Experts assess use of genome sequencing in multi-country outbreaks

Experts assess use of genome sequencing in multi-country outbreaks

Experts have discussed the major obstacles to adopting whole genome sequencing (WGS) for surveillance and monitoring of foodborne diseases in Europe.

The “Next Generation Sequencing to Tackle Foodborne Diseases in the EU” event was originally planned for March at the Istituto Superiore di Sanità in Italy but was moved online and to late September because of the coronavirus pandemic.

A survey with 100 responses during the conference revealed absence of a legal framework, issues with data confidentiality and ownership, an absence of bioinformatics expertise, and lack of funds to be some of the stumbling blocks.

Speakers included Martial Plantady of the European Commission, Saara Kotila from the European Centre for Disease Prevention and Control (ECDC) and Valentina Rizzi of the European Food Safety Authority (EFSA).

Presenters at the conference

Almost all of those surveyed agreed that WGS-based surveillance and monitoring at the EU level would be beneficial. The most useful features included deepness of the analyses, it can replace most, if not all, other methodologies, it is automated and the sensitivity.

Plantady said it was too soon for rules on making WGS compulsory as part of official controls.

“I am convinced in the coming years more member states will perform WGS and share data. At that point we will reflect internally with them on imposing use of the tool under certain circumstances but now is too early. We encourage, and put in place the European Union Reference Laboratory (EURL) network, to build capacity in National Reference Laboratories (NRL) and private labs doing official controls. WGS is not standardized enough to be part of official controls so it is a vicious circle,” he said.

WGS findings need epi data


Saara Kotila from ECDC said WGS-based methods have quickly become standard in foodborne and waterborne outbreak investigations.

“The high discriminatory power of the method allows you to confirm a link between cases and isolates, which was not possible with older methods, however to clarify the nature of the link other data is needed, such as epidemiological and sequence data from non-human isolates of various origins such as food, animals and the environment to track possible foodborne sources and vehicles,” she said.

“There are various different ways of analyzing WGS data available and used in different countries and laboratories. It is important that these can draw the same conclusions from the same raw data and that the full dataset is analyzed – this is why sequence data sharing between institutes is needed.”

Epidemiological data could include age, gender, region of country, travel information and consumption and exposure data of patients.

ECDC has been coordinating WGS-enhanced listeriosis surveillance since March 2019.

“Eighteen of 30 clusters containing microbiologically closely related patient isolates detected since beginning the surveillance had less than five isolates, which at EU level is small. We have a draft criteria as to at what point a cluster should be escalated,” said Kotila.

Escalation can mean more countries becoming involved but all clusters are communicated to affected nations. The level of escalation depends on the number of cases and countries involved.

“We want to have six or more isolates from the past 12 months from two or more countries. Every time an urgent inquiry is launched (usually done by national health institutes but can also be by ECDC), it is voluntary for countries to answer. This means work for them, and it is even more resource-intensive to start further investigations in collaboration with food safety authorities,” said Kotila.

“If too many urgent inquiries and investigations would be launched, national authorities would struggle with resources and possibly stop contributing. There is always a need for finding a balance of resources and public health value to prioritize investigations.”

EFSA to collect WGS data from non-human isolates


Valentina Rizzi, from EFSA, said centralized WGS data collection is needed to support prompt investigation of multi-country foodborne outbreaks.

“When there is the need to collect sequences from countries in the context of a multi-country outbreak investigation, EFSA is supported by the European Union Reference Laboratories for foodborne pathogens and their network of National Reference Laboratories,” she said.

“Starting from the end of next year EFSA will be able to collect from countries WGS data from non-human isolates of Listeria monocytogenes, Salmonella and E. coli submitted on a voluntary basis through the One Health WGS system. Foreseen data users of the new system will be competent authorities and laboratories of EU member states and other reporting countries that will sign a bilateral agreement with EFSA.”

The One Health WGS system will be two interoperating systems, one in EFSA and one in ECDC, collecting and storing data. The aim is to collect baseline typing information to detect clusters of foodborne diseases and to generate hypotheses on the possible food vehicles involved.

Data dilemma


Survey respondents said the main drawbacks of posting data in the public domain include disclosure of sensitive information that might affect the privacy of people, use by other scientists, and a lack of harmonization and standardization of methodological processes.

Photo illustration

Kotila said firms might be worried about cases being linked to their products, harming reputation, and having an economic impact on sales.

“But they could benefit from these investigations, as outbreaks could be detected earlier and controlled before possible escalation, e.g. ending up under intense press attention and/or court cases. On the other hand, sequencing data can also show that a company is not linked to a specific outbreak,” she said.

“Some worries have been that someone takes out the available data and makes scientific publications without acknowledging the data source/owner, which may want to do their own publications with the same data. Hopefully, when more and more institutes/people share sequence data, others will follow as they will see that there is nothing to worry about.”

Rizzi said data submission will contribute to food safety and protection of consumers within the EU.

“Submitting data to our system should provide an added value for the providers. It is essential to stress that the ownership belongs to the producers of the data. In the EFSA system the data owner will be the provider organization who bears the responsibility to obtain the consent for data sharing from the original data producer,” she said.

“Data from industry should be collected at country level and their sharing at EU level is under the responsibility of the data provider officially nominated in the country. Confidentiality is ensured through the data sharing in a secure network and data management regulated by agreements.”

An example of EFSA services is giving back to data providers the results related to their data and how they relate with other isolates in the database.

George Haringhuizen and Eelco Franz both from the Dutch Institute for Public Health and the Environment, Annemarie Kaesbohrer, of the German Federal Institute for Risk Assessment, and Patrick McDermott, director of the National Antimicrobial Resistance Monitoring System  also presented at the event organized by the EURL working group on NGS and Med-Vet-Net Association.

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