Escherichia cob infections in Scotland

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1 J. Med. Microbiol. - Vol. 4 (1994), The Pathological Society of Great Britain and Ireland REVIEW ARTICLE Escherichia cob 1 57 infections in Scotland J. C. M. SHARP, J. E. COIA", J. CURNOW7 and W. J. REILLY Communicable Diseases (Scotland) Unit, Ruchill Hospital, Glasgo w G2 9NB, * Central Microbiological Laboratories, Western General Hospital, Edinburgh and -f Department of Public Health Medicine, Health Board, Aberdeen Introduction Verocytotoxin-producing Escherichia coli (VTEC) were first described in Canada in 1977l and have been recognised increasingly as a cause of haemorrhagic colitis (HC) and of the haemolytic uraemic syndrome (HUS). Serotype 157 : H7 accounts for over one-half of all VTEC isolates from man.2 Although clusterings of HUS had been reported in Canada,3 Argentina4 and the UK,',' it was not until 1983, in Canada, that an association was first demonstrated between faecal cytotoxin and cytotoxin-producing E. coli in stool^.^ The public health implications of VTEC infection were first recognised in 1982 following outbreaks of bloody diarrhoea in the USA associated with two "fast-food " restaurants.' During the 198s, further clinical, microbiological and epidemiological information emerged, particularly from North America where VTEC infection is now regarded as the commonest cause of HUS. There had been little evidence of E. coli 157 infection in the UK before the occurrence of community outbreaks of HC and HUS in England during the mid-1 98Os,'-l1 but relatively little was known about the epidemiology of E. coli 157 infection other than the interest taken by individual mi~robiologists.~~~~~ An increasing awareness among paediatricians of the clinical importance of HUS resulted in the British Paediatric Association in 1983 including it among several clinical syndromes under surveillance," and an increase in childhood cases was observed during the late 198s in parallel with the increase in VTEC infect ions. Since 1989, in particular, isolates of E. coli 157 have been reported with increasing frequency in the UK," along with numerous community and point- source outbreak~.l~-~~ The highest rates of infection have been observed in Scotland, with 22 cases (4./ 1) in Only Canada, particularly the province of Alberta, has reported higher rates. Received 4 Feb. 1993; revised version accepted Downloaded from 3 by E. coli 157 infections in Scotland The surveillance of VTEC infection in Scotland is based upon the routine weekly voluntary reporting of isolates of E. coli 157 to the Communicable Diseases (Scotland) Unit (CDSU), Glasgow, by hospital and university laboratories as part of the national surveillance of communicable diseases. Coincidental with the increasing awareness of the public health importance of VTEC, the '' Reportable Infections" surveillance programme was introduced in Scotland in January 1989; this surveillance is based upon laboratory reporting of isolates of 32 informally selected organisms including E. coli 157 ; these are infections which are not statutorily notifiable.26 An integral part of the programme has been the nomination of national surveillance co-ordinators; two of the authors (J. E. C. and J. C.) have the joint responsibility, in collaboration with microbiological, public health and environmental health colleagues, for co-ordinating the surveillance of E. coli 157 infections in Scotland. From 1984, when the first cases were reported, until December 1992, a total of 63 isolates of E. coli 157 was reported. Only 1 cases were identified during the first 3 years ( ), followed by an exponential increase over successive years to a peak of 22 in 1991 (fig. 1; table I). Further E. coli 157 infections, including several cases of HUS, where the diagnosis was based on serological evidence, were reported but are excluded from the analysis. From 1989 onwards, E. coli 157 isolates were submitted to the PHLS Laboratory for Enteric Pathogens (LEP), Colindale, for further characterisation. The majority of these belonged to phage types 49 (36 YO) and 2 (31 Oh) ; amongst other strains identified were phage types 1,4, 14 and 32. Thirteen infections were associated with recent travel abroad-spain (9, Turkey (2), Germany (2), Italy (l), Gambia (l), France (1) and Majorca (1)-and in a further episode the apparent index case in a family outbreak had returned recently from France with diarrhoea. Other enteropathogens-carnpylobacter spp. (7), Aeromonas hydrophila (3), Salmonella spp.

2 4 J. C. M. SHARP ET AL Year Fig. 1. Incidence of reported E. cofi 157 infections in Scotland, (2), adenovirus (2), Shigella sonnei (l), Clostridium dificile (1) and E. coli 127 (1)-were also isolated from individual patients. Whereas the 1 cases during were all reported from one laboratory in Glasgow, most isolates thereafter were from laboratories in health boards in the east of Scotland. Of these, five health boards (,, Tayside, Fife and Borders), servicing 41 YO of the Scottish population, reported 74 YO cases in the last 3 years, (fig. 2)., with < 1% of the total population, accounted for 198 (31 %) of all isolates (table 11), of which 67 (13~/1) were in In contrast, laboratories in the west of Scotland reported significantly lower rates. Most infections occurred during the summer and early autumn; 71 % of cases were reported between May and October (fig. 3). The age range of cases was between 2 weeks and 96 years (mean 31 years, median 24 years). There was a female : male predominance of cases of 3 : 2, although males were more common up to 14 years of age (table I). PrBschool children and persons over 65 years old had the highest infection rates with the lowest in the year age group (table 111). Two hundred and thirteen patients (34%) were known to have been admitted to hospital for treatment, 46 of whom, aged from 6 months to 81 years (mean 21 years, median 5 years), developed HUS. Fifteen deaths, age range 9-96 years (mean 61 years, median 74 years), were recorded, of which five were in frail, elderly patients in outbreaks in long-stay health care facilities (table 111). No clustering of cases was apparent until 1989, when four persons were identified in a town near Edinburgh. In 199, five general outbreaks occurred (table IV), of which three were apparently food-borne involving a restaurant21 and two nursing homes; an outbreak in a village community, in which C. jejuni was also isolated from two of the four laboratoryconfirmed cases, was water-borne in origin; and an outbreak in a psycho-geriatric hospital unit was associated with person-to-person spread involving both patients and nursing In 1991, eight general outbreaks were reported. One outbreak affected two residential homes in the Borders with the same butcher meat supply,22 one was associated with food from a delicatessen in 2 and another with an ethnic take-away restaurant in. Concurrent with an outbreak in NW England in early 1991,24 two cases infected with the same uncommon, urease-fermenting strain of E. coli 157 were identified in the west of Scotland; both cases had eaten hamburger-type food in a Glasgow restaurant belonging to the same fast-food chain. Amongst the many family outbreaks were two separate episodes in which three persons developed HUS. Other notable outbreaks included four members of an Edinburgh family who were infected following the return from overseas of the index case, and two young sisters in who were infected 12 months apart with E. coli 157 organisms belonging to two different phage types. In 1989, surveillance was intensified in Scotland, particularly in where all cases were visited and a detailed epidemiological and clinical history was obtained. Food histories frequently implicated undercooked hamburgers or poultry, and occasionally other meats or unpasteurised milk.27 outbreaks and clustering of cases were also identified from time to time. In one town (population 2), 17 cases of E. coli 157 infection were identified between 1989 and E. coli 157 infections in England and Wales A similar increase in cases and outbreaks has also been observed in recent years in England and Wales

3 E. COLI 157 INFECTIONS IN SCOTLAND 5 Table 1. E. coli 157 surveillance reports (a) Year (1 9-) Number of reports '84 '85 '86 '87 '88 '89 '9 '9 1 ' (b) Four-weekly period Number of reports > 65 Mean age Median age where a total of 476 isolates of E. coli 157 (-9/ 1) were confirmed by LEP, Colindale, in In Wales, where active surveillance by screening for E. coli 157 in all faecal samples submitted from cases of acute diarrhoea has been undertaken since 199,29 isolation rates have remained relatively unchanged (1.2/1) over the past 3 years (R. L. Salmon, personal communication). E. coli 157 infections in North America During the 198s, an exponential rise was observed in E. coli 157 infections in Canada;3 several community and point-source outbreaks involving nursing homes and school groups were identified. Isolates submitted to the National Reference Centre for Enteric Bacteriology, Laboratory Centre for Disease Control, Ottawa, doubled each year rising from 25 in 1982 to 247 in 1989 (H. Lior, personal communication). VTEC infections were notifiable in Alberta and British Columbia throughout the 198s and became notifiable across all Canada in In the USA, where E. coli 157 infection is not under national surveillance, a few states only, such as Washington, Oregon and Minnesota, undertake semiactive surveillance. Between 1982 and 199, 12 outbreaks involving schools, day-care centres, institutions and restaurants were investigated, seven of which occurred in states bordering Canada.3' Most recently, between November 1992 and February 1993, the largest recorded outbreak with over 5 laboratoryconfirmed cases associated with eating hamburgers from one restaurant chain occurred in the western USA, in particular the state of Wa~hington.~~ E. coli 157 in other countries Given the clinical severity of many cases, it is surprising that neither VTEC nor HUS have been more widely reported outside the UK and North America. Isolates and outbreaks have been reported on occasion from Belgium,33 Denmark,34 Italy,35 and Southern Africa.37 Prospective surveys undertaken in several countries have generally yielded very low isolation rates of E. coli However, a more recent multi-centre study has demonstrated the clinical importance of VTEC infections as a cause of HUS in Germany and other central European countries.39 Whether the incidence of infection internationally is as low as would appear or whether there are differences in awareness and in laboratory techniques, is unclear. Laboratory aspects Laboratory reporting of E. coli 157 isolates plays a central role in monitoring these infections. In contrast to most E. coli isolates of human origin, E. coli 157: H7 does not ferment D-sorbitol within 24 h,4*4' and sorbitol MacConkey agar (SMA) has been developed as a simple, rapid screening medium for these organisms.42 Sorbitol non-fermenters are then subjected to various further tests which may include O-agglutination serology (OAS), 157 latex agglutination and H-agglutination serology (HAS).43, 44 Verotoxin (VT) production can be demonstrated by testing strains for a cytotoxic effect on vero ce1ls.l VTEC may also be detected by hybridisation with specific VTl and VT2 DNA These latter two methods are suitable for the detection of VTEC of serogroups other than Further characterisation of 157 VTEC for epidemiological purposes may be performed by phage typing.46 During the first 5 years of reporting ( ), when very few laboratories were known to be screening, five laboratories, mainly in the west of Scotland, accounted for the 61 isolates of E. coli 157

4 6 J. C. M. SHARP ET AL. Orkney (3.4) Western Isles (1.1) Highland (-) (9.8) Tayside (3.8) Argyll & Clyde (1.1) Greater Glasgow (1'1) Lanarkshire (1'8) Ayrshire & Arran (1.1) Dumfries & Galloway (2.5) Fife (3.6) Forth Valley (2.7) (4.) Borders (1 1.5) Scotland rate = 3.2 Fig. 2. E. coli 157 infection in Scotland. Mean annual isolation rates per 1 population by Health Board of reporting laboratories, 199g1992. (Registrar General for Scotland estimated mid-year population, ) Table 11. Geographical distribution of cases of E. coli 157 infection in Scotland by health board of reporting laboratory, Table 111. Age distribution of cases of E. coli 1 57 infection, hospital admissions and deaths, Health board Tayside Greater Glasgow Fife Lanarkshire Borders Others Number (YO) Mean annual of cases rate/ (31) 16 (17) 67 (11) 63 (1) 51 (8) 42 (7) 37 (6) 66 (1) * *4 Age group Number Admitted to Deaths (years) of cases hospital (6*)* (1-5) (.9) (.6) (.9) (1.) (.9) (1-5) Not known (2-3)* 31 (1.) 14 (.2) 9 (.1) 12 (.2) 18 (-3) 21 (.4) 39 (.6) (.4)* 1 (.2) 3 (.6) 9 (.13) 15 recorded. In 1989, 87 isolates were reported from 16 laboratories. In April 199, a survey (V. J. Dev, unpublished data) of the 34 National Health Service bacteriology laboratories in Scotland, revealed that 29 *Numbers in parentheses are the mean annual rates/ 1 population. were examining for E. coli 157 either routinely (five laboratories) or selectively (24 laboratories). A followup survey 1 year later showed that this had increased 1 1 D 9 a, 8 t 1 t I I I I 1 I Four-weekly period (all years) Fig. 3. Distribution and incidence of E. coli 157 infection throughout 4-weekly periods when all years were considered.

5 E. COLI 1 57 INFECTIONS IN SCOTLAND 7 Table IV. E. coli 157 general outbreaks, Number Date Location Type of outbreak of cases Mode of spread (deaths) 1989 May 199 May/ August October November 1991 January February February August September November 1992 May Glasgow Lanarkshire Edinburgh Perth Borders Tayside Borders Glasgow Ayrshire Nursing home Restaurant Hospital Nursing home Two social work homes Birthday party Hospital 4 >4 Water 8 (2)?Food 16 Food 9 (4) Person-to-person 5?Food (1) > 1 3? Vegetables Delicatessen Restaurant(s) Butcher s shop 5 Paddling pool > 5 Person-to-person 3 to 33, reflecting the increasing level of interest; of these, eight routinely cultured all faeces and 25 cultured selectively. The selection criteria included various clinical (e.g., bloody diarrhoea, HC, HUS and fluid stools) and age-related (e.g., babies and children under 1 years old) parameters. Nine laboratories have since relaxed their selection criteria and increased the number of faecal samples screened for E. coli 157. All the Scottish laboratories employed SMA for preliminary screening of faecal samples ; 23 laboratories performed OAS testing, but only three tested for HAS. Approximately 5% of the laboratories employed a latex agglutination test of some description. Only two laboratories tested for the production of VT and none used DNA probes to detect VTEC. All but one laboratory referred isolates to LEP, Colindale, for confirmation of serotype, detection of VT, DNA hybridisation studies and phage-typing. The success with which laboratories in Scotland have been able to isolate E. coli 157 from faecal samples is in marked contrast to the failure to isolate the organism from foodstuffs. There are a number of possible explanations. Some laboratories still rely on direct plating of foodstuffs on to SMA for detection and isolation of E. coli 157. However, North American studies have demonstrated a 1-fold increase in sensitivity by enrichment in a modifed tryptic soy br~th.~~-~ This may be important, as several studies combining filtration and immunological techniques have demonstrated that food associated with outbreaks of E. coli 157 infection may contain as few as 1 organisms/g.**~ Furthermore, some routine procedures for the detection of presumptive faecal coliforms in foods use incubation temperatures in the range C, at which some strains of E. coli 157 : H7 grow poorly. Veterinary aspects There have been many, often conflicting, reports of the presence and significance of E. coli 157 in animals and animal products. In the USA, in a survey of retail fresh meats, E. coli 157:H7 was isolated from 6 (3.7 YO) of 164 samples of beef, 4 (1.5 YO) of 264 pork, 4 (1.5 YO) of 263 poultry and 4 (2.%) of 25 lamb,51 and, more recently, from ground beef associated with the multi-state outbreak involving a fast-food restaurant chain.32 However, in one Canadian study, examination of beef, pork and chicken samples failed to demonstrate E. coli 157, although other VTEC serotypes were isolated.52 As part of the investigation of outbreaks of human VTEC infections in North America, E. coli 157: H7 was isolated from apparently healthy dairy53* 54 and beep5 cattle, although in the latter investigation the plasmid profiles and relative frequency of production of VTl and VT2 differed between the bovine and human isolates. In another survey, E. coli 157:H7 was identified in healthy cattle and in milk.56 E. coli 157 has been isolated from bovine faeces in abattoir surveys in Sheffield, UK5. 58 and from healthy cattle in Germany.59 However, there is little evidence of pathogenicity in cattle. In Argentina, in 1977, three strains of E. coli 157 : H7 were isolated from calves suffering from colibacillosis.6 In the UK, E. coli, usually enterotoxigenic strains, are a common cause of enteric disease in young farm animals. A survey in Scotland and northern England in the early 198s identified

6 8 J. C. M. SHARP ET AL. verotoxin production in one of 28 E. coli isolates from cattle, but the organism was not serotyped. l More recently, a survey in Scotland begun in early 1992, resulted in the isolation of verotoxigenic E. coli 157:H7 from five calves out of 1247 bovine faeces examined; no isolates were made from 4 sheep, 114 pigs and 29 miscellaneous species.62 Since this report, isolates have been made from further calves and from older cattle (B. A. Synge, personal communication). In most instances, the isolates were from animals with diarrhoea, with other pathogens such as Cryptosporidiurn sp. or rotavirus also present. A continuation of this survey will investigate the role of VTEC as a bovine pathogen and its epidemiology in infected herds. Other investigations are currently being undertaken in the UK to try to establish the importance of E. coli 157 in animal disease or as a reservoir for human infection. Conclusions E. coli 157 has become an enteric pathogen of increasing importance. Although the incidence of infection reported in the UK overall is low compared with North America, the clinical severity of the disease and the increasing number of cases recorded in recent years are of concern. As with the surveillance of any infectious disease, the available data probably underestimate the true incidence and it is possible that this increase merely reflects increased awareness. In Scotland, laboratory practice has changed during this time, with the majority of laboratories culturing for E. coli 157 from 199 onwards. In 1991, the five laboratories that started to examine for E. coli 157 in that year reported six isolates. Paradoxically the nine laboratories that had relaxed their screening criteria reported nine fewer. The decrease in the number of reports during 1992, in the absence of any known changes in laboratory practice or active intervention References 1. Konowalchuk J, Spiers JI, Stavric S. Vero response to a cytotoxin of Escherichia coli. Infect Immun 1977; 18: Pai CH, Ahmed N, Lior H, Johnson WM, Sims HV, Woods DE. Epidemiology of sporadic diarrhea due to verotoxinproducing Escherichia coli: A two year prospective study. J Infect Dis 1988; 157: Lamvik JO. Acute glomerulonephritis with hemolytic anaemia in infants. Report of three fatal cases. Paediatrics 1962; 29: Gianantonio CA, Vitacco M, Mendilaharzu J, Mendilaharzu F, Rutty A. Acute renal failure in infancy and childhood. Clinical cause and treatment of forty-one patients. J Pediatr 1962; 61 : 66& McLean MM, Jones CH, Sutherland DA. Haemolytic uraemic syndrome. A report of an outbreak. Arch Dis Child 1966; 41: Ruthven IS, Fyfe WM. The haemolytic uraemic syndrome-an epidemic disease. Scott Med J 1968; 13: Karmali MA, Steele BT, Petric M, Lim C. Sporadic cases of haemolytic uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet 1983; 1 : measures, suggests that additional factors are influencing the epidemiology and merits further attention. Another intriguing feature is the difference in isolation rates between laboratories located in the east and west of Scotland. This geographical variation is difficult to explain, even when allowing for the more active surveillance in recent years, particularly in and now also in. Whether the differences relate to enhanced surveillance, to different agricultural practices or to local food preference between the east and west of the country, is unknown. HUS is an important life-threatening complication of VTEC infection, but the available epidemiological data are considerably less comprehensive than for E. coli 1 57 infectionsper se. It is regrettable that HUS was dropped from the list of conditions reportable by paediatricians in Britain in 199. Phage typing of E. coli 157, still the most readily available typing scheme, has proved an invaluable epidemiological tool, complementing surveillance by facilitating not only the detection of commonsource community outbreaks which otherwise might have remained unrecognised, but also in differentiating concurrent outbreaks as was experienced in in September 199 (C. N. Ramsay, personal communication). The failure in the UK to isolate E. coli 157 from food or water continues to frustrate attempts to devise effective intervention strategies. The need to improve the definition of risk factors for infection and to identify food sources has resulted in the Chief Scientist s Office of the Scottish Office Home and Health Department providing funds for a pilot descriptive epidemiological study during , with the objective of generating the hypotheses required to establish a full analytical case-control study. Meanwhile, the reports of isolations from veterinary sources in the UK are particularly exciting, and take us a step closer towards establishing the source(s) of human infection by this important pathogen. 8. Riley LW, Remis RS, Helgerson SD et al. Haemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med1983;38: Taylor CM, White RHR, Winterborn MH, Rowe B. Haemolytic uraemic syndrome : clinical experience of an outbreak in the West Midlands. BMJ 1986; 292: Morgan GM, Newman C, Palmer SR et al. First recognised community outbreak of haemorrhagic colitis due to verotoxin-producing Escherichia coli 157 : H7 in the UK. Epidemiol Infect 1988 ; 11 : Salmon RL, Farrell ID, Hutchison JGP et al. A christening party outbreak of haemorrhagic colitis and haemolytic uraemic syndrome associated with Escherichia coli 157: H7. Epidemiol Infect 1989; 13: Smith HR, Rowe B, Gross RJ, Fry NK, Scotland SM. Haemorrhagic colitis & verocytotoxin-producing Escherichia coli in England & Wales. Lancet 1987; 1 : Liddell KG. E. coli 157 and haemorrhagic colitis in South Lanarkshire. Comm Dis Scot Wkly Rep 1988; 22(27): Lafong AC, Graveling E. E. coli 157 in Fife. Comm Dis Scot Wkly Rep 1989; 23(42): Paterson A, Gould IM, Cashmore C, Reid TMS. E. coli 157-one year s experience in. Comm Dis Scot Wkly Rep 199; 24(5): &lo.

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