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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
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8
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◎20∩6Bla⊂kvノ亡tlPub上Isllingl.td.t布∫5叫‖川L用00引91,ユ2l一之】0
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一demen百a一丁e〔Ord亡don伽dea山c∈血ざ1Ca【cJuこご、′六:1Ⅲ1完工0.
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Pa柚oglぐ甜yas uFfeTingFro−−1V⊂JD【7」・⊥L:ム;こatミぐ∵
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VCJDinlhedonor,F泊yp∈rCentOrlivere(iptent5We代tranS一
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一之bl亡コ しrv∈「〔ぐ1P料代用=訳I亡bc〕】〔ごrJ」rrlこ5don∼tご亡し、
weremadewithin20monthsorc]inicalonset.inseven⊂aSeS
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⊂Ljr√いt〕リ(、Or
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surviving>】Oyears(oneforover18year5)・Thes亡Patients,
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befoTeOnSetOFclinicalsymptomsr9】.ThedonoTOFthisthird
probabletrans餌sion−tTanSm庸dvCJDirlFeぐtiondeveloped
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re⊂ipほntlsacodon129P尺〃Pme也onin亡homozygot亡・
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donors.bled be亡W亡亡n6moれths and17y亡a円,‖month5
beforeons∈tOfclini⊂alv⊂JDsyrnptoms.w∈r亡SuPpli亡dforUK
Fra⊂tionationdunngthepehod1986−1998・Productbatches
manuraぐ山red打om23 plasma unib d∈nV亡d たom rline
donors have been traced,Th亡fhte oFbatches o[pTOduct
9−く10Y巳月代
>10Ye∂巧
deTivedFromthetworemainingplasmadonations,Frorntwo
】「三
differentdonors,ha5nOtyetbeentra⊂ed.andthissear(h
isstillongoing・Tabl亡4ti5亡S山亡Plasmaprodu(tSdedv亡d
h・Om the23tra⊂ed donations and the number ofbatches
impli亡ated,山勇d亡dintor15k亡at鴫0血5aSu5亡di∫l也eplasma
bAn叩∂:】Vぐ■=ミ3【d印0⊂ithal□OJ・′二Cノ伸∴
■A5i【1∼1∂「⊂hコOC6
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ー〔し、 コ⊂二▼ し‥ tlぐ …「= 川」〔rlて〕▼1ShslOn・
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scJDcaseswithhistoryofblooddona也On
Nin吋一山R⊂(aS弔OFsC皿iden鮪∈db亡帥eⅢ1980and2000
were reported to have bcen blood donors・Withonly38
r叩正ed to bavedonat亡d fTOm19800nWards・Dona血n
records for mosts〔JD cases were untraceable sin⊂e rnOSt
datedbackmanyyea円befbre1980・insom亡CaSeS亡0也亡
1940s.Donadonr亡ぐOrdswerEわundわr亡ights⊂JDcas巳S.but
only山∈亡hada蝕ally加natedlabueblood(OrnpOれent5f8r
ho5pitalu5e(on亡W血18recipi亡nt5,andoneea⊂hwi仇on亡
r亡Cipi亡珂whi⊂hcouldb亡加⊂edtor亡Cipi印也・AtotaユoF20
re亡ipi印也W∈re廿a口5hs∈db⊂帥e印1995and1999witbcom−
pon亡ntSFrom伍ese仙てedonorswhowentontodevclop
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ameanag∈atdea山oF74±15ぺこj、;l・こnぐ5e.:
afl∈rtrエロS九5jorl的urwi亡hlr二;」しい」c.L〔」!:
and5er√enSUrⅥヽredrorb亡tヽ、イ〔ご∴こ∴亡ノ1,′ぐししISここて
their打ansFusion b∈Fore d)一㍗二○∴ ▼′訂lここ〉(
reLated⊂auS仁5(⊂⊂rCbrova5⊂uここ㌻くここ⊂、ししこ/sこrL〕∴⊂,′
myeloid上Ⅲka∈血a,,⊥=〕,Gビニ王こユ:dしノ1=n舟(1
S∈Venr∈⊂岬ientsarenotkno、・1ン十両∵行ノ十「し こrl
todae,rl∂「hTP亡ミしユ・∴C〔jこモ:ノて
∴∴二
し〔
2−く3l′e3巧
Fromaround5monthsto191monthsaRermakingthedorLaT
〔
ノ〕Jし
ミl∼− r
OFLh∈5eS∈V⊂nreCip代ntSIS5;1二1コ)′〔.;ち二上こごこ
Sin⊂e山巳汀けan5軋5血−rang〔51じ:1i7、.9ンCこir、
a餌代h亡rre⊂岬t∈nti5unkno、㌧nニ」0Ⅰ−e r血5こご:ノハし.ヱ
identiFほda5haⅥngr⊂Ceivcd{〕:nod「r〕ヱⅥdo三1〇rて1∴・〔・、
OntOd亡V亡】opsCJDhav∈a押亡ユ㌻亡Jo【1theNCJこ〕三しー:〔
to da〔e.
CJDandb;00dlran5氏ユSion:一触UKTMERs【udy 22丁
1aいぐ4f)rJdし′〔こbJ。↑rrlC∼nlヨ(1F・−∨Ukrrコ〔こn=月ト∵∴こ一〔「・、・′ぐO rrO汀P185mヨ
resp∈⊂tiv亡1y(NB5earCh如donors10CaS亡6is血omple【亡】・
dnr言1亡d卜/川づ】リ上り1仇hoj;t〔√dご・ノ・廟〔(巨ノ.1√ L、・ぐしjtZr⊂1di−L∂kob
Todate,On亡donorwhogave代dc亡1lstocase5andanother
donorwhogaveredcellstoc且Se6arealsoregi5teredonthe
d.シニ声(T一卜上
トこunlbぐ「Or
Fnrcこい.1
C【コ1く∩(吊nrl⊂
PL〕、・TりP川(≡じ仁一
=nPlぐコt仁一−hat⊂h亡i
228 P.E.H∈Wl【てrr山.
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〔[∩▼:(
havedi亡dfromONSftaggingtodat亡,arldareth亡reforepre−
bJ」J㌣・F占:⊂0√こ∼rP√;nl√,=∼ぎ「っmト′′〔′ 〔、/ニ〔3∼し∼ニく亡亡【亡XtFor
dAlbしmけf叩rTlrPlごJlてdp∂S−¶∂don∂t0n」iぐし:〔∼⊂人こ1P】州〔「で「【
suし〕、t3−−⊂こ3ddぐC【〇Prロリ1dぐリリ坤npr叩8・3しCn−し、言し〔≧1nfF〕〔て0「∨川
199G
6−
1997
7
1日82
b
(鋸上c∂いこgO=CS3、“⊂かnpr・−こ「¶aP√n口U⊂こ∩〇てf「 =〔ペ「⊂・i亡
5】
◆
sum亡dtobealive.The如eoFa知rtherthreedonorsisnot
known.Them亡anag亡Of血donorspr亡Sumedst51laliv亡is
51土9y亡a汚・NoneoFth亡traCeddonorswhogavebloodto
pati印bWhower⊂Subs亡叩ntlydiagnosedwlthsUDhav亡
appearedontheNCJDSUregistertodater
いト・・十
lTwoorth亡∼亡⊂3S亡5ト【nk⊂dtodono′∼古Lr(8dYC〔T∫1〔rJ8t■即融⊂∴∴∵ぺl=狛〔
bcompn印tde∂−」sra(.uち∩〇ミ】招いRl⊂
∴/て(.j†¶
Timingofc佃⊂a】it【∩⊂∬亡XChJd亡iblc〇d=ns†LJユーOna5tト1て5山rこノnr∝t」nr r
Thrc〔rご⊂1Pl亡=rtS一汗川0てknov川【oL〕⊂r・しくLj:rot¶Or、」Snagging
tn(ユat〔,alldaretEICrC「OrCPrCSu−¶Cdtロー仁′−LlV〔・Tl−=neanag∈
0「lぎIe∴⊂th†ぐC rぐC:Pier心〒s…±2C二▼て∵=1Tl−⊂t汗1仁亡】ap5ed
5lncどこ1(Lrtra−15r、1Sio[rang∈5Fromて1し0ニIy亡arS・Th∈Fat亡
0「aトニこ1herti−LrC⊂rCCIPl⊂Ⅰ一日L∼−−0=・[ハ・‡二Ncn⊂ロー‡he忙JD
Jon亡Orth⊂dono√5alr⊂呵0nN⊂」D5」rcヨF51(−∬∨じDcd5いつリ ードr:5∪け−ぐ已・(
mcaseswithhistoⅣOFtra皿5氏1Sion
亡0∩亡dono「招くadYOnNCJDS〕−亡9」5tこra5VO〕⊂aゝ亡5c∂rChF〇トl∧+血∩□巧〔い:.二
oneca5eOFf⊂Jl〕identin∈din1992wasr叩Ortedtohav亡
代C亡ived山eebloodtran5知sion5董n1965・1970,and1987
non〔OrWhich⊂Ouldbetra亡d,
deceasedr亡Cipient5;a51gnifl⊂antPrOpO∫1iono「t}1⊂5⊂mdト
Ⅵdu且bmayl−Othav⊂SumVedLong亡〔Oughto⊂XPr⊂Sユ⊂−1ni⊂al
srondm)(F■【‥】e〔C日1j、aート53ざ≡t∫cミ=Ui叫I
両1=・ぐnt口■∴CGc・−・el叩r〔Jロー1a\・ea:】∫こnr∈don症〔N〔JDSU
Discussion
㌻叩ISt⊂rtn(ユ11c
Thisstudyhasiden鵡edthre亡instanc亡Sir)Whichareclplertt
oFatTanSRLSionderived育omalvCJD.donorhasdeveloped
v(丁口⊂;lSe51\刷1his〔0「)′OFいa∫1S:l:上、iOII
EIc\′CrV⊂」○⊂1Se川Cr亡rC叩「{eCしCt・【べ【し⊂⊂−VぐGPaStblood
i、爪知tionwithvCJp,inぐ1udingtwo⊂1ini⊂al⊂aSeSandont
pre−OrSub⊂1ini⊂山nfection【7−91・mび亡are山亡edl仔e代nt
tr、l:15F,ユ5∼OrlShehvrCn195ユ昌一l(il〇ウつ ′二
donorlrecipientpairs・InviewoFthesmallsizeofthetotal
「て11∈rCa∼亡「巳⊂⊂iv亡d
5S TlLう C∂S〔15
n t】L「)こ1し1.1:㍉巨ゝつ†− こIL亡「川1′二:
cx⊂Lしユー仁d fこ∩、11「豆正1こr a−1こl)′Sl、こ・
、‥′り CaSCi.血spital
∫ユ1S「11S〔d.Nohos−
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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
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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
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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
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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\′
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the UK.†orlong periods.between1987and1996
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the UK,but thereTemainanumbervvh;chappear to have b已en己ご】)
inlrelandltheNetherEandsISaudiATabia.Spanand Port明a[andこ了○
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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「
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three・Therec】PEent,genDtyPeし「M.d■edlyearafl己r Preさ㌧.rrここ1こCJ∴ 二
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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
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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
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−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
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=¶OmEecteds]b】eCtbecomes∩:ectNefortherecipientoftheblood:anhlfecteddonor,donatin9
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StUCfleSl:〕]oodlnfec=ⅥtyCan beden10nStratedatJeastatthestart ofthesecondhaJfoftheincubation
Fつer(Oda「1叩e「「aPSa/soearrerいhe−nfect仙yofbloodprecedesthepresenceofpatho10gicarprionin
thcbraFnandtheorgans)166Evc=thoughexperimentssug9eStthatinfectivltyw‖beabsentorminjmal
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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
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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
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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
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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
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Pljコ
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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
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ソニ・:血10ナcLnLCaJ10日「、1el・Met cases?俺v中畑抑血/由両e凡/わ〟叫e2006:5ヰ:111−5.Links
′1.V;a座),[血rrer N.ZerrI,DueTrHP,Lef畠vreH.SeifrTed E,L6werJ.BIoodtransfusiohand
=「eJ’zr亡:dトJakob d15eaSe.白¶e「g血/ec†αざ2007;13:89・96.Links
eCDm=deuropeenSCENHIFIActuaJjt6ssurFerisqu8iatrogenedlinfectionparagent畠
and plasmaprodu〔t5
Mar⊂L.TurncrandChEistopher^.Lu(】仁一m
ぬ椚揖けれ血相=地dTね明偏一冊Jcrt′化tL汗汀・/〕〃「いJ川一り
J‖「,
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WG・Beyolld厄Ui(OdepLet■On‥remOVinginfectiousprionsbyfiltration・Transfusjon
Summary
20つ5.45−1836−8 」け斥S
10乱1ahbo=廿∵㌦rner「古PrJOnSandthe b00dandimmunesystems・伯emato10gica2005:90:542.8.Links
Thel’e hユV亡b仁en†ou=再伸=−rObabt⊂1・−∼lく1;1∴、∫Cr、a㌻LJ1
C【eUtZ丘1dりak〔)b dlSeaSe(vCJD)11anSrll15ゝlD;1【1仁ロ.こt一こJ・
叫ede〆etedl⊂d⊂亡uCO】−⊂en【rdte5andl川−−…二・⊂‘灯し上 ・L〔
こ ′.=1】⊂く、1ロ【L
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l「】し▲1〇l・ Llrl」
山erein no r叩01ted…den⊂=llatlhclローe⊂【・ロ、こ51SeJl:トーさ
beenしran5−¶1tled by丘ac【血1aこ亡d;山5n−dリー○(iし】こ:5.ぐ昌.r′l⊂ニー1こ
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こ1.=でrt】「こ1c.c ▲ Jノ.ノ\
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asceL.tainwhether【hesepatlentShavebcenblooddonorslnthe
Pa5t・ln血1SeVentat加−PtSaremadetoidell呵tlleねteoFthe
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し1〕Dlし〔(。
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1し∴∴1
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Broa(11y,Whllstn=ro川1SO「do【1‘lて】(〕nnrぐぐ入亡こJr∴、
EIShteenpa【1ent5WithvCTDhave,Orhadprevjous[y,been
blooddonors】Fromwhon−atOtaJo(66recIPlentShavebeen
identほed,26o(whomares【t11alLVe.0(thosewhohavedied,
(ourcasesoftransmissiono[vCIDpr10nShavebeenidenti百ed
WlthCrDol山口S∈CD〔Sldercdi叫ご∩しlル汗−kにい\∴こじ=110.1
Lつl、う
】】「
lldematOPOi⊂【に5ほnlこe!】sdlld sc=〔】rJr三ー川‥くi
lhoseconsldered‘at=Sk「〔−1【Ⅷ卜LこL㌧し=Lrし1
J rl、、
PreVlOU51y【lan5「uSぐd,51」bド⊂tしし1コr】SL rl∫SビュSrlしこ
【】 ヽ⊂ −
(5eebelow)・MdnyOrthesepat脚ItShow亡V亡「叫l】havediedor
【hcrlSko「、′CTDtra】1ゝ【¶15さiロ【1∂gL吊15tこぃ⊂;1Dしし・rl
tl−eirunderlylngCOndItions肌Ihin5yearso一山ell叩−】mted
【ransんsion 8nd willno【have had【1me tO5how clini⊂al
−へd加eor∴1川【ト1亡r、、r15e川Lt LJL‥▼ユーlL∼;∴一1r−:」ご、・
)〔し1 rl
tlS5∪亡S LS bas亡〔lorlし】1ぐ5311ほd(」∴0「し二⊂:一亡=‘1こ〔1.しし
l】n、〕LL「(
evidenceorvCTDlrin一号cted,
Dotl(〕r derビrrd】こrLtビ‖a rCnldl】1【10、Vし、仁r,Jll一
The氏r5tSymptOmaticcaseo(vC7DdLSeaSeaSSO⊂1ated、}ith
blood trれ11Shsion wa5identi鮎d】n Decenlber2003.Thi5
indlViduaL dev亡lopedvCID6・5yearsaFtertEanSむsion ofred
’ellsdonatedbyanindividualwhodeYelopedsynlPLomsof
meど1(100−=、′11hilOこCn【131d亡】亡しぐ.】Cl]くご「J亡亡t、′ :り〕(−し:い1し
1(lし’、
】mpo「t8tjon ofblood〔0‖−PO11erltS
SlnCE Ourlast report(Lし】d乙・川1ふこて、」rr、どr.ニC二う しJl亡し⊥Sぐ了
inlPOrt亡d n−et】1〉′【ビ∫−ぐ−L−luc tL亡.1Lビし】rl⊂5.11⊂)こしni∴し1㌧汀L、1けi、i
hdSbeenexほ−、d亡dlna【Il)ユt】C【二ニュし⊥T豆k=he【lSビし−L▲‥′CJ■==1
to hlgl−=Sぐr55nl、′ビntd亡し亡ー昌Cilト汀⊂.、こ亡」ト「PIS.しこC【て1rnご=二eし
ゎrl)a【ients undcrgnln喜 Plas−1、⊂− C入」ヒ1・11じど、r しnr〔1=1】)仙こ
tl−▲On−bocy沌P川1⊂Pし汀PUr−10■l=−Cgrし、〕〔し、↑ ∴er=S、、1
evld亡nCelO SしIgSeSt tha【1−1⊂t上㌧′:cr:トヒ)t・‥rしL】r㌧r、FP:1Lll
delet肌0∪51mP∂こ【OnOUに〇nlCl∫ト1LSPユ:一ビ=.t∈:、」∫−仙、′.1∴ト
Po5m−Or【elT−il−Ve5hgaてions bund abnorn−alpr−On PrOtein
accumulation行=hespZeenandacervica11Yn−Phnode,butnot
inthebrail一.andnopatholosi⊂aIfeaturesoFvCIDwerefound
La⊥rnビJ‘−ゝヱ01)′Co5i(edし・抑⊂〔ノ:t【ミ∵くき∈\こ
(Ped亡ngr4J,2004).
^【hirdpatien【developedsymP【omso[vCTD6γearSand
di亡d8・7year!ar【亡rreC飢Vlngatran血sionoFredbloodceus
】l さ〕\
a】1Jor£JnSt】PP一)
1aterinareclp】餌【ofredceus丘omadonorw】−OdeveIoped
SymPtOmS O(vCJD18months af[er donaticn.This patlen【
dicdtromcausesunTelated【ovCTD5yearsattertransEusion.
コごrl、ee!1nlan and
し」、」叫
TMER study alten−PtS tOident坤whichindividuals who
dcYClopvCTDhavere⊂eivedblood[ranshlSiol−Sandtoiden【1Fy
VCIDう5y∈ar5a氏erdona【io爪(Llew叶M…=004).
Asecolldcaseorl一之llSlllisslOnWaSidentはeda kwIT10n【h5
tI−〔r〕er甲llerこ:bro(つ(一
「
exposurc toln−〆】こaしed st・「5LここL L二くしrJrl−ビ=、しく、し.
bLood⊂On−POnentS(hup‥//www.cjd.ed.ac.uk/TMER)andtrace,
no【呵andnlOnitor】jv−ngreClpほIlt5.Th亡Irever5e一之rnlOfthe
;115】いノeSa叫)le501】t
ハ、\1「l…1⊂・k′− rCしl【0−1S/topl⊂5_aZ/
Jlし
a【n5k oト′⊂JD「or pub二L⊂:ヒ▲LtlJし汗ドロ5亡こ こ
around tllePOS51b▲ll亡yo「1:T−Pn…▲1S r㌘E)よ㌻−∴こ:⊃ユ汀叫−【ユ:C
hron−adonorwhodevelopedvCTDabout20monthsafterthis
わr addltio■1a】grot】PS Orl〕○乙1L【1t5!11;〕0rtt▲∴Or′・一心eL亡こ5LJ
bloodwasdonated(HealthProtection^gencY2006),
The Fourth case ortra爪Sn−i5Siondevelopedsymp【on−50r
VCJD85yearsa(【er【eCeivingatranshsiono(redbIoodccus
たomadonorwhod亡VelopedvCIDabout17montllSaherthis
bZood wasdonated.Thedonor to(hispatie】l【aLso donated
PrOdu⊂t5・トiowev∈r−1t!1−a〉′しc puくJ】し1:c【 rごJこ
COl−⊂e机rate5rOr5口nle glOUP5ロfl一刀こLぐこIrS,に「し、.−∵晶二「∴
Ch11dT∈n叩tO16㌢CarSO「dg亡 ⊂or一誌土日h∬パ∴∵h市Lい㌧
glVen【0(05t,qUallty aI−d reg皿こL〕し LCll・Lごこ1郎し5 ′−【1
l▲kぐ1y to b亡Ir11P▲aC{l⊂11slV巳∩【h巳5抽「こ ∼ilCナ r=1〔エー
the vCID−1mPli⊂ated blood−tranSFused to the third patient
〔Ounほ「ValJlnSr15k50rlra115Ill−さS∼OnUrい【1ごⅠけ両∵∴両日5ご=イ〟圧
(EdltOrialT亡am,ヱ007),
OL OF⊂OmpOn∈n〔Shortas⊂S
人‖burpa【ientsreceived【ra】−Sh5ユOnSOrnOn−1eucodepleted
l−ed b【00dceusbetween1996and1999.SinceOctober1999.
1eu⊂0⊂yteS have been removed 丘om allblood used for
Advan(eSinthedeve】0【)−−−entOfas〔∫eこニー…1ヨt=し
tl・an5ん5ionln the UK.
Asp一己V【0しISlv no亡亡(1(LudL∂m訣て1tlr∴已「∴り〇さ、 L・亡r r−t】し.し
Thes亡daしa thereわre demon5【rale⊂1early that no爪−1euco−
a⊂ld tlanSnllS510n nOrimmし⊥叩Lo51⊂‘】LニCSし1∩[〔rてrL】しrビ1…
depleted〔亡dc鵡hnlaSymP【omaticindividua】sincuba【ing
VCJDcantran5n−ittheinkctlOnbyb王00dtransrusioIl【00ther
indl>idualsaEld【hattheriskQfthemdoingsoisreLanYelyhishT
品n叫′ denこ▲丘ed】r−a550(・封1ロnlし、′lt≧ Lr…Jニ1▲\\い〔0【ll−
dlSeaSeS、re−1d巳r】nSくtand3rJn−0トニこしjlardFlゝ1くぐ「‥ 二〔、11さ〔re亡㌻−
ingdSSayさUr−FビaS・b:e Surro紳e:.1JrLごrS,5し1〔h.‡】‘トユーさ、Sい〕
and ery=10■d dlrrビl・enli紬On−1C.atごd r.1C【Ol‥1,∨ピ ー〕しj5【
r
」 \し】し、・「iつ−dcnl10logy
∧∼」い亡し、 し」し【ハ」√さし・11rOr COllatlng
\∴∴∵∴
川1
い、t、1し)Od compo−
.しし こご㌧〕5・、ぐIrlユ.1Ce Unltln
PrOVぐd上n5urhc■∈−1tly s仁l−S】ti、′ごRrld sト1⊂亡・=1こし(1 L cLLr1い−
Va:ue ⊂onsldcrablごPrO呂re55tlユ、11い、e、し「し吊 ∴〕こしLn・
Donor deferral criteria
Tllerehasbe亡nl⊥ldesub51antiYeChangeinblooddonorcr−t∈l・ia
dビVelopmcntFas沌γSrO由仁ミJ−〇】〔Lこ口1」=ご机ドい
\/n「刷こ⊂」〔porl川】】S∼rO−ト【−ソt〕oo〔Jtrdr15fus10n
Since ourpreviousTeView(Ludlam&TurrLer.ZOO5),Whilst
pl▼0【e▲nlPrPL5ヒ
NornlalprlOnPrnt巳エn(PrPtノ)】ゝal、rJし・L)こ∴i・re.、。Cd5う;:〕コ
O【her⊂Ountrie5⊂Ontinuetodefer【hosewhohユV亡5p印【mor∈
thanaspeci鮎dcum山tivep仁一iodor【im∈intheUK,Within
コ 針購ハノou√∩∂/or〃∂em∂rO/0卯.144.14−2ヨ
15
250amlnOa⊂・d裏y(05γトpLl〔ゝ;)l−・山J)【‖10日Ola【1こtlt〕rぐJlr沃∵「
16
ノO」「ロコ〔′〕「√〇dてこ∩、
Review
−rlCl∴r、k汗刷∴ムhⅦ」旧し化石1ごてn dぐ;亡⊂t PrPIS亡iれ痛亡
P〔こ一1r二「れb加こ1≡1ご:ぐSt mn【ご…【lくこre∂こCd㌧、・吊1PrOteinase
Pけ‘Sど−5匹ゆl甘川血Avarietyorotherligきndshavモbeen
Shown to bhd sele’tive】γ【o the abnormauy conEcrn−ed
moLecule・Plasminogen has been proposed as a means of
ユn(こ】恒〔川く−⊂0【11Peこ▲1いe拙・b口dvう・−l山l乙↓0naSSayu51ng
5ele⊂tiveblndingPrP■l■Sヒ・bu【∂Silcanal50bind【oavarietyor
】・1L、eL】c〔JP叩こl⊂:亡 r05】1〇⊂〇汀P⊂い=ぐけ)1ndlnlOnO⊂lonal
ar二こ・「叫1h−1【re〔√一言㌻「・くe5 し)州L P・Pbヒ、=d【he peplide
(Sこ!、・「1CTT e「て’こリJl==SJ・・、三nC5)・TtlClぐCllnlqしL亡has
Otherprotei爪革itistherebrettn此eLytobe5u仏⊂iendyspecほc
l〔)\、′ご\Cr Pl(汗仁d(]】Jl〔−▲1しtn r叩√ウJu⊂e−n(Hhnhbor8tOrjes
PTP’l−Sヒ
払ras見ydevelopment(Fis⊂herどr¢J,2000).
Polyanioni⊂⊂OmPOund5al▲e knownl05elec【jvely♭1nd
andthispropertyhasbe亡nemPloyedintheSepr10n
t‖1d ≡一山kJ【∩こ1S(rⅢ1J.1【ビb亡1、、′CC−1‖1「e〔=亡d andし111infモCted
a$ay(LaneピーdJ.ZOO3),Whi⊂hus田COa【亡dmagneticb〔ad5tO
h加d、dn−PC∼Jn a b】l;1し1cd 川ユれ(C亡rVenakova〟広J,
QPtUre the mol亡CuIe・The as5aylS nOldependen【on PK
trea【n−印Iandis not spぬe5−SpeCi丘c proyided a5ui【able
dete’tion aTl(ibodyis used・ltislicensed Eor postmortcn−
2〔ロコ卜)
dia帥05isor8SEandChronicWastingDi5eaSeandi=ePOrted
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thepathoto6】Calpnonl−1tモー亡Uにmre⊂【1n昌【亡CIPし∈:1こ汗【…
Yuan.r・,XL&O,X・.McGeehan.TりDong.Z・,Cali,Ⅰ.Fu)LOka,H”Kong.Q,、
Kneale,CりGamb亡tti.P■&Z恥W.Q・(2006)In50lub」亡a鍔rega【e5and
PrOteaSピ・r亡SISta】llCOllbrmelSOFpl10nPlOほ汀=nuntnF亡⊂【edhu口1れIl
braini.Jo〃用月吋β10hgfcβJCJl帥‖りツ,ヱ81.54糾8−54858,
Fa⊂tOr COnCentrateS,tllCSe are rlO、、・Onlγn−aIlu「ゝ∴:已▲
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the rlSk of varlant CrDln〔he populatiDn15、
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:10.1−(1りSOt:Sわ「‖−Ct三1・0=∫1‥こ血s t口二lユS,11%arehomozy一
口nし】Sざ0=・a二ineand5こ%t−ete・07)′SOU5・ト1∈thionin亡homo町g−
∩叫・1Sニー1し】⊂hmore⊂Om∫T一口Jl由nexマー二〔t仁damongstpatien也
、、rltilCJD(v−dei′一再).PrP−5ir−1亡rted:ntOthe亡eurhembrane
prcd州−1IlaTltly Ⅵa a がy⊂叫・1phospllユtid)rlino5itol(GPI)
a[lChor・although[ransmcmbra【leand501ubletormshaveaLso
bcぐndesc−tbcd.Th⊂かyくOPrO【亡tnisp−Cdominantlylocatedi−1
⊂al、・亡Olar乙OnC5int【leC亡Unlembrancand15eStimatedtく〉havea
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1ドrOPOrtion recγ〔lingto‖−CCCl】5Urra⊂e(Shy〔gピーαJ,1993)・
一111C毎1⊂tlonoFthep一口telnreTT−alnSun〔1ear,itha5t〉eerlSbown
!し〕と川1d【oaIamin・nrC⊂CPtnr‡−rCCur50rP川t仁in(Mar【ir15gI塊
lウリ7;M⊂gerビrnJ,1997)aI−Jd〔【asa(OPPCrm亡tauOPrOt亡ina∫e
川【り、、TlどrロJ,ユ997a).PJP nuu】¶l⊂亡 aPPear tO develop
−t仰仙据−0しlかsnIn亡5こralnS Sぎー0・、▼SubUe neurolqglCal
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l)C【かP≧eated5he∈い−1ai−11さ・ユ⊂tllCeXper−5eOrthemembrane・
(il封山u‖5【r11⊂拍r亡dregI肌丁吊s⊂t一皿g〔5止ephy5icochemicd
prop招iぐ50「tI−CmOle〔t】1candeng巳nde・∼rClatiYer督i5はnCetO
lrてOt⊂1−1aSC digestion▲Pr1011Prnte−n aSgreg拇S(prP5⊂)aTe
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l−て1再=d一】ikep】aqu亡5aロJi∫=:1亡nCr、′0り55r5tem【oneurOnal
しミ〔ここ†、バごIro;ミ=in51Sand叩Or甘わ丁:ll⊂l−ユ∫1Se・
・「∴川e⊂厄n15nlbl▼、V㌣lに!、PrP⊂lS〔0【−、CrtCdtoPrPS‘remains
し川⊂:ご・1r.▲15CnC5i〔5Pr∈⊂】∼CrO2亡‖1山ea(【三0logγOrthedi5eaSe.
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nlロ:cここ11∈it5こ1Fcoい・crls PrP⊂†O tllじablO川1alconわーmation,
c∫lユーごrけ汀OUShユPrO⊂⊂SS Orl−eterOdlnlCrisation or through
T…⊂1earI)Ol)▼mCri5aこ10n(八gtェzこi&、∼′eisくmann,1997)・PrP5くi5
rcjユti、叫・rC51Stant tO PrO【e−na5e−K dl昌eStion and di脆ー亡nt
ciぉ.S∈Yeralmolec山=train占OrPrPSくoccurin5pOradicCJD;
however,Onlyasin由estrainorPrP5‘i5b皿dinYadantCJD,
whidlissim鮎r to thats亡亡min natⅣ迅γ○∝∬rlng bo扇ne
5POngiform encephalopathγ(BSE)in00ttlち弧d BSE【Tan‡−
mittednaturauγand叩erimentauγtOOtheranimals(Couinle
g川J,1996;Hi山亡【αい997a).E扇dellCe血atvariaれtCJDand
BSErepr亡鍾mtth亡姐meS【rainofpriondi5ea5eakoste爪5丘om
in托ctiY吋Stu山ぢinapriondiseaさ=traint汀ingpanelor
inbred甲perimen山mice,Wh亡rethepattモーIⅦOfincubation
pedodlnd neuropath0logicd也rgetin8Vere5imilar弧d
揖駄托d丘。mぬ紀S亡中nspoTadicC了D,SCrapl亡抽dothe−
priondi5亡揖eS(Bmceど一月J,1997)・
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AraれgeOfpriondi∽rdersbYebeende5dbedinduding仏05e
invoIving th亡SuP35plmd Urdp prot血5inγeaSt・Whi⊂h
appeartobenon−Pathogenicandconv町a5uⅣiv山dvantage
underc仁rtaill⊂ir00mStanCe5(Bur正成el亡fAJ,2004).
Scr叩▲eWび丘rs【血αibed85adi5ea諾Or血eepandgoat5
0Yer250years agoand demonstratedto be亡坪er血en【auγ
t−aMm適地Ie50years a騨(Agu認i&Pol叩Ienidou、ヱ004)・
Thereisnoevidencethtscrapichasevertransmittedtoman・
neonlyoth亡Tbown5dトs那はinmさanim山priom山ea5ei5
dronicwastingdiseaよeinmuledeerand曲b㌍Ve一山state50f
tlleUSんÅgain血亡r∈kno⊂u汀亡nt涙dence血8tthiさdi父おe
ha5tranSmittedtoman.
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
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「こ1一丁l=】†1t」…こ「Iノ1 ′、し一J
:”l、Lミdesin01rpamuhdebLr⊂sdtr丘ehsawDJC⊂idarop5
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、「
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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
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:、 ‥、
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
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■
∴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
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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,
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5)111ご〈
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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
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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
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trJrlS、L
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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
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Uに,】‥rarCC∴三亡1£lU‖二,「r=−1エロyandlLaly,IntheUKitappears
〔hこ:tミ、:⊥n⊂ゝ〔三亡rl亡亡n「\rこⅠヒ描CJDp亡akedinaboutZOOlandis
no、くノCこいⅠ=■Lご(F・さ1
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fewerCattEethanintheU,K.However,methodstopreventBSEfromgetting
in〔ohumanf00darenot⊂OmPletelytnptaceinatlEuropeancountriesISOWe
re⊂Ommend deFerra=」PtOthepresenヒtime.
H。WeffectivearethenewdonordeferralsatrcducingriskbfvCコD
from tranSfusion?
二Ombinedw冊=hee仔ectoFourpreviousrecommendations.ournew
−eCOnlmenda[10nS,addedtothepreviousU.K.deferraJ,eliminatean
ヨS亡imatedto亡a】90%c)Fovera=risk(Ca[cutatedby..risk−WeightedlTperson−daYS
っfexpOSUretOinFe⊂〔edbeeF)L,andmaydecreasethenumberofdonorsan
∃VerageOFanaddit70na15%nationwide・Thenewdeferra[sreF(ectanattempt
〔ominimize[hetheoretica(riskoftransmission’ofvC】DIWhfIema‡ntaining
criticaisuppl;eSOFb(00d p「Oducts.
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」
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1980to1996;Or
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havereccivedatransfbsionofwhoIc:て、〕(1Jし1▲日00dc刷1∵{l:’【∴∼=.1l】.じし∴
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i=iS[〕n=Jthc王LICko「⊂3hどIIOSticproceduresavailablefbrearlydetection・Consequently,HeaZth
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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
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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
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andbloodconlPOnentSfortrans[1ln,PE
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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
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h:oodtrこInSL、しlゝ一しⅢ、・‖兄tWOblooddonorsinvoIveddidnotdevelopsymPtOmSOfvCJD
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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
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donorba5eSandthesupp】)′Orblood.
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、’ariユntCJDthroushtheBIoodSupply”shouZdbedirectedto:
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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/
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12. StatisticsontheUnitedKillgdol¶’sしこ二〉
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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
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