The authors represent the European Surveillance Network for Vigilance against Viral Resistance (VIRGIL), an EU funded research project which is producing important data on markers of antiviral resistance in influenza and other viruses identified in Europe.[3] They do so working with the European Influenza Surveillance Scheme (EISS) and National Influenza Reference Laboratories. The evaluation of both neuraminidase inhibitor and adamantane resistance of European influenza isolates is carried out in London by the Health Protection Agency Centre for Infection in collaboration with one of the four WHO Collaborating Centres for Reference and Research on Influenza.[1,2] Such data are important in informing the choice of clinicians for antivirals especially since the emergence of resistance markers to the adamantanes in a number of countries and a few reports of resistance to oseltamivir in Japan.[4,5] Generating and gathering data relating to anti-viral resistance should become a routine function annually in the EU. However in a pandemic it would be important to quickly determine any resistance and to monitor for it emerging following mass use of antivirals. Currently, Europe has no routine monitoring of antiviral resistance for influenza though there are a number of published individual reports and a global network.[6]

We agree that there should be monitoring of influenza antiviral resistance in the EU and support the VIRGIL activities in promoting routine resistance monitoring, however we are cautious in recommending that influenza susceptibility testing should be developed in all 27 EU countries as a priority activity for pandemic preparedness. Therefore this recommendation does not seem to take into account the large differences existing between European countries in term of resources and organisation of the healthcare systems, and hence their need to differently prioritise preparedness activities. Antiviral resistance testing and monitoring is expensive and would inevitably detract from investment in other laboratory work. Secondly, the presence of a national laboratory performing antiviral resistance testing in each country, does not necessarily imply that antiviral resistance monitoring for clinical and public health purposes will be effectively carried out in Europe during a pandemic. For effective monitoring of antiviral resistance, laboratories should be able to:

• routinely collect and test an adequate and representative number of samples;
• continuously provide resistance figures to public health policy makers in a timely way;
• with others gather relevant epidemiological data for monitoring risk factors for resistance should it emerge at a significant level.

This might not be feasible in all countries in Europe in the short term. Therefore in preparation for a pandemic, a possible solution to guarantee an efficient monitoring of antiviral resistance would be to have an agreement between countries so that some pre-defined laboratories can be supplied with a representative number of viruses and then constantly feed information on the drug resistance profile of the pandemic virus to all Europe. This strategy entails that there is prior agreement that samples/virus isolates and data from all countries are shared and tested according to previously agreed protocols. Common shared protocols should form the basis for regulating this collaboration including estimates of the maximum number of samples that can be tested in the different phases of the pandemic. Such approach would also be valuable for countries with difficulties not only in testing but also in collecting samples as they will receive information on the drug resistance profile of the pandemic virus circulating in Europe.

This kind of collaboration exists already between countries in the WHO Global Influenza Surveillance Network where National Influenza Centres collect specimens in their country, perform primary virus isolation and preliminary antigenic characterization, but they ship newly isolated strains to one of the four WHO Collaborating Centres for high level antigenic and genetic analysis, the result of which forms the basis for WHO recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year.[2,7]

On a more general perspective, we can expect that during Phase 6 of a pandemic the request for data from policy makers and the politicians to public health institutes will probably run ahead of what can be delivered. Careful planning is therefore needed to select the information that is of public health value. In this context it would be crucial to distinguish between what data should be collected in every Member State, and what has an EU added value and can be agreed as being done at EU level (in some but not all countries) but the results being fed back to all the Member States. If a pandemic starts in the next few years, antiviral resistance monitoring would probably fall in the latter category as well as other specific surveillance information including those on characteristics of transmission, case fatality rates, antiviral and vaccine effectiveness, etc. This is the subject of work being led by ECDC with a working-group of experts from Member States working on surveillance in a pandemic.

Bruno Christian Ciancio, Angus Nicoll (angus.nicoll@ecdc.europa.eu)
European Centre of Disease Prevention and Control (ECDC), Stockholm, Sweden