What Causes Tamiflu Resistance?

Helen -   Many countries have responded to the swine flu pandemic this year by giving people with 'flu symptoms a course of an antiviral drug called Tamiflu - oseltamivir. But, now we're seeing patients with 'flu infections that are resistant to this drug. To explain why this happens and what the consequences might be, is Professor James Wood, director of the Cambridge Infectious Diseases Consortium. I thought perhaps we should start off by just going into some detail about how Tamiflu actually works.

James -   Yes.  This is one of the two sets of proteins of influenza and it stops or dramatically inhibits the production of infectious viruses from infected cells.

Helen -   Right.  So how is it that then we see some resistance occurring.

James -   The use of any [anti-microbial] drug, just as with antibiotics in patients with a bacterial infection, creates a lot of pressure on the infection to evade the drug that's being used.  And although viruses aren't exactly living, they behave like living beings within cells because they have replication machinery that allows them to change very quickly; so they make very simple genetic changes, which can occur by chance, and this creates a new strain of the virus that's not sensitive to the drug.

Helen -   So the nuts and bolts of this is the genetic mechanism by which viruses work.   We get mutations, and that's when the resistance comes in.

James -   That's absolutely right.  And that's very similar to the development to any drug resistant to either viruses or bacteria.

Helen -   So it was just a matter of time until we saw some resistance coming up to Tamiflu?

James -   I think so.  And I think what matters is whether or not the drug resistant form of the infection is transmitting widely.

Helen -   Do we have any idea if it is?

James -   Well, I think at the moment that there are a few special cases where drug resistance has been detected, but it's not being transmitted widely in the community and most strains that people have been infected with are still not resistant.

Helen -   Do we understand what it is about a particular resistance pattern that makes it become widespread or not or is that another big question mark?

James -   Well, I think that's a big question mark; many changes that are occur in many infections are frequently deleterious [to the fitness of the virus].  So the change towards Tamiflu resistance actually can make the virus slightly less good at transmitting.  Therefore you're more likely to catch a form of the infection that's not carrying the Tamiflu resistance.  But you might expect to see widespread transmission of resistance when the drug is being used very, very widely.

Helen -   And so, are we seeing it as a big problem in the U.K. at the moment?

James -   What we're finding is that there's not a significant problem at the moment; most of the people that are treated with Tamiflu at the moment are not infected with resistant virus.

Helen -   So we see this resistance occurring and perhaps to some extent it's a little bit inevitable that it will happen.  What can we do about it?

James -   Well, I think that one of the most obvious ways is to try and make sure that people who are receiving Tamiflu, but are still infected, are not walking around in very  high risk situations in terms of transmission. So a degree of quarantine would be a very effective means of stopping people transmitting drug resistant virus.

Helen -   So ultimately, give someone Tamiflu, keep them on their own until we know that they've got better and there's no problem.

James -   I think that's absolutely right.  I mean, we're not talking about in long lived infections of influenza.  The majority of people have stopped shedding large amounts of virus within a few days.

Helen -   So thanks, James.  That's Professor James Wood, Director of the Cambridge Infectious Diseases Consortium.