Re: Flu Found Resistant to Main Antiviral Drug
Tamiflu resistance had been reported previously in Japan, where usage had been widespread, and children had been given sub-optimal doses (which had been used at levels below recommendation).
The sub-optimal usage led to resistance in children, but the resistance was found in H1N1 and H3N2. Moreover, the resistance was linked to the emergence of alterations at multiple positions in each serotype.
Over a year ago, Norway announced that resistance levels of 67% had been observed, but all resistance was in H1N1, and all genetic changes were at position 274, which changed from H to Y (H274Y). This high level, coupled with the fact that Norway rarely uses Tamiflu, and the resistant H1N1 isolates were from patients not taking Tamiflu, led to a series of media reports on "baffled" flu researchers, as well as an accelerated review of influenza elsewhere.
It was soon clear that H274Y was widespread and not only was concentrated in H1N1, but was primarily in clade 2B (Brisbane), and was primarily in a specific clade 2B sub-clade. Other examples in H1N1 made it clear that there were multiple independent introductions, but the vast majority of cases evolved from the dominant sub-clade.
Thus, it was quite clear almost a year ago that the spread was not linked to usage, because virtually no cases had recently had Tamiflu, and the spread was not only at position, H274Y, in H1N1, but was largely linked to one particular sub-clade.
Moreover, that sub-clade not only became dominant in clade 2B, but clade 2B largely displaced clade 2C, which was widespread in Asia, leading to levels approaching 100% in H1N1 in most countries (China still has clade 2C in circulation, so H274Y levels there are about 30%).
Thus, the spread of Tamiflu resistance worldwide, and the increase to 100% is clearly not linked to Tamiflu usage. Last season the level in Japan was 3% even though Tamiflu usage was highest. This year Tamiflu usage has declined in Japan, and Relenza usage has increased, yet H274Y levels approached 100%, as clade 2B displaced clade 2C (which happened in virtually all northern Asian countries except China).
Therefore, ProMED's comments are rather late, because the lack of ANY reported resistance in H3N2 has been known for over a year, as has the absence of resistance in H1N1 at any position other than 274 (which is sometimes called 275).
Suggestions that the increase is due to recent Tamiflu usage and/or linked to traveling salesmen are curious, but not based on reported data, which could not be clearer.
Here's a bit more info on why the ProMED commentary, over a year after the H274Y in H1N1 was reported in Norway was worthy of comment.
Tamiflu resistance had been reported previously in Japan, where usage had been widespread, and children had been given sub-optimal doses (which had been used at levels below recommendation).
The sub-optimal usage led to resistance in children, but the resistance was found in H1N1 and H3N2. Moreover, the resistance was linked to the emergence of alterations at multiple positions in each serotype.
Over a year ago, Norway announced that resistance levels of 67% had been observed, but all resistance was in H1N1, and all genetic changes were at position 274, which changed from H to Y (H274Y). This high level, coupled with the fact that Norway rarely uses Tamiflu, and the resistant H1N1 isolates were from patients not taking Tamiflu, led to a series of media reports on "baffled" flu researchers, as well as an accelerated review of influenza elsewhere.
It was soon clear that H274Y was widespread and not only was concentrated in H1N1, but was primarily in clade 2B (Brisbane), and was primarily in a specific clade 2B sub-clade. Other examples in H1N1 made it clear that there were multiple independent introductions, but the vast majority of cases evolved from the dominant sub-clade.
Thus, it was quite clear almost a year ago that the spread was not linked to usage, because virtually no cases had recently had Tamiflu, and the spread was not only at position, H274Y, in H1N1, but was largely linked to one particular sub-clade.
Moreover, that sub-clade not only became dominant in clade 2B, but clade 2B largely displaced clade 2C, which was widespread in Asia, leading to levels approaching 100% in H1N1 in most countries (China still has clade 2C in circulation, so H274Y levels there are about 30%).
Thus, the spread of Tamiflu resistance worldwide, and the increase to 100% is clearly not linked to Tamiflu usage. Last season the level in Japan was 3% even though Tamiflu usage was highest. This year Tamiflu usage has declined in Japan, and Relenza usage has increased, yet H274Y levels approached 100%, as clade 2B displaced clade 2C (which happened in virtually all northern Asian countries except China).
Therefore, ProMED's comments are rather late, because the lack of ANY reported resistance in H3N2 has been known for over a year, as has the absence of resistance in H1N1 at any position other than 274 (which is sometimes called 275).
Suggestions that the increase is due to recent Tamiflu usage and/or linked to traveling salesmen are curious, but not based on reported data, which could not be clearer.
