Unprepared for a Pandemic
By Michael T. Osterholm
From Foreign Affairs, March/April 2007
http://www.cidrap.umn.edu/cidrap/files/67/foraffosterholm0307.pdf
Summary: The need to prepare for an influenza pandemic has not yet sunk in, partly
because disaster has not yet struck. But that good news could turn into very bad news if it
leads to slacking off on necessary preparations today: although no one can predict when
or how, a pandemic will occur for sure, and it will have implications far beyond its toll on
human health.
Michael T. Osterholm is Director of the Center for Infectious Disease Research and
Policy, a Professor in the School of Public Health, and an Adjunct Professor in the
Medical School at the University of Minnesota.
SOUNDING THE ALARM, AGAIN
More than a year and a half ago, Foreign Affairs published three articles that sounded a
clarion call to prepare for the next pandemic. They warned that another pandemic could
occur at any time and at a staggering cost to human health and the world economy. These
facts remain incontrovertible. At the time, many public health scientists believed that
recent outbreaks of the H5N1 influenza virus in birds in Asia, Europe, and Africa, with
occasional infections in humans, were precursors to the next pandemic. They still do
today.
Like earthquakes, hurricanes, and tsunamis, influenza pandemics are recurring natural
disasters. The natural reservoir of influenza virus is wild aquatic birds. But for a human
influenza pandemic to occur, a strain of an avian influenza virus must develop to which
humans have no preexisting immunity and undergo critical genetic changes that allow it
to be readily transmitted from person to person. The H5N1 strain of the influenza virus
has had a limited impact on human health so far, but a human influenza pandemic could
occur -- and be devastating -- if a current strain underwent the right genetic changes.
For decades, scientists believed that the only way for an avian influenza virus to become
transmittable between humans was through a process known as reassortment.
Reassortment occurs when an avian virus and a human virus both infect the same cells of
an animal (a pig, for example) or a person and swap genes, creating a new virus adapted
to humans. (This is how the 1957 and 1968 influenza pandemics began.) Over the past
two years, however, studies of tissue samples from 1918-19 influenza victims have
suggested that an influenza virus can also become a pandemic strain after undergoing
genetic mutations of its own. Recent studies of the virus' genetic material have
demonstrated that the 1918-19 virus likely evolved by a process known as adaptation, a
series of critical mutations that rendered it capable of being transmitted between humans.
Although it is impossible to know for sure whether H5N1 will ever evolve into the next
human pandemic virus, more and more of the genetic changes documented in the 1918-
19 virus have also been found to have occurred in recent H5N1 strains affecting both
birds and people. Meanwhile, the spread of H5N1 infections to more avian species and to
more humans continues to point to H5N1 as a likely strain of the next pandemic.
No one can predict when the next pandemic will occur or how severe it will be. But it
will occur for sure, and because of the interdependence of the global economy today, its
implications will reach far beyond its toll on human health. A recent study by the Lowy
Institute for International Policy, which provides the most comprehensive estimate yet,
found that a mild pandemic similar to that of 1968 would kill 1.4 million people and cost
approximately $330 billion (or 0.8 percent of global GDP) in lost economic output. Were
a pandemic as severe as that of 1918-19 to occur, over 142.2 million people would die,
and the world's GDP would suffer a loss of $4.4 trillion.
Yet the issue has generated only limited attention in both the public and the private
sectors worldwide because preparing for a pandemic is a daunting challenge to begin
with and because disaster has not yet struck. But that good news could turn into very bad
news if it leads to slacking off on preparedness activities today. In a world filled with
competing international priorities, preparing for something that may not happen in the
next year may seem hard to justify in terms of both financial resources and time, but that
is no excuse for inaction.
FOWL PLAY
Avian influenza caused by H5N1 first received widespread attention in 1997, when an
outbreak in poultry in Hong Kong subsequently spread the virus to humans. Eighteen
human cases were recognized; six of the patients died. (There was no evidence of personto-
person transmission.) In the fall of 2003, H5N1 avian influenza appeared in domestic
poultry farms in Asia. After subsiding briefly, it reemerged in the summer of 2004 in
Cambodia, China, Laos, Thailand, and Vietnam, where it persists today despite the
widespread vaccination of poultry. Studies of recent H5N1 isolates in Southeast Asia
have indicated that the virus' predominant lineage today originated in southern China.
Other lineages are believed to have emerged in Southeast Asia, which suggests that the
virus has been present in the region for a long time. A report by the UN Food and
Agricultural Organization published in September 2004 found that existing reservoirs of
the H5N1 influenza virus in ducks, wild birds, and -- potentially -- pigs are already
resilient enough to "pose a serious challenge to eradication."
In 2005, H5N1 expanded beyond Asia. It was identified in Kazakhstan, Mongolia, and
Russia in July, and in Turkey and western Europe in October. By February 2006, it had
reached northern Nigeria; it has since been documented in several other African nations.
As of August 2006, over 220 million birds had been killed by H5N1 or culled to prevent
its spread.
H5N1 is believed to spread geographically mostly through the movement of domestic
poultry and wild migratory birds. Wild birds are thought to be the principal transporters
of H5N1 from infected areas to new geographic locations. Once introduced, the virus is
then disseminated more widely by poultry, especially domestic ducks and geese.
(According to the World Health Organization, mallard ducks are the "champion" vectors
of its spread.) The spread of H5N1 from Siberia to the Black Sea basin is consistent in
time and location with the movements of migratory birds. In Africa, it most likely spread
through the trade of poultry for human consumption, although migratory birds may have
contributed to the problem there as well. There has been no documented spread of H5N1
to migratory birds or poultry in the Americas, but that may change: Asian and European
flyways overlap in the Arctic regions of North America, and the importation of poultry
and other birds from Asia and Europe into any American country could result in the
infection of indigenous bird populations.
SPREAD THICK
The H5N1 virus has also been spreading to more humans. As of January 15, 2007, it had
infected 265 people, 159 of whom died, in ten countries over the previous three years.
Cases of human infection have occurred in Azerbaijan, Cambodia, China, Djibouti,
Egypt, Indonesia, Iraq, Thailand, Turkey, and Vietnam. Seventy-nine fatalities were
confirmed in 2006, compared with 42 in 2005, 32 in 2004, and 4 in 2003. As the number
of cases has risen, the mortality rate has remained stable, at roughly 60 percent.
Several studies have now confirmed that H5N1 infection in humans is fundamentally
different from infections caused by the current seasonal influenza strains. H5N1 infection
typically involves progressive primary viral pneumonia, acute respiratory distress, and
liver and kidney damage. Some studies have suggested that in contrast to seasonal
influenza, which primarily involves lung infection, the H5N1 virus might be
disseminated throughout the body and affect multiple organs thanks in part to a condition
of the immune system known as a cytokine storm. This is a significant finding since
clinical studies of cases from the 1918-19 pandemic have indicated that the presence of
cytokine storms helps explain why that pandemic was so deadly.
H5N1 has several other alarming features. Studies comparing samples over time have
indicated that the virus has become progressively more pathogenic for poultry. The
current strain of the virus can survive in the environment several days longer than could
earlier strains. Its range of mammalian hosts appears to be expanding. It has been found
in more and more dead migratory birds, which supports the conclusion that it is becoming
more virulent. Recent genetic work performed on viral isolates from Turkey found
evidence of two mutations that may enhance its transmission from birds to humans and
between humans.
One critical question that remains is whether the virus would become less lethal if its
ability to spread among humans developed. According to a September 2006 report by the
World Health Organization, "Should the virus improve its transmissibility by acquiring,
through a reassortment event, internal human genes, then lethality of the virus would
most likely be reduced. However, should the virus improve its transmissibility through
adaptation as a wholly avian virus [as what occurred with the 1918 pandemic strain], then
the present high lethality could be maintained during a pandemic." Even the former
outcome is no reason for comfort: with six in ten infected people currently dying from the
virus, an H5N1 pandemic caused by a virus that had lost much of its disease-causing
characteristics as it adapted to humans would still have catastrophic consequences.
THE FOG OF WAR
The Foreign Affairs articles published in July 2005 contributed to a flurry of calls to
prepare for a pandemic. In September 2005, President George W. Bush announced an
international partnership on avian and pandemic influenza before the General Assembly
of the United Nations, and in November of that year he issued the National Strategy for
Pandemic Influenza, setting out measures to prepare the United States for a pandemic.
President Bush also submitted a request to Congress for a $7.1 billion emergency budget
supplement to invest in, among other things, international health surveillance and
containment efforts, medical stockpiles, and the production of emergency supplies of
vaccines and antiviral medications. (In the end, the Pandemic Influenza Act, which was
signed into law in 2006, only provided $3.8 billion.) In May 2006, the White House
released the Implementation Plan for the National Strategy for Pandemic Influenza --
more than 300 recommendations to coordinate the federal government's response to the
threat of pandemic influenza. A month later, Congress passed the president's budget for
fiscal year 2007, which includes a $2.3 billion allowance for implementing the next phase
of the Bush administration's pandemic preparedness strategy. Australia, Canada, France,
Israel, Japan, New Zealand, Singapore, Switzerland, and the United Kingdom have
announced similar plans.
As positive as these steps may seem, there are critical problems with the preparedness
plans worldwide. Many crucial questions remain unanswered and even unaddressed.
What are the technological challenges and barriers to achieving a higher state of
preparedness? What steps should be taken to significantly reduce the impact of a global
pandemic? How does one measure preparedness? Who should pay for it? What are the
economic costs of being more prepared compared to the costs of being less prepared? In
some ways, a fog of confusion has settled over these issues. Like soldiers in battle,
policymakers and planners in the private sector are overwhelmed by the many
uncertainties and complexities surrounding the threat and by the question of how to
anticipate and respond to such a catastrophe.
Partly as a result, the issue has not retained people's attention as much as it should have
(or as much as, say, terrorism has), and preparedness continues to compete for priority on
the agendas of policymakers. President Bush and other U.S. officials held numerous
conferences and meetings on pandemic preparedness throughout 2005, but in 2006
discussion of the issue all but disappeared. No major midterm election debates or position
papers mentioned it, and Congress held no relevant hearings. (In the last months of 2006,
the media lost interest, too. A LexisNexis search of general news articles on H5N1 in 50
major international newspapers yielded more than 850 articles for October 2005 but
fewer than 75 articles for November 2006.) The same is true in virtually all developed
countries. And it is unclear whether the surge in H5N1 activity in birds and humans
documented in Asia in January 2007 will increase awareness among the media,
governments, private-sector leaders, and the public of the urgent need for pandemic
preparedness.
Some public health experts had anticipated that planning fatigue would quickly set in if a
pandemic did not materialize shortly after the first warnings. Lassitude is a normal
reaction to the perception that public health experts have been crying wolf and to the
challenge of staying on high alert over a sustained period of time. But the price of such
apathy will be very high, because avoiding the consideration of key issues will compound
the devastating effects of the next pandemic. For one thing, not enough attention is being
paid to developing an effective vaccine and an effective way to produce it and deliver it
to both developed and developing countries. For another, little thought is being given to
what effects the structure of the world economy will have on the spread of a pandemic --
and, in turn, what effects a pandemic will have on the basic functioning of the world
economy. Meanwhile, the private sector has been largely left to its own devices as it
prepares for a calamity, even though its collaboration with the public sector will be
critical to any prevention campaign or emergency response.
HIT ME WITH YOUR BEST SHOT
Ideally, the risk of pandemic influenza could be eliminated today with a protective
vaccine available to everyone that could be administered in advance of the pandemic. But
that possibility is years away at best. Currently, licensed influenza vaccines are produced
using chicken eggs, and output is limited to approximately 350 million doses a year. To
supplement production down the road, more than a dozen international drug companies
are researching new vaccines (27 human clinical trials of new vaccines against several
strains of avian influenza are under way). But most of them, although using cell cultures
rather than egg cultures, are growing a vaccine antigen similar to that grown in chicken
eggs. In other words, these second-generation vaccines are just a fancy way of producing
the antiquated first-generation vaccines used over the last 50 years. Moreover, cellculture
vaccines, like egg-culture vaccines, provide maximum protection against a
pandemic when they are produced using the virus strain causing it. This means that
although cell-culture vaccines can supplement egg-culture vaccines during the first three
or four months of a pandemic, no production can start until after the pandemic itself has
begun. And it will take years of research and clinical trials before cell-culture vaccines
are approved and years after that before they can be widely produced. Then, because the
H5N1 virus is rapidly changing, it is unclear whether the vaccines now in research and
development -- which are based on strains of the H5N1 virus that have circulated in
Vietnam, Indonesia, and Turkey -- will offer any protection against new strains of the
virus. A working group of the World Health Organization recently cautioned countries
purchasing "prepandemic vaccines" that these may offer only limited, if any, benefit.
Unfortunately, the U.S. and other governments have not made a major financial
commitment to the research and development of new kinds of influenza vaccines and to
building extensive production capacity; they are treating vaccine research and
development as though it were about business as usual, not a pending catastrophe. Over
the past two years, all the governments in the world have collectively invested less than
$2.5 billion in developing new influenza vaccine technologies, including thirdgeneration,
or universal, vaccines. This is too little, but it is hoped that ongoing research
will demonstrate that it might be possible to develop such vaccines, which would be
effective against an array of influenza viruses, and to start doing so before a pandemic
strain is at hand.
The availability of an increasing amount of antiviral drugs, particularly Tamiflu,
represents welcome news for preparedness. Roche, the pharmaceutical company that
makes Tamiflu, recently announced that it will be able to make up to 400 million doses
per year beginning in 2007. Although it remains unclear whether the drug will be as
effective against H5N1 as it is against current seasonal influenza, it appears to be
effective in preventing H5N1 infections in animal subjects when taken before exposure.
Unfortunately, even if enough of the right kind of vaccines were produced, most of the
world's population would not have access to them in the throes of a pandemic. In the
United States, the effects of a pandemic would likely be compounded by the country's
ailing health-care system -- which itself would be further weakened by the crisis. More
than 30 percent of the 5,000 hospitals in the United States are losing money. Almost half
of all emergency departments report being continually at or over capacity; 100,000
additional registered nurses are needed. Last year, some 550,000 critically ill or injured
Americans -- an average of one person every minute -- were diverted from the emergency
rooms nearest to them because these were full. It would take only a mild pandemic to
overwhelm the United States' health-care system. And in many communities it is unclear
whether even basic nursing care would be available during a severe one.
IT'S A SMALL WORLD
The interconnectedness of the global economy today could make the next influenza
pandemic more devastating than the ones before it. Even the slightest disruption in the
availability of workers, electricity, water, petroleum-based products, and other products
or parts could bring many aspects of contemporary life to a halt. The global economy has
required wringing excess costs out of the production, transport, and sale of products.
Inventories are kept to a minimum. Virtually no production surge capacity exists. As a
consequence, most of the developed world depends on the last-minute delivery of many
critical products (such as pharmaceuticals, medical supplies, food, and equipment parts)
and services (such as communications support). In the United States, approximately 80
percent of all prescription drugs come from offshore and are delivered to pharmacies just
hours before they are dispensed. An increasing number of U.S. hospitals now receive
three rounds of deliveries of drugs and supplies a day to meet their needs. With such long
and thin supply chains, a pandemic that closed borders, caused worker attrition, and
suspended travel or the transport of commercial goods would seriously disrupt the
delivery of everyday essentials.
Yet the consideration of such disturbances has been largely absent from preparedness
planning. This oversight is partly due to past experience with disasters, such as
earthquakes or hurricanes, for which relief supplies from nonimpacted areas were quickly
available for impacted ones. Such disasters are limited in time, meaning that rescue and
recovery can begin in short order. A pandemic, on the other hand, would affect the whole
world for months, and relief efforts would put a strain on resources everywhere.
Unfortunately, there are no easy answers to solve the supply-chain problem; it may
simply be too big. None of the published models estimating the macroeconomic
consequences of pandemic influenza fully account for it, reflecting a lack of imagination
on the part of both the private and the public sectors.
A related problem is the lack of planning for business continuity in the event of a
pandemic. The private sector has been involved to varying degrees in pandemic
preparedness planning. Some companies have attempted to account for all the
contingencies that could affect their employees, their supply chains, and even their
customers. Typically, the biggest challenge they face is anticipating how workers,
suppliers, buyers, infrastructure providers, and the government would respond. Given the
interdependence of all those players, figuring out what would happen if disaster struck
and how to prepare for it is a Rubik's Cube-like brainteaser. With so many unknowns,
one leading business continuity planner said at an off-the-record meeting at Harvard
University recently, "Planning for a pandemic is so different from anything we've done in
business before that we're writing the book as we go -- and it won't be finished until the
virus is finished." Some companies require their suppliers to sign affidavits indicating
that they have a workable pandemic plan in place. But most of these statements are barely
worth the paper they are printed on, because suppliers are in no better position to prepare
for a pandemic than are their buyers. Even well-intentioned efforts, in other words, have
been largely ineffectual. As a September 2006 report by the Department of Homeland
Security put it, "Eighty-five percent of critical infrastructure resources reside in the
private sector, which generally lacks individual and system-wide business continuity
plans specifically for catastrophic health emergencies such as pandemic influenza."
Many questions remain. Would consumers willingly pay a higher price for products sold
by a company that invested substantially in pandemic preparedness, or would competitors
gain market share by taking advantage of its increased costs? How should the stockpiling
of critical emergency products be promoted in this global just-in-time economy? If
solutions to these problems cannot be developed, expectations about how much can be
done should be revised.
NOW OR LATER
The world will experience another pandemic, and it will get through it, as it has all
previous ones. The challenge is to figure out now how to minimize the number of deaths
and the economic and psychological devastation it will cause. It is a particularly
complicated problem because preparing for a pandemic challenges the very basis of the
global just-in-time economy. Recent scientific findings about H5N1 infection in animals
and humans have also challenged a number of facts about influenza that scientists had
previously held sacred. So one must expect the unexpected. Winston Churchill once said,
"It is no use saying, 'We are doing our best.' You have got to succeed in doing what is
necessary." The difficulty in confronting the possibility of an H5N1 pandemic is figuring
out what is necessary.
In the short term, people around the world must understand that when a pandemic
unfolds, their communities will largely be on their own to get through the crisis. They
should plan now and learn to depend on themselves, their families, their neighbors, and
their co-workers. In the medium term, governments should devise national strategies. In
the United States, either President Bush or Congress should create a national commission
of elected officials and senior leaders in the fields of public health, vaccine and drug
research, emergency management, law enforcement, business continuity, and economics,
and it should issue, within 120 days of its creation, a report on the status of pandemic
preparedness in the public and private sectors in the United States. It should also detail an
aggressive agenda for additional investment.
Finally, the long-term goal must be to develop universal influenza vaccines. The impetus
must come from an initiative as bold as the man-on-the-moon agenda that President John
F. Kennedy articulated in May 1961. The fact that no world leader has called for such an
effort reflects a lack of comprehension about the devastation an influenza pandemic
would wreak. The opportunity to save millions of lives cannot be passed up. Even if such
efforts come too late to stave off the next pandemic, at least they would help in the one
after that.
