A European outbreak of Salmonella enterica serotype Typhimurium definitive phage type 204b in 2000

Authors

  • P. D. Crook,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 1 J. F. Aguilera,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 1,2 E. J. Threlfall,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 3 S. J. O'Brien,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 1 G. Sigmundsdóttir,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 4 D. Wilson,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 5 I. S. T. Fisher,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 6 A. Ammon,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 7 H. Briem,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 4 J. M. Cowden,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 8 M. E. Locking,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 8 H. Tschäpe,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 7 W. Van Pelt,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • 9 L. R. Ward,

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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  • and 3 M. A. Widdowson 9

    1. 1 Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, London, UK,
      2 European Programme for Intervention Epidemiology Training (EPIET) Paris, France,
      3 PHLS Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK,
      4 Division of Infectious Disease Control, Directorate of Health, Reykjavik, Iceland,
      5 County Durham and Darlington Health Authority, Durham, UK,
      6 Enter-net Surveillance Hub, PHLS Communicable Disease Surveillance Centre, London, UK,
      7 Robert Koch Institut, Berlin/Wernigerode, Germany,
      8 The Scottish Centre for Infection and Environmental Health, Glasgow, UK and
      9RIVM, Department of Infectious Disease Epidemiology, Bilthoven, The Netherlands
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Corresponding author and reprint requests: S. J. O'Brien, Gastrointestinal Diseases Division, PHLS Communicable Disease Surveillance Centre, 61 Colindale Avenue, London NW9 5EQ, UK
Tel: +44 208 200 6868
Fax: +44 208 200 7868
E-mail: sobrien@phls.org.uk

Abstract

Objective  To describe the clinical, epidemiologic and microbiological features of a large outbreak of infection with a multiresistant Salmonella enterica serotype Typhimurium definitive type DT204b infection involving at least 392 people in five European countries.

Methods  Icelandic public-health doctors responded to a report on an Internet news site of an outbreak of infection with a multiresistant strain of Typhimurium DT104 in England by contacting the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). An international alert was sent out through Enter-net. All strains from England & Wales, The Netherlands, Scotland and Germany, and 17 of the outbreak isolates from Iceland, were phage-typed, screened for antimicrobial resistance, and subjected to molecular typing. Hypothesis-generating interviews were conducted, followed by case–control studies performed in Iceland and England.

Results  Isolates from cases in Iceland, England and Wales, The Netherlands, Scotland and Germany were identified as Typhimurium DT204b. The antimicrobial resistance pattern was ACGNeKSSuTTmNxCpL. All strains tested displayed an identical plasmid profile. Strains from five cases in England & Wales and five cases in Iceland possessed identical pulsed-field profiles. Although a common source was suspected, only Iceland implicated imported lettuce as a vehicle, with an analytic epidemiologic study (OR = 40.8; P = 0.005; 95% CI 2.7–3175).

Conclusion  The identification of international outbreaks, necessary for investigation and control, can be facilitated by standardized phage-typing techniques, the electronic transfer of molecular typing patterns, formal and informal links established through international surveillance networks, and the early reporting of national outbreaks to such networks.

Introduction

The International Surveillance Network for Enteric Infections (Enter-net) is a network of 17 European and four non-European countries with the purpose of detecting and aiding in the investigation of outbreaks of infection with Salmonella and Escherichia coli[1]. Salmonella enterica serotype Typhimurium constituted 14.4% of the 136 704 Salmonella isolates in the 1999 Enter-net database (Enter-net, unpublished data). Serotypes of epidemiologic importance are further classified according to phage type. Background rates of Typhimurium definitive phage type DT204b infection in Europe are very low. Of the 10 025 phage-typed Typhimurium isolates in the database for 1999, only eight (0.08%) were DT204b.

We describe an international outbreak of a multiresistant clone of Typhimurium DT204b infection. That the outbreak was international was confirmed on 28 September 2000, when strains of Typhimurium DT204b with an identical antimicrobial resistance pattern (R-type) were associated with outbreaks of salmonellosis in several countries.

Icelandic public-health doctors had responded to a report on an Internet news site of an outbreak of infection with a multiresistant strain of Typhimurium DT104 in England by contacting the Enter-net surveillance hub at the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). They reported an outbreak of multiresistant Typhimurium around Reykjavik. Unlike the other countries involved in this outbreak, Iceland does not routinely perform phage typing, so 17 isolates from the outbreak were sent to the PHLS Laboratory of Enteric Pathogens (LEP) in London for full characterization. To further identify international involvement, an Enter-net message was sent to all participants, requesting enhanced surveillance of this phage type, and details of any local outbreaks.

Materials and methods

Microbiology

Phage typing and antibiogram determination

All Typhimurium isolates from England and Wales, The Netherlands, Scotland and Germany obtained during 2000 underwent routine phage typing. In addition, 17 of the outbreak isolates from Iceland were phage-typed [2,3]. All strains were screened for resistance to ampicillin (A), ceftriaxone (Cn), chloramphenicol (C), gentamicin (G), kanamycin (K), neomycin (Ne), streptomycin (S), sulfonamides (Su), tetracyclines (T), trimethoprim (Tm), nalidixic acid (Nx), and ciprofloxacin (Cp), using an agar dilution breakpoint method in IsoSensitest agar [4]. The final plate concentrations of the respective antibiotics were (mg/L): ampicillin, 8; ceftriaxone, 1; chloramphenicol, 8; gentamicin, 4; kanamycin, 16; neomycin, 8; streptomycin, 16; sulfonamides, 64; tetracyclines, 8 and 128; trimethoprim, 2; nalidixic acid, 16; and ciprofloxacin, 0.125 and 1.0. With the exception of ciprofloxacin, these concentrations corresponded to those recommended by the British Society of Antimicrobial Chemotherapy (BSAC) for the testing of resistance to antimicrobials in Enterobacteriaceae [5]. Ciprofloxacin resistance is tested for at levels below those recommended by the BSAC, because of increasing international concern over treatment failures and decreased susceptibility of S. enterica to this antimicrobial. Strains resistant to ciprofloxacin at 0.125 mg/L but sensitive at 1.0 mg/L are designated as exhibiting low-level resistance to this antimicrobial (CpL).

Plasmid extraction and analysis

Plasmid DNA from strains of Typhimurium was extracted [6], and molecular masses were calculated in megadaltons (MDa) in relation to plasmids of known molecular mass carried in Escherichia coli K12, strain 39R861 [7].

Pulsed-field gel electrophoresis (PFGE)

Genomic DNA for analysis by PFGE was prepared essentially by the method of Powell et al. [8], as modified by Hampton et al [9]. The electrophoresis conditions were 4.5 V/cm (150 V) for 47 h, with pulse time ramped from 5 s to 60 s. Gels were stained with ethidium bromide (0.6 mg/L), and visualized under UV light (302 nm). Five strains from cases infected in England & Wales and five strains from cases in Iceland were studied by PFGE. To facilitate rapid identification of the outbreak strain, pulsed-field profiles (PFPs) of isolates of Typhimurium DT204b from Germany and Scotland were transmitted electronically to the LEP and compared with those of the isolates from cases in England and Iceland.

Descriptive epidemiology

An international investigation was instigated on 28 September, and a line listing of cases was compiled. A case was defined in England and Wales, Scotland, Germany and The Netherlands as any person from whom Typhimurium DT204b R-type ACGNeKSSuTTmNxCpL was isolated from a fecal sample received in the respective national laboratory between 16 August 2000 and 31 October 2000. In Iceland, a case was defined as any person from whom Typhimurium with the above R-type was isolated in the same time period. Hypothesis-generating interviews were conducted among cases in England, Iceland, and The Netherlands.

Analytic epidemiology

Analytic epidemiologic studies were performed in Iceland, England and Wales. In Iceland, a case was defined as a person who had eaten at an implicated restaurant on 2 September and had developed acute gastrointestinal symptoms two to six days later. A control was defined as a person who had accompanied a case to the same restaurant on that day but who did not have symptoms. Nine cases and nine controls were identified in this way.

A case–control study was also conducted in northern England. A case was defined as a person from whom the outbreak strain had been cultured. Cases previously interviewed using the hypothesis-generating questionnaire were excluded from the analytic study. Two controls for each case were selected. They were matched for residence in the same postcode district and five-year age group. Twenty-one cases and 42 controls were identified. Single risk variable analysis was conducted using chi-squared tests in Epi Info [10]. Variables that had a P-value of < 0.2 from this analysis were examined further by logistic regression using SAS.

Environmental investigations

Food premises associated with more than one case were contacted or visited in order to establish the origins of implicated foodstuffs served around the time that the cases occurred.

Results

Microbiology

The antimicrobial resistance pattern (R-type) of all strains was ACGNeKSSuTTmNxCpL. All strains were sensitive to ceftriaxone. All isolates from England and Wales, Scotland, The Netherlands and Germany, and the 17 isolates from Iceland, were identified as DT204b. All these strains displayed an identical plasmid profile and possessed five plasmids with molecular masses ranging from approximately 120 MDa to 2.0 MDa.

The five strains from cases in England & Wales and five from Iceland examined using PFGE possessed indistinguishable PFPs. The PFPs of strains in Germany and Scotland transmitted electronically to the LEP were indistinguishable from those of isolates from patients in England and Iceland, confirming the clonal identity of the multiresistant strain.

Descriptive epidemiology

In total, 392 cases were identified. Iceland (181 cases) and England and Wales (140 cases) had the most cases (Table 1). Ten cases (3%) were asymptomatic. Onset dates were available for 301 (77%) of the cases (Figure 1). Most of the initial cases in August were in England and Wales, where the outbreak peaked on 20 August. The outbreak in Iceland occurred later, peaking on 8 September.

Table 1.  Descriptive epidemiology of the cases of Salmonella Typhimurium DT204b infection
 IcelandEngland
& Wales
NetherlandsScotlandGermanyTotal
Age (years)
 Median age2330.516.524.52124
 Range0–961–740–536–528–800–96
Sex
 Male96 (53%)61 (44%)8 (29%)16 (67%)12 (63%)193 (49%)
 Female85 (47%)74 (53%)19 (68%)8 (33%)7 (37%)193 (49%)
 Not known051006 (2%)
Hospitalized
 Yes32 (18%)18 (13%)3 (11%)1 (4%)7 (37%)61 (16%)
 No32 (18%)61 (44%)23 (82%)13 (54%)12 (63%)141 (36%)
 Not known117 (65%)61 (44%)2 (7%)10 (42%)0 (0%)190 (48%)
Total no. of cases181140282419392
Figure 1.

Cases of Salmonella Typhimurium DT204b in five European countries by day of onset.

In Iceland, most of the cases were in the capital, Reykjavik (63 cases, 35%) or in the nearby towns of Harfnarfijordur (16 cases), Keflavik (23 cases), and Kopavogur (16 cases). In England and Wales, 89 (64%) cases were in the north. In Germany, all the cases came from either Saxony (12 cases) or SA-Anhalt (seven cases). In each country, some cases were linked to localized outbreaks. Five cases were linked to a fast-food restaurant in Scotland. The German cases were linked to two food establishments (with no other cases identified by the German National Reference Center). A family outbreak of five cases and a cluster of another five cases around one town were detected in The Netherlands. Eighty-one cases formed part of an outbreak in the north of England. In Iceland, 37 cases were linked to two restaurants, and 21 to a home for the elderly.

Overall, males and females were affected equally (Table 1). The median age was 24 years. Most cases were in young adults aged between 15 and 24 years (147 cases, 38%) and between 25 and 34 years (87 cases, 22%) (Figure 2). The median age of cases was higher in England and Wales (30.5 years) than in Scotland (24.5 years), Iceland (23 years), Germany (21 years), and The Netherlands (16.5 years). There was a higher proportion of cases over 65 years old in Iceland than elsewhere, mostly explained by the outbreak in a home for the elderly.

Figure 2.

Age and sex distribution of all cases. NK, not known.

Sixty-one (16%) of the 392 patients were known to have been hospitalized (Table 1). Travel information was obtained for 218 cases (56%). Eighteen of these had recently traveled outside their country of residence, including six cases who had traveled between the affected countries. In The Netherlands, hypothesis-generating questionnaires revealed that, of the 17 primary cases, 15 had eaten salad in the week preceding illness, and 12 had eaten out. No particular establishment was linked to the outbreak, and no analytic study was conducted. In Scotland, no source was identified. In Germany, a fast-food restaurant was linked to the outbreak in Saxony, and a take-away kebab stall was linked to the outbreak in Saxony-Anhalt. In Iceland, descriptive epidemiology linked the majority of cases to fast-food restaurants. In northern England, results from the initial hypothesis-generating questionnaires administered to 13 people revealed that most people had eaten out in the three days prior to their sickness, with salad items, kebabs and pork products the most frequently consumed items.

Analytic epidemiology

In the case–control study conducted in Iceland, using cases identified from one of the restaurants, in which 13 of the cases had eaten, shredded lettuce was the only food vehicle associated with disease on single risk variable analysis (OR of 40.8 (P = 0.005; 95% CI 2.7–3175)).The case–control study conducted in northern England failed to identify any particular food vehicle.

Environmental investigations

Environmental sampling from two restaurants in Iceland, linked to more than one case, did not yield any positive results. However, both restaurants bought their lettuce from the same distributor. Although the exact origin of the lettuce was unclear, it was known to have been imported.

Discussion

Although a closely related Typhimurium phage type, DT204c, was a common cause of outbreaks, mainly of bovine origin, during the early 1980s in the UK and Europe [11,12], Typhimurium DT204b is a highly uncommon phage type. This is the first reported international outbreak of this multiresistant strain of Typhimurium DT204b. The concomitant temporal increase of an extremely rare strain suggests a common source. However, limited evidence supports this, as only in Iceland did an analytic study implicate imported lettuce as the vehicle. The origin of the implicated lettuce was unclear, and there was no confirmatory evidence from food samples. Lettuce is an unusual source of a salmonella outbreak, but has been reported before [13].

Background rates of Typhimurium DT204b have been very low in European countries. Between 1996 and 2000, only 40 cases of Typhimurium DT204b were reported from England and Wales (CDSC, unpublished data), and no cases were reported from The Netherlands [14] or from Scotland (Scottish Centre for Infection and Environmental Health (SCIEH), unpublished data). There had also been no reports of Typhimurium with this R-type in Iceland.

The potentially international nature of this outbreak was recognized late. Prior to an Enter-net alert at the end of September, public-health professionals in England and Wales had been investigating what appeared to be two coincident national outbreaks (Typhimurium DT104 and Typhimurium DT204b). The Enter-net alert then prompted other countries to report cases, and the international extent of the DT204b outbreak became apparent. Routine surveillance data in Enter-net are collated quarterly in arrears, which is why the clustering was not detected by the system. This is compensated for by an active process of outbreak alerts from participant countries, based on national surveillance data. A lesson from this investigation is that national centers should alert Enter-net immediately since what appears to be a national outbreak in one country might have wider implications. In this incident, late notification to Enter-net hindered conducting a single outbreak investigation across all five nations involved.

The identification of the international dimension to this outbreak was dependent on phage typing. Strain comparison was also facilitated by the electronic exchange of PFGE data between England and Wales, Scotland and Germany, following the adoption of standard running conditions for PFGE gels [15].

One important aspect of this outbreak was the high degree of antimicrobial drug resistance, including low-level ciprofloxacin resistance, shown by the outbreak strain. Multiresistance has been a major feature of Typhimurium DT204 and related strains since the emergence of Typhimurium DT204 with resistance to chloramphenicol, streptomycin, sulfonamides and tetracyclines in the UK in the late 1970s [11,16]. Resistance in this organism has been associated with the sequential use of a range of antimicrobials in bovine husbandry, in attempts to combat infection with this highly virulent strain in calves [7]. Decreased susceptibility to ciprofloxacin has, however, been very uncommon in isolates of this phage type in the UK, although such resistance has been reported in isolates of Typhimurium DT204 in Germany [17]. Since 1994, there has been a substantial increase in the incidence of strains of S. enterica with decreased susceptibility to ciprofloxacin isolated from humans in England and Wales. The appearance of these strains has been linked to the licensing in the UK of the related fluoroquinolone antimicrobial enrofloxacin for use in food production animals [12,18,19]. Treatment failures in patients infected with strains of S. enterica with decreased susceptibility to fluoroquinolones have been reported in several countries [20]. The international spread of a clone of Typhimurium DT204b with resistance not only to ampicillin, chloramphenicol, gentamicin, kanamycin, streptomycin, sulfonamides, tetracyclines and trimethoprim, but also to nalidixic acid, and decreased susceptibility to ciprofloxacin is particularly worrying.

A high rate of hospitalization was observed in this outbreak, but is an underestimate of the true value, as the level of ascertainment of hospitalization information was low. As the total population of Iceland is relatively small, the high number of hospitalized patients represents a significant public-health burden in Iceland. There are few references to hospitalization rates or case-fatality rates relating to Typhimurium DT204 in the literature for comparison. In one report of 611 infections with multiresistant strains of types 204, 204a, 204c and 193 recognized between 1976 and 1984 in England and Wales, three persons died and several persons developed severe diarrhea, while most suffered mild-to-moderate enteritis [11]. In outbreaks involving multiresistant Typhimurium DT104, hospitalization rates of around 10% have been reported in Washington, USA (9%, 5/54), California, USA (13%, 10/79), [21,22] and Ireland (12%, 7/58) [23], but a much higher hospitalization rate was reported in Denmark (44%, 11/25) [20].

The concomitant rise of an extremely unusual Salmonella strain in five countries strongly suggests that a common source was responsible, such as a foodstuff either imported into or originating in one of the countries. The rapid distribution of foodstuffs across economic regions (such as the European Union), via complex distribution networks, has the capacity to distribute food-borne infection swiftly and widely. This highlights the importance of international communication networks such as Enter-net. Furthermore, the fact that public-health officials in Iceland, which is not a member of Enter-net, stimulated the exchange of information that led to the identification of the outbreak highlights the importance of forging international communication links outside established networks.

Acknowledgments

The international surveillance network for enteric pathogens (Enter-net) is funded by the European Commission, Health and Consumer Protection Directorate, agreement No. SI2.326441. The European Programme for Intervention Epidemiology Training (EPIET) is funded by the European Commission, Health and Consumer Protection Directorate, agreement No. SI2.74030.

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