Enter-net is an international network for the surveillance of human gastrointestinal infections, which monitors salmonellosis and Vero cytotoxin producing Escherichia coli (VTEC) O157, including their antimicrobial resistance. When the network began it involved all 15 countries of the European Union (EU), plus Switzerland and Norway (map). The network is funded by the European Commission (EC) and represents a continuation of the Salm-Net surveillance network (1994-97), which concentrated on harmonisation of salmonella phage typing and the establishment of a regularly updated international salmonella database. Salm-Net showed, through the recognition of outbreaks and investigation, that the timely exchange of information between experts in different EU countries could lead to effective public health action in Europe and beyond. Enter-net is continuing to extend these benefits to the prevention of E. coli O157 infections.

Increasing international travel and current manufacturing and distribution practices play important roles in the occurrence of foodborne infections. All parts of the globe are now accessible within 24 hours, less time than the incubation period for most enteric pathogens. Foodstuffs are manufactured or harvested at one place and then distributed within a country or across economic regions (such as the EU), continents, or even worldwide. Events in one country, which previously might not have had implications outside its borders, now have the potential to affect many other countries. Outbreaks of infection may occur far from the source of contamination. Free movement of people and goods between countries can be effective ways of distributing disease internationally (1-3). A coordinated international response is required to control this threat.

The response that has been created is that of a surveillance network that can react swiftly to international outbreaks of foodborne infections. The participants in Enter-net are - for each country - the microbiologist in charge of the national reference laboratory and the epidemiologist responsible for national surveillance. By involving the key national experts directly, high quality data and information from reliable sources are available readily to those with the experience needed to interpret them.

The overall aims of the Enter-net project are to improve understanding of the extent and evolution of antimicrobial resistance in salmonella isolates and of the distribution of VTEC O157 infections in the EU. The objectives selected to achieve this aim are given in table 1.

Table 1: Objectives

The project involves harmonising parts of the work of national reference laboratories in countries, extending the work where necessary, and pooling the resultant data in a timely way to create an international database. Antimicrobial resistance of salmonella isolates is being determined and VTEC isolates will be typed according to an agreed protocol. To aid interpretation of resistance patterns, salmonella strains will be serotyped and phage typed as appropriate, according to existing Enter-net standards. An external quality assessment scheme for laboratory identification/typing of salmonella and VTEC is being piloted.

Surveillance of antimicrobial resistance is an important part of Enter-net. It is vital, therefore, that the results of antibiotic resistance testing from national reference laboratories are harmonised. This area is of considerable concern worldwide, and most groups emphasise the importance of being able to compare results between laboratories, by ensuring that the same methods are used. Enter-net is bringing its experience of harmonising typing schemes to address this important issue.

Each partner collects basic data on each person for whom a salmonella or VTEC isolate is submitted for further identification and typing. Such data include sex, age group, date on which illness began, travel abroad before the onset of illness, date of receipt of specimen in source laboratory, date of receipt of specimen in reference laboratory, region of source laboratory, specific VTEC serogroup, salmonella serotype, phage type, and results of antibiotic resistance testing.

Data are collected and transferred regularly by electronic link to the central databases. Surveillance reports based on analysis of these data are issued within and outside the network on behalf of all the participants, each of whom has full access rights to the database. All unusual multinational events are brought to the attention of all partners immediately. An annual workshop is held to agree protocols and priorities, review progress, and discuss results. An annual report comparing trends between countries and summarising the results of outbreak investigations is issued following discussion at the workshops.

All participants have access to common phage typing schemes for Salmonella typhimurium, S. virchow and S. dublin. Progress has been made in harmonising the phage typing of S. enteritidis. Most countries now use and report results using the enhanced phage typing scheme developed by the Public Health Laboratory Service (PHLS) Laboratory of Enteric Pathogens in London. This enhanced scheme is a result of the harmonisation work that took place during the Salm-Net collaboration.

A pilot study into the surveillance of antibiotic resistance testing results has been conducted between 18 national salmonella reference laboratories. The study showed significant concordance between results from national laboratories and has highlighted areas that still require development. This exercise has shown that valuable surveillance of antimicrobial resistance can be achieved successfully on an international basis.

Dynamic international databases have been created. The salmonella database has been in existence for several years with data from 13 countries for 1995 and 16 countries for 1998. The database for VTEC infections was set up in January 1999, and data from 1995 onwards were included retrospectively, where available. The data requested are simple enough for all participants to supply, but sufficient to allow a high sensitivity for outbreak detection. Data are sent to the central databases each month. As the infrastructure develops the frequency of reporting will increase, first to twice a month, but with the aim of weekly reporting, thus allowing events to be analysed as they occur. The database is being made available to participants on-line as part of the EC project Interchange of Data between Administrations - Health Surveillance System for Communicable Diseases (4). The creation of these databases provides an opportunity for the incidence of these diseases to be monitored.

The twin objectives of surveillance are to monitor long term trends and identify unusual short term events. The salmonella database has demonstrated its epidemiological value in both of these. Enter-net showed that isolations of S. enteritidis in western Europe were decreasing between 1993 and 1995 (5); early in 1997 they were seen to be rising again (6). Current Enter-net data show that this increase has now stopped (7).

International outbreaks can be recognised in two ways. One country may recognise an outbreak and inform the network, members of which recognise a similar occurrence in their countries. Alternatively, outbreaks may be identified by analysing pooled, international databases for unusually high levels of infection.

Individual countries that identify apparently isolated incidents can now feed this information into the network, receive replies from other participating countries, and learn quickly whether the incident is confined to their country or if it is part of a wider international event. The knowledge that a problem is confined to one country helps to eliminate potential vehicles of infection, thus allowing public health authorities to concentrate their resources more effectively.

The application of software written by the PHLS (8) facilitates the recognition of clusters of infection of international importance that would not be ascertained by national surveillance alone. This software compares current levels of infection with those expected in the light of historical data. The unusual event report flags up any serotypes that are above expected levels in more than one country. In the past Enter-net has identified outbreaks belonging to the first category but the outbreak of S. livingstone was identified by the international pooling of data alone (table 2).

Table 2:  International outbreaks recognised and investigated by Enter/Salm-net

Outbreak

Number of cases

Countries with cases

S.newport ⁹

The surveillance loop is completed by feeding back information to participants in various ways. The unusual event report is run monthly and reported back to all participants if any anomalies are detected. A quarterly report is prepared and shared within the network five to six weeks after the end of each quarter. A public domain version of this report is also made available on the world wide web (http://www.Enter-net.org.uk). Reports of the investigation of international outbreaks of foodborne infections are circulated within the network and published in scientific journals.

The creation of Salm-Net and then Enter-net was not without its birth-pains. It was soon recognised that such a surveillance network would require a clearly defined set of rules by which to work. Principles of collaboration have been written to ensure that each participant is aware of the responsibilities of membership of Enter-net. All participants are expected to sign up and adhere to these principles, which are still evolving, as new situations arise that require new solutions.

The recognition of international outbreaks of foodborne pathogens also requires new methods for the management of their investigation. This has been experienced and discussed within Enter-net, and the results of these discussions are presented elsewhere in this issue of Eurosurveillance (22).

One of the most important aspects of Enter-net is the manner in which decisions are agreed. An annual workshop is held at which consensus is reached on the major areas of development of the project. This may be preceded by the preparation of a draft document by a small working party for agreement at the workshop. The workshop is also an opportunity to promote professional trust between participants and is an essential component in building and strengthening the network.

The future of Enter-net lies in several directions: expansion of the network to include other countries, improvement of data quality in both timeliness and completeness, universal implementation of harmonised typing schemes, and standard setting for primary laboratories. Work has already started on some of these areas: discussions have already taken place with several countries in eastern Europe, and Australia, Canada, Japan, and South Africa are now full participants in the network.

Enter-net is funded by the European Commission, Directorate General XII under the Biomedical and Health Research Programme - BIOMED 2.

Project Leaders: Noel Gill, Bill Reilly, Henry Smith.

F. Allerberger, H. Halbich-Zankl, W. Thiel (Austria)
ML. Chasseur-Libotte, S. Lauwers, F. Van Loock (Belgium)
K. Mølbak, P. Gerner-Schmidt (Denmark)
S. O’Brien, H. Smith, J. Threlfall, L. Ward (England and Wales)
P. Ruutu, A. Siitonen (Finland)
JC. Desenclos, P. Grimont (France)
A. Ammon, H. Karch, H. Tschäpe (Germany)
J. Kremastinou, N. Legakis (Greece)
M. Cormican (Ireland)
A. Caprioli, I. Luzzi, A. Tozzi (Italy)
P. Huberty-Krau, F. Schneider (Luxembourg)
Y. van Duijnhoven, N. van Leeuwen (Netherlands)
V. Hasseltvedt, J. Lassen (Norway)
J. Machado, T. Paixão, I. Pires (Portugal)
J. Cowden, G. Edwards, H. Pennington (Scotland)
G. Hernández Pezzi (Spain)
Y. Anderson, S. Löfdahl, R. Wollin (Sweden)
A. Burnens, H. Schmid (Switzerland)

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