August 04, 2005
Prompt Response Might Stop Avian Flu Pandemic

We have some bad news and we have some possibly good news.

If Asian bird flu mutates into a form that spreads easily between humans, an outbreak of just 40 infected people would be enough to cause a global pandemic. And within a year half of the world’s population would be infected with a mortality rate of 50%, according to two studies released on Wednesday.

And yet, the models show, if targeted action is taken within a critical three-week window, an outbreak could be limited to fewer than 100 individuals within two months.

This result comes out in a pair of papers published in Nature and Science by teams of British and American researchers.

Neil Ferguson, a professor at the Imperial College in London and lead author of the Nature paper says that if the pandemic happens half the world's population could be infected within a year.

Prof Ferguson said if nothing was done, half the world could be infected within a year. But a stockpile of Tamiflu, along with a policy of closing schools and workplaces, could have more than a 90 per cent chance of stopping a pandemic virus.

Bummer dudes. If I survive I'll probably have a much smaller readership. Could all my readers please plan in advance and buy provisions to allow themselves to flee to isolated cabins for a year? I don't have a big marketing budget to attract new readers. So you guys and gals have got to be careful and stay alive. Oh, and stop smoking, get more exercise, eat better food, lose weight, and don't drink and drive.

During the pandemic using cellular broadband on broadcast towers you'd still be able to read me from your mountain cabins while I hole up in a cabin of my own. Note to self: Buy a cabin with a water well and a bunch of solar panels and batteries and in sight of a cellular internet modem tower. Stock it with lots of pop corn, Total cereal, and other vital necessities.

The American team also found that early intervention with antivirals and quarantines has the potential to stop a pandemic.

Another team from Emory University in Atlanta, the US, led by Dr Ira Longini, simulated an outbreak in a population of 500,000 in rural Thailand, where people mixed in a variety of settings, including households, schools, workplaces and a hospital.

Provided targeted use of antiviral drugs was adopted within 21 days it would be possible to contain an outbreak, they found, as long as each infected person was not likely to infect more than an average of 1.6 people.

If it was more infective than this, household quarantines would also be necessary, they said.

But among the many reasons such a strategy might fail is the possibility that the outbreak strain could develop esistance to the anti-viral drug Tamiflu (chemical name oseltamivir).

Another problem is that the earliest victims must be identified promptly.

Professor Ferguson then considered what would happen if Tamiflu were given rapidly to everybody within a 5km (3.1m) or 10km radius of an infected person, and measures were taken to reduce contact by closing schools and workplaces.

These approaches will contain an outbreak, but only if Tamiflu is given swiftly, preferably within 48 hours of a case being diagnosed. Prevention must begin before more than 30 to 40 people are infected, and 90 per cent must take the drugs they are given.

Well, imagine that the early victims are in Laos or Cambodia or Burma (all quite plausible) and since large areas of those places are pretty primitive what if nobody of importance notices for weeks? Also, to enforce household quarantines and other measures one needs a fully functional government with plenty of public health workers. Well, in some parts of the world government is dysfunction or effectively non-existent.

Even with prompt response we'd still have to get lucky.

"If we end up with a pandemic like [previous catastrophic pandemics], we'll have a lot of people dead," said study team member Elizabeth Halloran, professor of biostatistics at Emory University in Atlanta, Georgia.

Halloran added that the simulations show that it should be possible to contain an outbreak at its source. But the results are unpredictable. "We have shown in these simulations that—even given the same [hypothetical] situation—sometimes when we intervene it's successful and sometimes it's not," Halloran added.

Bottom line: Do not count on this approach working even if the political will and resources are available to execute the containment strategy.

The experts are aware that success of a prompt containment strategy depends on many "ifs".

"The models show that if you combine well-directed, targeted treatment with some social interventions like closing schools, ideally together with some vaccination, it's conceivable you'd be able to stop the epidemic," said Anthony S. Fauci, chief of infectious diseases at the National Institutes of Health, which funded much of the work through its National Institute of General Medical Sciences.

But the odds of success are tempered by many "ifs," Fauci and others warned.

Here's one problem with this strategy: A reluctance to commit resources. They assume a few million doses of Tamiflu available and some panel or person authorized to employ it. Well, as it stands now the WHO is reluctant to raise the warning level for a pandemic because raising the level causes stuff like the use of Tamiflu stocks. They know if they use it prematurely they will basically shoot their guns but without ammo to reload. So there is going to be a bias against committing resources until absolutely certain. Well, how to determine that a strain that has pandemic capability has finally emerged and how to do that very quickly?

Suppose that the WHO and national governments got together 10 million or 20 million Tamiflu doses. Then public health officials could afford to commit resources against each potential outbreak before being absolutely sure. Would this work? Maybe. But then again, maybe widespread use of Tamiflu would help select for Tamiflu-resistant strains.

But there's another problem: The H5N1 strains that are popping around in animal populations could mutate into a human pandemic capable form more than once. We might need to stop it 2, 3, 4, or 5 times. Are we going to get that lucky? Heck if I know. But I'm not optimistic.

I think governments and public health officials ought to consider the rapid development and widescale delivery of vaccines to populations in Southeast Asia right now. Even if the vacines would be only partially effective against some future avian flu strain the ability to slow the spread of a new strain using partial immunity might give the containment strategy a much better chance of working.

My joking aside, this is serious business. Lots of us could die. We ought to be doing orders of magnitude more to avoid getting killed by an avian flu pandemic. Think about it. Complain to your elected representatives. Buy the sorts of supplies you'd need to survive a major societal disruption.

Update: Even a slowing of the pandemic would provide more time for vaccine development and production.

"Our findings indicate that we have reason to be somewhat hopeful. If -- or, more likely, when -- an outbreak occurs in humans, there is a chance of containing it and preventing a pandemic. However, it will require a serious effort, with major planning and coordination, and there is no guarantee of success," said coauthor Elizabeth Halloran of Emory University.

"Early intervention could at least slow the pandemic, helping to reduce morbidity until a well-matched vaccine could be produced," she said.

The danger of avian flu is that the virus could develop into a new strain that could be transmitted among humans. The virus might mutate, or it might jump over to a human already infected with the flu and then mix, or "reassort," with the human flu virus. Because humans would have little or no immune protection against this strain, it could potentially cause a massive pandemic.

"There were three influenza pandemics in the 20th century alone. The threat of another pandemic, related to avian influenza, is real and very serious. Fortunately, as the new study shows, for the first time in human history, we have a chance of stopping the spread of a new influenza strain at the source through good surveillance and aggressive use of public health measures," said Katrina Kelner, Deputy Editor, Life Sciences, at Science.

The effectiveness of containment depends on quick decisions to do targeted antiviral drug use, a fairly low multiplier for how many others each infected person passes the virus on to, a high level of use of antiviral drugs, and effective quarantine measures.

They found that targeted use of antiviral drugs could be effective for containment as long as the intervention occurred within 21 days and the virus' reproductive number (which represents the average number of people within a population someone with the disease is able to infect) had a relatively moderate value of roughly 1.6.

A process of administering antiviral drugs to the people in the same mixing groups as the infected person, called TAP for "targeted antiviral prophylaxis," could contain the outbreak as long as it reached 80 percent of the people targeted. A related strategy, GTAP, for "geographically targeted antiviral prophylaxis," which targets people within a certain geographic range of the initial case, produced similar results as long as it achieved coverage of 90 percent.

Vaccination before the outbreak, even with a vaccine that is poorly matched to the actual virus strain, increased the effectiveness of TAP and GTAP.

For even higher viral reproductive numbers, household quarantines would also be necessary to contain the virus. A combination of TAP, prevaccination and quarantine could contain strains with a reproductive number around 2.4. A value of 2.4 is relatively contagious, though some other viruses such as measles are substantially higher. In all cases, early intervention would be essential.

We can't have a wonderful long future if we die first. Future rejuvenation therapies are useless to anyone who dies from bird flu next year.

Update: Do not expect Western governments to allocate sufficient vaccines and drugs to implement the early preemption strategy to stop an outbreak.

Would the United States, Europe and Japan be willing to donate their precious vaccine supply to mount this long-shot defense? This is perhaps the biggest unanswered question in pandemic flu planning -- and one likely to be answered only at the moment of truth.

Officially, it is a possibility.

"If it was done in consultation with the WHO [World Health Organization] -- and with other governments that would make contributions, as well -- we would be more likely to consider it," said Gellin at HHS. But observers both in and out of the government said, not for quotation, that they doubt the U.S. government would ever send a significant amount of its vaccine stockpile overseas.

Production of a sufficient supply of vaccine could take years. The economic disruption of a pandemic will be enormous. I am expecting an economic depression. The threat of terrorism will seem tiny by comparison.

Also see my previous posts "Yet Another Avian Flu Preparedness Warning Report" and "More Warnings On Avian Flu Danger To Humanity".

Share |      Randall Parker, 2005 August 04 05:32 PM  Dangers Natural Bio

michael vassar said at August 5, 2005 7:50 AM:

Take vitamin pills, not Total. A long term diet consisting substantially of Total would be likely to lead to hemochromatosis, just like eating many vitamin pills per day would. 100% of the RDA of iron in a cereal is a terribly bad idea.

Nick said at August 5, 2005 8:31 AM:

*100% of the RDA of iron in a cereal is a terribly bad idea.* I think you meant to say: 100% of the RDA of iron -per serving- in a cereal is a terribly bad idea. It really is, isn't it - those servings are mighty small, and so it's easy to eat several just for breakfast. I'll have to check the brands in my pantry...

Randall Parker said at August 5, 2005 8:57 AM:

Nick, Michael,

I probably eat meat at most 5 times a month. I do not eat a high iron diet. So for me getting iron from Total does not pose an iron toxicity problem. In fact, if I didn't eat Total I'd make myself eat something else high in iron just to get enough iron.

Meanwhile, all of us might die from avian flu before decades before hemochromatosis has any chance of killing us...

Richard R said at August 5, 2005 9:36 PM:

Why wait for the government to stockpile it?

I have 10 courses of treatment (10 pills each) tripple ziplock bagged in my wine refrigerator, and 2 courses in powder form for my baby.

Grumpy Old Man said at August 6, 2005 7:39 AM:

The silence on this issue is grotesque. It's both a "national security" issue for the center-right and a public health issue for the "enfironmentalist" left.

It's a lot biger deal than pesticide residues and the like. Read The Great Influenza for a description of the last really lethal pandemic.

The silence is deafening, especially when there are now some things that can be done.

Jay Manifold said at August 6, 2005 8:31 AM:

That silence may be ending -- the latest political cartoon by Tom Toles, which I unfortunately cannot find online but was in the dead-tree edition of the KCStar this morning, is about bird flu.

Randall, you're performing a great service here. Keep it up.

jerry said at August 6, 2005 9:46 AM:

I have talked to my physician about bird flu lethality. She is very concerned about it but agrees that we really don't have an idea about its lethality. Right now we have a hand full of cases in third world countries where the reported mortality rate of those patients showing up in hospitals is 1 out of 4. The problem with estimating mortality is that we do not know how many people have contracted bird flu and never come in for medical attention because they weren't that sick. I would be interested in knowing what the mortality rate for those admitted to hospital with normal flu stains. I bet it would shock most people. Only the sickest go to hosptial with flu. Remember, SARS? The US and Canada both had the same number of reported cases yet there were no clusters or fatalities in the US. Of course Canada does have a third world style socialized medical system and that could explain it. My doctor also told me that the mortality rate could be higher in the developed world then in the third world because we are never exposed to these kinds of diseases. So when anybody comes in with modeled mortality rates for bird flu (or any disease) treat them with a grain of salt. We just don't know. The way these studies go we could soon see mortality estimates exceeding 100%.

Chuck Simmins said at August 6, 2005 8:49 PM:

We have only seen three influenza pandemics, all in the twentieth century. The most lethal of which, the first, happened just on the edge of modern public health management, so we know far less about it than we would like. We have far too little data to make predictions about which flu variant will be the next pandemic, or how it will behave.

I believe that I can say with certaintude that it is not physically possible to stockpile, distribute and administer enough Tamiflu to make a difference.

Based on what we know, the flu pandemic will probably erupt in China. I see no possible means by which the Chinese government will recognize the first 40 cases, much less do anything about them. The SARS epidemic is proof of that. The Chinese government lied from the beginning about that illness and to this day continues to lie about it.

Much of Africa and Asia as so poor, in infrastructure and medical care, and the health of the population is so poor, that the chances of any sort of relief effort succeeding are zero. We're currently fighting a world wide polio outbreak caused soley by the backwardness and superstition of Moslem leaders in Nigeria. There is nothing that says that they will be any more receptive to the WHO on the influenza issue.

The reality is that the First World will have a higher than normal death rate from an influenza pandemic. It will not be much higher than we already have in a normal year, perhaps in the U.S. an increase from about 30,000 to about 60,000 deaths. In the Third World, where medical care is lousy, and people's health is lousy, a lot of people will die. There's little that we can do about it. There aren't enough roads, enough trucks, enough helicopters, enough medical personnel to make even a dent in the potential illness numbers in places like Somalia or Timor or Bolivia.

Medicine: Flu, and Pandemics

Medicine: Epidemic of Fear

Bioterror du Jour

TJ Green said at August 8, 2005 3:34 PM:

I think early intervention is our best option. Perhaps the use of the pneumonia vaccine would help save lives.

Peter said at August 10, 2005 9:51 PM:

Jerry says:

"The reality is that the First World will have a higher than normal death rate from an influenza pandemic. It will not be much higher than we already have in a normal year, perhaps in the U.S. an increase from about 30,000 to about 60,000 deaths."

Says who? Wildy optimistic, contradicting even the rosiets expert predictions of mortality rates if there's a crossover.

Hope said at August 13, 2005 12:04 AM:

Looking for a reliable source of Tamiflu...Anyone got one?

Bob Badour said at August 13, 2005 4:05 PM:


I think you took the wrong approach with this one. Instead of asking your readers to protect themselves to preserve your readership, ask them to include you in their wills.

That way, you will have bungloads of dough for marketing to a new audience...

Bob Badour said at August 13, 2005 4:09 PM:


I bet I could stockpile enough tamiflu to make a difference ... to me.

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