Non-pharmaceutical interventions for a pandemic: getting it right (with Addendum from John Barry)

A Commentary by John Barry (author of The Great Influenza) in CIDRAP News and accompanying meta-commentary by CIDRAP Director Mike Osterholm highlight an interesting controversy about a JAMA article by Michigan's Howard Markel and colleagues. Markel's article was a detailed compilation of public health responses to the 1918 influenza pandemic in 43 cities in the US with the aim of telling whether any was associated with better community outcomes. The Markel paper bore the following conclusion:

These findings demonstrate a strong association between early, sustained, and layered application of nonpharmaceutical interventions and mitigating the consequences of the 1918-1919 influenza pandemic in the United States. In planning for future severe influenza pandemics, nonpharmaceutical interventions should be considered for inclusion as companion measures to developing effective vaccines and medications for prophylaxis and treatment. (Markel et al., JAMA [abstract; annoyingly, article is subscription only; discussed in more detail by us here])

Barry's book seemed to corroborate this for some of the major cities considered in this paper, particularly New York City. Now Barry is saying his review of the data suggests both his earlier judgment and Markel's paper were in error on a key point: New York City did not practice isolation and quarantine. Moreover Barry alleges the same error is made in Markel's data on the only other city Barry re-reviewed, Chicago, and these discrepancies raise doubts about the rest of Markel's data. Barry broached these concerns in a letter to JAMA (also subscription only), but he was not satisfied with the authors' response.

This isn't just an academic squabble. Markel's work, first discussed at an Institute of Medicine meeting, has been cited as support for CDC's recommendations for community mitigation measures in a pandemic. Mike Osterholm was one of the earliest and remains one of the most informed and insistent warning voices on the possible serious consequences of an influenza pandemic. Without a vaccine for a pandemic strain, nonpharmaceutical interventions (NPIs) like school closing and isolation and quarantine are among the few things we can do at the moment, so there efficacy is of crucial importance:

Frankly, our one real hope is that all the other public health tools we have employed in past infectious disease epidemics will make a difference. These tools have largely tried to change individual and community-based behavior to avoid exposure to the infectious agent until after the epidemic has run its course. These are often referred to as nonpharmaceutical interventions (NPIs) and include familiar approaches such as isolation, quarantine, and social distancing. While all of us might believe that these measures will work, until recently very little evidence has been available concerning their efficacy in reducing either morbidity or mortality in an influenza pandemic. This is due in part to the infrequency of such pandemics (three in the last century) and an absence of systematic studies during those pandemics of our collective public health actions and their impact. (CIDRAP News)

The key point here is we shouldn't say something works just because we have nothing else to offer. If you are a public health scientist you should have a better reason for recommending something. In the case of isolation and quarantine, there is an additional reason to be careful. These are measures that limit individual liberties. This might (or might not) be a trade-off worth making if the stakes are vital and they actually make a difference, but if taken they should be based on accurate information. It is not a matter of better being safe than sorry. Isolation and quarantine can also make things worse by inducing the sick or exposed to flee authorities, spreading the disease. Unfortunately, this administration (of which CDC is not only a part but under Director Gerberding a willing participant) has a bad record on social control and we have little trouble suspecting it might seize on any data to justify decisions it wishes to take by virtue of its own preferences.

Like Osterholm I read Barry's critique with concern. You can judge for yourself by reading the details. Some of Barry's points are not completely germane (e.g., that the New York Health Commissioner Royal Copeland was a homeopathic doctor and not an allopath; this doesn't recognize the historical roles of various medical sects at the turn of the century and adds nothing to his argument), but his questions about specific documents are important and call into question the support for some of Markel and colleagues' conclusions, conclusions that surprised some of us at the time. As so often, Mike Osterholm goes to the heart of the matter:

This concern does not disprove that NPIs altered the course of the pandemic. But we in public health will face overwhelming challenges with risk communication and credibility during the next pandemic. While we will surely recommend the use of NPIs at that time, we have an obligation to society to tell exactly what we know and explain the science that supports our conclusions. How will we ever be able to dismiss and even condemn the crazy things that some will try to do during a pandemic if we don't base recommendations on the strength of our science? We must hold ourselves to that standard now and in the future.

Addendum: John Barry sent me the following response and wished me to post it for him:

I agree entirely with your observations in Non-pharmaceutical interventions for a pandemic: getting it right. If I may do a little fly-specking, however. You mentioned that my comment that Royal Copeland-- Markel's sole source of information, especially what the NY Times quoted him as saying-- was a homeopath was irrelevant. I agree with you that that is a side issue, but that was not my key point re: his credibility. The key point is the fact that he was a Tammany Hall political hack-- that and that he told 2 gatherings of physicians something different than what the told the NY Times. (For those of you who don't know, Tammany Hall was the most corrupt political machine in American history.) Tammany had only in early 1918 regained control of New York, after reformers had rule dit for several years. Copeland would do anything Tammany wanted. This included eviscerating the New York City health department, which had been probably the best municipal health department in the world, by replacing public health experts with other patronage hacks. The reason he never closed saloons, theaters, and the like, which most other cities were doing, was not because of his public health judgment but because of the power those businesses had in the Tammany organization. Copeland's loyalty was rewarded, and he later rose to the very highest reaches of the organization.

More like this

"The key point here is we shouldn't say something works just because we have nothing else to offer."

You've touched on the (seemingly) inalterable formula for success, exhibited with unconscionable certitude by the current Administration, Revere: Select a course of action, no matter how clearly it is destined to lead to failure, and then deny, vehemently, that any other avenues are even available. When it becomes clear that catastrophe is inescapably on the horizon, then alter the definitions of "success," and "failure," and continue on about your business, just as before.

I think that we may avoid having to deal with the incipient pandemic, while this moribund Administration retains its stranglehold on the country; I certainly hope so, at least, because I see their probable response to it as their crowning achievement, and a monumental testament to their unparalleled talent for incompetence. Their vision will probably include draconian measures as the very first response; just as soon as they begin to appreciate the real nature of their utter lack of preparedness; this will be coupled with the depth of the spiraling panic that will drive their actions; that will, in my opinion, expose a level of disorganization and internal breakdown that we have had only "vague" glimpses of, in the past.

If these people are still in office, expect the very, very worst, at best. That is the only way they might possibly appear to be any more capable than they have clearly demonstrated that they are: They could do something right, I suppose, by sheer accident. But I certainly wouldn't count on it.

Nice post. Trying to tease out the effect of NPIs based on data from 1918 is fascinating. I hope they're able to reach a reasonably well-supported conclusion.

As an aside, I wonder where the term 'nonpharmaceutical interventions' came from? Seems like 'nonmedical interventions' would be more accurate. (There are plenty of medical interventions that are nonpharmaceutical, e.g. IV fluids, breathing support, but it seems clear that those aren't considered NPIs in this context.)

There is a grave danger in allowing a fascist government like ours to control public health. In 1918 our Constitution and Bill of Rights existed. Now, with the passage of the Patriot Act, we no longer have the protection of our Constituion and Bill of Rights. We can be arrested as a terrorist, taken to a secret prison, tortured, and killed by the FBI and CIA. I know some will protest this latter statement; if so, please read about the Rendition Program of the CIA. And read about the experience of some American citizens who have been arrested under or new anti-terrorist laws.
It is good the Homeland Security Department protects us from a terrorist attack. But there is also a darker side.
The CDC and Homeland Security also have police state and neoliberal economic policy functions.
What will happen to us if public health functions are perverted to implement police state functions? Who would be able to oppose this? How could they be stopped?
If during a flu pandemic, the government implements quarantine and isolation of those infected, who is to say they will not use these powers to control all those suspected of being political opponents of government policies?
If you think this is impossible, please note that in Russia, some political opponents were declared insane and placed in mental hospitals, some for life.
In Nazi Germany a government plan was systematically implemented to exterminate the mentally retarded and insane.
The Third Reich also ordered doctors to perform incredibly painful medical experiments on prisoners in concentration camps. Many of those who survived the experiments, were sent to the gas chambers. And of course many Communists and other political opponents were arrested and executed.
Can we trust our government not to imprison, torture, and kill political opponents during a pandemic emergency, now that the Justice Department has made torture legal, and the CIA has a Rendition Program? And what about all those on the FBI lists, obtained after spying on US citizens. Will those lists be used to identify opponents and eliminate them, as was done during the Third Reich in Germany?
Our new attorney general says he does not know if waterboarding is or is not torture. Would you like for him to order your arrest? As you know, the FBI can obtain the record of all books you have checked out of the public library. Have you recently checked out any books on Islam? If so, then please make final arrangements for your estate before your are arrested.

I have a lot of respect for Markel (he was a classmate) but I share your worry about the potential impact on civil liberty. In fact, based upon Naomi Klein's book (The Shock Doctrine) I would expect that the Administration already has plans for how to economically exploit a pandemic. Note that this is not quite the same as infringing on civil liberties. Rather, it is the exploitation of a catastrophe to reshape society in a manner that is economically favorable to some group.

Obviously, each crisis is also an opportunity; that is not a new concept. But the problem is that in a public health crisis, the first priority is to protect the public health. It is a conflict of interest if the people planning the crisis response have a different agenda.

Although I share the worry about the potential impact on civil liberty, I worry more about the potential for a hidden agenda to exploit the crisis for economic gain.

On the issue of civil liberties, FYI all of the interventions proposed by the CDC are voluntary, including home isolation and quarantine, so that really is not the issue under discussion here. Rather it is the efficacy of certain public health measures.

Susan: I must disagree. The possibility of this administration instituting isolation and quarantine is very much one of the things under discussion, although it is not the only one.

Additionally, even though the point under debate between John Barry and Markel, whom I respect equally, has to do with New York and whether a quarantine was imposed, the bigger picture is that quarantine is not the most efficacious public health measure by any means. The findings of the Markel study and others by Hatchett & Lipsitch, and Bootsma & Ferguson (both in PNAS) on the 1918 data all point to a combination of non-pharmaceutical interventions including especially school closures and banning of large gatherings as the more important factors. Additionally, timing of intervention is also crucial, a point that is again consistent across all 3 studies.

I agree it is important in any scientific endeavor to make sure that the methodology used stands up to scrutiny, and I applaud Barry and Osterholm's efforts in this regard. Personally, I'm not sure I can draw any conclusions at this point, so I'm following this issue with interest.

revere,

Susan: I must disagree. The possibility of this administration instituting isolation and quarantine is very much one of the things under discussion, although it is not the only one.

What I meant was specifically in relation to the recommendations made in the Interim pre-pandemic guidance on community mitigation strategies by the CDC, which is the policy under debate as far as I can ascertain, as per the Markel paper.

Of course everything is under consideration, but that is not the context under which John Barry is objecting to the Markel data, at least I don't think so.

Good data is always important. (GIGO) Perfect data is non-existent.

That said, challenges to the historical accuracy of historical studies should be viewed as just that, not challenges to the recommendations that might rely, in part, on the findings of those studies.

Both Barry and Osterholm make a point of limiting their critique accordingly:

Fianlly, it is important to note that the errors in Markel's article do not disprove the hypothesis that NPIs impacted the course of the pandemic.

(Barry - last paragraph of CIDRAP commentary).

This concern does not disprove that NPIs altered the course of the pandemic.

(Osterholm - last paragraph of his Introductory Remarks to Barry's Commentary.)

And at least in this discussion, neither Barry nor Osterholm takes issue with the more recent computer modeling that projected signficant positive results from early, layered application of NPIs. I don't know if they have elsewhere.

Apart from differences they may have with Markel's study, I believe both Osterholm and Barry support/advocate personal preparedness that may help ameliorate a pandemic's potentially devasting impact on our global Just In Time delivery system of essential supplies/materials. I also assume that they both support/advocate continued coordinated and comprehensive planning at local levels in the event implementation of NPI's is required (because as my broker recently reminded me, past results are no guarantee of future performance).

I look forward to hearing more of this very interesting discussion.

By Into the Woods (not verified) on 28 Nov 2007 #permalink

@Into the Woods
I think you are taking this post somewhat differently than it was intended. I don't think Revere was trying to say that questioning the Markel paper's conclusions throw the effectiveness of NPI's into question as well, rather he says that they have never been proven in the first place.

I think the point being made here is that *because* NPI's have never been proven effective, we need to do all that we can to clearly understand all the evidence available that would suggest they would or wouldn't be effective. In this case whether or not the conclusions of this particular study are adequately supported is not just a matter of historical accuracy, but relevant to the discussion of what steps we are to take.

Your quote from Osterholm was also included in this post, I think giving it a second reading would help to clarify the point.

Allen

My last reading of the Pandemic Preparedness Plan said the Homeland Security was the lead agency if a pandemic threatens, They are as capable of making informed decisions as Tommy Thompson was in discussing anthrax.

I recommend a novel, The Last Town of Earth to point out some of the practical and ethical issues related to quarantine. Not the greatest novel, but raises important issues.

When I was being interviewed by Ed Koch for the Commissioner of Health post in NYC I told him that I would not recommend to him actions for the sake of action. He said, "What do you mean?" I told him that I would not have recommended and would have condemned the hosing down of 34th St. to control and outbreak of Legionnaires' Disease in Macys. His response, "No one told me it was the wrong thing to do."

In thinking about the problems of NPI in New York City, I shudder. Has anyone thought things through? Groceries in NYC don't maintain much of an inventory and are dependent upon frequently deliveries. Do we allow trucks in and out? Do we close the subway? Do we close the bridges, do we close the airports? Are we serious or doing something for the sake of doing?

By David Sencer (not verified) on 28 Nov 2007 #permalink

For those of you who don't know, Tammany Hall was the most corrupt political machine in American history.

Shush! Karl Rove thought he'd retired that title. If you keep saying nice things about the political entrepreneurs of the *first* Gilded Age, Rove'll be back in the West Wing and we'll all have to look at his ugly mug in the news every day.

By Anne Laurie (not verified) on 28 Nov 2007 #permalink

Allan: I am not sure I follow when you say:

I don't think Revere was trying to say that questioning the Markel paper's conclusions throw the effectiveness of NPI's into question as well, rather he says that they have never been proven in the first place.

(Emphasis added)

I went looking for where revere says that and could not find it. Could you please provide a specific reference where he did?

What I did find was that in revere's post on the study back in August (linked in his post above), after describing the scope of the study and several important limitations on the study, revere said:

What is quite clear from the analysis, however, is that information about when, how long and in what combination NPIs were used in relation to the onset of the epidemic in a city explains a great deal of the variation in epidemic experience....

The bottom line is that the earlier a city acts and the more coordinated and multifaceted its response the better off it seemed to be -- in general.

revere's August Post

That may not be "proven", but it sure sounds like he thought it was headed in that general direction.

I agree that "whether or not the conclusions of this particular study are adequately supported are ... relevant to the discussion of what steps we are to take."

Accordingly, I would hope for a more measured discussion of the study, instead of approaching this or any other supporting study for NPI (or PI for that matter) as either gospel or garbage.

Barry's concerns about the two cities he carves out for discussion may have validity. Certainly, finding the facts about the 1918 pandemic is often a long and difficult process with more than a few twists and turns - as Barry well knows.

But his CIDRAP commentary feels more like something out of a political slugfest than a scientific inquiry. I was surprised by both the tone and the approach.

I reviewed my Osterholm quote from revere's post again as you suggested, seeking better understanding from the context. It continued in this vein:

...But we in public health will face overwhelming challenges with risk communication and credibility during the next pandemic. While we will surely recommend the use of NPIs at that time, we have an obligation to society to tell exactly what we know and explain the science that supports our conclusions.

(Emphasis added)

Seems clear enough for me.

By Into the Woods (not verified) on 28 Nov 2007 #permalink

Gee, Now GWB is responsible for a possible pandemic breaking out under this administration.... What are you guys going to do when it breaks out under another administration, blame the previous one. Cant possibly be anything under the sun other than this administration.

Left wing drive by....take your shots and run. Fortunately I hear that this Administration has a new variant made up of H5N1, it is specifically geared towards left wing media types. Karl Rove will personally deliver it and in the Republican Party its called H5N1 FOR FUN!

You guys can harp about the CDC and that would be partially right and the NIH but its a different philosophy people. You need to just trot down in November next and vote your conscience on what you believe should be going on in the country. If you are in the majority, you will have to just blame Bush for the next 20 years. I want to remind everyone that 2 Republican Presidents were blamed for hurricane responses that the DEMOCRAT Governors refused to nationalize conveniently for 3 days and both knew and know the law relating to it. Both of those DEMOCRAT Governors are responsible for people dying. Now they dont call them lame ducks for nothing, dont be surprised by anything that happens in the quick near future. But dont blame "this Administration" for anything other than a cautionary approach to spending the entire GNP for something that might not come.

The plan is published and its being followed to the T. Perhaps you should read it before being quite so critical. Also remember thats a highly contentious Congress he is dealing with. You dont get any money for anything unless the DEMOCRAT CONGRESS votes it.

Corrupt? Please.... the Previous Administration was corrupt...I can lay a lot at their feet too. But that always escapes you guys.

By M. Randolph Kruger (not verified) on 28 Nov 2007 #permalink

Randy: I didn't suggest this administration was going to cause a pandemic, only that they would use a pandemic for their own political ends. You like to make things Republican/Democrat oriented, a particularly bad disease of our day. Democrats in congress (23 of them) have a lot to answer for as far as getting us into and keeping us in this war. At least 22 of them voted against it, which is a damn sight better than the Republicans. But the rest were cowardly and remain cowardly. The reason GWB gets blamed for so many things is that he is probably the worst president in American history in terms of damage done to the country and overall competence. He's bad on civil liberties, but not as bad as Woodrow Wilson, so he's not the champ at everything. Just close. there have been and continue to be a lot of bad Democrats, too. Was Clinton corrupt? Yes, in the usual petty ways of American politicians. GWB is corrupt in large ways as well, distorting and harming American interests for the sake of his friends. Much worse than renting out the Lincoln bedroom for campaign contributions.

what I remember best from past discussion is
that "strong leadership" was considered the most
important thing in 1918.
That was a military study last year.
That means, that measures are effective, when carried out
rigorously.
We may hate this "strong leadership" today,
but we might wish for it in a pandemic.

I can accept that opinion Revere. As usual even though its biased its well thought out and presented. In reality, IMHO its going to be history that judges the last three presidents. I honestly dont know if Iraq was a good idea or not except militarily. Well planned and thought out attack. But not the post Saddam plan. Obviously not politically. Neither domestic and internationally could that be the case. He lost the Congress to the Democrats and there are those lefties that want him impeached, but unlike Clinton he did get a resolution to do it. Kind of hard to indict someone for something that 435 and change members of Congress signed on for.

As for this leadership as Anon states it, I would rather have a strong authoritarian at the helm if it comes. It could get ugly and if a tumbledown started in one or more states it would take that to keep things going.

As I always say Revere, you could be right. The long run will tell the tale on this one.

With respect to your opinion.
.

. .

By M. Randolph Kruger (not verified) on 29 Nov 2007 #permalink

the whole JAMA/CIDRAP NPI Howard-John-Marty-Mike drama is all very interesting -- but hold on, was that really a post from David Sencer?

if so, David, this is just to say,
some of us in public health are trying to "think things through".

take care

By anon anon (not verified) on 29 Nov 2007 #permalink

Randy: If an eight-hundred-pound gorilla should take it upon himself to suddenly make you his "bi-atch," would you necessarily credit him, somehow, with being a strategic and tactical genius? Hardly think so.

And this? "I honestly dont (sic) know if Iraq was a good idea or not except militarily."

My, now that could certainly lay claim to establishing yet-to-be-acknowledged standards for disingenuous remarks on political topics; at least during the course of this discussion. On what particular aspect of this little misadventure might you feel the need to equivocate, with regard to its perceived wisdom? We've invested in this singularly spectacular debacle on several different levels; which one do you think we might focus on as having extracted the greatest possible return, for lives and treasure expended, to date? A stable Middle East? No? How about an oil supply that promises to hold down domestic prices? No? How about the establishment of a democratic state, that can be viewed as "a shining city on a hill," among the remaining (non-Israeli) despotic regimes (our "friends" included) that populate the region? No? How about the purely venal manner in which this fiasco has been conducted? Surely, you can find some excuse for the grievous, self-inflicted damage to both our economy and our currency -- both of which appear to be precariously unstable, to me, as a result -- ushered in, largely as a result of this war, by an Administration that is arguably the most financially inept, and institutionally corrupt, of any in our entire history?

Better yet...you choose which outcome you believe most inarguably justifies this war. That will make it much easier on you. Try to avoid "sloganeering," though...the Chimp and crew already have a firm corner on that market.

Anybody who -- still -- fails to see this war for what it is, must be absolutely, totally fucking brain-dead, and utterly beyond salvaging. I have never been so unspeakably ashamed of -- and thoroughly humiliated by -- the actions of my country in my entire life. This "thing" was, in its conception, the product of a criminal enterprise; in its conduct it has proven to be hideously demented. The unnecessarily dead, in that devastated country, continue to pile up...in obscenely twisted, incinerated, blasted-to-fragments remains of human beings. And "we" did that. If that does not somehow disturb you, then you are just as soulless as the people directly responsible for perpetrating this ineradicable stain on our collective history. Anyone who feels that it essentially a matter of waiting for the "verdict" of the various historians to be pronounced, with regard to everything having to do with this war, is simply not paying attention. Our guilt in this matter cannot be expunged; and those who possess a conscience, here, no that it can never be fully assuaged.

As someone who used to blast humans into small bits Dylan that statement doesnt particularly bother me. It sounds like you've been getting your scripts though from Pelosi and Harry Reid. Amazing how they have shut up in the last few weeks.

You dont know how close we came to WWIV in September and October Dylan. The entire place was almost incinerated....

Have a nice day and enjoy the freedoms you have in our morally, institutionally and financially corrupt society... You know, the fascist state.

By M. Randolph Kruger (not verified) on 29 Nov 2007 #permalink

Susan, I read your url and it will continue to fracture the argument about NPI/vax/antivirals further IMO. Its nervous people talking about a nervous subject. Good. Nervous people do something about it and Dr. O. is well known for his opinion that this or something like it is coming...soon.

Here is a question though and it should be the premise before starting any arguments pro or con on what to do. Here it is. What in Hell could we possibly do with a panflu that say cuts the current one year rate of almost 83% CFR to 1/2...around 40%?

That was and has been brought up time and again and I dont seem to get answers from the health people here, the EMA, the DHS or the FEMA reps that come out to train us. Last time I kind of pissed the EMA director off when I flopped a freshly inked up acetate onto the overhead and used my laser pointer to hit that graph that the WHO has been putting up. None of them had ever seen that there was right at 100% CFR in the last quarter. So please either you, Revere, Barry confirm or cool me down and tell me what anyone could possibly do at anything really past about 10% CFR. 5% in this state is 56%. 30% is 2 million. It doesn seem to be losing its affinity for humans, only gaining.

1918 flu herald waves I have been researching along with Tan06 in the NL and both of us have come up with pretty much the same thing and its relating to France and WWI. Its pretty obvious it was there for two years or more and in recurrent manner before it showed up in Kansas. Like what we have here now. The Grippe seems to have gotten a lot of people sick but little tracking, pneumonia seems to have a pretty good run for a couple of years in advance. You got it, you died. Also like now. Tracking it back towards China there are mandarins who reported deaths to the central government for years prior to it showing up in Europe.

What was the CFR? I really cant say because they classified every death as pneumonia, not pneumonia from flu. It would seem though that few survived it when they got it.

So in your opinion the conjecture about NPI is good, something to just talk about, or a really good idea say to start teaching the teachers? I remember drop and cover from the 50's and 60's twice a week. I still have the pamphlet here on how to build bomb shelters. Is it a good idea to start now or do you think it will just frighten people?

By M. Randolph Kruger (not verified) on 30 Nov 2007 #permalink

That 5% above in para 3 should be 56,000 people.

By M. Randolph Kruger (not verified) on 30 Nov 2007 #permalink

Randy,

Here is a question though and it should be the premise before starting any arguments pro or con on what to do. Here it is. What in Hell could we possibly do with a panflu that say cuts the current one year rate of almost 83% CFR to 1/2...around 40%?

First of all, I don't think it should be a premise. Because there is close to zero certainty about the 83% to 40% or whatever % scenario. Sure, it can happen, but anything can happen.

I'm not being flippant or complacent about this, I worry about it like everyone else. But to answer the question of what to DO, the issue is this: We are nowhere near prepared for even a 1% CFR pandemic. The way that I look at NPI, for example, or I call it CMG (community mitigation guidance) to identify it as the specific set of policies as recommended by the CDC, is to ask the question "What do we have in our arsenal?" I mean, what REALLY do we have, that is reasonably doable?

The 4 interventions in the CMG, voluntary home isolation of sick, voluntary home quarantine of contacts, early proactive dismissal of schools, daycare centers and colleges and keeping kids home, and general social distancing (eg avoidance of large crowds, etc) is IMHO the limit of what we can do. In other words, we are already throwing everything at the problem, assuming these get properly implemented.

But the GOOD NEWS is that CMG works BETTER the higher the CFR. Because the compliance will be higher. The modeling studies suggest very good results with only moderate compliance (eg reduction of AR from 40% to 10% with 30% compliance - re Ferguson). If you stretch out a pandemic wave using CMG to 12 or more weeks instead of 6-8 weeks, 10% cumulative AR with a flattened peak means that at any point in time, only around 1% (give or take) of people are infected and contagious, many of these will be sick at home or in hospital.

Which means that for someone who needs to go out, the chance of being infected is extremely slow!

Now, if you apply that to a 40% CFR scenario, sure, whoever gets infected, it's still 40% CFR. But IF we can get vaccines out to the public after 12 or maybe 16 weeks (using cell-culture eg the recombinant HA vaccine which can be available as early as 8 weeks into a pandemic) even if the protection is modest, we are STILL talking about a very large reduction in overall deaths.

The reason why I think the CMG deserves very careful scrutiny (and there are too many people who dismiss it lightly without looking in detail at the data available) is because it is unique in many ways.

Let's take antivirals and vaccines. BOTH of these 2 countermeasures are likely to work less well the more lethal the virus. Whereas CMG is the only countermeasure that works the opposite way, that you get a better relative result the higher the CFR.

In addition, both the modeling data coming out of multiple studies and the 1918 data (again multiple studies, not just the Markel one) suggest a very large reduction of overall deaths, in the order of 50%, with proper implementation but moderate compliance. That number increases by some estimates to as much as 70% if you add antiviral prophylaxis to household contacts.

Now, compare that to tamiflu, in the context of H5N1. There is no evidence that it reduces mortality to any significant degree. I would be happy if someone can achieve 10% reduction in mortality with tamiflu and H5N1 at this point, let a lone 50%!

Just as an addendum, the reason why CMG or targeted layered NPIs can produce such seemingly unbelievable results, is partly because it drastically reduces the chance of overshoot, which Ferguson explained in his study The effect of public health measures on the 1918 influenza pandemic in U.S. cities in PNAS.

For a Cliff's note version of that rather esoteric paper, go here. It's the second paper discussed on that commentary.

So in your opinion the conjecture about NPI is good, something to just talk about, or a really good idea say to start teaching the teachers? I remember drop and cover from the 50's and 60's twice a week. I still have the pamphlet here on how to build bomb shelters. Is it a good idea to start now or do you think it will just frighten people?

Well, here's the thing. A pandemic IS a frightening thing. You can't talk about something that is going to kill a lot of people without people becoming fearful. It comes with the territory.

The thing for me is, I don't think that fear needs to be a paralyzing nor long-lasting condition. When people first learn about it, yes, sure, they will be frightened. But you will be surprised how people can get used to the most horrible ideas; just go and ask people who lived through years and decades of civil war, like Lebanon in the 80s. Over time, you get so used to it it no longer drives your life, or at least not as much as in the beginning.

In the context of public education, the key I think is to give them the understanding, the information AND at the same time support them with suggestions of what they can do, AND ideally maintain that support over a longer period, of weeks and months rather than a one-off seminar.

The only way that can happen is with grassroots action, with local community action, when people can continue to support each other, as we have seen happen on online forums. IMHO the online experience CAN be translated into the actual community.

Right now, there's a small group of us (ReadyMoms.org) working on a model for disseminating such public education. It involves making making presentations that include physical displays of preparedness items and ideas, so that get both the information as well as a sense that it is something achievable. We put up a 'model' display at the recent APHA convention. You can read about it on Flu Wiki here and here with pics.

But perhaps more importantly, the conceptual framework in relation to your question on the issue of educating the public and fear, is written up as an Op-Ed piece for that event, titled By Parents, for Families, which you can access here

Well that pretty much confirms what I believe and that is that the only way to not get it, is well not to get it. That means hangin' at the house with the homies. You may not be aware Susan that the suggested "tip over" point in a fast moving, high CFR panflu is at about 8%. 10%? Forget it. Even I wouldnt be able to do what I am supposed to do in it except in the most limited of circumstances. I would be home weathering it in and thats the reason I harp that improving the public healthcare system really doesnt equate to any really higher outcomes to the plus side. It would be overwhelmed completely because 10% CFR means at least 1/4th of the population would be sick, unable to feed themselves, and unable to move about...maybe. I can tell you as an NGO that there is absolutely no guidance in this state other than to say that the planning is there but nothing to back it up in materials and money for the better part. You couple that up with about 30% of the US population who like Katrina have come to enjoy the fruits of other peoples labors thru the welfare system and you can write that segment of the population off IMHO. I have also said that until the disease does its dirty that the 30% are really an army. An army of hungry, disaffected but not disenfranchised people. They have the right to go out and do what is necessary now and that is to take personal responsibility.

That is really what is going to keep people alive here. Personal responsibility and helping where you can, when you can. As for the ref to the 50% or 40%. Even the 8% will do us if its in winter. I saw a report that was generated that said that 1/2 of the N.E. is TOTALLY unprepared even for a major winter storm that would last for three days, much less than three months. Add in the infrastructure failures and you got an exodus to the south like "Day After Tommorow" in our future.

I agree about the Tamiflu. Revere set some wheels turning down here at UT with his statin suggestion. Two grad students are doing something with it. What that something is I dont know but kudo's to the State Senate Majority leader who asked for something as he is tasked with funding either Tamiflu or an alternative. They started to order up Tamiflu and when people started flinging themselves out of buildings he said for them to hold up and lets examine where to put the bucks.

By M. Randolph Kruger (not verified) on 30 Nov 2007 #permalink

Gregory: "Is there any other point to which you would wish to draw my attention?"
Holmes: "To the curious incident of the dog in the night-time."
Gregory: "The dog did nothing in the night-time."
Holmes: "That was the curious incident."
--from Silver Blaze by Sir Arthur Conan Doyle

Looking at the effects of quarantine in the 1918 pandemic for clues to the effectiveness of quarantine in a pandemic today is worthwhile. But much better is to look at recent pandemics that didn't happen and why. The absence of a bird flu epidemic or pandemic today can be ascribed to luck, or to much more effective NPIs.

However there is a much clearer case. The SARS epidemic was stopped not by development of a vaccine, but by the discovery that certain antiseptics were ineffective against SARS. Changing hospital disinfecting procedures stopped the epidemic in days. As a result I think we can conclude that, since effective disinfectant measures for influenza have been known for decades now, bird flu never reached the levels that SARS did. In addition, the countries where SARS reached epidemic levels are exactly those where bird flu is most prevalent in humans. As a result I think the wake-up call from SARS has resulted in those countries taking bird flu very seriously.

Is the threat of a bird flu pandemic over? No. But I think that as long as public health officials take the risk very seriously, there will be no pandemic, and even an epidemic is unlikely.

By Robert I. Eachus (not verified) on 02 Dec 2007 #permalink

Susan, no I mean that if it has a 10% CFR it would mean very likely that there would be a smooth and easy 30% infected. The dying would be finished with very little that really anyone could do for them. You get it then its been about pushing on 3/4ths die. Of the remaining 1/4th, 1/4th of those have gotten post flu bacterial pneumonia and died. E.g. there was a surge in Vietnam during their human outbreak to the tune of something like 5000 "bacterial" cases of pneumonia. No information came out after that because I think they were busted and knew it.

If 30% of the work force goes down, so does the economy. If government was really smart they would simply manage it better by legislating that it would be elective to go to work and that certain types of debts could not be collected such as mortgages except for interest. Minimum payments on credit cards with no legal action against anyone for six months after the all clear. Some will have to work and I think they should also make double at least for doing it. Nurses in particular and any HCW.

Robert-WADR, I think that the SARS epidemic was really stopped by the efforts of the Chinese to isolate the suspected cases and to make sure no one bagged any Civet cats. The Canadians were furious over the fact that the Chinese hadnt told anyone and it took Boxun.com to put the news out. Everything you listed though is likely an intervention of somekind that was and is effective. There are a group that also think that just as suddenly that SARS mutated in, it mutated out of human capability. I read much on this and it likely was a combination of it all that led to the final interdiction.

Susan, So what d you think? 10% would equate to 30% infected or more? 10% of our fair country is 30 million. 30% infected is 100 million. Anyone got a warehouse they want to rent?

By M. Randolph Kruger (not verified) on 02 Dec 2007 #permalink

Randolph Kruger said: WADR, I think that the SARS epidemic was really stopped by the efforts of the Chinese to isolate the suspected cases and to make sure no one bagged any Civet cats. The Canadians were furious over the fact that the Chinese hadnt told anyone and it took Boxun.com to put the news out. Everything you listed though is likely an intervention of somekind that was and is effective.

I have to disagree. I was doing day to day tracking of new cases and posting weekly summaries. This http://boards.fool.com/Message.asp?mid=19169436 was about my final post on the subject at The Motley Fool. (Where I was also tracking the effect on the airlines and airline stocks. ;-) The estimated transmission rate went from 2.1 to 0.5 to under 0.1 in less than a month, right after the news that disinfection with (dilute) bleach did not work. (The experiment was done because the drains at the Amoy Gardens complex suspected of being the disease vector had been disinfected with bleach.)

There are a group that also think that just as suddenly that SARS mutated in, it mutated out of human capability. I read much on this and it likely was a combination of it all that led to the final interdiction.

WADR, I have to disagree, especially with the sudden mutation theory. I can also dig up posts that I made while the epidemic was in progress on mortality rates. There was evidence in the data that indicated a milder strain in China, but all cases outside China could be traced to a single index case, and showed identical statistical behavior.

I'd have to look back at the data, it has been years. But a second strain in (and only in) China? Sure, with at least a 25% lower mortality rate. Spontaneous simultaneous mutations around the globe? Get real. There were not enough infections with any strain of SARS that a more virulent strain but milder strain could crowd out the lethal strain(s).

Also note the very surprising corollary to the fact that disinfection with bleach did not work. Methyl, ethyl, and isopropyl alcohol were excellent disinfectants for SARS contamination. When researchers went back over the patient data, the absence of even serious social drinking on the part of SARS victims stood out. Two stiff drinks when you got home from work might not prevent SARS if you were exposed--but it was the way to bet.

By Robert I. Eachus (not verified) on 02 Dec 2007 #permalink

Robert I. - Take a trip on the really long side....

http://www.ncbi.nlm.nih.gov/sites/gquery?term=sars

It took me six months of reading but you will also find that bleach in the concentrations they suggested didnt work. OTOH in the concentrations that were discussed in the Joint Services Nuclear, Biological and Chemical Warfare manual in Survivability it did. Pretty hairy concentrations... Like something you would use to clean concrete.

By M. Randolph Kruger (not verified) on 03 Dec 2007 #permalink