Public Health Research Resulting from One of the World's Largest Outbreaks Caused by Entero-Hemorrhagic Escherichia coli in Germany 2011: A Review.

Decembe 2017 | Volume 5 | A icle 3321 Re iew published: 11 Decembe 2017 doi: 10.3389/ pubh.2017.00332 F on ie s in Public Heal h | www. on ie sin.o g Edi ed by: Alex W. F ied ich, Uni e si y Medical Cen e G oningen, Ne he lands Re iewed by: Zisis Kozlakidis, Uni e si y College London, Uni ed Kingdom Ana A onso, Uni e si y o São Paulo, B azil Robin Koeck, Klinikum Oldenbu g, Ge many *Co espondence: Gé a d K ause [email p o ec ed] Special y sec ion: This a icle was submi ed o In ec ious Diseases – Su eillance, P e en ion and T ea men , a sec ion o he jou nal F on ie s in Public Heal h Recei ed: 13Ma ch2017 Accep ed: 23No embe 2017 Published: 11Decembe 2017 Ci a ion: Köcke lingE, Ka aschL, Schwei ze A, RazumO and K auseG (2017) Public Heal h Resea ch Resul ing om One o he Wo ld’s La ges Ou b eaks Caused by En e o-Hemo hagic Esche ichia coli in Ge many 2011: A Re iew. F on . Public Heal h 5:332. doi: 10.3389/ pubh.2017.00332 Public Heal h Resea ch Resul ing om One o he wo ld’s La ges Ou b eaks Caused by en e o- Hemo hagic Esche ichia coli in Ge many 2011: A Re iew Elena Köcke ling1,2, Lau a Ka asch1, Apa na Schwei ze 3, Oli e Razum1 and Gé a d K ause 3,4* 1 Depa men o Epidemiology and In e na ional Public Heal h, Biele eld Uni e si y, Biele eld, Ge many, 2 Depa men Müns e , Ins i u e o Rehabili a ion Resea ch I R, Müns e , Ge many, 3 Depa men o Epidemiology, Helmhol z Cen e o In ec ion Resea ch, B aunschweig, Ge many, 4 Hanno e Medical School, Hanno e , Ge many In 2011, Ge many expe ienced one o he la ges ou b eaks o en e o-hemo hagic Esche ichia coli (EHEC) e e epo ed. Fou yea s he ea e , we sys ema ically sea ched o scien i ic publica ions in PubMed and MEDPILOT ela ing o his ou b eak in o de o assess he pa e n o espec i e esea ch ac i i ies and o assess he main indings and ecommenda ions in he ield o public heal h. Following PRISMA guidelines, we selec ed 133 publica ions, hal o which we e published wi hin 17mon hs a e ou b eak onse . Clinical medicine was co e ed by 71, mic obiology by 60, epidemiology by 46, ou b eak epo ing by 11, and ood sa e y by 9 pape s. Those on he las h ee opics d ew con- clusions on me hods in su eillance, diagnosis, and ou b eak in es iga ion, on esou ces in public heal h, as well as on in e -agency collabo a ion, and public communica ion. Al hough he ou b eak p ima ily a ec ed Ge many, mos publica ions we e conduc ed by mul ina ional coope a ions. Ou indings documen how soon and in which ields esea ch was conduc ed wi h espec o his ou b eak. Keywo ds: disease ou b eaks, Shiga- oxigenic/en e o-hemo hagic Esche ichia coli, hemoly ic u emic synd ome, Ge many, esea ch iNTRODUCTiON In sp ing 2011, Ge many expe ienced one o he la ges ou b eaks o en e o-hemo hagic Esche ichia coli (EHEC) e e epo ed, almos 3,000 people ell ill wi h acu e gas oen e i is, 855 o hem de el- oped hemoly ic u emic synd ome (HUS). In o al, 55 people died due o he in ec ion (1). The ou b eak a ec ed p ima ily i e s a es in No he n Ge many bu also isi o s om 15 o he coun ies and was linked o a smalle subsequen ou b eak in F ance (2). In con as o wha would ha e been expec ed om p e ious ou b eak epo s and su eillance da a, his ou b eak was cha ac e ized by high case a ali y, a highe p opo ion o HUS esul ing om he EHEC in ec ion (1.1 cases pe 100,000 inhabi an s in 2011 e sus an a e age o 0.1 cases pe 100,000 inhabi an s yea ly, in 2001– 2010), a p edominance o adul pa ien s (3.10 HUS esul ing om EHEC in ec ion and 15.5 EHEC cases wi hou HUS pe 100,000 inhabi an s in 2011 e sus less han 0.0 HUS esul ing om EHEC 2 Köcke ling e al. Resea ch on a La ge EHEC Ou b eak F on ie s in Public Heal h | www. on ie sin.o g Decembe 2017 | Volume 5 | A icle 332 in ec ion and EHEC cases wi hou HUS pe 100,000 inhabi an s yea ly, in 2001–2010) and a s onge p edominance o emale pa ien s (HUS esul ing om EHEC in ec ion: 68% emale pa ien s, EHEC wi hou HUS: 58% emale pa ien s) (1). The ou - b eak las ed 58days, om May 8 o July 5, 2011. On May 25, 2011, se en days a e he i s no i ica ion o he ou b eak, he causa i e pa hogen was iden i ied o be Shiga oxin (Ve ocy o oxin)- p oducing Esche ichia coli O104:H4, a bac e ium wi h a no el i ulence p o ile in compa ison o s ains usually p e alen in Eu ope. F om May 20 o July 8, 2011, he Robe Koch Ins i u e (RKI), he Ge man ede al public heal h ins i u e, oge he wi h local and s a e heal h and ood sa e y agencies, conduc ed a o al o 13 epidemiological ield in es iga ions, using di e en s udy designs. Ini ial in es iga ions poin ed a le uce, aw oma oes, and cucumbe s as po en ial sou ces o he in ec ion. On June 10—3 weeks a e he i s no i ica ion o he ou b eak—epidemi- ological e idence suppo ed ha enug eek sp ou s, p oduced in Ge many om seeds impo ed om Egyp , we e he ehicle caus- ing he ou b eak (3). The ou b eak esul ed in massi e challenges o hospi als, public heal h and ood sa e y agencies, and in ense in e na ional media co e age. The e we e signi ican economic epe cussions on he ag icul u e indus y o a ious Eu opean coun ies, pa icula ly Spain, a e he Hambu g sec e a y o heal h p ema u ely p esen ed an uncon i med labo a o y esul e oneously implica ing cucumbe impo ed om Spain as he po en ial sou ce o in ec ion (3). This, in u n, had in e na ional poli ical and economic consequences, including a empo a y emba go o ood p oduc s expo ed om he Eu opean Union. Al hough epidemiological s udies and in es iga ions suppo ed ha enug eek sp ou s we e he ehicle, a ious a emp s o de ec he pa hogen in sp ou s consumed by known pa ien s had ailed. In ea ly e alua ions o he ou b eak, K ause e al. (3), S a k e al. (4), and Beu in and Ma in (5) highligh ed he uniqueness and size o he ou b eak. They s ongly ecommended e alua ing he expe iences wi h he ou b eak as bes as possible in o de o be e p e en and con ol compa able si ua ions in he u u e. In his wo k, we sys ema ically e iewed he scien i ic li e a u e ela ed o his ou b eak 4yea s a e i s onse . The aim o he s udy was o ace he scien i ic p ocess in o de o assess o which ex en he di e en disciplines we e in ol ed, o iden i y he collabo a- ions es ablished, and o ind ou which public heal h- ela ed opics we e esea ched. The esul s o his wo k can help public heal h au ho i ies o be e unde s and how he scien i ic com- muni y wo ks unde he condi ions o a disease ou b eak. Wi h his knowledge, coo dina ion and collabo a ion be ween public heal h au ho i ies and scien is s can be acili a ed. This pape also encou ages scien is s om di e en disciplines o ake a b oade iew du ing ou b eak in es iga ions, and o con empla e he chal- lenges and po en ials o in e disciplina y collabo a ion. MATeRiALS AND MeTHODS Following he P e e ed Repo ing I ems o Sys ema ic e iews and Me a-Analyses (PRISMA) guidelines (6), we sea ched o li e a u e in PubMed and MEDPILOT using he sea ch e ms “EHEC” OR “O104:H4” OR “HUS” and hei ela ed Medical Subjec heading (MESH) “Shiga oxigenic Esche ichia coli” OR “hemoly ic-u emic synd ome” in combina ion wi h “Ge many” and i s MESH e m “Ge many” appea ing in i le, abs ac o key wo ds o a icles published be ween May 1, 2011 and Ap il 30, 2015. We did no apply any es ic ion ega ding he language o he publica ions. Since MEDPILOT does no allow e ospec i ely speci ying exac sea ch pe iods, we ini ially included publica ions om Janua y 2011 o Ap il 2015 and la e manually excluded hose published be ween Janua y 1 and Ap il 30, 2011. We also included any addi ional publica ions ha we e e e enced in e ie ed a icles and me ou inclusion c i e ia bu we e no lis ed in he wo da abases (Figu e1). We conduc ed a wo-s age sc eening o he e ie ed li e a u e. Fi s , i les and abs ac s we e sc eened. Second, eligibili y o inclusion in he e iew was assessed by ull- ex sc eening o a icles e ained a e he i s sc eening. Two e iewe s (EK and LK) independen ly sc eened he li e a u e in duplica e. In he case o disc epan o unce ain esul s whe e he wo e iewe s could no each consensus, a hi d e iewe (GK) was consul ed. Besides he o mal c i e ion o ime o publica ion, s udies had o mee he ollowing c i e ia o inclusion: hey had o be scien i ic a icles published in a publicly accessible jou nal, bu excluding wo k ha was ei he non-o iginal o no pee e iewed, such as go e nmen epo s, edi o ials, commen a ies, eplies, mee ing abs ac s, and dia ies (e.g., a icles e lec ing he cou se o he ou b eak in daily in e als om a pe sonal poin o iew). We also excluded all publica ions epo ing on o he ou b eaks o s ains, as well as publica ions on he ou b eak in ques ion bu no cons i u ing o iginal esea ch, such as ea men ecommenda- ions no based on esea ch ela ing o his ou b eak. We included a icles on cases o O104:H4 in ec ion ou side Ge many ela ed o his ou b eak. We hen assigned he a icles o one o mo e o he ollowing p e-de ined opics: Epidemiology, Food Sa e y, and Ou b eak Repo ing as Public Heal h opics and Medicine (including disease p og ession, non-mic obiological diagnosis and ea men ), and Mic obiology (including mic obiological diagnosis) as u he opics. Con en s o publica ions belonging o he opics medicine o mic obiology hough we e no analyzed, as his would be beyond he public heal h scope o his e iew. We also eco ded he coun ies o o igin o he au ho s’ ins i u- ions in he ca ego ies, “Ge many,” “non-Ge man coun ies,” and in e na ional collabo a ions in he ca ego y “Ge many and non-Ge man coun ies.” We assigned each a icle o one o mo e o he sub opics lis ed in Table1. Addi ionally, we assigned e e y a icle o one o he ollowing h ee ypes o publica ion: e iew, si ua ion epo , and o iginal esea ch. We di e en ia ed be ween e iews conduc ed o , o mo i a ed by, he ou b eak bu no p o- cessing da a on his ou b eak (oppo uni y e iews); and e iews sys ema ically p ocessing publica ions on his ou b eak (e alua- ion e iews). Si ua ion epo s comp ised ou b eak epo s ha we e p ima ily desc ip i e in na u e, while o iginal esea ch only included a icles ha epo ed analy ical s udy designs. Fo he summa ized analysis, si ua ion epo s and o iginal esea ch we e comp ised in he ca ego y “o he publica ions.” The pa e ns o espec i e esea ch ac i i ies, namely he publica ion la ency di - e en ia ed by opic and he opics di e en ia ed by coun ies o o igin o he au ho s and by publica ion ype, we e assessed o all included publica ions. Fo all publica ions ha belonged o he Public Heal h opics Epidemiology, Food Sa e y, and Ou b eak FiGURe 1 | Flow p ocess cha o li e a u e sea ch and selec ion. *Alloca ion o sub opics only o o he ypes o a icles and no o e iews. Mo e han one opic/ sub opic pe pape (sums highe han o als). 3 Köcke ling e al. Resea ch on a La ge EHEC Ou b eak F on ie s in Public Heal h | www. on ie sin.o g Decembe 2017 | Volume 5 | A icle 332 Repo ing, we ex ac ed he main indings and ecommenda ions using a da a ex ac ion o m de eloped o his e iew. ReSULTS By applying he sea ch c i e ia, we ound 346 publica ions in PubMed and 304 in MEDPILOT; 214 a icles (32.9%) we e duplica es, esul ing in a o al o 436 unique publica ions w i en in Chinese, Du ch, English, F ench, Ge man, Polish, Russian, Spanish, o Swedish. O hese, 255 publica ions we e excluded based on con en c i e ia, 47 o being edi o ials, commen a ies, eplies, dia ies, o mee ing abs ac s, and i e because o being submi ed o published be o e May 1, 2011, lea ing 129 (29.6%) a e ull- ex sc eening. We iden i ied an addi ional 11 publica- ions on sc u inizing e e ence lis s o eligible e iews, o which ou a icles ul illed ou eligibili y c i e ia. In o al, 133 eligible publica ions (published in Chinese, Du ch, English, Ge man, and Swedish language) we e included in he sys ema ic e iew (Figu e1; Table2). Fi y-one a icles we e published wi hin he i s yea a e onse o he ou b eak, 46 in he second yea , 19 in he hi d, and 17 in he ou h yea , wi h a peak o 19 publica ions in he las qua e o 2012 (Figu e2). In he i s yea a e onse o he ou b eak, 20 (24%) publica ions belonged o he ca ego y Epidemiology, anging be ween 17 (26%) and 4 (14%) in he ol- lowing yea s. Mos publica ions in he i s yea a e he ou b eak belonged o he opic Mic obiology (30 publica ions, 37%). The numbe o publica ions o his opic d opped o 16 (25%) in he second yea and o 8 (29%) in he hi d yea . In he i s as well as in he second yea a e he ou b eak, 24 publica ions appea ed wi hin he opic Medicine esul ing in 29 and 37%, espec i ely, ollowed by 14 publica ions (50%) in he hi d yea and 9 publica- ions (41%) in he ou h yea . As displayed in Figu e2, he opics TABLe 1 | De ini ions o opics and hei sub opics. Topics Con en o he opics Sub opics Con en o he sub opics Medicine – P ocedu es in medicine – Clinical ou comes, insigh s gained h ough au opsy – Long- e m ou comes, includes in o ma ion on shedding and seconda y ansmission – S a iona y and ambulan ou b eak managemen NA NA Mic obiology – Genome analysis – P ocedu es o genome analysis used o de eloped o diagnos ics wi h ega d o p ospec i e epidemics – Labo a o y in es iga ion o he i ulence ac o s and an ibio ic esis ance – De elopmen o accine NA NA Epidemiology – Cause s udy – Cases iden i ied ia he su eillance and o he sys ems – Used o newly de eloped me hods o p edic numbe s o new cases – Ou b eak- ela ed cases ou side Ge many – Managemen o he ou b eak on ede al and egional le el and in coope a ion wi h in ol ed ins i u ions Su eillance – Ge man su eillance and epo ing sys ems – Asymp oma ic cases and seconda y cases – Cha ac e is ics o he ou b eak Ou b eak in es iga ion – In es iga ion o he ou b eak sou ce – Me hods o ood ace back and o wa d used o in en ed a e wa d Ou b eak managemen – Ou b eak managemen , in o ma ion ans e Food Sa e y – Me hods used o newly de eloped o iden i y en e o-hemo hagic Esche ichia coli (EHEC) con amina ion o ood – En i onmen al in ol emen (was e wa e , d inking wa e , ba hing wa e , g ound, e c.) due o di ec o indi ec (e.g., ia ood p oduc ion chain) con ac o humans Iden i ica ion o EHEC in ood – De ec ion o EHEC in ood En i onmen al in ol emen – Wa e as he basis o ood p oduc ion – Animals as a ese oi Ou b eak Repo ing – In o ma ion passed on o (p o essional) public – Me hods o isk communica ion used du ing he ou b eak – Popula ion’s pe spec i e on in o ma ion co e age – Communica ion be ween expe s and gene al popula ion P o essional pe spec i e – In o ma ion eleased and hei con en - ela ed a angemen Lay pe spec i e – Scien i ic in es iga ion on how and wha in o ma ion has been eleased 4 Köcke ling e al. Resea ch on a La ge EHEC Ou b eak F on ie s in Public Heal h | www. on ie sin.o g Decembe 2017 | Volume 5 | A icle 332 Table 5. Wi hin he opic o Epidemiology, conclusions and ecommenda ions mainly add essed he ollowing issues: (1) au oma iza ion o disease no i ica ion and changes in no i- ica ion laws; (2) me hodological imp o emen s in su eillance; (3) pe sonnel esou ces in public heal h; (4) ac o s ela ed o seconda y cases; (5) no el ou b eak in es iga ion me hods; and (6) capaci y and collabo a ion be ween di e en agencies and ins i u ions. Wi hin he opic o Food Sa e y, conclusions and ecommenda ions add essed he issues o (1) sani a ion o was ewa e ; (2) sa e y o d inking wa e ; (3) me hods o de ec he pa hogens in ood/ om ood samples; and (4) hygienic handling o li es ock. Rega ding Ou b eak Repo ing, conclu- sions and ecommenda ions mainly add essed he ques ion o (1) iming o public in o ma ion; (2) de ail as well as cohe ence o communica ion; and (3) coo dina ion o isk communica ion be ween di e en agencies and indi iduals. DiSCUSSiON We ound a o al numbe o 133 o iginal publica ions di ec ly ela ed o one geog aphically and empo ally a he con ined ou b eak. Al hough majo publica ions appea ed wi hin days and weeks o he onse o he ou b eak (11), he median la ency o publica ions was 17mon hs wi h 17 pape s (13% o he o al) appea ing as la e as in he ou h yea . This indica es ha much o he esea ch conduc ed wi h espec o his ou b eak wen beyond immedia e ou b eak in es iga ions. I add essed esea ch ques ions ha a e o ele ance o ood sa e y, su eillance, and Food Sa e y and Ou b eak Repo ing we e he leas equen ly co e ed opics h oughou he 4-yea ime pe iod anging om 6 o 0% o Food Sa e y and 4 o 8% o Ou b eak Repo ing. Hal o he 133 a icles we e published wi hin 17mon hs a e he onse o he ou b eak ( e iews: median 16mon hs; o he publica ion ypes: median 17mon hs). As Figu e2 e eals, we did no ind any u he li e a u e ela ed o he analyzed opics Ou b eak Repo ing, Food Sa e y, o Epidemiology a e he hi d qua e o 2014. Publica ion la ency o all o he ypes o publica ions was lowes o he opic o Food Sa e y (median o 9mon hs) and highes o he opic o Ou b eak Repo ing (median 20mon hs). Fo e iews, publica ion la ency was 11mon hs in he opic o Mic obiology and 18mon hs in he opic o Medicine (Table3). The ex en o collabo a ion was de e mined wi hin he di e en publica ion ypes and opics: In e na ional collabo a ion could be ound in 3/20 e iews and in 28/113 o he publica ion ypes. Mos e iew a icles we e by ins i u ions om non-Ge man coun ies only (14/20), while o he publica ion ypes we e mos ly by Ge man ins i u ions only (57/113). In o al, in e na- ional collabo a ions we e seen in 31/133 a icles. Mos a icles in he opic Medicine (42/71=59%) we e exclusi ely au ho ed by Ge man ins i u ions, whe eas a icles on Mic obiology we e mos ly au ho ed by non-Ge man au ho s (32/60=53%). In he opic o Epidemiology he p edominan au ho ship se up was Ge man and in e na ional collabo a ion (19/46=41%) (Table4). A o al o 39 publica ions belonged o one o mo e o he opics Epidemiology, Food Sa e y, o Ou b eak Repo ing (Table 4). Thei main indings and ecommenda ions a e displayed in TABLe 2 | Publica ions included in he sys ema ic e iew (n=133). Re e ence Assigned opics Medicine Mic obiology epidemiology Food sa e y Ou b eak epo ing (7) X (8) X (9) X (10) X (11) X X X (12) X (13) X X (14) X (15) X (16) X (5) X X X X (17) X (18) X (19) X X X (20) X X X (21) X X X (22) X (23) X (24) X X (25) X X (26) X (27) X (28) X (29) X (30) X (31) X (32) X (33) X X (34) X X (35) X X (36) X (37) X X X (38) X X (39) X (40) X X (41) X X (42) X X X (43) X (44) X (45) X (46) X X (47) X (48) X (49) X X (50) X (51) X X (52) X X X (53) X (54) X (55) X (56) X (57) X X (58) X X (59) X X (60) X (61) X (62) X X (63) X (64) X X (65) X (66) X Re e ence Assigned opics Medicine Mic obiology epidemiology Food sa e y Ou b eak epo ing (3) X X (67) X X (68) X (69) X (70) X (71) X (72) X (73) X X (74) X X (75) X (76) X (77) X X (78) X (79) X (80) X (81) X (82) X (83) X X X (84) X (85) X (86) X (87) X (88) X (89) X (90) X X (91) X (92) X (93) X (94) X X X (95) X (96) X X (97) X X X (98) X (99) X (100) X (101) X (102) X X (103) X (104) X (105) X X X (106) X X (107) X (2) X X X (108) X (109) X X (110) X X (111) X (112) X (113) X (114) X X (115) X (116) X X (117) X (118) X X X (4) X X X X (119) X X (120) X (121) X (122) X (123) X (124) X TABLe 2 | Con inued (Con inued) (Con inued) 5 Köcke ling e al. Resea ch on a La ge EHEC Ou b eak F on ie s in Public Heal h | www. on ie sin.o g Decembe 2017 | Volume 5 | A icle 332 TABLe 3 | Median o publica ion la ency in mon hs wi hin he di e en opics. Publica ion ype Topic Medicine Mic obiology epidemiology Food sa e y Ou b eak epo ing To al Re iew 18 11 11 16 NA 16 O he publica ion ypes 18 11 18 9 20 17 FiGURe 2 | Numbe o publica ions by yea /qua e and opic (n=133 publica ions, one pape can be assigned o mo e han one opic). Re e ence Assigned opics Medicine Mic obiology epidemiology Food sa e y Ou b eak epo ing (125) X (126) X (127) X (128) X (129) X (130) X X (131) X (132) X (133) X (134) X (135) X TABLe 2 | Con inued TABLe 4 | Coun ies o ins i u ions in ol ed by opics. Coun ies o ins i u ions Topics Medicine Mic obiology epidemiology Food sa e y Ou b eak epo ing Only Ge many To al 42 16 10 4 5 % 59 27 22 45 46 Only non-Ge man coun ies To al 13 32 17 3 4 % 18 53 37 33 36 Ge many and non-Ge man coun ies To al 16 12 19 2 2 % 23 20 41 22 18 All To al 71 60 46 9 11 % 100 100 100 100 100 One pape may co e mo e han one opic. 6 Köcke ling e al. Resea ch on a La ge EHEC Ou b eak F on ie s in Public Heal h | www. on ie sin.o g Decembe 2017 | Volume 5 | A icle 332 ou b eak in es iga ion me hods in gene al, bu also ela e o clinical and mic obiological aspec s o EHEC. This is u he suppo ed by he b oad spec um o opics and sub opics co e ed by hese publica ions. We iden i ied some cha ac e is ic di e ences among opics no only wi h espec o publica ion la ency bu also wi h espec o he composi ion o ins i u ions con ibu ing o he publica ions (Table 3). As expec ed, he majo i y o he a icles we e published exclusi ely by, o led by, Ge man ins i u ions. Howe e , gi en ha he ou b eak p ima ily occu ed in Ge many, he p opo ion o non-Ge man collabo a o s o lead au ho s appea s o be high. Non-Ge man pa icipa ion o lead au ho ship was mos common in Mic obiological esea ch on he causa i e E. coli s ain and in e iews based on p io publica ions. This is easily explained by he ac ha hese kinds o publica ions did no TABLe 5 | S uc u al o e iew o main indings and ecommenda ions o he ex ac ed publica ions wi hin he opics epidemiology, ood sa e y, and ou b eak epo ing (n=39). Topic, sub opic, issue S udy design Con en Main indings Conclusions and ecommenda ions Epidemiology, Su eillance, S anda d P ocess – Timelines (9) – E alua ion (3, 69) – C oss-sec ional s udy (11, 40, 125) – Delayed epo ing o i s cases (3, 9, 69, 125) – Fi e no he n s a es o Ge many we e mos ly a ec ed (3, 11, 40) – Women a e mo e a ec ed han men (3, 11, 40) – Adul s a e mo e a ec ed han child en (3, 11, 40) – Change in he law: de elopmen and implemen a ion o an au oma ed no i ica ion sys em (3, 9, 105) – Sen inel su eillance (3, 105) – De elopmen o an ideal Shiga oxin-p oducing Esche ichia coli (STEC) su eillance (4) – Tes ing all s ool samples o en e opa hic E. coli (38) – 25–30 epidemiologis s o suppo au ho i ies (3) Epidemiology, Su eillance, Imp o emen Measu es – Timelines (9, 38) – E alua ion (3, 4, 49, 105) – C oss-sec ional s udy (125) – Cen al coo dina ion h ough he Robe Koch Ins i u e (RKI) (3, 125) – Implemen a ion o daily epo ing (3, 9, 125) – Implemen a ion o a synd omic su eillance sys em (3, 125) – Success depends on he compliance o he in ol ed pe sons (49) – E. coli in ec ions a e unde es ima ed h ough ou ine su eillance (38) Epidemiology, Su eillance, Seconda y and a ypical cases – Case-con ol S udy (13, 116) – C oss-sec ional s udy (41, 51) – Coho S udy (116) – Labo a o y in es iga ion (47) – E alua ion (4) – Median o shedding was 10–14days (116) – No seconda y in ec ion du ing pos dia hea (116) – O104:H4 seconda y ansmission, simila o o he S x 2 ypes (51) – 33 pos -ou b eak cases, all caused by seconda y ansmission (41) – Pos -ou b eak cases we e also es ed in F ance (47) – P opo ion o asymp oma ic cases is signi ican ly highe among people who consumed sp ou s in compa ison o people who did no (13) – Ex en o shedding is ele an wi h ega d o seconda y cases (4) – Resea ch on he ac o s in luencing he de elopmen o clinical symp oms (13) – Tes ing o he ou b eak s ain o s ool samples om con i med cases’ household membe s ee o cha ge enhanced apid de ec ion o seconda y cases (51) Epidemiology, Su eillance, Cases ou side and in Ge many – C oss-sec ional s udy (2, 42) – Case epo (59, 67, 83) – Coho s udy (64, 109) – E alua ion (3) – Impo ed and seconda y cases in 15 coun ies (2, 59, 67, 83, 109) – Mean age 46yea s, 71% emale (64) – 3,793 cases epo ed in Ge many, 827 hemoly ic u emic synd ome (HUS) cases, 53 a ali ies (3) – 3,816 cases epo ed in Ge many, 845 HUS cases, 36 a ali ies (42) – 88% o he cases a e adul s (42) – Gas oen e i is cases: median age 46yea s, 58% emale (3) – HUS cases: median age 43yea s, 69% emale (3) – Mos o he cases ou side he i e mos ly a ec ed s a es we e a el- ela ed (42) – Web-based case egis e : used by 73 hospi als in Ge many, 17 in Sweden, and 1 in he Ne he lands;631 HUS cases we e egis e ed (64) Epidemiology, Ou b eak In es iga ion, Gene al in o ma ion – C oss-sec ional s udy (2, 11, 40) – Coho s udy (24, 33) – Case-con ol s udy (24, 110, 116) – Case epo (59, 83) – T ace back and o wa d (24) – E alua ion (3) – In o ma ion on he ou b eak s ain (11, 40) – Fi s s udies ailed o iden i y he sou ce (3, 33, 59, 83, 110, 116) – Hin s on sp ou s a e ou h case-con ol s udy (2, 3, 24) – 13 epidemiological s udies conduc ed by RKI and local au ho i ies (3) – Local au ho i ies decla e sp ou s om a a m in Lowe Saxony as he sou ce, sp ou s we e wi hd awn om he ma ke (3) – Using da a ecipes and o de lis s o es au an cus ome s o educe dependence om ecall (24) – Sea ch o connec ions be ween di e en e en s and cases (3, 11) – Many case-con ol s udies ailed du ing he ou b eak (33, 110) – Educa ion o ca e ing pe sonal o in ec ious diseases (33) (Con inued) 7 Köcke ling e al. Resea ch on a La ge EHEC Ou b eak F on ie s in Public Heal h | www. on ie sin.o g Decembe 2017 | Volume 5 | A icle 332 8 Köcke ling e al. Resea ch on a La ge EHEC Ou b eak F on ie s in Public Heal h | www. on ie sin.o g Decembe 2017 | Volume 5 | A icle 332 Topic, sub opic, issue S udy design Con en Main indings Conclusions and ecommenda ions Epidemiology, Ou b eak In es iga ion, Food ace back and o wa d – T ace back and ace o wa d (24, 82, 126) – Coho s udy (24) – Case-con ol s udy (24) – E alua ion (3, 4) – 41 clus e s aced back o sp ou s om a m in Lowe Saxony (24) – De elopmen o he unde lying da abase ook 3weeks (126) – In o ma ion on dis ibu ion ways is equi ed (82) – De eloping isk p o iles o iden i y checkpoin s in ood p oduc ion chain (4) – T ace back/ ace o wa d should be enhanced as s anda d me hod (3, 4) Epidemiology, Ou b eak Managemen , Gene al in o ma ion – E alua ion (3, 69, 105) – C oss-sec ional s udy (2) – Cen al coo dina ion h ough RKI, collabo a ion wi h local au ho i ies, WHO, and EU (3, 69) – Special ask o ce implemen ed, consis ed o ep esen a i es o ede al agencies and he EFSA (3) – In e disciplina y collabo a ion o heal h and ood sa e y au ho i ies needed (105) – C isis managemen o be de eloped and p ac iced in ad ance (69) – P o essional associa ions, Uni e si ies and Labo a o ies o be inco po a ed in o de eloping c isis managemen (69) – In o ma ion sys em has o be imp o ed (69) – Educa ion o epidemiologis s has o be ensu ed (69) – Expe iences om Ge many o use o de eloping coun ies (2) – Pe sonnel o in e disciplina y managemen is needed (3) – S eady communica ion be ween clinicians and PH- Se ice (3) Epidemiology, Ou b eak Managemen , In o ma ion ans e – E alua ion (3, 73) – Daily epo o he RKI online a ailable (3) – Fi e join p ess con e ence o he RKI and he Fede al Ins i u e o Risk Assessmen (BFR) (3, 73) – O e 300 p ess inqui ies answe ed, 50 TV in e iews gi en by BFR (73) – Publica ions should be adjus ed be ween ede al and local au ho i ies (3) Epidemiology, Ou b eak Managemen , Secu i y o supply – E alua ion (3, 34, 37, 69) – C oss-sec ional s udy (55, 125) – Lack o in o ma ion on clinical ca é capaci y du ing ou b eak (3) – Ambula o y ea men in Hambu g and Lübeck was ensu ed (37) – Clinical ca e no ensu ed in 2/79 hospi als in 15/16 Ge man s a es (125) – Redi ec ing o in o ma ion o su ge ies was no su icien (37, 69) – U.S. Depa men o De ense independen ly bundled in o ma ion (34) – De elopmen o an in o ma ion sys em on clinical ca e capaci y (3) – Da a consis ency is mo e impo an han accu acy o case coun y (55) Food Sa e y, Iden i ica ion o EHEC in ood, NA – Labo a o y in es iga ion (60, 102, 120) – E alua ion (4) – Me hod based on U.S: Bac e iological Analy ical Manual sui able o de ec O104:H4 (60) – High-p essu e inac i a ion does no depend on es e ase ac i i y (102) – Me hod based on CHROMaga STEC sui able o de ec O104:H4 (120) – De elopmen o imp o ed me hods o iden i y O104:H4 in ood (4) – Reducing E. coli shedding o li es ock can educe in ec ion isk o humans (4) Food Sa e y, En i onmen al in ol emen , NA – E alua ion (4, 39) – C oss-sec ional s udy (53) – No e idence o O104:H4 in was ewa e (39) – No concei able i O104:H4 will es ablish endemeci y in humans o li es ock (39) – No in ec ion isk ia ba hing wa e (53) – Check on es ablishmen o O104:H4 in li es ock o humans (4) – Wa e used in ood p oduc ion should be o d inking wa e quali y (39) – De elopmen o decon amina ion me hods o was ewa e (4) – De elopmen o es s o en i onmen al samples o E. coli (4) – Regula es ing o d inking wa e (39) (Con inued) TABLe 5 | Con inued 9 Köcke ling e al. Resea ch on a La ge EHEC Ou b eak F on ie s in Public Heal h | www. on ie sin.o g Decembe 2017 | Volume 5 | A icle 332 Topic, sub opic, issue S udy design Con en Main indings Conclusions and ecommenda ions Ou b eak Repo ing, P o essional Pe spec i e, Gene al In o ma ion – C oss-sec ional s udy (11, 40) – The BFR gi es consume ecommenda ion and hygiene ins uc ions (11, 40) – In o ma ion on esea ch esul s a e gi en (11, 40) – Recommenda ions apply un il new e idence is ound (11) Ou b eak Repo ing, P o essional Pe spec i e, Risk communica ion – E alua ion (3, 34, 73, 105) – C oss-sec ional s udy (2) – Inconsis en in o ma ion was gi en du ing he ou b eak (2, 3) – Media was used o in o m he popula ion (73, 105) – Goals o isk communica ion we e eached (73) – In o ma ion should be objec i e, co ec and no inconsis en (34, 105) – To communica e in o ma ion on cause, impac , and measu es (105) – In o ma ion no o be wi hheld un il alidi y is ensu ed (73) – A oiding inconsis en in o ma ion (3, 73) Ou b eak Repo ing, Lay Pe spec i e, Pe cei ed In o ma ion – E alua ion (73) – C oss-sec ional s udy (123) – In o ma ion gi en by he BFR pe cei ed o be su icien , – suspension o p e ious ecommenda ion pe cei ed o be unde s andable (73) – Risk communica ion should be easily accessible (123) Ou b eak Repo ing, Lay Pe spec i e, Sou ces o in o ma ion – C oss-sec ional s udy (2, 114, 123) – E alua ion (37, 73) – Coho s udy (122) – TV is pe cei ed o be us able (73) – D ama izing con ibu ions in TV an ea (2, 114) – Web 2.0 o in o ma ion sea ch pe cei ed o be unsa is ying due o inconsis en in o ma ion (122) – Capabili y o educe pe sonal isk by ollowing ecommenda ion is pe cei ed o be high (123) – P ecise in o ma ion o he popula ion is needed (37) – Economic loss could ha e been a oided h ough be e in o ma ion o he public (123) TABLe 5 | Con inued equi e ac i e in ol emen in he epidemiological in es iga ion o clinical pa ien managemen (19, 118). This may also explain he somewha unexpec ed obse a ion ha e iews ended o be published ea lie han o he ypes o publica ions (Table3): while clinicians and public heal h agen s we e p ima ily occupied wi h managing he ou b eak and la e gene a ing and analyzing he da a de i ed om i , non-in ol ed (and hus mo e likely non-Ge man) specialis s in he ield could wi hou any delay ocus on analyzing he exis ing li e a u e. Such di ision o asks appea s a ional and use ul, since ea ly e iew on speci ic managemen ques ions could help hose p ima ily in ol ed in he managemen o adap hei in e en ions. Simila ly, labo a o ies ou side he p ima ily a ec ed coun y can complemen he mic obiologic esea ch ela ed o he ou b eak once an isola ed s ain is made a ailable, hus sup- po ing local labo a o ies o apidly cha ac e ize he implica ed pa hogen. The EHEC ou b eak was excep ional in many aspec s and p o ided a unique oppo uni y o be e unde s anding he disease (5). Some o he indings published on he ou b eak may appea edundan (Table 5). This does no necessa ily signi y duplica e publica ion, since a i ing a simila conclusions using di e en s udy popula ions o di e se analy ic me hods applied o he same s udy popula ion is a desi ed p ocess in science. I is also jus i ied in an acu e ou b eak si ua ion o quickly publish esul s o ea ly analyses and la e complemen hem wi h mo e comple e o me hodologically e ined s udies (73). We ound many case epo s, pa icula ly in he ield o Medicine. Due o hei speci ic me hodological limi a ions, indi idual case epo s ha e a limi ed po en ial o con ibu e signi ican ly o p essing esea ch ques ions, unless a pooled analysis o cases is pe o med. Un o una ely, no such analysis seems o ha e been done so a . Ou sea ch s a egy including wo independen da a bases and all languages is likely o ha e led o a a he comp ehensi e collec ion o publica ions. We belie e ou decision o exclude edi o ials, commen a ies, eplies and dia ies, is unlikely o esul in ele an o iginal esea ch indings o be missed. Fu he mo e, his app oach ensu ed ha only scien i ically e iewed publica ions we e included and i inhibi ed dissemina ion o poli ically mo i a ed communica ions by s akeholde s o in e es ed pa ies. Ne e heless, la ge and mo e comp ehensi e s udies on he ou b eak may s ill be published in he u u e, especially in he ield o Medicine. The in en ion o add ess he pa e ns o espec i e esea ch ac i i ies om di e se disciplines esul ing om his ou b eak, ins ead o add essing one speci ic esea ch ques ion, p ecluded us om conduc ing a me a- analysis. We limi ed da a ex ac ion o Public Heal h- ela ed opics as we wan ed o ocus on he scien i ic ou pu gene a ed in his ield. The obse ed la ency o publica ions on he Ge man EHEC ou b eak 2011 highligh s he ac ha e en se e al yea s a e such an e en , o iginal esea ch wo k con inues o be published. We also ound a conside able le el o coope a ion be ween la ge numbe o ins i u ions om wi hin and ou side Ge many. Ou e iew was no designed o judge he con en and scien i ic me i o hese publica ions. We do no expec ha he limi a ion o 4yea s a e onse o he ou b eak in luenced he esul s o his e iew as we obse ed ha he numbe o publica ions dec eased owa d he end o he inclusion pe iod. Mo eo e , no el indings and conclusions we e less common in he la e yea s o he obse a ion pe iod. This wo k e eals a unique map o how he EHEC ou b eak was