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_|SEASONAL HUMAN INFLUENZA, ANTIVIRALS RESISTANCE, UPDATE(S)|_|MARCH 19 +|
[SEASONAL INFLUENZA, ANTIVIRALS, ECDC, UPDATES] Resistance to oseltamivir (Tamiflu) found in some European influenza virus samples
Updated 19th March 2008
In late January 2008 antiviral drug susceptibility surveillance of seasonal influenza viruses in Europe (the EU-EEA-EFTA countries) by the EU-funded VIRGIL network and National Influenza Centres revealed that some of the A (H1N1) viruses circulating this season (winter 2007-8) were resistant to the antiviral drug, oseltamivir through mutation at position 274 in the viral neuraminidase gene.
Analysis of 1986 A/H1N1 viruses from 24 European countries isolated between November 2007 and mid March (data archived on March 19th) showed that 411 were resistant to oseltamivir, but retained sensitivity to zanamivir and amantadine.
The data are shown as a figure with a linked table(1).
The proportion of A/H1N1 viruses that are oseltamivir resistant varies significantly across Europe(2).
The highest proportion of resistant viruses to date have been in Norway where 127 (69%) of the 184 samples are resistant to oseltamivir, whereas no resistant viruses have been detected in nine of the 24 countries.
It should be noted that for some countries the numbers of viruses tested are low and therefore these proportions may change as more data accumulate.
Surveillance in previous years by the Virgil Project(3) found <1% of circulating viruses to be resistant
The predominant influenza A viruses in Europe in winter 07/08 are A/H1N1 viruses, antigenically similar to the A/Solomon Islands/3/2006 virus included in the 2007/08 N Hemisphere vaccine.
As the season progresses influenza B has started to circulate, but there is 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(4) which is also summarised in ECDC?s Influenza News(5).
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(6) and the public.
The country with the second highest proportion is France with 106 (38%) of 279 specimens showing the marker for oseltamivir resistance.
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(7) has been published by ECDC and comments on this are welcomed to influenza@ecdc.europa.eu.
Global surveillance has started coordinated by WHO and has this has found evidence of similarly resistant viruses in North America and the Far East.
All data including that on the WHO web-site(8) are updated every Thursday at present.
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 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 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, WHO, EISS, VIRGIL and authorities in the member states are undertaking intensive surveillance and progress will be reported through this and other relevant web-pages.
A summary of the arrangements for the EU EEA & EFTA Countries(9) is available.
Briefing for policy makers in the EU and EEA/EFTA Member States(10)
For information on seasonal influenza and how to protect yourself against it(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/...proj13_en.html and EISS is supported by ECDC.
Laboratories in EISS contribute to the Global Influenza Surveillance Network managed by WHO(12).
Information on Antivirals and Antiviral Resistance(13)
LINKS:
1) Courtries with human influenza virus resistant to oseltamivir
2) Number of isolates resistant for countries (Table)
3) VIRGIL Project
4) EISS Weekly Update
5) ECDC Influenza Update
6) Norwegian Advice to Doctors
7) ECDC Interim Risk Assessment
8) WHO Weekly Update
9) Summary of the arrangements for the EU EEA & EFTA Countries
10) Briefing for policy makers in the EU and EEA/EFTA Member States
11) Information on seasonal influenza and how to protect yourself against it
12) Global Influenza Surveillance Network managed by WHO
13) Information on Antivirals and Antiviral Resistance
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Updated 19th March 2008
In late January 2008 antiviral drug susceptibility surveillance of seasonal influenza viruses in Europe (the EU-EEA-EFTA countries) by the EU-funded VIRGIL network and National Influenza Centres revealed that some of the A (H1N1) viruses circulating this season (winter 2007-8) were resistant to the antiviral drug, oseltamivir through mutation at position 274 in the viral neuraminidase gene.
Analysis of 1986 A/H1N1 viruses from 24 European countries isolated between November 2007 and mid March (data archived on March 19th) showed that 411 were resistant to oseltamivir, but retained sensitivity to zanamivir and amantadine.
The data are shown as a figure with a linked table(1).
This weeks totals include a report of the first resistant A/H1N1 virus being detected in Italy and Slovenia.
The proportion of A/H1N1 viruses that are oseltamivir resistant varies significantly across Europe(2).
The highest proportion of resistant viruses to date have been in Norway where 127 (69%) of the 184 samples are resistant to oseltamivir, whereas no resistant viruses have been detected in nine of the 24 countries.
It should be noted that for some countries the numbers of viruses tested are low and therefore these proportions may change as more data accumulate.
Surveillance in previous years by the Virgil Project(3) found <1% of circulating viruses to be resistant
The predominant influenza A viruses in Europe in winter 07/08 are A/H1N1 viruses, antigenically similar to the A/Solomon Islands/3/2006 virus included in the 2007/08 N Hemisphere vaccine.
As the season progresses influenza B has started to circulate, but there is 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(4) which is also summarised in ECDC?s Influenza News(5).
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(6) and the public.
The country with the second highest proportion is France with 106 (38%) of 279 specimens showing the marker for oseltamivir resistance.
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(7) has been published by ECDC and comments on this are welcomed to influenza@ecdc.europa.eu.
Global surveillance has started coordinated by WHO and has this has found evidence of similarly resistant viruses in North America and the Far East.
All data including that on the WHO web-site(8) are updated every Thursday at present.
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 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 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, WHO, EISS, VIRGIL and authorities in the member states are undertaking intensive surveillance and progress will be reported through this and other relevant web-pages.
A summary of the arrangements for the EU EEA & EFTA Countries(9) is available.
Briefing for policy makers in the EU and EEA/EFTA Member States(10)
For information on seasonal influenza and how to protect yourself against it(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/...proj13_en.html and EISS is supported by ECDC.
Laboratories in EISS contribute to the Global Influenza Surveillance Network managed by WHO(12).
Information on Antivirals and Antiviral Resistance(13)
LINKS:
1) Courtries with human influenza virus resistant to oseltamivir
2) Number of isolates resistant for countries (Table)
3) VIRGIL Project
4) EISS Weekly Update
5) ECDC Influenza Update
6) Norwegian Advice to Doctors
7) ECDC Interim Risk Assessment
8) WHO Weekly Update
9) Summary of the arrangements for the EU EEA & EFTA Countries
10) Briefing for policy makers in the EU and EEA/EFTA Member States
11) Information on seasonal influenza and how to protect yourself against it
12) Global Influenza Surveillance Network managed by WHO
13) Information on Antivirals and Antiviral Resistance
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of the 234 samples are resistant to oseltamivir, whereas no resistant viruses have been detected in six of the 24 countries. 
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