EU and EEA/EFTA Briefing Document Update August 10th 2008
As you may be aware this issue emerged in late January 2008 following testing by the EU-VIRGIL research project and a WHO Collaborating Centre and notification by the Norwegian authorities through the EU Early Warning and Response System (EWRS) and the World Health Organization International Health Regulations (IHR) mechanism.
Subsequently an ECDC Interim Risk assessment was circulated though EWRS, an EWRS teleconference was held by the Commission and a stem ECDC webpage on Influenza and Antivirals was created through which all relevant information can be accessed. Similar information is available through the European Influenza Surveillance Scheme (EISS) web-site and global data through the WHO website.
It has become apparent from further testing that these viruses are to be found at very variable levels in most of EU/EEA/EFTA member states (MS). As of July 28th these transmissible human viruses have been detected in 21 EU/EEA/EFTA member states with levels up to 67%. However there are five other Member States where no resistant viruses have been detected at all. I.e. the situation is variable across Europe. Though the 2007/8 season is now over where the viruses were detected and testing was continuous there was indication that the resistable viruses declined away any quicker than their equivalent susceptible A/H1N1 viruses, indeed in most countries they became more prevalent until all A(H1N1) viruses were overtaken by influenza B viruses and the season finished. I.e. these were ‘fit’ viruses circulating in the community. This is the first time that fit oseltamivir resistant viruses have ever been observed anywhere in the world, though the fact that they have first been observed in Europe does not necessarily mean they originated here.
The purpose of this communication is to update relevant bodies in the EU and EEA/EFTA countries of what has happened more generally and what the arrangements are for further investigations and updates later in the year and into the next (2008/9) influenza season.
Following teleconferences among Member States, WHO, EISS, the European Medicines Agency (EMEA) and ECDC and the formal EWRS teleconference convened by SANCO C3 (which included the members of the Health Security Committee Influenza Section) the response to this incident has settled down to the following arrangements:
It has been agreed that all relevant virological and epidemiological data should be made available to member states, EISS, VIRGIL, ECDC, the Commission and WHO. This has been achieved on a practical level by National Influenza Centres uploading data to the EISS-Antiviral Susceptibility Database which was augmented to capture limited clinical and risk data as well as its usual virological information. Data descriptions, analyses and presentations are then produced from that database such as those displayed monthly on the ECDC, EISS and WHO web-sites.
In addition to the work done by the Central VIRGIL Influenza Laboratories and the WHO Collaborating Centre in London antiviral resistance testing using sequencing has been undertaken in a number of the National Influenza Centres of MS. Results have and are being entered in the dedicated EISS database mentioned above.
Monthly liaison teleconferences convened by ECDC are taking place at the end of each month with the relevant bodies (Commission SANCO-C3, EISS Centre, VIRGIL, WHO European Region and WHO HQ, EMEA and the Competent Bodies and National Influenza Centres (NICs) of the countries that are most affected, as judged by having detected more resistant viruses). Those on the teleconference review the most recent data prior to publication, review strategy, oversee the work by sub-groups and generally keep each other informed of developments. On occasion other authorities join in including ‘guest’ international centres (the US CDC and the Public Health Agency of Canada and the manufacturer of oseltamivir.
An initial peer reviewed article was published by the VIRGIL group with an accompanying editorial by ECDC in Eurosurveillance within a week of the initial discovery. Regular updates are published on the ECDC webpage in an agreed visual format and acknowledgements with an underpinning data table . These data appear also on the EISS and WHO websites. The results feed into the Global Influenza Surveillance Network managed by WHO.
The Global Perspective
Following the European announcement testing has begun in other parts of the world and it has become apparent that the virus is also present and transmitting in parts of North America, Africa and the Far East. Global data are updated regualarly on the WHO web-site at about the same time as the European data.
Information for the Public and Clinicians
As much information as possible is being into the public domain as quickly as it can be agreed. A common set of Q&As have been prepared in close collaboration between WHO and ECDC, and the document is being regularly updated. The Flu Communicators Network created by the Commission, ECDC and Member States have been used as one mode of communication.
To date these new viruses seem to be no more harmful to humans than other seasonal influenza viruses and the current influenza type A(H1N1) viruses are anyway milder in their effects than the other circulating A-type influenzas, A(H3N2). Where the proportions of these viruses that were resistant were high (e.g. in Norway and the Netherlands) some of the national authorities informed their health services and clinicians that a high proportion of the influenza A/H1N1 viruses in this country were highly resistant (A/H1N1/H274Y) to the antiviral drug oseltamivir. Generally though there have not yet been any changes to recommended treatments. Specific queries have come from doctors managing patients expected to have deficient immune systems (e.g. transplant patients). There are starting to be discussions on this topic and other implications, such as for those managing stockpiles. One country (France) has stated it is making a policy change to diversify its stockpile so that its not mostly reliant on oseltamivir and another (the UK) has been advised to do so by an independent advisory body.
It must be emphasised that last season (2007-8) the ‘fit’ of the seasonal vaccines for the A/H1N1 viruses was good and so it could be expected that these vaccines would have been effective against the resistant viruses. High uptake of seasonal vaccination, along with good hygiene remains the mainstay of primary prevention against influenza.
Further analyses of the data are underway by the group including EISS Centre, ECDC, WHO and the member states with the most positive viruses that have been on the teleconferences. Investigations were started and a number of studies are now underway. However there have been issues concerning data-sharing and coordination of epidemiological studies that still need resolution. This is important as this was essentially a rehearsal for gathering data during the next pandemic, or in the event of the emergence of other infectious agents. ECDC and WHO are organising a global consultation which will take place in September. However a number of European-level publications are already underway in addition to single country studies. A paper on EU trends and genetic typing is being submitted by the EISS group. ECDC, WHO, EISS Centre and the group of countries who have been on the teleconferences (the ‘Schipol Group’) are investigating some risk factors that may be associated with the infection. ECDC is undertaking work on levels of use of oseltamivir in Member States using data supplied by the manufacturer though the relationship between the appearance of these viruses and use of oseltamivir is unclear as yet.
It is not known whether these viruses will reappear in the coming 2008/9 season. It is unusual that a season where the dominant A virus is A(H1N1) follows another directly. However influenza is anything but predictable. Certainly there will need to be surveillance for these and other resistant viruses next season.