Interesting interview/very comprehensive

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Interview with Dr. Michael Osterholm
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Professor of public health and director of the Center for Infectious Disease, Research and Policy at the University of Minnesota. He co-authored the book entitled Living Terrors: What Americans Need to Know to Survive the Coming Bioterrorist Catastrophe.

(from www.survivetheflu.com)
A couple of weeks ago we sent you an article about Dr.
Michael Osterholm 'On the Perils and Politics of Avian
Flu'. Below you'll find an interview conducted by City
Pages (Online News and Arts Weekly of the Twin Cities) with
Dr. Osterholm. We think you'll find it highly informative.



The CP interview: Dr. Michael Osterholm of the University of
Minnesota's Center for Infectious Disease Research and
Policy talks about the flu bug that could bring the world to
its knees.


BY STEVE PERRY


Scare headlines about the possibility of a deadly flu
pandemic have been with us for a few years now, ever since
the H5N1 bird-flu virus that first appeared in Hong Kong in
1997 resurfaced in the region in 2003. But in the past month
the drumbeat of such stories has grown faster and louder:
Avian Flu Arrives in Poland. Turkey. Azerbajian. Germany.
Denmark. And, just last Friday, Israel. The good news,
according to Dr. Michael Osterholm, the director of the
University of Minnesota's Center for Infectious Disease
Research and Policy, is that the arrival of infected birds
in North America—sometime this year, in the estimation of
most experts—is not likely to result in large numbers of
human infections with the virus, because most domestic
poultry in this part of the world is raised in factory-farm
isolation units that prevent contact with wild birds.


The bad news is that that's pretty much the only good news.
What matters in judging the prospects for a human pandemic
version of H5N1 (the name is shorthand for the chemical
structure of two of the virus's key components,
hemagglutinin and neuraminidase) is not so much the global
reach of the bird version, but the question of if or when
the virus mutates to a form that's easily passed from human
to human. If that happens anywhere in the world, says
Osterholm, the virus would likely start hitching rides with
travelers and seed itself around the globe in a matter of
days or weeks.


Of the hundred-plus human cases of H5N1 flu recorded so far,
the vast majority have involved bird-to-human transmission,
mostly among open-air poultry handlers in Asia. In addition,
there are confirmed clusters in which it has passed from
person to person, though none of those has yet resulted in a
breakout of the virus. One thing is clear, however: In its
present form, H5N1 has killed over half of the people it's
infected. The great flu pandemic of 1918-19, by contrast,
killed about 5 percent of its victims.


Will it cross over? If it does, can it possibly remain as
deadly? Though Osterholm notes that viruses usually do lose
strength as they spread—it's not really in their own
evolutionary interest to kill the majority of their hosts—he
believes the only responsible answer on both counts is we
don't know. But it's not just the characteristics of the
virus that worry him.


One of the things that sets the former Minnesota state
epidemiologist apart from other public health officials is
his attention to the fate of the medical and social
infrastructure in any serious contagious outbreak. With
respect to bird flu, his outlook recapitulates in many ways
what he had to say in his 2001 book about bioterrorism
preparedness, Living Terrors—much of the human toll in
death, hysteria, and anarchy would be exacted not by
infection but by the wide-scale breakdown of global supply
chains and just-in-time delivery systems for vital goods and
services. 'I think [Health and Human Services] Secretary
[Mike] Leavitt has been brutally honest in telling American
communities, you're going to be on your own,' says
Osterholm. 'And I think he's right.'


City Pages: Let me start with the question of the likelihood
of a global flu pandemic. Yesterday alone, I saw two wire
service headlines with radically different-seeming
implications, one indicating that the H5N1 avian flu is
likely to go global within six months, and another
speculating that the threat of human transmission may be
passing as we speak. Is it possible to say, based on the
epidemiological evidence, how likely a human flu pandemic is
in the next six months, the next year, the next two years?


Michael Osterholm: First of all, let me take a step back and
say that's a typical question we hear from the public. But
it's almost like asking, how many apples can you harvest
from the ocean? Because flu pandemics are like earthquakes,
hurricanes, and tsunamis—they occur. There's going to be
another one. There have been 10 in the last 300 years. What
you're really asking, I think, is will it be H5N1? It's
important to understand that when you're preparing for
pandemic influenza, you're preparing for something that will
happen. To say anything to the contrary would be like
saying, now that Katrina's happened, we'll never have
another hurricane like it.


Will H5N1 be the pandemic strain, and will it occur in the
next six to twelve months? The answer is, we don't know.
What is troubling about this virus is that this thing has
continued to mutate from its earliest days, in Hong Kong in
1997. And what is very, very troubling to us is that it's
mutating in very similar fashion to the way the 1918 virus
did. We went back with the 1918 virus and found all eight
genes of that virus in tissue samples—five from soldiers'
pathology slides that had been stored away, three from the
recovered corpse in Alaska. They didn't have any live virus,
but they've been able to make the virus from those eight
genes. And by studying that, they could determine how it
actually mutated and jumped directly to humans from birds.
It didn't go through other species as the 1957 and 1968
viruses did, where a bird and a human virus got together,
most likely in a pig lot, because pigs happen to be the
universal recipients for both [birds and humans].


They combined to make a third, dumbed-down virus that caused
mild pandemics.


The 1918 virus jumped right from birds to people. There was
no combining with other viruses. One of the problems we've
had is, if you look at the 1918 virus and this one, they're
in essence kissing cousins. Genetically, these things look
very similar. Frank Obenauer and colleagues just published a
paper the last week of January in Science, and they actually
have gone back and looked at the full genetic codes for 169
avian virus genomes, dating way back. They looked at 2,169
distinct avian virus genes. There were two viruses that
showed a protein tag at the end of one of the nonstructural
genes that actually looks to help cause the cytokine storm
that makes this a unique illness.* And guess which two
viruses they were: 1918 H1N1, and the current H5N1.


Then, when you look at the Turkey virus—that thing mutated.
This is the case of the young girl in Turkey who died from
her infection, and so did her uncle. We definitely have
clusters where it's not just bird contact [spreading the
virus]. The uncle's only exposure to this virus was riding
in the ambulance with her from hospital one to hospital two.
He became ill three days later and died. Her virus has now
been fully sequenced, and there were three mutations that
occurred in that virus, between the bird version and hers.
One was the substitution of a glutamic acid with lysine at
the 223-hemagglutinin position. That is what changes it from
a bird-receptor virus to a human-receptor virus. The second
thing was two other substitutions that served to make it
look more and more like a human virus.


So this thing just continues to march. Changes are occurring
in it all the time. [Human-to-human transmission] could
happen tonight. Or it may never happen. But I don't know
what will keep it from happening, because when you have this
kind of worldwide bird population as we do now—China's a
good example. In 1969, during the last pandemic, China only
had about 12 million chickens. Now it's got over 15 billion.


CP: Do you think the rise of poultry farms of vast scale has
contributed to the viral soup that influenza viruses grow
in?


Osterholm: Not really, and I'll tell you why. When you look
at the rise of the really big bird operations, they are
actually raised in these bio-security barns, which people
have all kinds of problems with for entirely different
reasons—humaneness and that kind of thing. They actually are
very safe, generally speaking, because they keep the wild
birds and the domestic birds separate. It's in Asia where
you have all these small 20-, 40-, 50-chicken operations
where the birds are living in open space with you—that's
where the vast majority of the chicken population is at in
the developing world. A good example is Turkey, where we're
seeing the first cases outside of Asia now. This is taking
the virus out of a tropical area and putting it in a
temperate area that gets cold. Every night, those people
bring their chickens into the house. It's just a very
different mindset.


And for as much as this is going to come here someday,
[bird-to-human transmission] is not going to be a big risk
factor to humans on this continent, because other than
free-ranging organic birds that are out there, domestic
birds aren't going to be at big risk.


CP: Can you explain in lay terms what makes a strain like
H5N1 novel, and so potentially deadly?


Osterholm: Well, there are three things that make a strain
of influenza virus potentially capable of causing a
pandemic. First of all, you have to have a situation where
you've got a novel or a new strain, meaning you don't have
any antibody protection against it. Then you have to have
one that is able to go from human to human. That's what we
don't have yet. The third thing is, it has some virulence
characteristics that make it cause severe illness.


This virus is quite different from what we see with the
standard annual flu, and what we saw in 1957 and 1968,
because of the cytokine storm it causes. In 1918, the vast
majority of the people who died were healthy young people,
20 to 40 years of age. And that was in large part because
they had the strongest immune systems.


CP: You're saying that the symptoms that cause fatalities,
aside from secondary bacterial infections, are actually a
function of the immune system working overtime.


Osterholm: That's it. And that's what we're trying to
understand at this point, in terms of how to best prevent
this [immune reaction]. And right now it doesn't look like
there's much you can do. I mentioned this 'kissing cousins'
phenomenon. If you put 1918 H1N1 into animal models at very,
very low doses, it basically kills all of them in 24 hours.
The lab science people had never seen that. At 16 to 24
hours, that virus was different from anything they'd ever
seen in killing these animals. The only virus that was
similar was H5N1, and it was fatal at much lower doses. H5N1
is the most powerful influenza virus we've seen in modern
human history.


What makes them so similar is that they both cause this
cytokine storm phenomenon.


CP: Which essentially results in a person's drowning in his
or her own blood as it fills the lungs, right?


Osterholm: It's even worse than that. You get that kind of
leakage, yes, but it also goes in and begins to shut down
all your vital organs. It's a domino effect. Your kidneys go
down, then your liver goes down, you have all this
destruction through necrosis of your lungs and your internal
organs. Everything goes.


CP: In the limited human sample we've seen so far, this
influenza has exacted a much higher mortality rate than the
1918 flu. Are there mechanisms that tend to dilute the
virulence of a strain as it spreads?


Osterholm: That's a really critical question. We can only
anticipate that this will attenuate. Meaning that once it
starts spreading in humans, it will lose some of its punch
in order to better adapt to humans. That's traditional with
virtually all agents you see like this. The thing that is
very difficult to talk about is, we don't know how much. If
this were to go human-to-human—we talk about a worst-case
scenario in terms of what happened in 1918, when roughly 2.5
percent of the world's population died. Of those who
contracted it, roughly 5 to 6 percent of populations died,
varying by age.


The mortality rate so far for this virus is around 55
percent, so this virus would have to attenuate a lot to get
down to that level. And we do have good data. There are not
a lot of mild, asymptomatic infections out there [with
H5N1]. We're now aware of six studies involving over 5,000
close contacts of H5N1-infected people, in Indonesia,
Vietnam, and Hong Kong, in which less than one person per
thousand contacts had evidence of an H5N1 infection that was
missed—that is, a mild infection.


This [virus] is not causing a lot of asymptomatic infections
right now. Some people are saying there's a lot of mild
[H5N1-related] illness all over out there, but it's just not
true. That means we're not artificially inflating the
mortality rate by missing a lot of infections. I'm actually
pretty confident that the real mortality is almost that
high.


So for that number to drop all the way down to a couple
percent is a pretty big drop. Which says to me that when
people talk about 1918 as a worst-case scenario, well, maybe
that isn't the worst-case scenario. That's hard for people
to hear, because then they think you're really trying to
scare the hell out of people. But you know what? It's just
the data.


If this virus were to ultimately go human-to-human, none of
us know what the human mortality would be.


CP: Does the fact that it seems to be gaining more currency
in other mammal species augur one way or the other for its
becoming transmissible from person to person?


Osterholm: None of us know. In 1918, for instance, we don't
know whether it infected cats and dogs. We've been trying to
find that out. Nobody's got that data. There just weren't
good reports. It surely can't be good that it's adapting to
more species. It says that the lung receptors of chickens
aren't the only ones that will take this virus. And we know
humans surely will take it, on the off chance that they're
exposed [to infected birds].


The bird-to-cat thing is not new. Some people have made a
lot out of the German situation. That's not new. The Bengal
tigers at the Bangkok Zoo died two years ago. They got fed
H5N1-infected chickens, and 50 of the Bengal tigers died.
They also transmitted to each other—there were cats there
that did not eat the chickens. Even Albert Osterhaus's work
of the past couple of weeks, which has been really important
to confirm it, was not a surprise.


CP: I wanted to ask you about a scenario you described in
your New England Journal of Medicine article from last year,
'Preparing for the Next Pandemic.' If a flu strain
transmitted from human to human did break through in some
part of the world, how would you expect events to unfold
over the first weeks?


Osterholm: Well, look at what's already happening with the
bird situation. You've got countries like South Korea
saying, don't go to Egypt. You've got a lot of bird
embargoes already taking place. If you saw this morning's
Wall Street Journal, the travel industry in Europe is
tanking. And this is a non-threat to a vast majority of
humans. What we're concerned about is that if this takes off
in a given area, it's going to move around the world
quickly, just like SARS. Last year 750 million people
crossed a national border somewhere in the world, either by
plane, automobile, or on foot.


These things move fast. With SARS, we had one physician from
China who came to Hong Kong, stayed in the Metropole Hotel
on one floor where there were nine other individuals he
infected just through breathing the air. They then took it
to four different continents in the next two days. That
gives you kind of a model, though influenza is much, much
more infectious.


I was very critical of those models that came out last fall
that suggested you could put a blanket over this with
Tamiflu. My whole criticism was practical—that you would
never find this quick enough and confirm it. Despite the
fact we now know Turkey was going on for weeks before we
understood what was happening over there, it was only last
week that the uncle's isolates were confirmed, almost eight
weeks after the fact.


CP: There's been a lot of covering up by some governments,
hasn't there? It's been repeatedly alleged of the Chinese.


Osterholm: Exactly. So my whole point is that before anyone
will have even figured out that this is going on with any
certainty, it'll be gone—the cow will be out the barn door.
With influenza, that's just...it's something you can't pull
back in.


CP: Periodically we see stories about the race to derive
vaccines, but that's not conceivable, is it, until we know
which viral subtype will break through?


Osterholm: Well, even that's a misconception, I think. The
concern we have is that people all want to know if some new
vaccine is 'the answer.' The problem is, we do need a new
vaccine. We're dealing with a 1950s-technology vaccine with
only one update. Right now, given the amount of virus needed
to make vaccines for H5N1—it needs a lot more antigen [than
typical flu strains]—our total worldwide capacity right now,
in one year's time, is only enough vaccine to protect
100-200 million people worldwide. That's in one year after a
pandemic starts. And that's it. You can't make any more,
given the limited capacity we have.


So you know what? It doesn't matter if we invent vaccines if
we can't manufacture them. This is a point I've tried to
make over and over again. We also are approaching this from
a very American-centric point of view, which in the end will
be the death of us. What's going to happen is, even if we
could produce vaccines for our country in a timely manner,
this global just-in-time economy we live in today is going
to see the rest of the world shut down. Eighty percent of
all the drugs we use in this country—all the childhood
vaccines, everything—come from offshore. Your cardio drugs,
your cancer drugs, your diabetes drugs, 80 percent of the
raw ingredients come from offshore. I could go through a
whole laundry list of other critical and essential products
and services that come from offshore. If the rest of the
world experiences a pandemic, we're still screwed. That's
what people don't understand. Somehow they have this
attitude that we can wall ourselves off in the Eighth
District of Minneapolis and be okay.


The bottom line is, it will be years, even at the
accelerated rate we're going now, before we even get the
right candidate-vaccines. Then they still have to be
approved. No company's going to embark on building
manufacturing capacity without the certainty of a market.
And second of all, they have to know exactly what vaccine
will be used and how they need to develop their plant. All
this means that an influenza plant, from start to finish,
would probably take three to five years to build.
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CP: Why don't we have the capacity to produce more in the
way of basic vaccines here in the U.S.?


Osterholm: Because it's all about the market. Today, many of
the anti-infective antibiotics and vaccines are not
considered blockbuster products for any pharmaceutical
company. We have a number of our childhood vaccines that are
down to a single manufacturer now. If you go to the Society
for Health Care Pharmacists' website, you'll see a list of
42 drugs today that are in short supply because of the
just-in-time supply chain. Now, you put on top of that
products that are marginal in their [profit] return, and it
becomes a loss leader for these companies [to make
vaccines]. They want out of it.


This is not true just for vaccines, but also for
antibiotics. There, we tell people to hardly use them, and
only for specific purposes and limited periods. It's not
like the lifestyle drugs, where you're taking your statins
for the rest of your life. So they just don't see the
profitability [in antibiotics]. We're in real trouble. And
it's not just with respect to the flu.


CP: The one easy-to-use drug that's been shown to arrest
H5N1 in humans is Tamiflu—


Osterholm: Well, that's not really true. There's no evidence
that it makes a difference in H5N1 infection. I have a slide
here showing that the case mortality rate in Vietnam was
identical for those who got Tamiflu and those who didn't. I
actually believe Tamiflu could work, but the problem is,
we're applying it in the H3N2 [average seasonal flu] model.
Seasonal flu grows up much slower in a human, so that if you
get the drug into somebody two days after their onset, you
can still have a pretty measurable impact on the severity of
their illness and the likelihood they'll have complications.
With the H5N1 virus, the virus storm that precedes the
cytokine storm is so remarkable in those first 24 hours that
if you don't have the drug onboard in those first 24 hours,
it may only have limited impact.


The second thing is, we're using the same dosage levels we
use for H3N2 [seasonal flu]. This is a very different virus.
We may have to double the dosage for twice the length of
time. We have anecdotal data on people who got the drug
early and appeared to do better, but then, after the typical
five-day course was stopped, they died on day ten.


The problem we have is not whether Tamiflu is available and
will work, but can you get it soon enough and in high enough
amounts? How do you get the drug to somebody in the first 12
hours of their illness? The second thing is, when people
talk about having 20 million or 40 million protective doses,
what does that mean? If we're going to have to use twice the
dose for twice as long, that means maybe you've got
one-fourth as much of the drug you think you have.


That's the story on H5N1 and Tamiflu. I think it can work,
but it won't work the way we're approaching it.


In the next five years, with [Tamiflu manufacturer] Roche
outsourcing all of the production they can, our best
guesstimate is that—using the old, low dosage standards—we
could probably produce enough Tamiflu to treat about 7
percent of the world's population in the next five years,
because of the precursor chemicals needed and the
complicated nature of making this stuff. That's the sum
total of production capacity. It's no panacea.


CP: How would you rate the public health infrastructure in
the U.S. for its ability to deal with massive numbers of
very ill people? You wrote in the NEJM last year that our
system lacks 'surge capacity' to deal with a lot of sick
people at once—why is that?


Osterholm: It's much deeper and bigger than the public
health system. It's really the total care system. For
example, I talked [in that article] about the 105,000
mechanical ventilators? On any given day, 70,000-80,000 of
them are in use, and in a normal flu season we butt up
against the 100,000 mark. We have no excess capacity there
whatsoever. Just right here in our own Twin Cities, we've
reduced intensive care beds by 20 percent in the last four
years, as a matter of cost containment.


We'll run out of masks and respirators overnight, because
it's a global just-in-time supply chain. There are two
manufacturers who have the largest share of the market
there, but with virtually no surge capacity. We'll run out
of IV needles. We'll run out of IV bags. We'll run out of
drugs very quickly. Remember I talked about the 80 percent
offshore figure? Go to the Society for Health Care
Pharmacists' website and you'll see what I'm talking about.


So the whole medical system will collapse, at a time when we
still need drugs for heart attacks, cancer, and everything
else. We'll be in freefall. That may sound scary, but it's a
reality. And unlike Katrina, where the hurricane did some of
the destruction and separated people from health care
through evacuation or otherwise, the same thing's going to
happen here in every city, town, and village in this country
as well. We're all going to need things at the same time,
and there won't be any products.


At this Business Continuity Summit we just had, we actually
had a major discussion in which a lot of voices expressed
concern about the internet—that it doesn't have the backbone
and elasticity that everyone thinks it has, and just a
limited surge could bring down the internet.


Right after Katrina, when FEMA was trying to rescue itself,
they put out a call for anyone who had a refrigerated truck
unit to come and sit in one of several parking lots in the
Gulf states down there, in case they had 10,000 bodies, etc.
A contingent of them went. Not all of them, by any stretch
of the imagination. Within 72 hours, major food
manufacturers throughout the United States reported that
they couldn't ship their goods. They had no trucks. We have
a razor-thin capacity in this country right now on virtually
everything. They had to get FEMA to release the trucks.


Cities like Seattle have already come to the conclusion they
won't be able to have refrigerated trucks, because of that
issue. For their work with corpse management, for example,
they've already mapped out where every one of the ice arenas
in Seattle is. Because you won't be able to bury people,
either. In 1969, during the last pandemic, the average time
from when a casket was made until it was in the ground was
about six months. Today it's a little over a month, and in
some areas of the country it's less than that. There's no
surge capacity in casket manufacturing. Today, crematorium
space in this country is a just-in-time situation too. This
means we would quickly run out of the ability to handle
bodies in a timely, respectful way. That's in a moderate
pandemic, not at all like 1918. Everything now is done on
the basis of just-in-time delivery systems.


Now, think about Katrina. As horrible as it was seeing the
Superdome, seeing shots of bodies rotting would kind of take
you over the top. What really offends the sensibilities of
most Americans is when you see the dead handled in a
disrespectful manner. I worry that one of the tipping points
in a panic/fear situation over pandemic flu would come when
we can't, in a timely way, handle the bodies or get them
into cold storage. Those are issues we haven't dealt with at
all.


CP: Your answer to this is partly implicit in all you've
said, but let me ask you to sum up how you'd rate the U.S.'s
and Minnesota's state of preparedness for a pandemic.


Osterholm: I think the U.S. right now is leading the way in
terms of the overall issue of pandemic influenza
preparedness. The problem is that, for much of the
developing world, they don't have a lot to prepare for. They
don't have sophisticated supply-chain issues. In some ways I
think they're better off than we are, because they already
live a very simple, hand-to-mouth existence. For us, with
our complicated supply networks, we have a long, long way to
go. And I think that's as much a private-sector issue as a
government issue. I think Secretary Leavitt has been
brutally honest in telling American communities, you're
going to be on your own. And I think he's right. You know
how you creep, then you walk, then you run? We're still on
our knees.


CP: What kind of measures might we in the Twin Cities expect
to see undertaken in the short term if an outbreak did reach
the U.S.?


Osterholm: I can't say. I don't know. I know that the
governor today, in his State of the State address, said that
he's just committed $10 million to influenza preparedness.
What that means, I can't say. We don't have the details yet.


When the virus gets to this continent as a bird virus, it's
important that we not overreact and misinterpret it to mean
that now the pandemic's here. This will be an important
issue for poultry, but as I pointed out, I think most of the
poultry in this country—aside from the free-range organic
poultry—is going to be pretty well-protected.


It's about the birds and it's not about the birds. It's
about the birds now, but when real pandemic influenza
occurs, the birds become inconsequential. It's
human-to-human transmission that matters then. That's where
we're not any better prepared here than anyone else in the
world.


CP: How would you rate the media's performance in covering
this story—too salacious, too understated, just right?


Osterholm: It's like talking about the weather, I
guess—depends on which day, and where. There have been some
outstanding reporters on this issue. Helen Branswell, from
Canadian Press, covered SARS and has become the primary
person on this. She's done it as well as anybody. On the
whole, it has been poorly covered in the sense of
distinguishing H5N1 in the bird population from pandemic
influenza. That part has not been covered in depth. The
issue about covering preparedness—no one has really gone
into depth and explored the supply-chain issues to say,
okay, what does this all mean? Let's take a community and
say, what would happen here? We're so fixated on the news
cycle that it's too often about, 'what new country has just
been infected with bird virus?' and not really get into the
issues. Ted Koppel at Nightline did an excellent series of
stories and asked good, hard questions. But now he's gone
and Nightline hasn't picked it up since he left.


*Cytokines are a class of proteins produced by white blood
cells whenever the body finds itself responding to an
infection. They vary in function—some cytokines attack
invading microbes directly, others relay chemical messages
from cell to cell, still others bind with cells in the
hypothalamus region of the brain to produce fevers.
Cytokines are toxic not only to infectious agents in the
body but to the body itself: Much of the pain and discomfort
that accompany illnesses like the common flu, for example,
are in effect hangover symptoms from the toxic effects of
the body's own immune response. The term 'cytokine storm'
refers to the immune response that occurs when the body is
confronted with an infectious agent that reproduces at great
speed and in huge volume. This 'viral storm' generates an
equally huge immune response—the cytokine storm—that can
take such a toll on lung tissue (the main battleground where
the virus and the immune system face off) that it deprives
vital organs of enough oxygen to function, and sets off
cascading organ failure.

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Stay Healthy & Safe.

Bob & Julie
www.survivetheflu.com