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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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April 27, 2009

Don't Hit The Bunkers Just Yet

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Posted by Derek

Swine flu: is it time to panic yet? Actually, it never is, and this is a particularly useless time to start running in circles, despite the apparent non-stop coverage on the cable news channels. I had some exposure to those during my recent vacation, which only confirmed the complete ban on the damned things in my own house.

I’m reminded of a line from Michael Lewis’s article on New Orleans in the immediate aftermath of Hurricane Katrina. He described a neighbor as suffering from a severe information handicap: his TV was on. But I can’t get all superior about the Internet, either, since Drudge and others are running piled-up red headlines in the same manner. What’s the real situation?

As far as I can make out, it’s this: over the past many weeks, about one thousand cases of influenza have been reported in Mexico, with about seventy of them fatal. Travelers returned from Mexico have shown up ill in several other locations. But none of them have died – in fact, many of them don’t seem to be all that sick, and appear to be recovering without incident. This flu seems to have spread human-to-human in Mexico, but I’m not aware of any reports of that happening in other locations yet.

And here’s what we don’t know: the number of people actually infected in Mexico is unclear and will remain so. Seventy deaths in a thousand cases of flu is a very alarming figure, and that’s what’s driving all the attention. But we don’t know if that number should really be five thousand, or even ten. And we don’t know if all of those seventy patients even had influenza (or this strain of it) at all – the great majority of them don’t appear to have been serotyped.

So no, it’s not time to sound the sirens just yet. Odds are that this will wind down, just like many other outbreaks of influenza do. But we don’t know that for sure. If I had a nonessential trip to Mexico City scheduled, I’d postpone it. (Not that I’m looking to spend a lot of time in the city in general: one factor in the apparently high fatality rate there might be the awful air quality).

One thing an outbreak like this does, though, is to remind everyone that viral epidemics are potentially a real problem. I don’t think that this one is the Pandemic We’ve Been Waiting For, but that one might well be out there, and there’s no way to know when it might appear. If and when it does, we may not have many pharmacological weapons against it, for the reasons I’ve outlined here. For now, keep an eye on whether any of the cases outside Mexico develop into anything more serious than a day or two in bed, and whether any of these transmit to people around them. And don't watch any cable news. Here's the CDC's page on the outbreak, and here's the WHO.

Comments (34) + TrackBacks (0) | Category: Current Events | Infectious Diseases


COMMENTS

1. Retread on April 27, 2009 10:24 AM writes...

Hopefully Derek is right. However -- the following is a quote from an AP release yesterday.

"Nearly all those who died in Mexico were between 20 and 40 years old, and they died of severe pneumonia from a flu-like illness believed caused by a unique swine flu virus."

As Derek also notes, early reports from the front are often inaccurate. But assume the quote is actually true.

Why is this significant? Because most influenza virus infections kill the very young and the very old. This one is different (at least in Mexico) --frighteningly, this is the IDENTICAL clinical pattern to that seen in the 1918 flu pandemic, where mostly the young and healthy died.

It is very likely that the molecular biologists have already cloned the organism and know exactly where the mutations are that make this virus different (or the new assortment of genes from different species making up the new virus).

Consider how poorly we understand protein chemistry (and small molecule chemistry). If we really understood protein chemistry, theoreticians would have predicted all the new altered conformations of the new proteins by now, and computational chemists would have designed a small bioavailable molecule to inhibit those conformations, and synthetic chemists would have made tons of them. None of the last 3 desiderata is anywhere close to reality, which is why chemistry is more than just intellectually fascinating and a thing of beauty.

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2. dWj on April 27, 2009 11:06 AM writes...

I had some exposure to those during my recent vacation

I hope they're not contagious.

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3. Iridium on April 27, 2009 11:36 AM writes...

One of the grad students I work with brought up a very good point neither of us feel has been addressed in the Swine Flu incident so far. All of the news stories seem to stress that the Mexico strain appears to be much more virulent and exhibits a high fatality rate in healthy people. Whereas, those in the US who have been infected have had relatively mild to moderate symptoms, none of which have caused a death. Oddly, no one seems to know why people are dying so readily in Mexico while everyone else seems to recover fairly quickly. The grad student posited that simply the differences in healthcare and finances may be contributing to the 'high level' of virulence observed in Mexico. Both of us are unaware of the current economic situation South of the border. However, considering Mexico has, overall, remained a poor country, it is possible that those who are dying are simply not seeking medical attention until they're practically dying simply because they can't afford/won't pay to see a physician early on.

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4. Chemjobber on April 27, 2009 12:25 PM writes...

It is my understanding that Mexico, although poor compared to the US, is better described as a 'middle-class' nation, especially Mexico City. When this is all over, it will be interesting to see where in the socioeconomic strata the victims were.

I was amused to read on my favorite survivalist blog about predicted shortages of Cipro. Fat lot of good that will do you.

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5. trrll on April 27, 2009 12:27 PM writes...

A more optimistic interpretation is that only the most severe cases are coming to the attention of the authorities in Mexico, and that there are a huge number of people who never become sick enough to seek medical attention.

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6. Stu West on April 27, 2009 1:01 PM writes...

"I was amused to read on my favorite survivalist blog about predicted shortages of Cipro. Fat lot of good that will do you."

To prevent and treat seondary bacterial pneumonia? Reasonable amount of good that will do you.

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7. retread on April 27, 2009 1:07 PM writes...

Trrll -- you are absolutely correct. Severe cases always predominate when a new disease is discovered. Consider AIDS. The cases discovered initially all died in a few months. When we finally had a serological test for infection, much longer survival was noted (and many people were found to be HIV1 positive but clinically healthy). The median survival gradually increased by a factor of 10, as AIDS was (re)defined again and again -- and the increase antedated the arrival of effective drugs (such as HAART) for the condition.

But this still is not enough for us to relax. The case fatality rate of the '18 pandemic has been estimated at only 2.5% (no one really knows) yet millions died.

Iridium -- I don't think socioeconomic conditions are enough to explain the wide clinical differential between the (early) experience in the USA and Mexico (if it in fact really exists). However, not too many people on welfare vacation on spring break in Mexico, so there might be something to it. We'll see

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8. Lucifer on April 27, 2009 1:14 PM writes...

What if the thousand who sought medical attention in hospitals were the most ill of the tens of thousands who got a mild case?

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9. CMCguy on April 27, 2009 2:52 PM writes...

Is this another instance where the Science and the Journalism just have not mixed well? Certainly is a serious event and has potential implications but as many of the comments above express seems like much of the facts and details are still lacking so the signal to noise hard to distinguish. The Mass Media has been primed in recent years to create hyperbole with SAR scare(s) and other talk of possible Pandemic diseases however at the same is important function with global connectivity to provide information quickly. And how many Scientists who are questioned jump to what could worst case scenarios rather than truly emphasize the data is so limited that anything said is purely speculative. Problem with the sound bite and fragmented nature of today is that stories generate a life of their own that lose touch with the reality.

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10. The Epidemiologist on April 27, 2009 9:25 PM writes...

I spent a good portion of the weekend in the company of one of the US's leaders in pandemic preparedness. It was hard not getting the sense from him (and he's published on 1918 in both the ID and history of medicine journals) that the reports thus far suggest Mexico may already be behind China when the latter dealt with SARS in the early part of the decade. If so, don't be surprised if this thing explodes pretty fast into the major health event of the year, perhaps of the decade. For those who wonder if I've lost my mind in suggesting this, I suggest you take a look at some of the Tom Clancy books. In one, he hypothesizes a bioterror attack on the US with Ebola virus. Pie in the sky stuff, I know. But if you start to think about how to control any sort of virus spread from human to human, as swine flu appears to be, particularly one with significant case-fatality potential (as 2.5% is), then you quickly realize how big the social and economic impact could be. Let's hope this isn't what's about to happen. If it is, then the economic meltdown last fall when Lehman Bros went under will seem like a quaint economic panic by comparison. It would not be a pleasant experience. For anyone.

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11. MTK on April 27, 2009 9:52 PM writes...

I think most people on this blog will recognize that while this probably won't be a 1918 type pandemic, it's still prudent to keep tabs on this and to find out as much as possible about the real mortality rate and the virulence of this strain just in case.

You'd be amazed at the number of people who think this is just media hype and that it's nothing to be worried about. That may eventually end up being the case, but to dismiss it out of hand before we know more is irresponsible

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12. Dan Howitt on April 28, 2009 12:14 AM writes...

"A more optimistic interpretation is that only the most severe cases are coming to the attention of the authorities in Mexico, and that there are a huge number of people who never become sick enough to seek medical attention."

Interesting.

Dan Howitt

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13. Morten G on April 28, 2009 3:11 AM writes...

If this was like a regular flu virus then many more old people should have died than the 70 20-40somethings from the swine flu. But the fact that not a lot more instances are popping up and those that are sick with the flu outside of Mexico aren't terribly ill suggests that the virus mutated into something less dangerous, more infectious. Ebola is an example of a disease that gets less dangerous as it goes from (human) host to host.

But there is still the hypothesis that the 1918 pandemic was caused by an avian flu that had jumped to pigs and then to humans. Which is worrisome.

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14. EricM on April 28, 2009 3:25 AM writes...

There were an average of 44700/365 = 122 motor vehicle fatalities per day in 2006.

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15. Tom Clancy's Evil Twin on April 28, 2009 4:58 AM writes...

Yes, the media really do seem to have jumped on to this bandwagon, last Wednesday it was only a small footnote on p12 in the UK papers, now it makes all the front pages, forecasting the end of civilisation as we know it!
Although I'm not an authority on the flu virus, the fact that this is an H1N1 may explain the apparent difference in severity. This was the type responsible for the 1918 outbreak and as such the level of imunity to H1N1 strains is higher than for H5N1 for example. Although the Mexico outbreak is not an identical H1N1, enough of a similarity may be there for a higher level of resistance. I don't know how bad the Spanish flu outbreak hit Mexico, but isn't it just possible they got off light last time? Just a thought, to be honest I'd be more worried about a H5N1 going from birds, getting into pigs and then back to us!

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16. bradpalm1 on April 28, 2009 5:56 AM writes...

More concerning to everyone is whether this now "humanized" swine flu will mutate again and acquire the oseltamivir (Tamiflu) resistance seen with this past flu season's Type A influenza. Why can't the pharma community come up with other neuraminidase inhibitors than oseltamivir and zanamivir (Relenza)? Why no oral formulation of zanamivir which is difficult to administer and contraindicated in children, the elderly and in people with respiratory problems, the very people you're trying to treat?

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17. Anonymous Virology Researcher on April 28, 2009 6:58 AM writes...

First, to bradpalm1, while I cannot go into details because what I know is proprietary information, there IS significant research into novel flu treatments taking place in the biopharma industry. Unfortunately, the stuff I know about won't be ready in time to make a difference if the Mexican swine strain does go pandemic.

Like everybody else I hope we do not have a pandemic this year, because aside from the human cost in lives the world economy seems in rather shaky condition just now. I'm not an economist, but I would guess the impact of a pandemic on the global economy could be a very serious matter indeed.

Like most virology researchers, in recent years I have been most worried about the highly pathogenic avian H5N1 strains (usually called "bird flu" in the media). Actually I still am worried about the H5N1 strains, which remain a potentially serious threat should one ever become able to spread among humans. But this swine flu strain should remind us that avian flu is hardly the only threat.

There has been some speculation about whether this might have been a bioterror attack; at this point I don't consider such speculation very plausible. This crazy-quilt mixture of pig, human, and avian strains from multiple continents looks more like a natural recombinant to me.

HOWEVER, the world apparently has yet to understand something one of my professors said about 25 years ago: the best defense against a bioterror attack is something we should do anyway: spend MUCH more on public health services everywhere.

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18. MTK on April 28, 2009 7:15 AM writes...

I think most people on this blog will recognize that while this probably won't be a 1918 type pandemic, it's still prudent to keep tabs on this and to find out as much as possible about the real mortality rate and the virulence of this strain just in case.

You'd be amazed at the number of people who think this is just media hype and that it's nothing to be worried about. That may eventually end up being the case, but to dismiss it out of hand before we know more is irresponsible

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19. bradpalm1 on April 28, 2009 9:11 AM writes...

Anon Virology Researcher: I'm somewhat aware of current anti-influenza research including other NAI analogs, dimeric and polymeric inhaled zanamivir compounds and some other strategies, but for many reasons it seems an orally bioavailable zanamivir formulation would be ideal solution to your stated concerns. Are you aware of any research in this area?

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20. MBryant on April 28, 2009 12:13 PM writes...

If you want to read a great book on the 1918 influenza outbreak, I would recommend John Barry's "The Great Influenza". It was a fascinating account of how the medical/scientific establishment was trying to deal with a frightening epidemic, and how ill-prepared they were to answer even the most basic of questions on the disease. Although we are better equipped today, we also have the problem that such illnesses can spread much more quickly by airplane, than they can by WWI troop ships. The fact that the healthiest are dying from this recent influenza make it chillingly similar to the 1918 strain.

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21. Pfizerite on April 28, 2009 1:29 PM writes...

Bradpalm1 as an ex-Pfizer antivirals researcher I can give insight as to why big pharma is not interested in new influenza or any other acute viral illness. When you look at the current influenza drugs or the failed rhinovirus drugs they needed to be administered within 24-48 hours after infection which means in the US a patient would need to see a doctor and make it to a pharmacy within a very short window after first presenting symptoms and most patients present outside the treatment window. This means that the company is not selling very much drug and so senior management asks the reasonable question as to why they are investing in this area for no benefit to the company but a major manufacturing problem if there is an epidemic and demand for the drug increases diverting manufacturing resources and the the politicians demand the drug at cost or low profit. HIV and Hepatitis C were special cases because as chronic infections ther is no time window and for HIV a lot of pressure from the activist community to do something. If you notice Pfizer and GSK both got out of HIV by spinning out their HIV portfolios and effectively ending research.

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22. bradpalm1 on April 28, 2009 2:56 PM writes...

Pfizerite: I understand this perspective, but this recent swine flu outbreak certainly underscores the potential dire socioeconomic consequences of a true influenza pandemic which extend beyond any microeconomic decision by pharma companies. My larger point is given these rapidly mutating viruses, growing NAI resistance and the cyclical need for world governments and other health groups to stockpile these drugs I'd think there'd be strong incentives from the FDA, WHO, CDC and even BARDA to support this type of research. Additionally, I don't think either Roche or GSK are doing poorly with this outbreak so I wonder why there's such a disconnect here?

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23. Pfizerite on April 28, 2009 8:28 PM writes...

bradpalm1 in the US, big pharma has to turn a profit from sales of its drugs. Neither influenza drug has had the sales (+500 million a year) that would entice management to fund and support a new antiviral program. Additionally, the FDA cannot give big pharma the incentives that they would want for a flu drug program and simultaneously retain any integrity. To put it bluntly antivirals do not meet the profit margins demanded by senior management despite the occasional epidemic. Since med chem, CMC, WWSS assets are limited antivirals are defunded and current programs are canceled or deprioratized

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24. CMCguy on April 28, 2009 8:38 PM writes...

Pfizerite I was not aware most Pharmas had "Warfare and Warfare Support System" assets so assume acronym has different meaning...

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25. Anonymous BMS Researcher on April 28, 2009 9:03 PM writes...

CMCGuy I believe WWSS means World Wide Safety Science.

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26. Krillin on April 28, 2009 11:57 PM writes...

I have a 3-month stockpile of active hexose correlated compound (AHCC) that I can start taking if things start to look grim. It's quite expensive, so I just use Epicor (Well, actually the cheap livestock version: Diamond V XPC.) on a daily basis. Both have a few Pubmed articles about their effectiveness vs flu.

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27. Anonymous BMS Researcher on April 29, 2009 7:27 AM writes...

News media are reporting the first confirmed US death from the new swine flu strain. This sad but not surprising development will no doubt intensify the media frenzy. Unfortunately, substantive changes in the situation will take many news cycles. Time will be needed to develop, test, and manufacture any vaccine. Time will be needed to understand the epidemiology and pathology of this strain. While the world waits for substantive information beyond what we already know, the media will feed the public's understandable hunger for information with anecdotes and speculation.

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28. Incha on April 29, 2009 9:50 AM writes...

Does anyone know why H1N1 has a higher fatality rate in young adults vs other flu strains?

bradpalm1 - like any other business, pharma companies and biotechs have to look at profit margins. Where governments/general public are likely to want a drug at near cost price it makes no financial sense to invest money in developing it. Just because its for flu/malaria/TB doesnt make it any cheaper to develop and run the clinical trials. The same is true for some low incidence or chronic diseases.
Increasing patent life to 50 years, or giving 20 years market exclusivity from launch might make these areas attractive, but I doubt that would ever happen. Governments and the general public are way too taken with generics these days, when what are those companies really offering?

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29. CMCguy on April 29, 2009 10:03 AM writes...

Thanks for clarification Anon BMS Researcher although must say that after thinking about more relative to the Clinical and Reg dealings with FDA/Congress maybe the meaning I indicated does apply to Pharma.

In terms of the Media coverage of the Swine Flu in recent days based on "Headlines" I have seen actually seems fairly well balanced in presenting seriousness as well as expressing open questions/limited verifiable data regarding current event. Like many "crises" probably will have to wait for retrospective analysis to determine "good vs. bad".

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30. Anonymous Virology Researcher on April 29, 2009 5:48 PM writes...

Incha on April 29, 2009 9:50 AM wrotes...

> Does anyone know why H1N1 has a higher
> fatality rate in young adults vs other
> flu strains?

First of all, we do not yet know enough about the epidemiology of the strain causing the current outbreak, though the death in Texas is similar to what we see in ordinary seasonal flu. IF this strain turns out to kill mostly healthy adults that would be worrisome, but we don't yet know if that's the case.

Second, there are many H1N1 strains that don't hit young adults very hard; indeed about half the cases of ordinary flu in the winter of 2008-2009 were H1N1 strains and as is typical of seasonal flu they mostly killed small children and elderly people.

Certain strains of influenza, such as the avian H5N1 strains and the 1918 pandemic, do kill young adults. The leading theory as to why is described in the following Wikipedia article:

http://en.wikipedia.org/wiki/Cytokine_storm

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31. bradpalm1 on April 29, 2009 10:07 PM writes...

AVR: any thoughts about the likelihood of dimeric derivatives of zanamivir (below) being successfully deployed to treat this or future outbreaks of influenza?

http://aac.asm.org/cgi/reprint/48/12/4542

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32. Pfizerite on April 30, 2009 6:25 PM writes...

bradpalm1, without good data an solubility and stability it is impossible to say but those dimers look like they would be difficult to formulate into an aerosol delivery system and even more difficult to formulate as a soluble dosage form.

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33. Jose on April 30, 2009 9:10 PM writes...

Re: dimers- Gemini Surfactants 'R' Us!

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34. Jonadab the Unsightly One on May 4, 2009 6:03 AM writes...

The thing about Mexico is, the fact that it's right next door occasionally causes people in the US to forget that it is also pretty much a third-world country. If seventy people died of a flu strain in Chad, we would immediately guess that they probably didn't get proper medical care, and nobody would get very alarmed about what the same disease might do here. But when it happens in Mexico, people worry that it's going to cross the border and attack us here.

The other thing is, "swine flu", like "bird flu" and "mad cow disease" before it, has a catchy easy-to-remember name that even an uneducated person can feel they understand. The media loves this. You probably wouldn't see the same press coverage for something called "amoxycillin-resistant staphylococcus" (which I just made up out of whole cloth, but you get the idea).

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