Emily MacDonald 1,2*, Per Kjetil Dalane 3, Preben Aavitsland 4, Lin Thorstensen Brandal 5, Astrid Louise Wester 5 and Line Vold 1

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1 MDnd BMC Inu D hp//wwwbmdnm/ /14/673 RSARCH ARTICL Opn A Impn nng nd hd un p hdn wh Shg-n pdung hh nn n nd m n ub n d n Nw 2012 m MDnd 12* P Kj Dn 3 Pbn Avnd 4 Ln Thnn Bnd 5 Ad Lu W 5 nd Ln Vd 1 Ab Bgund In Nw mmndd h hdn wh Shg-Tn pdung hh (STC nn udd m d n un up v nuv ngv uu bnd Chdn wh gnn n unnwn g d mn hm 48 hu mpm ubd On 16 Ob 2012 w STC nn w pd m d n wh h hdn w mpm L hh uh mp d h d n nd hdn nd w nd phgn W pn h u h ub nvgn n d du h mpn nng nd h un p hdn ndng d n Nw Mhd S pmn hdn (n = 91 nd mp h d n (n = 40 w d phgn Inmn n dmgph mpm nd pn pu w d m pn hugh wng nvw nd wb-bd qunn C w mnd dmn h dun hddng nd h ung un pd m d Ru W dnd v hdn wh 1- nd v STC O103H2 nn nd n mmb nd n hd wh STC O91H- nn Th ddn hdn wh d pv 1 nd gn w ndd pbb STC Th w mpm Mdn ngh m un m d STC w 53 d (ng 9 d 108 d Suv pn 75 hdn vd md gnn mpm mng bh hdn wh STC nn nd hdn wh ngv mbg u Th w n vdn mmn pu; pn-n nmn w Cnun Th u nng nd h nn n pd n d n d n h ppn hdn wh STC nd PC nn Wh nng n dn mpm h mpn hud b u ndd n pdu unnpd u nd hv gnn nm nqun D un p hud b vwd dd h mngmn pngd mpm hdd Kwd hh Shg-n pdung hh nphgn hh D ub Chd Chd d n Nu * Cpndn mmdnd@hn 1 Dpmn Inu D pdmg Nwgn Inu Pub Hh PO B 4404 Ndn NO-0403 O Nw 2 upn Pgmm Invnn pdmg Tnng (PIT upn Cn D Pvnn nd Cn Shm Swdn Fu uh nmn vb h nd h 2014 MDnd ; n BMd Cn Th n Opn A dbud und h m h Cv Cmmn Abun Ln (hp//vmmng/n/b/20 whh pm und u dbun nd pdun n n mdum pvdd h gn w pp dd Th Cv Cmmn Pub Dmn Ddn wv (hp//vmmng/pubdmn/z/10/ pp h d md vb n h un hw d

2 MDnd BMC Inu D Pg 2 8 hp//wwwbmdnm/ /14/673 Bgund Shg-n pdung hh (STC dng u gnn n ngng n v m md dh hmhg Cmpn nud hm um ndm (HUS whh n d dh [1] STC n b nmd humn hugh numpn nmnd d w hugh d n wh nm h m hugh pn-n nmn [2] Oub STC nn n hd [3-7] p pu h pub hh hdn und 5 d m qun dgnd wh nn nd g dvpng HUS [2] Th mj STC gn ndng h hng nd ng (A/ pn nmn whh mpn h hmn h bum h ph n h n STC pdu n bh Shg n 1 (S1 nd Shg n 2 (S2 pdmg ud hv hwn h STC pdung S2 bh S1 nd S2 m mmn d wh HUS hn pdung n S1 [8] STC h bn nb n Nw n 1995 nd wng n ub STC O103H25 n 2006 mu b pd whn 24 hu upn h Nn Inu Pub Hh (NIPH Bwn 1994 nd STC w nd n Nw whh 38% (165 w hpzd nd 12% (53 dvpd HUS [9] Ahugh h g pd nmb b whn mpm p-mpm hddng n d mmun pd nn [1] Th dun hddng STC mpm hv d v nd n md nmn vb nn-o157 n [9] Hwv h mdn dun hddng pd m pvu ub n hd h bn und b bwn 20 nd 50 d [5710] A vw 90 ub STC O157 hwd h hgh nd nmn w und n ub wh h mdn g w <6 nd n ub ung hugh pn pn pd n hd [11] Th m b d n hdn wh mmu mmun m nd unddvpd pn hgn n ddn h ng dun hddng In d pvn nmn h nn h NIPH mmnd dn n mu dpndng n h n pnn pdmg n nd vun p nd STC gup h Th nud ngn d un p hdn dgnd wh STC nn [12] Chdn wh hv d pv STC hud mn hm un h hv hd p numb ngv n n 24 hu p Th pp bh uu-nmd nd n whh h nd gn n dd n mp I pd h - nd -gn pv bu uu ngv n mu mpmnd pndng uh u Th numb nuv ngv n qud dpndn n h v n pnn h vun h STC n nd h hd nmn Chdn dgnd wh 2v STC n STC gup h h bn qun d wh HUS hud hv v nuv ngv u b unng d gd mpm v Chdn wh unmpd dh wh n 1v STC hud hv h ngv n b unng d un h 1v p h bn pvu d wh HUS n whh v nuv ngv qud A hdn wh STC nn wh v n pnn uh bd dh HUS qu v ngv n Th NIPH mmnd h whn STC nn u n d ng h hdn n h d wh gnn mpm hud b d Ahugh gn n dvd mpm hdn nng hdn n d n n b ndd n un wh pn-pn nmn whn d upd h qu pub hh uh In ddn n hd wh gnn mpm unnwn g d mn hm wh mpm nd n un d 48 hu mpm hv ubdd On Tud 16 Ob h NIPH w nd b h Munp Hh O w 1- nd pv STC O103H2 nn mng hdn ndng d n n uhn Nw In ddn h d pd h dh n hd d ndb numb hdn ndng h d hughu Spmb nd Ob A STC O103H2 nwn hv pvu ud bd dh nd v HUS [1314] hh uh nd h d d h n nv nng n 17 Ob A m STC w upd hdn w d hv mp d STC p unng h d n Th d pnd n 22 Ob hdn wh hd ngv u STC An ub nvgn w nd n bn wh hh nd d uh n d dmn h n h ub dn u nn nd m h dun hddng n d mpmn n mu nd mnmz h mp n uu ub n d n W pn h u h ub nvgn nd du h mpn nng nd h un p hdn ndng d n Nw

3 MDnd BMC Inu D Pg 3 8 hp//wwwbmdnm/ /14/673 Mhd Dpn h d n Th d n nw nd mdn d n wh 40 nd p ppm 90 hdn dbud mng v n Tw n (A nd B ung hdn gd h nd und Tw n (C nd D d hdn gd h v Th h n ( n ud gup hdn gd u v wh pnd m h d ud n h wd C dnn nd dnn A m d n h ub munp d n h mmun hh n nd w d h ub un Th n mbg b w nmd h ub Th wng b-bd dnn w dvpd h ub Pbb An hd ndng h d wh pmn -gn ndng n n mp bwn 1 Spmb nd 31 Ob 2012 Cnmd An hd ndng h d wh STC nn nmd b h Nn Rn Lb bwn 1 Spmb nd 31 Ob 2012 Dnn pbb nd nmd nudd mpm dnd hugh h nng Mbg nvgn Th w n STC w d ndd gnn phgn (Smn Cmpb Yn nd Shg w STC Fwng h dn n hdn mp w d h mmun hh n nd hn n h b n ung PCR-mhd dng 1 nd 2 Spmn d hugh nng w n d phgn h hn Pmn u h hdn nd mp h d n w pvdd h Munp Hh O wh hn wdd hm d h NIPH Pv u w pd b h b h NIPH v h Nwgn Suvn Sm Cmmunb D (MSIS A nd v w n h Nn Rn Lb (NRL NIPH nmn OH png ubpng [15] nd gnpng b mup-u vb numb ndm p n (MLVA [16] F wh d pv STC w-up w n mnmum nv 24 hu un v nuv pmn w bnd Dun hddng w ud h pd bwn mpm n ( d ng mpm nd h d h ngv n Dun un m d w ud h pd mpm n ( d ng mpm h d h qud n pdmg nvgn Th bnh h Nwgn Fd S Auh (NFSA ndud nddzd wng nvw wh h pn pbb nd nmd n d gn hph nnng pb mmn u nn Th qunn w ud dd nmn n dmgph nmn n nmn nudng p nd dun mpm d numpn nm n nd nvnmn pu In ddn dpv h nvgn hdn ndng h d w ndud n d nvg h un dh pd b pn nd dn pb pu h pd 1 Spmb 17 Ob 2012 F h pup h ud n p dnn dh w pvdd pn Du h g h mn w wng dp nd h qun dh ung nvnn dnn uh m hn h whn 24 hu m hv bn du bh Pn w d p whh h hd hd hn nm m qun hn nm nd/ dh Pn w pvdd n wb-bd qunn ung Qub whh w md vb Ob 29 Nvmb 7 (Addn 1 Rmnd pnd h qunn w n b m n 2 Nvmb nd b SMS n 6 Nvmb Th n h qunn w mpnd b ng h ppn w vun nd h ndn pn wud b mnnd Rpn h qunn w ndd nn ppn A h uv nd h d n dbd n h p w p pub hh nvgn n u vn n m n h vw bd h w n n pmd b Nwgn gn A dpv n h u h qunn w ndud ung 2010 nvnmn nvgn Th NFSA vd h d n n 16 Ob n d np h In pu d hgn p nd d hndng pdu nng un hn hgn mu nd gnzn w npd Fd hnd pvdd h NFSA wh p mnu h pd p h ub An n nun npd h whm nd dp-hngng Ru Dpn STC A 91 hdn ndng h d n dung h ud pd ubmd mp p unng

4 MDnd BMC Inu D Pg 4 8 hp//wwwbmdnm/ /14/673 h d n S hdn w d nmd pmn m v hdn w pv O103H2 nd 1 wh dn m MLVA p (n u dn wh n hd hd pmn h w pv STC O91H- nd w 1- nd 2bv Th pnd n v 7% Th ddn hdn d pv nd 1 h b n md uu bu h NRL w unb STC w h hdn nd h hd hd dd n hv pmn pvdd h NRL Th w d pbb Th mdn g STC w 2 (ng 1 4 nd n n w m Th m mmn pd mpm w dh (6/9 wh v png v (4/9 N dvpd bd dh v mpn Th w mpm nd n dnd hugh nng On mpm ud bwn 8 Spmb nd 16 Ob 2013 Th pbb nd nmd w dnd mng hdn ndng h dn d n (Tb 1 A pbb nd nmd mng h d gup ngd m 0% n Gup C nd 21% n Gup A In ddn h nn n hdn h w n nmd mng mmb (STC O91H- 1 wh w mpm nd dnd hugh nng w w nmd (bh O103H2 1 nd nd h pbb mng m mmb h hdn whm hd md mpm Th mmb wd pm wh Gup D wh h d m mmb w nd hdn n Gup A nd B (Fgu 1 Fuhm nng dnd wn-nn hdn n h d wh pv n ndv nphgn hh (PC Th pmn w n uh pd n d h v n nd w n ubmd h NRL uh n Th hdn w n qud ubm w-up n pdmg nvgn Th pn gh hdn wh pbb nmd STC nn w nvwd b mp h NFSA In ddn qunn pn w ubmd hdn ndng h d (82% Rpn vd bwn h dn d gup ngng m 69% 96% A vw h wng qunn nd h dpv h ud dd n v n mmn u nn mng d d m w u n wh nm v h mng hdn h pn Twn-w hdn (30% hd pnd dh ( hn nm m qun hn nm nd/ dh n bwn 1 Spmb nd 31 Ob 2012 S pn hzd h hd mpm w dh bu nn pd bd dh Th dun mpm ngd m h d v u w Gup A B nd D hd v m hdn wh dh nd PC hn h h gup w nmd pdmg n wh n huhd mmb nd mp (Fgu 1 Amng Gup h ud gup n STC nd w dh w dnd Nn pn (12% pndd h w du dmn whh h hd hd dh Pn hd dng png h hd hm m d p h ub Wh m pn nwd h h wud p h hd hm h hd v md n ddn pnng gnn mpm n 65% wud p h hd hm bd n h nvnn dnn dh (m hn 3 whn 24 hu On 33% wud p h hd hm bd n hng n nn qun Dun hddng n STC Th mdn dun hddng w 48 d nmd (ng d (Fgu 2 F pbb h mdn dun hddng w 7 d (ng 2 10 d Th mdn dun un m d nmd w 71 d (ng d M hd nuv ngv u n h hd vd h ngv u nd dd n nd ng du pv u Hwv w ndd h nuv Tb 1 A pbb nd nmd b d gup Spmb 1 Ob D n N hdn Pbb Cnmd A (pbb + nmd A (nmd A ( % 14% B ( % 13% C ( % 0% D ( % 8% (4-5 * % 0% T % 7% *Oud gup

5 MDnd BMC Inu D Pg 5 8 hp//wwwbmdnm/ /14/673 Fgu 1 Pnd dh nd u phgn hdn h d b gup Ob 2012 Nw *h qu pn n pn ng n Th d pv PC ng pv STC whh w ndd ngv u nvnmn nvgn Th NFSA npn und h h d n hd gd d hndng nd hgn un n p Fd n h d ppd nd vd b nd d hnd A vw mnu pvdd b h d hnd h d n vd n upu d m Tmpu n p w n p nd d pvn h d w w gnzd Th d u d m uppd b wh d dbu nd upm In ddn h dgnd ng nd hngng dp w w mnnd nd hd wh bn wh h w p dpn nd hn dpn vb h n Th mp hd undgn hgn nng nd h n hd w bhd un Dun Th ub nn n h d n nduv h pd gnn n mng hdn Th u h ub Fgu 2 D mpm n pv nd ngv nmd nd pbb h d Nw

6 MDnd BMC Inu D Pg 6 8 hp//wwwbmdnm/ /14/673 unnwn bu h h STC O103H2 nd STC O91H- p w ndud h d n b p nd nd hn nmd bwn h hdn nd m mmb Th uppd b mpm n d mng nmd bng ggd v w-mnh pd In ddn h w n ndn m h wng qunn h nvgn n mmn u nn A h m h dbd ub ppd h mup hdn ndng h d n ud hv STC nn nd STC O103 L hh dmd ppp h d mp nd n hdn Th n mu n mmndd d ub bu n b ndd n v umn Um n dvpd u mpm nd h ub w nupd whh m hv bn bub h mpmnn h n mu Hwv v hdn ndng h d h w pv STC w mpm A nng n v unpd u h nqun mpmnng nng mu b hugh ndd pu n m hw hdn h mpm bu pv phgn w b mngd Th mpm hdn n nmn h nn n h ub unnwn A v nmd STC w n dnd hugh nng w n pb dmn h pn whh h w nd h dun b hddng p nng whh h ub w ppgd b mpm hdd pu h bgund v dh mng hdn wh ngv STC u w hgh un p bd n h pumpn h hdn n nm STC nn h hdn whn mpm nd h nung hdn n ng hddng h b b h un d w pvn pd d Hwv h dun h ung un pd n b nv nd png mpm hdn hm wh wng mup nuv ngv u n hv ubn nm mp Pn w n b qud m w nd hdn w b d m h p h dun hddng whh h bn pd up 140 d [10] In h nn hdn w udd m d 459 d wh mdn un pd 53 d p hd Th w ng hn pvu Nwgn hd ub O145 wh h mdn dun w 20 d (ng 0-71 d Ahugh un p v ndb m un un Nw h php h m v pph n h wd wh h mmndn hv up v nuv ngv u b unng d Th w dvpd n pn w n u ub STC ng hdn h d v HUS nd n dh [17] Oh Nd un [18] p Cnd h Und S Au nd h Und Kngdm gn qu w h ngv b unng d Th dn bwn qung w ngv nd v ngv m n um u n ubn ng un pd un w ngv wd b pv In h ub h hdn h hd h b ng pd m w nn pv un h ngv whh h w vn bwn ngv nd pv u Th dn bwn w nd v n nd h un pd b 3 4 d whh nggb m hn 100 d pv In h ub pmn w n d b PCR nd nmd b uu Hwv h nng u uu ndpndn dgn m mp h ppn n mu whh n Nw un bd n nwng h vun p nd gup A h nmn n w vb wh PCR n m gu n mu hn n m b mpmnd pndng uh nmn nd h m b h un numb nuv ngv m b ndd Th nd mu h nmn nm ppp n mu n ub un hud n b undmd M h ndd gdng h ng-m mpm hdd nmng n n dn ng nudng hd [19] A uh ng h PC pmn w n ndud unnwn whh h PC nn und hugh nng pdmg nd h STC PC u dh p mng hdn bu und n mpm hdn nd gn d n nu g pbm n nduzd un PC h bn nb n Nw n 1994 wh m hn 1200 pd bwn 1994 nd 2011 Sp O103H2 h n bn und n p PC n Nw bu h pvu bn und n v nd p PC (PC F m p uh O26H11 h bn hwn h PC nd STC phgn nd gn d nd h h v n dnm nhp n whh gn mgh b gnd [2021] Th ubn numb hdn pv PC nd h hdn wh w n pv STC nd ubqun pv PC m nd h h w nhp bwn STC nd PC n h ub hugh h nn b nmd n h PC pmn w n ndud Hwv h bvd pvn PC und hugh nng n Nwgn

7 MDnd BMC Inu D Pg 7 8 hp//wwwbmdnm/ /14/673 d wng n ub STC O145 n 2009 [7] nd ud mng hh hdn nd hdn wh md gnn mpm nd h PC nn qun mpm nd h h ndm v PC hgh n Nw [2223] I h n nwn whh h PC u dnd hugh nng bub h hv h 1-ndng bphg nmn ub PC pd dn p PC m n pn nm Th nmd nd pbb STC w hgh mng h gup ung hdn mn whm w n dp wh h ud gup hd n nmd STC nd h w hdn wh h PC pd dh Th hdn n h gup wud hv md n wh h hdn ndng h d nd h b nd hugh pn-n n Th n h hdn wh hv gnn mpm pu h wng dp m p g h hdn nd mmb hn mpm hdn wh Rgd h g gnn mpm hdn hud b p hm h mmndd 48 hu wng h mpm Pn p dun mpm nd numb d hm m d n h ub ugg h hdn n w p hm u 48 hu mpm ubd qud b h d p whh bd n mmndn m h NIPH Chdn h nm hv n qud hm m d bu h pn pnb whh hd h n unuu hng n qun nn A h u h nvgn nd h m pn nd hngng dmn whn ppp p hdn hm m d pdu d n hud b nd gu nd pn hud b nugd hv w hhd png hdn hm Fwng h ub h d n dd h p mng nd pn bu vgn hud b mnnd dung nnub pd Th m mn h nvgn A nv dnn pb STC nn w ud nvb h gn dng g uh nvu ud dung h m pd Th nn b nmd p h w n STC nn h hdn w d phgn h hn Cnun In h ub nmn STC nn m pbb ud hugh pn-n n nd h w n vdn nppp d hndng d hgn p h d n Th ub hw h mpn hvng gd un n p hdn n ju h wh bvu gn n n nmd nd n pbb w mpm nd m hv bn hddng phgn b whu n gn n I hghgh h nun h m mng pn wh nu dh n h hdn Wh nng n dn mpm h mpn hud b u ndd n pdu unnpd u nd hv gnn nm nqun D un p hud b vwd dd h mngmn pngd mpm hdd nd m h hud b ndud n h ng-m mpm hdd n nmn STC n d n W mmnd hghnng wn mng bh nd pn gdng h mmndn h hdn wh gnn mpm hud b p hm 48 hu mpm hv ubdd Addn Addn 1 Wb-bd qunn dpv ud h d Ob-Nvmb 2012 (n Nwgn Cmpng n Th uh d h h hv n mpng n Auh nbun M dd h mnup nd nbud h pdmg nvgn PKD dnd h nvgn nd p n h n mngmn h PA uppd h ub mngmn nd pdmg nvgn LTB nd ALW nbud h mbg nvgn LV dnd h ub mngmn upp pvdd b Nwgn Inu Pub Hh A uh nbud h wng h mnup nd ppvd h n vn Anwdgmn Th uh wud hn h mp nd pn hdn ndng h d n h upp n h ub nvgn Th uh wud nwdg h Munp Vnn nd h V-Agd D O h Nwgn Fd S Auh uppng h nvgn nd A B m h PIT pgmm vwng h mnup Auh d 1 Dpmn Inu D pdmg Nwgn Inu Pub Hh PO B 4404 Ndn NO-0403 O Nw 2 upn Pgmm Invnn pdmg Tnng (PIT upn Cn D Pvnn nd Cn Shm Swdn 3 Munp Vnn Pb Vnn Nw 4 pdm L Odd 4610 Knnd Nw 5 Dpmn Fdbn Inn Nwgn Inu Pub Hh PO B 4404 Ndn NO-0403 O Nw Rvd 10 Jnu 2014 Apd 1 Dmb 2014 Rn 1 T PI Gdn CA Chnd WL Shg-ndung hh nd hm um ndm Ln (

8 M Dn d BMCIn u D h p / /www b md n m / /14 /673 2 Cn Cmmun b D Mnu W h ng ndc Am n Pub H ha n ; G b M Mn C W ng H L D p K L nd L S n ngp d nd n nd mnu b O157 H7nd n W On CnJPub H h ( A J d L S mnr L W AM W m HM W h wga Ch T Ou b h h O157nnu n p vn n A hd Ch d ( B wnja H D S G m -R LA M gu H F Bnn JK P nj J Cm NA W n AK Gh ht S Vg R L Ou b h g n du ng h h p O26 H11n n h d n nc d P d In D J ( G gh L S m K Cn v C Au nc S h -Hub L N ns b h h O157 H7nh d Chudb M V nn M Ou n nc Cun I n w hp ngdhdd ngnd hu h d n m n AmJIn Cn ( W h V dl L nd d BA B uh mt A J Inv g n n h h O145u b nh dd n n v mp ngndh z n -nd 1 v d p dm g nd nm n gh BMCIn D C TG Th Sh g n du ng h h n hm hg ndhm u m nd m S m np d 15( In D [? pp -N? ng m dd b? nn jn 2012 ]Annu p O N w ;2013 Fdb nn n n2012 In 10 D b G L Mn ha B A G mb nj P m M B hl Du n hdd ng V n du ng h h nh d nnd n m nnh d nng nd p d m In ( Snd KG Sh wd J L ng M P R J P m nd nd n h h O157u b n BMCIn D Sm v nb N wg nin u Pub H h ; und M S hu zf S nna C n nn -O157Sh g n du ng h h p v u n h nd m u p n hm p JC n M b ( T P I Fu L S S p na W nra K mhh V JCJ C u ncr Hm -u m nd mn - - dg u n n n w hsh g n du ng h h O103 H2 Nng JM d ( S hu zf T LD Bu nl P dd Bu vn G K hh M m nna C p A T z z R M b S S b nna M n -C AR S n h zm P ns OB nad Mu n v u n qun -b dp ub p ngsh g n nd nd d z ngs nmn u JC n M b ( gh u ngn p ng dndh 16 Lb I H ugumk L nd d BA Rp h h p u ng10gnm p n n ng JM b M hd ( S h mm B N g dk nhm L nj L nd d BA B nd L T K pp udg A v ndp Ou b hm u m nd mn N w u db 2 v h h O103 H25 d u d mu nu g BMCIn D S hu zf S N d M ngnd nndu v n VTC n n nhumn Cpnhgn7-8 M 2007 In S n S um In u ; Md RK G npm F hdd ng Sh g n du ng h h wh hu dbdnp vn nd?c nin D O Pub In D S Am ( B zw M M ddnd B K R F d haw F u ha K hh S hm d MA M m nna Sh g n -ng v h ngnd ng h h d n n n w hb ph gn ndv u n ndn dn -h p hgnv u n C nin D O Pub In D S Am ( B zw M P g R K R M m nna Zh ng W T h ph T P I K h H Sh g ngn nd n nv ndnv v P g8 8 du ngn hm hg h h O26n nnhumn App n v n M b ( A J B ghk B v ng L H ghp v n p n p hg n h h (PC n N wg nh d n w hd h JM d (P M b 2 23 A J B v ng L Rmund dp B ghk A n p n p hgn h h (PC w hp ngdd h JM d M b (P d / C h M Dn d Imp n n ngnd h d u np h d nw hsh g np du ng h h n n n n d mnu b nd n N w 2012 BMCIn u D Subm u n mnu p B MdCn ndu dvn g Cnvn n n nubm n Th ughp v w Np n n gu h g Immd pub nn p n In u nnpubmd CAS S pu ndgg S h R h wh h v b d bu n Subm u mnu p www b md n m / ubm

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