EU and global data updated at the end of September 2008
In late January 2008, antiviral drug susceptibility surveillance of seasonal influenza viruses was carried out in Europe (the EU-EEA-EFTA countries) by the EU-funded VIRGIL network. The National Influenza Centres revealed that some of the A (H1N1) viruses circulating this season (winter 2007-8) are resistant to the antiviral drug oseltamivir through mutation at position 274 in the viral neuraminidase gene.
Analysis of 2898 A(H1N1) viruses from 25 European (European Union, EEA/EFTA) countries isolated between November 2007 and late July 2008 (data archived on August 6th) showed that 704 were resistant to oseltamivir, but retained sensitivity to zanamivir and amantadine. See data below:
This season influenza virus type A (H1N1) was initially the predominant virus among those reported to EISS. For example as of the end of January where typing has been done to give an A/H Type or B virus, around 64% has been A/H1, under 2% A/H3 and 34% Type B. However more recently influenza B has been predominating, accounting for around 70% of the typeable isolates in week 11.
Data were provided by the European Influenza Surveillance Scheme http://www.eiss.org/index.cgi and the VIRGIL Project http://www.virgil-net.org/ ECDC would like to thank all countries, virologists, clinicians and others for contributing data. Funding for the VIRGIL project comes from the European Union FP6 Research Programme http://ec.europa.eu/research/health/influenza/proj13_en.aspx and EISS is supported by ECDC. Laboratories in EISS contribute to the Global Influenza Surveillance Network managed by WHO
The proportion of A(H1N1) viruses that are oseltamivir resistant varied significantly across Europe. The highest proportion of resistant viruses to date have been in Norway where 184 (67%) of the 273 samples are resistant to oseltamivir, whereas no resistant viruses have been detected in five of the 25 countries.
Surveillance in previous years by the Virgil Project found <1% of circulating viruses to be resistant The predominant influenza A viruses in Europe in winter 07/08 were A(H1N1) viruses, antigenically similar to the A/Solomon Islands/3/2006 virus included in the 2007/08 N Hemisphere vaccine. As the season progressed influenza B viruses started to circulate and then predominated. There was only limited circulation of other influenza A in Europe. Further details on country to country virus distribution this season are available on the European Influenza Surveillance Scheme (EISS) weekly update as well as in Influenza News.
Following the observation of a high level of resistance to oseltamivir in the A(H1N1) viruses circulating in Norway, the Norwegian authorities notified their EU partners and the World Health Organization (WHO) of this situation at the end of January. The Norwegian Public Health Institute also published an advisory to doctors and the public. The country with the second highest proportion is now Belgium (53%) followed by France with 231 (47%) of 496 specimens showing the marker for oseltamivir resistance. This is then followed by the Netherlands and Luxembourg with proportions of 27% and 26% respectively. There is no evidence that the appearance of these new viruses are related to use of oseltamivir which is currently seemingly not widely prescribed in most European countries. ECDC is now working with the manufacturer and national authorities to gather more information on routine oseltamivir use in Europe.
Experts from the European Centre for Disease Prevention and Control (ECDC), the European Commission, the European Influenza Surveillance Scheme and the World Health Organization (WHO) are currently assessing the significance of the data from the EISS VIRGIL network. An interim European risk assessment has been published by ECDC and comments on this are welcomed to email@example.com.
Global surveillance started immediately after the detection in Europe and is being coordinated by WHO, and evidence has been found of similarly resistant viruses in North America and the Far East. All data including that on the WHO web-site are updated at monthly intervals at present.
The latest global data were posted on September 29th 2008 August 20th and now WHO is showing data separately for the 2007/8 winter season (Last Quarter 2007 to March 2008) and the 2008 season (Table 1 Second Quarter 2008 to August 20th). At the global level the most recent notable finding was from South Africa where now all 12907 influenza A/H1N1 specimens gathered since the start of the second Quarter 2008 and tested for antiviral resistance showed the marker of resistance. Their findings have been confirmed by WHO Collaborating Centres. To date there have been 16136 specimens influenza A/H1N1 specimens tested from WHO’s Africa Region but only tennine of these have shown the markers of resistance apart from those from South Africa. Other significant national proportions of A/H1N1 specimens for the Southern Hemisphere or Equatorial regions showing resistance for which there are data are from Australia (2510 out of 2610), Chile (4 out of 13), Argentina (2 out of 5) the Phillipines (10 out of 11) and the Hong Kong Region of China 97 out of 483 (17%). The finding of these viruses in the Southern Cone of South America in Chile (6 out of 44) and Argentina (11 out of 25) is considered significant as this is the part of the world that is usually last affected when other new influenza A viruses spread.(1)These are the first of these viruses reported from the Southern Cone of South America.
Looking back to the earlier period (Quarter 4 2007 to end of Quarter 1 2008 equivalent to the Northern Hemisphere winter season where there are data on more than 50 specimens the results are: the Russian Federation 45%, (58 of 128), Canada 26% (127 of 486), United States 12% (126 of 1026), Japan 3% (44 of 1652), Hong Kong 12% (98 of 797), Australia 4% (3 of 83), Madagascar (none of 59), Korea (none of 99%) and New Zealand (none of 88). As well as the WHO monthly table. WHO is publishing less frequent analytic summaries on the WHO web-site. WHO also published regular summaries on influenza in the world. The last of these was published in late July. These data are interesting because they firstly indicate that these A(H1N1) viruses are not going away and also that they seem to be following the pattern suggested for A(H3N2) viruses of spreading eventually to even the Southern Cone of South America.(1)
Although sporadic low level transmission of drug resistant viruses may have taken place since 1999 when the Neuraminidase Inhibitor drugs first were licensed, the 07/08 winter season is the first time there has been widespread and sustained transmission of such viruses in the community. Similar viruses have been seen before, but usually following treatment. Such viruses previously have not been able to readily transmit and have rapidly disappeared. Clinical experience in Norway and elsewhere suggests that people who become ill with an oseltamivir resistant strain of A(H1N1) have a similar spectrum of illness to those infected with “normal” seasonal influenza A which can cause severe disease or death in vulnerable people (older people, those with debilitating illnesses and the very young). This is now being investigated in national studies and international studies coordinated by ECDC.
At this stage the significance of these findings remains uncertain. The emergence of drug resistance in the context of limited drug use is unexpected, and the extent of future circulation is difficult to predict. ECDC, and the WHO Regional Office for Europe organised a Global Consultation in September with attendance from the, WHO Global Programme on Influenza, the Four Global Influenza Collaborating Centres, the Community Network Reference Laboratory EISS, VIRGIL, the European Commission and authorities in the most affected EU member states. Reports from that meeting are now being prepared along with a number of papers going towards peer-reviewed journals. These member states are undertaking intensive surveillance and progress will be reported through this and other relevant web-pages.
It cannot be predicted whether these viruses will return to Europe this coming season. It is unusual to have one A(H1N1) dominated season following another, but everything about these viruses has been predictable. However surveillance is in place through the MS and the CNRL. A summary of the arrangements for the EU EEA & EFTA Countries is on the ECDC web-site this is also available in a pdf version as a briefing for policy makers in the EU and EEA/EFTA Member States .
(1) Russell C, Jones T, Barr I et al The global circulation of seasonal influenza A (H3N2) viruses Science 2008; 320 340