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11.07.2019

“One Health Meets Sequencing” symposium

A summary of the most important issues discussed on 21 May. By organisers Adrian Egli, Jaques Schrenzel and Roger Stephan.

In recent years, a revolution in microbiology has taken place: whole genome sequencing (WGS) technologies have enabled us to very quickly decipher the entire genome of microorganisms, including pathogens. As a result, we can now analyse the genetic data of all bacteria, fungi and viruses. These developments not only advance research; they also open up completely new possibilities for practice. Thanks to WGS, we have been able to identify the transmission patterns of pathogens, genetically coded antibiotic resistance mechanisms and virulence factors such as toxin genes in unprecedented high resolution in samples from patients as well as from animals, food and the environment. By aggregating and comparing data, we can track pathogens and resistance along the distribution chain in the event of disease outbreaks.

Application to public health

The new methods and associated bioinformatics analysis have already become the gold standard in science. But a number of legal, ethical and economic issues have emerged with regard to practical application, not least of which is exactly how WGS is going to benefit public health.

On 21 May, over 90 experts from research, practice and the public sector gathered together at the “One Health Meets Sequencing” symposium at the KKL Luzern to discuss these important issues. The first-class line-up of both speakers and audience testified to the urgency of such exchanges. And, as the concluding discussion made clear, WGS is poised to become the standard for outbreak investigations and monitoring. But when and how, and how much is to be gained in terms of public health, depends on many factors that need to be addressed.

Building capacity and clarifying legal questions

What federal officials have repeatedly emphasised is borne out by observation: research is moving ahead, while the legal framework and routine diagnostics struggle to keep pace. However, an important finding of the symposium is that various bodies are already heavily involved in WGS, and concrete plans for setup and standardisation are already in the works.

The major challenges have also become clear. We will summarise these briefly in light of the comments and discussions at the symposium:

Capacity building in laboratories

At present, the infrastructure, expertise and sufficient experts to carry out WGS on a larger scale and to process data are almost exclusively the province of university hospital laboratories and larger institutions. Yet, effective monitoring of multiresistant pathogens in humans, animals, food and the environment, for example, depends on large-scale technological coverage. Smaller institutions lack the necessary capacities. The federal government currently focuses on reference laboratories, most of which collaborate with university centres on WGS analyses. In the future, it is foreseeable that WGS data will also be generated in smaller laboratories and that structured archiving and analysis of the data will become increasingly important.

Reporting in Switzerland across all sectors

Monitoring pathogens in the context of One Health requires many different stakeholders to work together, in particular federal agencies, cantonal agencies and diagnostic laboratories. But the authorities are not organised in a way suited to the One Health paradigm. The federal government’s One Health interagency group will most certainly assume an important function in this regard. In order for data sharing to be successful, all areas of the WGS process must also be standardised. Every step of the process from sample acquisition to analysis and interpretation would benefit greatly from central data management.

International data sharing

To date Switzerland remains an outlier in international monitoring of antibiotic resistance, as the data are not linked to other European centres. However, in setting up any new type of monitoring, it will be essential to connect to international databases. In the veterinary sector this is already planned at the federal level. In the area of human medicine, unfortunately, it depends on factors which lie outside the reach of individual bodies, namely the framework agreements with the EU. Last but not least, legal questions regarding the use of data must also be considered.

Legal basis

Monitoring requires a clear mandate. This is essentially provided by the Epidemics Act, but depending on the estimated affected range, responsibility may fall to the cantons or the federal government. Clarifying this question will have a decisive effect on how data on hypervirulent and multiresistent pathogens are shared across Switzerland. This in turn raises legal questions, because effective monitoring links WGS data with (encrypted) patient data. However, if the data are completely anonymised, chains of transmission can no longer be reconstructed down to individuals. For example, valuable time would be lost during a national outbreak of a highly dangerous pathogen. Here is where the Epidemics Act could provide an important basis for data sharing, but its application in monitoring pathogens is still unclear. Although the Human Research Act already allows examining data for scientific purposes with the consent of patients, a more extensive legal mandate is necessary for continuous monitoring.

Clear priorities

Not everything that is feasible also makes sense in terms of public health. From the point of view of authorities, clear priorities are necessary, including a cost-benefit analysis. Because developing and implementing a new system will require additional resources, where WGS can provide the greatest benefit needs to be determined. However, the data basis for such a determination is lacking. Nonetheless, because the potential of WGS lies not least in its ability to detect, for example, novel resistance through continuous monitoring beyond the confirmation of already suspect samples, in our view restricting a new technology for special cases is not helpful. This is another challenge for science: it must demonstrate the possible medium- and long-term benefits of WGS by means of innovative studies.

We need to communicate – now!

The issues outlined here are obviously closely related. Questions of data protection are just as crucial in organising the reporting system in Switzerland as they are for international data sharing. Clarifying the responsibilities of the federal government and the cantons will have an impact on how monitoring is organised – and financed. Moreover, a standardized data format agreed by the scientific community is a prerequisite for cross-sectoral analysis in a One Health approach.

Consequently, it is all the more important that all stakeholders discuss the use of WGS in practice jointly, and at an early stage. This reinforces what is probably the most common feedback we received after the symposium: it is precisely these discussions that are needed now, and we have to keep them up. That is what we are doing.

Adrian Egli, Jaques Schrenzel, Roger Stephan

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Dr. Adrian Egli Departement Biomedizin Universitätsspital Basel Hebelstrasse 20 4031 Basel +41 61 265 42 44 adrian.egli@usb.ch