# 4142
Today the NEJM has published a letter from investigators in Vietnam that outlines the community transmission of a `fit’ oseltamivir (Tamiflu) resistant strain of the pandemic H1N1 virus.
While several dozen cases of Tamiflu resistant novel H1N1 have been reported, up until very recently we mostly heard about single cases of presumably `spontaneous’ mutations that occurred in patients taking the antiviral.
Oseltamivir (Tamiflu) Resistance is associated with the swapping of the amino acid histidine for tyrosine at position 275 (N1 numbering) in the neuraminidase glycoprotein (H275Y).
Up until a couple of years ago, it was assumed that this mutation reduced the transmissibility, or biological fitness of the virus.
That theory evaporated when resistant seasonal H1N1 began to circulate widely in 2008.
Efficient transmission of resistant novel H1N1, with the exception of two clusters among immunocompromised patients in hospitals, had not been established.
Until today.
Helen Branswell has the details, and I’ve a link to the correspondence published today in the NEJM (New England Journal of Medicine).
As with any Branswell story, follow the link to read it in its entirety.
Transmission of Tamiflu-resistant H1N1 on a Vietnamese train 'a concern': WHO
By: Helen Branswell, Medical Reporter, THE CANADIAN PRESS
9/12/2009
TORONTO - Seven healthy people on a train from Ho Chi Minh City to Hanoi in Vietnam caught Tamiflu-resistant H1N1 flu, researchers reported Wednesday in a prominent medical journal.
The transmission event, which occurred in July, is one of the largest clusters of cases of resistant H1N1 seen so far and the first time so many linked cases have been seen in previously healthy people who had not been on the drug.
Surveillance since the summer has only turned up three additional drug resistant viruses, the authors note in their letter to the New England Journal of Medicine. But they say they cannot rule out the possibility of ongoing transmission of resistant pandemic H1N1.
The event is a warning that resistant viruses can spread among healthy people and more such events may be in store, an antiviral expert with the World Health Organization said.
The the link to the NEJM letter, along with the opening paragraphs.
Published at www.nejm.org December 9, 2009 (10.1056/NEJMc0910448)
A Community Cluster of Oseltamivir-Resistant Cases of 2009 H1N1 Influenza
To the Editor: Oseltamivir-resistant infection with the 2009 pandemic influenza A (H1N1) virus has so far been described only rarely and is conferred by the H275Y substitution in the neuraminidase enzyme.1
Only 3 of the 32 patients with oseltamivir-resistant infection reported on as of this writing were not receiving oseltamivir when the resistant viruses were detected, and ongoing community transmission has not yet been shown.1
However, the emergence of oseltamivir-resistant 2009 H1N1 influenza remains a grave concern, since widespread oseltamivir resistance has been observed in seasonal H1N1. This resistance was unrelated to selective drug pressure, and the H275Y substitution did not appear to reduce transmissibility or severity.2,3 We report on a cluster of seven cases of oseltamivir-resistant 2009 H1N1 infection in Vietnam.
In July 2009, during a 42-hour journey, 10 students socialized together in the same train carriage. None of the students knew each other before the journey, none had contact with a person with suspected influenza in the week before the trip, none were symptomatic during the journey, and none were previously or currently receiving oseltamivir.
It should be noted that for now, at least, Tamiflu remains effective for the vast majority of novel H1N1 infections around the world. We don’t yet know if the novel H1N1 virus will follow its seasonal cousin’s lead, and eventually become widely resistant.
And even if that happens, we don’t know how long it would take.
Presumably months, anyway.
So yes, this is a `concern’. At least in the long run.
Antivirals were always assumed to be a temporary stop-gap measure during a pandemic. Not only are the supplies of antivirals limited, resistant viruses were predicted to evolve over time. So reports such as this one are not unexpected.
That is why the focus has been so heavily on vaccines.
While Tamiflu may continue to be useful for months or possibly even years to come, preventing an infection is always preferable to treating one.
The potential loss of treatment options over time is another factor to seriously consider when deciding whether to take the H1N1 vaccine.
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