Case Analysis

As a future leader in the field of public health, you may face many chronic health threats to various systems. As you work to combat these threats and ensure community wellness, you are likely to become an agent of social change. This objective may be more challenging, although more critical, to achieve in matters such as in public health emergencies and outbreaks. For leaders, outbreaks, epidemics, and pandemics elicit critical and timely attention to situations in public health. In this week’s article by Osterholm, the author presents a possibility of another pandemic. Using this Learning Resource as well as 2–4 additional resources you may find from the Walden Library, current events, etc., consider your leadership perspective during a pandemic influenza outbreak in the United States. By selecting the following leadership role that would respond during this outbreak: (Incident Response Commander) After selecting your leadership role, use a systems approach to work with your group to establish immediate response in preventing another pandemic. Then, using your leadership assignment for the case study (attached folder), collaborate with your colleagues to create a Group Case Study Analysis that includes: An explanation of how the challenges identified in the individual case analyses collectively affect crisis response by the system and the individuals within it
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PERSPECTIVE
Preparing for the Next Pandemic
Michael T. Osterholm, Ph.D., M.P.H.
Aventis Pasteur MSD/Getty Images.
An interview with
Dr. Osterholm can
be heard at www.
nejm.org.
Annual influenza epidemics are like Minnesota
winters — all are challenges, but some are worse
than others. No matter how well we prepare, some
blizzards take quite a toll. Each year, despite our efforts to increase the rates of influenza vaccination
in our most vulnerable populations, unpredictable
factors largely determine the burden of influenza
disease and related deaths. During a typical year in
the United States, 30,000 to 50,000 persons die as a
result of influenzavirus infection, and the global
death toll is about 20 to 30 times as high as the toll
in this country. We usually accept this outcome as
part of the cycle of life. Only when a vaccine shortage
occurs or young children die suddenly does the public demand that someone step forward to change
the course of the epidemic. Unfortunately, the fragile and limited production capacity of our 1950s eggbased technology for producing influenza vaccine
Technician Working on Egg-Based Production of Influenza Vaccine.
n engl j med 352;18
www.nejm.org
may 5, 2005
and the lack of a national commitment to universal
annual influenza vaccination mean that influenza
epidemics will continue to present a substantial
public health challenge for the foreseeable future.
An influenza pandemic has always been a great
global infectious-disease threat. There have been 10
pandemics of influenza A in the past 300 years. A
recent analysis showed that the pandemic of 1918
and 1919 killed 50 million to 100 million people,1
and although its severity is often considered anomalous, the pandemic of 1830 through 1832 was
similarly severe — it simply occurred when the
world’s population was smaller. Today, with a
world population of 6.5 billion — more than three
times that in 1918 — even a relatively “mild” pandemic could kill many millions of people.
Influenza experts recognize the inevitability of
another pandemic. When will it begin? Will it be
caused by H5N1, the avian influenzavirus strain currently circulating in Asia? Will its effect rival that of
1918 or be more muted, as was the case in the pandemics of 1957 and 1968? Nobody knows.
So how can we prepare? One key step is to rapidly ramp up research related to the production of an
effective vaccine, as the Department of Health and
Human Services is doing. In addition to clinical research on the immunogenicity of influenza vaccines,
urgent needs include basic research on the ecology
and biology of influenzaviruses, studies of the epidemiologic role of various animal and bird species,
and work on early interventions and risk assessDr. Osterholm is the director of the Center for Infectious
Disease Research and Policy, the associate director of the
National Center for Food Protection and Defense, and a
professor of public health at the University of Minnesota,
Minneapolis.
1839
Baxter Vaccine
PERSPECTIVE
Cell-Culture–Based Production of Influenza Vaccine.
Microcarriers with Vero cells are shown before (top) and
after (bottom) infection with influenzavirus.
ment.2 Equally urgent is the development of cellculture technology for production of vaccine that
can replace our egg-based manufacturing process.
Today, making the 300 million doses of influenza
vaccine needed annually worldwide requires more
than 350 million chicken eggs and six or more
months; a cell-culture approach may produce much
higher antigen yields and be faster. After such a process was developed, we would also need assured
industrial capacity to produce sufficient vaccine for
the world’s population during the earliest days of
an emerging pandemic.
Beyond research and development, we need a
public health approach that includes far more than
drafting of general plans, as several countries and
states have done. We need a detailed operational
blueprint of the best way to get through 12 to 24
months of a pandemic.
What if the next pandemic were to start tonight?
If it were determined that several cities in Vietnam
had major outbreaks of H5N1 infection associated
1840
Preparing for the Next Pandemic
with high mortality, there would be a scramble to
stop the virus from entering other countries by
greatly reducing or even prohibiting foreign travel
and trade. The global economy would come to a
halt, and since we could not expect appropriate vaccines to be available for many months and we have
very limited stockpiles of antiviral drugs, we would
be facing a 1918-like scenario.
Production of a vaccine would take a minimum
of six months after isolation of the circulating
strain, and given the capacity of all the current international vaccine manufacturers, supplies during
those next six months would be limited to fewer
than a billion monovalent doses. Since two doses
may be required for protection, we could vaccinate
fewer than 500 million people — approximately 14
percent of the world’s population. And owing to our
global “just-in-time delivery” economy, we would
have no surge capacity for health care, food supplies, and many other products and services. For
example, in the United States today, we have only
105,000 mechanical ventilators, 75,000 to 80,000
of which are in use at any given time for everyday
medical care; during a garden-variety influenza season, more than 100,000 are required. In a pandemic,
most patients with influenza who needed ventilation would not have access to it.
We have no detailed plans for staffing the temporary hospitals that would have to be set up in highschool gymnasiums and community centers — and
that might need to remain in operation for one or
two years. Health care workers would become ill
and die at rates similar to, or even higher than,
those in the general public. Judging by our experience with the severe acute respiratory syndrome
(SARS), some health care workers would not show
up for duty. How would communities train and use
volunteers? If the pandemic wave were spreading
slowly enough, could immune survivors of an early
wave, particularly health care workers, become
the primary response corps?
Health care delivery systems and managed-care
organizations have done little planning for such a
scenario. Who, for instance, would receive the extremely limited antiviral agents that will be available? We need to develop a national, and even an international, consensus on the priorities for the use
of antiviral drugs well before the pandemic begins.
In addition, we have no way of urgently increasing
n engl j med 352;18
www.nejm.org
may 5, 2005
Preparing for the Next Pandemic
PERSPECTIVE
H5N1
influenzavirus
Epithelial cells
Macrophage
Virus replication
and release
Viral peptide
Immunorecptor
Activated
macrophage
T cell
Activated
T cell
Uncontrolled exuberant
immune response
Chemoattractants
Proinflammatory
cytokines
Proinflammatory
cytokines
Chemoattractants
Proinflammatory
cytokines
Acute respiratory distress syndrome
Necrosis
Tissue destruction
Influx of leukocytes
Dilatation of blood vessels
Proposed Mechanism of the Cytokine Storm Evoked by Influenzavirus.
The key element in generating the storm is an uncontrolled exuberant immune response to the virus, in which there is an outpouring of proinflammatory cytokines and chemoattractants. An animated version of this figure is
available at www.nejm.org.
production of critical items such as antiviral drugs,
masks for respiratory protection, or antibiotics for
the treatment of secondary bacterial infections. Even
under today’s relatively stable operating conditions,
eight different antiinfective agents are in short supply because of manufacturing problems. Nor do we
have detailed plans for handling the massive number of dead bodies that would soon exceed our ability to cope with them.
What if an H5N1 influenza pandemic began not
now but a year from now? We would still need to
plan with fervor for local nonmedical as well as medical preparedness. Planning for a pandemic must be
on the agenda of every public health agency, school
board, manufacturing plant, investment firm, mor-
n engl j med 352;18
www.nejm.org
may 5, 2005
tuary, state legislature, and food distributor. Health
professionals must become much more proficient
in “risk communication,” so that they can effectively provide the facts — and acknowledge the unknowns — to a frightened population.3
With another year of lead time, vaccine might
have a more central role in our response. Although
the manufacturing capacity would still be limited,
strategies such as developing antigen-sparing formulations — that is, intradermal formulations that
take advantage of copious numbers of dendritic cells
for antigen processing or formulations including
adjuvants to boost the immune response — might
extend the vaccine supply. Urgent planning efforts
are required to ensure that we have the syringes
and other essential equipment, as well as the workforce, for effective delivery. Finally, a detailed plan
for vaccine allocation will be needed — before the
crisis, not during it.
What if the pandemic were 10 years away and
we embarked today on a worldwide influenza Manhattan Project aimed at producing and delivering a
pandemic vaccine for everyone in the world soon after the onset of sustained human-to-human transmission? In this scenario, we just might make a real
difference.
The current system of producing and distributing
influenza vaccine is broken, both technically and
financially. The belief that we can greatly advance
manufacturing technology and expand capacity in
the normal course of increasing our annual vaccination coverage is flawed. At our current pace, it will
take generations for meaningful advances to be
made. Our goal should be to develop a new cellculture–based vaccine that includes antigens that
are present in all subtypes of influenzavirus, that do
not change from year to year, and that can be made
available to the entire world population. We need an
international approach to public funding that will
pay for the excess production capacity required during a pandemic.
Today, public health experts and infectious-disease scientists do not know whether H5N1 avian
influenzavirus threatens an imminent pandemic.
Most indications, however, suggest that it is just a
matter of time: witness the increasing number of
H5N1 infections in humans and animals, the documentation of additional small clusters of cases
suggestive of near misses with respect to sustained
1841
PERSPECTIVE
human-to-human transmission, the ongoing genetic changes in the H5N1 Z genotype that have increased its pathogenicity, and the existence in Asia
of a genetic-reassortment laboratory — the mix of
an unprecedented number of people, pigs, and
poultry.
It is sobering to realize that in 1968, when the
most recent influenza pandemic occurred, the virus
emerged in a China that had a human population
of 790 million, a pig population of 5.2 million, and
a poultry population of 12.3 million; today, these
populations number 1.3 billion, 508 million, and
13 billion, respectively. Similar changes have occurred in the human and animal populations of other Asian countries, creating an incredible mixing
vessel for viruses. Given this reality, as well as the
exponential growth in foreign travel during the past
50 years, we must accept that a pandemic is coming — although whether it will be caused by H5N1
or by another novel strain remains to be seen.
Should H5N1 become the next pandemic strain,
the resultant morbidity and mortality could rival
those of 1918, when more than half the deaths occurred among largely healthy people between 18
and 40 years of age and were caused by a virusinduced cytokine storm (see diagram) that led to
the acute respiratory distress syndrome (ARDS).4
The ARDS-related morbidity and mortality in the
pandemic of 1918 was on a different scale from
those of 1957 and 1968 — a fact that highlights the
importance of the virulence of the virus subtype or
genotype. Clinical, epidemiologic, and laboratory
evidence suggests that a pandemic caused by the
current H5N1 strain would be more likely to mimic
1842
Preparing for the Next Pandemic
the 1918 pandemic than those that occurred more
recently.5 If we translate the rate of death associated with the 1918 influenzavirus to that in the current population, there could be 1.7 million deaths
in the United States and 180 million to 360 million
deaths globally. We have an extremely limited armamentarium with which to handle millions of cases
of ARDS — one not much different from that available to the front-line medical corps in 1918.
Is there anything we can do to avoid this course?
The answer is a qualified yes that depends on how
everyone, from world leaders to local elected officials, decides to respond. We need bold and timely
leadership at the highest levels of the governments
in the developed world; these governments must
recognize the economic, security, and health
threats posed by the next influenza pandemic and
invest accordingly. The resources needed must be
considered in the light of the eventual costs of failing to invest in such an effort. The loss of human
life even in a mild pandemic will be devastating, and
the cost of a world economy in shambles for several
years can only be imagined.
1. Johnson NP, Mueller J. Updating the account lobal mortality
of the 1918-1920 “Spanish” influenza pandemic. Bull Hist Med
2002;76:105-15.
2. Stöhr K. Avian influenza and pandemics — research needs
and opportunities. N Engl J Med 2005;352:405-7.
3. Sandman PM, Lanard J. Pandemic influenza risk communication: the teachable moment. 2005. (Accessed April 14, 2005, at
http://www.psandman.com/col/pandemic.htm.)
4. Kobasa D, Takada A, Shinya K, et al. Enhanced virulence of
influenza A viruses with haemagglutinin of the 1918 pandemic
virus. Nature 2004;431:703-7.
5. Peiris JS, Yu WC, Leung CW, et al. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 2004;363:617-9.
n engl j med 352;18
www.nejm.org
may 5, 2005
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.

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