Prevention and control of enterohaemorrhagic Escherichia coli

Memoranda/Memorandums

Prevention and control of enterohaemorrhagicEscherichia coli (EHEC) infections:Memorandum from a WHO meeting*A. Reilly1 on behalf of the WHO Consultation on Prevention and Control ofEnterohaemorrhagic Escherichia cofi (EHEC) Infections2

Escherichia coli is a commonly occurring inhabitant of the intestine of humans and other animals, but thereare several pathogenic types of E. coli which cause a variety of human diseases. One of these pathogenictypes, E. coli 0157:H7, belongs to the group of enterohaemorrhagic E. coli (EHEC) which produce potenttoxins and cause a particularly severe form of disease, haemorrhagic colitis (HC). About 10% ofpatients withHC can go on to develop haemolytic uraemic syndrome (HUS), a life-threatening complication of E. coli0157:H7 infection that is characterized by acute renal failure, haemolytic anaemia, and thrombocytopenia.These sequelae are particularly serious in young children and older people. On average, 2-7% of patientswith HUS die, but in some outbreaks among the elderly the mortality rate has been as high as 50%.

This Memorandum reviews the growing importance of E. coli 0157:H7 as a foodbome pathogen andreports on the issues of surveillance, outbreak investigation, and control strategies with respect to EHECinfections that were discussed at the WHO Consultation on Prevention and Control ofEHEC Infections, heldin Geneva on 28 April to 1 May 1997. Recommended measures for prevention and control include thefollowing: use of potable water in food production; presentation of clean animals at slaughter; improvedhygiene throughout the slaughter process; appropriate use of food processing measures; thorough cookingof foods; and the education of food handlers, abattoir workers, and farm workers on the principles andapplication of food hygiene.

IntroductionIn 1982, Escherichia coli 0157:H7 was recognized asa human pathogen for the first time, and since then

* This article is based on: Prevention and Control of EHEC Infec-tions. Report of a WHO Consultation, Geneva, 28 April to 1 May1997(unpublished document WHO/FSF/FOS/97.6, available uponrequest from Director, Programme of Food Safety and Food Aid,World Health Organization, 1211 Geneva 27, Switzerland).I Scientist, Food Safety, World Health Organization, 1211 Geneva27, Switzerland. Requests for reprints should be sent to Mr Reillyat this address.2 The participants at the Consultation were as follows: G.K. Adak,S. Ahmed, A. Ammon, Y. Andersson, L. Beutin, S. Cameron, M.L.Costarrica, 0. Fontaine, A. Hazzard, D. Heymann, S. lwao, F.K.Kaferstein, H.J. Koornhof, P. McClure, P. Mead, S. Minami, K.Miyagishima, Y. Motarjemi, K. Nakajima, M. Neill, H. Pennington,L. Persson, A. Reilly (Secretary), W.J. Reilly, H. Richter, M. Rivas,T. Roels, J. Schlundt, R. Skinner (Chairperson), N. Skovgaard,H.R. Smith, K. St6hr, Y. Takeda (Vice-Chairperson), E.C.D. Todd,A.W. van de Giessen, R. Vanhoorde, M. Van Schothorst, K.Wachsmuth (Rapporteur), P. Wall, H. Watanabe, and J. Wilson.Reprint No. 5856

has been a steadily increasing cause of foodborneillness worldwide. Although the main reservoir ofthis pathogen appears to be cattle, the dynamics ofE. coli 0157 in food-producing animals and the envi-ronment is not well understood. It is transmittedprincipally through consumption of contaminatedfoods, such as raw or undercooked ground meatproducts and raw milk. Faecal contamination ofwater and other foods and cross-contaminationduring food preparation are important routes of in-fection. Examples of foods implicated in outbreaksof E. coli 0157 infection include hamburgers,roast beef, raw milk, unpasteurized apple juice, yo-ghurt, cheese, fermented sausage, cooked maize,mayonnaise-containing dressings, lettuce, and seedsprouts. The pathogen is relatively tolerant to acidand can survive in fermented foods and fresh vegeta-ble produce. Waterborne transmission has also beenreported, both from contaminated drinking-waterand from recreational waters. Person-to-person con-tact is an important mode of transmission, particu-larly in institutional settings, such as day care

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Memorandum

centres, nursing homes and hospitals. Direct contactwith farm animals and birds carrying the organism isalso a recognized source of infection. The role ofasymptomatic food handlers in outbreaks is unclearbut it may be important in view of the low infectiousdose. The range of foods reported as vehicles oftransmission and the numerous transmission routescreate a major challenge in terms of designing pre-vention and control strategies.

More recently, there have been unprecedented,large outbreaks of E. coli 0157:H7 infection in Japanand Scotland, and outbreaks due to other entero-haemorrhagic E. coli (EHEC) in Australia and Euro-pe. There have also been a significant number ofoutbreaks in the USA linked to the consumption ofcontaminated vegetable products, such as lettuce andalfalfa sprouts. The largest ever recall of food onrecord occurred in the USA in 1997, when about10 000 tonnes of raw frozen hamburgers were recalledbecause of suspected contamination by E. coli 0157.

In view of the magnitude and severity of re-cent outbreaks of foodborne diseases caused by E.coli 0157:H7, there is an urgent need for all sectorsin the food chain to work together to reduce or elimi-nate the health impact of this hazard. Achieving asignificant reduction in the incidence of foodbornedisease caused by this pathogen will require the co-operative efforts of public health and environmentalhealth agencies, farmers, animal producers, foodprocessors and caterers, together with researchscientists.

Global overview of EHECinfectionsDuring the consultation, participants presentedoverviews of current national situations with respectto EHEC infections as outlined below.

African RegionBloody diarrhoea is a major cause of morbidity andmortality among children in African countries, yetthe proportion caused by E. coli 0157:H7 and otherEHEC is largely unknown. In South Africa, forexample, infections caused by EHEC are not notifi-able and there is very limited information on E. coli0157 infection in animals. Since 1988 three cases ofE. coli 0157 colitis have been identified in Pretoria,one of which was associated with eating a hamburgerfrom a fast-food outlet. Many cases of haemorrhagiccolitis caused by nonmotile E. coli 0157 fromSwaziland and the adjacent South African provincesof Mpumalanga and KwaZulu-Natal were identified

in 1992. Isolates of E. coli 0157 were obtained frompatients, water, cattle faeces and one sample ofcooked maize. An undocumented number of casesof haemolytic uraemic syndrome (HUS) occurredduring this outbreak.

Reports of EHEC as a cause of diarrhoea inother African countries are sporadic. In a study ofchildhood diarrhoea in Nigeria, samples of EHECwere isolated from 5.1% of children with diarrhoea(10). EHEC was suspected to be the cause of bloodydiarrhoea and deaths in refugees in Angola (3) andin Malawi (11). E. coli 0157:H7 has also been iso-lated in Kenya as a cause of severe childhood diar-rhoea (12). In Egypt, haemorrhagic colitis and childmortalities have been linked to eating hamburgers,koshari and dairy products, and E. coli 0157:H7 hasbeen reported in beef, chicken, lamb, and unpasteur-ized milk (1). Since 1996, an increasing number ofcases of acute bloody diarrhoea reported in theCentral African Republic have been associated withE. coli 0157:H7 (8); kanda, a meat pie that is pre-pared from smoked zebu meat and cooked marrowsquash, was identified as the main food vehicle.

Region of the AmericasIn the USA, laboratory-based surveillance for E. coli0157:H7 infections was first implemented in late1992, and the results obtained up to mid-1995showed that the number of states reporting isolatesincreased from two to 40. During this period 2946cases were reported, equivalent to an annual averageincidence of 0.74 cases per 100000 population.Annual, state-specific incidences ranged from 0.03 to4.99 cases per 100000 population. Since 1982, morethan 100 outbreaks of E. coli 0157 infection havebeen reported. Of those outbreaks for which themode of transmission was identified, 52% werelinked to foods derived from cattle, 16% to spread ofinfection from person-to-person, 14% to fruits andvegetables, 12% to water, and 5% to miscellaneousfoods. Recently, fruit and vegetables have increas-ingly been implicated as vehicles of infection. Since1995, there have been five outbreaks in NorthAmerica associated with lettuce, and one with com-mercial, unpasteurized apple juice.

Infection with verotoxin-producing E. coli(VTEC) continues to be a significant public healthproblem in Canada. In 1991, the reported annualincidence of infection reached a maximum of 5.3 per100000 inhabitants and by 1993 had decreased to3.0 per 100000. More recently, the reported inci-dence has again increased, prompting renewed con-cern over the health impact of this organism. Themajority of cases in Canada are believed to be spo-radic and in 1995, 16 outbreaks of E. coli 0157:H7

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infection were reported in this manner; nine of thesewere family outbreaks (19 cases phage-typed), twowere restaurant outbreaks (10 cases), three wereinstitutional outbreaks (21 cases), one was a day careoutbreak (9 cases), and one was a waterborne out-break (index case only phage-typed). Preliminarydata indicate that 18 outbreaks were reported in1996; twelve were family outbreaks (28 cases phage-typed), four were community outbreaks (28 cases),and one was a day care outbreak (25 cases). MostVTEC infections reported in Canada are caused byE. coli 0157:H7.

In South America, HUS has for many yearsbeen the most common cause of acute renal failurein childhood and infancy in Argentina, with anestimated annual incidence of 7.8 per 100000 amongunder-5-year-olds. Over 5500 cases of HUS were re-ported in Argentina from 1965 to 1993. Childrenaffected are usually aged under 5 years, mostly 6-36months. Both sexes are equally affected and casestend to come from middle-income socioeconomicgroups, who are well nourished and living in goodsanitary domestic conditions. The illness is distrib-uted throughout Argentina, but cases are reportedmore frequently in southern provinces duringwarmer months (from October to May). VTEC0157:H7, producing verocytotoxin 2 (VT2), is themost frequently isolated serotype of VTEC fromdiarrhoea-positive (D+) HUS cases, with bloodyand nonbloody diarrhoea. Until now, no foodborneoutbreaks have been reported. HUS constitutes animportant clinical problem in other South Americancountries, where it has been reported in Chile andUruguay (5).

Western Pacific RegionIn 1996, Japan reported 9451 cases of EHEC infec-tions, 1808 of which were hospitalized and 12 died;three-quarters of all these cases occurred during sixmajor outbreaks. In the largest outbreak, in SakaiCity, 5727 people (0.5% of the city's population)were affected, and white radish sprouts served atschool lunch were the most likely food vehicle. Inoutbreaks reported in other areas E. coli 0157 wasalso isolated from the salad and seafood sauce thatwere served at school lunches. In 1997, E. coli 0157was detected in wild venison and white radishsprouts associated with sporadic infections.

In other parts of Asia, EHEC infections havebeen reported. In Malaysia, E. coli 0157:H7 has beenisolated from the stools of patients with diarrhoealillness (13). In a study at a Bangkok hospital in Thai-land, EHEC was identified in 7% of children withbloody diarrhoea in whom other enteric pathogenswere not identified (4). In the Republic of Korea,

EHEC was isolated from 1.3% of children withnonbloody diarrhoea. An investigation into theetiology of childhood diarrhoea in China isolatedEHEC from 6.8% of children with diarrhoea (9); therarity of E. coli 0157:H7 identified in this study ledthe authors to conclude thatEHEC may be caused byserotypes other than 0157:H7 in China.

There have been two documented outbreaks ofinfection with EHEC in Australia. The first, in SouthAustralia in 1995, was of serotype O111:H- and in-volved 22 cases of paediatric HUS, four cases ofthrombotic thrombocytopaenic purpura (T1P), andreports of approximately 200 cases of haemorrhagiccolitis (HC) and diarrhoea. The source of the out-break was an unpasteurized semi-dry, fermentedsausage. The second, in Queensland in 1996, in-volved serotype 0157:H7 and involved six cases ofdiarrhoea, several of which were bloody; an infectedfood-handler is thought to have been the source. In1995-96, sporadic cases ofHUS occurred throughoutAustralia in children under 15 years of age at anannual incidence of around 0.93 per 100000, includ-ing outbreak-associated cases. This rose to 2.79 per100000 among children aged under 5 years, and 95%of such cases demonstrated a diarrhoeal prodromewith the following VTEC serogroups being isolated:0111, 0157, 0113, and 0130.

European RegionIn Denmark, the annual incidence of VTEC from1986 to 1996 was 0.1 per 100000. During this period,different serotypes of VTEC were isolated from atotal of 60 sporadic human cases. The predominantdisease-causing VTEC serotypes were 026:H11,0157:H-, 0157:H7 and 026:H-. VTEC 0157:H7have been isolated from cattle herds and cattle atslaughter. E. coli 0157 has been isolated fromminced meat in Denmark, and minced meat otherthan beef may play a role as a source of infectionfrom possible cross-contamination at the retail level.However, the presence of pathogenic VTEC in cattleand foods has not resulted in any reported out-breaks. At present it is unclear why only a fewsporadic VTEC cases are diagnosed each year inDenmark, suggesting that the number of VTEC-associated cases may be underestimated.

Data from Germany indicate that EHEC infec-tions, including E. coli 0157, occur in all parts of thecountry. During 1994 and 1995, EHEC was isolatedin 2-3% of hospitalized children with diarrhoea,with E. coli 0157 being the most frequently isolatedserotype (94 out of 118 cases, i.e. 79.7%) in childrenwith HUS. Data for 1996 suggest that the proportionof non-0157 VTEC implicated in HUS cases maybe increasing, because 0157 was isolated in only

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about two-thirds of HUS cases from which a VTECcould be isolated. The following non-0157 E. coliserogroups were associated with HUS: 015, 026,0103, 0111, 0118, and 0145. In an outbreak ofHUS in Bavaria between December 1995 and March1996, 20 of the 32 children with HUS had stool cul-tures that were positive for EHEC; E. coli 0157 wasdetected in samples from 17 of the 20, at least 12 ofwhich fermented sorbitol. In one case E. coli 0103and in two cases E. coli 055 were identified.

In Germany, farm animals, especially rumi-nants, constitute the major natural reservoir forVTEC. Repeated examination of cattle and sheephas revealed that nearly all individual animalscould excrete VTEC at one or more periods duringtheir life. A large variety of VTEC serotypes hasbeen isolated from animals. Sporadic isolates ofVTEC belonging to the classical EHEC types, suchas 0157:H7, 026:H11, and 022:H8, have beenmade. Only 1-2% of the animal VTEC isolatespossess the eae gene and about 60% express theenterohaemolytic phenotype.

The incidence of HUS in the Netherlandsamounts to about 30 cases per year, mainly amongunder-5-year-olds. Studies on sporadic cases of HUSrevealed E. coli 0157 to be the predominant causa-tive agent. The relative importance of EHEC as acausative agent of human diarrhoeal illness in theNetherlands is unknown. Since 1992 various studieshave been conducted on the occurrence of E. coli0157 in raw meat products and in faecal samplesfrom different categories of cattle. Between 1992 and1995 a total of 2330 samples of meat products wereexamined and E. coli 0157 was isolated from onlytwo samples of minced meat (beef/pork). In 1996 thepathogen was reported in a sample of fermentedsausage and a sample of sausage batter. In 1995, E.coli 0157 was detected in 30 (11.1%) of 270 faecalsamples from dairy cows; nine of the 30 isolates werepositive for the VT2 and the eae gene.

Since 1988 up to three cases of EHEC havebeen reported in Sweden annually, including thosepeople who contracted the infection abroad. Thissituation changed between July 1995 and early 1996,when an outbreak occurred with 99 confirmed cases,24 of which developed HUS. The total number ofcases in 1995 and 1996 were 114 and 118, respec-tively, with the principal serotype reported being E.coli 0157. The National Veterinary Institute andthe National Board of Agriculture are carrying out asurvey of the prevalence of EHEC in the faeces ofcattle at the 16 main abattoirs which produce 90% ofall domestic beef. Up to April 1997 a total of 2195samples had been analysed and 25 (1.1%) found tobe positive for VT-producing (VT1 and/or VT2) E.coli 0157, which were positive for eaeA genes.

In 1996 the reported rate of infection withEHEC in England and Wales was 1.29 cases per100000 population, which compares with 0.49 per100000 population in 1990. The increase in thenumber of cases reported during the 1980s may beattributed, in part, to increased surveillance as morelaboratories began to screen diarrhoeal stool speci-mens for E. coli 0157. However, the continued risein isolates during the 1990s probably reflects a realincrease in the incidence of the pathogen. Recentstudies on the incidence of VTEC 0157 in animals atslaughter and in retail foods have revealed the pres-ence of VTEC 0157 in cattle (15.6%) and sheep(2.2%), but not in pigs or poultry. Also E. coli 0157was found in 9% of lamb products, particularlylamb-burgers, and in 1.5% of beef products.

Laboratory reports of VTEC in Scotland haverisen from a total of three in 1984 to 506 in 1996, withthe annual rates of infection having increased from2.24 per 100000 in 1992 to 9.85 per 100000 in 1996.Within these totals there is considerable geographi-cal variation, with the rates in different health boardsvarying from 2.3 to 33.0 per 100000 in 1996. Thislatter value includes cases in the largest outbreakreported in the United Kingdom (496 cases, of which272 were confirmed by laboratory diagnosis), whichresulted in 19 deaths. The incidence of VTEC inScotland is considerably higher than that reportedelsewhere in the United Kingdom; also, the variationbetween Scotland and other parts of the UnitedKingdom, or indeed the variation within Scotland,has not been explained.

Data reported at a recent international confer-ence on VTEC infections (2) in the Czech Republic,Finland, Italy, and Belgium suggest that EHECinfections in these countries are not common. Also,the incidence of HUS in Austria during 1995 wasreported to be 0.37 cases per 100000 people aged 0-14 years; in Belgium the annual incidence was 4.2cases per 100000 children under 5 years of age (0.4cases per 100000 residents); and in Italy the inci-dence was 0.2 cases per 100000 population.

Surveillance of EHEC infectionsSurveillance is defined as the systematic collection,analysis, interpretation, and dissemination of healthdata for the purposes of disease prevention and con-trol. The need and ability to conduct surveillancefor EHEC infections and their sequelae vary acrosscountries depending upon the specific patterns ofclinical disease, the relative importance of specificEHEC strains, and the resources available. Theobjectives of surveillance for EHEC infections inhumans are identification of outbreaks, determina-


Prevention and control of EHEC infections

tion of disease trends, estimation of the burden ofillness, and compilation of other data with which tobase decisions for resource allocation. When estab-lishing surveillance for EHEC infections, emphasisshould be placed on timely collection, analysis, andtransmission of data to those who can undertakeappropriate responses at local, regional, and nationallevels. Suitable incentives must exist to encouragesupply of the needed data in a timely manner. One ofthe most important of these is the timely feedback ofsurveillance information in a useful format. Surveil-lance systems for EHEC should not be developed denovo but rather within the framework of surveillancesystems for other diseases transmitted through food,water, and contact with animals.

A variety of approaches has been used to carryout surveillance for EHEC infections. The principalmethods for surveillance include hospital-based sys-tems for identification of HUS cases and laboratory-based systems for the identification of infectedindividuals. Laboratory-based systems can be sup-plemented by active, sentinel-site surveillance insome circumstances; for example, in regions whereculture for E. coli 0157 is not routine. The develop-ment of outbreak surveillance systems is of greatvalue in view of the magnitude of past outbreaks, theserious nature of the disease, and the valuable les-sons to be learned from outbreak investigations.

For surveillance and reporting purposes, a caseof EHEC infection may be defined as diarrhoea withlaboratory evidence of EHEC infection; or bloodydiarrhoea or HUS linked to a laboratory-confirmedcase. Case reports based on individual cases shouldbe made and include, as a minimum, the following:the patient's age, sex, date of onset of the illness,place of residence, and basis of diagnosis. Dependingon the availability of resources, countries shouldconsider collecting additional data on risk factorsdeemed appropriate to their setting; examplesmay include recent travel, restaurant exposure, andanimal contact. To detect outbreaks, local healthauthorities should review case reports on at least aweekly basis. An EHEC outbreak should be sus-pected whenever there is an unusual increase in thenumber of patients with bloody diarrhoea or HUS.

HUS is a serious illness whose diagnosis doesnot depend on stool culture, and its incidence may beused as a robust and consistent marker for EHECinfections over time. Thus, in addition to surveil-lance for EHEC infections, per se, countries shouldconsider establishing an independent surveillancesystem for HUS cases and attempt to define theiretiology. This will have the added benefit of provid-ing an efficient means of identifying non-0157strains that are of public health importance. Coun-tries whose resources prohibit the establishment of

surveillance for EHEC infections should none theless consider establishing surveillance for HUS.

Laboratory confirmation of EHEC infectionmay be defined as isolation from stools of E. coli0157 or other VTEC previously shown to causehuman disease (e.g. 0111, 026); or evidence of anacute serological response to one of these knownpathogens. Laboratory confirmation of EHEC infec-tion should be sought for all patients with HUS,visible bloody stools, or a history of bloody diar-rhoea. Where resources permit, laboratory confirma-tion should be sought for patients with nonbloodydiarrhoea and asymptomatic individuals epidemiolo-gically linked to a culture-confirmed case. Forsurveillance, isolation of E. coli 0157 should beattempted using readily available methods (e.g.cefixime/tellurite/sorbitol, MacConkey agar, andtesting of nonfermenting sorbitol colonies with 0157antiserum). Efforts should also be made to isolatenon-0157 EHEC.

The above definition of laboratory confirma-tion is for surveillance purposes only. The range ofVTEC strains implicated in human disease continuesto expand, and attempts to identify them should beencouraged. Similarly, ancillary tests such as detec-tion of free verocytotoxins in enriched stool culturesor specialized tests for the identification ofverocytotoxin or eae genes (e.g. PCR, gene probes,etc.) may be indicated in some outbreaks and insome clinical situations (e.g. when EHEC infection issuspected on clinical grounds). If these tests areused, an effort should still be made to isolate theorganism. The identification of verocytotoxin alonedoes not constitute laboratory confirmation ofEHEC infection.

Outbreak identificationAggregation of data at regional, national, and inter-national levels is essential to identify widespreadoutbreaks, especially those in which the number ofcases per unit area is small. Countries should havethe ability to aggregate surveillance data at variouslevels (region, state, country) and to share these dataacross jurisdictions in a timely manner. Effortsshould be made to improve the capacity to under-take this sharing of data electronically and to linklaboratory and epidemiological data.

Because the identification of EHEC strain byserotype alone may not be a sufficiently specificepidemiological marker for the identification ofsome outbreaks, countries should establish andmaintain national reference laboratories forsubtyping of EHEC. To facilitate the identificationof multinational outbreaks, efforts should be made


Memorandum

to standardize subtyping methods so that data maybe exchanged between countries.

When an outbreak of EHEC infection is de-tected, local, provincial (or national) health authori-ties should be notified immediately. Initial outbreakreports should specify the serotype, the number ofpatients, their ages, the dates of onset of illness, thetowns or areas affected, and the basis of the diagno-sis. Local health authorities should be encouraged todirectly notify officials in adjacent localities. Reportsof outbreaks should be shared with neighbouringcountries and countries whose residents may haveconsumed the suspect product.

In view of the severity of EHEC-associated ill-ness, there is a special urgency to provide accurateand timely surveillance information so that datamay be linked to an appropriate response. Thus, datashould be disseminated to all levels of government,industry, and the general public in a readily usableformat, subject to restrictions related to accuracyand patient and proprietary confidentiality.

Experience with recent outbreaks shows thatmedia attention will be swift, dramatic and intensebecause of the serious nature of EHEC infection andthe age groups affected. Accurate and consistentinformation from the outbreak team should be chan-nelled to the media via regular press briefings by adesignated officer. It is advisable for public healthauthorities to have a robust media-handling strategyas part of their major outbreak plans for the contain-ment of foodborne infections. Public health authori-ties must be prepared in advance to deal with largenumbers of enquiries from the media, and personsdesignated to deal with the media must have re-ceived adequate training. It is also advisable foragencies dealing with an outbreak to speak alwaysfrom the same brief. Experience has demonstratedthe advantages of pre-empting the demobilizingeffects of news coverage of outbreaks by runningregular food safety campaigns and for producingaccurate, consistent, and user-friendly press releases.Alternative and supplementary approaches toconveying preventive health information could beconsidered, such as buying advertising space in news-papers for food safety information/bulletins, buyingradio or television time for food safety informationadvertising, or providing a free telephone help linewhere members of the public can obtain accurateinformation during the outbreak.

Outbreak investigationThe objectives of outbreak investigations are as fol-lows: to identify how EHEC transmission is occur-ring and take timely corrective action; to enlarge

knowledge about EHEC, the diseases they cause,and their epidemiology; and to use such knowledgefor the further prevention of EHEC transmission.Successful outbreak investigations often depend oneffective communication between agencies involvedwith public health, food, and agriculture. Coordina-tion between agencies is critical to ensure efficientmanagement of outbreaks and the dissemination ofaccurate information to the public.

The conceptual framework used to investigatean EHEC outbreak does not differ substantially fromthat used to investigate outbreaks caused by otherenteric pathogens. Nevertheless, EHEC have distinc-tive features that may complicate the investigation,including a propensity to affect children, high mor-bidity and case fatality rates, and a low infective dose.

Outbreaks may be recognized from data in thesurveillance system or by an unusual cluster of clini-cal disease (bloody diarrhoea or HUS) not yet regis-tered by a surveillance system. An outbreak isdefined either as two or more linked cases of thesame illness, or as an unexplained increase in thenumber of cases above the background level. It isimportant to verify that an outbreak is occurring andthis will include ascertaining the details of the clinicalillness in the index cases and the details of any micro-biological or laboratory testing if performed. Labo-ratory confirmation of initial cases is essential.

The case definition used during an EHEC out-break may differ from that used in EHEC surveil-lance. An agreed case definition should be usedthroughout the investigation. Potential choices ofcase definitions that were proposed during the WHOConsultation include those outlined below.

* Confirmed symptomatic case (gastrointestinal ill-ness in a person with microbiological confirmation ofEHEC infection).* Confirmed asymptomatic case (an asymptomaticperson in an outbreak setting with microbiologicalconfirmation of EHEC infection).* Probable case (bloody diarrhoea and/or HUS in aperson without microbiological confirmation ofEHEC infection).* Possible case (nonbloody diarrhoea in a personin an outbreak setting without microbiologicalconfirmation).

Control measuresOnce a food, beverage or facility has been demon-strated to be associated with EHEC transmission,control measures must be taken in a timely manner.These may include removal of a commercially avail-



able product from distribution, collection of the al-ready purchased product, closure of a facility, ormodification of a process. Dissemination of this in-formation to the appropriate public audience is akey component in eliminating EHEC transmission.Before recall of an implicated food or beverage cantake place, records of distribution and sale need tobe sought.

Where an outbreak has been attributed toperson-to-person transmission, control measures in-clude the following: strict hand washing and goodhygienic practices among residents and those caringfor ill persons; infection control precautions for hos-pitalized or institutionalized persons; and medicalclearance of patients before returning to schools oremployment.

An important control measure in the manage-ment of an outbreak is continuous communicationbetween the investigation team and the public, pro-fessional groups, authorities and business. Theobjectives of informing professional groups are toassure accurate case-finding and a smooth imple-mentation of control measures. The objectives ofinforming the public should be to give accurate infor-mation on signs and symptoms of EHEC infection;on what steps need to be taken for those that havebeen exposed; to provide information on implicatedproducts and how they should be handled; and toprovide advice on personal hygiene to reduceperson-to-person spread. Information should beregularly exchanged between the outbreak team andthe producer of the food implicated in an outbreak.The objectives are to keep the business abreast ofthe findings of the outbreak investigation and to pre-pare the business for the possible implementation ofcontrol measures. For producers of related products,the objective of communication is to increase aware-ness about food safety issues with the type of productor process causing the outbreak.

Recommendations from the Consultation withrespect to investigation of EHEC outbreaks includethose shown below.

* Creation of effective lines of communicationamong the different national agencies involved inpublic health, food, and agriculture. Ideally, theseshould already be in place before an outbreakoccurs.

* Coordination between representatives of the rel-evant agencies should be a very high priority duringthe outbreak. Ideally one person should be in chargeof the outbreak investigation and facilitate coordina-tion between agencies.* Notification of neighbouring health jurisdictionsand regional or national health authorities to deter-

mine whether other cases have been or are occur-ring. Preferably the same case definition should beused in the other locations. Depending on the natureand extent of the outbreak, national authorities mayconsider notifying other countries.

* In-depth investigation of EHEC outbreaks shouldaspire, not only to stop the actual outbreak, but alsoto determine the point or process where EHEC con-tamination has occurred, so that changes can be in-troduced to prevent reoccurrence.

* There is a clear need to train individuals to con-duct epidemiological investigations.* Effective press management is crucial at all stagesof the outbreak investigation. Information from theoutbreak team should be channelled to the mediavia a designated officer by means of regular pressbriefings. The information should be accurate andconsistent.* Strong epidemiological evidence identifying afood or beverage vehicle is sufficient grounds to ini-tiate a trace-back effort and recall a product. Ideally,the epidemiological data should be reviewed by anindependent panel.* An environmental investigation of the implicatedfacility, source, or process is an integral part of theepidemiological investigation. It is of great impor-tance for this part of the outbreak investigation toinvolve persons with the technical knowledge (e.g.food, sanitation, animal health, water) relevant to theitem that has been implicated in disease transmission.

* The effectiveness of any control measures under-taken will need to be monitored. Even with a markeddecrease in cases with the outbreak strain, thecontinued presence of the organism at a lowerfrequency can imply continuing transmission. Thiswould prompt a further reassessment of all controlmeasures.

Prevention and control ofEHEC infectionsIn general, the prevention of foodborne diseasesmust be based on good hygienic practices and con-trol of the contamination of foods by biological andchemical hazards. This can be achieved most effec-tively through the application of food safety assur-ance programmes, based on the principles of theHazard Analysis and Critical Control Point(HACCP) system. Such a system should be appliedby primary producers, manufacturers, retailers, andfood service establishments. Guidelines can be found


Memorandum

in the Codex Code of Practice on General Require-ments of Food Hygiene (7).

Specific controls for EHEC contaminationthroughout the food chain can best be identified byconducting a systematic risk assessment exercise asdiscussed in the Joint FAQ/WHO Expert Consulta-tion on the Application of Risk Analysis to FoodStandards Issues (17). Risk management then weighspolicy alternatives in the light of the assessment andselects appropriate control options (6).

EHEC is assumed to be present in animal andhuman faeces; therefore, appropriate animal hus-bandry practices should be adopted to minimize thespread of contaminated material to animals or onground used for crops. If faecal contamination orEHEC is present in any raw material, the organismsmust be eliminated at some point in the productionprocess or by the consumer prior to consumption.

The recommendations shown below are basedupon current, albeit limited, knowledge and under-standing of EHEC and experience gained throughthe investigation of EHEC infections and outbreaks.They are presented in the order of the food chain,from animal and plant production through to thepoint of consumption, followed by general issues,and are not prioritized.

RecommendationsAnimal and plant production* Because of the low infectious dose of the E. coli0157 group of organisms, all producers should rec-ognize the importance of hygiene and good manu-facturing practice. Particular attention should bepaid to maintaining the cleanliness of animals andprevention of spread of faecal material, which is theprimary source of contamination. At the point ofslaughter, animals should be clean and free of visiblecontamination.* Animal slurry and human faecal waste (night soil)should not be used on or near crops intended forhuman consumption, unless it has been adequatelytreated.

* Animal and human (faecal) waste must be dis-posed of in a manner that does not contaminate thewater supply. Both run-off water and proximity ofanimals to wells have been shown to contaminatewater supplies.* Crops used for raising seeds that are going to beused as sprouts should not be fertilized with animalslurry or human faecal waste, even if some form oftreatment has been applied.

* Crops for food should be irrigated with water thatis not faecally contaminated.

Transportation* Animals for slaughter should be transported in amanner that maintains cleanliness, minimizes con-tamination from other animals, and limits unduestress.

* Transport vehicles should be cleaned and driedbefore any further use.

* Water should be decontaminated before cominginto contact with fruits and vegetables for coolingand rehydrating purposes during packing, transpor-tation, and processing.* Fruits and vegetables should be transported insuch a way to minimize damage and to prevent entryof EHEC and other pathogens into these products.

Harvesting of animals and plant produce* Any water used for washing and/or processing ofanimals, fruits, and vegetables should be of potablequality.* Holding of animals prior to slaughter should bedone in such a manner that they are kept clean.

* All abattoirs/establishments where animals areslaughtered should have in place a system of goodhygienic practice and an effective HACCP plan cov-ering all stages in the production process, from thetime animals arrive until the carcasses or meat prod-ucts leave the establishment.

* In handling carcasses, particular care shouldbe taken during the dehiding stage, removal ofhoofs, evisceration, and cutting to minimize cross-contamination. In addition, care should be taken tominimize spillage of intestinal tract contents.

* Good abattoir practices should include the mini-mal use of water, especially where this contributes tothe spread of faecal material.

* Special care should be paid to fruit and otherproduce to prevent its accidental contact with soilor animal faeces (e.g. fallen apples), since thesehave been implicated in the transmission of EHECinfections.

Processing of animal products andplant produce* Food producers who purchase meat from abat-toirs, or those who have their own slaughtering facili-ties, should undertake regular hygiene inspections of



the slaughter premises. In addition, food producersshould establish raw material specifications, sincethese have been shown to improve the quality ofmeat, reducing the risk of EHEC being present onraw material.

* Experts agreed that it is practically impossible toproduce raw milk without faecal contamina-tion, and felt strongly that to prevent EHEC trans-mission from milk it should be pasteurized or treatedusing procedures able to deliver an equal level ofsafety.

* Post-pasteurization contamination in the plant orafter packaging must be avoided by adherence to acomprehensive HACCP plan.* For raw, ready-to-drink fruit or vegetable juiceswhere the safety of the product cannot be assured, aprocessing step that can remove or destroy EHEC,such as pasteurization, should be applied.* Irradiation should be considered as a decontami-nation step for some products, especially if there isno other practical control or prevention step avail-able, or if they are ready-to-eat foods for highly sus-ceptible individuals.

* Manufacturers of fermented foods (such as cerealproducts, salami, mettwurst, yoghurt or cheese madefrom unpasteurized milk) which use raw materialsthat may harbour EHEC should assure their absencein a serving portion (i.e. demonstrate that their pro-cess is sufficient to remove or destroy the organismsin a serving portion).* Producers of sprouts from seeds (manufacturers,retailers, food service establishments, and thosedoing so at home) should use potable water.

Food retail and food services* The objective here should be to reduce the risk ofdirect and indirect cross-contamination between rawand ready-to-eat foods; this can be achieved throughtime and spatial physical separation, together withsafe food hygiene practices. Decisions about thedegree of separation and handling practices shouldbe made within the framework of an HACCP ap-proach. In practice, consideration will need to begiven as to how the separation will be achieved instorage, production, sale, and display; for example, itmay involve separate refrigeration, work areas,equipment, utensils, and staff.* Food handlers, including home caterers, should betrained in the principles of food hygiene and theapplication of HACCP, with particular attention tothe special precautions for preparing and serving

food to vulnerable groups, in accordance with WHOrecommendations (14).

Non-foodborne transmission of EHEC* Regulatory authorities should be made aware thatEHEC infections have been attributed to drinkinguntreated well-water, and swimming/playing in (un-treated) water contaminated by a variety of sources;and they should take appropriate action.* Both adults and children having contact with ani-mals on farms and at other sites should be madeaware of the extremely low infective dose of E. coli0157, and possibly other EHEC, and the poten-tial for transmission from such contact. Measuresto implement and enhance strict hygienic practicesin these settings should be encouraged. Visitors tofarms, who may be unaware of the highly infectiousnature of EHEC in these settings, must also be in-structed to maintain good handwashing and otherhygienic practices. This is of particular importancefor children, as several outbreaks have occurredamong school-children after visiting farms.

* Staff in laboratories working with EHEC organ-isms should be made aware of the due care requiredbecause of the low infectious dose and the severity ofdisease caused by these organisms.

Consumer educationThe reported low infectious dose of some EHECstrains, such as 0157:H7, necessitates fundamentalchange in the way meat and other foods likely to becontaminated are handled by the consumer.

* Existing education programmes should be re-viewed to ensure that they adequately address thelow infectious dose of EHEC, the understanding ofsevere, long-term effects of infection, and the needfor thorough cooking of food.* Food hygiene training should be carried out wher-ever possible within the primary and secondaryschool curriculum through the use of well-designededucational material, such as those provided byWHO (15).* An education strategy on food safety for the con-sumer, conducted by a variety of organizations (e.g.government, the food industry, consumer associa-tions, trade associations, and consumer groups)should provide consistent, clearly understood mes-sages, soundly based on scientific principles. Mes-sages could be tested by focus groups. Conflictingmessages must be avoided.


Memorandum

* Educational programmes should use all meansof disseminating information, including the media(newspapers, TV, radio) leaflets, lectures/lessons,training courses, labelling, and in-store posters/leaflets.* The concept of risk communication involving allinterested parties, including consumers, should beadopted to reduce EHEC infections.

Enacting regulatory changes* Where regulatory change affecting food supplyis considered by governments, risk assessmentsand cost-benefit analyses should be conducted first.These analyses should be transparent, available to allinterested parties, and clearly document food safety,consumer risk, and economic trade-offs.

* In order to enhance the success of trace-back ofcontaminated foods, sufficient information should berecorded or documented at each stage of movementalong the food chain, to identify the origin and desti-nation of the product.

Role of international organizations* EHEC outbreaks are rare and not all countrieshave sufficient experience or capacity to investigatethem adequately. Countries may be reluctant toaccept direct assistance from other countries. WHOshould therefore strengthen its capacity to providesupport rapidly to countries for outbreak investiga-tions and in applying prevention and control strate-gies when EHEC outbreaks are suspected.* International organizations should coordinateinternational exchange of food safety informationspecifically on EHEC to eliminate duplication ofcountry efforts.

* WHO, in collaboration with countries, should actinternationally as a collection point and clearinghouse for EHEC data. National authorities can alsodisseminate information on EHEC.* The Joint FAO/WHO Food Standards Pro-gramme (Codex Alimentarius) should support anddevelop the principles of risk analysis in developingcountries, through coordination of international ex-perts and those in developing countries, to collectrelevant data, educate and train expert teams in riskassessment to prioritize risk management optionsand develop risk communication approaches.* Codex Alimentarius should promote the applica-tion of the HACCP system and encourage both de-veloped and developing countries to design andimplement HACCP plans for specific food com-

modities, from production to marketing of locallyproduced foods and food products.

* WHO should recommend that countries enter-ing into specific control programmes, such asherd-control systems, should make available to theorganization information on the success of suchsystems.

* Following the "WHO 10 Golden Rules" will resultin a reduction of foodborne disease in general (16);however, it is recommended that these rules be re-viewed and, if necessary, revised, in view of morerecent information about foodborne EHEC infec-tions. Particular attention should be paid to the lowinfectious dose, washing of fruits and vegetables,cooking and reheating temperatures, and alternativeprocessing procedures, such as sous-vide cooking.

Resume

Infections a Escherichia colienterohemorragique (ECEH): preventionet lutteEscherichia coli est un h6te habituel de l'intestinchez I'homme et I'animal, mais il en existe certainstypes pathogenes a l'origine de diverses maladieshumaines. L'un de ces types pathogenes, E. coli0157:H7, appartient au groupe des E. colient6rohemorragiques (ECEH) qui produisent destoxines puissantes et sont a l'origine d'une maladieparticulierement grave, la rectocolite h6morragique.Chez environ 10% des malades, I'affection peut secompliquer d'un syndrome uremique hemolytiquegravissime, caract6ris6 par une insuffisance r6naleaigue, une anemie hemolytique et unethrombopenie. Ces sequelles sont particulierementgraves chez les jeunes enfants et les personnesag6es. En moyenne, 2-7% des malades atteints decette complication d6cedent, mais lors de certainesflamb6es la mortalit6 a atteint 50% chez lespersonnes ag6es.

Le pr6sent Memorandum montre l'importancecroissante de E. coli 0157:H7 en tant qu'agentpathogene transmis par les aliments. 11 traite de lasurveillance, de l'investigation des flambees et desstrat6gies de lutte, questions debattues lors de laConsultation OMS sur la pr6vention et le contr6ledes infections a ECEH. Parmi les mesures deprevention et de lutte recommand6es figurentl'utilisation d'eau potable dans la productionalimentaire, la proprete des animaux conduits al'abattoir, I'am6lioration de l'hygiene a toutes lesetapes de I'abattage, l'utilisation appropriee des



techniques de production alimentaire, la cuissonsuffisante des aliments, et I'education desmanipulateurs de denrees alimentaires, destravailleurs des abattoirs et des travailleursagricoles sur les principes et la pratique deI'hygiene des denr6es alimentaires.

References1. Abdul-Raouf UM et al. Isolation of Escherichia

coli 0157:H7 from some Egyptian foods. Intema-tional journal of food microbiology, 1995, 29: 423-426.

2. Third International Symposium and Workshop onShiga Toxin (Verocytotoxin)-producing Escherichiacoli Infections, 22-26 June 1997, Baltimore, MD, USA(in press).

3. Bernardino L et al. Haemorrhagic colitis epidemic inAfrica. Lancet, 1993, 342: 495-496.

4. Brown JE et al. Determination by DNA hybridizationof Shiga-like-toxin-producing Escherichia coli in chil-dren with diarrhoea in Thailand. Journal of clinicalmicrobiology, 1989, 27: 291-294.

5. Cordovez A et al. Enterohemorrhagic Escherichiacoli associated with haemolytic uraemic syndrome inChilean children. Journal of clinical microbiology,1992, 30: 2153-2157.

6. Risk management and food safety: report of a JointFAO/WHO Consultation, Rome, Italy, 27-31 January1997. Rome, Food and Agriculture Organization of theUnited Nations, 1997 (FAO Food and Nutrition PaperNo. 65).

7. Report of the Twenty-Ninth Session of theCodex Committee on Food Hygiene. Food and

Agriculture Organization of the United Nations Rome,1997.

8. Germani Y et al. Enterohaemorrhagic Escherichiacofi in Central African Republic. Lancet, 1997, 349:1670.

9. Kain KC et al. Etiology of childhood diarrhea inBeijing, China. Journal of clinical microbiology, 1991,29: 90-95.

10. Ogunsanya TI et al. A study of the aetiological agentsof childhood diarrhoea in Lagos, Nigeria. Journal ofmedical microbiology, 1994, 40: 10-14.

11. Paquet C et al. Aetiology of haemorrhagic colitis epi-demic in Africa. Lancet, 1993, 342: 175.

12. Sang WK. Prevalence of diarrhoeagenic Escherichiacofi in Kenyan children. Joumal of diarrhoeal diseaseresearch, 1996, 14: 216-217.

13. Son R et al. Isolation of verotoxin-producingEscherichia cofi associated with diarrhoea in Malaysiacontaining plasmids showing homology withbiotinylated Shiga-like toxin DNA gene probes. Worldjournal of microbiology and biotechnology, 1996, 12:243-246.

14. Jacob M. Safe food handling: a guide for managers offood service establishments. Geneva, World HealthOrganization, 1989.

15. Williams T, Moon A, Williams M. Food, environmentand health: a guide for primary school teachers.Geneva, World Health Organization, 1990.

16. Kaferstein FK. Pleasures and pitfalls of eating. Worldhealth, November 1988, 6-7.

17. Application of risk analysis to food standards issues:Report of a Joint FAO/IWHO Expert Consultation,Geneva, 13-17 March 1995. (Unpublished documentWHO/FNU/FOS/95.3, 1995; available upon requestfrom Food Safety, World Health Organization, 1211Geneva 27, Switzerland).


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Prevention and control of enterohaemorrhagic Escherichia coli