲rSrl三っ㌢−し recordedin(he genera】population,F(Om theご3(eSUhs.こ.〕(e、/こ:en:こ 責mea=OflLl∵Onths・V/hC(11SSjowerthanthesporadicform・10Nuclearmagneticresonance行nag■ng S二arlnjnG Sh⊃、〟S hypersEgrlaL5S:;uated hthe posteriorthalamus(“pulvinarsign.1),Unlikeotherhumanprion こ WaSPrOPOSed(95%contidenceintervaE.49・7〕2).En【he【11CSt P已さh highest rangeo=hisintervaE).41.2500f60pr川0∩】ndV山こ1s vvc、,、二 thelatest count ofvuDcases■nthe UK弓smor巳nagre≧化rl−∨∴い f1Lm□ChlefZy「ad山【s unclerLlO years of age.contrastingwiththerneanageforsCJD.Thedi$eaSeisfatalln =ト (jモSC「Ebed「「1E19G bソ廿e UKN己い0naE CJDSurve川ance Unit(NC)DSU)basedinEdinburgh.Thediseasewas C t「e clnl)’h∬1己r−i〕r10ndlSOr〔1e{that hasc「OSSedthespeciesbarrier・ThefirstseriesoflOpatientswas Britishre(rospectivesIudy revealed【hepresc;lCC CftheこL)nOrmE「 ︵ CSeaSe。「lつ0V]]leO=g[.汗aいS,Var・a〔{CJD(VCJD)isseeninsubjectsinfectedwiththeBSEagent,8・9Thisis . C′a†ls己U(a「llE;ter,and jnt「a「:1しJSCUjarr−jeCt10n Ofpituitaryhormones,Obtainedfrom cadavers,Acquired lnFrance.wherethe EeveEof exposurev/aS】0∴・erthaninlLle U卜こ,しSt・ 〔ゴ30rders、(10こa乙〕卜/SCJD、1Tl∵再1rCh theaこCLImUEa【jon ofabnorrnarprlOnPrOteinaffectsthecentTalnervous S′5tem1.YJl=「aTllnfma】perPherElけ1VO】、}erTlerlt,VCUDprogresseswithinvasion,bytheabnormalprotein,Ofth8 60yearshave been suggestedinone s(Udy.ノaTld205cases[n nnOこ「、C P(edictIOnSuggeSted a(0【alnumberof33cETSCS(0−100LYJL=11Jcこ、,〔ニニ ニu3こ CL州raとne「vous叩Slem.川e pe=Pherarnervoussystem,andothertissues.notabFylymphoid:tOnSils, 11(1・20)overthe2006−2010period.一8Th〇Sedataarecロ∫TIPatbjt? ㌻.c こ叩erldLXIPel,/erSPa!ches・nrldlhymuさ11TonsL‖arbiopsymayreveaLthepTeSenCeOfPrPSC,butanegative Arecent studypredrcted39(6・99)subsequlつ∩†cases21T恒仁.VCrStしこ:3一 −こr yearsis,however.majntained Enthe epEdem0:GgrCeS(lmalrons.En PartCU;r【〇し〔し: 耐ectioninthe bboddonorpopula【lOn. 「つS山does∴01c∂!egorCか」)′eXCude tlle d】agnOSis・ GENEr[C[NFl−UE=C∈S MeasurestakenagalnSt thevCJDepidemic,V/1ih screen■nC for【he BS≡占.lL:1こ1 animalsfrornthefoodchainland【heIa:est epldem▲OEog{=Observa:1Cr三Sし∵てここt 回酎]回匡・=E Origin(sunrikeryinthecomingyears.Theunk{、OVJnS nOVJTeSdt3Frlつミ:1う:こ∴㌧Jr::〔∴ The p「on Tjr(〕terrlEjerleS Sllualed〔n the sh〕riarm ofchromosome20and codesfor254amino acids.with eith8r vaj・rleV)0{me汗LO[1[e(こソl)at posいCn129 W冊twocopiesofthegene,anhldivjdualcan beMM(39%0= nc「miTT pcp山ar卜つ;「:’11V(50%).o「1八/(11%)ThESPOlyn10rPhismisfundamenta(lyimportantinthedeve10Prnent Of Ce仙Iarvecto「sこb100dt「ansf=S将∩.graI【sofいこSUeSCrOrSar−S,0「しほじ∴∵∵∵∴再∵ けeV(”aElt ty?…f〔:d■こ一eaSe・Sl〔⊂Cthere sahostsusceptibilityJinkedtothegenetictype・12・13=omozygosity COntaminatedwilhthe abnormaIp‖On.TransfL;SiontransロJS5にrlrS〔∴ 一JNowadays.shcefood contamlnation.whlCh、,・!云S the ma‖1S〇し汀Ce Clf∴∴∴∵〇=.二 transmissionby bl00dcomponentstaken圧s恒Ce?hthe UKnsE[l㌦∵J∵二 fo「「・巨爪勺aニP・こE:S▲rj CO[1feT SL:SCe轟沈油tyこC CEinicarexpressionandtohfluencethejncubationperiod ofthe e[imjnatedfrom beef,they are】ikelytobeprcsentinthcし)r〇OdoTas∴ ニr一「〔へ □】S〔JごIa川C」;〕∴よS二さ・【odaLelLll//n〇mCOゴon129typlnghasbeenperformed,areMMhornozygot8S.14(none CZ{Sコ1両ec(・つl.、山こ「etF「e HldV七u己」dEed≡、yearS afteranimplica(ed b(oodtransfuslonbut did not haveany to the recipients oftheir b100ddonations,The(e己r Of hu:−∴Mlll).FrJ[T interspeciescontamEnation. Cl=11ここSymPt〇rr≡Uf\∴ニ正〕at the Eいeofdヒこ1廿thegenotypewasMV・Furthermore,PrPSChasb8endetectedh the印;うendrx〇†い・/0\′v・cases・15T:reMVGerrOtyPeandperhapsrnoretheVVgenotypecouldconferaprotectjve EXPE剛MENTAL BAS(S OFvCJD TRANSMISSlON L:Y TRAト」三,一し」しニ〕r」 臥・・園田固…固 Unti[about1996it wasacknowJedgedthat the CJDagc〔i∧′ri effecl,bLJt thjS r∈m己rlSt「ueOn】yurltLEasym;〕tOrnaticcaseofvCJDisdescrib郎=naMVorVVsubj8Ct,(nfact.we kn〇V:(lat=(lCVjjHa:ソバ=1こ=lhreeQenOtyP(、SCanaCCUmuIat8PrP$CinvCJD−SPqCifictissues.butwedonotknow W11e汗〔r S)仰PtOr「「∂tr二CaSCS州=deve【opln∂rr genOtyPeS. Il=P/ル1・∴√j.い1terS〔−が1⊂亡.“亡ソ.(0∫¶/⊂g−bLn什」【;lexり1211SO6285/HTMしiTART faiEed to showanyassociationbetv/een【he c;CUrrenCe〇f sこノ〇a、1こ:∵こ、 ページ2/18 http://www〕」爪ers⊂l印⊂e.Wll叩.⊂Om/⊂gトbln/fu仙exり1216C62た5/HTトIL_Sてく、r汀 Uy/Ub/Jbl):さユ yea「0!the bbod trans†usOn己nd7ヒCい〟e∈√1.1㌻r」7)′Cこ「ニr⊥ L7、L,r〔∵CJL)い笥=〔SC^J⊃L′13rt・rrlT)己rCfnfectlouspartrcleslnblood and/Orthelrdistributioninindividuals 訂=c二■lヒy sC」〇a[C O「eSLJFl∵鳥′Jこ00′0、∧′tC CaUSe†ranSmissIOn through ab100dtransfusiorl.Thus,befo(ethe first 、:ニ」「)〔,:〔、S.†上巳い/C P−1こ1in crCしrl’S‘nr「cじSOfこ〕「On【ranSmission between humans had been kuru andiatrogenic し dead and have su「∨】Ved7TO9years aftcr trこrlこごしニ0n「rrCニ dono「S)were assoclated w】てhll化ent吊鳥「=亮己nls,Cf、・1こ「 ∨ 3.10,and17yea「s afte「【ra:1Sチリsjon.Three rec.コerl!sニ1)◆hrl〇. 〔Or「て 、J:pO=∵ノn已CTEOn Cf::r:〕∴trlho竹「O「eSCf p圧止tary origin,Ft should be noted that transmission ofthe kuru 叩已r、:ObrlSSこCミh〔】【〕aSt S∩二C t「e rlrOい;b:tつn Of certain rituals jn NewGJineaandthat the excZusive use of = C二5・1、「いrL.rl「コr、1ra:1SJllH)5つrrロ‘vC∼D「1こCソし【been described.the possibiEity oftransmlSSion by biood transfusion Tモ、1、:;1けEJCTCJミrこalr」S・くLJL L:・rhL、亡∃nl叫Cr tranSfuslon−tTanSmltted virusesobservedin the past decades ﹂ q∵ン∴:「「∵)(=10rT己=Of rec〇’、と、け1こr’1こP〇jrlロリ亡 抑end tolatrOgenic transmissionsthrough(his route.Though no し t「ans†uston.Among川e97「ccP■e[tS川usけに∩こfCd,4Jこ】ソe〔」⊂ died of the d戸seaseこthese己ir belong to tIle frS1日rOUP,;L、〇5e O/二 evidence that e】thersCJD crfCJDhasbeenlrarlしr吊tecj:)1′i〕c)ロ∴rr mfo「med and none vノe「e teS!e(】For ev氾ence ofrrfe〇tOrl IEltlrLr’(;3…‥5「γりrnarl=1;TIL」rこい」fECerlCy、▼′汀リS〔川∨】.hepatitis Cvirus).th8VCJDagent did not jmmediately THE FJRST UK C^SES OF vCJDIN RECIPrENTS OF=BLOこ)L)(ニC・.汗J】ON王11.、) r=: ミロ■ト1C‘n 「】)Of bい:○〔ト【1:7「rle∂ぢCr「:S 屈・・・月日回…回 ′ し,∵∵∵∵㌧誉∵こ 一丁つC:コ15.:r∵鉦豆r=!亘rTIFつhc)】dこ【S5Ue byabnornlalprionhasbeen observed rap榔y afterjnfect10n, AlJfour t「ansfusron−aSSOCated vnDlnfecl】OnS O〇CJrredn P∂=eFtじlrこ⊥r レエコ(】 し∫‥リ blood ceJis(RBCs).The「e have been no transfus0n−aSSC〉Cated cこ5誉eI∴’Jつ:r、・「こ]ロJIJ describedin these tvJO】aこter groups.evenin re:rcspectVeockhこ.C、二{二∵王汗三 rr,、}.‥. 1nfectlOnShavebeen detected mthe bFoodrle叩e=menlar a1「一1こ]Jrし\」、ノ、」祀∫ こ^rSGC{「し SuSCeP=ble【O the disease.ar!houghlt LS nOt POSSb:e to formaい、シ′∴」 」、rli, /:;.ニCS havepassed unnoticed=∴けey r:OSSeSSed excep【rorla≠feEitL:「亡S己rlcrこ∵∵一こし r.L, \′川ト「 5iSt(ご〔CO=1「〇しヨhouこthe、J/rCbJnCUi:atOn Per10d,lt hasbeen suggested(but not demonstrated)that the rT一㍗(,lmい1「二1こOn{Sbroし)コTlt nO〔し」T by c汀CLJa【Lng C釧s,Whichledtothe hypoth8Sisthatin†ected rymphocytes 〔ロ]′ノいこrlSrl〔・作○仁rOn〔nroc;⊃〔OrlこSnfbLq雨C口mPOnentSCOntainlnglymphocytes.32lntracerebral叫ec=0nln rlr1〔・?二∵】しff)′COn:sn・rdpr;ユSmaCOOCt〔ラリfrc〔1Pat】entSWithvCJDhasnot$hownsuchtransmissibility,33butthese EJン′r)・∵r・〉nrS〔)叫rソ∩∴′eO Ei511㌫【lrlし」rTl加rc)f cases andthesensitivityofthetechniquernay havebeeninsufficient 、′1IJ・二:恒eノつFcf・rre二tr叫さノ:〕S〇qJerl:【ソとransf=Sion=唱nSmissjonofp=0=SWaSShow両nrode=tS.34in por: nrrlCOm云utつSUニCC;]t【)〔:つJCjコつ536=owever.theturningpointwastheresultofexperimentsaimlng ;」、)∴Pこ∩ざ・TりニjbT し㌢rroL」lLL}○己ro(71〕㌻aFFyFnfectedsheeptoheaJthysheep=37itwasthenfoundthatthe rL〕r、、)rr二F)「.0∩:rrノユS【3reSCrlt=C・こ,nL「∈;○れ〕d EInd that b100dcould beavectoroftransmission.BIoodinfectivity The f云「st oftne four p∂trentSnfected v川h vC几い廿roug「1bb⊃d t g「OUP】Whodevelopedlheijness rn2002andded the ne〉ノこ/拍r O」r、」」L .′J7)一 norlleukoreduced RBCs,One Ol、州chvJaS donaト:□by a)′OJrG C::「{ :、「′ fo】10Wing yea「・Bo=1dono「∂ndrecLPlem VJereト爪1homozノ;〇uS ㌔ exc】udedin tnis case(asln【he o【hersトbut the:rarlSrUSトOロリノこS〔トニ ・1㌻ the[eCIPlent Which was greate「thaTlthe medan for cases t)Cい1・,・ 二P L,1∵ いi,d仁rll=r、str㌫【Cd.コこ1ヒ03こ「こOr!訓1ニけCUrTIStanCeS,French and British Hea(th Authorities,aS a P「eCaution. Crつ「:」∵∵冥】EIC r)ごSSこ〕tyつf rr:hPISr、、ぅrjC)「Df=revCJDagent by transfusion. tミこ:Slrejp貞cしnaodhb;Esitfl r、こ、〔L nr El/(]ヒ′merr− tralSf」3Cr〕HlC州hゝSheep vv]th b[00dfroTllinfected sheepJed to t(anSmission rat8SOf17 p伸二t」′1‘〇l已SEarlC19pcrcし∩こ圧r scrapLe3日AmoreTeCent animalexpeTimentwasbasedondetectionofFY声Cin bっ 二 l〔 」 hzl: 1 Ster〇 e灯 用 rmeTlt〔 ミ 1, JCし 1rltEl; rl] naiec] by thescrapleagent h( OUghintraperjton8aFinocuration = nfected し thesetw00bserva=om50†vCJ⊃vould haveトニi〕Jノerled Ln〇rPerr」亡 infection,WaS■nthe order ofl:15.000(a11d rDSO tOl・3C,CJO† f行st transfusFOn・aSSOCa†ed case jn worrd Htera【Ljre VJaS rヒ;二Orい〕已 .)「こrr・ミニ、し]已:”rrbotrlCaSeS汗〔、「▼fcこミOi」S…一〇ent WaSPreSentincjTCU■atingb■00dduringapartoftheincubation r1nf;C∴バ=1C〔jSOこSe、;ln(7theてrDr15rrl:SSOrlr封evJaS Showntobequltehigh・How8Ver,itisimportant todistinguish tンrc srL.1eS CO∫lCt,C†e(〕 T)la、∴′c31crr7bbt E3SSay detecting theampJifiedamyJoid proteinandthoseinvorvLnga The second case was arlelde「い,′reCPlerlい,VnO〔畑鳥Of OfvCJD・Asymptomat■C【nlccてト〇〔Wjth FTPSC肌一S亡StabE胤1しこ3と))′F Pr8SenCe Of abno「ma】p「jOn P「〇いが∩【∩阜m封Ⅷ烏tSSUe(什c叩c〇r;1 tonsllso「appendix).but n0l∼nthe braln T=s patl巳nt hadヒ叱erl r′、′′rl】f c−「(「〇二CrにH」51「′c【二■ r::{、E二ニソト?TILつ●畑〕:C川・?dc5Crこ:Lひ∵二f†heトrst numan transfusion cases.these animalexpeTimentshad shown }1ここ一しj r ;SLj廿,′GF pr0「†3Elrr!:1〔]rI3SS3r=ty of ashortincubationperiod o=hediseaseth「Oughthis ( 二C〔 い∵汗∵号Y∵∵つn「(〕L.†ウ Sし)Ii\ノF:1_LANC仁OF=TFソトNSf USiON用SlくOF CJDIN THE UK r 1こ∩CeSnTrコロoFIbd∂h乙Nノ、usf],eミartDJGV 1 1999.、a nOnr8ukoreduced RBCcomponent had bたen PrOVl(1⊃〔:frc∵二 dona−ion・The PTPSC】SOlated from=1e SF)Eeerl卜aclarlESOfcrrrr〔]crl・=㌧ donorwas an MMhomozygo【e.but the recIP‘ent W;1S aheiercニy、↑ nalure of t裾S CaSe.aSS一弓[ed a5、p「ecmCEIEors」bc=nlC六/CJ infectionwasreported】∩山車2こ04.49 E…[▲〕完針‥屈 リK〔汀高上汀m〇′〕ち二Stし′:ご5Lニ√」・1CしSL」三日eSt tranSfus10naSamQdeo†transmlssionofthevqDa9enしand い・f?†r三 ・∋こミ(二rlP:つnSOf r己二いr仇Cf;i【〕l〇rtTl:ユ′Pr0nS W.thinthebodyhadindjcatedthat the bIood(0UteWOU(d be rTiつ/Jこここ1[)ト三一SこしrCLCf⊂J吊nrr〔こ:へ〔Sub5eqUently,eXPerimentsintob100d−bornetransmisslonoftheBSEagent 「5l・〕El。いrC廿C〕bs亡「ソaトOr=〕fム::こjごrこj5trbLJて】On OfPrPSClnthe bodyofsubjectsinfected bythevariant agent Tト・一丁r・ Theth■rdcase,rePOrted∩2006.月215051\VaSこLs00neC一丁ト1リCC「〕rt nonPeukoreduced R8Cs and hこId been nolf】ed cf‥1er rSト TLrニ「(一 had「ecei>edt「ansfus】0n SUPPC{iduringasurg・Can!erVCrlこ0「−CC deveIoped vCJDln2005,7years after the transfLJS;Cn eP5〇L:eE,∵∴ PreSented wIth vCJDinlS99(18months afterいe donil【Grl)こin√ 二・二 bboddonat旧∩トBoth donorand rec−PJen【∨祀reM㌧1いロnl〇ご、ノ′ヨCleL ここr丁lココ′ こ1▼リ1しr s」○ドここ5㌻(ざ亡=【1こ】汗、封ニ⊃jodlo recons■de「at−0n O†thisview・ ∵十}こrt”j LJ・一、汗e二つし∴1い∵「告∵一・〕、;1つSコ/iこO the BSErisk.putinprace anationaIsu(Ve=ancesystem named finally”demonstrated.‖There are anumc)er Of LJn,川口V;nS rr!1LIVr but thecomblnatlon of thelo、r▲JPreValence of vCJ〕】n the E;亡rlしモrこ1 individua!∪柚Va「‡eSbeいVeenl.15.000and13ロ〕001∩汗亡し揖 the smaligroup of recIPlentS/Jt「つhave beerlrCn血rud at rこ: theseaトrjsk recIPFentS have djed v/Lthout su(Vいノ爪SIc}n3已÷10しユ′/、し testedforthe presence ofrlfect」On)makeshl臼n)′PrOb己〇∴J∵∵ar L thesecases reln(0「CeS tne【rleCry tha【the bLccdじf adc)「L,(仁r t「し「 冊ectlVefor recJPFentS,ThlS eVldence of the tr∂nS一JSIOn trarlSnlSニ:∴ P†eVentative measu「es preいロリ中ロPP11edin thビ∪ト、and】n Frコ・「こe http://仰〟】.inter5⊂j即〔e.Wl】ey一〔0nl′′〔匂ぃと−川/Fu=【exり12160Gヱさ5ノー}1丁ト1」Sl八にT lし ページ4/18 Thesecasesrep〇rtedin pr〇fcss・〇naFjOurna】5:己−こ。bし」bse〔,ししr、こノ transfusion・aSSOCla†edvCJ〇rllOVrng PrOgreSSル〔けfrorTl“:㌢こCrr;こ U h=P:/VNVilnterS〔1Cn⊂e/∧eYC(1m/⊂ql一し一Lfl(f」Lte\【!121606285/HTML5TART three・Therec】PEent,genDtyPeし「M.d■edlyearafl己r Preさ㌧.rrここ1こCJ∴ 二 ヽ cIICこ{㌣∴こ廿忙thc da:es anこPraCCSOfthedorlatjDnSY/ereeSta釧Shed,Thefateofthedonat10nSWaStraCed, 1r、Cl一こコrlrこ㌧仙e什ごr they v√erCL」SCC forbbt3d component prepaTationand/Orforfractionated plasmaproductsIand 什e h・∴/〇いeこら;)tentSOf bbodcor叩Cne一rtSVl′aSeStabushed・Theseenqu.Tiesidentilieddono−TeCQTdsrelaling1024 HIcjLY.れ 3、、・恒bter c巳VCbT)已d vCJDて18c)卜・・/†1Om haddonated bFoodthat hadbeen used topreparecomponents LS.,:」√二}こj 亡,n⊂SPlてause AtotalcJG6{CCP;e(rtSWereidentifiedfrornthese18donors:230fthesearesti11alive・ E3加d crr)r reCOrdsvノE3reH3erl==e已f〇rC叫3of93indrviduaEswholaterdeveFopedsCJDandwerereportedto h[りuトリ∴〔づ0nCrSln:ne PこtStWth20recrpICnてShjen川上ed,Ofwhom12areknowntcbedead:5diedwithinl Thefourlhandlast case to date、〃aS areC戸pent〟h〇deveOP・二「】∴二ニ donor who p「esented両th vuD17morllh5af:erJonこいCr「r−Jし二二 ︹し anl〇∫l〇:lCSC.31(21?c)卜耳a【eastacc〇rd〔gtOtheirfamiries.do=atedtheirb■oodatleastonce・42Fbcordswere ⊂ \ r二rJlcrrnL Cre:iz{〔鳥ト」こ↓くO!;〇3C;一ニeSLJr㌧ejance Unit∼‘0(NCJDSU,Chargedwithidentifyingandmonitoring aJI cJSC5(・こ」〇;:11A5し)三,【亡⊂巨汀C〕Sこい▲べ汀eてObereportedbyheaFthprofessjonals(PrlnCipalJyn8ur01ogistsand r:l」r〔一つこ㌢一〇リコSこS,こr1〇=こ、CCLT↑rrTl・1dこirJcat已gOrized accordingtothedefineddiagnosticcriteria・Asfaras rこ、rこ)(LJ・二nSこじr:,〇rrl(:Cj.trC rlreJしこ1j rlS:ory〇f each patient wasexaminedandfamllymemberswereinterviewed, 加†、〔Lq′、1丁卜=51〔パOfb00〔うG〇T12㌧、こtlCrC‘TeCひPt Oflrans†usわ∩・Acoltaborativesludybelw8enlh8NGjDSUand tlli3∪どくしう00Cj TrET{Sfし引OrlScr、′一CeSCヨ=・3C:T卜′1∈打(Transfus10n MedicjneEpidem10Eogy Fbview),WaSSet uPin1997 ((、CÅar、・、Oa・CヨさeS〇f CJ[つ1nCL・JrⅦSCJDTCJD.andvCJD,Whohadeithe「donatedorreceivedbloodinthepast・ C:r「〕EjC r−1!一Crl.2〕C7 arnこ[]けe165Uト(CaSeSOfvCJD,150wereo−denoughtohavebeenb100ddonorsand・ / いr、 epidemic・ThebEo dcomponen!swere5concentrated rlミCし二rl tこ1(し10Ll」:一÷ 】nfac:desprミC the snlaFnL」{11bc「C)f rep〇「led transfusioncases.manyobservatlonshavebeenpropos8dorare reukoreduced)IFordonatFOnSmadeafter1994.7 ̄re叩1‡5:je・、[,二∴とこ′ ハ【・ al「ead/kIln仇′n d(〕nationswere used fo(fractionalion. l 「■heposs心l】=yof∂「etatIVe)′ShortInCUba【ionperiodwithatransfusionsource:6鳩yearsbetwe8nth8 ■「a[SfusLC)naTldミhefl「St CiL再ca】sLgnS LnCasel.6yearsinCaso3.8シiyearslnCase4,Thisshortincubation ;)erlOC]〔emOnSlra‡es the ef†lCaCy O仁汗e transfusion route.1t m[ght suggest apartlcuEarpathogeniccharacter ロ■川C aヒつnO((Tla】pr;0n C汀C山a〔1nglnthe bloodandlransmitted bythisroute.evenifitisestab=shedthat /ltraSPeCleS【ranSmESSrOnS USし」arFy accompanied by ashorterincubation thaninterspeciestransmis$ion. Thethirdcase(13th ntheseTies,rePOrtedinOcIclberニCCLl)、▲ノこSコ∴仁;二こ「・⊂∩こ 1991and2004・Thecomponentswereone行csトfぎOZe、;〕「己S√Ⅵ;1(「トPノこ∴〕15∴、こ、 themLeukoreduced),A‖16recipients\VereLOen律叶Cf L′ノ㌢11Chい∵E[ea∴′,〕 lntotal・these3donorsaccount for42rec.pLe−1tS〇[Fu∋こsor F・L_TsこつT.、川11ち− investigat10nニ20fthese.transfused before1984.1・/ere r10trlfc/rrnCdbLJこ14wcr.二n⊂こてト○∴ rldeed.川e shor[eslnC血atC)n PerlO〔】hasbeen observedinkuru.intheiatrogenicform afterinjection of transfusionsbetween1991and2004Todate.no[e卜EISPrむSe←宜已・・tlt13.・mr∴て3Tl 】rO、・ノinhormo㌻l亡,53and∩いans(u引0∩aSSOCiatedvCJD.54 rnc「a!已0(l{nrlSmi3SLOn Erlthe popu】a=0nOtat−risk recipientsIShigh,eVenthoughitisnotinevitableinthe recIPientsweretestedforevidenceofinfec=on,becauseコHdrec sevcrこ1ン′〕arSこ】Lニつrし{ donor・Therewerec(early more(eC.P{entSOffracl0nated pEE:SmこLPrOCUCrSpr叩〔rこ(; affecteddono「s■Twoofthedonorshadg戸ven p【asma(】esいnedぎor rra〇†一針at:0rl:「汁′モニ donationsinonecase,121nth80ther).These2donor3aCC〇∪侶己d rcr即OU1ゴJ〇.ノ〇二′.上Cr −CiaiEV叫S≡ror{foE加/・し」PPerOd55ArevleVJOftheUK・sTMERstudypub■ishedin2006gav8gnindicationof hetransfus○′lriskoいノCJDandofthtつincubationperiodofthe†irstobservedcases:42amongthe66blood 二OnlPOnent(eこ1;〕Len:s:ransfし」Sed frorTdonorswholaterdevelopedvCJD,37diedwithinthefiTSt5y8arS つOSトいて「「5fus0∩拙tn aCal」Se O†death LEnked totheexisting川ness.Apart fromtheonecaseshowntohave (1、ノ】dence o=nfcctlO(「.nCne Of汗e otlle(deceased recipientswQreteStedfor evidence ofinfection because t(eatmentofchronjcdlSOrders(hemophi=a,FmFlr]nOdcficienCy).律〇rCSif〇rOCCr∴こ,r.こ immunogJob山】nS), lnresponsetothef.rst threecasesofbioodconors、Vho b!ごr dcvc=jFつed vtlt〕∴「しI: jnto pZacein France: :heけdca=lS〇「edaled=1e行け引ma=onlhat theirdonorshaddeve10Ped vCJD.Furthermore.no postmortem :SSUe、Y’JaS aVEirFable!or re【rospectlVe teStrng. lmmediaterecal10f Ln・datefraclionated plasrTlaPr⊃山CヒSこ∫rd・a:」Jb Lcodし∧「,ノし∵ニノ AmcII11the29v/ho survr\一ed over5yeこ1rS.コO are s==aliveandhave no signs ofvCJD.and9arenow decc∂うeづ Arて「nnコt:1CSe3∴6d■〇C Of pathoJOgy nOtllnk8d tovCJD(aはhoughonlylo†thes8hada POStrT、Ortem〔o L〕Ok specf【Cay f〇r:∩!eCibrl.Whichwasdemonstrated)and3developed(and died from) donors・Whenthe州nessvJaSdiscoveredrlLhedc㌻「Cr,bjoこし3rr〔九(二こS卜a〕r∴∵1:・ transtusedlbut thESS【「ategy allowed the fo【EoL//IrCユ=て揖rlS Enformatfontothe prescribersofIhe■abrFe b=00dccrTIF⊃0(lerlis叩ilLニュこし1 VCJこ 3 ・ Direct and personal巨nforma=0n tOthe recFP−en【s cJfミ)Eocd〔∵TIDこ・rl二LtS㌔e:‘「 〕√ epidemic):eXCIus.0nOfallrecipien【sasdo10rSC)forlIaEIS.tF3S〕。S.:∵」ここh b100ddonationbecauseoftheirh▲StOry Oftransfu5[:叶a〔こ「「∴y,㌢∴しtn  ̄h已1∩=uenccつf cocon129GenOtyPeis not refutedinthe context ofthe transfusionroute:the soLe ecPent kno\∧n tO be毒口fected but asymptomaticwasaheterozygote(MV).althoughit should be noted Jrla‡the oL)Se「ValtorlPerOd v:aS the shortest oftheseriesofinfccted recipients,Sincethisrecipient died5 UP・ ・ Adecisiontonotinformindiv■dualrecり)EertSCIffrこ⊂t Orlう【くJ」心J・し」Lノしし..、 1′e∂rS af†e「r「ans−usFon 4. Athe冊ected recp?entS had recelVed nonleukoredリCed RBCs between1996and1999.R)Utine received Factor(F)∨=o(FEXproduced(rcm theこ「・L:Cトミd.0∴エいこrl、 厄uko「edし」Ctlon・Vaいnt「Oduccd】∩【he UKby Octobe「1999. 州ormationa∫med at川egeneraJpopuは=on ondd・∴ミニ「:さ1「〕∴Cfoニコト⊃ニーこSこに 5 ▼「he foしj「TeCiplentSWho deve10Ped evdence ofinfection hadbeentransfused respectivelywithcomponents transmission of vuD. 一「om5.EIPr)rCXinlateLy3−10(f弓gu「e uncertain).56.and23bIooddonors,[0)rreCtionadded after on‖ne こ八fbCa【io「12−Jan−2009−Nunlbe「○†dono「shas been岬dated,】 TheinformationgivQntOthebloodtransfusionrecPrCnlニb)/the・rdcC;OrPrいre已{rrし 6 Fl【he UKElnd France.no case of vCJDhas been reportedinrecIP18ntSOffractionated plasmaproducts,As rld:Catedln the tEtle of†hlS a「ticle.vJe have Fimited ourreviewtolabi(e bIoodconlPOnentS.aWareOfthe morethan20yearspreviousEy・tOthefirst b【00dconorstoしe(′1L」rJh」:、ソi〕03rて・∵ ノ theLargenumberofuncertaIn【iesatthe【imeabou{the prognoニ=SOf[rTec【〇rlこ㌻∵+:∵ejl・∵○∴ Thosewhosupportednotinformjngrecipientso[theris:\Ofprbn!ransmES=bn【!′∴J昌Jlこ lddironaヨp「ocedu「es【hat con【rlbute【o thesafetyofplasmaproductswithrespecttoprIOnS. fol;ow‘ngargUmentS:itisno【poss−b■etoquanl■fythedとつSC=uier【5k,b己CaリSeOf∴1、.甘心つ absenceofadiagnostic[est=the xistenceofpreveniNミ「一IeaSUrCSa打外海dlnr仁CJ: SU11VEILLANCE OF TR∧NSFUSLON RJSKIN FRANCE:FIRST CASES OFvGJD WITH PREV10US tolab”eb100dcomponents;thema)OrPSyCho】0針CaIhar”lreSUrt;ng fors]ChJnfo{rn、・1=ニrl majoranxJety;absenceofanydia9nOSticorproGnOStctes!s(exceptforco〔加12こr5こ;」い⊥ uLO(〕D DON^TIONS AND FIRST MEASURESTAKEN WLTH REGARD TOTHE REC(P]ENTS PrOPhylaxisortreatmen【,OnNovember4,2004.the Nat10nar∈汗ICaF Cぐ「、S)[lElt、:ニOr 回…ヨE針‥瓦 A=hcしGh epl□Cm10】ogrc‖「VeStr〇a:・⊃nS COndl)Cted】nFrancehavenot reveaEedpreviousb100dtranslusionsduring thelrSk period【fo「vCJD(0ne CaSe had TeCeived ablood transfusion,butin1971,beforethe epidemic),SOme COnfi{meditspos■t■OneXPreSSedin1997:tOnOt WOrryV川nout bcn洲,nOtab■yソI10「已n availablelandtotakeJntOaCCOUnt theriskofexcrudEngaPa=en=fTOrTnJ己仙cこ一 ニr PreCautionaryprincipJe・FlnaEZy・theCCNEFnsisted onthe,1eed fcrcorTP■e:etrac(:こ :‘〔 PatLentS had been b]00d donorsas woし血]ヒe predicted.inthesame period.ln1992−anationa[survei([ance donors、〃hohadsubsequentEydeve10Ped vCJD TletV・}〇rk for cases oICJD\りaS Set uPn FrarlCe,COOrdinatedbylnserm Unit U708andinctuding representatives of Thoseinfavorofinfo{m■ng reCipienlSOfthe rJSk poLntedoじtlhert∋eGicL[rfo(n11己n∴ ehtdna.sirot balecnrf,stigolhaPOruen,stigolO(Uen:SCIvreshta「idnse=ミ;cepslaCdm3uoiraV ■rns‡;」!deVe帖三Slnrtalre’〔FnVS二TheaJm Of thisnetworkwastocoEIect andinvestigaterepoTtSOfsuspected CaSeS Of CJD,fo冊∨・the「P「Cqre55,C】assrfy thetype(SPOradic.fami‖al.latrogenic)andthedegreeofprobability (dEStlrQu喜shrlg COnfrmed caご}eS f「〇m PrObabdecases).andestablish epidemiofogiccharac(eristics,lncaseswith PreV】CJShEStOrY Of b】coddonatC)rl.∩VS、」ノaS Chargedwithinforrningthe FrenchB(ocdService(q臼abIissement FrElnGE,S du San?)so thaしa:rar5fusOn[ntreStlgation could besta(ted.1t appeared that thr8eOfthe FrenchvCJD CaSeS/扉10had cevclopeいhc dgsease H12CO4.hadahistory ofb100ddonation. The fLrSt CaSe(eEgh=1En HleSe「1eS,rePOrted弓n February2OO4)wasa32・year−Oldfemalewhodonatedb100d belL〟een1993and2003.The componen【s prepared from thesedonationswerc13concentrated F8Cs(Ofwhjch lO vJere短ukoreduced)andone platelel(PLT)concentrate,Fourteen(eCipients,Ofwhom10werest=alivc.were tracedTen p】EISma donallOnSWere USedlo「fraclionated plasmaproducts. The s・つCOnd〇aSe(∩一n【hlnthe se「Fes,rePOrtedinAp川2004)wasa52・year・01d manwhohaddonatedbEoodsince T984,Ch;efZy between1996and2002 NcHnVeStigations werecarried ou=ntodonatjonswhiehprecededth8VC)D hup.//vN.W3.rrllerS(leTl〔e.VJEIeY.(Om/(gトb▲n/fLJHtext/121606285/HTMLSTART ページ6/1モ donate(inprlnCipre,becausetheyhadbeentransfused.thesし」b」CCtいVerコ由eaこ、ノノ・:・二」しトコ′r b100ddonation)・butaEsothatthepatien【shad”therLghtさOkno∴′汗∵PGSCdhy Whichputsanobligationonthedocto{tOaEerlihepa(1Cn…tclai(、・1叫:】即伸し′: individua川skisnotquan川■ableandlherejsnoava】」abre畑∂g〔○ここFc;⊃√つC〔∴∫「・コこ・、 Anotherfactorfavor]ngJnformFng reCtPientsist〇redL」CCi・1e r【Sトつ‘三FJCC/tC7Gr∵こ∵∵∴ dentistslandotherpatients・TheFrenchc汗cularnu[Tlber1360fLJ;.「こA.L†2〇:㌻「 PrincipJesof【heriskso=ransmis ionofMnonco[Vent〇nltrans〔1JSミru、1己:Je〔:S一 し PrOCeduresandhadclas if=∋dlherecipientsof Eabi】eb】〇O二comFO{1C{1ミニ1rLhc =/ rfskofcontamination by thevCJDagenl.Ford=hcsereこS〇FIS.Inrranこ己.r=・.EiS、r∴ Patientsat high riskofprioninfection. PRECAUTJONARYMEASURESFORDONORSAND L^L31LEuLOOr〕CO」い○トに:.Liこj FRANCE ht【p://W、V】・jnlers(jen⊂e.WjteY,⊂Om/⊂gトbin/ru=texり1216062呂5′′mMし5Tん汀 】nfo「m∂!rcローcrdoc:G「S「L二√P‘已∩こS∴㌃将「∴∵「 且・・・さ1〔∃且…且 S:1ご・二t∋reI、l机言0Jnfcこte⊂:bこし三f F)r〇山CtこfromthefoodchainlaPUblicheaLthmeasuretakentoprotectthe qcr二÷;;10E〕し}こt〇∩∴〕re=aL山○〔ar/‥1亡OSし「eS tO「edLJCetheriskof†ransfusiontransmissionofpr(0nSWere r「1い三r「つ,lted r「ltrleJ卜(dn〔j Fra㌻lCI:三・rlrCV山こhadvancesinepjdemio10gicknowJedge・Somewereputinplacebefore trlel二rl(ロe「CeC∫【)1e fけSt CaSe n「t「arlSfLJS⊃∩一己SSOC■atedvCJD.prlmar[1y toreducetherisk oftransmissionof 汗r「C=11S Ofこ」D=lrld[「Pa「[⊂∴こr!10こ‖「〇genrC forms,Thefirst case oft(anSfusiontransmission ofvCJD ・ハ、ノ Ll]〔:=1e:「亡〔lt卜aLJ川つ「teS「t:n亡∪べa「cF「ancetotakenewandcompJementaryriskreductionrneasures, /=\r「(:h廿e・二八CしS瓜1nrこit「S・′し二O「lご「5.けe LntrOduction ofleukoreduction hascontributedtothereductionof One dEfficuny両th the cu「「cnt sJtua【On LS=1こ∴ C㍑りCua∴ thoyarea川Skandmaybed〇.atngt卜1。「じ。。C T。,。。/1。、√こ.。∴1 reはtive】y young and ccuEC donここe the]r b00Clコe、ヾPl「aHLrT∴[;Jr;こ∴ OnlyspecIflCPreVentVe meaSU「eagalnSt P川⊃「、Cし、「lIa[nnここ∴lこf p)二 trlClrl′7C=oLJS〇く、L(いIPrCPltrarエrT1∫)Crl叫”〇Od56(.thasbeenshownthatthiscou(dreducetheinfectivityof 油つL‥lつOdLン′己mこ3:5〔(一′こ57)コ⊂S〕1{e=lご、己SihecasesofvCJDtransmissionbybloodtransfusionobservedin :こhに一丁 一しr」5ュミ1−r ⊥し「亡lregar0.sron d fO n0いaC」fjJauq「of【set d0 1b fo「pr10n f【1te「s).0「bo【h hJコL/・∴Crea:(}JC tCJ:l〇:1hノ」kぐ‥r・」=こeごb〇つ′】components,it couldbeconcIudedthat thedecreaseisby 己C†・「11n aCC〇し」「こed:Cr Ll〉/cuLしOr二rl、」〔ミミC〇=〕(】COmPOnentS.and abovea[=hatit hasbeen estabIjshed that the 佃:T00dce;(/ほC)Ea㌧′e「(‥Jcl?5「「〔【cし7「∴に、[la:ZtheFnfectivity=aneqUaFarnountofinfectivityexists.wenow Ll「いIl㌻「P】os;ll;iJcL−′/O「CCJこ:Crlr C:efcrc[[:;]e∂「SaneCeSSarymeaSUre,but certai両ynot sufficient・ lnthe prevent弓0n Of any t「こnSfL・SOn rSka[仁}「−」brLJnlし二二こ、∴しlし「: blood componentsS neCeSSこ1「1′ Be】nglhe nlニニ【亡※「〕OSe〔1二 ∵∵ナ transmission by b】00d trans[usLOn、SUCh E.S= rl;〕⊃rta:、ノ : the exclus0nOf numercus b〇C二Idcnors己2・h亡=,,r−て亡aSLlr .し「:【 ′JニtSlrl二・rCIC○=Cこorc= −ニ=ruし、こuいOnarymeaSUreS,SPeCificornonspecific.putinp!aceintheUK58・59 r「e rに汗ごし;inSfLJSこC「1〔:71Sこ011つr VCJD・lnFrance.theprecautionarynleaSUreSfoILowedthesame rll‥eI汗「ごし=しr.i〕erし†collrニ己rY、: EH=こ⊂:rS ThecjrcularofSeptember23.2005.60concern■ngthereportsoI Transfusjon measures takenln〔〕ther coLlntrじさ,こ]・L:eSSer.し have stayedin an【endemEC a「Ca For cxam;〕J.’he Chr Ll「r こr?「GLノ訂∴しノ〇rこ1S卜[己。t:ニこ∵ −Tこrし;3・C∴trこnSmlSSion of vCJDandthefirst casecf aFrenchdonorwho しに∴心ごつ雨theこrcs31「aSコJ【卜しノ二=、ilCrS亡、Onda(y tranSmESSionbytransfusiQnOflabiLeb100dcomponentso,by L5e C′3]rgCヨjつtrL}rlent3O「er:I,)=こ一;一e3Cl〇atrentSWhohadreceivedtransfusionsofbioodcomponents Cr骨lErlE3f「OrT”;0[つ「SV/h〇r呂l〔∃r(jevu:opedJCJD・ThesuccessiverneasuresinstitutedinFranceandinc=」ding 川nf)}コrake「fc)(てン1eロtlてe「tO「mS二L CJL]i)eforf:川e emergenceofvCJD,areShowninTabEe2. VGJDep厄emic二in1999.己;ドeO;〕≡e vノho nad s;O「−こユCu∫−1L∴◆ excluded from donatEOrlr120C].t WaS Lhe s汀∵し〇・庸( France o「the UK vノaS re(]uc(ゴd!03months:′コrrコてrld:〔=∴ し′< measures to excude from〔」crlこ.こCn】∩〔】いJlduこl二\「ニ ヒecこ period of 5 yeais.6566 TAt3LEl・PreYCnlLVC nlea3urCSin the UKa9ainst the transfusion risk of vCJD After a case of vCJDln ar11ndNこ」ua〉∨/ho visト∴=∴∵ ∪ト、ト 2001an=ness that【ed to「1LS(]ea=「【n2〔)0こ,しこ∴つ○:1こ1二5こ、 COnSide「ing thalthe pat佗nt naJbecor¶e冊こ二:C二 律こ し have beenident【fjed\Vth5S已卜旬∨[g ajread、′・rJ)∴J亡d〔三ニ。∴ Japanese hearth autho吊−eS:ock the〔eCS】Onこ0∴※CUduト′「′二∴ COUntry between1980arld19S6.0rle Can Sこり:11F3(・○:、 ∴し two common poIntS:they c「OSコa[L fronterSこ1Jd=;つ「C己drし」rlf〇ト「′三r′亡1r eVEtaviredamsaEpfodnaStlre ’ 「 こ つF 「 、 {C 】 二 こ 二 し 己 : ヒbf ロjC 「a こSc1 「 こ ■l ごce ミF 「lT1 、、′CJO 一丁[)O「ほて忙r【Of p己Sr「、こidesミrl亡づ‘or卜云⊂tご、rdtl〇nfromnon−UKsources. しtヨし:ぺ0「edu二tOr、O「a∂ヒcヒこニCド√ニロリ二てS 「1P〇「t責こ二「「しrF=ドP「o「「cこPle‘、!さbc「n∂√1ミニ「」anu∂「yl」1996. Pe「∩㍉〕ne「†Cこ「こゝr:ゴヒTe「「己「こrl…eOr汗訂SfしJS将na托e「」∂nUa「yl.1980. THEVARZABLES OF RISK OF TRANSFUSl〔〕N TR八「、と:L‖Sこ二IC= し て1PCrlaLニー、O「F=「⊃仁「「○こPC■「−5日;○’○きS【厄n16yea「S. COMPONENTS d010′Cビデe「「こrlこ;】SeロFt「3「Srし引OnヨnyVノhe「eれthewo「」d∂Re「Janua「yl.1980. 【、し三rr−甘1C「1こ 計・・回田回り・回 Pe「n「a「C’tdE・一声’「=[lnjTl0√3しCn〇[〇1nC(SVJhosedonatlOnShavebeentransfusedtorecJPlentSWholater こ】いノ亡〇POつ、ノC」口 At thisstage o†med】Ca【krlO〟【cdge,」t jsc】eこぅ√tn。、てaL【tト he「esIS(Sngte−donor)PLTs Aphe「esISPLTsrecommendedfor rl、こ←∴ニ1 are not c】arified.CerlaJn elemerl【s are hG^′e\′Cr、三rr【二fこし二: 1. The numbe「ofねb】eじ竜OJCOmPOrlen一三′eこ己トノCd blこ、L;j(1■三「こ to the dates o†汗e ep]巳r「1C and H=h巳叫号一CこいC、・、r {、 Eeukoreduction.etc) 2. The prevaLence of∼nfectCnln b【00d dcnJTS こqreこ−1C亡■ ) l八LiL≡2r‡’rcvi;=・、▼′しImULIこ・urCSin France against the transfusion risk of vCJD UPOn that】n the gerleraJrニOP山aいO「Whc∧,王√こeズP(つ∴∵汗一つ」】 taking FntO aCCOUnt the㌻1〕卜er enc ofい〔i(三こIl−rldt亡 eナ三こ○「こ∵㌻Gこ「J〔こ「n「eP 二ノ;1 一 French population and【mLtヨnHlg these二3〕Cニこ三SCS:J l こIernl月〔Lコ〔t已rr{=「ニ〔Jterra′こaSOC・卜jSニrly′OfneurodegeneratrvedLSeaSe・ be b】00d donors(1β一65)earS)and e;コ、e:○こ)e〔∴「二‘〇 Re=3こa「二C]SCこrC]こfaヒCヒニ○こ」こOTjPつ10∩こS∂ndbatchesofp(asmaproductscontainlngPlasmafromdonors ノ、f10a!er「」e\′已opecsCJDfCJつc「air⊃ヨenJCCJD.havlngahistoryoffCJD:OThav.ngbeentreatedwlth 1〇「nlC「eSOf芦Llヨn′C「3「 ,こcna′∴「ニFミ。lstEJSer03HPObUC】ohw individuats pe「1m柚即=出口orswhdrゎこk号已t ha(eCent reeVa山at:C)∩.汗把「Umber of・:咋じCIcdい∴二こ′∴し Pe「「Tこ【e√1†C⊂「〇rCefe「「ヨ【′「こ(うSご0「hrs◆〇γOfneu「osurge「Y. 1:ニ「 T「ac「コC「「eC〇e「!5CFこLjc・rニノ〕OdcoITPC「entSCOHectedf「omdono「SWho)aterdevelopedCJD, 100cases−nStead of3GO)▲Lead【∩ヨtO己・eニ■r「at〕し Per「1訂己「、こコC「こrdcre∫「ヨrlここSeCrし「己「Srし」SOnOfgr舐 Ca】c山atlon椚ti「e UKgVeS aPreVこIenc亡ニー r11こJ∴ノ ト、eこ3arlC G′5Ca「doTLalこ己ここ〇dこ::「1Pり’「entSandptasmaproductsobtalnedfromdonorswholaterdeve10Ped avallable】∩【heしK vvth res山【s from th亡「1三こリJl己Aニ1「†1ニ∴ ソCJ〇 P「Og「eSS・ ■こ1こら 」eし。korcコし」こtCrl亡fce=いar00C二[rC山C・s一っ「8reS】dualleve!く1xlO6/un!t. γ⊃e「「¶〔ミne‘「tl亡テ亡「「己がc⊃∩ニ「Sい「〇皿ed・1J卜くfo「1yea「ormorebetween1980and1996. 冊ect仙ty of alab【【e b00d componentl・・∴:h rcコa「dlJこ∵主∵1【∴ an‘一冊ectious dose,rqef】ned asけe mLnnlこ一dose⊂tlrノ;1こ/〔ラ亡い つ∩′「■ −e」JKO,COしこtC〔こ汗岩pasrll亡う:FFPo{匝S[radest■nedforfractionation)toaresiduaIlevel<1xlO6/unit the mode of corltamFrla:将n glVen.At pr(iSer’t the:㌧1∴、 The stage of■∩†ect■C[■∩けほCOnCr trLeleve:○ざc,r⊂しj】こ: rJ n01tca「f「ofdenitsedtOnにて亮にD「七=「し→〇1×1くeノeCB‘Jノし ∂」、己ご己R 「モcごjJCtCnC卜:こLi「1eO’piosr、コT「PLTccPT■POnentSthroughuseofPLTaddltivesoIut10n.POtentiaLlyreduclngan ′_」〔二こ inc「eases仙再h t卜c duratLOn Oざthe【r「C」とこ右0rl巨∴、.、一 mf′≡こ:〇し。S○∂ご rt!「,/「・jIlterS〔C・l〔eL、、rrl\⊂OrT、叩rtJrllてext/iコユrこ口ら2SS/HTMLSTART ページ8/18 h【tP■//WW〕」nte「S〔■enC亡.W■」ev.〔Or¶/(弓l−し)れ′ru】ltexて‘12ユ6C5Z♪]′HTMし㌻′\;、て 09/06/Z615:SI =¶OmEecteds]b】eCtbecomes∩:ectNefortherecipientoftheblood:anhlfecteddonor,donatin9 山「:nq汗ee叫PartOftheErlCUbattonperiod・maynOtbeinfectioustoarecfpient・Accord<ngtoanlmaE StUCfleSl:〕]oodlnfec=ⅥtyCan beden10nStratedatJeastatthestart ofthesecondhaJfoftheincubation Fつer(Oda「1叩e「「aPSa/soearrerいhe−nfect仙yofbloodprecedesthepresenceofpatho10gicarprionin thcbraFnandtheorgans)166Evc=thoughexperimentssug9eStthatinfectivltyw‖beabsentorminjmal dJ‖[lq廿efirS【th両ゴ0仁けeincuヒat】OnPe{iodrcaut10ndictateslinthecurrentstateofknowEedge,that humantransfuslOntranSmission rema【nStO be、ノニュrdこi、Jd一〇二 a− PrIOnCircu(atjngin different human blocd corllPCne{1tご「71こ・/、三 manner,inpar【icula「†「om b「ain e∧:「acts Th仁ふ己こ′∴Fし】JlさL( quan川atlVe Characte「jstics oflhe hum乙n Pr‘C:ler7「ra ;[e71Cj3L :3tr a蘭rebFoodcomF)○[ent O「g【na・一ngfromadono,intheincubationperiodcontainsatleastone are those thala[e formed of141026pllO】ecues/l:。T t「し三:.こ: Unknown.Fu「thermore.the consequences ofし」5trL与[;rLOr rモJL,:tlr p:=し maintenance of PしT†unct】0∩)and on p≦asma prcte∩いS!○;こ1 ・rl ̄ the risk of neoantigeniclty andinduc=on of tnn≦bio「S lnfecい○甘Sdos巳69Asmanyye己rShavepassedsincethepeakofthedietaryepidemic.infected 佃、ノ1C=aSarenO:onger∩(hem=arstagesofinfection・Theparadoxcou■dbethateventhoughthe A MUCH−^WAITED DtAGNOST[C ̄「EST nLJl「be「oFrrl(ecIFOnSFSnOb[gerFnCreaS.ng.【henumbero=nfectioussubiectscouldstiF=ncreaseover 回・・・回国回…匡 Lacking nucleic acld and not p「0VOking any EmnlUne「CSP detected by m01ecu!ar orsero10glC me川Ods usua【Lyし」Sed tlme S?CO「1()I.heeffFcacycf】eukoreduc−jonforceE.u■arcomponentsandfo{PTasrna:Eeukoreductionof hanlS!c「bbodcontanllnated、■再=「ascrapi8PrionremovedonEyalittleIessthanhalf(42%)ofthe markers has.up to now.reached a−dead end i{1fecilVLT/PreSCnt・becausetheinfectivitydividesa■mostequallybetweentheW8Csandthe pL3S(lrこ5’170r7’ Leukoreduct■OnTTlaythereforebeZesseffectivethanongIna‖ycalcuJat8d.As demo{lSiraこedIIStUdeSbascdo「experimentaJJyinfectedrodentbFood.tota.bIoodjnfectivitywillbe. Lnasympt(〕maいc orsymptomatic冊ecいC}∩.the mcs;JSefl」r d1C‥ Pathologic pnonin the bIood.Ho、VeVer.the fo「m什aこthe prCJl:∴ノ∴∴ Centra(nervoussystem・PTPSChasanaggregated forrてi一∩:he1rこ du「」「;}川e町「Pt〇mこhcprase・from20・30IUpermL135andthedistributioninthecompartmentsof that difference cou]dinfluencethe effectivenesso†(j;己つZl〇:、こ1(二;二/:::C、 b】m己LS】l:hcorderof30pe「Ce=lてinthebuffycoatand50percentinthepIasma.71Thepresenceof H工〕C貢IdごLrTrnFeciN叫′hasnoiLcenestablishedinaforrnalmanner:it$8emSatanyratetobelnJeor CaPaCity to detect the cerebraJform.Fur【hermore,けte FJ:ここ:l〇:1l :C’ Prions.butitisthis patho】ogic form thatlhe【est mL.S:deこL):r dependon【hephysicochemicaldEfferencesm=1et∴Ofcms〔Tr]− Onthe resistanceof the patho10gicalformlc)PrOle・:1こ1S己iこ norlO・二273Thl」ニ▼afterthempEcrlentationofleukoreductJonof[abileb−00dcomponents(Whichmust r′ havcar亡SjuaV/BCcountofく1ylO6/unit)・theinfectivityof和CorPLTcomponentsisdependent A】a柑e nUmberof unknowns「elaling to the t「ans otspJeh n mocraluIJe fsnoitul ev d a mitpof esUL ミ ;m aEp udserfo !nJHCmaOl no doubt be resoLved when one orseveraE dbgnos reduce t卜equarlti!yofp】asmaa←dthereforetheinfec=ousdoseinthecaseofaninfectedblood SPeCiIicity.and「eproducib=【y,become ava厄bJe anJ」Saヒ)e二 ∴〔( being′madetodeve】opsuchtoo■s.whichcoJIdbcし㍑七C Er=∵二二 J COm「)0∩ごnt reduce even furtheT the risk of transfus0n tranSm13SlOn Cデ▲〕[,1: ,_、ごノ 4・f屯cIPren(n「ethIOnFnごh〇mOZygOSEtyatCOdon129hasanfmpactontheriskofdevelopingi‖ness,With Pe「hapsahFern「Chyof「】sk・mOVhgIn〔1escendingorderfTOrnMMhomozygotestoMVheterozygotestoVV 「10mOZygOtCS F=「tho「morelnOnhomozygosityfoTMMdoesnotappeartocon−erabsohJtePrOteCtionfrom ・lfectOn・aS柚catedbythesecondUKrec■Pient case(anMVheterozygote,nOnetheFessinfectedthrough lherrans↑us【OrrCUte−andjnexperE=renLafanjmals・13whatiscertainisthattheclinicaroutcomeof criteria:93・94 1. Avery high sensitivity,tO detect anlnfecttoL:Soao that1l、. 、・rC:∵ aiowIevelo†PrPSCEnCirc山atingb■00dFSltkeEIJ,tC)bcZrfここL∴′ r 2・=ighspecificItylSeSSentia..shlCelhenorma−proteLnlS;rC、二一 lr二 :ransfus0n(rarlSmFSS】OnaPPea「StObegreatest forMMhomozygotes・Sinceth8ya−oneofthe・exposed” 【10PUはt0n d乙rSトくha■ノe deve】oped川eこJISeaSe, 5▼ Flna】y・=1eenコthoflheincubatronpcr】Od・aneSSentialfactorando†whichmuchiscurrent−yunknownand tov/hlChmus!beaddedtwo】mPOrtanてParameterS:theageoftherecIPlentandtheposttransfusionsurvival, V舟ch】5heこ叫1nf[]こnCedbydeathsduetotheunderlylngllInessintheinitialyearsafte(theblood いansfusr(〕JI PRlOH FILl ̄EHS resuZtscou(d havedisastrous consequences.m terms〇巨l〇:f L COnCluded’lpositive,”not to mentton the unjust云f巳ed ce:亡rra1[:.1ar{rしし infections,eVery(eaCtiv8reSUlt obtaFned throuGh b【〇Od(jo・.ニ1:「〇二二′ COnfjrmatory test to separa!e true・POS.=ve resLts frcHTIFa\)3ト trueconfirmatoryleSt WHlbe avaEiabLe.vJhelher=1e SC=しtに1 rrPL∴ Simultaneously,Orif one wiEEbe used for’confrmaいC}:「○!r. .Lv SPeCificFty.it has been caEcu:atedlhaいf adlEIGrlOStCこし;こ SPeCiflCity was applied【o the screenirlg Olblco(」dorlalF〇TIS:・l−rlri〕i inlO,O (Whichislhe stimate for don rs Hrと1reし’K,l.二0l, L」こ1;ミ 計=摺日夏・‥屈 Spec狛二PrO′lrC〔了→C巨CPlfr=e「SaPPIJCabFeforcertainIabiJebtoodcomponentshavebeenundergo●ngVa咽ation,The fけSid(natに、TISP「つ⊂(ノSSed∵ノ冊けCSePr.0nfFte[Sdernonstratedtheircapacitytoreducespikedinfectivityofb.ood bylhTr:e0qSl、・Jh]Ch㌧・/0山いJ仙0じIadoubい11akeas.gnificant contributiontoreducingtransfusionrZsk.74Th8Se f■ters L−aVe Dee[P「CdJCed bゝ′tVJOCOmPanleSWi【haviewtouseforRBCpreparations:aPPficationtoPLT P「ePa川上on5a∫1d:ロこ〕加mlか・ノa」【hr=「e川Crk・Theva冊at【onworkhasb8enCarrledo=tOntheね‖始ukotrap Phaseofthe王nfection and、VOUtd correspond totruc;:こL・rt ∴ てつrl donoTSWOUEd giveafa【se−POSitjve result.0∩=1C C)け已r .し 1∩雨Hiontestsr96lnFra=Ce,Whereanest−ma Carriersof the va‖ant VJOU】d be detected.bu【t:lt;∩Jr鳥: the UK:10,000perlm州ion donors.∨/ho vJC,し]1d n⊂′てt・(二 二へ・ informed ofthei「bio10g■CSt封US. FinaHy.【hese testswIElhave to be(ePrOduc】h】e,−5El}いこ time scaZ8thaIis compatEble w侶1the sheEf Hle cイ戸T Oblained)for nucleic acldlest■ng由tほnSfus=〇「. affn叫Pr〇nre山CtrO1fjltcr,ntegratedErltいefiuerCompoSafePrFresenius.75・77andtheTSEaffinity[一gandof theFla◆hogenTer110V0an(3(頼柑nOSI】C teChnc0gleS,integratedintheP−ChptMC(MCforMacopharma)frEter.78 Changcswe「emade:othc Pa‖仙e「afterthe■∩一tialvalidation,Whichaffectedperformanceandled†oits 抑thd「a■〟a上ノ\ne・ソ⊂OmblnedJeukoreduc=on and p「ion「8∩〔0VaI川拍r from thesamemanufacturerisnowunder develo;)ment T[leSea畑∩=y FLrterSa{e aSSLImed to removea”detectabEetracesofinfectioninacontaminated unit androreducernfech/■Lゝ′byt「ansfus■On・ThlSCaPaCityhasbeendemonstratedbyastudybas8donfnoculation.inl hamstc「s.Dfeし」kc)reducedwhoebloodlake「lfromanimaEsinfectedbyaTS巳Whentheibl0Odwastreatedwith PaSSaOtラ○VeTa†吊err「ohamsterbecameLnreCted・Whenthebloodwasnot用tered,SOrnehamst8TSdeveloped 川nessassocEatC山vl柏thepreseFICeOfprEOnSintissues・79Nevertheless,althoughth叩Otentia10fthese川tershas beendcmonsirarcd byexperEmenta?infectEV}tytranSmissionsinanimalmodels,theirefficacylnthepreventlonof h【tp’//廿V∴・J3.ntC「iC]en(巳.、〟】eY,CO=/〔grLL)r,/(uEhext/121506285/HTMし5TART ページ10/1さ The Eack of a test with the above−mentlOned charact,二「St,=S h from b]ooddona【ion allthosewho are carr■erSOfvCJDanJH r Jノ.、 blood donat10nSOn nOnSPeCifico(PartLa[Ey e‖ectivc rTICa5JrUS Sl」ここr 二入J【r、、 18Ukoreductionofb100ddonat10nS.andso forth;thい「¶POSS■上州JJ−..しJ、 risk TeCIPlentS:the dけficultyln CO】】ecting dataaboLJithe meardし{こl;二、 Cl∴(∴∴L, hltP://VW3.1nteTS⊂ien(e.W(leY.⊂dnl/CgFqbin/fulI【ext/121606285/H’T■MLST八代T ∵告(ごJhabri[tat■ngdonorsexcIudedbecauseofastayJntheUKduringthe aハ1C[1:nccasesofvCJDjdentifiedinFrance,SUChahistory hasbeenfound e二こ1rユrコ、J:(tしIilfC・dedono「SOn the pretext o†avJSjt10(he UKwhen almost aIF the ( こノい Do non−MMsubleC!s(thatJS.60O/c Of= し「10「こI 「 yノ migh(they deve】opt a=er akMlge(PC「○〔iつ:rEICL・∴ ′、へつ r 〕「erl†○こtedIntheirowncountry)・1t wouldbenecessary,furthermore,tO lこrehabElltation’lfoTSOmedonorswasnot offset byanega仙eeffecし ai,7・コ〇Jrc transfus10nSCreenmgteSしTh(SCOUId raise concernjnthe donor rl三t they carry theJnfectiousagent of an川nessforvvhich thereisno the epidemic.vJhLCh mEgh【,fu=he=¶Ore1つC=〕Ll【こ、;▲ニr(・{ し二 Situa【ions.Jnfected asympto「丁柑古C Subいここここ∴∴′○〕鳥:ノごト (eCIPFentS COUld becorTle SymPtOTatEC‘巨」yいL▲VL= epldemio0g忙ay dj5aSい0US an「−㌦/o「、∴1’こ∴cゝ 「1〈 and not becomel=hm−Or he「se【†,butlヒ/こここつC∴ 「r二’POtentaJuseindetecting donorswhoareinfected byvCJD.the付st Circumstances have been obse「veこゴln Vドコ:,=rl 〔・つf三a[Tl;〕e reposEtOries,tOdelerminethe spreadoftheepLdemlCinthe lJ;〕∴atC)nlAssessrnent ofthepreva]enceofvCJDindonorsandrecipien†s L,lrrJlrli血smaproducts.couldbecarriedout vjaanonymouspLasma infected rec岬Ient C〇UEd devcLop s、ブ′mPト∵一1;∴こ∴11C: donors who are carrers of vCM〕but d〔ノ「こし ひJ、ノ0.0.ノ 129wou【d not be】den川【ab;e v川卜Out こニ【ニ〕こfこ〔」√ l l≡sISO=eOfthepossibiJitiesprovided bythereposito,y PreSentIy 30∴A”(BI00dandOrganTransmissjbIelnfectiousAgentsト971ndeed.for their comr¶On dono「StatUS】n t\∼0(Or rTコ「し「已こr: because of anonp「otec=ng genotype こJClニ∴ 「7:〕rfectyvalidatedtestson nonanonymoussampres Je=1’〃∴el ●「「r、 reguFar.infected donor and o=ntc(r「UP【二 =ノし∴ extent the deferra】○†t「ansfusedコaいer○「C■て1J▼ eSt17「dst「0ngUnCertaintiesabout atransfusionepidemicofvCJDrequires 1亡」ニL・P亡3亡こrlb:Shed by the UK,France,andothercountries.Ffaspecifictestis ■一contamlnatjon cycLebeい〟eenけe dc「 ノノ′′ USeここ いd[二;fこニ「−〔ノ L」re!=−「・1 しC the opportunityto considerre‡axationofthese measures. t川S P「eCaUtion nas p「obabl)′aVO【しCJs、 based on a malhcmatica[modeい1aS Cし1こ^二, う ミ 廿 トl ∧T I 三ECNU majority of dono「S\Vere EnfecteJ†「Om : ∴LJ‥ Eい・rヨロE琵琶 exc山ded from b【00d dona【ion.9ジ ∧「「、ち5∴車1ご二 、コ〔「、二!/さrl=1 ト∴PCWnlWithanuncertainprevaLenceoftheinfectjousagentinat−rjsk 「】「〔)し」[「ご n′1こ」 r→r r r、り Jr)†・「「 6. Howmany dono「s and「ec■P】en【s\・Jjdこ1・こ」二 〔3r/1亡:aEllコi「じ言出rr、、1已a:SenCe Of ascreenIng teSt.infectiousnessanddurationofincubation 「∵ト・ユ/ ェ′lCe\〕lETl hp∋r’け′′r make up the eFementsthatinfruencethe transfusion risk ofvCJD transfusion Eookbacks and由vestgationr)ノ) L ご・ O「ごnaVe nOanSWeTSlandtheorderinwhichweenurneratethemprobabry SO=」tions w川be found Pe「iod oftime(】ess川an adecadeトtこi\’「1 genetic staius of codon 129 7. 肌用=廿e threa【0†transfu5】On tran5mSS∴rlOf pr○∫1、1、○し.こ 已rlC and afterthe peak ofthevuDepidemicln1999,W川therebea 1n other countrles such as SpaEn arld S:】L〔∴:、r;1L二.こr∵∴jC=JF∵ニ∴「 EmTLISトニrl:ノrコr「つし」;つ:つnOWltheepidernichasremainedreLatively(imitedこaPPrOXimateLy / t こL C・J〇 that the prob弓em has novJlaken〔)n an、rnしl:つ「 rl「∵∵∵ il「terShavebeenintheUKrThe両iarpessimistichypotheseson e:さed downward・Furthermore,thepeaks(ha(foHowedtheinitialpeak こnL一∴5 t「ansfus10n Safety 〔う○:CJ「○二:′JrlFcc「∵二「TlnatedgTOWthhormoneweresmaJ)erandsmalFeT,aS,fpatientsof 卜㌣ 祀e上5:l〉J二1=Cこ二:LニLtこO mfectlOnand/Or10the development ofclinica==ness.1tisnot CONCLUSIONS VC」つbut thehypothesisofasecondarytransfusionepidemic.with e v 回…回国田宮瓦 gh asymptoma=c carrlersof the prLOn.CannOt be excIuded The posslb拙け〔=abooc component「むCPeこし」L」い∋しト regulardonor deve]oprngt afte「the sこme ar「0∴1iし† 1己frSt CaSeS Of vCJDoccurred,and no evidence of c=nicalcasesin C㌻し「′こ t‡00bservationsinthegrowthhoYnlOneePidemic,FlnaFFy With the hetp of at「ansfus0n traCeaヒL≡】tソa喜〔1コSTこ3.こ「C CS.COmPared tointeTSPeCiestransmission.ashorterincubation dietary epidemlCISnOVJa PrObtem of chronLCIS,「∴てコ∵ 「El「S血ss10n Thiscou)dcausealargeroutbreak ofinfectlonthrough infection vIa medica】dev<CeS USedn S_」rE3e「)′つ「■l∴J「: ∂=「1己■に1bソfood つ †1:!Lユニ 「・Crこe○‘Tt二「 「( 山 し An essen=d notic)nislhat of protect SCenario.where cases of vCJDvJOU:d s仁o b100d components arld thusinfectedヒハ the screening of bIood conat0nS,Vハ○しd be and harmlessnessIS reSO[ved.0r tO OnLソUSe concernslO㌧−eVen】fap己Ttla】re□]Cticr10f infected recEPdenLs and/0「tOinduce aにng P「OPOrtjonalto the o「lgl√1aJconta「¶1naいng rerS t∵∵汗V/aS血坤ed by the known numberofsymptomaいCCaSeS 〔「ト亡G C Of epidemic. l亡)E3CneraipopuIation ofthe UKandin France.andhowmany L()「rl己reSUltsof aretrospective Britishstudyonthe prevalenceofvCJD rこ)arld tons‖ectomiespointedinthedLreCtionofamuch higher ニ}∵車Cr−1 L」′こさ1「 †/口「Sfused recipient carryingthevariant,PrPreSwasonlyd8teCtablein 1rlニご・ニand notInthe appendix orthe tonsL(S,this retrospectlVe C⊂O「 (iし」(りt;;lSし〉Cl(二’1しご(・t∈こtC㌻「Of the pathoIog−C P「トOninthe appendixcourd have underestimated 〇ここ ㌧ご叩(○ )〇P山at‖〕∩ C Cf cJrCUJating pr10n during theincubation phase?Forestimation of ‥い Many profess】Ona【s【∩汗佗feFd of t「ansf=Sl〇・「1f〕二いし: acknowIedging that demonstrat10rlOf thelr C=nc=c ∴ and w付ch a「e dom【nated by the absen⊂e Of∴已。1G「C3い these州ers†sprobEema!C and EeadsIo asl∵こ1rl;qUC5t、二:・こ∩亡∴一こJ、二† te5t thalwou【d be appl■Cabre fo「biood con;jてC∫1三j 「 ・−○・〔ノニbこ」† test? eSS>5that of bloodinfectivi【yandthuspoten=altransmESS■b=ty ㌻「し‥’行vem CけCUIathg b100d may bet0010W.inthefirst monthsorfirst 「【cニ:O「by t「ansfusion 口「し1「 L・∵已l:[∵仁CiJt=nary meaSUreSin transfusion.especiaElyleukoreduction?The 1L〕こ ( 一 一「;1r151、S Pljコ し▲J infected dono「s川e p「OPO「tと〇n Of rec㌻;’」「 ユCr一こ二「・二二」「 relJ∵=S SUnknown.Hasareductionininfectivityp(eVented,OrW‖=t ○:;こOnlPOnentS?Up to now.the most feared contradictlOn WOu蔓d be th8 FYocedures for the LnaCtVat一OnOf Erlfect0∪5′コC「∴3ゝrlこ∴コ:二or’∴ Since they are armed at the nuc】e∈C aCds of:r巳こO aS己rLこ∴「rl JSed soEelywithleukoreducedcomponents.Suchafindinghasnot S5ノ11TMし5TART ページ12/18 http://WWヨ.inter∼⊂■en⊂e.W出け.(Gm/〔gトb∩′リ∪=Hり【′′121ト滝∴バ∴1 thcじr〇rlC、うuLc:becl√「let「Cし帖n「zltetrarlSfJS0∩・tranSmissibleagent−Whi)eth8riskconnectedtoviruses.bacteria 18・Chadeau・Hyam M.Ta(d A.Bird S.LeG」eTlneC S.t3em「ah卜」1∴〕El:Or、∴ exposureofthe Frenchpopulat10n10the E3SEaコCnt:COrnIつa;∴;二n C)(= COntainzng mechanicallyrecovered nleat」nF「anceand=1e小′「r’ /鞄52003;12ニ247・60,Ljnks 19.AIperovitch A.W[LIRG PTedlCting the s】こeOT the vCJDepde「1.1こ’二C・い L/∴ 20・CooperJD.Bird SM.UKbovineca「cassmeat con〇LHTledasbし「3(?r3Sこ/;こ1コU〇、∴申〉r COhort and gender.JC∋nCe(申Idem/0/F[針/20027:49・52・し1l√て 21・01adeau一日yam M.A‡perovitchAIRskoTvElr†ant Creutzferdt−∴▲kc:)JLS\JLlニtJn 2005;34:46・52.L【nks 22・Hi(ton D,QlaniA.ConyeTS L,Edwa[ds P.McC3「d:〇L.Fncど1C[).;コJl:lC一 1 0†lymphoreticuFarpnon protein accumuEatic)n h U(く1LSSUe SEiTr甘:=JrLt 23.VaHeronAJ.BoeHe PY,Ⅵ川=1.CesbronJY Eslma=on of eF〕CElr「l−CニニCこ1〔j:「、 a:「d〇」「記さ=トPニ∴\nCハ‘・「;Cr加1C「針nS.VJ〇UEcj bく∫COntrOlledby pathogeninactivation. t「こ「れSOr− り「■S「「三ニ〇∫10「、ノuDL5昌Ce侶血け行OmnOWOn.b即efitsoftransfusjonobvjous】yr8main l{「川1er′Sし」「Elと「トつ、つ「て「;つこ’Od:(:t「LS TSk OneETILjSIputinperspectivethenurrIberoflivessavedevery dayby いI=Tlこミ†」さO「Lrrてト・C LIJ:11こr3(⊂f c’ミSeSO=「己IISfusedvCJDcounted onaworFdwidescale.OneaJsomust comparethis L・川Il∴「L、r ′こ∴「CIコ「「ニt:、′C Eu「OPeanC〕Unlries,Withtheinfectiousrisksfacedbytransfusedpatientsinparts OざけこGつ:二〔:、一;rl仁rC:ho r、「亡〕:1SこIre5C‖mte′j that saletyJSnOt aZwaysassured evenformaJOTb(00d−borncagents. 「]cノCr L〕巳fこ′〇≧「L∴′e三、LJ;、IE”ソmeaSし」rOS Lj・三enlakenintransfusion tocounteract ariskthatisnurne(icaELysolow. r、こ1’「【jUSミロ:いノ∴tユ′嵩≡直OPeadhsn. Smlご:ahe、モい一r L’〕rfさ守つf「S:cEIS〔)Cf v(LDby b100dtransfusionhadbeen reported・Theprecautionary princIPle ∧CK=0守パ」三り〔訂Jに=1て CharacteristicsofvGJDlnthe Unlted K・ngdonl.Sご′enCe2CJl2ミ〕・117と己≡」1 T...丁∵ご∵ご∵∵∵ご こ二Jここ二」、._ 24.Rcketts MN.Cashrnan NR.Stra=0n EE,EJ・Saadany S.Ls Cr仁山’こ[ヒl、1こ・Jこh( こ汗二さ二二)乞1c〔二叩ek(lnstitut de Vei[[eSanitaire.Saint−Maurice,France)fortheir 「i’1、■P「L「′ノ J]Ll・ i、r‥「‘ し?し′Jlへ「1p_∩こS/一「:I「SlrtJCFe and Marina Mobed forsecretariaEassistance. 血/ecJβ毎1997;3:155・63.Links 25.Kondo K.Ku(iowaY.A case con(rot study of CrcL・こZ(erコトJ己Lく〔∴ ∴こ−E・=・′ 〟e(ノ′0/1982;11:377−81.Links 11[二「EこIf二N(二…三∴ E・‥ご∃互且〔±三 (Ls GJ\.こハニニ=:、CJ:}、rlSC[lCT.CurlⅢ∩〕RFHancock Fg.Jeffrey M,DawsonM.Bradley R.Anoverprogressiv8 Slつ〔rrコ直つ「「1「ご■1こ・一 い己IJJ)∈う:rl)’(「C己こ!】e し′cJ俺c1987;121:419・20.Ljnks 26・Davan中0UrZ.Alter M,S〇be=三Ashcr DM.Gコjdu〇こk Dじ dietary risk†actors.AmJ&idem10/1985122:LiL13−5 27.Head MW,円tchie D.SrT1 th N.McLoug柚n V.Nal:{「 「W Periphera=lSSUe[nv01vemen【inspo「adrc,.air03L三∴C,こ−1d:云「㌻∴こ〔∵:J」・ 2 FLLl,rlCr S臼’\′「;1rウこerlaCe〇L」S r「fcc†CuS Par†icles causescrapie,Stienee1982:216:136.44.Links immunohistochemical.quantltatIVe.こnd bわChem;C二】st」CZyJJ 3[1こ〔ノe「て○,■Jl【く‥‘晶誉/し障.PrusS巳∨ミOdanp篭0丹ocN∂A5ブリ982;7:・4Ik 28.Dodd R.Su=1Van M.CreutzfeEd−Jakoヒ〕dSea5e anこゴ〔「こnrlfusp〕r「J ‘i Clrl㍍こユh〔、ノ、、ノ 丁,1ご√OCOnSt・tし∫こ‘Cn Of mamma=anp「ionhfectivitydenovo.髄2007:274:576−87.しjnks 5 Cje、Ch[】Vl‘∴S!a:rnl;D ^ノa;ch=rLJlrJc[く仙丹MP.Kent SB.AebeTSOld R.Barry RA,Tempst P,TepFow DB.Hood LE Prし1r、亡r SB.L・’・〕SSma「C A ce己Fua「cene encodesscrapie PrP27・30proteln.C5〟1985;40:735−46.Links 1998:38:22ト3.Llnks 29.∈vatt B.Austln H.Barnhart E,Schonヒ)erger L,Shこ:er L.J〇∩こハ1F二「L)A「;、、ニ:】こ Jakob diseaseamong persons wEth enlOP畑=a.Tr;‡nSfLIS D[1 ロrlEミ:1Li61 〔5一「7し石目cトミ詫∴一寸k・1∴ノ号つご∧’a/」rパご∂けSc/しS月1998;95:13363−83.しhks 7H古・1こ「[■CL!(−、arFS.ミ㌔叩E0chbe:gDTutZfdJkoIsinUl,9q4 30・HoeyJ,GuIuviA.Todki‖AM.Newvaranr Cr巳Utニfe】dt−Jak〇し) music?Cか丁ルねdA5SOCJ1998:159669・70.L:nトニ3 U:1‥;)r「′一:〇’J’什∵に由]/dEILaトO ZISSeSS†「le POSSjbJ8OCCurrenCeOf variant cases.Eme付h7fec[Dj5 31.TurnerML,lronsideJV ,New・VarianL Creutz[eLdt−Jakob dEscaミe.けL:[]S′、つ、Lr二、 101623〕○/ rハS 昌[P∴こ亡r・こ.・ rつ(二し1JeJl∴.rVIcCc「rle;【、Drummond D.Sut=eA−McCardle L.α1reeA,HopeJ.Birkett C. Cci5(”C S・;raSこ「11Et)5【〇Ck CJTrElnSnESS▲0nS tO miceindicatethat−new variantsN CJDiscaused by the BSE a‡lい1tl−、▼′言′し「己「〔()了,3じ亡ト19己−50「・しnki 〇1v,jrこ rV3.:,つ∴3hL上E・J:.三・三二:巳「「vIL CnしJS已nS SN,Estibei「o K.AIperovitchA.PoserS,Pocchiar=帆HofmanA,Smith PG ノ1rlC\り 二.=言行∵く†⊂」[)∩ニー1e U・く Lこ7∩ご、ビ/1996;3ヰ7:92ト5.Link$ 8bod/宅ル1998こ12:255−68.Links 32,AguzziA,Heppner Fし.Heikenwa】der M.P「DnZ佑SeeEICr H.G・]こごご: rTl「て1J PrOPagationo†pr10nS tOCNS.β「んねdβu//2003:66・141・59∴口上5 33.Bruce ME,McConne=L.WiH FIG.汗0nS;deJW DetcctFOn Of vn「E・、t C「二」t: e沼raneura】tissues,」8nCeJ2001.358.208・9 LlrlhS 34.Brown P.Can C(eutZfeldt・Jakob dlSeaSe be rrar15rm=ed bソIr 10、′ノ【R3ご{r,:つ「Stc‥JミG亡三.一vてコ=edトA[onsiW−CuNMakzEbK(} L毒nks 付「‘川◆ ニミS[こ】コ・、ニS O’′、巧∴‥、甘ほ◆、■こごC・eリーニfeldトJakob disease.月〃〃/血u√0/2000:ヰ7:575・82.Ljnks 35.CervenakovaL.YakovEeva O,McKenこje C,Ko≦chLr「S朽S,MしS上・L二」0「/{; infectivitylnthe bJoodof miceinfec【edv/rth humEln−dcrVe:」∴「〕1・rldlこ1三う:1 、八’1t三っ′′「′T+「「、つ、○ ∵lJll;;、F C<、1「F)l)Cll’A.OesbTuSlaisM.Lulhert PJ.Co川ngeJ,TissuedistrlbutIon of 〕〔言一、二′{l 「つ、’:Otヒr■ ′「/こrElrC[eUtZfeldt−Jakobdiseaseusing ahigh.ysensitiveimmunobtottng ;バ3l,しゝj′ encepha10Pathy.け∂∩5付∫′0∩2003:43:1637−○・∴L=(ks こぅ:一J∵/1」∴∴」∫\こ〉 121/jユ15∴:、「: 「〔e Ejlこr:5し〕r」rl3Tvl.LnehanJM.JoinerS,G:〉Wlandl.WelchJ,Stone L,L10yd SE.H州AF. uTコ1C);lC「、⊃ /)Lr√r;・二)・:「「〔1r「「〕rlC「Iつ:〇†=TlⅥ川h valine129preventsexpressionofvariant CJDph8nOtyPe. 36.Brown P,Fbhwe[RG.Dunstan BC..MocAu]ey C.Gユノdusek DC COmPOnentSand plasma derivalEVeSn eXPe=me[ll;:h11 T「∂∩∫血∫/0〃1998:38:810−8166.Llnks Sこ∴、/「ごeこつ?ニ 30(i一7′1:−Iう 」17「ペニ \ノElrd〔!CreL」t.:f〔リ】・J己√、Cb cl;scase.p「0(l:〕「Otein genotypeanalysISOf positive appendixtissue samplesfrom a 37・Houston F,FosterJD,Chong A.Hunこer N,Bos†oこk CJ,Tra1Sr r、〔‘ L∂〃CeJ2000;356:999−1000。Links 38・Hunter N.FosterJ.ChongA.McChtcheonS,Par「∴E}mつEJT:こ…こ.:lC: Priondiseasesby br00d t(anSfusron.JG2nし′lrO!2r}C2,!i3二’、ご:∴「こ)− 39・SaaP.Casti=aJ.Soto C.Presymptoma【一Cdc〔ecこ〇rlOf p「=C:Lし一 40.Cousens SN.Zeidler M.Esmonde TF,DeSllva R∴▲∴已Srl「1th∴′J∴.:PこI disease由th8United Klngdom:analysisof epいゴeこ11○:〇SC∂Lさ、一「t■「二e∴− 1997;315:389−b5 Links retりSrほC【ハ′・コ「〕rこノ○しH「⊂e S:ucl′ 占んJJ2003.332:1186−8.Links 41.Hewitt P.vCJDandtransfusioninthe Unjted KEn〕こ30m Tra,7S/∴′S(‖′】B:プ/こ′)二 13BIS)op r.1「1rr!つ t:・{「SOr−L Bユ)buこtJNt PtInStOn C,Thomson V.TuziNL.Head MW,▼ronsideJW,Wi‖RG, MEi[S〇nJC、roJ:宮;′iL;SCePt三じ;:LTy E}11d r「cubationtimeof human・tO・human transmissionofvCJD.Lancet ノ\J〔)く.rC/2CO仁5 3〕3−8 L「1ks 14.Gl∵∩;ACFc「gLJさ二!lトご「J.〇()rlr「C[Fy CA.Anderson恥1.Factorsdeterminingthe pattern ofthevariant C(eutzfe[dt・ T5rc、;eJ∴′.S「√}ごL!Conつ卜/KHgE・ZyD,wl甘jM円thidA 」a・(つb dさ仁王、〔∨√二」○、j C;〕d・コr¶C】∩=1e U†く 砕ocβわ/曳ゾ2003;270:689・98.しInks 16rlJ^/I33ト鳥!三v・∋{∩〇●o’1D.Chusだ11〇SN.S川畑・Bathgate8,LeitchM.CooperS.HeathC,Knight FS.Smith PG.W川 42・Hewitt PE.Llewe‡ynCA,MackenzieJ.W■‖RGr Creu;ヱfeid卜」akDし〕〔】†3コaSCこrlこ:Lつ RG F苛Sト:「こ▲Cl(〕rS㌧=ノ封arl亡 CreJにrejdt一山hob disease:aCaSe・COntrOl$tUdy.A〝〃〟e〟′0/2006;59:11■1−20. UKTransfusionMedicine Epidernio10glCa卜Fk,View s:udy.VoxSu7U2C〇6.91ごご■−’・「i 43・HeyeN.Hensen S.Muller N.CreulzfeEdt・Jakob d」SCaSeand L}c)Ci[anSfし;5rC= し_「・5 17・E3r;1†d亡」Pご「コ1∴二「0叫〕CTCVi〔h^ EpcZemioIogie deIavariantedetamaladjede C>eutzfeEdt.Jakob en 44・Wilson K.Code C,Rcke=sMN.Rskofacquirlng C「eutzfe】dトJ’i(CL):]lSeこむ(ユfr〇− ●ユにへ∴ 「rRICC T′rヨ√:ニ/リ占て…1ごJ′20〇6:133〔\1−〔∴しlnks 卜t:P.//しヽP.▲八・三.rlてC[∼〔it:PICr!.ソ∵e/⊂Crl、こ(7T一ヒ)・rlI「u【こ亡XこJr121ら0ら2S5/HTMしSTART revjewo†c隻Se・COnい0王studies・助U2000.321二17−9・しnks ページ14/18 hltp://肌W3.inters⊂knくe.Wi‡ey.⊂Om/⊂gトb川/r=l【texり121606285/=1手・1しST人RT 」Ⅵ ▲;5EsrlOnこjeTFGIV”FCSEtti呵′J「vlトくnrgき1;R.Harries−JonesR,DeS‖vaR,MatthewsWB.CIeutzfeldt−Jakob in an expe‖mentaJmode0f t「ailSmlSSb】e spc’ヨ1‘っ「m e「=C「†1こし1ま〕∴【 ト▲・こ’ COmPOnentSdo not trarlSmH CreutzfedトJこkcD C3eaSerH「し」n∵J、エ′rし「’7ニIJS/C}} d−S〕aSe arld bJood【「a「Sfuson」占∩ごe/1993:341:205・7.Links t16Va−〇∪こ)nC「∴Dea5[CrC−La]P「etrehMasurloC,Zerrl.SilvaRde,WientjesDFWM,BrandelJ−P.WeberT. E3cnavr[コVIZeld≡crr−1,叫占「oJLtCh APoserSIC>anieriETHofmanA.W”RG,・Case−COntrOrStudyofriskfactors Of二「eut二子eJ:−Jakcb〔】3〇aSeノrlE」Jr〇Fedし」「∩9−993・1995・」∂nCeJ1998:353:108ト5.Links 17〇二nSSL”1rr、1GIF:etc卜erA巳cYJAIKユ】dl⊃(JIMastersCL・SurgicaItreatmentandriskofsporad.c Crr」tZfeし」トノ∈エペ00コJSCこSe−a⊂aSe・ニCnい(1!s【udy・L∂nCe′1999;353.693・7.Links 72・Brown P.Bk)Od tnfectVty.PrOCeSSn]and scr己e「rlコtCS!srlt J、、∴一叫二 お喝2005:89:63−70」nks 73.H0ladaK,VostalJG.The;SerlP〟t Ma〇Suay C C{O」〇rL.Fh/ハJ し1し,/−こ:)い3 assoclated v川h pate】etsJV/rO/2002二76−L:〔1Sr5〕」rl、S 74.PTOVJSe C Prion removaE vJ旧「川ters/SBT S=!Sこr200G1∵コニ −1已」el相ソ■1CA、Lrle\ノ・t P/1Krliuht FSGAmarK,CousensS,MackenzieJ.W■■rRG.Posslbletransmissionofvariant 75.Sowemimo・Coker S.Kascsak R.Km A.Andra:jc[=.PescL5√く′, exogenous(SP−ked)and endogenous pr[Onrl†二Ct∴しy f「○′1r己、二二 C「く」てZ†cdl−」己koヒこ】LSeaSel叩t〕‘○〇C:ranさfusLOn.」∂nCeJ2004;363:417−21.Lmks ‘i9Pe:en AHl卜」eadトノい/FnchEe uLIB二「JE・け0nS■deJW・Prec=mcaLvCJDafterbEoodtransfusioninaP剛Pcodon 川ter.Tr∂nS/u5/0∩2005.45:1839−4こ 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BSEwas負rstdescribedinUKcattlein1985(Wells etaE. 1987)弧diいhoug山tohaYe甲read山oughor山comsumption orrumhant−deriYed meat aれd bone m亡山(WiI蛮mi血∼rαJ, け鱗Brown,1998).The disea5e5Preadwiddγ,Peakmgin 1992w血oYer180000dini⊂d c犯e5in鵬e UK,d血ough ma血emat血16timat亡5Su鵜郎t血atl−2m皿on弘也e∽山d havebe畑山良亡tedbut slaugbtered and ent亡red血e human bod chain be払ーモtb町Wer亡01d en011gh to demon5加te dden亡亡Ofdiniddisea異(figl)(AndeT50m亡I■い996),BSヱ b補くrO∬edintouptoユ80the−甲eCies,h血dhgdomesti…nd ばOtic cab(Wγa恍grdJ,1991;Ⅲrkwood&C皿血れ勒 ⑳ヱ00581∂⊂kwモーtPubli∼hingしtd.帥由hぬUr桐Jor抽モma輌y.1氾.13一之4 −」dハ′.し1〕1く、、 し ( 血h85%oF patie山∫hom叩′gOu5わr thc叩re5くこm ur 1=ミ「−】uC巳joM.)891,Jdビ5γ1cD(u⊂olsihta亡noihtem 叩1ng Sugg∈S【5that six f8rm50rd15ea5e ar亡depellし1〔t−し・つn codon129phenotγpeands【rainorpriond】SeaS⊂.0n亡−;岩−= P之thologl亡alh山1marks orsporadi⊂CJDIS【11∈「亡5tr】(二し】r川上 accumulation or pLaques or prLOn PrOし亡in toしh⊂r 宜=汗山㌦;⊂rilにa】polγ川0小情m at〔t)しionユ29⊂Odjngわー =山一oll汀ほ(r Valln⊂lcdムこn slgnl「⊂ユnt Variationin the 14 〔 「こ1一丁l=】†1t」…こ「Iノ1 ′、し一J :”l、Lミdesin01rpamuhdebLr⊂sdtr丘ehsawDJC⊂idarop5 一−−・− d卜冒l†′⊂05)▼1a一己d,n−0nO一如⊂05),1ユtedandnon−gly⊂OSylated5pe− 、「 1_く 冒。。。。。。」ヨこ喜ご喜二:;;≡:器:by て) nlロl亡Cl、⊥ミarstl・ail SOrdiseas巳Canbcldent沌edbY山ebal ncモOf 11ユ L rgC ▲▼し】⊂「 山⊥ nervous syst∈m(CNS)・Howev∈r.Wi【h recen申de・叫1ごし三, rnor亡SenSj【ive【echnlqueS,P‖On3⊂⊂Um山a【ion ha5∂∴二 作ご1・∨ Acqし=・U(」†1」、に1ド011 −1C tJl【.1ほ しJ〇’t、1】l1 1ぅう○、へ 11し しl − 」E〕‘1 been reported【o b亡PreS印【1n PerlPhera上nelr′亡(Fェ‥⊂「▲−11二)ニ 亡†dJ,ヱ004〉aswellaいnmUS⊂1e,l)・mPholdt155U⊂andolr■∴1n∵ epithelium(G】atzele′♂J,2005)∂【An8dvan⊂ed5tag亡O「し「、‖)ト ∴ 「■.5 j・ピは disea5e. Although there are a sma11number of repoLLS〔ハ・=nr tlanSmisミion orsporadic CJD bγ1nOCUlatLOn Orbio c・Jじ∵ 〔 1こニ 卜し【∩〕 「し Patほnt∫扁th⊂linicaldiseas亡intocxperimenしalrodcnti 1しHl㌧∵1∴: uelldi5e川J,19紙Tatei5hi,1985).the5ereふJlt5hav亡n二こ 1 .こ「こ SuPpOrtedbyFurther5tudleSlnprlrrlatC5(BrowT”:nI. SimiIarly一之【thoughthereareah3=dhIo「reporlsorsヱノー CJDarisinga毎rbloodorpla5maPrOdu⊂【tran5h▲5.0「.ニト∴c一 &DumbIe,1993;CrcaTlgeeta/,1995.1996;deS11va∴t二′;L、J. patryef¢‘,1998いnnon亡0〔しhesehasa⊂auSa川爪ktD.∃L∴∴しr WlthCIDbeenestabllShed・Moreo、′e[aserieso[epid亡r∴=i,r i(山ca$eCOn【rol(Kondo&Kurol、Va,198Z;DavA叩Ot二「一に 1985;Hユーries一丁ones er□J,1988こWill,1991iWienり⊂ニ、 1996;VarlDuりInビrβ王,1998;Collln5eJdJ,1999),kr√ノ (むmonde‘rdい995;Heyeどfβい994.0perskalskl&?\t√ 1995)and5ur√eiけan⊂e(Evatt、1998;Evattefd/,199さ、Leご 1998)5tudiescarri亡doutoveralmos【Z5yearshaしだhこ:ごしjtし demon呵ate eViden⊂e Oftransm155ion of5POTad▲⊂C:こt} blood componen【S Or pla5ma PrOduct5・1【5e⊂m5 エkご∴′ ther血ethatthepre(】lnlCalin(ubatlOn Per【OdlnSiつ0rlと【二 CJD155u楕⊂ientlyshorT.or perlPhel・alblQOdlnkくこぃ・H 芦u楕cientlylo叫a=o make tl・anSmis510n OFthe d15C.1、,ししノ bloodcomponen【sand/orplasmaproductsatworsta、−C11rr・ユrC everlt(deSilva&Ma【hew5,1995、Brow拓1995;Rにkctてく「了√ 王997;Will&Kimberlれ1998). Thus・althoushindivldualssuspected oFha、1nssFOLLIJ=二 CTDarepermanentlydeEerredrrombl00ddonation.。。。.・1ノニr pre⊂aution5】5u〔h a5W油drawaIorpl己5ma PrOducし5L donorhas⊂Ontributed【0【h亡Pla5nlaP001】areunderこ「ご= ◎2005B庇kweJ=㍉b■■5h】∩9L吋β仙5∧ノOU√∩∂/or〃∂e〔1∂こごこ1.〉ノ_ .−t. Varldnt(」D \こ1ぐ、nし「二j0.、こ :、 ‥、 し ⊂ヱ1∵∴ぐ.OL Sし一㌧C▲。トーこし し 【 u.・▲)ー.一 J†1。 こ1己\ \▼、 (、_Lつ 」′1 し ■ ∴古1ぐI rしトビ▼こ l⊂ニnO【し一丁Cl」tZrビ】dt7akobdi5亡a5亡. Clini⊂alcasesofvariantCTDhaveoccurredinmethioniTle129 homozγgOuSindiv−dua15;its亡em51ikelythatvalinehomozy− gousandmethionine/v乙1ineheterozγgOuSindi、〔dualsarem?【e re5istant toinfe⊂【10n Or・irinfe⊂ted,tO the developmentor CllnicalYariantCID・IT・thiscontextitmayberelevantthat methionine129humanprionproteinoligomisesmorerapidlγ ト’」rl「ご「1n⊂Ubat10np亡riod(momlhs) 1ニーヱ8 1占一之0 1 l昌一21() wlth beta−Sheet formation wherea5129Yaline tends to Eorm alpha,helix ri⊂h monome【S(Tahiri−Alaouie[aE,2004).Fur− 16−)20 550−456 144−19ヱ ユ〔E 亡・1J一:さ1√・Jく・りつrlS【ranSmltled ♭γ peripheral ∈亡t10n15dir亡CdyiJlthebrain 【re ・「〔1 し1〔r PermlSSlOn 丘om Blユ⊂kweu thermoreiti50rintere5t that fouowlnginoc山tion with PrlO恥mi⊂e homozγgOuS br human methionine developed ‘tYPical’variantCID,WhilstthosethatwerehomozY$OuSfor Valine appeared more re51Stan【【oinfection and when thi5 Unlikesporadl⊂and familialforms o[CTD,Pユtl已:1こ3T^LL variantCIDshov′eV−denceoFabL10{malpr】Ona⊂⊂umし1】こtこ〉n・:一 わuic山ardendriticc亡I151nPerlr)llerallγmPhoIJ〔1ゝSし▲ビ・rl⊂∴ ding tOnS]s(m刃 e=江1997b;Ka≠ra5hima どJ【:リソ丁 appendi⊂e5,SPleen(H11【om訂正1998)andl叩−Pl‥nCJご5ニト三1 erdJ,1999),In two pa【i∈nt5,aPP仁l−dlC亡S TemOVed呂∫−け‥;−∵−S and2γear5PrlOr tO the onset orcllnicaユd15ea5e h{j・、・しaL5〔− 1 5ho呵1eVidence orprlOn aCCumulatlOn,althougl一三5ユ「=1r−Lご r亡mOVedlOyear5PrlOr tO OIISet OrClinl⊂aldisビュ5∈(吊Il・「し (Glatzele一口J,ヱ004)・ ThemedianageatdeathlSZ9)’ear5(ran呂e14−74ト甘耳aヱ1J has not al【ered over【he hrstlO〉・earS O「tlle O点㍑立 OCCurred−the clinicaland pathologicalfeatures were more 5uggeStlng an age−relat∈d5uS⊂叩ub山†Or叩OSur⊂ししニ;三 「1 Similar to sporadi⊂ CID(Wadsworth eEaL,2004),Itis er瓜′,1998a;Boeue erd7.2004)Åt th巳tlrneロト∼・rlU=1ご【」⊂Lご notewor叫,intムi5COnteXtthat山e5eCOnd⊂aSeOrPrObable havebeen154de丘nlteandprobabIccユ5eSOrVarlユ11t〔二J[〕LL UK】nlneinFrance,hvoinJrctandandon亡inea⊂h(〕!【 t magnetlC reSOnarlCe Yariant CJD prion transmission bγbiood transfusion was 、Vlth cha叩eSln the tc t 、 5ナ1tい こ〔ソヽ, ユーー し 1【−⊂ヽ、 tト1C† dし1こrl・し a岩Cnt 〉 nll昌rdし「 0⊂こJr「( 5)111ご〈 C\JS lIltしra、 rロr t: P圧、▲− ▼)H recordedinamethionine/valineheterozygouspatientwhodid Canada,ltaJy.5audlArabia a∫1dJapユnIn tlle notdevelop⊂1irucalfモatureSOr血edi5ea5edesplteSuⅣmng CilaraCtert5亡dbyneural 5yearsaftertmn血510n(PedenerβJ,2004).Thispat血thad hange with particularly beenidcnti丘edasparto(山eYariantCIDIookbackprocessand Omk r由ture(Flg2) po5tmOrtemeXaminationwa5reque5tedrouowlngdeathたom ld亡,ZOO4)Todateau unrelatedcause5(v一壷呵項 inciden⊂e OFcllnicald15ea5e aPPeユrS tO ha、’e P ュ000 and has51nCe た11en sl昌nlfi⊂且ntユy(h【lp ac.uk).Howev∈r,althoughthcoutbreak一三1uSたr mu⊂hl巳5ithanthatwhich、Va5】nitiaUyredred( 1997;Ghanierβい99的)、urltllanuPPerboし1nd叫 山rther70newcascs nowpredlCted bas亡d on tile r〔1こtこ吊 ⊂linicaldlSea5e(\Vlu,ZOO5,5nllthビrdJ,2004.5Il⊂ユこ∴. recent retrospe⊂【ive s【udy or tonslland appc:1dlX、、‖−;〕・し′ demonstrated thTee Of12500sam?Ie5POSitlVe(DT L一しl;)r prlOna⊂CumulatJOn・SuggC5tingLhatupto3500pcD;)▲CL仇∴ beinrec【ed凧th a pre、′alen⊂e Or Pre−Or Sub⊂:lr=こ111しこ15CしLご among5tth亡10to50−y∈a卜01dtJにpopulユt10nOFo−−い)F・【 (Ⅲ1toロビrdJ,2004).Gha山どrロJ(1998a)ha、・e Sし1gSごS【eしミ up to 90% orlndiⅥduai5inr亡⊂ted nlay h8V⊂ と1ir㌧・〈rr【∈ PreClinicalor tru亡Sub⊂11nlCald15巳aSe and【hat tl−iゝ〔しノ1:ニ」L、e rela【edtocodonlZ9genot叩∈SenCOdlngValineho▲−10∠・ノ〔−〕ゝ∴ Or methlOnine/vaune helerozγgOS岬,Ir tran5nl!551三っ1〔;一丁Ll i11昆cti扇町is presentin【he pcrlPheralbloodorsu⊂さ.コくナrlrロー tomaticindivldua15,the⊂On⊂亡rn15tha【blood−d亡rlVe(i【)丁卜 ductscouldprovldearoutctolong−1e[mPeTSistenceoト(i[1、一= CJDw正hinthepopulat10n・ l ㌧L、「い 二 ∴ し1しし 「)乙1 1【Lノし l lハ .▲▲C〔’し tr.。亡1 †ran).▲ Anima(studjesofperlPheralbloodinfe⊂tJV】ty and transmissibility The rou【e by which the prlOnS dlS5emLnate a buo、ⅥngPeripherallnOCulatlOn150FlmPOrla!1⊂ Standing the故elγdlStributIOn O一山たctlVlり,an recently re扇ewed(Mabbo【t &Turner,2005) \■∵こ 〔「dlS TrこIn.・t trJrlS、L I− し Systems,haveled to the⊂ロn〔1usLOElthatimtiala⊂Ⅲ・1Ti( ■ 工亡 し ■ bo⊂kout mlC∈ 減th d亡h⊂i∈n⊂1e5in Pr 亡叩rC5ミ【L】= 1a血ng variou5 Ce11山r con−Partnlent5 0F tiほ1rlr Or repllCationl几b山(山r dendritl〔〔eu515 已SSC:∴ 二、 p町iph亡raltra弟5mis510n(ト1⊂Brld∈er点上.1992,じuこ▲ごr 1993;fraser er(lJ,1996,Brown(豆ム,1997b;に▲〔1こ二 J) rL;::mrT’J’1(⊂11てロこ卜erlr」SこIlい1rl‡一r10nPrOteiTl(P・P)1nlymPhonldtLSSueSlnVarian【CTeut乙kldりakobdiseaseshow5Stainingoffoul(ular 章:nしぃtに亡ごIlil:「し:一一こ1こγしドlミ;亡5】〔(/:こhetonsi[,(B)spl亡亡nand(C)lymPhnode・^Tlti・PrPantlbody(KG9)両thhacmatoxYunCOurlt亡r5tain【&om 1997,1998;Mabbott e[al,199S).ln〔ieed,ln[e⊂Llご1ar abnor汀Ialprion ac亡um山【10n Can be d巳mOnStra[eJlI十r 已nl‘1 ⊥「Or−i∴一ごanごLi廿1:二二:1:、†「:∋11’CrrT\SLOn丘omBliCkweuPubli5hlngト lγmphatictis5uC50fscraple−Inr∈Ctedrodcnuand5h〔已i、 上▲1さだし ⑥20058【a〔kwe=Pub【ish【ngし隠β仙5ハノOUrn∂/○川∂em∂ねb釘.13Z.1ユー24 ◎ZOO58L∂(kwe1Pub=抽ngLtd.鍬′∫カノourn∂/○川∂ビ¶j・こ′OJノ√1ニヱ.こヨーニ・1 rしし1ト 〔♪「∵L「 Reハe∵ノ 代=甲−ご・11ミ0ざいエ()0しミ(0=叩1JnCntS・17ares【山allVe・PlasmafTOm Zコdorllt】叩=・▼コ5Fr∴こtl。て1己Icdtoprodu(ealbum血immuno− 昌一O卜し高1ar−C〔1。ここ・nご】1三ル〕rCnn⊂e・1trate5tha【wereusedin山e Uに,】‥rarCC∴三亡1£lU‖二,「r=−1エロyandlLaly,IntheUKitappears 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Iations.To reduce therisk cfva【iant CID transmission to cbilむ印,in2002血ede(kionwぉmadetoonlyu5eimported non・UKpla5matOtreat仏05eborn摘er31●Dec亡mber1995・ ユ弛rminewhomay,OrmaγnO【,belnCubadng【hedlSea5ご.: MayS涙Ilthereforene∈dbevalidatedonbraJnhomogご、に・C− ;Pikedhumanbloodorarlirnalendogenou5inFe⊂tivln,SaT71: mk date wa5⊂hosen be⊂au5ei【wa$COn5idered血at BSE− )OSlngque5tionsaroundth亡亡XtraPOla【10nOFtheda【a t=) in良d亡dbod5hadbeenlargdyd血inated丘omthedietby血i5 da叱andtherebr亡,⊂hildrenborn痛即山15timeγereunlikely 【o beinf£⊂ted丘omf00d.Inaddition,With rela【ivelγSm迅 YOlume!Orpla5ma,th亡prOduct canb‥tOred,tranSPOrted 1umanSetting.fina封yitshouldbeborneinmind【1−a【】 一Otbepossibletode【ermi爪eWhichoEthedonorsw−thpoさ′ll・ぺ ほS叩訂eaCt11auγincubatingvariantCJDandwhkl−OrしトこSC 丘me両山va山肌tCJDandlargeamountsorbl00d⊂an…1工 ‘′′0 ⊂ 11 reし √亡 ◆ p T Ill.ニ∵こ1ト=J」 l一 っこ ▲ 1Jr コ r、− ユ\、1■r し こ し ▼11 (L−ノ_→1 irawn for ethic扇re那On5.A5iti5nO【⊂urr亡n]y pos5Ⅰこ‥こい し仁 、ノし L「、ヽ三【(し Pio川1Ji).0し」こ∂=し√d〔し」」 Tn 997,, ⊂ し、ご ▲ r り (Co;rr‖ 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WhycanPeOPlewhohaveLivedinEuropefor5yearsormOre,gtVe Whatmeasuresare being takcr二tOこぅ†∴ donor deferra[s? 1・Wehave「ecommendeclヒWl⊃ニニニ:; SPreadou亡亡hepote「lヒ厄=rr㌢∵∴ M∂y31′2002′∂ndin⊂∃、jdeさうし 、▼ナ.“.ル…、,rん仰,,m;(−ハ。iハ。Rl(ハ爪J狛〔;n.。/∩,,;」帥作付m{1;只n用恥卯l如のⅣI¶h¶… 、 ノlしニ J 〕「 Fo「b100d dono「swho=ve已in Eい〕;〕しニテ′〕  ̄1 ′㌧一し・′ addi亡ton∂t「isk「edu⊂亡ion∂⊂こOmけふ1亮○ ㌻1こ▲トじ、Jlココ、〕 estimated亡Oeliminatean己dditk汗三311三q†1トニし い〕r、1 2.We have asked bJ00dヒ月nksしIILlt二仁c13.∴○㌻1二、、三b:−r thosewe「ecommend,tOimF∴ヨJrr工「こ「二∴〕しSLP,.\1S′ト 10SS OFdonorscan be.Lc,厄「己ヒ亡:い,.[!〇L∴⊂三.い訂∵r Oここ 3.The DepartmentoFHe己;ヒh arr:二. Fo「mon圧OringthebJc)Cj{」supF\:′ ‥己∴ SUPPIYShortages. 1巨二「′ 4.Wecontinuetoencour乙ヨe m(rこ ∂mOng b王00d banksk〕己SSi5し・∴ IfIamdeferred,W‖Ievc{be;、・ゝ、 BecauseitisstHluncertain vY・;rethヱr∴二 ispossJblethatdono「s⊂re巳nH gヒヒIS /〝 Bl。。ddonorsaredeFerred,butdonorsofl−SourcePlasma,.’whohavetivedin DonorSWhohavelivedinEuropehavea10WliketihoodofincubatingvC]D′ ⊂OmParedヒOPeOP[ewh01ivedinFranceorthelUTK・Furthermorq,PubIished studieSShowthatsomeofthestepsusedinptasmaderivativ畠manufacturing removeagentswhi⊂haresim‖artothevCコDagentlthusadding’apotentfal 、 S亡∂代On Octobe「31′2002.Ph占S〔二こト Futu「e・Alongwithou「expe「⊂Tra「si・・、h Adv7soryCommittee(TSEAC)′WCa上し三ここ:−】 produC亡S(一・pEasmaderivatives.1),SeVera10f・Whl亡hhavebeeninshortsupply・ ひ∴ 一 し Ofcu「「enヒPOヒential\′⊂J〔つri3k Ca「ry[ng thedJSeaSe,ltlS POS(,J31e〔.Pr r u柚keblood,SourcePlasmaundergoesmanufacturingintohighlyprocessed ㌢ Ll∴⊃⊥ monthso「mo「e′19こjO−L996 baeS(asdes⊂ribedab、!e二II Iw=p「0Vide82%oF汁e己d三 「evised deferralpo=cY−indニ SourCeP]asma,butnotb100d? Europe(ex⊂ePtFranceandtheU・K・aSabove)′′mayCOntinuetodonate・ ・」r.L∴∴∴三上洋一 t ■\ i′ i∂ bJoodcomponentsareabJeヒ〇ヒransr、さt;L〕 epidemioJogymayenabreyoutod〇r】aこミ:・こ三√J;:11‥ し,し ClノこJr⊂ 、 i.1tOPほ⊂ebeForeヒheE=rOPeandeferral(#5・,below)・ B∂Sed upon∂1999sun/ey′ソ、eeS〔け一1己いr 三こ〕Cし‥ニッ㍍ bedeFerred.However,insorTeJc⊂と∴joTl三′‡:二、−j〔∴二E−C15 Wheremo「epeop[etrave[,L;[亡01〔;/七、ニ 1√ ﹁○ R抽OrlaLe:TheFren⊂h7mportedatleast5%oftheirbeef!UPPlyfromtheU・K・ beFore1996,Therearealso5casesofvC〕DinFrance・Thisdefe「ralw=go }  ̄、  ̄■■一 ̄  ̄ ̄● ̄、▼■ノ ̄ ̄ ノ’ ̄− ̄’ ̄、′▼、■ ●  ̄▼ ■ ▼ ̄ ̄ ̄ ̄’▼ ▲’ ̄■ ̄、●、′、‘ト■+、′−− −〉  ̄ ̄=● 汎里atvJil≡1コ封)CTl∵/hen newcountries,nOtnOWOntheb暮00ddonor (lcFe「「こ】=;st,ボl−C〔i盲s⊂OVCred to haveBSE? つ二ou;−d「aFtgufdanceinAugust2001,BSEwas 畑ch s noton thebl00d donordeferral=st.Thesource 巳dヒO becontaminatedmaterialFrom BSEcattle, f;喜;Tこ亡しぃ○ こ1∴C5こ三〔 。 鳥㍉十王ト∴」ヒ d Fejto〕apanesecpws・Thenewsmediahasreported 「「にい∴」S::lt; ̄こ)r,ここ lこぅこn〔1三「(二ニノし∴こ「.:亡’r11ハ′aSO have「eceivedpotentlalBSE−COntaminated 1ここ亡▼ ヤ・’′二;止=iaVefedtothei「OWnCOWS・WemaY⊂OnSider EdCi;to「「コ】〔]己三「し∵∵:・i5::;jf:edし」POn POSSibleexposuretoBSEinAsiaor し:Ese、::he:C,し〕し」l〇rlい,′Jt3「ajditionaJinfo「mationaboutthepotentialrevelof うSEcxFOSL「e己[「CL FこOC⊂hE<in⊂0ntrOIsintheseothercountriesisacquired こ・n〔j,P「C「ビ:▲Obi.;},/V化Lj】d an[iこipatedoingsoafterthecurrentlYre⊂Ommended eFeT ̄Trds haveヒ佗enImpementedandtheirimpactisassessed. LJueStlOnSandAnswersonrlGuiLi ●叩∂亡t触 Manufacturcrs Assls,s, Division ofM∂nu戸∂⊂し 0fficeofCommuni〔ご Food and Drug Adn 1401Ro⊂kv川e Pike Sui亡e200N/HFM−41 Rockv川e′MD2085二 Howis FDAI−10n圧0「ing theriskofvCコDtransmjssionbYb]00d? :仁∃mO「;喜t〔′「J打沈「†skハノkeeping uptodatewith newpublished,and 叩Ubl】5hヒd s(二ほnt:rlI:\∴O「kf「om academiaandindustrY.MuchofthismateriaI ;IllaCle F)し直Hcい7′E3Vこノi:a2〕】e atmeetingsoftheTSEAC.Wemaintain cfose Cr−」こ己Cこご′し;∩〔Iこ〇㌻1SしJL二、::】th・ヨ×PertSin otheragenciesthatarea‡soinvoJvedin )SEこ1nC Vこ〕D,Sし」⊂h E」Sしhe U.S.DepartmentofAgricultu「eandtheCenters 〇「Dis已I15L三⊂orl〔「C)iこ汗d P「evention,aSWe‖aswithinternationalgove「nment しq〔mCies.=t]^aisこr「1こぅ:rlヒai1Sitsown poo10fscientiFicexpertsinthese r了sし二aSCさい1車○:〕erJF〇rJ∴:j⊂しぎ㌧e「eSea「Chtoaddressquestionsoftransmissionof POn扉〔「「、1enこeこ〕卜こうこ;二己ヒhi三S′SUCh as BSEandvC]D bYb100d. 、ノざ1己rC 二こiiこⅠ(ノしtここ盲 i‘.10「(三information? ri⊥ノ ∴)○し」こTT:r 1、Jr∴ 「封1L;C「ipts,COntahlng discussion andinfo「mation cis5ueSand decisions′above: ・TSE・㍉こT「a∴S :=’L]しS,[eCember18.1998 ・−「SE′1C「▼「己rlS⊂ご十〕ヒS〕し11el−2.2000 ・TS[AニーlTdilSこ「▼】p[s′〕ヨnU∂Ⅳ18−19′2001 ・rT.SEACTr己nS⊂rJi:〕こS〕Lne28.2001 iミefcrcrlCじd Gし由来川Ce ・∴、、LL 二 ∴:T∴;▲【ミe\′ised Pr皇Ventive Measu「es to Redu⊂ethe 色‡史 ▼ Ⅱ江た里J上ユ上土勇辻ヨjkobDisease(VC〕D)bvB‡oddandBlood Products Iモ怯三二】片やこ二‡1ご上道1 し:orltaC‡しノ三ユ ・〔ヒ○デノ」1こご}∴∵∵ ・こ二〇:15三フ「二∴〔 tr卜 ∩ イ 八 ヽ ′ \ ㍉ rl、 ヽ イ rl】 く − ∩ い iミ . 1 ハ 、 ・ く 「 く ; 1l. 1∩ 【 iV只 「 . rinl} く / 「 ; 1】 iバ 帥 ne「 nmTl ; 只 n 巳 R ロ 1 l只 † ∩ √ V† 什 丘 Im } n q/ ∩ ‘ i/ フ 占 .1 hナナ【,/人、【、_‥√」.、【(、.m三_1__:_▲Tヽ1 = 上こ㌻。 ■ ⑲ さ.トン∴ 1. PURPOSE ThepurposeofthisDirectiveistじ:こdvis fbrthermeasurestoreducethethじ、.)retica SuPPly.Thisis10beaccompZISl−e、i−yeXじlし▲ havespentacumuIalivepし:▲;odofしi:し〉L COnSistlngOfEngland,Scoこ:and,WaL Islandsbehveentheyear5.リ80tolリノr l havespentacumulativeド)「;OdoI、こi上 1980to1996;Or havespentacumulativepc∴〇do[ii− Europe(WE)consistingo[しicrman〉P. Spain,Republicorlreland・i−ortug㌻1L ノし years1980andongolng;ロ; havereceivedatransfusiorこ〔〕flVh〔,lし years1980andongolng. DonorExcl115ion10AddressTheoreticalRiskofTransmission Or、・3riantCreutzfeldトJakobDisease(VCJD)throughtheBloodSuppIy TheperiodoftimeofthreemonthニてOrmOreし:l」 COmbinationoftimeineithercouI一こ=y.Theド e COnSiderseitherthetime5Pentin(jこ、′iduaIIv∴一C 汀 thevariouscountriessothatcumuiLlii、′ely,L:1J…−、こLしi=lい′I?ご:’1O〔 UNITEDKINGDOM,FRANCE& yearSOrmOre ヱ. BACKGROUND VariantCreutzfbldt,Jakobdiseaseト′CJD),汗 WiththcoutbreakofBovineSpon呈」!oTmEll VvrhiletherehavebeennocasesoF\CJDこ1tl derivativestodate,lackofexperiじ17Ce、V兄=十、 limitedknowledgeavailableoncertainbiolし二=ご lackofinformationontheconcentrLitionan」 allowforconclusicInthatitcannotc)CCur.1I, い !(r S )∴ ∴∴ )tl)−しノ ,\、 し し し上ノ」 J J柁ざWg【Ⅶ昭 transmittedwithinthatspeciesthr(:・し1ghblur \ havethepotcntialtospreadthroug:こllum;ミヱ1 theTransmissibleSpongiformEnこ:t)halo;l:lL incubationperiodoftheknownTS:三infcこt diagnosticproceduresavailableねTJaTl)7〔…e tom】tlgatetherisksofpotentialhし;mantOi donordeferTalforperSOnS、、′hohal:じSPenLtL・こ InconsideringthispotentiaIriskarl\imeasし;て thatonemustseektoapplymeasurEこS、Vhich Ll 、.し ・、 1Jl、! ■ ごJl、】 thesafetyofthebloodsysteminoti−er、、′aン′S∴:s一、 〔、、n、1:} 上 DirectivesonAugust17,1999andÅugust:).二(7(:’ニ(1し・LLL。」・こ、∴・・、、・Cニ ,ersons who had s Blooし】1)c「rrrこl】PDlic〉−し1K.丁ニr、コnこC&\\’cstcmEurope ′\uよ:USt30,2nOI Clna.d琵 P喝elor5 enttime己rlOUntin;!∴I7−し1∴T∵〃∵.;C):「、≡.1 BIoodDeftTTaZPolicy−UIく,France&WcsトニmEurop已 August30,200l L∴ 1⊂り 4. REGULATORYlミEQt’: ▲、 C(〕UIlけ1CS〔1「\)「E. 入na†tachme両111し1Stbcinclし】(ieし rhisrlC、、′iつ・reCtj、’Cisし「こ1Seしlonrcccntscientificknow】edgeavai】ablesincetheissuanceofthe l()舛∴11dコロOロー〕irecti、ノeゝこ−=(1tlleFo王王0、V】ngneWinfbmation: thedonorba5eandp】anstol油上 materialstobcし】Sedinexp】airli approi〕riatcしIndcTStandi−1gDt’れ 一n古 TllCtOT;山1ⅢlltlCrC)1、じaSeSO(vCJDisincreaslng,WithacumulativetotalthatreachedllO 信八し1呈し一SLユ0し)い、油IO6intheUK,Francereportlng3casesandonecaseinthe Regardingthet、′ithdra、Valotpr thatallavailabkcompone爪SC( 〉 1し B【00dcstablistlT−1e11tSarerCqU汀 TissuesDivisionofltheBiolo〔:i〔 1\ thJし‡こoTI:Tl】rlCei−Cll▼\′CじrlLlleyCarS1980to1996,inclusive.Basedonrecentscient描c kno、、・ledgea\・:lJhhles=1Ceihciト5uanCeOfthe1999and2000Directives,liealthCanada,jn COn5u]tatio!=、仙5【こ一keho;Jersi‖CiudingCanadianB]oodServices(CBS)andHima− Qし1dbec(IIQ),is〔jjrecting‡ndustrytotightentheblooddonordefb汀a】fbrtheUKandFranceto3 =1〔血hsornlOrCnndtoLi〔i(lndererralbasedon5yearsorrnorespentintheabove−nOted ⊥うし 、t .s、、 ∴沃 I 目しiヽ ∴1∴訓1、 三■⊃i l OrPOOIedforfurthermanuractu †ミ叩しユh=co「lrcll川〔:: =、 PI;一e11し‖11beroI、し〕t)SCrVedBSEcasesisincreaslngSteadiZyinWestEuropeanCOuntries n【lCCtllOしdltしObcrrceoFttledisease; 5. C−J’ Br‘一m‥∬し⊥C「「し一∫一1DSl三−iTlfectedprlmateS,呵ectedintravenouslylntOOtherprimates,has TheexchjSionistobcintroducc COト11}LI人TiCEDAT王 ユ iユ51、:し、 し monthsfromthedaLeof−this[)ir hし、Cヱ1S!〕〔冊′rltnl;一こ「巨訂1」t(1iscase; し−Y ficここi−treSCarじhhLiSSho\\’neXPerirnentalsheep−tO−SheeptransmissionoftheBSEagent b\i)lぃいし=mm付点H ileこCnlSし二:’、じ:、ゝCOl一〔卜し根”ib)C11SandHQindicatethatreducingthedefも汀alperiodtothree 6. ADI)ITIONAL打(yORl∴∴∵1=) B】00doperators“・illbcrequire〔i −「しさ donorbasesandtlleSuPPl)′Orl〕1 lrlO侶hミ0:rllOrじfbrci〔さ1CrドrnnccortheUKandtheaddition,OfadefbrraIbasedon5yearsor Ⅲ刷℃高11い【)eJlしjIlt!一C∴しlいe−L10〔CdcountriesofWE,WillnotjeopardizethebJoodsupply. 1ien;1hC肌血、sP叩J∴i∴tH:⊃11andPublicHealthBranchhascarriedoutanumberofmodeling ㍍u(lLe5tOeStjr−1ntCl)lClhcc”Ctjc;i】ri5kofacquirlngVCJDfbrthosepersonswhohavespenttime ‖11llCUKSi‖lj:こ1rmOLie】iLlごStuJieshavebeendonetoestirnatevCJDriskfbrpersonsspending Onanonso】ngbasis,Hca】【hCa knowledge,1Fotl−CrCこ1SeSOr、ノC Ca血edouttodet亡‖11inespccけc いmci11FTanCCnndthi:ilboヽrCnOICdcountriesofWE.Theserisksarenotidenticaland TheDirectivい、ritildlistofs岬 CロnSCqLle:一tl)・,liC、、rOし高=一Otreqし‖readeftrralbasedonacombinationoftimeintheUKwith timc叩en【=1ドra†1Ceこ口rnCOmbinationoftirnesspentbetweentheabove・nOtedWEcountries nnしicithcrthcUKorド「こ1:1じe.トiDWeVer,WEdeferraldoesallowfbracombinationoftirnesspent anHCwebsitc nJllOrlどtl−亡nbo、e一∫10tC〔川ノ’Ecountries. 八IlleOTCt。Cn弓r】Skredt」Cliorl(一r7つ%isachjevedunderthe1999and2000Directives.Withthe inlP】e‖lent3tlC”lO川1CCUrrCntDirectjve,therejsexpectedtobeanadditiona116−1$%reduction of、IhclhcJrCtica】risk hranestlmatedoveraIlriskreductionvalueof88−90%,Ablooddonor Questionsconccrnhlgthe’、Do VariantCJDthrc)UghtheBZooJト Bio】ogtcsaIl〔iGcnc亡icTherap】C BIoodandTissしユじS Division 3「dFIoorLCDCBui】ding舶 Postal LocatorOhOjC losゝO「こ1「一IuTIJ3ウ′∩し)rlessis亡StimatedunderthecurrentDirective, Tu11ney’sPastし1rC Otta\Va,Ontario 3. S(二()lリニ MAOL2 1?1】SDircごtI、e叩EつJiesto;iHCanこ1dianbloodestablishmentsthatarelicensedtofabricateblood 川LlbIoodco】叩Onenr5「OTlrこnSruSionorfoTfur[hermanufacture.Productsaffbctedbythe 7. 王)j∫亡Cい′じ=1いuuC∼11=症し一〔jconlr10nentSfbrtransfusionwiththeexceptJOnOfhutologous Scientincrefcrcnces usediIltlle RE甘ERENCES 血1乙1:i(1−1S、;ler小11Cra川0し)しistcmcellscollectedfbrautologoustransplants,rarebloodtypesand I.Monthlystatist董csロnthcしn;t irr口山ct5血ハedr「D=1しノSんs口u「CedpIasma・ B】00dDef七汀a=)0】ic)’・UK,Francc&\し し 甘小鳥DLござtr・a7’〔】⊂)・しに・【「rいrlしC止ⅥcstemEurope ノ\∪邑uSこニ0,ニ0、〕】 Page30f5 August30,200l ‖ご∴∵J立∴〔∵ h【tP=/八∨、、′“P(†()h・どO\′・uk/ejd/stats/augOl,htm and EUROCJDaIldNEUROCJD:TheEuropeanandAJliedCountriesCo11aborativeStudy Groupo[CJD(EUROCJD)plu5theExtendedEuropeanCollabordtiveStudyGroupof CJD〔トEUROCJD) http:/ん「…・.eurOCid.d.ac.uk/ 2・Monthl〉′StatisticsonthecascsofBSEdeterminedthroughtestingintheEuropeancountries. Mo:1ヒhly SSE亡es亡土ng− Cumulaヒ土ve ヒable fromJanuary to May 2001hヒ亡r)://euroロa.eu.int/comm/f00d/fs/bse/testinq/b$e teStO 6琳f − BSE ヒesヒ土ng − May 2001 and O[flcelntemationaldesEpizooties−NumberofreportedcasesofBSEworldwide 甘す荘 ㌫㍊慧8 …怒浩a Apri122,2005 AdditionalDonorExclusion Mcastl▲i:こ 、LLl:−Ll、こJl l TransmissionofvariantCr・eutZfcl山・]こ i)iここl∴iSい:1Jl)/て;il−oi・ Supply htlp‥/八、∫、川′・Oje・int/eng/infb/en_eSbmonde・htm 3.CorinnerdnLasmさzasetal.PNAS,March27,2OOl,VOI.98(7),4142−4147”Adaptationofthe bovinespongiromencephaIopathyagenttoprirnatesandcomparisonwithCreutzft)dt− Jakobd[SCユSe:TmpllCationsforhumanhealth’’ 恒け:ノ八、≠・、\′.nnnS−0rdc扇/dni/10.1073/口naS.041490898 4.HoustonF,FosterJ.D.,ChongA,etal.TransmissionofBSEbybloodtransfusioninsheep. Lancctユ000;356:999−1000 ThemodellmgstudicscarTiedoutbyHea]thCanada’sPopulationandPublicHealthBranchto CStimatcthctheoreticalriskofacquiringvCJDundertheconditionsoftheDiTeCtivecanbefbund l.PURPOSE ThepurposeofthisnewDirectiveistoadvi三い、:t】ir’、11こここj=Em、JCJ ∴「l】\11:て一C−1:し fabricatebloodandbloodcomponentsforL=.し1㌻1:くllL▲>lいコrlz−e:1CCiし1一・し、・1亡∴t ;111− measurestoreducethepotentialriskoftrans=∴∬証mc)[vCJ[〕出てt】二L2−Jl);0山 tobeaccomplishedbyscreenmgandexcIudli∴;L’!(、rlL血1aLz2hL岩b】c∴∴;測:)eご」し〕!151・ receivedatranshsionofwholeb】00doTblo口し;c(,∴l(、○:lCnt5‡‖Fr㌻lIlこ∴つrl∴‘cさLcrf betweenthe)′earS1980andongolng・Thesc;トこ=’∴∴∴==◆CIl−C=15Ll「亡:‘こ(ユし三:tル:1てコ HealthCanada’sDirectiveDonorEてC[u5ion;,)(、5.\T72ビ(フ/L7[・Cp:J;1jK.ノflハ:7」、 onthe HcaIthCanada\VebsitewithURL: l・ . hup://www.hc−SC,gC.C訂sab−CCS/sep2000_BSE_VCJD_Slide11TeJLtml TosummarizethecurrentrequlrementS,risゝ;:?il ∴1StOしIJこここ∴こ∴rこJ∴し、\ごlし、 donatingblood,allpersonswho: havespentacumulativeperiodo[tiIl∴い ・し、=ths(l川:rAし ㌻=Jこし=\ COnSistIngOfEngland,Scotland,Wn∴:L l・J:■日加l:in」 Islandsbetweentheyears19SOto19’∴㌧ havespentaCumulati、′ePeriodoftiI「 ̄ ^、:ltrlSし: 1980to1996;Or havcspentacumulativeperiodoftirr ∴し;・SO:=∵=∵1∴∵左=∴∵∴し[1 0rGemaIly,ItaIy,Netherlands,S、、’信∵∴=∴予しユ5t∫− ∴うごご ∴\’ニ1’∴iミ\ Ireland,Portugal,Denmark,Luxemb:H :LICC;1しごT−Stご∴PLしL\l:ニJ:・しJIC OngOlng;Or havereccivedatransfbsionofwhoIc:て、〕(1Jし1▲日00dc刷1∵{l:’【∴∼=.1l】.じし∴ WEbetweentheyears1980aI−dongL)‥li BlooJDcrぐ汀alI)0】ic\J・Uに,France&WestemEurope August30,コロO】 Page50r5 Apri122,2005 ニ.IL\Cトニ〔;Ⅰモ0し7ヽ1) 3.REGULATOlミYRE(〕t二日iい、11、! \′「a「iantCreuこ∠(e】(1トJ;1」し、〉hdisc;一Se(vCJD),firstdescribedin1996,isafataldi5eaSelinked Basedonthecurrentscicntiflじk:lしl∴1ed[∴ 、、′吊1血∩し1tbreユko「[;しハinごSpし〕ngifbmlEncephalopathy(BSE)incattleandtheconsumptionof establishmentsthatarelicenceJL〔∴bric hlrtherreducetheri5kofvCJDtr.::りmiss t−eerコndbccf、llrC)dし1ごLS「E川11CattleinfectedwithBSE2. excZusionofdonors\VhorecciveJ∴L)loo(;t:い.、 OngOlng,tOinclし1deFranceこlnd\l∴ Tllしゝ」 Sci亡nLillごkIIJ\、Eeしigeし〕ElheTra:1SJllissibleSpongiformEncephaIopathies(TSEs)hasbeen h∴叩ごrCJbythcbnど;Ilごし血t血1PeriodofthekJlOWnTSEinfbctiousagents(e.g.vCJDand i=iS[〕n=Jthc王LICko「⊂3hどIIOSticproceduresavailablefbrearlydetection・Consequently,HeaZth 〔11rlし1しhりl⊂い、Ishcs【(川11【】ぎa【(、therisksofpotentialhumantohumantransmissionofvCJD 、−、r】叫)0):CicsⅣ膏】0しlし5〔3しりrOrde[crralforpersonswhohavespenttimeorreceived(ransnlSionof ト1日し1しjcrb】00し三ごDIlljlし1:1ご㌻1t5∴ぎ1;11CUK,OrFranceorWE LicenceAmendmeIltSubmissiollし、rthe臼10 reVle\V AnattachmentmustbeincIし山ed\\「Chirし thedonorbaseandplanstoLlli転諒1an〉′1しtこ∴ developmateria15tObeuscd】nい▲1ニュinhご ねster訂IaPPrOPrlatCunder5tandこ‖ごJF血ゝ∴▼しし rncon轟鳥「inglnisi〕Ole:1し1nlJ・1Siこandmeasurestodealwithit,theprlnCipIehasbeenadopted th・一〔〔パーCTllし1S【てごCkto叩伸一一1e∼3ureSWhichwillreducethetargetedriskwithoutJeOpardizing Regardingthcwjthdra、Valorlつrinrぐ)nati州 汗亡;1ull諒‖il)L)「SユFel二、OI、b】o〔、JinCanada.UsingthisrationaIe,HealthCanadaissued thatallavailablecomponentscol】しご■edfい: Dl「CCこi、′し5bas:Jorlてho、)こ】enti「cknowJedgeavailabTeatthetime,OnAugust17,19993,August OrPOOZedforfurthernlanufac[ure.卜JretT=い 二(]t二仁()(∴m=明し1〕し;:l:001;・llleflrs[twodirectivesrequiredtheexclusion什omblood 〔i川l二11‥()∫川Fa】≡irCrSOぎl、・巨ohad叩CnttimeamountlngCumulativcly,tOaperiodof6monthsor mし‘汀ヾ一l==しし∴こぃ「]:h片し:bc【、、′CCntheyears1980to1996,inclusive,basedontheBSEepjdemic コJl〔1thじし一ごCし1「r亡ご1CC=r、\しfDhltheUKandFrance.TheAugust30,2001Directivewasissued Lotせ1tenthc巨爪正し5ロ!い「〔1c[crra】fbrtheUKandFranceto3rnonthsormore,tOaddadefbrral 卜こ一Sビ(l(Ⅲ5〉’e‘ir=)rT−1ごけ:さ;lCIlt=l=heabove−nOtedcountriesofWモ,andtoaddadefbrralfbr JL川しl「S、、hoT・eCCive〔jこ1hh〕〔jtrこ1nSfusjonintheUK,betweentheyears1980andongolng・ 4.SCOI)E ThisDirectjveapplle5tOal王Can(⊥J∴lb】e andbloodconlPOnentSfortrans[1ln,PE COmPOnentSfortransfusionw出1∴こXCe:し Cel】scollectedfortransp)ants,;inこi:いrebIし、、し Thescle=lt喜flcトゝIlい、1ed;:一CL:11eし】tovCJDsincetheissuanceofthe2001Directivehasincreased, ItisrecommendedthatCanEi(!ill:l:Z norl 【TIClし】〔三lnご拍cIし砧〕“i【1ご fbllowthedonorexcトusionrcしiLi情∴∴ntS()し∴ /L\さ【tld)rlrlコロUコ\こJmOnS:ratlngthatscraplein良ctedasymPtOmaticsheepcouldtransmit tilCJiseユSCtOn‥1∵rlll亡ePb〉′tranSfbsion5, 5.CONSULTAT10NS 三ミesearこh汗山icnteHh3=一e皿ravenOuSrOUteOftransmissionofBSEi5high1yefficient6 rlhcrc!lこユ、’ebecrlこ、、rOrCCご7−trePOrtSOfpotentialhumantohumantransmissionofvCJDby h:oodtrこInSL、しlゝ一しⅢ、・‖兄tWOblooddonorsinvoIveddidnotdevelopsymPtOmSOfvCJD しl:1tlト川こ肌11ト【l刷hsnflerthedonation・Oneoftworec]P[entSOfthesuspectedblood い=llPO‥一enい、rLlゝL一一:1Cthl〔lnine−ValineheterozygotF(MV)atcodon129oftheprionprotein gごtlC(PRNr))tcし1∴:[叩t叩reViousdatasuggestingthatsusceptibilitytovCJDwas rcstricleL=o一山=7二ご1h=OnlnChornozygous(MM)PRNPgenotype7. ThescientiflcflndingllaVebccnし!二:し1SSCJこミ:1 AdvisoryCommitteeonB]00JIくじr∴iatio…㌔ PublicAdvisoりノ’Col¶Inittec.人1ゝし1∴ユn雨irユ!1 beenconsuItedinthedevelopmしr∴、[thisT〕… TheblooddonorlossasaresuI【し 1:Snい\・L ′l、㌢1CrC!]どiSbしCこ∴ =[こreこ⊥SeinBSEandvCJDcasesreportedworldwide91]Ol‖.Thetotal T}I7−llし・−し1rし≡ごⅠ 川、ユfrrObablecasesofvCJDhasreached168asofFebruary7,2005, ㌧、】tLllくしi亡しlさじ‥1…こ:1じtJト」9inFrance,andonecaseeachintheRepublicofIreland, 「■川口C∴!tこ11\こ1:い1【こed States12・り ぺ乙、畑ニ∴二ぺ5 6.COMPLIANClこDATl三 Theexclusionistobeintrく)dしICC(iL、,00nこい; 2 Apr1122,2005 morltllSrrOllltlledateoFt!1isDircctive, 7.ADDrr工0ドALIバFOlil√IATION 6, HerzDg,C.,etal.Tissuedis出butic㌃r一 三ヒ :さ 一 Prlmate5aRerjntravenousorora=1 7. Lle、Vel)Tl,CA,etal.‖PossibleTrJ∴ bloodtransfusion,r’TheLanci:t(2Ch〕iニ BIoodoperatorsw用berequiredtoreportsemi鴫nnualZyontheimpactofthispoIicyontheir donorba5eSandthesupp】)′Orblood. 0IlanOngOingbasis,Hca】thCanadamayupdateitsguidanceinresponsetonewscientinc kno“′lcdge. Question5COnCemingthe”DonorExclusiontoAddressTheoreticalRiskofTransrnissionof 、’ariユntCJDthroushtheBIoodSupply”shouZdbedirectedto: Bjo王ogzcsandGenctic111Cr叩iesDirectorate CenけCねrBiologicsEva】し−ation Director’sO[「lCe 3rdF】00rLCDCBuildingtf6 PostalLocatorO603D Tし1n【1Cy−sPasture J一「山! −、− 、.‥ 9, MonthIystatisticsonthecaseso[t3S;∴≦∴:∴=1Cdl:し1・ COuntr】eS. htlて〕://eumlつぃ.eしl.int/c(〕mm′′hpd/mnd∴毒「 \\吊\し・∵リ 10. OfficelntemationaldesEpizooties−:\:==ト∴石‘〕r):11ごi hth):/h・W\V.Oie.j帆/en亡パnわ/en esト什二⊥⊥ユニ ヽト \ 11, EUROCJDandNEUROC]D:TheE。rいIr::㌻∴1nC∴1∴ご」 GroupofCJD(EUROCJD)p)us【hc亡1仁・ざ1jLい1rJ∵∴圭一 CJD(NEUROCJD) hnp:〟、VWW両dcdac=k/ Otta\ヽ′ユ,OIltari口 12. StatisticsontheUnitedKillgdol¶’sしこ二〉 K⊥八OrJ三 hm)://\いV\VCid.ed.ac.t】U〔ビt汀じSぎ1=∵ 臥REFERENCES 13. Numberofcasesof\′CJDinFrこ1nC〇 】. Donorcxc]usiontoaddresstheoreticalrjskoftransmissionofvariaJltCreutzfbldt−Jakob discase(vCJD)throughthcbloodsuppけ.HealthCanadaDirective,2001 htlD://wヽVⅥ7,invs.santc,Fr/「巾Iicatinn・「−L htlr):/^v\∨Ⅵ′.hc−SC,ビC.⊂a/hDfb,dmsarbgtdJt)btdbloodde良mluk 什ance we e.htm1 2・ CorinneldaLasmezEiSetal・PNAS,March27,2001,VOl・98(7),4142−4147“Adaptationof thebovincspongiformenccphaIopathyagenttoprimatesandcompa血onwith Creutzfeldト]akobdiscase:Implicationsfbrhumanhcalth” ■ 坤町〃“′、∨、∨.抑aS.nr巳ノ′cご童′rdo=0.1073/DM.錮1490898 3. Directive99−01:Donorl三xclusiontoAddressTlleOreticalRiskofTransmissionof Variant CJD through ihe Blood Supply. h=n・/八\′≠′\∨.hcTSC.⊂CCn,/ht)fb−dどDS〟bEtd−dDbtdd99−01e.htm】 4. DircctiYeD2OOO−Ol:DonorExclusiontoAddressTheorericalRiskofTransmissionof VariantCJDThroughthcBIoodSuppけ httロ:/八ヽ・≠′町11C−SC.ごC.C打11口付−dms〟b如ddDbtdd2000−0】Og30eムtm】 5, Hunter,N,,etal.TraT−Smissionofpriondiseasesbybloodtransfusion.J.Gen.Virol.,83: ユS97一三905,2002. ・\:、■∴二∴∴ ∴ Apri122,2005