Tamiflu: Dylan's retort, part I

Once again one of our readers, "Dylan," forces me to acknowledge the extraordinary raw talent in the mindhive that is the blogosphere. In a very extended comment to the Tamiflu-storage post he has raised a number of points that deserve wider readership and also some comment from me. The Haloscan Comment system, even with my ponying-up some extra dough, is limited to 3000 characters a Comment (for which I apologize). Dylan had to split his extensive remarks into four segments which I have pasted together, interspersed with some of my own remarks.

To avoid really long posts, I will divide his remarks into separate items over the next few days.

For readability I am not "block-quoting" his remarks in reduced font size as I usually do for quotes. Instead his remarks are full width and mine will be block-quoted with reduced font.

What follows is not intended to discourage anyone from purchasing or using Tamiflu. I, and my wife and daughter, will all be using it when the time comes, since it's the only thing available at this point. The purpose here, then, is to promote discussion.

I strongly encourage discussion, hence these posts. First, a personal comment of my own. I have not bought Tamiflu, partly as a matter of conscience. As Dylan notes, if a disaster strikes, this drug will be rationed and, I hope, apportioned on some ethical and rational basis of need. I would be short circuiting that by having the foresight to buy my own supply, so at this point I have not done so. I agree with Dylan that it is not even remotely the solution to dealing with a pandemic. It is only one tool and, given the numbers, probably would be effective only around the margins.

Okay, here's my two cents worth; well, maybe three-or-four cents before I'm finished. This has to do with Tamiflu, but I'm going to begin with H5N1 to limn the current state of events, and what all of this may imply (stockpiles of antivirals, mutations in H5N1, etc.). Vietnam is looking more and more like the launch-pad for the pandemic (doesn't mean that it has to be though; there is plenty going on in other places, too). The latest familial cluster in the Thai Binh Province area (assuming the female nurse proves positive for H5N1, and the isolate is identified as essentially identical to the others that comprise the cluster) is the latest example of the pathogen's rapidly advancing adaptability to human beings. Zero human flu genes are involved here, so it should now be assumed that this can no longer be considered as an absolutely necessary component of a potential pandemic flu strain, as had previously been thought to be the case.

This is probably correct, but I am not aware of any sequences of the latest round (late December 2004 onward and especially the northern Vietnam viruses). So some human, or least, non-avian genes might conceivably be involved.

It's doing things that we haven't figured out, yet. On the other hand, H5N1 is doing an enviable job of figuring us out, even though this may have required a (temporary?) suspension of its extremely high level of lethality (all four people in the largest cluster are still alive, but none of them are out of the hospital yet, either, so lethality here remains an open question).

Given the current case-fatality rate, this is certainly a remarkably lethal virus. However I am of the mind that there are many inapparent infections (and probably substantial human-to-human transmission to go with them) so that the true virulence is being overestimated by a Vietnamese government that has only counted the most serious cases, and probably not all of them. Having said that (and in agreement with Dylan), if the case-fatality rate even goes down to single digits (from the current 70%) we have a gigantic problem on our hands.

I mention "temporary" here because a signature of H5N1 in many early poultry infections was an initial low pathogenicity that spiraled into high pathogenicity that ultimately raged through a flock of birds like a firestorm, and resulted in lethality levels approaching 100%.

Here is my take on the incredible lethality for chickens. I think it is caused by high confinement poultry farming, which makes it possible for the virus to kill a chicken quickly and still be transmitted to another bird. Remember that for the virus the chicken is just another way of making another virus. "Backyard" chickens are not so densely congregated, nor are people. Thus for traditional farming and for humans one might expect a far less lethal virus. Let me try to differentiate this from unwarranted optimism. I don't know, nor does anyone else, what is going to happen. From the public health ("precautionary") perspective one needs to plan for the worst, and in this case the worst is unimaginably bad and quite plausible. What I am doing is giving my "best guess" as to what I think will happen, based on my view of the biology. I am sure there is much room for disagreement, and I welcome it (as long as it isn't also disagreeable, a line that no one on this site has yet to cross).

And this current intensified infectiousness of pure avian H5N1 doesn't in any way alter the fact that H5N1 could still mate up with something like H3N2/California, for instance, and undergo an antigenic shift; it just suggests that there are far more options on the table for H5N1 to pursue than could have been considered feasible even a few short months ago. We are orders of magnitude beyond where this thing was at the beginning of 2004, and light years beyond the state represented by the first expression of H5N1 in human beings in Hong Kong, in 1997. We have gone from a state where there was absolutely no evidence whatsoever of transmissibility between human beings, to a state where not only is that apparently a common component, but the evidence increasingly suggests that transmission through casual contact is now occurring.

I agree with this, but to be fair, there are others, who I consider knowledgeable, who do not.

The overall state of affairs being what it is right now, I find myself thoroughly ensconced in the camp of those who insist that we will be dealing with a full-fledged pandemic before the end of next winter. To qualify as alarmist these days, one would have to insist that the pandemic has already begun, and we're all just in a state of global denial. Alarms are sounding all over, and unfortunately our Government seems to be one of the few that is virtually deaf to all of them. Maybe the same in-house scientists who are advising the Administration on the causes of global warming are providing the advice on this issue, too?

I think this is a reasonable judgment, which I share.

Now for Tamiflu.

[To be continued in the next post].