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_|SEASONAL HUMAN INFLUENZA, ANTIVIRALS RESISTANCE, UPDATE(S)|_|MARCH 19 +|
The detection of an increased number of A(H1N1) viruses with resistance to oseltamivir was initially reported to WHO from Norway on 25th January (see WHO website).
Before recent detection of a high prevalence of oseltamivir resistance in influenza A (H1N1) viruses with a specific neuraminidase mutation (H274Y) in Norway, such resistance was rarely observed in community isolates.
During the previous northern hemisphere winter season (2006/07), surveillance through GISN laboratories found no oseltamivir - resistant H1N1 viruses in isolates from Japan and Europe, and less than 1% prevalence in H1N1 isolates from the USA.
In addition to Norway, several other countries in Europe and North America have found an elevated
prevalence of oseltamivir-resistant viruses this season (Table).
However, insufficient data are available at present to determine the full geographic scope, origins, or patterns of transmission of these oseltamivir resistant H1N1 viruses.
WHO is collecting global data about this phenomenon from multiple laboratories participating in GISN.
Data for European countries participating in EISS were provided by the EISS and VirGil project.
WHO would like to thank all countries, virologists, clinicians and others for contributing data.
This summary table will be updated regularly as new data and reports become available.
Oseltamivir resistance results were obtained with using phenotypic and/or genotypic analysis.
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Re: _|SEASONAL HUMAN INFLUENZA, ANTIVIRALS RESISTANCE, UPDATE(S)|_|MARCH 19 +|
Previous Update: 6274 total isolates; 891 resistant;
This update: 6465 total isolates; 982 resistant;
New resistant isolates since previous update: 91.
New isolates tested for resistance: 191.
Resistance ratio: 91/191*100=47 % --
Re: _|SEASONAL HUMAN INFLUENZA, ANTIVIRALS RESISTANCE, UPDATE(S)|_|MARCH 19 +|
Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere 18 July 2008
During weeks 26?27 (15 -28 June), the level of overall influenza activity in the world increased reflecting the situation in southern hemisphere.
However, influenza A(H1N1)virus circulation remains generally low in all countries reporting influenza activity at this time (see Seasonal influenza activity in the world, 2008 http://www.who.int/csr/disease/influ.../en/index.html )[Already at FT Seasonal Influenza thread, CURRENT NEWS FORUM - IOH].
WHO has received several reports from National Influenza Centres in the southern hemisphere regarding influenza A(H1N1)virus resistance to oseltamivir.
In South Africa, a total of 90 A(H1N1) viruses have been isolated during the 2008 influenza season to date, and all of the 23 influenza A(H1N1) viruses tested by the WHO collaborating Centres in London and Melbourne were found to have resistance to oseltamivir by neuraminidase enzyme-inhibition assay.
None of these patients were receiving oseltamivir at the time of sampling, and no unusual clinical feature or underlying conditions have been found.
To date, preliminary test results show that the viruses carry the specific neuraminidase mutation (H274Y) that confers oseltamivir resistance in N1, while no sign of adamantane resistance by genetic analysis have been found.
From Chile, three of the 24 A(H1N1) viruses tested showed the specific neuraminidase mutation (H274Y).
WHO is collecting global data about this phenomenon from multiple laboratories participating in Global Influenza Surveillance Network.
Data for European countries participating in EISS were provided by the EISS and VirGil project.
This summary table will be updated regularly (every four weeks).
Oseltamivir resistance results were obtained with using phenotypic and/or genotypic analysis.
For background and summary until week 24, 2008, see Influenza A(H1N1) virus resistance to oseltamivir, Last quarter 2007 to first quarter 2008, Preliminary summary and future plans http://www.who.int/csr/disease/influ.../en/index.html
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Re: _|SEASONAL HUMAN INFLUENZA, ANTIVIRALS RESISTANCE, UPDATE(S)|_|MARCH 19 +|
South Africa is one of three nations (China, India, SA) producing generic oseltamivir.
Norway, France, Switzerland, Finland and others ordered enough oseltamivir in 2005 to cover a fraction (~20-30%) of their population against pandemic, as part of preparedness planning.
Those stockpiles 'came due' during the 2007-08 flu season.
Could be just coincidence.
Regardless of the source of selective pressure, multiple phenotypes with antiviral resistance (against HA and M2 channels) are maintained within the environmental influenza gene pool; this characteristic was detected in isolates obtained before antivirals were in general use.
Commentary
H1N1 Tamiflu Resistance at 100% in South Africa Recombinomics Commentary 23:50
July 18, 2008 In South Africa, a total of 90 A(H1N1) viruses have been isolated during the 2008 influenza season to date, and all of the 23 influenza A(H1N1) viruses tested by the WHO collaborating Centres in London and Melbourne were found to have resistance to oseltamivir by neuraminidase enzyme-inhibition assay.
None of these patients were receiving oseltamivir at the time of sampling, and no unusual clinical feature or underlying conditions have been found.
To date, preliminary test results show that the viruses carry the specific neuraminidase mutation (H274Y) that confers oseltamivir resistance in N1
From Chile, three of the 24 A(H1N1) viruses tested showed the specific neuraminidase mutation (H274Y).
The above comments from the WHO update on oseltamivir (Tamiflu) resistance indicate the frequency has now reached 100% in South Africa (based on the first 23 H1N1 samples tested). In the southern hemisphere, the 2008 flu season is ongoing. Consequently, Chile is also reporting H274Y in the current season. These isolates are almost certainly Brisbane/59 (clade 2B), which has been linked to the vast majority of Tamiflu resistant isolates from the 2007/2008 season.
Earlier positives from last season were on New Caledonia (clade 1) genetic backgrounds in the United States and Hong Kong (clade 2C) backgrounds in China. This season there have been multiple introductions of H274Y onto the Brisbane (clade 2B).
The expansion of H274Y has been facilitated by the vaccine mismatch, which targeted Solomon Islands (clade 2A) this season. There is no evidence for any clade 2A in circulation this season.
The expansion of H274Y via the Brisbane strain is cause for concern. It has now reached 100% in South Africa, which represents a growing reservoir of H274Y, which can clearly jump from one H1N1 clade to another, which is most easily explained by homologous recombination.
This polymorphism is identical to the H274Y on H5N1, suggesting that oseltamivir will have limited value for blunting an H5N1 pandmeic.
.
"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
* respondence to Tamiflu-use
or
* very few independent introductions in a country
Wrong. The 59 tested in Madagaskar are on the first report on this thread, so the samples were collected some time ago, before the H274Y version of Brisbane/59 arrived.
In contrast, the South African data is obly on the most recent report, indocating it arrived more recently.
The story is in the sequnece and the story is VERY clear.
At this point, the H274Y has NOTHING to do with Tamiflu use and much to do with the H1N1 mismatch for 2007/2008 in the northern hemisphere and 2008 in the southern hemisphere.
South Africa is one of three nations (China, India, SA) producing generic oseltamivir.
Norway, France, Switzerland, Finland and others ordered enough oseltamivir in 2005 to cover a fraction (~20-30% of their population against pandemic, as part of preparedness planning.
Those stockpiles 'came due' during the 2007-08 flu season.
Could be just coincidence.
Regardless of the source of selective pressure, multiple phenotypes with antiviral resistance (against HA and M2 channels) are maintained within the environmental influenza gene pool; this characteristic was detected in isolates obtained before antivirals were in general use.
Well into the coincidence category. Most of the isolates are from the same "northern EU" sub-strain, indicating H274Y is NOT due to recent Tamiflu useage.
Moreover, in the past Japan demonstrated that treatment of children with sub-optimal doses of Tamiflu led to resistance in both H1N1 and H3N2 and the resistance was in multiple polymorphisms.
The current outbreak of Tamiflu resistance has been limited to H1N1 and H274Y in N1.
Re: _|SEASONAL HUMAN INFLUENZA, ANTIVIRALS RESISTANCE, UPDATE(S)|_|MARCH 19 +|
How relevant is the vaccine in driving the evolution of the strains?
Those vaccinated are mainly in wealthier countries and either old, young or in 'at risk' groups i.e. most people who catch flu are not vaccinated even in years where the vaccine is poorly matched to the circulating strain. So even if the consultative committee on seasonal flu composition selected strains to target the Brisbane/59 with H274Y how effective would that be?
How relevant is the vaccine in driving the evolution of the strains?
Those vaccinated are mainly in wealthier countries and either old, young or in 'at risk' groups i.e. most people who catch flu are not vaccinated even in years where the vaccine is poorly matched to the circulating strain. So even if the consultative committee on seasonal flu composition selected strains to target the Brisbane/59 with H274Y how effective would that be?
Although a well matched vaccine won't eliminate a given strain, it will reduce it. This past season was one of the worst in recent history and there were mismatches for all three vaccine targets (H1N1, H3N2, influenza B).
Brisbane/59 (clade 2B) is prevalent in wealthier countries, such as northern Europe, Russia, and North America, where vaccine usage is higher. In Asia, most of the H1N1 is clade 2C.
Thus, at this time clade 2B is most prevalent in countries were vaccine usage is highest.
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of their population against pandemic, as part of preparedness planning.
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