Swedish scientists are warning about Tamiflu in the environment because it passes through sewage treatment plants more or less unchanged. Readers of this blog may remember this coming up before when Andrew Singer and his colleagues in the UK published an article in Environmental Health Perspectives a year ago asking a logical question: what would happen in a pandemic if everyone started taking hoarded and stockpiled Tamiflu at once? Singer gave good reasons to think the active form of Tamiflu, oseltamivir carboxylate, would pass through the wastewater system. The Swedish study apparently confirms this:
Scientists at Sweden's Umea University found the drug isn't removed or degraded in normal sewage treatment, and its presence in waterways may allow flu-carrying birds to ingest it and incubate resistant viruses."That this substance is so difficult to break down means that it goes right through sewage treatment and out into surrounding waters,'' said Jerker Fick, a chemist at Umea University and leader of the study, in a statement yesterday distributed by EurekAlert, a Web-based science news service. (Bloomberg)
The main concern is that the current presence of active Tamiflu product in wastewater and thence to the shallow marine environments into which the treated effluents empty will promote drug resistance. Aquatic waterfowl like ducks are a natural reservoir for H5N1, so the active drug, the virus and the hosts are all mixed together in that environment, a recipe for the emergence of resistance. When we last wrote about this, Harvard's March Lipsitch (an authority on the dynamics of Tamiflu resistant spread in the population) commented correctly that "under the scenario envisaged by this paper (massive Tamiflu use on a worldwide scale), introduction of a new neuraminidase gene (or a new strain) from waterfowl is not likely to be our greatest concern -- the problem will only occur during a full-scale pandemic in which the more immediate threat is from human-to-human transmissible virus. The bigger question is whether the use leads to selection of highly transmissible resistant strains of the pandemic virus itself." Clearly if a resistant virus became a pandemic strain that would be a very bad thing, but there is no reason to think at the moment that the two are connected. It might even be that resistant strains are less likely to be easily transmissible so the spread of resistance could be considered a good thing (as strange as that sounds). On the other hand, if resistance becomes extremely prevalent in circulating H5N1 from which the pandemic strain develops, it is not such a good thing.
As Lipsitch pointed out here a year ago, the central question remains what makes the virus more easily transmissible? The Tamiflu resistance question may turn out to be important but at the moment it is not front and center.
Medicine & Health
Comments
Revere-Do you think that this Tamiflu stuff will apply to all of the anti-virals out there or just Tamiflu?
Posted by: M. Randolph Kruger | October 5, 2007 12:54 AM
Randy: It depends on what your question is. This paper is just about passing through a sewage treatment plant, not about drug resistance. Some kinds of resistance might apply to more than one NI and some kinds only to Tamiflu. It also depends on the mechanism of antiviral resistance. So there is no general answer to your question.
Posted by: revere | October 5, 2007 7:22 AM
Is this really important, as far as resistance goes? Aren't we pretty sure most disease (and especially flu) will mutate around drugs anyway? Wouldn't it just "speed up" the process?
At this point, I'd be more concerned about other environmental concerns, rather than resistance.
But maybe I'm missing something?
Posted by: Patch | October 5, 2007 10:17 AM
Psatch: No it's not a given bugs will become resistant, or if they do, in what way. They often pay a price for resistance, which makes a difference. I agree this is a side issue but it is not foreordained that resistance will develop or if it does, what its impact will be.
Posted by: revere | October 5, 2007 11:04 AM
Everything we have done and everything we do is plays into the hand of this family of viruses.
It can do what it took bacteria forty years to do in five minutes.
It has harnessed genetic instability (mutability) in an almost supernatural way and at the moment and for the forseeable future, we have no defense against it...no matter the reassuring public pronouncements.
Lets hope we have a few more years to sort this out...and to rediscover the effective tools including vaccines against secondary bacterial septicaemias and pneumonias.
Posted by: Tom DVM | October 5, 2007 11:37 AM
is the OC effective in birds ? I remember the discussion
about drinking one's urine with the conclusion
that it won't work.
If such small concentrations of Tamiflu do work,
then why don't we add some routinely to the drinking
water, lemonade,bear,juices in a seasonal wave ?
Wouldn't it be a good thing to have our best antiviral
in the environment to kill the virus ?
Posted by: anon | October 7, 2007 2:46 AM
anon: aside from all the other reasons we wouldn't put it in the drinking water, Tamiflu doesn't kill the virus. As another commenter has noted, it prevents it from detaching from a cell and going on to infect another cell. So Tamiflu in the environment wouldn't do anything to the virus. It might select for resistant strains that were infecting hosts (like birds) that were expopsed to virus in the water where the Tamiflu was.
Posted by: revere | October 7, 2007 9:20 AM
Given past reports (and I have no way to measure accuracy), it is entirely possible that a copy of Tamiflu has already been incorporated in poultry and duck feed and is already in the environment in areas where H5N1 is endemic and other human seasonal viruses exist as well.
Posted by: Tom DVM | October 7, 2007 10:31 AM
The comment about this substance being so difficult to break down that it goes right through sewage treatment and out into surrounding waters caught my attention and made me want to find out more. I found the following to support your blog: Since the World Health Organization's first warning of an avian flu pandemic two years ago, nations worldwide have been stockpiling Tamiflu for treatment and outbreak prevention. The drug, which minimizes flu symptoms and duration, inhibits the movement of the influenza virus from the cells it infects, and also helps uninfected people avoid contracting the flu. However, Tamiflu's active agent, the metabolite oseltamivir carboxylate (OC) would be excreted into sewers for several weeks during a pandemic and is expected to withstand biodegradation. According to the researchers in the current study, once birds drink OC-laced water from catchments receiving treated wastewater, they could produce Tamiflu-resistant strains and pass them on to other birds who share the same waters. I am really curious to find out the answer to your question: what makes the virus more easily transmissible?
Posted by: Liz Henderson | November 15, 2007 9:14 PM
Liz: ". I am really curious to find out the answer to your question: what makes the virus more easily transmissible?"
You and everyone else. We've talked a lot about it here (e.g., here. Click on Bird flu/biology category on the left sidebar for some of the many, many posts on this and similar topics.
Posted by: revere | November 15, 2007 9:23 PM
can tamiflu be obtained for households to keep on hand , if there is an outbreak?
Posted by: shawn landrum | July 5, 2008 11:22 AM
shawn: Yes, but you need a doctor's prescription for it. I'd pick Relenza at this point if you go to the trouble of getting a script, but you have to inhale it.
Posted by: revere | July 5, 2008 11:29 AM