• No results found

Epidemiologic studies of bovine respiratory syncytial virus and bovine coronavirus in Norway

N/A
N/A
Protected

Academic year: 2022

Share "Epidemiologic studies of bovine respiratory syncytial virus and bovine coronavirus in Norway"

Copied!
158
0
0

Laster.... (Se fulltekst nå)

Fulltekst

(1)

Philosophiae Doctor (PhD) Thesis 2019:32

Ingrid Toftaker

Epidemiologic studies of bovine respiratory syncytial virus and bovine coronavirus in Norway

Epidemiologiske studier av bovint respiratorisk syncytialvirus og bovint coronavirus i Norge

Philosophiae Doctor (PhD), Thesis 2019:32Ingrid Toftaker

Norwegian University of Life Sciences Faculty of Veterinary Medicine

(2)
(3)

Epidemiologic studies of bovine respiratory syncytial virus and bovine coronavirus in Norway

Epidemiologiske studier av bovint respiratorisk syncytialvirus og bovint coronavirus i Norge

Philosophiae Doctor (PhD) Thesis

Ingrid Toftaker

Department of Production Animal Clinical Sciences Faculty of Veterinary Medicine

Norwegian University of Life Sciences

Adamstuen 2019

(4)

Thesis number 2019:32 ISSN 1894-6402 ISBN 978-82-575-1591-1

(5)

1RUZHJLDQ5HGFDOILQIHFWHGZLWKERYLQHUHVSLUDWRU\V\QF\WLDOYLUXV

µMamma?Universet,erdetdetsammesomuniversitetet?¶

7XYD\HDUVROG

(6)
(7)

7DEOHRIFRQWHQWV

$FNQRZOHGJHPHQWV

$EEUHYLDWLRQV /LVWRI3DSHUV 6XPPDU\

6DPPHQGUDJVXPPDU\LQ1RUZHJLDQ ,QWURGXFWLRQ 7KH1RUZHJLDQFDWWOHSRSXODWLRQ +LVWRULFDOEDFNJURXQGDQGRFFXUUHQFHRI%569DQG%&9 ,QIHFWLRQVZLWK%569DQG%&9 ,PSDFW 7UDQVPLVVLRQ +HUGOHYHOULVNIDFWRUV 'LVHDVHSUHYHQWLRQDQGFRQWURO 'LDJQRVWLFWHVWVDQGFODVVLILFDWLRQRIKHUGV .QRZOHGJHJDSV

$LPVRIWKH6WXG\

0DWHULDOVDQGPHWKRGV 6WXG\VDPSOHVDQGUHJLVWHUGDWD 0XOWLYDULDEOHUHJUHVVLRQPRGHOV 6SDWLDODQDO\VLV 'LDJQRVWLFWHVWVDQGFODVVLILFDWLRQRIKHUGV 3UREDELOLW\RIIUHHGRP 5HVXOWVDQGGLVFXVVLRQ 5LVNIDFWRUDQDO\VLV 6SDWLDOSDWWHUQV (YDOXDWLQJWKHFRQVHTXHQFHVRIZLQWHUG\VHQWHU\

(8)

(YDOXDWLRQRIWKH%&9%569PXOWLSOH[LPPXQRDVVD\

3UREDELOLW\RIIUHHGRP

$QWLERG\WHVWLQJRIKHUGV 'DWDTXDOLW\RIUHJLVWHUGDWD 9DOLGLW\

,PSOLFDWLRQVIRUFRQWURO )XWXUHSHUVSHFWLYHV

&RQFOXGLQJUHPDUNV 5HIHUHQFHV (QFORVHG3DSHUV,±,9

(9)

$FNQRZOHGJHPHQWV

7KHZRUNSUHVHQWHGLQWKLVWKHVLVZDVFDUULHGRXWDWWKH'HSDUWPHQWRI3URGXFWLRQ$QLPDO

&OLQLFDO6FLHQFHVDWWKH)DFXOW\RI9HWHULQDU\0HGLFLQH1RUZHJLDQ8QLYHUVLW\RI/LIH 6FLHQFHV7KHSURMHFWZDVIXQGHGE\WKH5HVHDUFK&RXQFLORI1RUZD\1)5SURMHFW1R (WKH1RUZHJLDQ5HVHDUFK)XQGLQJIRU$JULFXOWXUHDQG)RRG,QGXVWU\

5HJLRQDO5HVHDUFK)XQGVUHJLRQZHVWSURMHFW1RDQG7,1(6$,DPJUDWHIXOWR WKHIXQGLQJSDUWLHVIRUPDNLQJWKLVZRUNSRVVLEOHDQGDFNQRZOHGJH10%8IRUWKHLU ILQDQFLDOVXSSRUWRIPHDVD3K'VWXGHQW

,ZLVKWRH[SUHVVP\VLQFHUHJUDWLWXGHWRP\PDLQVXSHUYLVRU$QH1¡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‘VWHUnVP\FRVXSHUYLVRUIURP7,1(6$

7KDQN\RXIRUEHLQJP\DQFKRULQWKHLQGXVWU\IRUDOO\RXUKHOSZLWKGDWDPDQDJHPHQWDQG IRUVKDULQJ\RXUYDVWNQRZOHGJHRQFDWWOHSURGXFWLRQ

7KDQN\RX,QJULG+ROP¡\IRUVKDULQJP\QHUG\HQWKXVLDVPIRUHSLGHPLRORJ\DQGDOOWKH JUHDWWULSVDQGFRXQWOHVVOXQFKHVZHKDYHKDGLQWKHVHSDVW\HDUVLQJULGRJLQJULG ,ZLVKWRWKDQNPHPEHUVRIWKHRXWVWDQGLQJUHVHDUFKJURXSµ9LUDO,QIHFWLRQVLQ&DWWOH¶

7KHD.OHPDQG0HWWH0\UPHOIRULQWHUHVWLQJGLVFXVVLRQVDQGVKDULQJKDSS\RFFDVLRQV$

VSHFLDOWKDQNVWR\RXGHDU9HVOHP¡\IRUVKDULQJDQRIILFHZLWKPHGXULQJWKHVH\HDUVDQG IRUSDWLHQWO\OHWWLQJP\IUXVWUDWLRQVDQGMROWVRIMR\LQWHUUXSW\RXUZRUN<RXKDYHEHFRPHD FKHULVKHGIULHQGDQG,KDYHEHHQVROXFN\WRVKDUHWKLVMRXUQH\ZLWK\RX

,DOVRZLVKWRWKDQNP\LQWHUQDWLRQDOFROODERUDWRUV-HQQ\)U|VVOLQJDQG(VWHOOHcJUHQDWWKH 6ZHGLVK1DWLRQDO9HWHULQDU\,QVWLWXWHIRUOHWWLQJPHYLVLWIRUDOO\RXUKHOSDQGIRUPDNLQJ 3DSHU,9SRVVLEOH7KDQNVDOVRWRFRDXWKRU-DYLHU6DQFKH]DWWKH$WODQWLF9HWHULQDU\

&ROOHJH3(,&DQDGDIRUNLFNVWDUWLQJP\3K'E\LQWURGXFLQJPHWRVSDWLDOHSLGHPLRORJ\

DQGWR1LOV7RIWDWWKH7HFKQLFDO8QLYHUVLW\RI'HQPDUNIRULQYDOXDEOHKHOSZLWKWKHODWHQW FODVVPRGHOOLQJ

(10)

,DPJUDWHIXOWR/LY6¡OYHU¡GDQGKHUFUHZDW7,1(0DVWLWLV/DERUDWRU\0ROGHIRUGRLQJ VXFKDJUHDWMRELQRUJDQL]LQJWKHFROOHFWLRQDQGODERUDWRU\DQDO\VHVRIDOOWKHPLONVDPSOHV

$VSHFLDOJUDWLWXGHWRDOOP\FROOHDJXHVDWWKH'HSDUWPHQWRI3URGXFWLRQ$QLPDO&OLQLFDO 6FLHQFHVIRU\RXUFRQWULEXWLRQWRDJUHDWZRUNLQJHQYLURQPHQW$VSHFLDOWKDQNVWRPHPEHUV RIWKHSRSXODWLRQPHGLFLQHJURXSIRUVKDULQJLGHDVDQGLQVSLUDWLRQDQGIRUPDQ\

HGXFDWLRQDOMRXUQDOFOXEV

)LQDOO\,ZRXOGOLNHWRWKDQNP\IULHQGVDQGIDPLO\P\PRWKHUIDWKHUDQGPRWKHULQODZ IRU\RXUVXSSRUWDQGIRUKHOSLQJRXWDWKRPHZKHQ,ZDVRFFXSLHGDWZRUNP\ORYHO\NLGV ,YHUDQG7XYDIRUVKRZLQJPHZKDWUHDOO\PDWWHUVDQGP\GHDU.MHWLOIRU\RXUORYH HYHUODVWLQJVXSSRUWDQGLPPHQVHSDWLHQFH

$GDPVWXHQ0DUFK

,QJULG7RIWDNHU

(11)

$EEUHYLDWLRQV

%&9 %RYLQHFRURQDYLUXV

%/&0 %D\HVLDQODWHQWFODVVPRGHOV

%5' %RYLQHUHVSLUDWRU\GLVHDVH

%569 %RYLQHUHVSLUDWRU\V\QF\WLDOYLUXV

%70 %XONWDQNPLON

%9'9 %RYLQHYLUDOGLDUUKRHDYLUXV

&+& ,QGLYLGXDOFRZKHDOWKFDUGV

(/,6$ (Q]\PHOLQNHGLPPXQRVRUEHQWDVVD\

/&$ /DWHQWFODVVDQDO\VLV

1'+56 1RUZHJLDQGDLU\KHUGUHFRUGLQJV\VWHP 1'35 1RUZHJLDQ'LUHFW3D\PHQW5HJLVWHU

139 1HJDWLYHSUHGLFWLYHYDOXH

339 3RVLWLYHSUHGLFWLYHYDOXH

573&5 5HDOWLPHSRO\PHUDVHFKDLQUHDFWLRQ

6H 6HQVLWLYLW\

6S 6SHFLILFLW\

917 9LUXVQHXWUDOL]DWLRQWHVW

:' :LQWHUG\VHQWHU\

(12)

(13)

/LVWRI3DSHUV

, 7RIWDNHU,6DQFKH]-6WRNVWDG01¡GWYHGW$%RYLQHUHVSLUDWRU\V\QF\WLDO YLUXVDQGERYLQHFRURQDYLUXVDQWLERGLHVLQEXONWDQNPLON±ULVNIDFWRUVDQGVSDWLDO DQDO\VLV3UHY9HW0HG±KWWSVGRLRUJMSUHYHWPHG ,, 7RIWDNHU,+ROP¡\,+1¡GWYHGW$‘VWHUnV26WRNVWDG0$FRKRUWVWXG\

RIWKHHIIHFWRIZLQWHUG\VHQWHU\RQKHUGOHYHOPLONSURGXFWLRQ-'DLU\6FL KWWSVGRLRUJMGV

,,, 7RIWDNHU,7RIW16WRNVWDG06¡OYHU¡G/+DUNLVV*:DWW12¶%ULHQ$

1¡GWYHGW$(YDOXDWLRQRIDPXOWLSOH[LPPXQRDVVD\DQGWZRLQGLUHFW(/,6$VLQ EXONPLONDQWLERG\WHVWLQJIRUERYLQHUHVSLUDWRU\V\QF\WLDOYLUXVDQGERYLQHFRURQDYLUXV XVLQJODWHQWFODVVDQDO\VLV3UHY9HW0HG

KWWSVGRLRUJMSUHYHWPHG

,9 7RIWDNHU,cJUHQ(6WRNVWDG01¡GWYHGW$)U|VVOLQJ-+HUGOHYHO HVWLPDWLRQRISUREDELOLW\RIGLVHDVHIUHHGRPDSSOLHGRQWKH1RUZHJLDQFRQWUROSURJUDP IRUERYLQHUHVSLUDWRU\V\QF\WLDOYLUXVDQGERYLQHFRURQDYLUXV3UHY9HW0HG

KWWSVGRLRUJMSUHYHWPHG

(14)

(15)

6XPPDU\

%RYLQHUHVSLUDWRU\V\QF\WLDOYLUXV%569DQGERYLQHFRURQDYLUXV%&9FDXVHUHVSLUDWRU\

LQIHFWLRQLQFDWWOHZRUOGZLGH,QDGGLWLRQ%&9DOVRFDXVHVGLDUUKRHDLQFDOYHVDQG FRQWDJLRXVGLDUUKRHDLQDGXOWFRZVLHZLQWHUG\VHQWHU\7KHRFFXUUHQFHLVHQGHPLFLQWKH 1RUZHJLDQFDWWOHSRSXODWLRQDQGWKHSODQQLQJRIDQDWLRQDOFRQWUROSURJUDPPHDJDLQVW WKHVHYLUDOLQIHFWLRQVSURPSWHGWKHQHHGIRUPRUHUHVHDUFKIRFXVHGDWWKHKHUGOHYHO7KH RYHUDOOREMHFWLYHRIWKLVWKHVLVZDVWRSURYLGHNQRZOHGJHDERXWWKHHSLGHPLRORJ\RI%569 DQG%&9LQWKH1RUZHJLDQFDWWOHSRSXODWLRQDVDVFLHQWLILFEDVLVIRUV\VWHPDWLFFRQWURO ZRUN7RUHDFKWKLVDLPZHXWLOL]HGUHJLVWHUGDWDEXONWDQNPLONDQWLERG\WHVWLQJDQG UHSRUWVRIGLVHDVHRXWEUHDNV

$ULVNIDFWRUDQDO\VLVVKRZHGWKDWODUJHKHUGVL]HDQGVKRUWGLVWDQFHWRQHLJKERXUVZHUH DVVRFLDWHGZLWKLQFUHDVHGRGGVRIDQWLERG\SRVLWLYLW\LQEXONWDQNPLONIRUERWKYLUXVHV 3XUFKDVHRIOLYHVWRFNZDVDQDGGLWLRQDOULVNIDFWRUIRU%&96SDWLDODQDO\VLVUHYHDOHG JHRJUDSKLFGLIIHUHQFHVLQWKHGLVWULEXWLRQRISUHYDOHQFH

$FRKRUWVWXG\ZDVSHUIRUPHGEDVHGRQDUHJLRQDORXWEUHDNRIZLQWHUG\VHQWHU\7KH HVWLPDWHGGURSLQPLONSURGXFWLRQZDV/FRZDWPD[LPXPRUIRUWKHDYHUDJHKHUG VKRZLQJDQRWDEOHHIIHFWRIZLQWHUG\VHQWHU\RQPLONSURGXFWLRQDWWKHKHUGOHYHO

7KH09'(QIHUSOH[%&9%569PXOWLSOH[LPPXQRDVVD\ZDVGHYHORSHGWRVFUHHQKHUGV IRUDQWLERGLHVLQEXONWDQNPLON$GLDJQRVWLFWHVWHYDOXDWLRQZDVSHUIRUPHGIRUWKLV DSSOLFDWLRQE\FRPSDULQJLWWRWZRFRPPHUFLDOO\DYDLODEOH(/,6$VXVLQJ%D\HVLDQODWHQW FODVVPRGHOV$GMXVWLQJWKHFRQILJXUDWLRQDQGFXWRIIYDOXHVRIWKHWHVWUHVXOWHGLQ DFFHSWDEOHVHQVLWLYLW\DQGVSHFLILFLW\IRUERWK%569DQG%&9

$IUDPHZRUNIRUKHUGOHYHOFDOFXODWLRQVRISUREDELOLW\RIIUHHGRPPostPFreeIURP%569 DQG%&9DQWLERGLHVRYHUWLPHZDVGHYHORSHGE\XVHRIEXONWDQNPLONWHVWLQJJHRJUDSKLF LQIRUPDWLRQDQGDQLPDOPRYHPHQWGDWDPostPFreeZDVXSGDWHGHYHU\WKUHHPRQWKVDQG YDOLGDWLRQDJDLQVWDVXEVHTXHQWEXONWDQNPLONVDPSOHDIWHUWKUHH\HDUVVKRZHGWKDWLW SURYLGHGDQLPSURYHGHVWLPDWHRIDKHUG¶VDQWLERG\VWDWXVFRPSDUHGWRUHO\LQJRQWKH SUHYLRXVWHVWUHVXOW

$OWRJHWKHUWKHUHVXOWVKDYHSURYLGHGLQVLJKWVDWWKHKHUGOHYHOUHJDUGLQJULVNIDFWRUVIRUD SRVLWLYHFODVVLILFDWLRQFRQVHTXHQFHVRIGLVHDVHDQGWKHXQFHUWDLQW\RIKHUGFODVVLILFDWLRQ 7KLVNQRZOHGJHFDQEHGLUHFWO\DSSOLHGLQV\VWHPDWLFFRQWUROZRUN

(16)

(17)

6DPPHQGUDJVXPPDU\LQ1RUZHJLDQ

%RYLQWUHVSLUDWRULVNV\QF\WLDOYLUXV%569RJERYLQWFRURQDYLUXV%&9HUnUVDNWLO OXIWYHJVOLGHOVHUKRVVWRUIHRYHUKHOHYHUGHQ,WLOOHJJNDQ%&9RJVnIRUnUVDNHNDOYHGLDUpRJ VPLWWVRPGLDUpKRVYRNVQHVWRUIHNDOWYLQWHUG\VHQWHUL)RUHNRPVWHQHUHQGHPLVNLGHQ QRUVNHVWRUIHSRSXODVMRQHQRJSODQOHJJLQJHQDYHWQDVMRQDOWNRQWUROOSURJUDPPRWGLVVH YLUXVLQIHNVMRQHQHVNDSWHEHKRYIRUPHUIRUVNQLQJSnEHVHWQLQJVQLYn'HWRYHURUGQHGHPnOHW PHGDYKDQGOLQJHQYDUnJHQHUHUHNXQQVNDSRPHSLGHPLRORJLHQWLO%569RJ%&9LGHQ QRUVNHVWRUIHSRSXODVMRQHQVRPHWELGUDJWLOIRUVNQLQJVEDVHUWV\VWHPDWLVNNRQWUROODUEHLG )RUnQnGHWWHPnOHWEUXNWHYLUHJLVWHUGDWDWDQNPHONVHURORJLRJUDSSRUWHULQJDY V\NGRPVXWEUXGG

(QULVLNRIDNWRUDQDO\VHYLVWHDWVWRUHEHVHWQLQJHURJNRUWDYVWDQGWLOQDERJnUGHUYDUDVVRVLHUW PHG¡NWRGGVIRUDQWLVWRIISRVLWLYLWHWLWDQNPHONIRUEHJJHYLUXV,WLOOHJJYDUNM¡SDYOLYG\U HQULVLNRIDNWRUIRU%&95RPOLJVWDWLVWLVNDQDO\VHDYGHNNHWJHRJUDILVNHIRUVNMHOOHUL IRUGHOLQJHQDYSUHYDOHQV

(QNRKRUWVWXGLHEDVHUWSnHWUHJLRQDOWXWEUXGGDYYLQWHUG\VHQWHULYLVWHDWGHWHVWLPHUWHWDSHWL PHONHSURGXNVMRQYDU/NXSnGHWPHVWHHOOHUIRUHQJMHQQRPVQLWWVEHVHWQLQJ'HWWH YLVHUDWYLQWHUG\VHQWHULKDUHQEHW\GHOLJHIIHNWSnEHVHWQLQJHQVPHONHSURGXNVMRQ

(QQ\XWYLNOHW09'(QIHUSOH[%&9%569PXOWLSOH[LPPXQRDVVD\KDUEOLWWEUXNWWLO VFUHHQLQJDYEHVHWQLQJHUIRUDQWLVWRIIHULWDQNPHON7HVWHQEOHHYDOXHUWIRUGHQQH DQYHQGHOVHQYHGnVDPPHQOLJQHGHQPHGWRNRPPHUVLHOWWLOJMHQJHOLJH(/,6$WHVWHUL

%D\HVLDQVNHODWHQWNODVVHPRGHOOHU0XOWLSOH[WHVWHQNDQYHGnHQGUHNRQILJXUHULQJRJFXW RIIYHUGLHURSSQnDNVHSWDEHOVHQVLWLYLWHWRJVSHVLILVLWHWIRUEnGH%569RJ%&9

(QPHWRGHIRUnEHUHJQHHQEHVHWQLQJVVDQQV\QOLJKHWIRUIULKHWPostPFreeIUD%569RJ

%&9DQWLVWRIIHURYHUWLGEOHXWYLNOHWYHGnLQNOXGHUHWDQNPHONWHVWLQJJHRJUDILVN LQIRUPDVMRQRJG\UHIRUIO\WQLQJHUPostPFreeEOHRSSGDWHUWKYHUWUHGMHPnQHGRJYHG YDOLGHULQJPRWQ\WDQNPHONWHVWHWWHUWUHnUJDYGHQEHGUHHVWLPDWHUIRUEHVHWQLQJHUV DQWLVWRIIVWDWXVHQQGHWPDQILNNEDUHEDVHUWSnIRUULJHSU¡YHVYDU

$OWLDOWKDUUHVXOWDWHQHJLWWPHUNXQQVNDSSnEHVHWQLQJVQLYnRPULVLNRIDNWRUHUIRUSRVLWLY NODVVLILVHULQJNRQVHNYHQVHUDYV\NGRPRJXVLNNHUKHWHQUXQGWNODVVLILVHULQJDYEHVHWQLQJHU 'HQQHNXQQVNDSHQKDUGLUHNWHDQYHQGHOVHLV\VWHPDWLVNNRQWUROODUEHLG

(18)

(19)

,QWURGXFWLRQ

%RYLQHUHVSLUDWRU\V\QF\WLDOYLUXV%569DQGERYLQHFRURQDYLUXV%&9DUHHQGHPLF SDWKRJHQVLQFDWWOHWKURXJKRXWWKHZRUOG9DODUFKHUDQG7D\ORU%RLOHDXDQG.DSLO

%RWKDJHQWVDUHFRQVLGHUHGLPSRUWDQWLQWKHGHYHORSPHQWRIERYLQHUHVSLUDWRU\

GLVHDVHDPDMRUFKDOOHQJHWRFDWWOHZHOIDUHDQGOLYHVWRFNHFRQRP\ZRUOGZLGH$GGLWLRQDOO\

%&9FDXVHVFDOIGLDUUKRHDDQGHSLGHPLFVRIGLDUUKRHDLQDGXOWFDWWOHFDOOHGZLQWHU G\VHQWHU\UHVXOWLQJLQDGYHUVHHIIHFWVRQPLONSURGXFWLRQ7KHOLYHVWRFNLQGXVWU\WRGD\LV IDFLQJDJURZLQJSXEOLFFRQFHUQUHJDUGLQJWKHLPSDFWRQWKHHQYLURQPHQWVWDQGDUGVIRU DQLPDOZHOIDUHDQGWKHXVHRIDQWLPLFURELDOV$WWKHVDPHWLPHWKHLQGXVWU\LVIRUFHGWR UHWDLQHFRQRPLFVXVWDLQDELOLW\,PSURYHPHQWRIFDWWOHKHDOWKWKURXJKWKHUHGXFWLRQRI HQGHPLFGLVHDVHVLVWKHUHIRUHPRUHWRSLFDOWKDQHYHU

TheNorwegiancattlepopulation

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

(20)

)LJXUH1RUZHJLDQ5HGFRZLQDPRXQWDLQSDVWXUH

&DWWOHKHUGVFDQEHIRXQGWKURXJKRXWWKHFRXQWU\DQGWKHFRXQW\ZLWKWKHKLJKHVWQXPEHURI GDLU\FRZVLV7U¡QGHODJPLG1RUZD\IROORZHGE\5RJDODQGLQWKHVRXWKZHVW7KH 1RUZHJLDQ$JULFXOWXUDO$JHQF\+RZHYHU5RJDODQGLVVPDOOHUDQGWKHUHIRUHKDV WKHKLJKHVWFDWWOHGHQVLW\LHFDWWOHSHUXQLWRIDUHD)LQQPDUNLQWKHQRUWKKDVWKHIHZHVW FDWWOH7KHVSDWLDOGLVWULEXWLRQRIWKH1RUZHJLDQFDWWOHKHUGVLVVKRZQLQ)LJXUH

(21)

)LJXUH3RLQWPDSRI1RUZHJLDQFDWWOHKHUGVGDLU\DQGEHHI$XJXVWJHRFRRUGLQDWHV7KH 1RUZHJLDQ$JULFXOWXUDO$JHQF\EDFNJURXQGPDSGLYDJLVRUJ

7KH1RUZHJLDQFDWWOHSRSXODWLRQLVRIWHQSURPRWHGDVKHDOWK\,WLVIUHHIURPPDQ\

LQIHFWLRXVGLVHDVHVVRPHKDYHQHYHUEHHQGHWHFWHGDQGVRPHKDYHEHHQHUDGLFDWHGWKURXJK VXFFHVVIXOFRQWURODQGHUDGLFDWLRQSURJUDPPHV6RPHGLVHDVHVXQGHUVXUYHLOODQFHIURP ZKLFKWKHFDWWOHSRSXODWLRQLVFXUUHQWO\IUHHDUHERYLQHYLUDOGLDUUKRHD%9'EUXFHOORVLV LQIHFWLRXVERYLQHUKLQRWUDFKHLWLVDQGERYLQHWXEHUFXORVLV6YLODQGHWDO6YLODQGHWDO cNHUVWHGWHWDODE)XUWKHUPRUHSalmonellaVSSDQGMycobacteriumavium VXEVS.paratuberculosisDUHUDUHO\GHWHFWHGDQGMycoplasmabovisDQGCoxiellaburnetii KDYHQHYHUEHHQGHWHFWHG.DPSHQHWDO+HLHUHWDO.DPSHQHWDO

HistoricalbackgroundandoccurrenceofBRSVandBCV

%569ZDVILUVWLGHQWLILHGLQ(XURSHDURXQG3DFFDXGDQG-DFTXLHU:HOOHPDQV DQG/HXQHQ,Q6FDQGLQDYLDWKHILUVW%569UHODWHGRXWEUHDNZDVGHWHFWHGLQ 1RUZD\LQ‘GHJDDUGDQG.URJVUXG,QWKH\HDUVIROORZLQJIHZUHSRUWVRI

(22)

%569LQ1RUZD\H[LVWXSXQWLOZKHQDODUJHRXWEUHDNLQYROYLQJPDQ\FDWWOHKHUGV RFFXUUHG$QLPSRUWRIEHHIFDWWOHIURP'HQPDUNLQ'HFHPEHUKDVEHHQVXJJHVWHGDV WKHOLNHO\VRXUFH1RUVWU|PHWDO/LPLWHGNQRZOHGJHH[LVWVUHJDUGLQJKRZORQJ

%&9KDVH[LVWHGLQ6FDQGLQDYLDKRZHYHUZLQWHUG\VHQWHU\ZDVILUVWGHVFULEHGLQLQ 6ZHGLVKGDLU\KHUGV+HGVWU|PDQG,VDNVVRQ7KHHWLRORJ\ZDVQRWNQRZQDWWKH WLPHEXWGXHWRWKHODFNRIEDFWHULRORJLFILQGLQJVWKHDXWKRUVFRQFOXGHGWKDWWKHFDXVDWLYH DJHQWZDVPRVWOLNHO\DYLUXV7KHILUVWGHVFULSWLRQVRI%&9FDPHIURP(XURSHLQWKH VHYHQWLHVRIDµFRURQDYLUXVOLNHDJHQW¶DVDFDXVHRIQHRQDWDOFDOIGLDUUKRHD6WDLUHWDO 0HEXVHWDO%&9ZDVQRWUHFRJQL]HGDVWKHFDXVDWLYHDJHQWRIZLQWHU G\VHQWHU\XQWLOWKHQLQHWLHV6DLIDQGWKHDVVRFLDWLRQZLWKUHVSLUDWRU\GLVHDVHZDV UHFRJQL]HGHYHQODWHU6WRU]HWDO6DLI21HLOOHWDO7RGD\%569DQG

%&9DUHKLJKO\SUHYDOHQWLQFDWWOHZRUOGZLGH9DODUFKHUDQG7D\ORU%RLOHDXDQG .DSLO7KHHQGHPLFRFFXUUHQFHLQ6FDQGLQDYLDLVZHOOGRFXPHQWHGWKURXJKYDULRXV VHURORJLFVWXGLHV+lJJOXQGHWDO%LGRNKWLHWDO*XOOLNVHQHWDOE.OHP HWDO2KOVRQHWDO,Q1RUZD\*XOOLNVHQHWDOEIRXQGD

VHURSUHYDOHQFHDWWKHFDOIOHYHORIIRU%569DQGIRU%&9ZKLOHWKH SURSRUWLRQRISRVLWLYHKHUGVZDVIRU%569DQGIRU%&9LQDUDQGRPVDPSOH RIGDLU\KHUGV%569DQG%&9KDYHJDLQHGLQFUHDVHGDWWHQWLRQLQ1RUZD\DQG6ZHGHQ GXULQJUHFHQW\HDUVDVWKH\IUHTXHQWO\FDXVHGLVHDVHRXWEUHDNVLQDFDWWOHSRSXODWLRQWKDWLV RWKHUZLVHIUHHRIPDQ\LQIHFWLRXVDJHQWV

InfectionswithBRSVandBCV

Theviruses

%569DQG%&9DUHHQYHORSHGVLQJOHVWUDQGHG51$YLUXVHV%&9EHORQJVLQWKHRUGHU NidoviralesIDPLO\CoronaviridaeJHQXVBetacoronavirusDQGVSHFLHVBetacoronavirus1

%569EHORQJVWRWKHRUGHUMononegaviralesIDPLO\ParamyxoviridaeJHQXV

OrthopneumovirusDQGVSHFLHVBovineorthopneumovirus,QWHUQDWLRQDO&RPPLWWHHRQ 7D[RQRP\RI9LUXVHV%RWKYLUXVHVKDYHFDWWOHDVWKHPDLQUHVHUYRLUEXWVHURORJLFDO DQGH[SHULPHQWDOVWXGLHVKDYHVKRZQWKDWRWKHUVSHFLHVFDQEHLQIHFWHG,VPDLOHWDO

&LWWHULRHWDO.DQHVKLPDHWDO7UDQVPLVVLRQIURPRWKHUVSHFLHVWRFDWWOHKDV QHYHUEHHQGRFXPHQWHGDQGLVWKXVOLNHO\WREHRIPLQRULPSRUWDQFH2QO\DVLQJOHVHURW\SH KDVEHHQGHVFULEHGIRUERWK%569DQG%&9KRZHYHUDQWLJHQLFGLYHUVLW\H[LVWV9DODUFKHU DQG7D\ORU)XOWRQHWDO

(23)

BRSV:Pathogenesis,clinicalsignsandimmuneresponse

%569UHSOLFDWHVRQO\LQWKHHSLWKHOLXPRIWKHUHVSLUDWRU\WUDFWDQGWKHYLUXVLVSULPDULO\

VKHGLQQDVDOGLVFKDUJH9LXIIHWDO9DODUFKHUDQG7D\ORU,QDVWUXFWXUHG OLWHUDWXUHUHYLHZYLUDOVKHGGLQJZDVUHSRUWHGIURPWRGD\VDIWHULQIHFWLRQZLWKPHGLDQ WLPHWRSHDNVKHGGLQJRQGD\*ULVVHWWHWDO,QDUHFHQWH[SHULPHQWDOVWXG\

GHWHFWLRQRIYLUDO51$ZDVUHSRUWHGIURPGD\VWRDIWHUH[SRVXUHZKLOHWKHLQIHFWLYH YLUXVZDVLVRODWHGRQGD\VDQG.OHPHWDO:KHQVHQWLQHOFDOYHVZHUH

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

,QIHFWLRQZLWK%569FDQEHOLPLWHGWRWKHXSSHUUHVSLUDWRU\DLUZD\VRUUHVXOWLQSQHXPRQLD ZLWKRUZLWKRXWVHFRQGDU\EDFWHULDOLQIHFWLRQV9DODUFKHUDQG7D\ORU7KHLQFXEDWLRQ SHULRGLVUHSRUWHGWREHIURPWZRWRILYHGD\V9DODUFKHUDQG7D\ORU&OLQLFDOVLJQV LQFOXGHFRXJKQDVDOGLVFKDUJHIHYHUDQGGHSUHVVLRQDQGLQVHYHUHFDVHVDQLPDOVPD\

GHYHORSG\VSQRHD(OYDQGHU9DODUFKHUDQG7D\ORU7KHVHVLJQVDUHPRVW HYLGHQWLQ\RXQJDQLPDOVEXW%569FDQFDXVHGLVHDVHLQFDWWOHRIDOODJHV3RHOHWDO 9DODUFKHUDQG7D\ORU7KHVHYHULW\RIGLVHDVHYDULHVIURPVXEFOLQLFDOWRIDWDO (OYDQGHU/DUVHQHWDO6HFRQGDU\EDFWHULDOLQIHFWLRQVDUHFRPPRQEDFWHULDO FRORQL]DWLRQLVIDFLOLWDWHGHLWKHUE\GLUHFWGDPDJHWRWKHUHVSLUDWRU\WUDFWDQGRUE\DOWHUDWLRQ RIWKHKRVW¶VLPPXQHV\VWHP/DUVHQ7D\ORUHWDO

7KHLPPXQHUHVSRQVHRIWKHKRVWLVEHOLHYHGWRSOD\DQLPSRUWDQWUROHLQWKHSDWKRJHQHVLVRI

%569LQIHFWLRQ9DODUFKHUDQG7D\ORU0H\HUHWDO,QIHFWLRQRIUHVSLUDWRU\

HSLWKHOLDOFHOOVDQGDOYHROLOHDGVWRLQGXFWLRQRILQIODPPDWRU\FKHPRNLQHVDQGF\WRNLQHV ZKLFKLQWXUQDWWUDFWVDGGLWLRQDOLQIODPPDWRU\FHOOV9DODUFKHUDQG7D\ORU7KH LQIODPPDWRU\UHVSRQVHOHDGVWRQHFURWL]LQJEURQFKLROLWLVDQGLILQIHFWLRQUHDFKHVWKHDOYHROL LQWHUVWLWLDOSQHXPRQLD

(24)

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

BCV:Pathogenesis,clinicalsignsandimmuneresponse

%&9UHSOLFDWHVERWKLQWKHUHVSLUDWRU\WUDFWDQGLQHSLWKHOLDOFHOOVRIWKHJDVWURLQWHVWLQDO WUDFWKHQFHYLUXVLVVKHGERWKLQQDVDOGLVFKDUJHDQGIDHFHV+HFNHUWHWDO3DUNHWDO 2PDHWDO([SHULPHQWDOVWXGLHVKDYHVKRZQVKHGGLQJRI%&9IURPWR GD\VDIWHULQIHFWLRQ(O.DQDZDWLHWDO7UnYp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

+RZHYHUYLUXVVHTXHQFLQJZDVQRWSHUIRUPHGDQGWKHSRVVLELOLW\WKDWLQIHFWLRQZDVFDXVHG E\UHLQWURGXFWLRQFDQQRWEHFRPSOHWHO\UXOHGRXW7KXVIXUWKHUVWXGLHVDUHZDUUDQWHGWR FRQILUPWKHILQGLQJV

(25)

6LPLODUWR%569VHURSRVLWLYLW\IROORZLQJ%&9LQIHFWLRQLVORQJODVWLQJ8QGHU

H[SHULPHQWDOFRQGLWLRQV%&9VSHFLILF,J*ZDVGHWHFWDEOHLQVHUXPDQGPLONIURPGD\V WRDIWHULQIHFWLRQRIVHURQHJDWLYHDQLPDOV7UnYpQHWDO$QWLERG\SURGXFWLRQKDV EHHQVKRZQWRODVWIRUDWOHDVWRQH\HDUDIWHULQIHFWLRQ$OHQLXVHWDO+RZHYHUWKH SURWHFWLYHLPPXQLW\LVEHOLHYHGWREHVKRUW7UnYpQHWDO6DLI7ZR

H[SHULPHQWDOVWXGLHVUHSRUWHGWKDWFDOYHVFRXOGEHUHLQIHFWHGQHZVKHGGLQJRIYLUDO'1$

WKUHHZHHNVDIWHUWKHILUVWFKDOOHQJHEXWGLGQRWGHYHORSFOLQLFDOVLJQV(O.DQDZDWLHWDO

&KRHWDOD,QWKHVWXG\E\2PDHWDOVHQWLQHOFDOYHVZHUHLQWURGXFHG WRLQIHFWHGFDOYHVDIWHUWKUHHZHHNVEXWGLGQRWEHFRPHLQIHFWHG9DULDWLRQLQLPPXQLW\KDV EHHQVXJJHVWHGDVDUHDVRQIRUYDULDEOHFOLQLFDOVLJQV7UnYpQHWDO&DOYHVERUQWR DQWLERG\SURGXFLQJFRZVRIWHQKDYHPDWHUQDODQWLERGLHV:KDWOHYHORISURWHFWLRQWKH\

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

'LVHDVHFDXVHGE\%&9YDULHVLQVHYHULW\IURPVXEFOLQLFDOWRVHYHUHDQGIDWDOLWLHVKDYH EHHQUHSRUWHG%RLOHDXDQG.DSLO,QIHFWLRQZLWK%&9FDQSURGXFHGLIIHUHQWFOLQLFDO PDQLIHVWDWLRQVRIWHQGLIIHUHQWLDWHGLQWRWKUHHFOLQLFDOV\QGURPHVLQFDWWOHGLDUUKRHDLQ FDOYHVUHVSLUDWRU\GLVHDVHDQGZLQWHUG\VHQWHU\

Respiratorydisease

5HVSLUDWRU\GLVHDVHFDXVHGE\%&9RFFXUVLQDQLPDOVRIDOODJHVDOWKRXJKFOLQLFDOVLJQVDUH PRUHFRPPRQO\VHHQLQ\RXQJDQLPDOV&ODUN$QLQFXEDWLRQSHULRGRIWKUHHWRHLJKW GD\VLVUHSRUWHG6DLI&OLQLFDOVLJQVLQFOXGHFRXJKLQJUKLQLWLVIHYHUDQG

LQDSSHWHQFH6DLI$QLPDOVPLJKWDOVRVKRZFRQFXUUHQWUHVSLUDWRU\VLJQVDQG GLDUUKRHD+DVRNVX]HWDO

(26)

Calfdiarrhoea

&DOIGLDUUKRHDFDXVHGE\%&9W\SLFDOO\RFFXUVEHWZHHQDQGGD\VRIOLIHZLWKPRUH VHYHUHFRQVHTXHQFHVLQ\RXQJDQLPDOV&ODUN%RLOHDXDQG.DSLO7KHGLVHDVH RFFXUVLQERWKGDLU\DQGEHHIKHUGV&ODUN7KHSDWKRJHQHVLVLQYROYHVVWXQWLQJDQG IXVLRQRIYLOOLLQWKHVPDOOLQWHVWLQHDORQJZLWKDWURSK\RIFRORQLFULGJHVLQWKHFRORQ OHDGLQJWRPDODEVRUSWLYHGLDUUKRHD%RLOHDXDQG.DSLO$IWHUDQLQFXEDWLRQSHULRGRI WZRGD\VFDOYHVEHFRPHGHSUHVVHGWKHVXFNOLQJUHIOH[LVZHDNHQHGDQGWKLVLQFRPELQDWLRQ ZLWKZDWHU\GLDUUKRHDOHDGVWRGHK\GUDWLRQ*RPH]DQG:HHVH

Winterdysentery

:LQWHUG\VHQWHU\LVDFRQWDJLRXVGLVHDVHLQDGXOWFDWWOHFKDUDFWHUL]HGE\DFXWHRQVHWRI GLDUUKRHDRIWHQZLWKEORRGIHYHUORVVRIDSSHWLWHGHSUHVVLRQDQGDUDSLGGHFUHDVHLQPLON SURGXFWLRQ%RLOHDXDQG.DSLO(QWHULFOHVLRQVDUHVLPLODUWRWKRVHVHHQLQFDOI GLDUUKRHD'XUKDPHWDO6RPHDQLPDOVPLJKWDOVRVKRZUHVSLUDWRU\VLJQV7UnYpQHW DO&KRHWDO2XWEUHDNVRIZLQWHUG\VHQWHU\PDLQO\VWULNHDGXOWDQLPDOVEXW GLDUUKRHDLQFDOYHVLQWKHVDPHKHUGLVDOVRUHSRUWHG$OHQLXVHWDO

Impact

Bovinerespiratorydisease

Whatisbovinerespiratorydisease?

%RYLQHUHVSLUDWRU\GLVHDVH%5'LVDJHQHUDOWHUPXVHGIRUUHVSLUDWRU\GLVHDVHLQFDWWOH 7KHDHWLRORJ\LVPXOWLIDFWRULDODQGVHYHUDODQWLJHQVDQGKRVWPDQDJHPHQWDQG

HQYLURQPHQWDOIDFWRUVLQWHUDFW(GZDUGV0XUUD\HWDOE%5'FDXVHVSUREOHPV LQERWKODUJHIHHGORWVDQGVPDOOHUKXVEDQGU\V\VWHPV6PLWK.OHPHWDOD 0XUUD\HWDOE%569DQG%&9DUHLPSRUWDQWDJHQWVLQWKHGHYHORSPHQWRI%5' 2WKHUYLUDODJHQWVRILPSRUWDQFHLQFOXGHERYLQHKHUSHVYLUXVERYLQHYLUDOGLDUUKRHDYLUXV

%9'9DQGSDUDLQIOXHQ]DYLUXVW\SHRIZKLFKRQO\WKHODWWHULVFXUUHQWO\SUHVHQWLQ 1RUZD\9LUDODJHQWVDFWERWKDVSULPDU\DJHQWVRIGLVHDVHDQGDVSUHGLVSRVLQJDJHQWVIRU EDFWHULDOLQIHFWLRQV*ULIILQ,QIHHGORWVDQLPDOVRIWHQGHYHORSUHVSLUDWRU\GLVHDVH VKRUWO\DIWHUWKHLQWURGXFWLRQRIQHZDQLPDOV7KHVHUHVSLUDWRU\LQIHFWLRQVLQSRVWZHDQHG EHHIFDOYHVRIWHQUHFRUGHGIROORZLQJVWUHVVHJZHDQLQJVKLSSLQJFRPPLQJOLQJDUH NQRZQDVshippingfeverZKHUHDVLQIHFWLRQVLQGDLU\RUYHDOFDOYHVEHWZHHQWZRDQGVL[

PRQWKVRIDJHDUHFRPPRQO\UHIHUUHGWRDVenzooticcalfpneumonia0XUUD\HWDOE

(27)

+RZHYHUWKHVHGHILQLWLRQVDUHQRWVWULFWO\IROORZHGDQGWHUPVDUHLQFRQVLVWHQWO\XVHGLQWKH OLWHUDWXUH

ImpactofBRD

7KHKLJKRFFXUUHQFHPRUELGLW\DQGPRUWDOLW\RI%5'PDNHVLWDVHYHUHFRQFHUQIRUDQLPDO ZHOIDUH)XOWRQ(FRQRPLFORVVHVIROORZLQJ%5'DUHPDLQO\GXHWRPRUWDOLW\

WUHDWPHQWFRVWVPHWDSK\ODFWLFDQGRUWKHUDSHXWLFXVHRIDQWLELRWLFVYDFFLQDWLRQDQG UHGXFHGZHLJKWJDLQ%RLOHDXDQG.DSLO6DFFRHWDO/RQJWHUPHIIHFWVRI

%5'KDYHDOVREHHQVKRZQDQGDUHFHQWVWXG\IRXQGUHGXFHGPLONSURGXFWLRQGXULQJILUVW ODFWDWLRQIRUFRZVWKDWZHUHGLDJQRVHGZLWKOXQJFRQVROLGDWLRQDVFDOYHV'XQQHWDO 6HFRQGDU\EDFWHULDOLQIHFWLRQVOHDGWRLQFUHDVHGXVHRIDQWLELRWLFVDQGUHVSLUDWRU\GLVHDVHLV WRGD\FRQVLGHUHGRQHRIWKHPRVWLPSRUWDQWFDXVHVRIDQWLELRWLFWUHDWPHQWLQFDWWOH

FRQVHTXHQWO\SRVLQJDFRQFHUQIRUWKHHPHUJHQFHRIDQWLELRWLFUHVLVWDQFH$UHFHQWVWXG\RI 'DQLVKKHUGVIRXQGWKDWUHVSLUDWRU\GLVRUGHUVDFFRXQWHGIRURIDQWLPLFURELDOVXVHGLQ YHDOFDOYHVDQG\RXQJEXOOV)HUWQHUHWDO7KHFRQVHTXHQFHVRI%5'LQVPDOOHU KXVEDQGU\V\VWHPVDUHOHVVVWXGLHGWKDQLQIHHGORWVZKHUH%5'FRQVWLWXWHVDPDMRU FKDOOHQJHZLWKVHYHUHLPSDFWRQDQLPDOZHOIDUHDQGSURILWDELOLW\/RQHUDJDQHWDO 6QRZGHUHWDO+RZHYHU%5'DIIHFWVDQLPDOKHDOWKDQGDQWLPLFURELDOXVDJHDOVRLQ RWKHUSURGXFWLRQV\VWHPVZLWKHIIHFWVRQZHOIDUHDQGSURILWDELOLW\

TheroleofBRSVandBCVinBRD

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

%569LVNQRZQDVDPDMRUFRQWULEXWRUWR%5'LQPRVWSURGXFWLRQV\VWHPVDFURVVWKHZRUOG 9DODUFKHUDQG7D\ORU%URGHUVHQ5HVSLUDWRU\GLVHDVHLQFDOYHVLVFRPPRQLQ 1RUZD\DQGLQDVWXG\E\*XOOLNVHQHWDODFDOIGLDUUKRHDWRJHWKHUZLWKUHVSLUDWRU\

GLVHDVHDFFRXQWHGIRUPRUHWKDQRIDOOUHSRUWHGKHDOWKHYHQWVLQFDOYHVGD\V,QD 1RUZHJLDQVWXG\RQRXWEUHDNVRIUHVSLUDWRU\GLVHDVHWKHPRVWFRPPRQO\LVRODWHGDJHQWZDV

(28)

%569.OHPHWDOD6LPLODUILQGLQJVH[LVWIURP'HQPDUNZKHUHDVPDOOVWXG\RI RXWEUHDNVLQGLFDWHGWKDW%569ZDVDQLPSRUWDQWFDXVDWLYHDJHQWLQFDOIUHVSLUDWRU\GLVHDVH 8WWHQWKDOHWDO)HZVWXGLHVKDYHDVVHVVHGWKHFRQVHTXHQFHVRI%569LQIHFWLRQLQ 1RUZHJLDQKHUGVEXWRQHVWXG\HVWLPDWHGDORVVLQSURGXFWLRQRINJPLONSHUFRZIRU GD\VDIWHUD%569RXWEUHDNFRPSDUHGWR!ZHHNEHIRUHRXWEUHDNDQGKHQFHFRQFOXGHG WKDWWKHHIIHFWRQPLONSURGXFWLRQZDVOLNHO\RIPLQRULPSRUWDQFH1RUVWU|PHWDO 7KHPLONORVVLVLQFRQFRUGDQFHZLWKDVWXG\IURP7KH1HWKHUODQGVZKLFKUHSRUWHGD UHGXFWLRQRIDSSUR[LPDWHO\NJIRUFRQVHFXWLYHGD\VGXULQJWKHLQIHFWLRQSHULRGYDQ GHU3RHOHWDO$QRWKHU1RUZHJLDQVWXG\GHVFULELQJD%569UHODWHGRXWEUHDNLQD EXOOWHVWLQJVWDWLRQIRXQGUHGXFHGZHLJKWJDLQDQGDUHGXFWLRQLQIHHGFRQYHUVLRQUDWH.OHP HWDO

7KHUROHRI%&9LQ%5'LVVWLOOQRWIXOO\XQGHUVWRRGKRZHYHUDQLQFUHDVLQJQXPEHURI VWXGLHVHPSKDVL]HWKHLPSRUWDQFHRI%&9DVDQLPSRUWDQWUHVSLUDWRU\SDWKRJHQ/DWKURSHW DO6HYHUDOVWXGLHVIURPIHHGORWVKDYHVKRZQDQHJDWLYHDVVRFLDWLRQEHWZHHQ%&9 VKHGGLQJDQGZHLJKWJDLQ&KRHWDOE7KRPDVHWDO3DWKRJHQHVLVDQG HSLGHPLRORJ\RI%&9GLIIHUVDFURVVSURGXFWLRQV\VWHPVWKXVPRUHUHVHDUFKLVQHHGHGWR DVVHVVWKHLPSDFWRIUHVSLUDWRU\%&9LQVPDOOHUKXVEDQGU\V\VWHPVDQGGDLU\SURGXFWLRQ Diarrhoeaincalves

1HRQDWDOFDOIGLDUUKRHDLVRIWHQUHSRUWHGDVWKHPRVWFRPPRQFDXVHRIPRUELGLW\DQG PRUWDOLW\LQSUHZHDQHGGDLU\FDOYHVDFURVVWKHZRUOG0HJDQFNHWDO*RPH]DQG :HHVH%&9URWDYLUXVEscherichiacoliDQGCryptosporidiumVSSDUHWKHIRXUPRVW LPSRUWDQWHQWHURSDWKRJHQVFDXVLQJGLDUUKRHDLQFDOYHVZRUOGZLGH0HJDQFNHWDO 7KHUHODWLYHLPSRUWDQFHRI%&9DVDFDXVHRIGLDUUKRHDLQFDOYHVYDULHVEHWZHHQVWXGLHV,Q D6ZHGLVKVWXG\GLDUUKRHDZDVWKHVHFRQGPRVWUHSRUWHGGLVHDVHDIWHUUHVSLUDWRU\GLVHDVH LQFDOYHVXQGHUGD\VRIDJH2UWPDQDQG6YHQVVRQ$QRWKHU6ZHGLVKVWXG\

IRXQGDKLJKHUSURSRUWLRQRIGLDUUKRHDLQKLJKPRUWDOLW\KHUGVKRZHYHUQRIDHFDOVDPSOHV ZHUHSRVLWLYHIRU%&97RUVHLQHWDO6LPLODUUHVXOWVH[LVWVIURP1RUZD\ZKHUH

*XOOLNVHQHWDODUHSRUWHGWKDWWKHUROHRI%&9DVDFDXVHRIFDOIGLDUUKRHDDSSHDUHG WREHPLQRU

Winterdysentery

,QDGGLWLRQWRUHVSLUDWRU\GLVHDVHDQGGLDUUKRHDLQFDOYHV%&9LVUHVSRQVLEOHIRUHSLGHPLFV RIZLQWHUG\VHQWHU\7KHGLVHDVHLVPRVWFRPPRQLQGDLU\KHUGVEXWFDQDOVRDSSHDULQEHHI

(29)

FDWWOH'XUKDPHWDO&KRHWDO2XWEUHDNVDUHPRVWFRPPRQGXULQJDXWXPQ DQGZLQWHUDOWKRXJKRXWEUHDNVGXULQJVXPPHUKDYHEHHQUHSRUWHG3DUNHWDO

%RLOHDXDQG.DSLO7KHGLVHDVHLVRIWHQUHSRUWHGWRUHVXOWLQKLJKPRUELGLW\DQGORZ PRUWDOLW\&ODUN&KRHWDO'XULQJZLQWHUG\VHQWHU\RXWEUHDNVFDOYHVDUH RIWHQFOLQLFDOO\XQDIIHFWHG+HGVWU|PDQG,VDNVVRQ7UnYpQHWDO7KHPRVW HYLGHQWFRQVHTXHQFHIRUWKHIDUPHULVWKHDVVRFLDWHGPLONSURGXFWLRQORVVLQDGXOWFRZV,Q H[SHULPHQWDOO\LQIHFWHGFRZVDGURSRI±IURPWKHSUHLQIHFWLRQOHYHOZDVUHSRUWHG 7UnYpQHWDO-DFWHOHWDOFRPSDUHGPLONSURGXFWLRQWRDVWDQGDUGL]HG ODFWDWLRQFXUYH:RRGDQGUHSRUWHGDGURSRI±LQDIIHFWHGFRZVIURPRXWEUHDN KHUGV2WKHUVWXGLHVDOVRUHSRUWDPLONGURSLQKHUGVZLWKZLQWHUG\VHQWHU\+HGVWU|PDQG ,VDNVVRQ'XUKDPHWDO7UnYpQHWDO+RZHYHUTXDQWLILFDWLRQEDVHGRQ PRUHWKDQDIHZKHUGVDQGORQJLWXGLQDOVWXGLHVDVVHVVLQJWKHHIIHFWRYHUWLPHLVODFNLQJ (VWLPDWHVRIWKHHIIHFWRQDQLPDOSHUIRUPDQFHLVDQLPSRUWDQWSDUWRIWKHWRWDOHFRQRPLF LPSDFWRIWKHGLVHDVHDQGLVWKXVFULWLFDODVLQSXWIRUDFRVW±EHQHILWDVVHVVPHQWRI V\VWHPDWLFFRQWUROHIIRUWV

Transmission

9LUXVWUDQVPLVVLRQRI%569DQG%&9ZLWKLQKHUGVLVQRUPDOO\YHU\HIIHFWLYHUHVXOWLQJLQD KLJKOHYHORIPRUELGLW\&KRHWDO9DODUFKHUDQG7D\ORU%LGRNKWLHWDO

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

WKURXJKDWXEHLQWKHZDOO0DUVHWDO$LUERUQHWUDQVPLVVLRQRI%569RU%&9 DFURVVORQJHUGLVWDQFHVLHEHWZHHQIDUPVKDVQRWEHHQGHVFULEHGDQGLVOLNHO\RIOLPLWHG LPSRUWDQFH%HWZHHQIDUPVGLUHFWWUDQVPLVVLRQLVSRVVLEOHWKURXJKSXUFKDVHRIDQLPDOV IURPRWKHUIDUPV/LYHVWRFNFRXOGFDUU\WKHLQIHFWLRQIURPWKHKHUGRIRULJLQRUWKH\FRXOG EHLQIHFWHGGXULQJWUDQVSRUWLIDQLPDOVIURPVHYHUDOKHUGVDUHPL[HG&RQWDFWEHWZHHQ

(30)

DQLPDOVIURPGLIIHUHQWIDUPVLVDOVRSRVVLEOHRQVKDUHGSDVWXUHV,WLVQRWXQFRPPRQIRU KHUGVWRFRSDVWXUHLQ1RUZD\

%569DQG%&9FDQDOVREHWUDQVPLWWHGLQGLUHFWO\YLDFRQWDPLQDWHGVXUIDFHVSHRSOHRU IRPLWHV7KHSRWHQWLDOIRULQGLUHFWWUDQVPLVVLRQRIYLUXVODUJHO\GHSHQGVRQVXUYLYDORXWVLGH WKHKRVWZKLFKLVLQIOXHQFHGE\WHPSHUDWXUHKXPLGLW\S+DQGH[SRVXUHWRXOWUDYLROHWOLJKW /D5RVDHWDO(QYHORSHGUHVSLUDWRU\YLUXVHVOLNH%&R9DQG%569DUHJHQHUDOO\

UHJDUGHGIUDJLOHRXWVLGHRIWKHKRVW+RZHYHULWKDVEHHQVKRZQWKDWLQDOLTXLGVXVSHQVLRQ

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

VWHWKRVFRSHV2PDHWDO,QWZRVHSDUDWHH[SHULPHQWVFDOYHVZHUHLQIHFWHGZLWK

%569DQG%&9UHVSHFWLYHO\)RUERWK%569DQG%&9DKLJKORDGRIYLUXVZDVIRXQGRQ IRPLWHVKRXUVDIWHUH[SRVXUHWRLQIHFWHGFDOYHV%569VHHPHGWRORVHLQIHFWLYLW\PRUH UDSLGO\WKDQ%&9DVWKHUHZHUHQRLQIHFWLYH%569DIWHUKRXUVZKHUHDV%&9ZHUHVWLOO LQIHFWLYH7KHODWWHUVWXG\HPSKDVL]HVWKDWYLUXVFDUULDJHRQIRPLWHVOLNHO\SRVHVDQ LQIHFWLRQULVNWRFDWWOH7KHUHODWLYHLPSRUWDQFHRIGLUHFWWUDQVPLVVLRQEHWZHHQIDUPV WKURXJKDQLPDOWUDGHYHUVXVLQGLUHFWYLDYLVLWRUVDQGIRPLWHVLVQRWNQRZQ

,WLVEHOLHYHGWKDWIDUPRXWEUHDNVRIGLVHDVHFDXVHGE\%569DQG%&9FRPPRQO\UHVXOW IURPQHZLQWURGXFWLRQRIYLUXV7KLVLVVXSSRUWHGE\WKHKLJKUDWHRIUDWHRIVHOIFOHDUDQFHDW WKHKHUGOHYHOLHFOHDUDQFHRIYLUXVIURPWKHKHUGZLWKRXWVSHFLILFLQWHUYHQWLRQV

SUHYLRXVO\UHSRUWHG.OHPHWDO6LPLODUG\QDPLFVKDYHDOVREHHQUHSRUWHGIURP 6ZHGHQ2KOVRQHWDO$VWKHSURWHFWLYHLPPXQLW\DFTXLUHGDIWHULQIHFWLRQLVVKRUW UHLQIHFWLRQRIDQLPDOVLVOLNHO\FRPPRQ&RQVHTXHQWO\SUHYLRXVKHUGRXWEUHDNVGRQRW SUHYHQWWKHKHUGIURPLQIHFWLRQIROORZLQJUHLQWURGXFWLRQRIYLUXV7UnYpQHWDO UHSRUWHGWKDWDPRQJKHUGVZLWKZLQWHUG\VHQWHU\VHYHUDOKDGH[SHULHQFHGSUHYLRXV RXWEUHDNVLQWKHSUHFHGLQJWZR±IRXU\HDUV:KHWKHUFKURQLFLQIHFWLRQRUUHDFWLYDWLRQRI ODWHQWYLUXVRFFXUVLVDGHEDWHGLVVXHLQWKHOLWHUDWXUH6RPHDXWKRUVVXJJHVWWKDWWKLVLV SRVVLEOHDQGPLJKWSOD\DUROHLQVXVWDLQLQJLQIHFWLRQLQDKHUG9DQGHU3RHOHWDO

(31)

.DQQRHWDO9LUXVFLUFXODWLRQIRUSURORQJHGSHULRGVRIWLPHLVOLNHO\SRVVLEOHLQ ODUJHKHUGVLIVXVFHSWLEOHDQLPDOVDUHLQWURGXFHGUHJXODUO\'H-RQJHWDO+RZHYHU IRU1RUZHJLDQFRQGLWLRQVWKHVPDOODYHUDJHKHUGVL]HPDNHVLWOLNHO\WKDWWKLVLVRIOLPLWHG LPSRUWDQFHFRPSDUHGWRQHZLQWURGXFWLRQV

Herd­levelriskfactors

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

)HZVWXGLHVKDYHHVWLPDWHGWKHHIIHFWRIDQLPDOSXUFKDVHDVDULVNIDFWRUIRU%569DQG

%&9)U|VVOLQJHWDOIRXQGWKDWSXUFKDVHRIOLYHVWRFNZDVDVLJQLILFDQWULVNIDFWRU IRUKHUGOHYHOSRVLWLYLW\PHDVXUHGE\VHURORJ\RI\RXQJVWRFNIRU%&9EXWQRWIRU%569

$QRWKHU6ZHGLVKVWXG\UHSRUWHGWKDWRXWEUHDNVRI%569UHODWHGUHVSLUDWRU\GLVHDVHRIWHQ VWDUWHGZLWKWKHSXUFKDVHRIDQLPDOV(OYDQGHU5HPDUNDEO\7UnYHQHWDO IRXQGWKDWDORZHUSURSRUWLRQKHUGVZLWKZLQWHUG\VHQWHU\KDGSXUFKDVHGFDWWOHGXULQJWKH SUHYLRXV\HDUFRPSDUHGWRQRQRXWEUHDNKHUGVKRZHYHUWKHGLIIHUHQFHZDVQRWVWDWLVWLFDOO\

VLJQLILFDQW/DUJHKHUGVL]HLVDIUHTXHQWO\UHSRUWHGULVNIDFWRUIRUERWKYLUXVHV7UnYpQHW DO1RUVWU|PHWDO2KOVRQHWDOE)U|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

$VXUSULVLQJSUHYHQWLYHHIIHFWRIDUWLILFLDOLQVHPLQDWLRQ$,E\H[WHUQDOWHFKQLFLDQV FRPSDUHGWRIDUPSHUVRQQHOZDVIRXQGLQWZRVWXGLHVIURP6ZHGHQ%LGRNKWLHWDO

(32)

2KOVRQHWDOD2KOVRQDVXJJHVWVWKDWGLIIHUHQFHVLQJHQHUDOELRVHFXULW\OHYHO DQGPDQDJHPHQWFRXOGEHSRVVLEOHH[SODQDWLRQV&RQIOLFWLQJILQGLQJVH[LVWZLWKUHJDUGWR GLIIHUHQFHVEHWZHHQFRQYHQWLRQDODQGRUJDQLFSURGXFWLRQ%LGRNKWLHWDOIRXQGWKDW FRQYHQWLRQDOO\PDQDJHGKHUGVKDGKLJKHURGGVRISRVLWLYLW\FRPSDUHGWRRUJDQLFKRZHYHU WKLVFRXOGQRWEHYHULILHGLQDODWHUVWXG\ZLWKDODUJHUVDPSOHVL]H:ROIIHWDO)HZ VWXGLHVRIULVNIDFWRUVH[LVWIURP1RUZD\+RZHYHU1RUVWU|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±

WLPHFOXVWHULQJRIWKHGLVHDVH$QLQWURGXFWLRQRIYLUXVYLDSHRSOHRUIRPLWHVKDVEHHQ UHSRUWHGDVWKHOLNHO\WUDQVPLVVLRQURXWHLQVRPHRXWEUHDNVRIZLQWHUG\VHQWHU\+HGVWU|P DQG,VDNVVRQ5REHUWV

,QJHQHUDOWKHUHLVDODFNRIVWXGLHVRQIDFWRUVDIIHFWLQJWKHULVNRI%569DQG%&9 LQWURGXFWLRQWRKHUGV

Diseasepreventionandcontrol

)LQGLQJVWUDWHJLHVWRFRQWUROLQIHFWLRXVGLVHDVHVLQDZD\WKDWOLPLWVWKHXVHRI

DQWLPLFURELDOVPHHWVDQLPDOZHOIDUHUHTXLUHPHQWVDQGUHGXFHVSURGXFHUDQGFRQVXPHU FRVWVLVDSULRULWL]HGLVVXHDURXQGWKHZRUOG

(33)

Preventionofdiseasewithinherds

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

Vaccineefficacy

%HFDXVHWKHKRVWLPPXQHUHVSRQVHSOD\VDQLPSRUWDQWUROHLQWKHSDWKRJHQHVLVRIERWK KXPDQ569DQG%569LQIHFWLRQGHYHORSLQJHIILFDFLRXVDQGVDIHYDFFLQHVKDVSURYHGD FKDOOHQJLQJWDVN,QWKHVIRUPDOLQDGMXYDWHGKXPDQ569YDFFLQHVXQIRUWXQDWHO\

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

(34)

9DODUFKHUDQG7D\ORU(OOLV$JHQHUDOSUREOHPZLWKFKDOOHQJHVWXGLHVIRU

%569LVWKHLQDELOLW\WRSURGXFHFOLQLFDOGLVHDVHZLWKDFRPSDUDEOHVHYHULW\WRZKDWLVVHHQ DIWHUQDWXUDOH[SRVXUH

,Q1RUZD\RQH%569YDFFLQHZDVDYDLODEOHGXULQJWKHFRXUVHRIWKLVSURMHFWDWULYDOHQW YDFFLQHIRUSDUHQWHUDODGPLQLVWUDWLRQWKDWLQFOXGHVLQDFWLYDWHG%569SDUDLQIOXHQVDYLUXV 3L9DQGMannheimiahaemolytica%RYLOLVŠ%RYLSDVW563YHW$IHZSXEOLVKHG H[SHULPHQWDOFKDOOHQJHVWXGLHVKDYHHYDOXDWHGWKHHIILFDF\RIWKLVSDUWLFXODUYDFFLQHDOORI ZKLFKLQFOXGHGFDOYHVZLWKPDWHUQDODQWLERGLHV7ZRRIWKHVWXGLHVHYDOXDWHGWKHHIILFDF\RI DVLQJOHGRVH0DZKLQQH\DQG%XUURZVGHWHFWHGDVWDWLVWLFDOO\VLJQLILFDQWS LQFUHDVHLQ%569UHDFWLYH,J*LQYDFFLQDWHGFDOYHVDQG9DQGHU6OXLMVHWDOIRXQG WKDWYDFFLQDWHGFDOYHVKDGVLJQLILFDQWO\OHVVYLUXVVKHGGLQJLQQDVDOGLVFKDUJH$WKLUGVWXG\

HYDOXDWHGWKHHIILFDF\RIWZRGRVHVRIWKHYDFFLQHJLYHQRQHPRQWKDSDUWDQGGLGQRWGHWHFW QDVDOVKHGGLQJRIYLUXVLQYDFFLQDWHGFDOYHVZKHUHDVYLUXVZDVVKHGE\DYDULDEOH

SURSRUWLRQRIXQYDFFLQDWHGFDOYHV3DWHO6LJQLILFDQWGLIIHUHQFHVLQFOLQLFDOVLJQV EHWZHHQJURXSVZHUHQRWGHWHFWHGLQDQ\RIWKHDERYHPHQWLRQHGVWXGLHV3DWHO 0DZKLQQH\DQG%XUURZVYDQGHU6OXLMVHWDO

)RU%&9WKHUHDUHIHZYDFFLQHVDYDLODEOHDQGVLPLODUWR%569WKHGHYHORSPHQWRIVDIH DQGHIILFDFLRXVYDFFLQHVKDVEHHQGLIILFXOW+XPDQYDFFLQHVDUHDOVRODFNLQJGHVSLWHHIIRUWV WRGHYHORSYDFFLQHVDJDLQVWVHYHUHFRURQDYLUXVHVVXFKDV6$56&R9DQG0(56&R9 7KHUHLVQRDYDLODEOHYDFFLQHODEHOHGIRUSUHYHQWLRQRIZLQWHUG\VHQWHU\RU%5'FDXVHGE\

%&91HYHUWKHOHVVRQHUHSRUWGHVFULEHVUHGXFHGULVNRI%5'WUHDWPHQWDPRQJFDOYHVLQDQ

$PHULFDQIHHGORWIROORZLQJLQWUDQDVDODGPLQLVWUDWLRQRIDFRPPHUFLDOO\DYDLODEOHYDFFLQH DJDLQVW%&9DQGURWDYLUXV3OXPPHUHWDO,Q1RUZD\WKHUHLVRQHWULYDOHQWYDFFLQH FRQWDLQLQJLQDFWLYDWHG%&9URWDYLUXVDQGE.coliDYDLODEOH,WLVODEHOHGIRUDFWLYH

LPPXQL]DWLRQRISUHJQDQWFRZVWRFRQIHUSDVVLYHWUDQVIHURIDQWLERGLHVWRFDOYHVIRU SURWHFWLRQDJDLQVWQHRQDWDOFDOIGLDUUKRHD/DFWRYDF=RHWLV7KHYDFFLQHKDVEHHQUHSRUWHG WRLQFUHDVHDQWLERG\WLWHUVLQFRORVWUXPDQGVHUXP.RKDUDHWDO+RZHYHUERWKWKLV VWXG\DQGDQRWKHUILHOGWULDOIDLOHGWRILQGDSURWHFWLYHHIIHFWRIYDFFLQDWLRQRQRFFXUUHQFHRI FDOIGLDUUKHD:DOWQHU7RHZVHWDO.RKDUDHWDO

$OWRJHWKHUWKHHIILFDF\RIDYDLODEOHYDFFLQHVDJDLQVW%569DQG%&9LVTXHVWLRQDEOH 'HFLVLRQVUHJDUGLQJYDFFLQDWLRQDOVRLQYROYHVFRQVLGHULQJDVSHFWVDSDUWIURPYDFFLQH HIILFDF\VXFKPDQDJHPHQWDQGDVW\SHRISURGXFWLRQ1RWDEO\WKH%569DQG%&9

(35)

YDFFLQHVDUHPXOWLYDOHQWDQGFRQWDLQRWKHUSDWKRJHQVWKDQWKHYLUXVHVRIWHQEDFWHULDO FRPSRQHQWV3URWHFWLRQDJDLQVWVHFRQGDU\EDFWHULDOLQIHFWLRQHJMannheimiahaemolytica FRXOGPHDQWKDWWKHYDFFLQHSURYLGHVGLVHDVHSURWHFWLRQLQWKHILHOGUHJDUGOHVVRIZKHWKHULW SURWHFWVDJDLQVWWKHSULPDU\YLUXVLQIHFWLRQ7KLVDGGVWRWKHFRPSOH[LW\RIGHFLVLRQV UHJDUGLQJZKHWKHURUQRWWRYDFFLQDWH7KHXUHUHWDOVXJJHVWVWKDWLGHDOO\GHFLVLRQV UHJDUGLQJYDFFLQDWLRQVKRXOGEHEDVHGRQGDWDREWDLQHGIURPUDQGRPL]HGFRQWUROOHGWULDOV SHUIRUPHGLQWKHFDWWOHSRSXODWLRQLQTXHVWLRQ7RGDWHQRYDFFLQHWULDOVIURP1RUZD\DUH DYDLODEOH

Preventionoftransmissionbetweenherds

5RXWHVRIEHWZHHQKHUGWUDQVPLVVLRQDUHQRWIXOO\XQGHUVWRRGKRZHYHUOLYHDQLPDOFRQWDFW UHSUHVHQWVDOLNHO\WUDQVPLVVLRQSDWKZD\IRUERWKYLUXVHV$VPHQWLRQHGSUHYLRXVO\WKH VWXG\E\2PDHWDOLQGLFDWHGSRVVLEOHYLUXVFDUULDJHWKURXJKIRPLWHVIRUDVORQJDV KDIWHUH[SRVXUH,PSOHPHQWLQJDKLJKOHYHORIELRVHFXULW\DQGOLPLWLQJOLYHVWRFN SXUFKDVHDUHJHQHUDOPHDVXUHVWRUHGXFHWKHULVNRIWUDQVPLVVLRQEHWZHHQKHUGV+RZHYHU NHHSLQJDFORVHGKHUGLVRIWHQQRWSRVVLEOHEHFDXVHRIWKHQHHGWRSXUFKDVHUHSODFHPHQW DQLPDOV+XPDQWUDIILFLVDOVRKDUGWRDYRLGHVSHFLDOO\SURIHVVLRQDOYLVLWRUVVXFKDV YHWHULQDULDQV$,WHFKQLFLDQVDQGDQLPDOWUDQVSRUWHUV$6ZHGLVKVWXG\VKRZHGWKDWDKLJK SURSRUWLRQRIYLVLWRUVKDGGLUHFWDQLPDOFRQWDFWDQGDOWKRXJKH[SHFWHGIRU$,WHFKQLFLDQV DQGYHWHULQDULDQVLWLVQRWHZRUWK\WKDWHYHQDQLPDOWUDQVSRUWHUVKDGDQLPDOFRQWDFWGXULQJ RIYLVLWV1|UHPDUNHWDO([DPSOHVRIELRVHFXULW\PHDVXUHVWRUHGXFHWKHULVN RILQGLUHFWWUDQVPLVVLRQEHWZHHQKHUGVDUHFORWKLQJDQGIRRWZHDUDYDLODEOHIRUYLVLWRUV ZDVKLQJIDFLOLWLHVDQGXVHRILQIHFWLRXVVOXLFHURRPIRUDOOYLVLWRUV,QDTXHVWLRQQDLUHWR 6ZHGLVKIDUPHUVPRUHWKDQRIIDUPHUVSHUFHLYHGELRVHFXULW\DVLPSRUWDQW QHYHUWKHOHVVUHSRUWHGWKDWERRWVIRUYLVLWRUVZHUHQRWSURYLGHGRUZHUHQHYHUXVHG 2KOVRQHWDOE7KLVSDUDGR[KLJKOLJKWVWKHQHHGWRLQFUHDVHDZDUHQHVVRIELRVHFXULW\

URXWLQHV

%569DQG%&9KDYHVRPHFRPPRQIHDWXUHVWKDWPDNHWKHPERWKFKDOOHQJLQJEXWSRVVLEOH WRFRQWURO7KHKLJKRFFXUUHQFHRIERWKYLUXVHVWKHSRWHQWLDORIERWKGLUHFWDQGLQGLUHFW WUDQVPLVVLRQDQGWKHKLJKLQIHFWLYLW\PDNHVFRQWURODFKDOOHQJLQJWDVN/LPLWHGSHUVLVWHQFH LQWKHHQYLURQPHQWDQGWKHOLNHO\OLPLWHGLPSRUWDQFHRIZLOGOLIHUHVHUYRLUVIDYRXUVFRQWURO 1RUZHJLDQKHUGVDUHVPDOODQGGLVSHUVHGWKURXJKRXWWKHFRXQWU\VXJJHVWLQJWKDWFRQWURORI

%569DQG%&9FRXOGEHSRVVLEOHE\OLPLWLQJWUDQVPLVVLRQEHWZHHQKHUGVDQGUHJLRQV )XUWKHUPRUHWKHKLJKUDWHRIVHOIFOHDUDQFHDWWKHKHUGOHYHO.OHPHWDOVXJJHVWV

(36)

WKDWSUHYHQWLRQRIQHZLQWURGXFWLRQVRIYLUXVFRXOGEHDQHIIHFWLYHPHDVXUHWRUHGXFHKHUG SUHYDOHQFHLQWKH1RUZHJLDQFDWWOHSRSXODWLRQ

ControlofBRSVandBCVinNorway

TheNorwegiancontrolprogramme

7KH1RUZHJLDQFDWWOHSRSXODWLRQLVDVPHQWLRQHGIUHHIURPPDQ\LQIHFWLRXVGLVHDVHV7KLV QRWZLWKVWDQGLQJHSLGHPLFVRIUHVSLUDWRU\GLVHDVHDQGGLDUUKRHDDUHFRPPRQUHGXFLQJ DQLPDOZHOIDUHDQGKDPSHULQJWKHHFRQRPLFVXVWDLQDELOLW\RIWKHLQGXVWU\$JDLQVWWKLV EDFNGURSWKHUHKDVEHHQDJURZLQJGHVLUHRYHUUHFHQW\HDUVDPRQJVWDNHKROGHUVLQWKH 1RUZHJLDQFDWWOHLQGXVWU\WRLQLWLDWHV\VWHPDWLFFRQWURORI%569DQG%&9LQWKHFDWWOH SRSXODWLRQ$ELRVHFXULW\EDVHGFRQWUROSURJUDPPHZDVODXQFKHGE\DMRLQWFDWWOHLQGXVWU\

LQ0DUFKDIWHUVFUHHQLQJQHDUO\DOOGDLU\KHUGVIRU%569DQG%&9DQWLERGLHVLQEXON WDQNPLON%707KHSODQQLQJGHVLJQFRVWEHQHILWDVVHVVPHQWDQGLPSOHPHQWDWLRQZDV SHUIRUPHGE\WKHLQGXVWU\SDUWQHUVLQWKHSURJUDPPH%DVHGRQWKHLQLWLDOVFUHHQLQJKHUGV ZHUHFODVVLILHGKHUGVDVµUHG¶DQWLERG\SRVLWLYHRUµJUHHQ¶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µ+HDOWK\KHUG¶FHUWLILFDWHE\IXOILOOLQJWKHIROORZLQJFULWHULDDµJUHHQ¶VWDWXVSXUFKDVH OLYHVWRFNIURPRWKHUWHVWQHJDWLYHKHUGVRQO\IDFLOLWLHVWKDWDOORZDQLPDOVWREHORDGHGRQWR WUDQVSRUWZLWKRXWWKHWUXFNGULYHUHQWHULQJWKHEDUQDQGDQDSSURYHGLQIHFWLRXVVOXLFHURRP 7KHFHUWLILFDWHPHDQVWKHIDUPHULVDZDUGHGZLWKSUHPLXPSULFLQJRI\RXQJVWRFNDQG EUHHGLQJDQLPDOVDQGDGGLWLRQDOO\UHFHLYHVDGLVFRXQWRQOLYHVWRFNLQVXUDQFH+DUDOG+ROP SHUVRQDOFRPPXQLFDWLRQ-XQH

TheroleofthePhD­project

7KLV3K'SURMHFWLVSDUWRIDODUJHUSURMHFWHVWDEOLVKHGLQIXQGHGE\WKH5HVHDUFK

&RXQFLORI1RUZD\ZLWKVXSSRUWIURPWKHLQGXVWU\$OWRJHWKHUWZR3K'VWXGHQWVRQH HQJLQHHUDQGRQHUHVHDUFKHUZRUNHGLQWKLVODUJHUSURMHFWZLWKWKHDLPWRLQFUHDVHWKH NQRZOHGJHRI%569DQG%&9LQ1RUZD\$UHDVRILPSRUWDQFHIRUV\VWHPDWLFFRQWUROZDV

(37)

RISDUWLFXODULQWHUHVW7KHUHVHDUFKJURXSZDVQRWGLUHFWO\LQYROYHGLQWKHGHFLVLRQPDNLQJ EHKLQGRUWKHLPSOHPHQWDWLRQRIWKHFRQWUROSURJUDPPH+RZHYHUWKHLQLWLDWLYHWRFRQGXFW V\VWHPDWLFQDWLRQDOFRQWURORIWKHVHYLUXVHVSURPSWHGWKHQHHGIRUPRUHUHVHDUFKERWK UHJDUGLQJWKHGLVWULEXWLRQDQGVSUHDGRIWKHYLUXVHVDQGUHJDUGLQJWHVWLQJDQGFODVVLILFDWLRQ RIKHUGV

Diagnostictestsandclassificationofherds

Diagnostics

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

DQGDQWLJHQ(/,6$V6FKRHQWKDOHUDQG.DSLO/DUVHQ%RLOHDXDQG.DSLO 6DLI0HWKRGVIRUDQWLERG\GHWHFWLRQLQFOXGHGLIIHUHQW(/,6$VDVZHOODVYLUXV QHXWUDOL]DWLRQWHVWV917$OHQLXVHWDO/DUVHQ

$QWLERG\GHWHFWLRQLVSHUIRUPHGRQHLWKHUPLONRUVHUXPVDPSOHV7KHSXUSRVHRIWHVWLQJLV RILPSRUWDQFHIRUWKHFKRLFHRIWHVW)RURXWEUHDNLQYHVWLJDWLRQVWKHPHWKRGRIFKRLFHZLOO RIWHQEHHLWKHUDQWLJHQGHWHFWLRQRUDQWLERG\WHVWLQJXVLQJSDLUHGVHUXPVDPSOHVIRU GHWHFWLRQRIWLWUHLQFUHDVH%HFDXVHLWLVFKHDSHUDQGPRUHSUDFWLFDOWRSHUIRUPDQWLERG\

WHVWLQJLVFRPPRQO\XVHGIRUVFUHHQLQJZKHQVDPSOLQJRIPDQ\KHUGVRUDQLPDOVLV QHFHVVDU\

Evaluatingdiagnostictests

3XWVLPSO\WKHSXUSRVHRIDGLDJQRVWLFWHVWLVPRVWFRPPRQO\WRGHWHFWRUUXOHRXWGLVHDVH

$OWKRXJKGLDJQRVWLFWHVWVDUHXVXDOO\WKRXJKWRIDVDODERUDWRU\SURFHGXUHWKHWHUPKDVD ZLGHUPHDQLQJ$FFRUGLQJWR'RKRRHWDOSµ$WHVWPRUHJHQHUDOO\LVDQ\

GHYLFHRUSURFHVVGHVLJQHGWRGHWHFWRUTXDQWLI\DVLJQVXEVWDQFHWLVVXHFKDQJHRUERG\

UHVSRQVHLQDQDQLPDO7HVWVFDQDOVREHDSSOLHGDWWKHKHUGRURWKHUOHYHORIDJJUHJDWLRQ¶

(38)

,GHDOO\DGLDJQRVWLFWHVWZRXOGDOZD\VDQVZHURQH¶VGLDJQRVWLFTXHVWLRQZLWKRXWHUURUDQG XQHTXLYRFDOO\LQGLFDWHSUHVHQFHRUDEVHQFHRIGLVHDVH+RZHYHUSHUIHFWWHVWVDUHUDUH7KXV WKHUHLVDQHHGWRTXDQWLI\RQH¶VWUXVWLQWKHWHVWUHVXOW3UHIHUDEO\DWHVWVKRXOGEHSUHFLVH DQGDFFXUDWH+LJKSUHFLVLRQRUFRQVLVWHQF\PHDQVWKHWHVWUHVXOWVVKRZOLWWOHYDULDWLRQ EHWZHHQEDWFKHVUXQVGD\VDQGHYHQEHWZHHQGLIIHUHQWODEVHVSHFLDOO\LIUHVXOWVIURP GLIIHUHQWODERUDWRULHVDUHXVHG7KHDFFXUDF\RIDGLDJQRVWLFWHVWLVFRPPRQO\PHDVXUHGE\

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

Diagnostictestevaluationagainstaperfectreferenceprocedure

7KH6HDQG6SDUHFKDUDFWHULVWLFVRIWKHWHVW+RZHYHULQDFOLQLFDOVHWWLQJFDOFXODWLQJ SUHGLFWLYHYDOXHVLVRIWHQPRUHLQIRUPDWLYH7KHSRVLWLYHSUHGLFWLYHYDOXH339LVWKH SUREDELOLW\WKDWJLYHQDSRVLWLYHWHVWUHVXOWWKHWHVWVXEMHFWWUXO\KDVWKHGLDJQRVLVLQ TXHVWLRQ7KHQHJDWLYHSUHGLFWLYHYDOXH139LVWKHSUREDELOLW\WKDWJLYHQDQHJDWLYHWHVW WKHVXEMHFWGRHVQRWKDYHWKHGLDJQRVLVLQTXHVWLRQ7UDGLWLRQDOO\HYDOXDWLRQRIGLDJQRVWLF WHVWVKDVEHHQSHUIRUPHGDJDLQVWDSHUIHFWUHIHUHQFHSURFHGXUHLHDµJROGVWDQGDUG¶,QWKLV VFHQDULRWKH6H6SDQGSUHGLFWLYHYDOXHVFDQEHFDOFXODWHGGLUHFWO\IURPFURVVWDEXODWLQJ WKHUHVXOWV:KHQWHVWDFFXUDF\LVNQRZQWKHSUHGLFWLYHYDOXHVFDQDOVREHFDOFXODWHGIURP WKH6H6SDQGSULRUSUREDELOLW\RISRVLWLYLW\LHWKHSUHYDOHQFHLQWKHWHVWHGSRSXODWLRQ 7KHFRQFHSWRIHYDOXDWLQJDGLDJQRVWLFWHVWDJDLQVWDJROGVWDQGDUGPHWKRGLVLOOXVWUDWHGLQ WKH[WDEOHVKRZQEHORZ7DEOH

(39)

7DEOH'DWDOD\RXWIRUGLDJQRVWLFWHVWHYDOXDWLRQDJDLQVWDSHUIHFWUHIHUHQFHSURFHGXUHJROG VWDQGDUG

7HVWUHVXOW

7UXHGLDJQRVLVJROGVWDQGDUG

7RWDO 3RVLWLYHGLVHDVHG 1HJDWLYHKHDOWK\

3RVLWLYH ܽ ܾ ܽ ൅ ܾ

1HJDWLYH ܿ ݀ ܿ ൅ ݀

7RWDO ܽ ൅ ܿ ܾ ൅ ݀ ݊

6HQVLWLYLW\ ܽȀሺܽ ൅ ܿሻ 3RVLWLYHSUHGLFWLYHYDOXH ܽȀሺܽ ൅ ܾሻ 6SHFLILFLW\ ݀Ȁሺܾ ൅ ݀ሻ 1HJDWLYHSUHGLFWLYHYDOXH ܿȀሺܿ ൅ ݀ሻ

Diagnostictestevaluationintheabsenceofagoldstandard

8QIRUWXQDWHO\DSHUIHFWUHIHUHQFHSURFHGXUHLVUDUHO\DYDLODEOHDQGWKHWUXHVWDWXVRIWKH WHVWVXEMHFWVLVWKHUHIRUHKDUGWRYHULI\7KXVVWDWLVWLFDOPHWKRGVKDYHEHHQGHYHORSHGRYHU WKHSDVWVHYHUDOGHFDGHVIRUWKHHYDOXDWLRQRIGLDJQRVWLFWHVWVLQWKHDEVHQFHRIDJROG VWDQGDUGQDPHO\ODWHQWFODVVPRGHOV7KHVHPRGHOVDOORZIRUHVWLPDWLRQRIWHVWDFFXUDF\

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

BCV/BRSVcommercialELISA

7KH6YDQRYLUŠ%569$EDQGWKH6YDQRYLUŠ%&9$EDUHFRPPHUFLDOO\DYDLODEOH(/,6$

WHVWVXVHGLQPDQ\SUHYLRXVVWXGLHVERWKLQ1RUZD\DQG6ZHGHQ%HDXGHDXHWDO 2KOVRQHWDOD2KOVRQHWDOE.OHPHWDO7KH6YDQRYLUŠ%569$ELV FXUUHQWO\XVHGLQ6ZHGLVKKHUGVLQDYROXQWDU\VDPSOLQJSURJUDPPHIRUGDLU\RSHUDWLRQVDV

(40)

SDUWRIWKHFRQWUROLQLWLDWLYHFDOOHGµVDIHDQLPDOWUDGH¶UXQE\9l[D6YHULJHWKHODUJHVWGDLU\

FRRSHUDWLRQLQ6ZHGHQ

)RUWKH6YDQRYLUŠ%569$EWKHSDUDPHWHUVSURYLGHGE\WKHPDQXIDFWXUHUDUH6HDQG 6S7KH\RULJLQDWHIURPDYDOLGDWLRQVWXG\ZKHUHWKH6YDQRYLUŠ%569$EZDV FRPSDUHGWRDQRWKHULQGLUHFW(/,6$LQXVHDWWKH&HQWUDO9HWHULQDU\/DERUDWRU\&9/

:H\EULGJH(OYDQGHUHWDO7KHVWXG\GHVLJQZDVFRPSOH[EXWLQRQHSDUWERWKWHVWV ZHUHXVHGRQVHUXPVDPSOHVRIZKLFKZHUHH[FOXGHGGXHWRDEVRUEDQFHYDOXHVLQ WKH³JUH\]RQH´IRUWKH&9/(/,6$OHDYLQJVDPSOHVIRUFURVVWDEXODWLRQRIUHVXOWV 7KH&9/(/,6$ZDVXVHGDVDJROGVWDQGDUGDQGUHODWLYHHVWLPDWHVRI6HDQG6SZHUH REWDLQHGIRUWKH6YDQRYLUŠ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

)RUWKH6YDQRYLUŠ%&9$EWKHWHVWSDUDPHWHUVSURYLGHGE\WKHPDQXIDFWXUHUDUH6H DQG6SZLWKDUHIHUHQFHWRDVWXG\FRQGXFWHGLQ$OHQLXVHWDO7KHDLP RIWKLVVWXG\ZDVQRWWRYDOLGDWHWKH(/,6$WHVWEXWLWLQFOXGHGDVHURORJLFLQYHVWLJDWLRQ DQGWKXVNQRZOHGJHRIWKHSHUIRUPDQFHRIWKHWHVWZDVUHTXLUHG7KH(/,6$ZDVFRPSDUHG WRD917LQDVXEVHWRIVHUXPVDPSOHV7UDGLWLRQDOO\917KDVEHHQXVHGDVDJROG VWDQGDUGWHVWWRZKLFKDQHZDQWLERG\WHVWFDQEHFRPSDUHG1HYHUWKHOHVVWKHDVVXPSWLRQ WKDWWKHUHIHUHQFHWHVWLVHUURUIUHHLVTXHVWLRQDEOH917VDUHRIWHQFRQVLGHUHGKLJKO\

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

(41)

%RWKWKH%569DQG%&9(/,6$KDYHWHVWSDUDPHWHUVREWDLQHGIRUVHUXPVDPSOHVRQO\

KRZHYHUWKHWHVWVDUHLQXVHIRULQGLYLGXDOPLONVDPSOHVDQG%70DVZHOO7KH

GRFXPHQWDWLRQRIWHVWSDUDPHWHUVDUHEDVHGRQDVLQJOHVWXG\IRUHDFKWHVWZLWKOLPLWDWLRQV DVGLVFXVVHGDERYH7KHUHIRUHPRUHHYLGHQFHWRVXEVWDQWLDWHWKHWHVWSDUDPHWHUVIRUVHUXP VDPSOHVDVZHOODVHVWLPDWLRQRIWHVWDFFXUDF\IRURWKHUDSSOLFDWLRQVZRXOGSURYLGHXVHIXO LQIRUPDWLRQWRWHVWXVHUV

BCV/BRSVmultipleximmunoassay

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

Classificationofherds

Herdtesting

&KULVWHQVHQDQG*DUGQHUGHILQHDKHUGWHVWDVµDQHYDOXDWLRQRIDVDPSOHRIRUDOO DQLPDOVIURPDKHUGDQGWKHDSSOLFDWLRQRIGHFLVLRQUXOHVWKDWFODVVLI\WKHKHUGDVSRVLWLYHRU QHJDWLYHEDVHGRQWKHWHVWUHVXOWVIURPLQGLYLGXDODQLPDOV¶:KHQDGLDJQRVWLFWHVWLVXVHGDV DKHUGWHVWLWLVWKHKHUGVHQVLWLYLW\+6HDQGVSHFLILFLW\+6SWKDWDUHRILQWHUHVW7KH +6HLVWKHSUREDELOLW\WKDWDSRVLWLYHHJVHURSRVLWLYHKHUG\LHOGVDSRVLWLYHKHUGWHVW UHVXOWDQGKHUGOHYHOVSHFLILFLW\+6SLVWKHSUREDELOLW\WKDWDQHJDWLYHHJVHURQHJDWLYH KHUG\LHOGVDQHJDWLYHKHUGWHVWUHVXOW0DUWLQHWDO$KHUGGLDJQRVLVFDQEHEDVHG RQDQXPEHURILQGLYLGXDOVDPSOHVRUYDULRXVSRROLQJVFKHPHVLQFOXGLQJ%70

+HUGFODVVLILFDWLRQLVDNH\FRPSRQHQWRIDQ\KHUGOHYHOFRQWUROSURJUDPPHKHQFHWKHUHLV DQHHGIRUKHUGOHYHOGLDJQRVWLFWRROVWKDWDFFXUDWHO\FODVVLI\WKHKHUGVLQDFRVWHIILFLHQW PDQQHU)RU%569DQG%&9DQWLERG\(/,6$VDUHUHDGLO\DYDLODEOHDQGFKHDSDQGHDV\WR XVHRQDODUJHVFDOHWKXVGHWHFWLRQRIDQWLERGLHVKDVEHHQXVHGWRFODVVLI\KHUGV2KOVRQHW DOD.OHPHWDO:ROIIHWDO)RUERWKYLUXVHVVWXGLHVIURP6ZHGHQ

(42)

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

\RXQJHUWKDQVL[PRQWKVLVXVXDOO\DYRLGHGGXHWRXQZDQWHGLQWHUIHUHQFHRIPDWHUQDO DQWLERGLHV/DUVHQ

Bulktankmilktesting

$VSHFLDOFDVHRIKHUGWHVWLQJZKHUHDOOODFWDWLQJFRZVDUHLQFOXGHGLQWKHSRROHGVDPSOHLV

%70WHVWLQJ%70WHVWLQJLVFRQYHQLHQWIRUVDPSOLQJDODUJHQXPEHURIKHUGVDQGLV HFRQRPLFDODVRQO\DVLQJOHVDPSOHLVUHTXLUHGWRFODVVLI\WKHKHUG,WKDVEHHQXVHGLQ VHYHUDOREVHUYDWLRQDOVWXGLHVDQGVXUYHLOODQFHDQGFRQWUROSURJUDPPHV/LQGEHUJDQG

$OHQLXV1XRWLRHWDO/¡NHQDQG1\EHUJcJUHQHWDO)RU%569 DQG%&9WKHEXONWDQNPLONFDQEHDQWLERG\SRVLWLYHIRUDORQJWLPHSRVVLEO\PDQ\\HDUV DIWHUYLUXVKDVFLUFXODWHGLQWKHKHUG$OHQLXVHWDO.OHPHWDOE$SRVLWLYH

%70DQWLERG\WHVWGRHVQRWHTXDOKHUGLPPXQLW\$VDQWLERG\SURGXFLQJFRZVFDQEHUH LQIHFWHGGHWHFWLRQRIDQWLERGLHVLQ%70VKRXOGQRWEHXVHGIRULQIHUHQFHDERXWWKHOHYHORI KHUGSURWHFWLRQ$OWRJHWKHUWKHLQIHUHQFHWKDWFDQEHPDGHIURPDSRVLWLYH%70WHVWLV OLPLWHGIRUWKHLQGLYLGXDOKHUGDQGIROORZXSWHVWLQJRISULPLSDURXVFRZVRU\RXQJVWRFN FDQEHXVHGIRUDPRUHXSWRGDWHKHUGGLDJQRVLV$QHODERUDWLRQRIWKHLQWHUSUHWDWLRQRI

%70WHVWVIRU%569DQG%&9LVSUHVHQWHGLQWKHGLVFXVVLRQ Probabilityoffreedomattheherdlevel

:KHQXVLQJDGLDJQRVWLFWHVWIRUGHFLVLRQPDNLQJDWWKHLQGLYLGXDODQLPDOOHYHOWHVWUHVXOWV DUHFRPPRQO\LQWHJUDWHGZLWKSULRUNQRZOHGJHDERXWKRZFRPPRQWKHGLVHDVHLV

DQDPQHVWLFLQIRUPDWLRQFOLQLFDOVLJQVDQGRWKHUIDFWRUVWKDWPLJKWLQIOXHQFHWKHSUREDELOLW\

RIGLVHDVH9HWHULQDU\SUDFWLWLRQHUVGRWKLVHLWKHULQWXLWLYHO\RULQDPRUHTXDQWLWDWLYH PDQQHUIRULQVWDQFHE\FDOFXODWLQJSUHGLFWLYHYDOXHV7KLVFDQDOVREHGRQHIRUKHUGWHVWV DQGWKHWUXVWRQHKDVLQDQHJDWLYHWHVWUHVXOWFDQEHTXDQWLILHGE\WKH139$VPHQWLRQHG WKH139GHSHQGVRQWKHDFFXUDF\RIWKHWHVWDQGWKHSULRUSUREDELOLW\RISRVLWLYLW\ZKLFK

(43)

IRUKHUGWHVWVLVWKHKHUGSUHYDOHQFHLQWKHSRSXODWLRQ+RZHYHUKHUGWHVWLQJLVRIWHQXVHGLQ VXUYHLOODQFHRUV\VWHPDWLFFRQWURO+HUHLWPLJKWEHXVHIXOWRDOVRDFFRXQWIRUKRZROGWKH WHVWUHVXOWLV,WLVLQWXLWLYHO\REYLRXVWKDWRXUFRQILGHQFHLQDQHJDWLYHWHVWGHFUHDVHVZLWK WKHWLPHHODSVHGVLQFHVDPSOLQJDVORQJDVWKHUHLVDULVNRIUHLQWURGXFWLRQRIYLUXV,QWKH

%569%&9FRQWUROSURJUDPPHDQHJDWLYHWHVWUHVXOWLVYDOLGIRURQH\HDUEHIRUHUHWHVWLQJ LVUHTXLUHGEXWEHFDXVHYLUXVLVFRQWLQXRXVO\FLUFXODWLQJLQWKHSRSXODWLRQWKHDVVXPSWLRQ RIDORQJODVWLQJQHJDWLYHVWDWXVLVTXHVWLRQDEOH)XUWKHUPRUHWKHUHDUHOLNHO\GLIIHUHQFHVLQ WKHULVNRILQWURGXFWLRQEHWZHHQGLIIHUHQWKHUGW\SHVHYHQIRUKHUGVZLWKHTXDOVWDUWLQJ SRLQWVLHDQHJDWLYHWHVW7KHUHIRUHWKHGHFUHDVHLQRQH¶VFRQILGHQFHLQDQHJDWLYHVWDWXV RYHUWLPHVKRXOGUHIOHFWWKHKHUG¶VNQRZQULVNIDFWRUVIRUYLUXVLQWURGXFWLRQ)RULQVWDQFH SXUFKDVHRIOLYHVWRFNVKRXOGHQWDLODGHFUHDVHGSUREDELOLW\RIIUHHGRPFRQWLQXHG VHURQHJDWLYLW\FRPSDUHGWRQRSXUFKDVHV

(VWLPDWLRQVRISUREDELOLW\RIIUHHGRPDUHFRPPRQO\SHUIRUPHGWRGRFXPHQWIUHHGRPIURP GLVHDVHDWDQDWLRQDOOHYHODVWKLVLVRIWHQQHFHVVDU\IRULQWHUQDWLRQDOWUDGHSXUSRVHV$OEDQ HWDO0XUSK\HWDO)U|VVOLQJHWDO+RZHYHUDIHZUHFHQWVWXGLHVKDYH XVHGWKHVDPHPHWKRGRORJ\ZLWKDQLQFUHDVHGIRFXVDWWKHKHUGOHYHO0RUHHWDO 9HOGKXLVHWDOcJUHQHWDO&DOFXODWLRQVRISUREDELOLW\RIIUHHGRPFDQEH XWLOL]HGDVDTXDQWLWDWLYHDSSURDFKWRHVWLPDWHWKHGHFUHDVHLQFRQILGHQFHRIDKHUG¶V QHJDWLYHVWDWXVRYHUWLPH,QWKHFRQWURORI%569DQG%&9WKHSUREDELOLW\WKDWDKHUGLV DQWLERG\QHJDWLYHRYHUWLPHFRXOGEHXVHIXOIRUFODVVLI\LQJKHUGVLQWRGLIIHUHQWULVN FDWHJRULHVZKLFKLQWXUQFRXOGEHXVHGIRUULVNEDVHGVDPSOLQJRUDVDULVNDVVHVVPHQWWRRO LQWKHRUJDQL]DWLRQRIDQLPDOWUDGH5HGXFHGFRVWVDQGIDVWHUSURJUHVVRIWKHFRQWURO SURJUDPPHZRXOGEHWKHGHVLUHGUHVXOW+RZLQWHJUDWLRQRIKHUGOHYHOGDWDFDQEHXVHGLQ

%569DQGRU%&9VXUYHLOODQFHDQGFRQWUROLVQRW\HWNQRZQ

Knowledgegaps

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

(44)

SUXGHQWXVHRIDQWLELRWLFVHQGRUVHGE\PRVWFRXQWULHV5HGXFLQJWKHFRQVHTXHQFHVRI GLVHDVHVFDXVHGE\WKHVHYLUXVHVE\SUHYHQWLQJLQWURGXFWLRQWRKHUGVFRXOGEHWKHNH\WRD PRUHVXVWDLQDEOHFRQWUROVWUDWHJ\%XWKRZFDQWUDQVPLVVLRQEHWZHHQKHUGVEHSUHYHQWHG"

:KDWLVWKHUHODWLYHLPSRUWDQFHRIGLIIHUHQWWUDQVPLVVLRQURXWHV":KDWDUHWKHULVNIDFWRUV IRUYLUXVLQWURGXFWLRQ"$QLGHQWLILFDWLRQRIULVNIDFWRUVIRUYLUXVLQWURGXFWLRQXQGHU 1RUZHJLDQFRQGLWLRQVKDGVWLOOQRWEHHQSHUIRUPHGDWWKHVWDUWRIWKLVSURMHFWDQGZDV LPSRUWDQWWRSURYLGHNH\LQIRUPDWLRQLQWKHGHVLJQRIFRQWUROVWUDWHJLHV7KLVOHGWRWKH IROORZLQJUHVHDUFKTXHVWLRQWREHDQVZHUHGLQWKLV3K'SURMHFW

x :KDWDUHWKHULVNIDFWRUVIRUDSRVLWLYHKHUGVWDWXVIRU%569DQG%&9EDVHGRQ GHWHFWLRQRIDQWLERGLHVLQ%70"

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

x :KDWLVWKHVSDWLDOGLVWULEXWLRQRI%569DQG%&9SRVLWLYHKHUGVEDVHGRQ GHWHFWLRQRIDQWLERGLHVLQ%70LQDUHJLRQLQZHVWHUQ1RUZD\"

6LPLODUWRULVNIDFWRUVWXGLHVPRVWVWXGLHVRQWKHFRQVHTXHQFHVRIGLVHDVHDUHSHUIRUPHGDW WKHLQGLYLGXDOOHYHO4XDQWLI\LQJWKHWRWDOFRVWRIWKHVHLQIHFWLRQVDWWKHKHUGOHYHOQRWWR PHQWLRQWKHQDWLRQDOOHYHOLVFRPSOH[7KHGLIIHUHQWFOLQLFDOPDQLIHVWDWLRQV%5'FDOI GLDUUKRHDDQGZLQWHUG\VHQWHU\DOOKDYHGLIIHUHQWLPSDFW7KHFRQVHTXHQFHVFDQIXUWKHUPRUH EHGLYLGHGLQWRHIIHFWVRQDQLPDOKHDOWKDQGZHOIDUHHIIHFWVRQDQWLELRWLFXVDJHDQGHIIHFWV RQSURGXFWLRQHJUHSURGXFWLYHSHUIRUPDQFHJURZWKUDWHDQGPLONSURGXFWLRQ7KHUHIRUHD GHFRPSRVLWLRQRIWKHSUREOHPLVQHFHVVDU\)RUZLQWHUG\VHQWHU\RQO\DIHZVWXGLHVDLPLQJ WRTXDQWLI\WKHDVVRFLDWHGGURSLQPLONSURGXFWLRQH[LVWDWWKHKHUGOHYHODQGWKHVHLQFOXGH RQO\DIHZKHUGV'XUKDPHWDO-DFWHOHWDO%HFDXVHDKHUGRIWHQFRQVLVWVRI FRZVZLWKGLIIHULQJVXVFHSWLELOLW\WRGLVHDVHDQGWKHVHYHULW\RILQIHFWLRQYDULHVLWLV SUREOHPDWLFWRGUDZLQIHUHQFHDWWKHKHUGOHYHOIURPVWXGLHVSHUIRUPHGDWWKHFRZOHYHO7KH LPSDFWDWWKHKHUGOHYHOLVRIXWPRVWLQWHUHVWIRUWKHIDUPHUZKRVHPDLQFRQFHUQLVWKHHIIHFW

(45)

RQQHWLQFRPH)XUWKHUPRUHDTXDQWLILFDWLRQRIPLONSURGXFWLRQORVVLVQHHGHGDVLQSXWLQ WKHFRVW±EHQHILWDQDO\VLVWKDWLVDQHVVHQWLDOVWHSLQWKHSODQQLQJRIDFRQWUROSURJUDPPH 7KLVOHGWRWKHIROORZLQJUHVHDUFKTXHVWLRQ

x :KDWLVWKHHIIHFWRIZLQWHUG\VHQWHU\RQKHUGOHYHOPLONSURGXFWLRQ"

+HUGOHYHOFRQWUROSURJUDPPHVJHQHUDOO\UHTXLUHFODVVLILFDWLRQRIKHUGVZLWKUHVSHFWWRWKH ULVNRIKDUERXULQJLQIHFWLRQ,GHQWLI\LQJDFRVWHIILFLHQWSURFHGXUHZLWKDFFHSWDEOHDFFXUDF\

LVQHFHVVDU\)RU%569DQG%&9VRPHSUDFWLFDOTXHVWLRQVDURVH6KRXOG%70VDPSOHVRU LQGLYLGXDOVDPSOHVEHXVHG",IXVLQJLQGLYLGXDOPLONRUVHUXPVDPSOHVFDQWKH\EHSRROHG DQGKRZPDQ\VDPSOHVVKRXOGEHLQFOXGHGLQWKHSRRO"+RZDUHDQWLERGLHVLQ%70 DVVRFLDWHGWRWKHZLWKLQKHUGSUHYDOHQFH"7KHRZQHUVRIWKHFRQWUROSURJUDPPHKDGGHFLGHG WRLQLWLDWHV\VWHPDWLFFRQWUROE\VFUHHQLQJDOOGDLU\KHUGVXVLQJDQHZPXOWLSOH[

LPPXQRDVVD\RQ%707KHGLDJQRVWLFDFFXUDF\IRUWKLVDSSOLFDWLRQZHUHWKHUHIRUHRI SDUWLFXODULQWHUHVWDQGWKLVOHGWRWKHIROORZLQJUHVHDUFKTXHVWLRQ

x :KDWLVWKHGLDJQRVWLFWHVWVHQVLWLYLW\DQGVSHFLILFLW\RIWKH%&9%569PXOWLSOH[

WHVWIRUGHWHFWLRQRIDQWLERGLHVLQ%70"

%HFDXVHRIWKHHQGHPLFRFFXUUHQFHRI%569DQG%&9WKHUHLVDFRQWLQXRXVULVNRI UHLQWURGXFWLRQRIYLUXVWRDOOKHUGV7KHXQFHUWDLQW\RIDKHUG¶VVWDWXVDWDJLYHQWLPH WKHUHIRUHGHSHQGVQRWRQO\RQWKHDFFXUDF\RIWKHWHVWEXWDOVRWKHULVNRIYLUXVLQWURGXFWLRQ )RUDOOKHUGVWKHFRQILGHQFHLQDGLVHDVHIUHHVWDWXVZLOOGHFUHDVHRYHUWLPHVLQFHWKHODVW QHJDWLYHWHVWKRZHYHUWKHULVNOLNHO\GLIIHUVEHWZHHQKHUGW\SHV$YDLODEOHGDWDRQWHVW DFFXUDF\KHUGORFDWLRQDQGPRYHPHQWVPLJKWEHXVHIXOWREHWWHUSUHGLFWWKHSUREDELOLW\RI DQDQWLERG\QHJDWLYHVWDWXVRYHUWLPH7KLVOHGWRWKHUHVHDUFKTXHVWLRQ

x +RZFDQWHVWVHQVLWLYLW\ORFDWLRQDQGDQLPDOPRYHPHQWVEHXVHGWRSUHGLFWWKHKHUG OHYHOSUREDELOLW\RIIUHHGRPIURPDQWLERGLHVRYHUWLPH"

(46)

(47)

$LPVRIWKH6WXG\

7KHRYHUDOODLPRIWKLVWKHVLVZDVWRSURYLGHNQRZOHGJHRIWKHHSLGHPLRORJ\RI%569DQG

%&9LQWKH1RUZHJLDQFDWWOHSRSXODWLRQ7RDQVZHUWKHTXHVWLRQVLGHQWLILHGXQGHU NQRZOHGJHJDSVWKHVSHFLILFDLPVRIWKHWKHVLVZHUHWR

,GHQWLI\ULVNIDFWRUVIRUDQGVSDWLDOGLVWULEXWLRQRI%569DQG%&9SRVLWLYHKHUGVEDVHG RQGHWHFWLRQRIDQWLERGLHVLQEXONWDQNPLON

4XDQWLI\WKHHIIHFWRIZLQWHUG\VHQWHU\RQKHUGOHYHOPLONSURGXFWLRQ

9DOLGDWHWKHQHZPXOWLSOH[LPPXQRDVVD\XVHGLQWKH1RUZHJLDQ%569DQG%&9 FRQWUROSURJUDPPH

'HYHORSDIUDPHZRUNIRUHVWLPDWLRQRIWKHKHUGOHYHOSUREDELOLW\RIIUHHGRPIURP

%569DQG%&9DQWLERGLHVRYHUWLPH

(48)
(49)

0DWHULDOVDQGPHWKRGV

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

$SSHQGL[,WR,90HWKRGRORJLFDOFRQVLGHUDWLRQVDUHDGGUHVVHGLQWKHGLVFXVVLRQ

Studysamplesandregisterdata

7KHVWXG\XQLWZDVWKHKHUGLQDOOIRXUSDSHUVLQWKHSUHVHQWWKHVLV1RQHRIWKHVWXGLHVZHUH QDWLRQDOEXWZHUHFRQGXFWHGLQGLIIHUHQWUHJLRQVRIWKHFRXQWU\$EULHIGHVFULSWLRQRIWKH VWXG\VDPSOHRIHDFKSDSHUIROORZV

3DSHU,ZDVDFURVVVHFWLRQDOVWXG\LQZKLFKWKHVWXG\VDPSOHFRQVLVWHGRIGDLU\KHUGVLQ WZRFRXQWLHVLQZHVWHUQ1RUZD\QDPHO\0¡UHRJ5RPVGDODQG6RJQRJ)MRUGDQH2IWKH GDLU\KHUGVWKDWVKLSSHGPLONLQWKHVWXG\UHJLRQDWWKHWLPHRIVDPSOLQJ GHOLYHUHGD%70VDPSOHDQGZHUHLQFOXGHGLQWKHVWXG\1RWHWKDWGLIIHUHQWVXEVHWVRIKHUGV ZHUHLQFOXGHGLQGLIIHUHQWSDUWVRIWKHDQDO\VLVVHH3DSHU,IRUGHWDLOV

3DSHU,,ZDVEDVHGRQUHSRUWVIURPYHWHULQDULDQVDQGSURGXFHUVRIRXWEUHDNVRIZLQWHU G\VHQWHU\WRDµKRWOLQH¶RSHUDWHGE\WKHDGYLVRU\VHUYLFHRIWKHODUJHVWGDLU\FRPSDQ\LQ 1RUZD\7,1(6$)URPWKHWKRI1RYHPEHUWRWKHWKRI0DUFKKHUG RXWEUHDNVZHUHUHSRUWHGIURPFRXQWLHVLQHDVWHUQ1RUZD\$UHWURVSHFWLYHFRKRUWVWXG\

ZDVFRQGXFWHGDQGKHUGVZLWKDUHSRUWHGRXWEUHDNZHUHFRQVLGHUHGH[SRVHG:'DQG ZHUHFRPSDUHGWRQRQH[SRVHGKHUGV:'FRQVLVWLQJRIDOORWKHUKHUGVWKDWZHUH PHPEHUVRIWKH1RUZHJLDQGDLU\KHUGUHFRUGLQJV\VWHP1'+56ORFDWHGLQWKHVDPHDUHD

$IWHUGDWDFOHDQLQJVWXG\KHUGV:'DQG:'UHPDLQHGIRUDQDO\VLVRI PLONSURGXFWLRQDQG:'DQG:'KHUGVIRUDQDO\VLVRIPLON

FRPSRVLWLRQ

,Q3DSHU,,,WKHVWXG\VDPSOHZDVVHOHFWHGIURPKHUGVWKDWVXEPLWWHGDEXONWDQNPLON VDPSOHIRUWKHQDWLRQDOVFUHHQLQJLQ$GLDJQRVWLFWHVWHYDOXDWLRQZDVSHUIRUPHGXVLQJ WZRWHVWVLQWZRSRSXODWLRQVZLWKDQH[SHFWHGGLIIHUHQFHLQSUHYDOHQFHDQGEDVHGRQWKLV

(50)

DVVXPSWLRQVDPSOHVIURPWZRGLIIHUHQWFRXQWLHVZHUHUDQGRPO\VHOHFWHG$VDUHVXOWRI 3DSHU,ZHNQHZWKDWSUHYDOHQFHLQ6RJQRJ)MRUGDQHLQZHVWHUQ1RUZD\ZDVOLNHO\WREH ORZDQGZHWKHUHIRUHVHOHFWHGKHUGVIURPWKLVFRXQW\DQGKHUGVIURP2SSODQGLQ HDVWHUQ1RUZD\ZKHUHSUHYDOHQFHZDVH[SHFWHGWREHKLJKHUEDVHGRQILHOGH[SHULHQFHDQG WKHNQRZOHGJHRIRXWEUHDNVDVGHVFULEHGLQ3DSHU,,

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µRXWEUHDNUHJLRQ¶RI3DSHU,,

)LJXUH9HQQGLDJUDPLOOXVWUDWLQJWKHUHODWLRQVKLSEHWZHHQWKHVWXG\VDPSOHVLQ3DSHUV,,,,DQG ,9

(51)

Registerdata

7KHUHDUHVHYHUDOQDWLRQDOGDWDEDVHVIRUOLYHVWRFNLQ1RUZD\5HJLVWHUGDWDZHUHXVHGLQDOO IRXUVWXGLHVLQFOXGHGLQWKLVWKHVLVDQGDEULHIGHVFULSWLRQRIWKHVHUHJLVWULHVIROORZV Norwegiandairyherdrecordingsystem

7KH1RUZHJLDQGDLU\KHUGUHFRUGLQJV\VWHPLVDGDWDEDVHRZQHGE\7,1(6$0HPEHUVKLS LVYROXQWDU\DQGLQWKH1'+56FRQWDLQHGUHFRUGVIURPRIDOO1RUZHJLDQGDLU\

KHUGV7,1($GYLVRU\6HUYLFH7KH1'+56LVDUHODWLRQDOGDWDEDVHFRQWDLQLQJ WDEOHVRQKHUGFKDUDFWHULVWLFVKHDOWKHYHQWVGLVHDVHDQGWUHDWPHQWODFWDWLRQGDWD SURGXFWLRQDQGPLONFRPSRVLWLRQGDWDRQFDOYLQJDQGUHSURGXFWLYHSHUIRUPDQFHDQG PRUH'DWDRQKHDOWKHYHQWVDUHUHFRUGHGRQIDUPE\WKHYHWHULQDULDQXVLQJLQGLYLGXDOFRZ KHDOWKFDUGV&+&DQGDUHODWHUWUDQVIHUUHGWRWKH1'+56'DWDIURPWKH1'+56KDYH EHHQIUHTXHQWO\XVHGIRUUHVHDUFKSXUSRVHV1RUVWU|PHWDO*XOOLNVHQHWDOD .OHPHWDO)RUVWXGLHVLQFOXGHGLQWKLVWKHVLV1'+56UHFRUGVZHUHUHWULHYHGIRU YDULRXVKHUGOHYHOYDULDEOHVHJKHUGVL]HPLONLQJV\VWHPDQGSURGXFWLRQW\SHLQ3DSHU, 3DSHU,,DQG3DSHU,9VHHWKHUHVSHFWLYHSDSHUVIRUGHWDLOV

Milkshipmentdata

0LONVKLSPHQWGDWDUHIHUVWRWKHURXWLQHO\UHFRUGHGPLONSURGXFWLRQGDWDFROOHFWHGDWHDFK EXONWDQNPLONVKLSPHQW0LONVKLSPHQWGDWDDUHUDUHO\XVHGIRUUHVHDUFKSXUSRVHV$Q H[WUDFWLRQIURPWKHODUJHVWPLONVKLSPHQWGDWDEDVHRZQHGE\7,1(6$ZDVXVHGLQ3DSHU ,,7KHUHWULHYHGUHFRUGVFRQWDLQHGWKHIROORZLQJYDULDEOHVYROXPHRIPLONVKLSSHGVRPDWLF FHOOFRXQWIUHH]LQJSRLQWDQGPLONFRPSRQHQWVIDWSURWHLQODFWRVHXUHDDQGIUHHIDWW\

DFLGV

Norwegianlivestockregister

7KH1RUZHJLDQOLYHVWRFNUHJLVWHULVPDQDJHGE\WKHIRRGVDIHW\DXWKRULWLHV7KHPDLQ SXUSRVHRIWKLVUHJLVWHULVWRHQDEOHWUDFHDELOLW\DQGWUDFNLQJRIDOOOLYHVWRFNLQ1RUZD\

7KHUHDUHWKUHHHYHQWVWKDWWULJJHUDPDQGDWRU\UHSRUWIRUDOOIDUPHUVRZQLQJFDWWOHELUWKV GHDWKVDQGPRYHPHQWV)RUVNULIWRPVSRUEDUKHWRJPHUNLQJDYVWRUIH%LUWKVDUH UHJLVWHUHGLQFRQMXQFWLRQZLWKWKHHDUWDJJLQJRIQHZERUQFDOYHVDQGWKHUHSRUWLQFOXGHV WKHDQLPDOLGHQWLILFDWLRQKHUGLGHQWLILFDWLRQGDWHRIELUWKVH[EUHHGDQGLGHQWLILFDWLRQRI WKHPRWKHU5HFRUGHGDQLPDOPRYHPHQWVLQFOXGHSXUFKDVHGDQLPDOVVROGDQLPDOVDQLPDOV VHQWWRVODXJKWHUDQGRWKHUUHDVRQVIRUPRYHPHQWV'DWDRQDQLPDOPRYHPHQWVKDYHEHHQ XVHGWRDOLPLWHGH[WHQWIRUUHVHDUFKLQ1RUZD\EXWWKHLUXVHKDVEHHQH[SORUHGLQRWKHU

Referanser

RELATERTE DOKUMENTER

A main finding of the present study is the clear effect on the growth and concentrate feed conversion ratio, and that the effect is present in not only the medically treated

Recent behavioral response studies have investigated how expo- sure to naval sonar signals affects the natural dive behavior in a range of species: Blainville’s beaked

The most pronounced is elastic scattering at the excitation wavelength (294 nm), but also remnants of 355 nm laser light (see Section 3.1), as well as Raman-scattering by

Genuine ballast water from Havila Subsea and sea water from Norway and Singapore spiked with 1 and 10 CFU/100 ml of V. cholerae VC 021 cells detected positive for V. cholerae

This report presents the analyses of the data from the NATO HFM RTG – 138 Leader and team adaptability in multinational coalitions (LTAMC) experiments with a focus on

The second part of the investigation was to analyse sediment and water samples for arsenic, chemical warfare agents and some of their decomposition products.. It was of interest

On the other hand, the protection of civilians must also aim to provide the population with sustainable security through efforts such as disarmament, institution-building and

Dorfman et al., “Prevalence of congenital cytomegalovirus infection and associated risk of in utero human immunodeficiency virus (HIV) acquisition in a high-HIV prevalence