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.
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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)
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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
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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