UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl)
UvA-DARE (Digital Academic Repository)
Studies on leptospirosis : clinical aspects and pathophysiology
Wagenaar, J.F.P.
Publication date
2010
Link to publication
Citation for published version (APA):
Wagenaar, J. F. P. (2010). Studies on leptospirosis : clinical aspects and pathophysiology.
General rights
It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons).
Disclaimer/Complaints regulations
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.
0XULQHW\SKXVDQG/HSWRVSLURVLVDVDFDXVHRI
DFXWHXQGLIIHUHQWLDWHGIHYHULQ&HQWUDO-DYD
,QGRQHVLD
-)3:DJHQDDU 0+*DVHP 0*$*RULV06$GL%,VEDQGULR5$
+DUWVNHHUO-05RODLQ'5DRXOWDQG(&0YDQ*RUS
'HSDUWPHQWRI,QWHUQDOPHGLFLQH6ORWHUYDDUW+RVSLWDO$PVWHUGDPWKH1HWKHUODQGV 'HSDUWPHQWRI,QWHUQDOPHGLFLQH'U.DULDGLKRVSLWDO 'LSRQHJRUR8QLYHUVLW\6HPDUDQJ,QGRQHVLD 5R\DO7URSLFDO,QVWLWXWH.,7.,7ELRPHGLFDO5HVHDUFK$PVWHUGDPWKH1HWKHUODQGV )DFXOW\RI3XEOLF+HDOWK'LSRQHJRUR8QLYHUVLW\6HPDUDQJ,QGRQHVLD 'HSDUWPHQWRI0LFURELRORJ\/HSWRVSLURVLV/DERUDWRU\ 'LSRQHJRUR8QLYHUVLW\6HPDUDQJ,QGRQHVLD 850,7(&156,5'805)DFXOWpGH0pGLFLQHHWGH3KDUPDFLH 8QLYHUVLWpGHOD0pGLWHUUDQpH0DUVHLOOH)UDQFH 'HSDUWPHQWRIYLURORJ\(UDVPXV8QLYHUVLW\5RWWHUGDPWKH1HWKHUODQGV %RWKDXWKRUVHTXDOO\FRQWULEXWHG (PHUJ,QIHFW'LV
&+$37(5
&KDSWHU 7RLQYHVWLJDWHWKHSUHVHQFHRIULFNHWWVLRVHVDQGOHSWRVSLURVLVLQXUEDQUHVLGHQWVRI 6HPDUDQJ,QGRQHVLDZHWHVWHGWKHEORRGRISDWLHQWVZLWKIHYHU0XULQHW\SKXV ZDVIRXQGLQFDVHV$QRWKHUFDVHVVKRZHGLQFRQFOXVLYHVHURORJ\7KLUWHHQVXEMHFWV ZHUHGLDJQRVHGZLWKOHSWRVSLURVLV1RGXDOLQIHFWLRQVZHUHGHWHFWHG
$%675$&7
0XULQHW\SKXVDQGOHSWRVSLURVLVDVFDXVHRIXQGLIIHUHQWLDWHGIHYHU
)HYHU LV DPRQJ WKH PDLQ UHDVRQV IRU VHHNLQJ PHGLFDO DWWHQWLRQ LQ ,QGRQHVLD7KH
HWLRORJ\RIIHYHUXVXDOO\UHPDLQVREVFXUHEHFDXVHRIOLPLWHGODERUDWRU\GLDJQRVWLF IDFLOLWLHV DQG H[SHUWLVH IRU SHUIRUPLQJ ODERUDWRU\ FRQÀUPDWLRQ )DYRUDEOH HQYLURQPHQWDO FRQGLWLRQV PHDQ WKDW ERWK ULFNHWWVLRVLV DQG OHSWRVSLURVLV DUH FRQVLGHUHGHQGHPLFLQ,QGRQHVLDDQGPD\UHVXOWLQFOLQLFDOO\LQGLVWLQJXLVKDEOHFDVHV RIDFXWHXQGLIIHUHQWLDWHGIHYHU$8)6HURVXUYH\VFRQGXFWHGRQ-DYD6XPDWUDDQG LVODQGVLQHDVWHUQ,QGRQHVLDUHYHDOHGDQWLERGLHVWR5LFNHWWVLDW\SKLPXULQHW\SKXV 2ULHQWLDWVXWVXJDPXVKLVFUXEW\SKXVDQGWRPHPEHUVRIWKHVSRWWHGIHYHUJURXS ULFNHWWVLD 6)*5 LQ KHDOWK\ LQGLYLGXDOV ,Q DGGLWLRQ VHYHUDO LQYHVWLJDWLRQV UHSRUWHGOHSWRVSLURVLVDVFDXVHRI$8)LQ,QGRQHVLD
0XULQHW\SKXVDQGOHSWRVSLURVLVDUHOLNHO\WRVKDUHURXWHVRIWUDQVPLVVLRQLQDQXUEDQ VHWWLQJZHUHUDWVDUHDEXQGDQW7KHPDLQYHFWRUIRU5W\SKLLVWKH$VLDWLFUDWÁHD ;HQRSV\OODFKHRSVLV+XPDQVXVXDOO\EHFRPHLQIHFWHGZKHQ5W\SKLLQIHFWHGÁHD IHFHV FRQWDPLQDWHV H[FRULDWHG VNLQ RU LV LQKDOHG /HSWRVSLURVLV LV PDLQO\ VSUHDG E\ UDWV DQG RWKHU VPDOO PDPPDOV VKHGGLQJ WKH EDFWHULD YLD WKHLU XULQH LQWR WKH HQYLURQPHQW +XPDQV DUH LQIHFWHG WKURXJK PXFRXV PHPEUDQHV FRQMXQFWLYDH RU DEUDGHGVNLQ7KHFOLQLFDOIHDWXUHVRIERWKPLOGOHSWRVSLURVLVDQGPXULQHW\SKXVDUH QRQVSHFLÀF&ODVVLFDOO\PXULQHW\SKXVSUHVHQWVZLWKIHYHUKHDGDFKHDQGDUDVK WKRXJKWKHODWWHULVRIWHQDEVHQW5HQDOIDLOXUHMDXQGLFHDQGKHPRUUKDJHVDUHWKH FODVVLFDOV\PSWRPVRIVHYHUHOHSWRVSLURVLVZKLOHIHYHUKHDGDFKHDQGP\DOJLDPD\ EHWKHRQO\SUHVHQWLQJV\PSWRPVRIPLOGGLVHDVH'XDOLQIHFWLRQVZLWKPXULQHW\SKXV DUHUHSRUWHGWRRFFXULQ6RXWKHDVW$VLDDQGPD\FRPSOLFDWHWUHDWPHQWDQGFOLQLFDO FRXUVH 7KLVVWXG\DWWHPSWVWRÀQGHYLGHQFHIRUDFXWHULFNHWWVLDOGLVHDVHOHSWRVSLURVLVDQG GXDOLQIHFWLRQVDPRQJSDWLHQWVSUHVHQWLQJZLWK$8)LQ,QGRQHVLDZKHUHULVNIDFWRUV IRUERWKGLVHDVHVDUHOLNHO\WREHSUHVHQW
,1752'8&7,21
&KDSWHU
7KH VWXG\ ZDV EDVHG LQ 6HPDUDQJ D ODUJH FRDVWDO KDUERU FLW\ LQ FHQWUDO -DYD &RQVHFXWLYH RXWSDWLHQWV ZHUH UHFUXLWHG DW WZR SULPDU\ KHDOWKFDUH FHQWHUV DQG KRVSLWDOL]HG SDWLHQWV DW D JRYHUQPHQWDO UHIHUUDO FHQWUH 'U .DULDGL XQLYHUVLW\ KRVSLWDOGHSDUWPHQWRILQWHUQDOPHGLFLQH$OOHOLJLEOH$8)SDWLHQWV\HDUVRI DJHGHÀQHGDVIHYHU&FHQWUDOIRUOHVVWKDQGD\VZLWKQRDSSDUHQWRWKHU GLVHDVHZHUHLQFOXGHG$IWHULQIRUPHGFRQVHQWDÀUVWEORRGVDPSOHZDVWDNHQ$ FRQYDOHVFHQWVDPSOHZDVGUDZQDIWHUDSSUR[LPDWHO\GD\V7KHVWXG\ZDVDSSURYHG E\WKHORFDOPHGLFDOHWKLFDOFRPPLWWHH $VSHFLÀFPLFURLPPXQRÁXRUHVFHQFH,)$DVVD\IRU5LFNHWWVLDVSHFLHVZDVSHUIRUPHG LQ0DUVHLOOH)UDQFHE\XVLQJZKROHFHOODQWLJHQVRI2WVXWVXJDPXVKL5MDSRQLFD 5KHLORQJMLDQJHQVLV5VORYDFD5KRQHL5FRQRULLVXEVSLQGLFD5LFNHWWVLD´$7,µ 5KHOYHWLFD5IHOLV5W\SKLDQG5SURZD]HNLL7KHDVVD\ZDVFRQVLGHUHGSRVLWLYH ZKHQDQWLERG\WLWHUVZHUHIRU,J*DQGIRU,J0RUDVHURFRQYHUVLRQ ZDVREVHUYHGRUIROGLQFUHDVHLQWLWHUVEHWZHHQWKHDFXWHDQGWKHFRQYDOHVFHQW VHUXPZDVGHWHFWHG/HSWRVSLURVLVVHURORJ\ZDVSHUIRUPHGLQ6HPDUDQJ,QGRQHVLD &URVVFKHFNVDQG3&5ZHUHSHUIRUPHGLQ$PVWHUGDPWKH1HWKHUODQGV&RQYDOHVFHQW VDPSOHVZHUHVFUHHQHGZLWKWKH/HSWR7HN'UL'RW%LRPpULHX[$OOSRVLWLYHFDVHVZHUH WHVWHGE\WKHPLFURVFRSLFDJJOXWLQDWLRQWHVW0$7DQG,J*(/,6$$GGLWLRQDOO\ DUHDOWLPH3&5PDQXVFULSWLQSUHSDUDWLRQVSHFLÀ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
7+(678'<
0XULQHW\SKXVDQGOHSWRVSLURVLVDVFDXVHRIXQGLIIHUHQWLDWHGIHYHU 0XULQHW\SKXVDQGOHSWRVSLURVLVZHUHERWKIRXQGWRFDXVH$8)LQWKLVFOLQLFDOVHULHV 7DEOH,QWRWDOQLQHSDWLHQWVKDGHYLGHQFHRIDQDFXWHLQIHFWLRQZLWK5W\SKL QRQHVKRZHGDUDVK,QKRVSLWDOPXULQHW\SKXVFRXOGEHGLDJQRVHGLQRXWRI SDWLHQWV7KUHHRXWRIRXWSDWLHQWVKDGDFXWHPXULQHW\SKXV$QRWKHU QLQHFDVHVVKRZHGLQFRQFOXVLYH5W\SKLVHURORJ\2QHFDVHVKRZHGHYLGHQFHRI DSDVWLQIHFWLRQZLWK5W\SKL,)$LQERWKVHUD(YLGHQFHIRUDFXWHLQIHFWLRQ ZLWK2WVXWVXJDPXVKLRU6)*5ZDVQRWIRXQG
/HSWRVSLURVLV ZDV GLDJQRVHG LQ RXW RI SDWLHQWV RI WKHVH ZHUH SRVLWLYHRQO\E\3&5(OHYHQOHSWRVSLURVLVSDWLHQWVZHUHUHFUXLWHGLQKRVSLWDOWZR SDWLHQWVZHUHUHFUXLWHGRXWKRVSLWDO&RQVHTXHQWO\WKHSHUFHQWDJHRI$8)FDXVHG E\OHSWRVSLURVLVLQKRVSLWDOL]HGSDWLHQWVZDVDQGLQRXWSDWLHQWV7KHPRVW IUHTXHQWO\LGHQWLÀHGVHURJURXSE\0$7ZDV%DWDYLDHFDVHV1RGXDOLQIHFWLRQV ZHUHGHWHFWHGKRZHYHUWKUHHOHSWRVSLURVLVSDWLHQWVVKRZHGWLWHUVLQWKH5 W\SKL,)$
,Q WKLV VWXG\ ZH UHSRUW IRU WKH ÀUVW WLPH PXULQH W\SKXV DQG OHSWRVSLURVLV DV DQ LPSRUWDQWFDXVHRI$8)LQ6HPDUDQJ,QGRQHVLD$SUHYLRXVVWXG\IURPUXUDO7KDLODQG LGHQWLÀHGERWKGLVHDVHLQUHVSHFWLYHO\DQGRI$8)FDVHV,QWKH FDSLWDOFLW\RI/DRV5W\SKLZDVUHSRUWHGWRFDXVHIHYHULQRILQYHVWLJDWHG VXEMHFWV FORVHO\ UHVHPEOLQJ RXU GDWD 8QIRUWXQDWHO\ OHSWRVSLURVLV ZDV QRW LQYHVWLJDWHG,QWKHSUHVHQWVWXG\ZHH[SHFWHGOHSWRVSLURVLVDVDFDXVHRI$8)VLQFH WKH'U.DULDGLKRVSLWDODGPLWVDURXQGVHYHUHFDVHVHDFK\HDU7KHVHFDVHVZHUH QRWLQFOXGHGLQWKHVWXG\EHFDXVHRIWKHKLJKFOLQLFDOVXVSLFLRQRQDGPLVVLRQZLWK MDXQGLFHD]RWHPLDDQGRUEOHHGLQJPDQLIHVWDWLRQV$GHÀQLWHGLDJQRVLVRIPXULQH W\SKXV DQG OHSWRVSLURVLV GRXEOH LQIHFWLRQV FRXOG QRW EH PDGH EXW LQ FDVHV WKLV VFHQDULR ZDV SODXVLEOH :H GLG QRW ÀQG HYLGHQFH IRU VFUXE W\SKXV DV H[SHFWHG EHFDXVH2WVXWVXJDPXVKLWUDQVPLVVLRQRFFXUVSULPDULO\LQUXUDODUHDV$OWKRXJK 6)*5KDYHEHHQUHSRUWHGLQ6RXWKHDVW$VLDDQGSURRIIRUWKHLUSUHVHQFHLQ,QGRQHVLD LV DFFXPXODWLQJ WKHVH ZHUH QRW LGHQWLÀHG DV D FDXVH$8) LQ WKH SUHVHQW VWXG\
&KDSWHU 7DEOH &OLQLFDODQGODERU DWRU\GDWDRISDWLHQWVZLWKULFNHWWVLRVHVDQGOHSWRVSLURVLV 3DWLHQW QR $JH VH[ 0RQWK RIRQVHW LOOQHVV 5W\SKL,) $,J*,J0 0$ 7 /HSWRVSLURVLV 3&5 &OLQLFDOIHDWXUHVDQGDQWLELRWLF WUHDWPHQW $GPLVVLRQ VDPSOH &RQYDOHVFHQW VDPSOH +LJKHVWWLWHU SDWKRJHQLF VHURYDU 3XWDWLYHLQIHFWLQJ VHURJURXS 0XULQHW\SKXV 0 )HEUXDU\ 1$ 1$ QHJDWLYH GD\IHYHU P\DOJLDKHDGDFKHFKLOOVFRXJK DEGRPLQDOSDLQ5[FLSURÁR[DFLQ 0 0DUFK 1$ 1$ QHJDWLYH GD\IHYHU P\DOJLDKHDGDFKHQDXVHDDEGRPLQDO SDLQ5[FLSURÁR[DFLQ ) 0DUFK 1$ 1$ QHJDWLYH GD\IHYHU KHDGDFKHFKLOOVQDXVHDYRPLWLQJ KHSDWRPHJDO\5[FLSURÁR[DFLQ 0 $SULO 1$ 1$ QHJDWLYH GD\IHYHU KHDGDFKHVRUHWKURDWDEGRPLQDOSDLQ 5[FHIDGUR[\O ) $SULO 1$ 1$ QHJDWLYH GD\IHYHU KHDGDFKHQDXVHDDEGRPLQDOSDLQ5[ FLSURÁR[DFLQ ) 1RYHPEHU 1$ 1$ QHJDWLYH GD\IHYHU P\DOJLDKHDGDFKHFKLOOVQDXVHD G\VSQHD5[FLSURÁ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ÁR[DFLQ 0 )HEUXDU\ 1$ 1$ QHJDWLYH GD\IHYHU KHDGDFKH5[DPR[LFLOOLQ ) )HEUXDU\ 1$ 1$ 1$ QHJDWLYH GD\IHYHU P\DOJLDKHDGDFKHQDXVHDYRPLWLQJ DEGRPLQDOSDLQ5[DPR[LFLOOLQ
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ÁR[DFLQ ) 0D\ QHJDWLYH QHJDWLYH D %DWDYLDH QHJDWLYH GD\IHYHU P\DOJLDKHDGDFKHFKLOOVQDXVHD YRPLWLQJQRDQWLPLFURELDOGUXJ 0 0D\ QHJDWLYH QHJDWLYH D %DWDYLDH QHJDWLYH GD\IHYHU P\DOJLDKHDGDFKHFKLOOVGLDUUKHD FRQMXQFWLYDOVXIIXVLRQ5[FLSURÁ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ÁXRUHVFHQFH DVVD\ 0$ 7 PLFURVFRSLF DJJOXWLQDWLRQ WHVW 0 PDOH ) IHPDOH 1$ QRW DYDLODEOH QF QRW FODVVLÀDEOH 33 SURFDLQHSHQLFLOOLQ5[PHGLFDOSUHVFULSWLRQ D3 DWLHQWVHURFRQYHUWHGIURPQHJDWLYHWRDSRVLWLYHWLWHUE\0$ 7RU(/,6$ E7KHUHZDVQRWHQRXJKVDPSOHWRSHUIRUP3&5SDWLHQWKLJKO\VXVSHFWHGIRUOHSWRVSLURVLV F,J*(/,6$ UHVXOWWKHKLJKHVWWLWHUE\0$ 7ZDV
&KDSWHU
)URPHSLGHPLRORJLFDOSRLQWRIYLHZ6HPDUDQJVHHPVWRHQFRPSDVVHQYLURQPHQWDO FLUFXPVWDQFHV WKDW DUH SUHUHTXLVLWHV IRU 5 W\SKL DQG OHSWRVSLURVLV WUDQVPLVVLRQ ,QGHHGSUHYLRXVVWXGLHVVKRZWKDWPXULQHW\SKXVLVSDUWLFXODUO\SUHYDOHQWLQWURSLFDO SRUWFLWLHVZKHUHUDWVDUHDEXQGDQW)RUWKH,QGRQHVLDQXUEDQVLWXDWLRQ5 UDWWXVDQG5QRUYHJLFXVDUHOLNHO\WREHWKHPDLQKRVWVKDUERULQJ5W\SKLLQIHFWHG ; FKHRSVLV 7KHVH UDWV DUH DOVR OLNHO\ WR EH WKH PDLQWHQDQFH KRVWV IRU SDWKRJHQLF/HSWRVSLUDLQ,QGRQHVLD,QIDFWWKHLGHQWLÀHGVHURJURXSVDUHFRPPRQO\ DVVRFLDWHGZLWKUDWV
$OWKRXJKVHURORJ\PLJKWEHKDPSHUHGE\FURVVUHDFWLRQVDQGVHQVLWLYLW\LVVXHVZH EHOLHYHWKDWRXUGDWDLVUHSUHVHQWDWLYHIRUWKHDUHD7KHFKRVHQFXWRIIYDOXHVDUH XQOLNHO\ WR FDXVH IDOVH SRVLWLYHV LQ DQ HQGHPLF VHWWLQJ ,Q UHJDUG WR OHSWRVSLURVLV VHURORJ\ZHXVHGDZLGHSDQHOIRUWKH0$77KLVSDQHOLQFOXGHG:+2UHFRPPHQGHG VHURYDUV DQG VHURYDUV WKDW ZHUH SUHYLRXVO\ LVRODWHG LQ ,QGRQHVLD 0RUHRYHU PRVW VHURJURXSVZHUHUHSUHVHQWHGLQRXUSDQHODQGFURVVUHDFWLRQVDUHOLNHO\WRSLFNXS PLVVLQJVHURYDUV
'XH WR QRQVSHFLÀF SUHVHQWDWLRQ DV UHSRUWHG KHUH ERWK GLVHDVHV DUH GLIÀFXOW WR GLDJQRVHRQFOLQLFDOJURXQGVRQO\0LVGLDJQRVLVFDQOHDGWRDEHUUDQWXVHRIDQWLELRWLFV DQGRWKHUSKDUPDFHXWLFDOV7KHUHIRUHUDSLGFKHDSDQGUHOLDEOHWHVWVDUHZDUUDQWHG WRVXSSRUWFOLQLFDOGHFLVLRQPDNLQJ $FNQRZOHGJHPHQWV :HJUDWHIXOO\WKDQN60+)DUDG]DQGSHUVRQQHO&(%,256HPDUDQJ,QGRQHVLDDQG WKHUHVLGHQWVRIWKHGHSDUWPHQWRI,QWHUQDO0HGLFLQH'U.DULDGLKRVSLWDO6HPDUDQJ ,QGRQHVLDIRUWKHLUKHOSDQGDVVLVWDQFHGXULQJWKHVWXG\:HJUDWHIXOO\WKDQN$$ $KPHG5R\DO7URSLFDO,QVWLWXWH$PVWHUGDP7KH1HWKHUODQGVIRUSHUIRUPLQJWKH OHSWRVSLURVLV3&5
0XULQHW\SKXVDQGOHSWRVSLURVLVDVFDXVHRIXQGLIIHUHQWLDWHGIHYHU
5LFKDUGV$/6RHDWPDGML'::LGRGR0$6DUGMRQR7:<DQXZLDGL%+HUQRZDWL7(HW
DO6HURHSLGHPLRORJLFHYLGHQFHIRUPXULQHDQGVFUXEW\SKXVLQ0DODQJ,QGRQHVLD$P -7URS0HG+\J-XO\
5LFKDUGV $/ 5DWLZD\DQWR 6 5DKDUGMR ( .HOO\ '- 'DVFK *$ )U\DXII '- HW DO 6HURORJLFHYLGHQFHRILQIHFWLRQZLWKHKUOLFKLDHDQGVSRWWHGIHYHUJURXSULFNHWWVLDH DPRQJUHVLGHQWVRI*DJ,VODQG,QGRQHVLD$P-7URS0HG+\J$SULO 9DQ 3HHQHQ 3) .RHVKDUMRQR & 6HH 5 %RXUJHRLV$/ ,UYLQJ *6$QWLERGLHV DJDLQVW
PXULQHW\SK\XVLQVHUDIURP,QGRQHVLDQV7UDQV56RF7URS0HG+\J /LJKW 5+ 1DVXWLRQ 5 9DQ 3HHQHQ 3) /HSWRVSLURVLV LQ IHEULOH KRVSLWDO SDWLHQWV LQ
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
% HW DO 5LFNHWWVLDO LQIHFWLRQV DQG IHYHU 9LHQWLDQH /DRV (PHUJ ,QIHFW 'LV )HEUXDU\
:DWW*3DUROD36FUXEW\SKXVDQGWURSLFDOULFNHWWVLRVHV&XUU2SLQ,QIHFW'LV 2FWREHU
,EUDKLP ,1 2NDED\DVKL 7 5LVWL\DQWR /HVWDUL (: <DQDVH 7 0XUDPDWVX < HW DO 6HURVXUYH\ RI ZLOG URGHQWV IRU 5LFNHWWVLRVHV VSRWWHG IHYHU PXULQH W\SKXV DQG 4 IHYHULQ-DYD,VODQG,QGRQHVLD(XU-(SLGHPLRO-DQXDU\
5LFKDUGV $/ 5DWLZD\DQWR 6 5DKDUGMR ( .HOO\ '- 'DVFK *$ )U\DXII '- HW DO 6HURORJLFHYLGHQFHRILQIHFWLRQZLWKHKUOLFKLDHDQGVSRWWHGIHYHUJURXSULFNHWWVLDH DPRQJUHVLGHQWVRI*DJ,VODQG,QGRQHVLD$P-7URS0HG+\J$SULO 5LFKDUGV$/5DKDUGMR(5XVMGL$).HOO\'-'DVFK*$&KXUFK&-HWDO(YLGHQFH
RI 5LFNHWWVLD W\SKL DQG WKH SRWHQWLDO IRU PXULQH W\SKXV LQ -D\DSXUD ,ULDQ -D\D ,QGRQHVLD$P-7URS0HG+\J$SULO
'XSRQW +7 %URXTXL 3 )DXJHUH % 5DRXOW ' 3UHYDOHQFH RI DQWLERGLHV WR &R[LHOOD EXUQHWWL 5LFNHWWVLD FRQRULL DQG 5LFNHWWVLD W\SKL LQ VHYHQ $IULFDQ FRXQWULHV &OLQ ,QIHFW'LV1RYHPEHU
,EUDKLP ,1 2NDED\DVKL 7 5LVWL\DQWR /HVWDUL (: <DQDVH 7 0XUDPDWVX < HW DO 6HURVXUYH\ RI ZLOG URGHQWV IRU 5LFNHWWVLRVHV VSRWWHG IHYHU PXULQH W\SKXV DQG 4 IHYHULQ-DYD,VODQG,QGRQHVLD(XU-(SLGHPLRO-DQXDU\
-LDQJ-6RHDWPDGML':+HQU\.05DWLZD\DQWR6%DQJV0-5LFKDUGV$/5LFNHWWVLD IHOLVLQ;HQRSV\OODFKHRSLV-DYD,QGRQHVLD(PHUJ,QIHFW'LV$XJXVW
&KDSWHU