Interim ECDC Risk Assessment - January 27th 2008
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Emergence of seasonal influenza viruses type A/H1N1 with oseltamivir resistance in some European Countries at the start of the 2007-8 influenza season
1. Summary Statement
Ordinary seasonal influenza viruses with significant resistance to the antiviral oseltamivir (Tamiflu) have been detected within the earliest part of this winter?s influenzas epidemics in Europe.
The viruses are known as influenza A/H1N1 (H274Y).
That is a type A influenza virus subtype H1N1 with a histidine to tyrosine amino-acid substitution at position 274 in the neuraminidase protein.
They were fully sensitive to other influenza antivirals.
These viruses have been detected by a European research and surveillance
project known as VIRGIL (supported by an EU grant) which has been underway since 2004-5. These viruses are a new phenomenon this winter. Specialist testing has been undertaken for ten countries and a proportion of A/H1N1 viruses detected in four countries Denmark, France, Norway and the UK, have been found resistant to oseltamivir. H1N1 viruses are predominant in this winters epidemics worldwide. Overall in Europe the proportion with oseltamivir resistant is around 13% but the proportions resistant are variable with Norway showing a markedly high proportion resistant (12 of 16). If the 16 Norwegian viruses are excluded the proportion with resistant would fall to around 5%. Data from Norway indicate that these viruses were transmitted in the country but they are not making people especially ill. Normally A/H1N1 viruses as a group cause milder disease than some other human influenza viruses. However it must be realised that all influenza A viruses are potentially lethal for vulnerable individuals (the old and the very young and those with chronic debilitating conditions). It also needs to be remembered that antiviral resistant is a relative not absolute term. Patients ill with resistant viruses often still seem to benefit when they receive antivirals. The source of these viruses is not known at present. It seems unlikely to have anything to do with antiviral use in Europe. Specifically the resistance is not explained by the source patients having taken any antivirals or any high levels of use of oseltamivir in Europe where generally the drug is used sparingly. These data come from around 150 viral isolates from very early in this winter epidemics in ten of the thirty European countries. However Norway is still seeing them in specimens collected this month. There are some
indications that A/H1N1 viruses with the same resistance mutation are being seen in some other countries, notably North America. However, Europe is showing the highest resistance levels at present. A conclusive risk assessment cannot be attempted at present and there seems little reason to change clinical guidance except possible where these new viruses predominate over all others. It could be that as the influenza season progresses these viruses will be overwhelmed by more fit and sensitive viruses (many resistant viruses lack ?fitness?) Equally however the resistant viruses could come to spread and predominate. We simply do not know at present. There is considerable risk of confusion of this development with the separate issues of avian influenza, pandemic threat and antivirals stockpile. Information for the public and professionals has therefore been developed by ECDC and WHO for adaptation and use by countries. Intense virological
and epidemiological surveillance and other scientific investigations are now taking place in Europe and elsewhere. This is coordinated by WHO overall globally and this will in time allow for better descriptions and risk statement to be made. Therefore ECDC anticipates highlighting the results of these investigations and updating this assessment at intervals.
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Emergence of seasonal influenza viruses type A/H1N1 with oseltamivir resistance in some European Countries at the start of the 2007-8 influenza season
1. Summary Statement
Ordinary seasonal influenza viruses with significant resistance to the antiviral oseltamivir (Tamiflu) have been detected within the earliest part of this winter?s influenzas epidemics in Europe.
The viruses are known as influenza A/H1N1 (H274Y).
That is a type A influenza virus subtype H1N1 with a histidine to tyrosine amino-acid substitution at position 274 in the neuraminidase protein.
They were fully sensitive to other influenza antivirals.
These viruses have been detected by a European research and surveillance
project known as VIRGIL (supported by an EU grant) which has been underway since 2004-5. These viruses are a new phenomenon this winter. Specialist testing has been undertaken for ten countries and a proportion of A/H1N1 viruses detected in four countries Denmark, France, Norway and the UK, have been found resistant to oseltamivir. H1N1 viruses are predominant in this winters epidemics worldwide. Overall in Europe the proportion with oseltamivir resistant is around 13% but the proportions resistant are variable with Norway showing a markedly high proportion resistant (12 of 16). If the 16 Norwegian viruses are excluded the proportion with resistant would fall to around 5%. Data from Norway indicate that these viruses were transmitted in the country but they are not making people especially ill. Normally A/H1N1 viruses as a group cause milder disease than some other human influenza viruses. However it must be realised that all influenza A viruses are potentially lethal for vulnerable individuals (the old and the very young and those with chronic debilitating conditions). It also needs to be remembered that antiviral resistant is a relative not absolute term. Patients ill with resistant viruses often still seem to benefit when they receive antivirals. The source of these viruses is not known at present. It seems unlikely to have anything to do with antiviral use in Europe. Specifically the resistance is not explained by the source patients having taken any antivirals or any high levels of use of oseltamivir in Europe where generally the drug is used sparingly. These data come from around 150 viral isolates from very early in this winter epidemics in ten of the thirty European countries. However Norway is still seeing them in specimens collected this month. There are some
indications that A/H1N1 viruses with the same resistance mutation are being seen in some other countries, notably North America. However, Europe is showing the highest resistance levels at present. A conclusive risk assessment cannot be attempted at present and there seems little reason to change clinical guidance except possible where these new viruses predominate over all others. It could be that as the influenza season progresses these viruses will be overwhelmed by more fit and sensitive viruses (many resistant viruses lack ?fitness?) Equally however the resistant viruses could come to spread and predominate. We simply do not know at present. There is considerable risk of confusion of this development with the separate issues of avian influenza, pandemic threat and antivirals stockpile. Information for the public and professionals has therefore been developed by ECDC and WHO for adaptation and use by countries. Intense virological
and epidemiological surveillance and other scientific investigations are now taking place in Europe and elsewhere. This is coordinated by WHO overall globally and this will in time allow for better descriptions and risk statement to be made. Therefore ECDC anticipates highlighting the results of these investigations and updating this assessment at intervals.
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