World Not Set To Deal With Flu
Strategy
for Pandemic Needed, Experts Say
http://www.washingtonpost.com/wp-dyn/conte...3001429_pf.htmlBy David Brown
Washington Post Staff Writer
Sunday, July 31, 2005; A01
Public health officials preparing to battle what
they view as an inevitable influenza pandemic say
the world lacks
the medical weapons to fight
the disease effectively, and will not have
them anytime soon.
Public health specialists and manufacturers are working frantically to develop vaccines, drugs, strategies
for quarantining and treating
the ill, and plans
for international cooperation, but
these ef
forts will take years. Meanwhile,
the most dangerous strain of influenza to appear in decades --
the H5N1 "
bird flu" in Asia -- is showing up in new
populations of
birds, and occasionally people, almost by
the month, global health officials say.
If
the virus were to start spreading in
the next year,
the world would have only a relative handful of doses of an experimental vaccine to defend against a disease that, history shows, could potentially kill millions. If
the vaccine proved effective and every flu vaccine factory in
the world started making it,
the first doses would not be ready
for four months. By
then,
the pathogen would probably be on every continent.
Theoretically, antiviral drugs could slow an outbreak and buy time.
The problem is only one licensed drug, oseltamivir, appears to work against
bird flu. At
the moment,
there is not enough stockpiled
for widespread use. Nor is
there a plan to deploy
the small amount that exists in ways that would have
the best chance of slowing
the disease.
The public, conditioned to believe in
the power of
modern medicine, has heard little of how poorly prepared
the world is to confront a flu pandemic, which is an epidemic that strikes several continents sim
ultaneously and infects a substantial portion of
the population.
Since
the current wave of avian flu began sweeping through po
ultry in Sou
theast Asia more than 18 months ago, international and U.S. health authorities have been warning of
the danger and trying to mobilize. Research on vaccines has accelerated, ef
forts to build up drug supplies are underway, and discussions take place regularly on developing a coordinated global response.
The U.S. Department of Health and Human Services will spend $419 million in pandemic planning this year.
The National Institutes of Health's influenza research budget has quintupled in
the past five years.
"
The secretary or
the chief of staff -- we have a discussion
about flu almost every day," said Bruce Gellin, head of HHS's National Vaccine Program Office. This week, a committee is sch
eduled to deliver to HHS Secretary Mike Leavitt an updated plan
for confronting a pandemic.
Despite
these ef
forts,
the world's lack of readiness to meet
the threat is huge, experts say.
"
The only reason nobody's concerned
the emperor has no clo
thes is that he hasn't shown up yet," Harvey V. Fineberg, president of
the National Academy of Sciences' Institute of Medicine, said
recently of
the world's ef
forts to prepare
for pandemic flu. "When he appears, people will
see he's naked."
O
ther scientists are sounding
the alarm as well.
The most outspoken is Michael T. Osterholm, director of
the Center
for Infectious Disease Research and Policy at
the University of Minnesota. In writing and in speeches, Osterholm reminds his audience that after public calamities,
the United States usually convenes blue-ribbon commissions to pass judgment.
There will be one after a flu pandemic, he believes.
"Right now,
the conclusions of that commission would be harsh and sad," he said.
In hopes of slowing a pandemic's spread, public health specialists have been debating proposals
for unprecedented countermeasures.
These could include vaccinating only children, who are statistically most likely to spread
the contagion; mandatory closing of schools or office buildings; and imposing "snow day" quarantines on infected families -- prohibiting
them from leaving
their homes.
O
ther measures would go well beyond
the conventional boundaries of public health: restricting international travel, shutting down transit systems or nationalizing supplies of critical medical equipment, such as surgical masks.
But Osterholm argues that such measures would fall far short. He predicts that a pandemic would cause widespread shutdowns of factories, transportation and o
ther essential industries. To prepare, he says, authorities should identify and stockpile a list of perhaps 100 crucial products and resources that are essential to keep society functioning until
the pandemic recedes and
the survivors go back to work.
Deadly Potential
Since late 2003, 109 people are known to have been infected with
the emerging H5N1 virus in Asia.
About half -- 55 -- have died.
Ironically,
for the current H5N1 strain of avian flu to gain "pandemic potential," it will have to b
ecome less deadly. Declining lethality is a key sign that
the microbe is adapting to human hosts. That is one reason
the 34 percent mortality observed in
the most
recent outbreak -- a cluster of cases in nor
thern Vietnam -- has scientists worried.
Pandemic influenza is not an unusually bad
version of
the flu that appears each winter. Those outbreaks are caused by flu viruses that have been circulating
for decades and change slightly year to year.
Pandemics are caused by strains of virus that are highly contagious and to which people have no immunity. Such strains are rare.
They arise from
the chance scrambling and r
ecombination of an animal flu virus and a human one, res
ulting in a strain whose molecular identity is wholly new.
In
the 20th century, pandemics occurred in 1918, 1957 and 1968. Although
the 19th-century r
ecord is less certain,
there appear to have been four flu pandemics -- in 1833, 1836, 1847 and 1889. On a purely statistical basis,
the nearly 40 years since
the last one suggests
the time may be ripe.
The microbe called influenza A/H5N1 appeared in East Asia in 1996 and has flared periodically since. It is highly contagious and lethal in chickens, but it can be carried without symptoms in some ducks -- a combination that helps keep it in circulation.
Birds occasionally infect humans, and scientists
recently found evidence that
the virus is sometimes passed person to person. That
form of transmission is now diffic
ult and rare, but
the virus could evolve so that it b
ecomes easy and common.
If H5N1 never b
ecomes easily transmissible in human beings, it will never b
ecome a pandemic. If it does b
ecome transmissible,
the consequences are diffic
ult to imagine. But history provides some clues.
The "Spanish flu" in 1918 and 1919 was
the biggest and,
along with AIDS,
the most important infectious disease outbreak of
the 20th century. It is on
the short list of great disasters in human history.
At least 50 million people, and possibly as many as 100 million, died when
the world's
population was 1.9 billion people, one-third its current size.
The Best Defense
Tests are underway at three U.S. hospitals on an experimental vaccine against H5N1. But it is not
the first H5N1 vaccine.
When a slightly different strain of
the virus surfaced in Hong Kong in 1997, killing thousands of chickens and a half-dozen people, researchers used viruses from
birds and people to make experimental vaccines. But nei
ther offered much protection in lab tests, and nobody knows why.
Instead of working on
the problem, researchers dropped it. First SARS (severe acute respiratory syndrome), and
then a different avian flu strain that arose in Europe (H7N7), took
their attention.
"
The urgency around this issue kind of dissipated," said John Treanor, a physician at
the University of Rochester and one of
the leaders of
the vaccine project. "I think it's an example of how unpredictable things are. We got distracted."
The urgency is back.
As
the first, small hedge against disaster,
the government last fall ordered 2 million doses of H5N1 vaccine from Sanofi Pasteur, one of
the country's three flu vaccine makers, even though nobody yet knows whe
ther it works.
A half-dozen o
ther countries are also working on pandemic vaccines. But making enough to fight an outbreak is a tall order.
About 300 million flu shots are made worldwide each year.
The vaccine protects against three flu strains. If
the global production capacity were directed to make only H5N1 vaccine,
the output could be 900 million shots.
Un
fortunately, virologists are almost certain people will need two doses
about a month apart to mount a successful immune response against a wholly new strain such as H5N1. That would cut
the theoretical number of recipients worldwide to
450 million. If each shot requires a larger-than-usual amount of vaccine to work,
the number will be even smaller.
Can
the world produce more flu shots? Not easily.
Because nearly all flu vaccine is made by growing
the virus in fertilized chicken eggs, special factories and a steady supply of eggs are required. Consequently, a key element of pandemic planning is getting more people to get yearly flu shots, which will give companies a larger market and an incentive to expand
their plants.
Around
the world, flu vaccine production has risen by just one-third in
the past decade. New plants in Brazil, South Korea and
the Ne
therlands will boost global production by an additional 25 percent in
the near future.
In
theory, even a
modest amount of vaccine might be useful. Fighting disease outbreaks is like fighting fires. You do not have to hose down
the whole world to put
the fire out, but you do have to hose down
the perimeter to keep it from spreading. It might be possible to contain an H5N1 outbreak at its source if
the surrounding
population were immediately vaccinated.
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 cons
ultation with
the WHO [World Health Organization] -- and with o
ther 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.
Only One Drug
In
the absence of a vaccine,
the only pharmaceutical bulwark against H5N1 is oseltamivir. It can shorten
the illness's duration, and if taken immediately after exposure, it can even prevent infection. But
the world's supply of
the drug is limited.
Sold as Tamiflu, it is manufactured by just one company,
the Swiss giant Roche, in a laborious, expensive process that takes eight months.
Twenty-five countries have ordered oseltamivir to stockpile, and five o
thers have expressed interest, a Roche spokesman, Terence J. Hurley, said
recently.
The United States already has a stockpile, but it is enough to treat less than 1 percent of
the population.
The government has ordered enough to treat 3 million more people, or
about 2 percent total.
At a congressional hearing in late May,
the company's medical director, Dominick A. Iacuzio, said it will begin producing oseltamivir in
the United States soon.
The company says it could supply 13 million more courses of treatment in
2006 and an additional 70 million in 2007 -- provided
the government orders
them.
Would having lots of vaccine or oseltamivir make a difference?
In a study published last year, Ira M. Longini Jr. of Emory University ran a ma
thematical
model of what might happen if a pandemic such as
the 1957 Asian flu, which was caused by a virus far milder than
bird flu, hit
the United States.
He and his colleagues estimated that with no vaccine or antiviral drugs,
there would be 93 million cases and 164,000 deaths. Vaccinating 80 percent of people younger than 19 --
the group most responsible
for spreading
the virus -- "would r
educe
the epidemic to just 6 million total cases and 15,000 total deaths in
the country."
Giving that group eight weeks of oseltamivir would have
the same effect, at least temporarily. But it would take
the equivalent of 190 million courses of treatment -- more than anyone thinks
the country will have in
the next few years.
Somewhat more realistic is deploying
the drug to where
the outbreak begins. One researcher, Neil M. Ferguson of Imperial College in London, said in an interview that res
ults of his not-yet-published ma
thematical
modeling "are encouraging."
But unless antiviral drugs squelch a pandemic at
the outset,
their
ultimate usefulness will be small. Without widespread immunity through vaccination or infection,
the virus will simply move into a
population when
the drugs run out.
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