[Senate Hearing 109-299]
[From the U.S. Government Publishing Office]
S. Hrg. 109-299
FUNDING NEEDS FOR PANDEMIC INFLUENZA PREPAREDNESS
=======================================================================
HEARING
before a
SUBCOMMITTEE OF THE
COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE
ONE HUNDRED NINTH CONGRESS
FIRST SESSION
__________
SPECIAL HEARING
NOVEMBER 2, 2005--WASHINGTON, DC
__________
Printed for the use of the Committee on Appropriations
Available via the World Wide Web: http://www.gpoaccess.gov/congress/
index.html
U.S. GOVERNMENT PRINTING OFFICE
25-120 WASHINGTON : 2006
_____________________________________________________________________________
For Sale by the Superintendent of Documents, U.S. Government Printing Office
Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800; (202) 512�091800
Fax: (202) 512�092250 Mail: Stop SSOP, Washington, DC 20402�090001
__________
COMMITTEE ON APPROPRIATIONS
THAD COCHRAN, Mississippi, Chairman
TED STEVENS, Alaska ROBERT C. BYRD, West Virginia
ARLEN SPECTER, Pennsylvania DANIEL K. INOUYE, Hawaii
PETE V. DOMENICI, New Mexico PATRICK J. LEAHY, Vermont
CHRISTOPHER S. BOND, Missouri TOM HARKIN, Iowa
MITCH McCONNELL, Kentucky BARBARA A. MIKULSKI, Maryland
CONRAD BURNS, Montana HARRY REID, Nevada
RICHARD C. SHELBY, Alabama HERB KOHL, Wisconsin
JUDD GREGG, New Hampshire PATTY MURRAY, Washington
ROBERT F. BENNETT, Utah BYRON L. DORGAN, North Dakota
LARRY CRAIG, Idaho DIANNE FEINSTEIN, California
KAY BAILEY HUTCHISON, Texas RICHARD J. DURBIN, Illinois
MIKE DeWINE, Ohio TIM JOHNSON, South Dakota
SAM BROWNBACK, Kansas MARY L. LANDRIEU, Louisiana
WAYNE ALLARD, Colorado
J. Keith Kennedy, Staff Director
Terrence E. Sauvain, Minority Staff Director
------
Subcommittee on Departments of Labor, Health and Human Services, and
Education, and Related Agencies
ARLEN SPECTER, Pennsylvania, Chairman
THAD COCHRAN, Mississippi TOM HARKIN, Iowa
JUDD GREGG, New Hampshire DANIEL K. INOUYE, Hawaii
LARRY CRAIG, Idaho HARRY REID, Nevada
KAY BAILEY HUTCHISON, Texas HERB KOHL, Wisconsin
TED STEVENS, Alaska PATTY MURRAY, Washington
MIKE DeWINE, Ohio MARY L. LANDRIEU, Louisiana
RICHARD C. SHELBY, Alabama RICHARD J. DURBIN, Illinois
ROBERT C. BYRD, West Virginia (Ex
officio)
Professional Staff
Bettilou Taylor
Jim Sourwine
Mark Laisch
Sudip Shrikant Parikh
Candice Ngo
Lisa Bernhardt
Ellen Murray (Minority)
Erik Fatemi (Minority)
Adrienne Hallett (Minority)
Administrative Support
Rachel Jones
C O N T E N T S
----------
Page
Opening statement of Senator Arlen Specter....................... 1
Statement of Senator Tom Harkin.................................. 2
Statement of Senator Thad Cochran................................ 3
Statement of Senator Patty Murray................................ 3
Statement of Hon. Michael O. Leavitt, Secretary of Health and
Human Services, Department of Health and Human Services........ 5
Accompanied by:
Dr. Anthony Fauci, Director, National Institute on Allergy
and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services.................... 5
Dr. Bruce Gellin, Director, National Vaccine Program Office,
Department of Health and Human Services.................... 5
Dr. Julie Gerberding, Director, Centers for Disease Control
and Prevention, Department of Health and Human Services.... 5
Dr. William Raub, Science Advisor to the Secretary,
Department of Health and Human Services.................... 5
Prepared Statement of Hon. Michael O. Leavitt.................... 8
Statement of John M. Barry, author............................... 40
Prepared Statement of John M. Barry.............................. 42
FUNDING NEEDS FOR PANDEMIC INFLUENZA PREPAREDNESS
----------
WEDNESDAY, NOVEMBER 2, 2005
U.S. Senate,
Subcommittee on Labor, Health and Human
Services, Education, and Related Agencies,
Committee on Appropriations,
Washington, DC.
The subcommittee met at 9 a.m., in room SD-106, Dirksen
Senate Office Building, Hon. Arlen Specter (chairman)
presiding.
Present: Senators Specter, Cochran, DeWine, Harkin, and
Murray.
OPENING STATEMENT OF SENATOR ARLEN SPECTER
Senator Specter. Good morning, ladies and gentlemen. It's 9
o'clock, and the Appropriations Subcommittee on Labor, Health
and Human Services, Education will now proceed.
We have a hearing of unusual importance in a subcommittee
which characteristically has hearings of very great importance,
but this tops the list of any in recent times. We are looking
at a very substantial appropriation to meet the imminent threat
of a pandemic flu. I had the opportunity to hear the
President's speech yesterday at the National Institutes of
Health, and the President really laid it on the line with the
potential problems, which are enormous.
Last week, when we had full Senate consideration of the
appropriations bill, Senator Harkin took the lead, having
spotted this problem some substantial time ago, and we worked
through a very substantial add-on to our appropriations bill,
in the amount of $7,975,000,000. We carefully fenced the money
so that the expenditures would be at the discretion of the
President and his very able team, many of whom are assembled
here this morning. But we did not want to face a situation
where Congress adjourned and then the program came forward. We
will be looking, perhaps in late November, at a supplemental
with the Congress out of session. Supplemental appropriation
bills are extraordinarily difficult. They become what we call
Christmas trees for many, many other items, so that if we can
appropriate for it in due course, which we are moving ahead on,
that's the way to handle it.
The President has come in with a figure of $6,660,000,000.
We have the defense appropriation bill, which has
$3,913,000,000. We have an amendment offered by Senator Frist,
the majority leader, to the reconciliation bill for $3.954
billion, slightly under $4 billion. So, we're talking about a
great many figures, and we're going to--we're going to work
them out.
That's under 3 minutes, and now I want to save time for our
witnesses, and I yield to my distinguished ranking member,
Senator Harkin.
STATEMENT OF SENATOR TOM HARKIN
Senator Harkin. Thank you very much, Mr. Chairman. I want
to join with you in welcoming our Secretary and Dr. Gerberding,
Dr. Fauci, Dr. Gellin, Dr. Raub here to this very important
hearing this morning.
I, first, want to salute the President for coming forward
with a plan to prepare our country for avian flu. It is long
overdue. We are behind. I--that's not to say that--to blame
anyone, other than all of us. We've--all, I think, shoulder a
little bit of the blame for not coming forward a long time ago.
So, I'm not pointing at any one person. I'm just saying that
we've all, sort of, kind of, put this off and put this off,
until finally it's staring us in the face. I might exempt from
that people who--like Dr. Gerberding and others at the Centers
for Disease Control and Prevention, who have been warning us
about this for some time, and her predecessor there, Dr.
Copland, Dr. Fauci and others at the National Institute of
Health, who have been warning us about the lack of the research
we needed for vaccines, and others in the past. But I think we
all share a little bit of responsibility for not coming forward
with something before now.
I also want to say, I thought the President's tone was
correct yesterday. His tone was correct. I listened very
carefully as he sounded the alarm but drew the curtain on
panic. We need to have the alarm sounded, but we don't need to
have people panic. I thought his tone was absolutely correct in
the way he outlined it yesterday.
So, now we have a plan from the administration, we have an
appropriation here of about $8 billion. Again, this was a
bipartisan effort. Senator Specter said--was giving me a lot of
undue compliments for that. Actually, Senator Specter has been
the lead in this for a long time. We've worked very jointly
together. Actually, nothing really happens around here unless
we, kind of, have all worked together on this thing. We worked
together on this amendment last week, as we did on the one
before, on the defense appropriations bill, to try to come up
with, you know, What is it that we need? What are the
parameters? What do we need to focus on?
Quite frankly, I was pleased, but maybe not too surprised,
that the President's plan very closely tracked the one that we
had offered 1 week ago. I got to thinking about it, and I
thought, well, of course; we're all talking to the same people.
We're talking to the Secretary, we're talking to NIH, we're
talking to CDC, and we're talking to the drug companies. So, we
all, kind of, have the same inputs on this. So, they are very
closely aligned.
There is only one or two elements that I would like to
discuss with you this morning. One is just on State and local
preparedness, where I think we have focused a little bit more
here than the President has. I think we need to talk about
that, because with the buildup of vaccines, the stockpiling of
anti-virals and stuff, if we don't have the public health
infrastructure out there to educate people, to handle the
stockpiles, to deliver the medicines, then it doesn't do much
good we have all these stockpiles. So, that's the one area
where I think there's a slight difference between our approach
and what the administration has asked. But, that said, that's
about it. I think we're going to have to, kind of, just focus
on that a little bit and get those straightened out.
Last, I would just hope that this remains as an emergency.
I was informed this morning by the Secretary that--it's
something I missed yesterday--that the President had asked for
this as an emergency. That's the way we put it in our
appropriations bill. I hope that the House will acquiesce in
that and not try to get into some battle over offsets and
things like this. This is a true emergency, and it ought to be
handled as such.
Last, this is the proper place for this, in the Labor,
Health and Human Services, Education Appropriations
Subcommittee of the full Appropriations Committee. I, again,
thank my chairman, Senator Specter, for taking the lead on
this, as he has on so many other events and things that deal
with the health of the American people.
With that, Senator Specter, thank you very much.
Senator Specter. Thank you very much. Thank you very much,
Senator Harkin.
We're pleased to have with us the chairman of the full
committee, who's also, in addition, a member of this
subcommittee.
Senator Cochran, would you care to make an opening
statement?
STATEMENT OF SENATOR THAD COCHRAN
Senator Cochran. Mr. Chairman, thank you for convening this
hearing. We appreciate your leadership and the leadership of
the President in this effort to protect the public health of
our country.
The President has submitted a comprehensive proposal to
defend against, and to prepare the Nation for, pandemic
influenza. It will require our best efforts. This includes the
Congress, our Nation's research facilities, and the capacity of
our public health officials and private industry all working
together to help ensure that we protect the public health of
our country.
We thank the witnesses. We appreciate the time and effort
you have put into this effort to this point, and your
willingness to come discuss the details of the proposal and
funding needs for successfully defending against pandemic
influenza.
I thank you very much.
Senator Specter. Thank you very much, Senator Cochran.
Senator Murray, would you care to make an opening
statement?
Senator Murray. I would.
STATEMENT OF SENATOR PATTY MURRAY
Senator Murray. Thank you very much, Mr. Chairman, for
calling this really critical hearing. I think that we all
recognize that a flu pandemic is a major public health threat,
and we can't afford to play catch-up after a major outbreak.
Yesterday, we did see the President unveil his new national
strategy, and I think it's important to hear now from the
administration about how we plan to carry this out.
But it's also really important to find out how we
responsibly pay for this $7.1 billion effort. Yesterday, the
President indicated, as Senator Harkin just mentioned, that it
would be funded through emergency spending. I agree that a flu
pandemic is an emergency, and it meets the requirements of an
emergency demonstration. I hope the administration doesn't make
the same mistake it made last week in its latest Katrina
package, something we all considered an emergency, where the
administration proposed $2.3 billion in cuts to pay for part of
that Katrina package. I don't understand, frankly, how
something is an emergency one day and then requires
corresponding budget cuts the next day. So, I hope there is no
attempt to offset this flu pandemic package with cuts to other
programs. Some of my colleagues may be inclined to take the
money away from other health programs to pay for this plan, but
that would create a lot more problems and more funding
shortfalls. We can't forget with this that it's the local
hospital, the local community clinic, and the local emergency
room staff who are going to the--on the front lines of any
outbreak. So, if we cut other funding from our public health
infrastructure to fund this new strategy, we're going to make
it even harder for those on the front lines to respond
effectively.
So, I would just encourage my colleagues to remember that
cutting our public health infrastructure to fund this new
strategy is going to create problems and dangers when local
communities are required to respond to any outbreak.
We have a lot of work ahead to do to protect our citizens.
We don't have a vaccine that's ready to be administered on a
global scale, and that puts an even greater emphasis on giving
our local public health officials the tool to diagnosis and
contain any outbreak that may occur.
So, Mr. Chairman, I thank you very much for holding this
hearing. I appreciate the Secretary, CDC, and NIH for being
here, and I look forward to your testimony.
Thank you very much.
Senator Specter. Thank you very much, Senator Murray.
Secretary Leavitt is joined by part of his really
outstanding team. We're pleased to have Dr. Julie Gerberding
here, Director of CDC. When I wanted some spot information
recently, she was available, in Bangkok, and--accompanying
Secretary Leavitt on a trip there on the scene. Dr. Fauci is
here today--does outstanding work as Director of the National
Institute on Allergy and Infectious Diseases; and Dr. Bruce
Gellin, Director of the National Vaccine Program Office; and
Dr. Raub, Science Advisor to the Secretary.
We appreciate all of your being here, because we may ask
some questions which go beyond the testimony of Secretary
Leavitt.
Secretary Leavitt is the 20th Secretary of the United
States Department of Health and Human Services. He's had a very
distinguished record in public service--the Administrator of
the Environmental Protection Agency, elected Governor of the
State of Utah on three occasions, served 11 years in that
position, has a bachelor's degree in economics and business
from Southern Utah University.
Mr. Secretary, we appreciate the job you're doing. You've
got your hands full, and we want to help. We won't have any
clock running for Secretary Leavitt, unlike the clocks for the
Senators.
The floor is yours, Mr. Secretary.
STATEMENT OF HON. MICHAEL O. LEAVITT, SECRETARY OF
HEALTH AND HUMAN SERVICES, DEPARTMENT OF
HEALTH AND HUMAN SERVICES
ACCOMPANIED BY:
DR. ANTHONY FAUCI, DIRECTOR, NATIONAL INSTITUTE ON ALLERGY AND
INFECTIOUS DISEASES, NATIONAL INSTITUTES OF HEALTH,
DEPARTMENT OF HEALTH AND HUMAN SERVICES
DR. BRUCE GELLIN, DIRECTOR, NATIONAL VACCINE PROGRAM OFFICE,
DEPARTMENT OF HEALTH AND HUMAN SERVICES
DR. JULIE GERBERDING, DIRECTOR, CENTERS FOR DISEASE CONTROL AND
PREVENTION, DEPARTMENT OF HEALTH AND HUMAN SERVICES
DR. WILLIAM RAUB, SCIENCE ADVISOR TO THE SECRETARY, DEPARTMENT
OF HEALTH AND HUMAN SERVICES
Secretary Leavitt. Thank you, Mr. Chairman. I'll do my best
not to abuse that privilege. I will summarize, briefly, so we
can get on to questions.
In my opening statement, I think it would be valuable for
me to just frame the subject. Pandemics. The bottom line is,
they happen. Ten times in the last 300 years, and three times
in the last 100 years, viruses have mounted a massive pandemic
assault that has made masses ill and caused millions to die.
They happened before, they'll happen again, and we need to be
prepared. Whenever there is a human-to-human transmission of a
dangerous killer virus, there is risk everywhere in the world.
Leadership, as Senator Harkin pointed out, right now is
creating an atmosphere of information without inflaming. It is
inspiring preparation and not panic. Our deliberate moving
forward on this plan constitutes that action.
The current worry, of course, is the H5N1 virus. It is
primarily an animal disease right now. The probability of it
making the transition to a human-to-human transmittable virus
is unknown, uncertain, but the troubling signs are clearly
there. The ramifications would be so significant, so world-
changing, that we have no alternative but to prepare. But if it
isn't the H5N1 virus, it will be another virus, as it has in
past, because, in fact, pandemics do happen.
As indicated yesterday, the President laid out a broad
national strategy. He called upon Congress to appropriate the
$7.1 billion that's been mentioned. Later today, or today--
simultaneous with this hearing, I will be laying out with more
granularity the plan that HHS is putting forward on the medical
and public health portion of it. It constitutes roughly $6.7
billion of the $7.1 billion.
I'd like to take just a moment and describe, in broad
outline, the nature of that plan. I've put a placard up that
lists the six primary components. I'll review them briefly.
The first is international surveillance. Many have compared
a pandemic to a forest fire. If you're there when the spark
happens that sets the fire off, you can mitigate its damage
simply by snuffing it out. If it's allowed to burn, it will
burn beyond containment very rapidly. In order to identify when
the spark happens in a pandemic or a forest fire, you need good
surveillance. In pandemics, good surveillance means
laboratories, it means epidemic investigators, it means rapid-
response teams, it means American experts on the ground in
Southeast Asia and other countries where we can be of
assistance to them, it means having a joint containment plan
with our friends and neighbors around the world so that when
the spark happens, if we can get there fast, we can contain it
and save the world from the destruction it could bring.
The second point is domestic surveillance. Just as in the
international arena, if a pandemic virus reaches the shores of
the United States, we need to know. We need to know fast, and
we need to know that--with the most possible certainly, how
broadly it has spread so that we can contain it. That, again,
means laboratories, it means medical training for local
providers, it means a good communication network.
The third point on the plan is the foundation of this plan,
which is vaccines. The good news is, we have a vaccine. The
scientists at NIH have developed a vaccine that produces
sufficient immune response that it can protect a human being
when given at the proper dosage. The bad news is, we
fundamentally lack the capacity to manufacture it in sufficient
volumes in time.
The plan lays out two broad objectives. The first is to
develop 20 million courses of the closest vaccine possible,
given our information today, and then the capacity to produce,
within a 6-month time, up to 300 million courses of the
appropriate vaccine once the virus has been detected and
isolated.
To do that, we'll undertake three major tasks. The first is
to expand our egg-based vaccine production. The second is to
develop new cell-based technology. The third is to test
adjuvant technologies, which are dose-sparing technologies,
allowing us to spread the limited vaccine that we have
available further.
In the long run, we would expect to see that 300 million
courses that we could produce within a 6-month period break
down roughly to 62,500,000 egg-based vaccines and roughly
237,500,000 cell-based vaccines.
As we begin the development, we obviously need to have a
great deal of flexibility in the way we approach it. We would
see ourselves developing a strategy that would operate within
four corners.
The first is that these technologies need to be
domestically produced. In a pandemic, it is a broad view that
we will undoubtedly only have the vaccine we can produce on our
shores. So, what we develop needs to be produced here. Second,
we need to achieve the lowest-cost, highest-quality quotient.
The third is that we need to have flexibility, the ability to
move within the technologies. If one is working better than
another, we need to be able to shift our capacity there.
Fourth, we need to produce continuous annual flu benefit so
that we're developing a public health asset in doing so.
The fourth category that you'll note is anti-virals.
I'd like to make an important point. Anti-virals are an
important part of a comprehensive plan, but anti-virals are not
the equivalent of preparation. There is no certainty of their
effectiveness on any particular virus. There is no capacity to
change the anti-viral if the virus adapts. There are
distribution dilemmas.
Nevertheless, it's a very important part of a comprehensive
plan, and the plan does call for us to build a stockpile of 20
million courses. The vendors have represented to us that those
could be delivered by the fourth quarter of 2006, and we could
build our collective stockpiles to 81 million by the summer of
2007. Again, that's a date vendors are able to meet.
We will focus on this as a locally deployable asset.
Senator Harkin, you mentioned the fact that we need to work
very closely with State and local officials. The timeframes
involved in the deployment of anti-virals are crucial.
I would like to point out that, in the anti-viral category,
400 million of it would be focused on the development of new
and better anti-virals. We think that's an important part of a
comprehensive plan, is the continual upgrading of our anti-
viral arsenal.
The fifth category is communication, informing the public
with available information so that every community knows what
to expect. We need to begin the development of these materials
before a pandemic strikes.
The last piece I would point out is State and local
preparedness--again, something that Senator Harkin and Senator
Specter both commented on. This is a unique kind of disaster.
It is not like Katrina or Rita or any other hurricane, where we
have a confined area of disaster. It is a disaster of unlimited
distribution, with an unconfined time, and has to be managed
locally. The President indicated, in his speech yesterday, the
need for us to immediately begin working with State and local
officials to develop readiness plans in every community.
Last, I would just say, the budget that's been presented is
in two major accounts: vaccine and anti-virals. The vaccine and
anti-viral portion totals $4.7 billion, and the other public
health efforts, roughly $500 million.
In conclusion, I would like to just make this point. We
don't know whether the H5N1 virus will be the spark that will
set off a global pandemic. We do know that, at some point in
time, a pandemic is likely to happen. History makes that very
clear. There may be those, if H5N1 does not become the spark,
that look back and say we overreacted, or there may be some who
would say, ``Well, they cried wolf.'' But I would like to
suggest that this is about long-term pandemic readiness, and
that at the conclusion of this plan, there will be five things
that will be true of this country that are not totally true
today.
The first is that we will have cell-based technology that
will be the key to surging up the production of pandemic flu
vaccines quickley and establish an enormous asset
scientifically and in public health.
The second is, we can make a giant step forward on our
annual flu capacity to be able to protect the citizens of this
country on a year-to-year basis.
Third, our State and local governments will be better
prepared, not just for pandemic, but for every kind of medical
emergency.
Fourth, we'll have an international network of surveillance
that will protect not just citizens of the United States, but
people around the world.
PREPARED STATEMENT
Last, we'll have the peace of mind of knowing that we are
ready.
Thank you, Mr. Chairman.
[The statement follows:]
Prepared Statement of Hon. Michael O. Leavitt
Good morning Senator Specter, Senator Harkin, and members of the
Subcommittee. I am honored to be here today to present the President's
request for funds for the HHS Pandemic Influenza Plan, which is an
integral component of the National Strategy for Pandemic Influenza,
which the President announced yesterday. In the event that an outbreak
of pandemic flu hits our shores, it will surely have profound impacts
on almost every sector of our society. Such an outbreak will require a
coordinated response at all levels of government--Federal, State, and
local--and it will require the participation of the private sector and
each of us as individuals. HHS has been a leader in this effort, and
today, with this budget request and the release of the HHS Pandemic
Influenza Plan, we are taking another major step forward to improve our
preparedness and response capabilities.
The threat of an outbreak of pandemic influenza is real. An
influenza virus strain with potential to cause a pandemic of human
disease could emerge with little or no warning and in almost any part
of the world, as occurred 3 times during the 20th century. Influenza
viruses infect birds, pigs, and other animals, as well as humans. The
ability of these viruses to cross the species barrier from time to time
creates the possibility for the appearance of new viral strains that
have the potential to be highly infectious, readily transmissible, and
highly lethal. If a pandemic virus strain emerges, it is estimated that
upwards of 30 percent of people exposed could become infected and the
death rate will likely be considerably higher than that seen with
seasonal influenza. Faced with such a threat, the United States and its
international partners will need to respond quickly and efficiently to
reduce the scope and magnitude of this serious health threat.
Today's threat is the H5N1 avian influenza strain, which is
spreading widely and rapidly in domestic and migratory fowl in Asia and
now in Eastern Europe. While the virus has not demonstrated the ability
to spread efficiently from person to person, it has infected more than
one hundred people in Asia and approximately 50 percent of these known
cases have died. The virus is now endemic in many bird species and in
several countries, so elimination is not feasible. The feared pandemic
could become a reality if this virus mutates further, remains highly
virulent, and acquires the capability to spread as efficiently from
person to person as do the commonly circulating virus strains that
produce seasonal influenza epidemics. But even if H5N1 does not lead to
a pandemic, the likelihood of an influenza pandemic at some point
remains high. This is why we need to prepare now in order to swiftly
and efficiently respond to an outbreak. I have come here today to ask
for your support for funding for the HHS Pandemic Influenza Plan, which
is our portion of the National Strategy for Pandemic Influenza.
This week, we are taking important steps forward. Today, I am
releasing the HHS Pandemic Influenza Plan, which is a blueprint for
pandemic influenza preparation and response. The HHS Plan provides
guidance to national, State, and local policy makers and health
departments. The goal is for all involved to achieve a state of
readiness and quick response.
The HHS Plan includes an overview of the threat of pandemic
influenza, a description of the relationship of this document to other
Federal plans and an outline of key roles and responsibilities during a
pandemic. In addition, the HHS Plan specifies needs and opportunities
to build robust preparedness for and response to pandemic influenza.
The preparations made for a pandemic today will have lasting benefits
for the future.
A pandemic outbreak will allow very little time to develop new
capabilities or build surge capacity for response if these efforts are
not already in place. Unfortunately, current capacity for domestic
manufacture of influenza vaccine and antiviral drugs can meet only a
small fraction of the need projected for a pandemic response. If we are
to have the capabilities and capacities needed when a pandemic emerges,
the investments to bring them about must be made now. That is why the
President is requesting additional fiscal year 2006 appropriations for
HHS totaling $6.7 billion for the HHS Pandemic Influenza Plan. Our
goals in seeking this funding are to be able to produce a course of
pandemic influenza vaccine for every American within six months of an
outbreak; provide enough antiviral drugs and other medical supplies to
treat over 25 percent of the U.S. population; and ensure a domestic and
international public health capacity to respond to a pandemic influenza
outbreak.
First, we must establish the domestic vaccine production capacity
our Nation will need to protect all Americans within six months of
detection of a virus that begins to spread efficiently from human to
human. In anticipation of an influenza pandemic, we must stockpile in
advance sufficient quantities of pre-pandemic vaccine that is
protective against circulating influenza virus strains with pandemic
potential in order to be in a position to initiate vaccination of
health care workers and front-line workers critical to the pandemic
response. These pre-pandemic vaccine stockpiles must be regularly
reevaluated and potentially replenished as the pandemic virus threat
mutates and changes, and as vaccine potency degrades over time. In
addition, as the virus strains evolve and potentially escape protection
by the existing vaccines, newer vaccines that better match the current
pandemic strain will need to be produced and stockpiled. The Nation
must also expand its stocks of antivirals, personal protective
equipment (masks, gloves, etc.) and other supplies to help provide a
potentially over-burdened healthcare system with the means to treat and
care for those who become seriously ill in an influenza pandemic.
Second, we must enhance the disease surveillance systems both
internationally and domestically and train the personnel needed to
reliably detect an outbreak quickly and to accurately determine its
lethality and transmissibility. This includes obtaining samples of the
virus from infected humans and animals and having laboratory capacity,
personnel, and supplies necessary to conduct rapid analysis.
Surveillance is our early warning system, and faster detection will
enable public health officials to make recommendations about
containment protocols, such as limits on travel and the assembly of
large groups of people. Faster detection and identification of emerging
influenza virus strains facilitate the conversion by industry to mass
production of pandemic influenza vaccines. Better State, Federal, and
international diagnostic laboratory systems will also allow for
increased surge capacity needed to support front-line medical
personnel, and effectively guide the use of scarce drugs, vaccines, and
other resources.
Improved surveillance systems, including near real-time collection
of data from hospital emergency departments in major metropolitan areas
through BioSense, will allow us to continuously track the spread of the
virus and the morbidity/mortality it produces and to evaluate the
effectiveness or our intervention strategies. This information will be
critical to determining the best uses of limited supplies of pandemic
influenza countermeasures. We will also track vaccines and
immunizations to ensure that we maximize its equitable use as well as
its effectiveness and safety.
Third, we must develop in advance domestic and international plans
for broad public education efforts that are culturally appropriate and
provide critical information in ways that acknowledge different levels
of health literacy. These efforts before and during a pandemic will
help guide individual actions to prevent and reduce infection and
clarify the need for prioritization of scarce vaccines and antivirals
and other materials. Our request also includes funding for States and
local municipalities to develop and/or update their pandemic influenza
response plans and to integrate them with Federal plans.
INFLUENZA VACCINE
The Administration has been aggressively working to be able to
acquire, over a two-year period, enough H5N1 vaccine and antivirals to
protect 20 million people should they become infected with the pandemic
virus. On July 15, 2005, the Administration submitted an fiscal year
2006 Budget Amendment totaling $150 million to implement our ``20/20''
plan. This strategy was designed to give us considerable experience
with commercial-scale manufacturing of this new vaccine, and provide
some pre-pandemic vaccine to our stockpile. However, as we are only
able to obtain pre-pandemic vaccine during the few months of the year
when influenza vaccine manufacturers are not running at full capacity
making the seasonal trivalent vaccine, we are severely limited in the
quantity of vaccine that we can stockpile. In addition to this
limitation, since the submission of this Budget Amendment, we received
results of H5N1 vaccine clinical trials funded by NIH. As part of this
strategy, the NIH has funded clinical trials of H5N1 influenza
vaccine--which provided good news and, at the same time, sobering news.
The good news was that the vaccine we developed works--it provides a
good immune response that augurs well for protecting people against the
H5N1 virus. The sobering news was that to achieve the desired immune
response, the vaccine needed to be six times as potent as the seasonal
vaccine--90 micrograms of the hemagluttinin component instead of 15
micrograms--and that two doses are needed for the protective immune
response. This has further driven home a point of which we were all
aware--that the nation's capacity to produce enough 90 microgram doses
of pandemic vaccine was woefully inadequate. We need an aggressive
strategy to achieve the needed domestic vaccine manufacturing capacity
as quickly as possible, and to initiate similarly aggressive action to
implement other immediate preparedness strategies beyond these critical
vaccine needs. This budget request is just such a strategy, building on
the July Budget Amendment and responding aggressively to the results of
the NIH clinical trials and our growing concern that a pandemic could
involve hundreds of communities across the United States and around the
world.
Of today's $6.7 billion funding request, approximately $4.7 billion
would go toward investments in creating pandemic influenza vaccine
production capacity and stockpiles that will ensure that enough vaccine
will be available to every American in the event of a flu pandemic. To
accomplish this, HHS will pursue a multi-faceted strategy to create, as
soon as possible, domestic influenza vaccine manufacturing capacity
aimed at producing 300 million courses (two doses of vaccine per
person) within six months of the onset of an influenza pandemic. With
this immediate investment, the increased production capacity and
related stockpile expansion will be achieved in phases between 2008 and
2013.
The initial component of this strategy is to expand the number of
licensed domestic egg-based influenza vaccine manufacturers from the
single one that currently exists. This would give the United States the
ability to develop a 20 million course (40 million doses) pre-pandemic
vaccine stockpile by 2009--without disrupting the production of annual
seasonal influenza vaccine. In the event of a pandemic outbreak, or
perhaps before, the vaccine stockpile would be used to immunize
healthcare workers, front-line responders, vaccine manufacturing
personnel, and others critical to the pandemic response. Once this
capacity is developed, current egg-based production techniques could
then provide about 60 million courses of vaccine within six months of
an outbreak, or about 20 percent of our goal of 300 million courses
within six months.
The ultimate surge capacity goal of 300 million courses of vaccine
cannot be achieved from eggbased production alone. Our best hope for
creating capacity in the United States for rapidly ramping up vaccine
production at any point in time is expansion and acceleration of our
investment in cellbased influenza vaccines--and much of our planned
investment goes toward this initiative. While promising, success of
cell-based influenza vaccine production and licensure is still years
off, and not a guarantee. Therefore, our vaccine capacity expansion
strategy invests in both cellbased vaccines and the traditional, tried
and true egg-based vaccines. Therefore, HHS, in collaboration with the
vaccine industry and its academic partners, will invest in the advanced
development of cell-based techniques for manufacturing pandemic
influenza vaccines. By financing the establishment of new cell-based
vaccine manufacturing facilities that could open in 2010, our plan will
develop the surge capacity needed to provide for the remaining 80
percent (approximately 240 million courses) of the population within
six months of a pandemic outbreak.
The HHS Pandemic Influenza Plan also acknowledges that existing
manufacturing facilities can be directed to this effort and finances
the retrofitting of existing domestic manufacturing facilities that
would enable them to convert to production of pandemic influenza
vaccine production, in an emergency. HHS will establish contingency
arrangements with vaccine manufacturers in conjunction with the Food
and Drug Administration so that, at the onset of an influenza pandemic,
they will be able to readily adapt their facilities either to produce
influenza vaccines or to provide a critical function, such as fill and
finish bulk vaccine produced by other manufacturers.
We will also work with industry and academia to support advanced
development of dosestretching technologies, such as the use of
adjuvants and new vaccine delivery systems. These investments, if
successful, will extend the pandemic influenza vaccine supply and allow
more Americans to receive pandemic vaccines sooner. We will also invest
in research that may have potential to lead to broad-spectrum vaccines
to protect against multiple and emerging strains of influenza viruses.
This would allow for stockpiling of vaccines that could be useful even
as the virus strains evolve and change.
However, as we seek to build domestic manufacturing capacity, we
also know that the threat of liability exposure is too often a barrier
to willingness to participate in the vaccine business. As we recognize
the desperate need to create and expand vaccine manufacturing capacity,
we have to remove such deterrents to participation by those with the
knowledge and experience to accomplish this. It is crucial that those
engaged in this work be shielded from unwarranted tort suits.
Accordingly, the Administration is proposing limited liability
protections for vaccine manufacturers and providers, with an exception
to allow suits to proceed against companies who act with willful
misconduct. We believe this proposal strikes an appropriate balance of
removing the liability risks that dissuade companies from producing
pandemic countermeasures, while still retaining appropriate access to
court remedies.
ANTIVIRALS
We also recognize the importance of having available a sufficient
supply of stockpiled antiviral drugs to treat and care for infected
individuals. For this, we request an investment of $1.4 billion. These
funds would help us achieve the national goal of having available 81
million courses of antivirals, which would be sufficient to treat 25
percent of the U.S. population (75 million courses) and a reserve
supply (6 million courses) that could be used to contain an initial
U.S. outbreak. Funding would also be used to accelerate development of
promising new antiviral drug candidates in collaboration with academia
and industry, since none of the antivirals today are likely to work
perfectly against pandemic influenza.
Of the 81 million courses, six million courses will be designated
to contain the first isolated domestic outbreaks. Of the 75 million
courses that will be used to treat those who are infected with the
pandemic virus, HHS would fully fund the procurement of 44 million
treatment courses to provide protection to the highest priority groups
in the event of an influenza pandemic. We will also work with our State
partners to encourage them to acquire antivirals for rapid use for
their populations. To help support these States efforts, we would
establish contractual arrangements with manufacturers of approved
antivirals whereby States may purchase up to 31 million treatment
courses and HHS would pay for approximately 25 percent of the costs of
these drugs. This arrangement will also ensure a more coordinated
inter-governmental approach in the acquisition of antiviral drugs and
pre-deployment stockpiles of antivirals around the nation. A guaranteed
acquisition of up to 81 million courses of antiviral drugs will enable
manufacturers to make significant expansion in its U.S.-based
manufacturing capacity--thereby positioning itself to meet future
demands much more readily than currently is possible.
I have personally been meeting with leaders of relevant vaccine
manufacturers to determine how they might participate in preparedness
for and response to a pandemic. To facilitate the development of new
antivirals, HHS will collaborate with industrial organizations to
develop, obtain approval, and establish commercial production of new
antivirals that would help protect the citizens of our Nation.
DISEASE SURVEILLANCE, PUBLIC HEALTH INFRASTRUCTURE, AND RISK
COMMUNICATION
In addition to the production and stockpiling of vaccines and
antivirals, enhancing domestic and international resources to expand
surveillance, strengthening public health infrastructure, and
effectively communicating with the public about risks of an influenza
pandemic are important components of the HHS Pandemic Influenza Plan,
for which we are requesting $555 million. A critical step in enhancing
public health infrastructure and international collaboration will be to
implement and refine surveillance and epidemiological response. These
investments will help us detect, investigate, and respond to the onset
of a potential influenza pandemic anywhere in the world without delay.
Because influenza characteristically spreads beyond country boundaries,
we have included in our request funding to be used internationally.
These funds will follow the evolution of the virus in Asia, detect
human cases, and help contain outbreaks, where feasible.
With an enhanced domestic and international early warning system,
we will be better positioned to mount an immediate emergency response
to characterize the outbreak; obtain viral samples for analysis and
possible vaccine production; and we will have a greater chance to
prevent, contain, and/or retard the spread of infection. The ability to
continually analyze data to help predict the further course of the
pandemic will help guide the choice and timing of interventions (drugs,
vaccine, and public health measures) and will help assess the efficacy
of these interventions.
Enhancing our public health infrastructure also includes expanding
the science base at the Food and Drug Administration, thus allowing for
expedited regulatory review of pharmaceutical industry initiatives to
develop the necessary new vaccine technologies, as well as speeding the
licensure of the facilities and vaccines produced within them.
Risk communication is another integral part of an effective public
health response plan. We must have in place the capability to employ
effective risk communication practices that will guide us in providing
the American people with the accurate, timely and credible information
they will need to protect themselves and help others during an
influenza pandemic. To ensure that our communications efforts resonate
with target audiences, we will solicit the public's active
participation and involvement in our efforts to develop relevant, easy-
to-understand information and materials regarding influenza in general,
and pandemic influenza in particular. To help in this effort, we have
established a website devoted exclusively to this topic,
pandemicflu.gov.
Public participation and involvement may include engaging the
public in discussions on State and local community preparedness;
assisting communities in developing procedures for disseminating
information and guidance for all segments of our diverse population;
and developing targeted informational tool-kits for distribution to
particular stakeholders such as educators, physicians, and employers.
STATE AND LOCAL PARTNERS
Pandemic planning needs to incorporate every department of the
Federal government but must also go deeper than that. Every State and
local government must have a pandemic plan. Unlike most disasters, a
pandemic outbreak can happen in hundreds or thousands of places
simultaneously. The Federal government will play an important role, but
engaged state and local partners are necessary for our success. Over
the coming days, I will be asking the governors, mayors and State and
local health and preparedness officials to join me in a concern we all
must share--preparing for a pandemic should one happen. Everyone in
society has a role.
For example, the Federal Government can deliver stockpiles of
medication and supplies to a city in the United States in a matter of
hours--but it is distribution at the State and local level that defines
victory. In a moment of crisis, if we are not able to deliver pills to
people over wide areas in short time frames, lives will be lost. We
need to create a seamless preparedness network where we are all working
together for the benefit of the American people. Of the $555 million
for surveillance and public health infrastructure, our Budget request
includes $100 million specifically for State and local pandemic
preparedness efforts. And, as mentioned previously, we will provide
incentives to States to purchase their own stocks of antivirals by
allowing them to buy off of HHS-negotiated contracts and subsidizing
about 25 percent of the cost.
The plan and budget request outlined above will greatly improve our
short and long term preparedness posture. We are well-positioned to
implement the plan and invest these new resources wisely and
effectively only because of the substantial pandemic influenza
activities already underway at HHS. Scientists at the National
Institutes of Health and the Food and Drug Administration, working with
industry, have developed a vaccine that produces an immune response
sufficient to provide protection from the H5N1 virus. This bodes well
for our ability to develop a vaccine against a pandemic virus that may
evolve from the current H5N1 strain. In September, HHS awarded a $100
million contract to manufacture 3.3 million doses of H5N1 vaccine,
which at two doses per person would be enough for 1.67 million people.
In addition, just last week we announced the award of a $62.5 million
contract to produce even more vaccine. We have also initiated contracts
to secure an adequate supply of specialized eggs to initiate surge
production at any time of year.
This is not a new undertaking. I have worked with many of you, and
appreciate the Subcommittee's commitment to helping our nation prepare
to meet this threat. We are making progress, and with your help will
continue to do so. We realize we are asking for significant funding at
a time when the Administration and Congress are trying to control
spending and reduce the deficit. But we have controls in place at the
Department, and within the structure of the funding request to ensure
that these funds are used wisely and responsibly. When American lives
are at stake, we must take action to protect them. We acknowledge that
investing in this plan without perfect knowledge of the future is
expensive, and not without risk. However, waiting until a pandemic
begins before preparedness is undertaken would be so much more
expensive in terms of American lives and economic impact. In our view,
waiting is not an option.
I look forward to answering your questions, and more importantly,
to working closely with you and all members of Congress as we move
forward together to protect our citizens.
PANDEMIC FLU PREPAREDNESS
Senator Specter. Thank you very much, Secretary Leavitt.
We'll now proceed with 5 minute rounds of questioning by
the Senators.
Secretary Leavitt, without seeking to ascribe blame, but
looking to preventative measures for the future, we find
ourselves caught up in an emergency situation. The President
was emphatic that nobody has pandemic flu in the United States
yet, and there are good reasons, as Senator Harkin points out,
to be alert, but not be panicked. But looking backward--20-20
hindsight is great--when did we first have any indication that
this kind of a problem might confront us? The subordinate
question--I don't like to ask two questions at the same time,
but the subordinate question is, Could we have acted sooner to
avoid a situation where we're now, in effect, running for
cover?
Secretary Leavitt. As I indicated in my opening statement,
Mr. Chairman, pandemics have been with us for as long as
recorded history, 10 in the last 300 years, 3 in the last 100.
Periodically, they happen. The current virus is our concern.
Senator Specter. They killed millions of people, so we know
how devastating they are. What is the answer to the narrow
question: When did we first have some inkling, however slight,
that we might be facing this kind of a problem in November
2005?
Secretary Leavitt. In 1997, the H5N1 virus first made its
appearance. It was in Hong Kong. The Hong Kong Government acted
in a bold way. They destroyed 1.4 million chickens and began
using basic public health techniques to contain the virus. They
did so successfully. It did not begin to manifest itself again
until 2001, where there were some limited number of cases, and
then in 2002-2003. We began to buy anti-viral medications, in
December 2003. We bought them again in 2004. The NIH began
working on a vaccine. I'll ask Dr. Fauci to give you a brief
answer on this, as well, because, in 2004, they were able to
isolate the virus by using a sample from a victim in Vietnam.
Senator Specter. What did the U.S. Government do in 1997,
when this issue first reared its ugly head?
Secretary Leavitt. I'm going to ask Dr. Fauci to respond to
that.
Senator Specter. That was long before your watch, but what
was done? Dr. Fauci----
Dr. Fauci. Mr. Chairman, in anticipation of the situation
where we are now with regard to the need for a vaccine, the
1997 isolate from the Hong Kong cases that the Secretary
mentions was actually used in collaboration with industry to
create a seed virus vaccine and test that vaccine in 1999. In
fact, the data that we're looking at now is looking at how that
vaccine has now covered the virus as it has evolved into the
2003, 2004, and 2005 version.
We updated the vaccine in 2004, when it became clear that
there was a considerable amount of accelerated activity among
birds with infections in Southeast Asia. We took a virus from a
Vietnamese patient 1\1/2\ years ago, made a vaccine, contracted
for a certain number of doses for the clinical trial, and the
data that we made public this past summer was related to that
vaccine trial that we actually started over 1 year ago in
isolating the virus and getting it. So, we started in 1997 and
continued it along, and accelerated it as we got into 2004.
Senator Specter. The information provided to the
subcommittee is that the only United States-based influenza
vaccine manufacturing facility is an egg-based facility owned
by Aventis Pasteur and located in Swiftwater, Pennsylvania.
This came to my attention last year. They had an emergency for
$10 million, which is not a huge sum of money. But we had to do
handstands to find a way to fund them for $10 million, or they
were about to lose their ability to provide what limited
facilities we had.
I'm interested to know--and I'm going to observe the time
limits, because I want everybody else to, and I've only got 16
seconds left, but I would like to have, in writing, the
chronology of what was known when and what you told Congress
and what we could have done to have avoided being precisely
where we are now.
[The information follows:]
HHS Pandemic Influenza Preparedness Initiatives
1989.--CDC establishes collaborative agreements between the
Institute of Virology, Bejing, and CDC's Influenza Branch were
implemented in 1989 to establish six surveillance sites in China,
considered a geographic focal point for newly emerging epidemic and
pandemic variants of influenza. In 1994, a five year contract was
awarded to the Institute to ensure the continuation of the program.
1993.--National Vaccine Program Office, in collaboration with CDC,
begins review of pandemic preparedness and drafting of national plan.
February 1995.--National Vaccine Program Office hosts national
stakeholders meeting on pandemic planning.
1995.--CDC initiates a cooperative agreement with the Council of
State and Territorial Epidemiologists to facilitate and local pandemic
preparedness planning.
May-December 1997.--CDC assists the Hong Kong Department of Health
in the investigation of 18 cases of influenza A (H5N1) in humans,
including the initial identification and molecular characterization of
avian H5N1 in the index case and 7 subsequent patient isolates.
On-going since 1997.--CDC generates sequence information on avian
influenza viruses to trace the origin of the H5N1 isolates, design
updated primer sets for PCR-based diagnostics and clone genes for
vaccine production.
August 1997.--CDC conducts outbreak investigations on Avian
Influenza (H5N1) infections which occur in both poultry and humans in
Hong Kong. This is the first time an avian influenza virus has ever
been found to transmit directly from birds to humans. The virus kills
six out of 18 people infected. All poultry in Hong Kong are culled
(World Health Organization).
August 1997.--CDC and FDA publish an update on pandemic
preparedness in the Journal of Infectious Diseases.
1997.--CDC develops a rapid and highly specific serologic testing
procedure to detect the presence of H5 antibody in humans which was
used to analyze over 2,000 serum samples collected from the Hong Kong
investigation. This assay was used to determine if person-toperson had
occurred and was a key tool in epidemiological studies to evaluate risk
factors for H5N1 infection. Results from these studies (1998) determine
that exposure to poultry in the retail markets was the primary risk
factor for influenza (H5N1) but that human-to-human transmission,
although rare, had occurred.
September 1997.--National Institute of Allergy and Infectious
Disease (NIAID) awards a grant to Baylor College of Medicine (Principle
Investigator (PI)--Pedro Piedra) to examine whether vaccinating a large
percentage of children can protect a community from a possible
influenza pandemic.
November-December 1997.--CDC develops and distributes over 350
supplemental kits for the identification of influenza A (H5N1) are
distributed to domestic and World Health Organization Collaborating
Laboratories in response to reported human H5N1 cases in Hong Kong.
December 1997.--CDC provides HA genes of 1997 virus to Protein
Sciences for production of recombinant HA.
1997.--CDC's Influenza Branch initiates development of H5N1
reassortant viruses as candidate vaccines. Two groups, A and B, of
influenza A(H5N1) are differentiated using antigenic properties; this
observation proves important for selecting potential vaccine candidate
viruses (1998).
1997.--CDC develops and local planning guide, and funds four States
and one local health department to critique it. Over the next 4 years
14 s were funded to develop their own plans: CA, CT, FL, IN, KS, MD,
MN, NE, NH, NY, NM, NJ, SC, WA.
1998.--CDC begins an active collaboration and provides funding to
the Los Alamos National Laboratories (LANL) to develop and improve an
international influenza database. The Influenza Sequence Database
features a web interface and can be accessed at http://
www.flu.lanl.gov.
January 1998.--In order to detect the possible importation of
influenza A (H5N1) strains into the United States, CDC issues
recommendations to s public health officials to establish hospital
based surveillance for influenza A (H5N1). Specimens collected as part
of this effort are sent to NIH's Vaccine Test and Evaluation Unit for
viral isolation. No influenza A (H5N1) infections were identified.
1998.--CDC develops serology testing to screen for antiviral
resistance.
1998.--National Institute of Allergy and Infectious Disease (NIAID)
awards a contract to Protein Sciences Corporation (PI, John Treanor)
for the production of a recombinant H5 hemagglutinin vaccine. Within
three weeks, the company produces an investigational vaccine which is
tested in NIAID-supported clinical trials.
January 1998.--National Institute of Allergy and Infectious Disease
(NIAID) awards the ``Influenza Pandemic Preparedness in Asia'' contract
to St. Jude Children's Research Hospital (PI, Dr. Robert Webster) to:
--Establish an animal influenza surveillance center in Hong Kong.
--Determine the molecular basis of transmission of avian flu viruses.
--Provide characterized viruses suitable for vaccine development.
--Support training of new laboratory personnel in the areas of avian
influenza epidemiology and virus diagnostics.
--Produce reagents.
July 1998.--CDC broadcasts a satellite videoconference on State and
local pandemic preparedness.
August 1998.--National Institute of Allergy and Infectious Disease
(NIAID) supported scientists discover that human influenza A viruses
employ the enzyme plasmin to help chop hemagglutinin in two. The
discovery may explain what amplifies the disease-causing power of
influenza A virus and makes the virus uncommonly deadly.
August 1998.--CDC seeks to strengthen international laboratory
diagnostic capabilities, improve surveillance for influenza, and
increase networking among participating countries by offering an
international course on the diagnosis of influenza viruses in Panama
City, Panama.
1998.--CDC engages in collaborative efforts toward vaccine
development by working with scientists at Aviron to produce an
attenuated virus that is immunogenic and protects chickens and ferrets
from wild-type H5N1 virus challenge. CDC also provides influenza A
(H5N1) cDNA to Protein Sciences for the production of recombinant H5
hemagglutinin vaccine, and to Dr. Harriet Robinson at Yerkes Regional
Primate Center for the generation of candidate DNA vaccines.
December 1998.--National Institute of Allergy and Infectious
Disease (NIAID) awards a contract to Protein Sciences Corporation (PI,
John Treanor) for the production of a recombinant H5 hemagglutinin
vaccine. The company produces an investigational vaccine which is
tested in NIAID-supported clinical trials.
1998.--CDC develops a mouse model (mammalian model) to investigate
the pathogenesis and immunity to influenza A (H5N1) viruses. This model
is also found applicable for H9N2 viruses in 1999.
January 1999.--National Institute of Allergy and Infectious Disease
(NIAID) awards a grant to the University of Wisconsin (PI, Dr.
Yoshihiro Kawaoka) to investigate the molecular mechanisms of influenza
pandemics. NIAID-supported researchers for the first time succeed in
engineering an influenza A virus entirely from cloned genes, a
breakthrough that could lead to improved influenza vaccines and new
influenza-based gene delivery systems.
March 1999.--National Institutes of Allergy and Infectious Disease
(NIAID)-supported researchers at St. Jude Children's Research Hospital
and the University of Wisconsin demonstrate that a new DNA-based
vaccine protects mice from experimental challenge with the H5N1 virus.
April 1999.--CDC provides technical assistance to the Hong Kong
Department of Health and participates in a notable investigation of
influenza A (H9N2) in two humans in Hong Kong. Although the threat from
this outbreak was determined to be low, it illustrates the need to
rapidly assess and monitor novel influenza viruses in both poultry and
humans.
October 1999.--CDC delivers 2 courses on the diagnosis of influenza
viruses in Beijing, China. Fifty-seven participants from 50 Provincial
and Municipal Anti-Epidemic Stations throughout China, as well as the
Institute of Virology, participated in these courses.
1999.--CDC provides funding to more than 15 Epidemiology and
Laboratory Capacity (ELC) sites to improve their ability to culture and
subtype influenza viruses and facilitate their participation in the
sentinel physician surveillance system.
1999.--CDC develops primer sets for Polymerase Chain Reaction and
genetic sequencing for all NA and HA genes of all influenza subtypes.
These primers enable characterization of ``untypable'' influenza
viruses that are sent to the World Health Organization (WHO)
Collaborating Center for Reference and Research on Influenza.
1999.--CDC uses molecular techniques to evaluate human influenza A
H5N1 virus isolates from China and their relationship to circulating
virus in China's bird populations. Analysis indicates that the highly
pathogenic influenza A (H5N1) from the 1998 outbreak was a reassortant
of avian influenza viruses, and although quite pathogenic in humans, no
reassortment between avian and human genes had taken place.
1999.--CDC evaluates the immunogenicity in humans of the
recombinant Influenza A H5 HA vaccine produced by Protein Sciences
(John Treanor). The highest rate of response was 52 percent.
December 1999.--CDC participates in the global Neuraminidase
Inhibitors Susceptibility Network (NISN) which is established to
address public health and regulatory concerns regarding the potential
emergence, and consequences of drug resistance in influenza viruses
after licensure of NIs in several countries. The Network includes
representative from the World Health Organization (WHO), the four WHO
Collaborating Centers for Influenza, and scientists from academic and
public health institutions in regions of the world where increasing use
of these drugs is anticipated.
December 1999.--CDC produces supplemental reagents kits for the
detection of H9 avian influenza viruses for global distribution and
shares with international collaborators on an as needed basis.
2000.--CDC trains staff from the National Institute of Hygiene and
Epidemiology, Hanoi, Vietnam at CDC for 3 months in virology laboratory
techniques.
May 2000.--National Institute of Allergy and Infectious Disease
(NIAID)-supported researchers at St. Jude Children's Research Hospital
streamline the use of reverse genetics down to eight plasmids--one for
each gene in the virus genomes--making the process simpler and less
expensive.
June 2000.--National Institute of Allergy and Infectious Disease
(NIAID) establishes an interagency agreement with CDC and the Johns
Hopkins University School of Public Health to evaluate the safety,
infectivity, and immunogenicity of live attenuated influenza A virus
vaccine candidates for the prevention and control of pandemic influenza
A.
June 2000.--A course on the diagnosis and antigenic
characterization of influenza viruses is conducted in Buenos Aires,
Argentina with support from Pan American Health Organization (PAHO) and
in cooperation with the CDC. Seventeen participants from six South
American countries participate in the course.
July, 2000.--CDC broadcasts a second satellite videoconference on
State and local pandemic planning.
August 2000.--National Institute of Allergy and Infectious Disease
(NIAID)'s Vaccine and Treatment Evaluation Units (VTEUs) conduct a
clinical trial to compare the immune responses of healthy adults World
Health Organization receive either a full dose or a half dose of flu
vaccine.
September 2000.--National Institute of Allergy and Infectious
Disease (NIAID) awards three challenge grants to industry partners for
vaccine development:
--NIAID awards a grant to Aviron for the production of a live
attenuated vaccine for pandemic preparedness and to develop a
cell culture-based flu vaccine (PI, Dr. Shengqiant Li).
--NIAID awards a grant to Aventis Pasteur for the DNA-based
generation of avian influenza virus vaccines (PI, Fred Vogel).
The project goal is to use a DNA-based system to rapidly
produce influenza vaccine candidates, including those against
H5 and/or H7 pandemic influenza, which will be tested in
clinical trials by NIAID.
--NIAID awards a grant to Novavax (PI, Dr. Louis Potash) to produce
several non-egggrown influenza vaccines, with the goal being
that the most promising will be prepared for use in clinical
trials by NIAID.
September 2000.--CDC organizes in collaboration with the Council of
State and Territorial Epidemiologists (CSTE) a 2 day workshop for
States on pandemic preparedness planning which includes a tabletop
exercise and expert led discussions on key issues.
2000.--CDC awards funding to 22 State and local health departments
through the Epidemiology and Laboratory Capacity (ELC) and Emerging
Infections Programs (EIP). The funds were provided to (1) culture and
subtype influenza viruses, and (2) recruit and retain influenza
sentinel physicians.
2000.--CDC works closely with WORLD HEALTH ORGANIZATION, NVPO, NIH,
FDA, Council of State and Territorial Epidemiologists (CSTE) and other
groups to develop international, national, and State plans that are
necessary to prepare for the next influenza pandemic. Through CSTE,
CDC's Influenza Branch provides funding for a pandemic planning meeting
in Atlanta for the States. The meeting includes a tabletop exercise as
well as discussions on pandemic surveillance, priority groups for
vaccination, and the potential role for anti-virals.
2000.--CDC works with WORLD HEALTH ORGANIZATION and the Chinese
Ministry of Health (MOH) on a 5-year (2000-2004) plan of cooperation
between the World Health Organization Coordinating Center for Reference
and Research on Influenza (WHOCCRRI) at CDC, the WHOCCRRI at the
National Institute of Infectious Diseases in Tokyo, Japan, and the
Chinese MOH to strengthen influenza surveillance in China. Eight
provinces begin participating in the program in 2000, and 11 more
provinces join the program in 2001. The establishment of active
surveillance sites in China provides an opportunity to document the
early appearance of influenza shift and drift variants, and immediate
isolation of these strains in China's laboratories may provide virus
candidates suitable for vaccine production.
2000.--CDC's Influenza Laboratory develops a supplemental kit for
the identification of avian influenza A (H6N1). It is known that
viruses of this type circulate widely in China and the possibility of
their transmission into the human population cannot be excluded.
2001.--CDC establishes a research collaboration on avian influenza
with the National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
to better understand the human animal interface.
Ongoing since 2001.--CDC pathotypes a wide range of avian H5N1
viruses, to better understand potential to cause disease in humans.
March 2001.--CDC and NVPO organize a 2-day pandemic preparedness
planning meeting of national experts to identify possibly ways to use
antiviral agents during a pandemic.
May 2001.--CDC produces a reverse genetics PR8 based reassortant
H5N1 vaccine against A/HK/491/97 (HA) and A/HK/486/97 (NA).
May 2001.--St. Jude scientists and University of Hong Kong (HKU)
collaborators detect the reemergence of H5N1 in live bird markets in
Hong Kong. More than one million birds are culled and ``market rest
day'' is instituted. Researchers also identify quail as the mixing
vessel for the spread of avian influenza viruses from aquatic birds to
land-based poultry. Live quail is banned from live-bird markets the
following year.
May 2001.--CDC provides financial and technical support to World
Health Organization (WHO) to conduct an assessment of 111 National
Influenza Centers that form the backbone of the WHO influenza
surveillance system.Analysis from this assessment helps WHO identify
critical gaps and helps the WHO corrdinating Centers in Australia,
Japan, the UK and U.S. target scarce resources to provide future
support for training and technical assistance to countries with
specific needs.
June 2001.--Funding is made available through the Association of
Public Health Laboratories to CDC to train personnel from State
veterinary labs in recognition of the need to increase the interface
between the veterinary and human sides of influenza research.
July 2001.--National Institute of Allergy and Infectious Disease
(NIAID) sponsors the Reverse Genetics Workshop, bringing together an
international group of researchers in influenza viruses as well as
scientists outside of the influenza field with research experience in
other human viruses, biosafety, and public policy. The Workshop
discussions are centered on using local biosafety committees to examine
the research work that will be done at federally funded universities
and to make risk assessments and safety recommendations.
September 2001.--National Institute of Allergy and Infectious
Disease (NIAID)-funded investigators at the University of Wisconsin use
reverse genetics to discover that the PB2 gene is key to the virulence
of the H5N1 influenza strain. This discovery provides important
information that may be useful in understanding the emergence of future
viruses that may have pandemic potential.
October 2001.--CDC produces H9N2 inactivated whole virus pandemic
vaccine candidate to A/ck/HK/G9/99 using conventional reassortant
techniques.
October-December 2001.--CDC describes an ISCOMs-based parenteral
vaccine strategy and a mucosal (intranasal) vaccine strategy that
induces strong cross-subtype immunity and protects animals from
sublethal H9N2 viruses and/or lethal avian H5N1 viruses.
October 2001-2003.--CDC supports a pandemic communications fellow
to assist States with assessing and updating their State pandemic
plans.
2001.--CDC's Influenza Branch joins the World Health Organization
Animal Influenza Network (AIN) in recognition of the importance of a
strong interface between human and animal surveillance systems to
improve pandemic preparedness. CDC provides course material and
technical expertise for a laboratory training course in Harbin, China
for Chinese laboratorians involved in animal influenza surveillance.
2001.--CDC's Influenza Branch works with National Vaccine Program
Office and several agencies to draft successive versions of the
national pandemic preparedness plan. The ``Pandemic Influenza Action
Plan'' was approved by the Assistant Secretary for Health in 2001.
2001-2002.--CDC conducts a study in collaboration with Dr. Doan
Nguyen of the National Institute for Hygiene and Epidemiology in
Vietnam on the prevalence of avian influenza viruses circulating among
domestic poultry in Asia and the risk of avian influenza infection
among poultry workers.
January 2002.--National Institute of Allergy and Infectious Disease
(NIAID) awards a grant to the American Registry of Pathology for the
complete characterization of the 1918 influenza virus (PI, Dr. Jeffrey
Taubenberger).
February 2002.--CDC produces an Ann Arbor, cold-adapted, live,
pandemic vaccine candidate to H9N2 using A/ck/HK/G9/99.
March 2002.--CDC reports findings of cohort studies in Hong Kong
poultry workers that suggested an increased risk for avian influenza
infection from occupational exposure.
May 2002.--CDC organizes another national pandemic planning
workshop in Atlanta to help States move further along with their
pandemic preparedness plans. Over 200 people from the States attend.
May 2002.--CDC published first report on the ferret as a model for
avian H5N1 virus pathogenesis studies in mammals. The ferret is now
recognized by many in the field to be the model of choice for
pathogenesis studies and safety testing of candidate vaccines strains
derived from highly pathogenic avian viruses.
June 2002.--St. Jude scientists and Hong Kong University
collaborators detect the second reemergence of highly pathogenic H5N1.
More than 20 farms are found to be infected and more than seven
different H5N1 genotypes are identified in wild aquatic birds.
June 2002.--CDC produces a whole virus H5N2 vaccine candidate with
A/Pheasant/NJ/96 using conventional reassortant techniques.
August 2002.--St. Jude scientists determine that the H5N1 avian
virus that killed six people in 1997 can bypass natural host defenses,
which may explain the high lethality of avian strains.
August 2002.--CDC scientists, in collaboration with FDA, reported
further studies on generation of cross-subtype immunity based on DNA
vaccination using conserved influenza A virus genes.
September 2002.--CDC and National Vaccine Program Office publish an
update on pandemic planning in Clinical Infectious Diseases.
October 2002.--CDC participates on a World Health Organization
mission to conduct site assessments for six sites in China to assess
gaps and needs in influenza surveillance and make recommendations.
November 2002.--CDC provides funding to the World Health
Organization in Manila (Western Pacific Regional Office) supported a
National Meeting and Expert Consultation for development of influenza
vaccine policy and a mid-term assessment of the comprehensive 5-year
plan for influenza. Two CDC staff participated.
November 2002.--CDC's Influenza Branch increases knowledge and
implementation of influenza disease surveillance to keep pace with
recent expansions in viral surveillance by hosting a 5-day CDC/World
Health Organization (WHO) influenza epidemiology and surveillance
training course in Atlanta. Twenty public health epidemiologists from
Asia, the Former Soviet Union, and Latin America were trained by
instructors from The Netherlands, the United Kingdom, Japan, and WHO.
2002.--CDC Influenza Branch works with national and international
colleagues to develop guidelines for the appropriate safety testing of
candidate vaccine strains against H5N1 influenza, particularly those
derived by reverse genetics, in a ferret animal model developed at CDC.
December 2002.--National Institute of Allergy and Infectious
Disease (NIAID) expands its intramural program to develop live
attenuated vaccines for pandemic influenza.
January 2003.--A medical epidemiologist from CDC goes to Hong Kong
to help investigate two human cases of avian H5 influenza. The outbreak
occurred in a setting of widespread reports of respiratory disease with
deaths in various parts of mainland China. It becomes clear that the
etiology and respiratory disease was not influenza and SARS CoV was
subsequently identified.
February 2003.--Using CDC laboratory testing procedures, a new
highly pathogenic H5N1 avian influenza virus isolate from a human is
compared to previous human and avian isolates and is determined to be
antigenically distinguishable from currently and previously circulating
H5N1 viruses in Asia, including the viruses previously isolated from
humans, which has important implications for H5N1 vaccine development.
2003.--A CDC publishes a modeling study in the Journal of the
American Medical Association that more accurately predicts influenza
morbidity and mortality using national virus surveillance data in its
estimates. An influenza modeling group, with personnel from within and
outside of CDC is established to formally proceed with further
mathematical modeling of influenza'a impact.
2003.--CDC generates multiple vaccine strains against avian H5N1,
H9N2, H7N7, and evaluates preclinical immunogenicity and protective
efficacy.
2003.--A CDC performs and publishes a study assessing State
pandemic preparedness in the Emerging Infectious Disease Journal. (EID
2003;12:1645-8)
February 2003.--HHS requests $100 million in fiscal year 2004 for
advanced development of pandemic influenza vaccines.
February 2003.--CDC deploys staff to Beijing, China to investigate
severe respiratory illnesses in Guangdong province following confirmed
H5 cases in Hong Kong.
2003.--In response to the SARS epidemic and two human cases of
avian influenza A (H5N1) in Hong Kong, CDC designs and tests primers
and probes for the rapid detection of influenza viruses in original
clinical materials isolated from patients with severe clinical
symptoms. This diagnostic format is compatible with real-time PCR
methods used for detection of SARS and other acute respiratory
infections and facilitates testing respiratory samples for multiple
agents.
2003.--CDC's Influenza Branch develops and conducts training for a
joint World Health Organization/CDC sponsored laboratory training
course in Atlanta for scientists from the former Soviet Union.
2003.--CDC collaborates with staff from Emory University to model
the best use of antiviral agents in a pandemic situation.
March 2003.--The World Health Organization and Chinese Ministry of
Health request CDC's help to train Chinese virologists in laboratory
methods for the urgent detection of avian influenza infections in
humans. Two CDC scientists travel to Beijing, China to train students
from the Chinese National Influenza Center and virologists from several
provinces in South China on microneutralization assays for the
diagnosis of H5 in human sera.
March 2003.--CDC produces and distributes supplemental H5N1
reagents kits for the identification of the new H5 viruses that have
surfaced in Asia.
May 2003.--CDC conducts an influenza laboratory course organized by
World Health Organization/CDC for Eastern European countries. Sixteen
participant from 12 European countries participated in the course in
Atlanta.
May 2003.--CDC produces supplemental reagents kits for influenza H7
viruses that can be distributed nationally and internationally as
needed.
June 2003.--St. Jude scientists and Hong Kong University
collaborators discover that H9N2 viruses are endemic in land-based
birds in China. It is also discovered that gene segments of H9N2 flu
viruses found in ducks had undergone many changes, with some new
combinations coding for antigens that could infect humans.
June 2003.--CDC establishes a ferret model to evaluate the biologic
and molecular basis of influenza virus transmission. CDC initiates
studies to compare avian-human reassortant viruses for their ability to
undergo airborne transmission.
June 2003.--FDA licenses FluMist, the scientific basis of which is
rooted in the work of National Institute of Allergy and Infectious
Disease (NIAID) intramural scientists from 1975-1995. Production of
FluMist leads to the establishment of infrastructure for the commercial
manufacture of live attenuated vaccines, including vaccines against
pandemic influenza.
August 2003.--National Institute of Allergy and Infectious Disease
(NIAID) expands its Pandemic Preparedness in Asia contract. This
expansion supports enhanced animal influenza surveillance sites in
Asia, the generation of high-yielding pandemic vaccine candidates, and
studies of a newly emerging influenza strain infecting swine in the
United States.
August/October 2003.--FDA prepares H5N1 antiserum (BEVS-derived A/
HONG KONG/213/2003) to be used for surveillance and vaccine potency
measurements.
August/September 2003.--CDC deploys laboratorians and
epidemiologists to Vietnam to assist the National Institute of
Veterinary Research, the National Center for Veterinary Diagnosis and
the National Institute of Hygiene and Epidemiology in Hanoi with one-
on-one laboratory and epidemiological training for H5N1.
September 2003.--CDC provides funding to the Western Pacific
Regional Office of World Health Organization (WHO) to directly support
the National Influenza Center in Beijing, China and 23 provincial
surveillance sites for reagents, personnel, and supplies. China sends
160 isolates to the Collaborating Center at CDC in fiscal year 2003.
September 2003.--National Institute of Allergy and Infectious
Disease convenes an international workshop on the Development of a
Clinical Trial Plan for Pandemic Influenza Vaccines to:
--Review data from earlier trials of pandemic influenza vaccines.
--Identify manufacturing and regulatory hurdles.
--Prioritize pandemic influenza virus subtypes.
--Develop an agenda for the conduct of clinical trials.
--Initiate development of a U.S. Pandemic Influenza Vaccine Protocol.
September 2003.--National Institute of Allergy and Infectious
Disease (NIAID) awards a grant to Stanford University (PI, Dr. Ann
Arvin) to study vaccine-induced and naturally acquired influenza A
immunity as a model for in-depth analysis of the innate and adaptive
immune response in children and adults.
September 2003.--National Institute of Allergy and Infectious
Disease (NIAID) awards a grant to the University of Maryland to
understand the transmissibility of influenza A viruses (PI, Dr. Daniel
Perez). The project's objective is to study the interspecies
transmission of avian influenza viruses.
August/September 2003.--National Institute of Allergy and
Infectious Disease (NIAID) awards three grants to industry partners for
influenza product development:
--NIAID awards a grant to the Massachusetts Institute of Technology
to investigate RNA interference of influenza virus infection
(PI, Jianzhu Chen) as a new way of preventing and treating
influenza infection.
--NIAID awards a grant to Dynavax Technologies Corp. (PI, Gary Van
Nest), to find a relatively stable component for use in a new
kind of more broadly protective influenza vaccine. The vaccine
candidate combines an internal flu protein that is less likely
to be altered through mutation, NP, with a bioengineered
molecule called an immunostimulatory DNA sequence.
--NIAID awards a grant to the University of Colorado at Boulder for
the development of a diagnostic microarray for influenza A (PI,
Kathy Rowlen), which may serve as a rapid diagnostic. The
project's goal is to develop the ``Flu Chip,'' that will
provide information as to whether or not an individual is
infected with influenza as well as provide both type and
antigenic sub-type characterization of the virus.
October 2003.--National Institute of Allergy and Infectious Disease
(NIAID)-supported researchers at the Vaccine and Treatment Evaluation
Units at the University of Rochester and Baylor College of Medicine
test an experimental vaccine to protect people against an H9N2 bird
influenza. Clinical trials are completed and results are expected in
early 2005.
October 2003.--National Institute of Allergy and Infectious Disease
(NIAID) conducts a Phase II study to evaluate the first trivalent
baculovirus-based recombinant influenza virus vaccine. The vaccine,
produced by Protein Sciences, was evaluated in healthy elderly subjects
and was shown to be safe and well tolerated. The vaccine may also
provide a suitable cell culture system for the large-scale production
of influenza virus vaccines as a viable alternative to the production
of the vaccines in eggs.
October 2003.--National Institute of Allergy and Infectious Disease
(NIAID) and CDC intramural scientists demonstrate that a live
attenuated vaccine against H9N2 is effective in mice.
October 2003.--CDC provides funding to Los Alamos National
Laboratories to establish an H5N1 sequence compartment for
international collaborators working on the sequencing of influenza
AH5N1 viruses.
December 2003/January 2004.--HHS/OS awards contract to AmeriSource/
McKesson for $10.6 million to acquire 238,000 treatment courses of
Tamiflu antiviral drug (tablet & suspension) using SNS funds.
2004.--National Institute of Allergy and Infectious Disease (NIAID)
supports animal influenza training courses in Hong Kong and Japan
(ongoing).
January 2004.--National Institute of Allergy and Infectious Disease
(NIAID) awards a grant to the Wadsworth Center entitled ``Discovery of
a Novel Promoter in Pathogenic Influenza'' (PI, David Wentworth) to
further understand the molecular mechanisms of pathogenesis in avian
influenza viruses.
January 2004.--Fiscal year 2004 appropriations of $50 million are
approved for HHS advanced development of pandemic influenza vaccines.
January/April/August 2004.--HHS contract awarded to Roche for $74
million to acquire 2.1 million treatment courses of Tamiflu antiviral
drug (tablet & suspension) using Strategic National Stockpile funds.
February 2004.--HHS requests $100 million in fiscal year 2005 for
advanced development of pandemic influenza vaccines.
January/February 2004.--CDC sends multiple staff including
epidemiologists and laboratorians to participate on the World Health
Organization outbreak investigation team for H5N1.
Ongoing since January 2004.--CDC performs serological studies to
determine extent of human infection with avian H5N1 viruses in Asia.
This has involved the testing of over 1,000 sera from cases, household
contacts of cases, health care workers and poultry and veterinary
workers from Vietnam, Thailand, South Korea, Indonesia, Cambodia and
Taiwan. In addition, individuals from Vietnam, Thailand, South Korea,
Singapore, Pakistan, have received extensive training in serological
methods so that they can establish serologic procedures to detect avian
influenza virus infection of humans in countries of origin.
February 2004.--CDC participates at Food and Agriculture
Organization meetings regarding avian influenza prevention and control
in Bangkok and Rome.
February 2004.--CDC plans a regional diagnostic Lab training in
collaboration with World Health Organization and the International
Emerging Infections Program for approximately 10 countries in Asia for
identification of H5 by laboratory diagnosis was held in Bangkok,
Thailand.
February 2004.--HHS issues Request for Proprosals (RFPs) for a
secure, year-round egg supply to the domestic influenza vaccine
manufacturers and cell based influenza vaccines.
February 2004.--National Institute of Allergy and Infectious
Disease (NIAID) awards a grant to St. Jude Children's Research Hospital
to study combination chemotherapy for pandemic influenza (PI, Robert
Webster) and test the hypothesis that combination therapy with two
classes of anti-influenza drugs offers clinical and strategic
advantages in the event of an influenza pandemic.
March 2004.--CDC plans and leads a laboratory and epidemiology
training for 31 provinces in China to train them on laboratory
identification of H5N1 in Beijing, China.
March 2004.--CDC provides several experts to participate in a
consultation on Influenza Pandemic Preparedness to look at
interventions before, during and after a pandemic, and to develop
surveillance and other guidelines.
March/April 2004: FDA prepares H9N2 antiserum (BEVS-derived A/
CHICK/HONG KONG/G9/2004) to be used for surveillance and vaccine
potency measurements.
April 2004.--CDC produces pandemic vaccine candidate for H5N1 using
A/VN/1203/04 using reverse genetics and PR8 backbone. This candidate is
produced under Good Laboratory Practice (GLP) conditions and is
suitable for human use.
April 2004-June 2005.--CDC supports another pandemic communications
fellow to assist States with assessing and updating their State
pandemic plans.
April 2004.--CDC conducts vaccine safety testing on SJCRH H5N1
vaccine candidate currently undergoing clinical evaluation.
April 2004.--CDC plans and sets up an emergency training for
laboratorians from North and South Vietnam. This week long training,
conducted in Hanoi, was to train in the laboratory diagnosis of H5N1.
April 2004.--CDC organizes and conducts a laboratory training
``Modern Methods for Influenza Detection and Typing'' for 16 students
from 16 States at the Georgia State Public Health Lab. This is the
first of three scheduled courses to cover all States on how to do the
Reverse Transcription-Polymerase Chain Reaction method for influenza
viruses including H5. This was planned and conducted in conjunction
with the Association of Public Health Laboratories (APHL).
April 2004.--CDC produces additional supplemental diagnostic kits
to update the H5N1 reagents so that they can identify the viruses as
they have changed and distributes nationally and internationally as
needed.
April 2004/May 2004.--FDA prepares H5N1 antiserum BEVS-derived A/
VIETNAM/1203/2004 H5N1 to be used for surveillance and vaccine potency
measurements.
May 2004.--CDC participates in planning and conducting a one week
training in Tokyo, Japan for approximately 12 countries in the Region
on epidemiological surveillance for H5N1 viruses.
May 2004.--FDA prepares and calibrates the H9N2 virus reference
antigen for pilot investigational lots of vaccine to A/CHICK/HONG KONG/
G9/2004 H9N2 for vaccine potency measurements.
May 2004.--FDA distributes of bulk antiserum to A/CHICK/HONG KONG/
G9/2004 H9N2 vaccine manufactured by Chiron for vaccine potency
measurements.
May 2004.--National Institute of Allergy and Infectious Disease
(NIAID) awards contracts to Aventis Pasteur and Chiron Corporation to
support the production of an investigational vaccine based on a strain
of H5N1 avian influenza. The vaccines will be tested for safety and
immunogenicity in Phase I and Phase II clinical trials conducted by
NIAID's Vaccine and Treatment Evaluation Units (VTEUs). Studies will
test the vaccine in healthy adults first with subsequent studies
planned in children and the elderly.
May 2004.--National Institute of Allergy and Infectious Disease
(NIAID) awards a grant to Innoject, Inc. (PI, Richard Gillespie) for
the development of an auto-injector vaccine delivery system. Not only
could the device be easy to use, but it could be broadly distributed in
the event of an influenza pandemic. The clinical trial of the new
delivery system, led by Dr. William Barr of Virginia Commonwealth
University, will be conducted during the 2005-2006 flu season.
May 2004.--CDC provides additional support to the International
Emerging Infections Program in Bangkok to enable comprehensive
influenza pneumonia surveillance in 2 provinces covering more than 1.1
million people and to enhance technical assistance in the region with
support to conduct training in collaboration with CDC and World Health
Organization.
June 2004.--CDC reports on isolation of highly pathogenic avian
H5N1 viruses from healthy birds in Vietnam live bird markets in late
2001. This was the first documentation of spread of H5N1 outside of PRC
and Hong Kong SAR prior to Asia-wide outbreaks in late 2003-2004.
June 2004.--CDC issues a Cooperative Agreement with World Health
Organization (WHO) Headquarters to support the revision of WHO National
Pandemic Planning Guidelines, revision of the WHO Laboratory Manual for
National Influenza Centers and establishment of a contract for shipping
funds with 57 eligible countries to prevent barriers to specimen
sharing for influenza.
July 2004.--CDC, in collaboration with Western Pacific Regional
Office of the World Health Organization and China, conducts site
assessments for approximately 6 provinces in China to assess current
status of influenza surveillance.
July 2004.--National Institute of Allergy and Infectious Disease
(NIAID) awards a grant to the Mount Sinai School of Medicine of NYU
(PI, Adolfo Garcia-Sastre) for the molecular and biological
characterization of the ``Spanish Flu'' to examine the reason behind
the high lethality of the 1918 influenza pandemic.
July 2004.--National Institute of Allergy and Infectious Disease
(NIAID) awards a grant to Washington University for the M2 Peptide
Based Vaccines Against Influenza project (PI, Andrew Pekosz). The
project's goal is to generate an influenza vaccine with activity
against a variety of virus strains using the M2 protein.
July 2004.--HHS issues Request for Proposals for the manufacturing
of H5N1 vaccine at commercial scale using licensed process.
July/August 2004.--FDA distributes bulk antiserum to A/VIETNAM/
1203/2004 H5N1 vaccine manufactured by sanofi pasteur for surveillance
at CDC and NIBSC and vaccine potency measurements at sanofi pasteur.
July/August 2004.--CDC receives sera and performs major serological
analysis of immunogenicity of H9N2 vaccine (National Institute of
Allergy and Infectious Disease supported) in clinical trial.
August 2004.--CDC delivers complete safety profile of PR-8H5N1
reassortant seed virus to USDA for exclusion from Select Agent Program
to enable sharing of seed virus with vaccine manufacturers.
August 2004.--HHS/OS awards contract to sanofi pasteur for $12
million to manufacture 0.33 million doses of H5N1 bulk vaccine (90 g
HA/dose) with Strategic National Stockpile funds and $0.96 million for
storage with stability study.
August 2004.--National Institute of Allergy and Infectious Disease
(NIAID) issues a task order to Chiron Corporation for the production of
an investigational H9N2 vaccine. Chiron will produce up to 40,000 doses
of vaccine with and without the MF59 adjuvant for clinical trials that
will be conducted by NIAID, slated for 2005.
September 2004.--HHS/OS awards contract to sanofi pasteur for $10.1
million to provide secure year round egg supply for influenza vaccine
production and clinical lot manufacturing of prepandemic influenza
vaccines for clinical evaluation in the base year.
September 2004.--CDC establishes an international study involving
>16 laboratories to evaluate and standardize the neutralization assay
for the serological detection of antibody to influenza viruses,
especially those with pandemic potential.
September 2004.--FDA prepares and calibrates the virus reference
antigen from pilot investigational lots of A/VIETNAM/1203/2004 H5N1
vaccine manufactured by sanofi pasteur for potency measurements of H5N1
vaccine .
September 2004.--National Institute of Allergy and Infectious
Disease (NIAID) awards challenge grants to six industry partners to
develop new diagnostics, therapeutics, and vaccines against influenza
virus:
--Shire Biologics, Inc., for the development of a tissue culture-
derived influenza vaccine (PI, Jonathan Seals).
--Delsite Biotechnologies, Inc., for the development of an
inactivated intranasal influenza vaccine (PI, Yawei Ni).
--Biota Scientific Management, for the development of a novel long-
acting influenza antiviral drug (neuraminidase inhibitor) (PI,
Jane Ryan).
--Columbia University/Griffin Analytical Technologies for the
development of new diagnostics (PI, Walter Lipkin) to
discriminate between several pathogens including influenza and
SARS.
--University of Texas at Austin/Radix BioSolutions for the
development of new diagnostics (PI, Steven Kornguth) to
discriminate between several pathogens including influenza and
SARS.
--BD Diagnostics (PI, Tobin Hellyer), for the development of new
diagnostics to discriminate between several pathogens,
including influenza and SARS.
September 2004.--National Institute of Allergy and Infectious
Disease (NIAID) awards a grant to Nexbio, Inc., to develop novel
therapeutics for pandemic and epidemic flu (PI, Fang Fang). This novel
class of fusion proteins may be capable of blocking infections by all
strains of influenza viruses.
September 2004.--CDC supports Cooperative Agreement with the
Western Pacific Regional Office (WPRO) Manila to conduct laboratory
assessments in Mongolia, Laos, Cambodia, Kazakhstan, Myanmar, and
Vietnam.
September 2004.--CDC details staff to World Health Organization
(WHO) in Geneva to work on enhancing collaboration between the animal
and human health authorities, particularly Food and Agricultural
Organization, World Organization for Animal Health (OIE), and WHO.
September 2004.--CDC awards bilateral agreements to 9 countries
(China, India, Indonesia, Malaysia, Mongolia, Pakistan, Philippines,
South Korea and Thailand) to address influenza surveillance
infrastructure and enhance influenza surveillance networks. These
grants enable training, technical assistance and funding for
infrastructure to fill surveillance gaps.
September 2004.--CDC provides funding to Western Pacific Regional
Office/World Health Organization in order to provide direct support to
the National Influenza Center in Beijing, China and 31 provincial
surveillance sites (expanded from 23 sites last year) for reagents,
personnel and supplies.
September 2004-September 2005.--CDC develops 11 supplements to
assist State and local governments in pandemic planning, such as
clinical care guidelines, surveillance guidelines, laboratory diagnosis
etc. These 11 supplements became part II of the overall DHHS pandemic
influenza plan.
October 2004.--CDC organizes and conducts a laboratory training
``Modern Methods for Influenza Detection and Typing'' for an additional
16 students from 16 States at the Georgia State Public Health Lab. This
is the second of three scheduled courses to cover all States on to do
the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method for
influenza viruses including H5. This was planned and conducted in
conjunction with the Association of Public Health Laboratories (APHL).
November 2004.--CDC plans and conducts a regional State pandemic
planning workshop in Atlanta for States in the Southeast. Immunization
coordinators, epidemiologists, laboratorians, and emergency management
coordinators participate.
November 2004.--CDC and the International Emerging Infection
Program (IEIP) organizes, in collaboration with the Western Pacific
Regional Office (WPRO), emergency training on neutralization assays for
serologic diagnosis of H5. Seven people attended from Thailand,
Vietnam, and Malaysia.
November 2004.--CDC, in collaboration with Western Pacific Regional
Office (WPRO), World Health Organization HQ, and other international
experts, organizes and conducts a pandemic tabletop exercise with the
Chinese Ministry of Health and CDC and provided feedback on the draft
pandemic plan presented.
November 2004.--CDC participates on a consultation on renewal of
China's next 5 year plan for influenza surveillance, prevention, and
control.
November 2004.--National Institute of Allergy and Infectious
Disease (NIAID) launches the Influenza Genome Sequencing Project that
will put influenza sequence data rapidly in hands of scientists,
enabling them to further study how influenza flu viruses evolve,
spread, and cause disease and may ultimately lead to improved methods
of detection, treatment, and prevention. This project is a
collaborative effort among NIAID, National Center for Biotechnology
Information/National Library of Medicine, CDC, St. Jude Children's
Research Hospital and others.
November 2004.--National Institute of Allergy and Infectious
Disease rapidly initiates a Phase III trial to evaluate the safety and
immunogenicity of GlaxoSmithKline's Fluarix vaccine in healthy adults
aged 18-64 years. The objective of the study is to generate data to
support possible licensure of Fluarix vaccine in United States for the
2005-2006 influenza season. FDA approved the vaccine for adults aged 18
years and older in August 2005.
December 2004.--Fiscal year 2005 appropriations of $99 million are
approved for HHS advanced development of pandemic influenza vaccines.
December 2004.--National Institute of Allergy and Infectious
Disease (NIAID) issues a notice to the NIH Guide highlighting its
interest in receiving grant applications focused on influenza research.
December 2004: National Institute of Allergy and Infectious Disease
(NIAID)'s Vaccine Research Center (VRC) begin conducting proof-of-
concept studies for the development of genebased vaccines. If these are
successful, VRC will expand and accelerate development of genebased and
recombinant vaccines. Synthetic DNAs for multiple constructs are
currently in preparation. Current Good Manufacturing Practices (cGMP)
manufacture of an H5N1 pandemic flu vaccine construct for human
clinical testing is expected to begin in fall of 2005. cGMP manufacture
of vaccine constructs for human clinical testing for endemic
circulating influenza strains is expected to begin in 2006.
January 2005.--CDC posts State pandemic planning tabletop exercises
on the website that was developed over the previous several months so
that States can test their plans using several different scenarios.
Helpful education materials about tabletop planning exercises are also
developed.
January 2005.--National Institute of Allergy and Infectious Disease
(NIAID) expands its Pandemic Preparedness in Asia contract to include
surveillance activities in Vietnam, Thailand, and Indonesia.
February 2005.--CDC plans and conducts in collaboration with
Council of State and Territorial Epidemiologists (CSTE) a regional
State pandemic planning workshop for States in the midWest in Denver,
CO. Immunization coordinators, epidemiologists, laboratorians, and
emergency management coordinators participate.
February 2005.--HHS requests $120 M in fiscal year 2006 for
advanced development of pandemic influenza vaccines.
February/March 2005.--CDC conducts an in-depth one-on-one training
at the National Institute of Hygiene and Epidemiology in Vietnam for
Polymerase Chain Reaction techniques and databases.
March 2005.--National Institute of Allergy and Infectious Disease
(NIAID) conducts a Phase I trial of investigational inactivated H9N2
vaccine formulated with and without MF59 adjuvant. Results are expected
in early 2006.
March 2005-July 2005.--National Institute of Allergy and Infectious
Disease (NIAID) begins recruitment for a clinical trial to investigate
the safety of an H5N1 avian influenza vaccine produced by sanofi
pasteur (formerly Aventis Pasteur). Clinical sites, part of the NIAID
VTEU network, will test the vaccine's safety and ability to generate an
immune response in 450 healthy adults. A preliminary review of data
from a subset of the study subjects shows that the vaccine is safe and
that stronger doses of the vaccine result in higher immune responses.
Full data analysis for this clinical trial should be available by the
end of 2005.
April 2005.--CDC supports and participates in an emergency
international World Health Organization consultation in Hanoi to go
over latest epidemiological data and assess pandemic risk level.
April 2005.--CDC plans and conducts in collaboration with Council
of State and Territorial Epidemiologists a regional State pandemic
planning workshop in Chicago, IL for States in the North. Immunization
coordinators, epidemiologists, laboratorians, and emergency management
coordinators participate.
April 2005.--CDC awards bilateral funding support to Vietnam for
the enhancement and development of in-country influenza surveillance
networks.
April 2005.--CDC organizes and conducts Laboratory Training: Modern
Methods for Influenza Detection and Typing for remaining States at the
Georgia State Public Health Lab. This is the third of three courses
conducted and will complete the training for the 48 States wishing to
be trained on Reverse Transcription-Polymerase Chain Reaction (RT-PCR)
methods for influenza viruses including H5. This was planned in
conjunction with the Association of Public Health Laboratories (APHL).
April 2005.--CDC conducts a session in Kuala Lampur entitled Human
Influenza Surveillance and Control, which included a special half day
session for recipients of CDC bilateral agreement funding. This is
planned in conjunction with WPRO and SEARO and included 2-3
participants each from Malaysia, Philippines, New Caledonia, Laos,
Vietnam, Indonesia, Thailand, Pakistan, South Korea, China, Brunei,
Mongolia, as well as additional participants from WORLD HEALTH
ORGANIZATION and Malaysia.
April 2005.--HHS awards contract to sanofi pasteur for $97.1
million to facilitate the advanced development of cell-based influenza
vaccine towards U.S. licensure in domestic manufacturing facilities.
April 2005.--HHS issues Requests for Proposals for funding more
contracts to facilitate the advanced development of cell-based
influenza vaccine towards U.S. licensure in domestic manufacturing
facilities to expand and diversify the domestic pandemic vaccine surge
capacity.
April 2005.--HHS establishes the first secure year round egg supply
for influenza vaccine manufacturing in a contract with sanofi pasteur;
these eggs can be made available for off-season production of H5N1
vaccine.
April 2005.--National Institute of Allergy and Infectious Disease
(NIAID) makes multiple awards examining new influenza vaccine
technologies. For example, NIAID awarded the following challenge grants
in 2005: Rapid Acting Vaccine for Pandemic Influenza (Corixa
Corporations), Alphavirus Replicon Vaccines against Influenza (Alphavax
Human Vaccines, Inc.), ReplicationDefective Adenovirus-Vectored
Pandemic Influenza (Vaxin, Inc.), and Biodefense Vaccine for Pandemic
Influenza (Vical, Inc.).
April 2005.--National Institute of Allergy and Infectious Disease
(NIAID) begins supporting animal studies to evaluate the efficacy of
Peramivir against seasonal influenza. Additional studies are planned.
April 2005.--CDC provides consultation and site visits with
Malaysian Ministry of Health and Philippines Ministry of Health to
review their national surveillance system and provide on-site technical
assistance.
April/May 2005.--CDC conducts on site training/consultation in
Atlanta for the Director of the National Influenza Center from China.
May 2005.--CDC plans and conducts in collaboration with Council
State and Territorial Epidemiologists a regional State pandemic
planning workshop in Boston for States in the Northeast. Immunization
coordinators, epidemiologists, laboratorians and emergency management
coordinators participate.
May 2005.--CDC conducts vaccine safety testing on the CDC H5N1
vaccine candidate.
May 2005.--CDC establishes an interagency agreement with the Navy
Medical Research Unit (NAMRU2) in Jakarta to strengthen influenza
surveillance in Indonesia and provide regional technical assistance for
seasonal and avian influenza.
May 2005.--CDC organizes a training course entitled ``Epidemiology
and Surveillance of Influenza and Respiratory Diseases'' and held in
Atlanta, Georgia. 20 participants from 10 countries of the Andean and
Central America Regions participated in this training which was planned
in conjunction with Pan American Health Organization.
May 2005.--CDC participates as faculty on World Health Organization
(WHO)-sponsored Training Course on Laboratory Diagnosis and
Surveillance of Influenza at the Health Protection Agency, Colindale
and the National Institute for Medical Research, Mill Hill in London.
Fifteen trainees from Middle Eastern and North African countries,
selected by WHO and the Eastern Mediterranean Office, are trained in
laboratory diagnostics for influenza.
May 2005.--CDC conducts laboratory training course for influenza
and other respiratory viruses including SARS and Metapneumovirus. One
participant from each of Mexico, Panama, Colombia, Brasil, Chile, CAREC
and Argentina participated in this training planned in collaboration
with PAHO. Diagnosis of avian influenza viruses, including H5N1, was
part of the instruction.
May 2005.--CDC supports an interagency agreement with Department of
Defense NAMRU-3 in Cairo to support technical assistance and training
in Oman, Syria, Kingdom of Saudi Arabia, Kyrgyzstan, Ukraine, Georgia,
Kazakhstan, Egypt, Kenya, and Pakistan to support humananimal interface
studies.
May 2005.--CDC provides support for Western Pacific Regional Office
(WPRO)/World Health Organization (WHO) to conduct in depth country
assessments in Cambodia, Laos and Mongolia. Develped equipment needs
list and supported procurement of equipment for these countries through
WPRO.
May 2005.--CDC supports and participates in an emergency
international consultation in Manila and produced the Manila report for
the current status of pandemic risk assessment. Consultation included
experts from all countries with human H5 infections.
May 2005.--National Institute of Allergy and Infectious Disease
(NIAID) subcontracts with Baxter for the production of whole virus,
Vero cell-derived H5N1 vaccine formulated both with and without alum as
an adjuvant.
May 2005.--FDA prepares and calibrates the virus reference antigen
from commercial scale lots of A/VIETNAM/1203/2004 H5N1 vaccine
manufactured by sanofi pasteur for potency measurements of H5N1
vaccine.
May 2005.--CDC details staff to Western Pacific Regional Office of
World Health Organization in Manila to provide regional technical
assistance for avian influenza, pandemic preparedness, and vaccine
policy.
June 2005.--CDC supports and participates in an emergency
consultation to assess lab results produced by another country
suggesting possible alarming increase in positive cases. The outcome of
this report was to avert panic in Hanoi by being able to provide expert
laboratory analysis which suggested other data was incorrect.
June 2005.--CDC produces a conventional PR8 H7N7 vaccine candidate
with A/mal/NL/12/00 (H7N3) and A/mal/NL02/00 (H10N7) and conducts
vaccine safety testing on this vaccine candidate.
June 2005.--CDC supports World Health Organization (WHO)
Cooperative Agreements with WHO Headquarters to continue enhancing
communications at the animal-human interface, enhance international
surveillance, and conduct pandemic risk assessment activities.
June 2005.--National Institute of Allergy and Infectious Disease
(NIAID) intramural scientists and CDC colleagues developed live,
attenuated H9N2 vaccine enters Phase I testing at Johns Hopkins.
June 2005.--HHS awards contract to Roche for $58 milllion to
acquire 2 milllion treatment courses of Tamiflu antiviral drug using
Strategic National Stockpile funds.
June 2005.--CDC details staff to Geneva to work on pandemic risk
assessment and pandemic planning.
July 2005.--Staff from CDC participates in the National Virology
Training Course to cover pandemic preparedness and surveillance for
avian influenza viruses.
July 2005.--CDC performs major serological analysis of
immunogenicity of H9N2 vaccine (with or without adjuvant) in clinical
trials.
July 2005.--CDC conducts serological analysis of subset of samples
from National Institute of Allergy and Infectious Disease (NIAID) H5N1
vaccine clinical trials to validate results from NIH contractor.
July 2005.--HHS issues Request for Proposals for the manufacturing
of H5N1 vaccine at commercial scale using licensed process.
July 2005.--National Institute of Allergy and Infectious Disease
(NIAID) conducts a trial of intradermal vs. intramuscular delivery of
H5N1 vaccine; results are expected by early 2006.
July 2005.--FDA distributes of antiserum to A/VIETNAM/1203/2005
virus to MedImmune for development of live, attenuated, H5N1 vaccine
candidates.
July/August 2005.--CDC trains two Vietnamese laboratorians at CDC
in laboratory methods used for detection of human infections of H5N1
viruses.
August 2005.--CDC participates in a World Bank consultation on
coordination of global avian influenza activities.
September 2005.--CDC produces an H7N2 vaccine candidate using A/
tky/VA/02 and conventional reassortant techniques.
September 2005.--CDC awards 2 new bilateral cooperative agreements
to address avian influenza Kazakhstan and New Caledonia which includes
a consortium of seven Pacific Public Health Surveillance Network
Countries and Territories including Cook Islands, Fiji, Guam, Wallis
and Futuna, Palau, and Tonga.
September 2005.--CDC and National Institute of Allergy and
Infectious Disease (NIAID)-funded collaborators reports on generation
and characterization of fully reconstructed 1918 pandemic influenza
virus; vaccine studies and evaluation of 1918 virus sensitivity to
influenza antivirals are ongoing.
September 2005.--In collaboration with World Health Organization
(WHO), CDC plans a National Influenza Center satellite meeting in Malta
for the purpose of working on WHO actions for NICs interpandemic,
pandemic alert and pandemic.
September 2005.--National Institute of Allergy and Infectious
Disease (NIAID) established a Cooperative Research and Development
Agreement with MedImmune, the manufacturer of FluMist, to develop live
attenuated vaccines against pandemic influenza.
September 2005.--A collaborative effort between National Institute
of Allergy and Infectious Disease (NIAID)'s Office of Clinical Research
(OCR), Oxford University, Wellcome Trust, and World Health Organization
is in the early stages of working to establish a small network of
clinical sites in SE Asia to research emerging infectious diseases with
an initial emphasis on avian influenza. An oseltamivir treatment
protocol is being considered for early 2006.
September 2005.--National Institute of Allergy and Infectious
Disease (NIAID) signs an Interagency Agreement (IAA) with Uniformed
Services University of the Health Sciences (USUHS) to establish a
NIAID/Department of Defense Emerging Infectious Disease Clinical
Research Program which can include Avian Influenza (AI) research in
Indonesia with NAMRU 2.
September 2005.--HHS makes a modification of the H5N1 vaccine
manufacturing contract with sanofi pasteur for $1.5 million to
manufacture H5N1 vaccines formulated with alum adjuvant for clinical
evaluation by NIH in Jan. 2006.
September 2005.--HHS exercises options on the contract with sanofi
pasteur of $32.4 million to continue for four more years of securing a
year round egg supply for influenza vaccine production and clinical lot
manufacturing of pre-pandemic influenza vaccines for clinical
evaluation.
September 2005.--HHS awards contract to GlaxoSmithKline for $2.8
million for 87,000 treatment courses of Relenza antiviral drug using
Strategic National Stockpile funds.
September/October 2005.--CDC staff provides on-site assistance to
the Director General of the Indonesian equivalent of CDC and
participates in outbreak investigations of H5N1 cases.
September/October 2005.--HHS awards contract to sanofi pasteur for
$180 million to manufacture 6 million doses of H5N1 bulk vaccine (90 g
HA/dose) with Strategic National Stockpile and Department of Defense
funds.
September/October 2005.--FDA distributes virus reference antigen
and companion antiserum to A/VIETNAM/1203/2004 vaccine to Chiron and
Baxter for potency measurements of H5N1 vaccine.
October 2005.--CDC provides 2 weeks of on-site technical assistance
for the National Institute of Hygeine and Epidemiology in Hanoi for
developing and conducting training for the start of the new National
Influenza Surveillance system, supported through the bi-lateral
cooperative agreement with CDC.
October 2005.--CDC produces a new reagents kit for H5N1 for
international distribution to keep up with changes in the H5 viruses so
that global labs can perform diagnostics.
October 2005.--FDA begins preparation of antiserum to H7N7 vaccine
manufactured at sanofi pasteur for surveillance and potency
measurements.
October 2005.--HHS awards contract to Chiron for $61.8 million to
manufacture 2 million doses of H5N1 bulk vaccine (90 g HA/dose) with
Strategic National Stockpile funds.
October 2005.--HHS/OS awards contract to Roche for $29 million to
acquire 1.2 million treatment courses of Tamiflu antiviral drug using
Strategic National Stockpile funds.
October 2005.--National Institute of Allergy and Infectious Disease
(NIAID) expands its intramural pandemic influenza research with a new
initiative focused on the molecular pathogenesis and epidemiology of
influenza.
October 2005.--National Institute of Allergy and Infectious Disease
(NIAID) initiates a trial of investigational H5N1 vaccine in the
elderly at 4 Vaccine Treatment Evaluation Units sites.
October 2005.--National Institute of Allergy and Infectious Disease
(NIAID) initiates an H5N1 vaccine Re-Vaccination Clinical Trial
(original study conducted in 1998 by John Treanor--see 24 above on
timeline) to determine whether having received an H5 vaccine in the
past primes the immune system to respond rapidly to another dose of H5
vaccine.
October 2005.--Through National Institute of Allergy and Infectious
Disease (NIAID)'s antiviral screening program, scientists screen more
than 1,300 compounds for in vitro activity against influenza during the
past two years.
October/November 2005.--Manufacturing begins of pilot
investigational lots of H7N7 vaccine by sanofi pasteur under HHS
contract for clinical evaluation by National Institute of Allergy and
Infectious Disease (NIAID) in 2006.
October/November 2005.--CDC provides in-depth technical support and
conducts site visits to the national sentinel hospitals in Vietnam.
November 2005.--CDC updates the global diagnostic reagents kits for
the identification of H5N1 viruses so that they can now identify the
newly circulating viruses from Indonesia.
November 2005.--National Institute of Allergy and Infectious
Disease (NIAID) plans to begin a chart review in selected pediatric
practices that used Tamiflu in infants last year to gather safety data
to help inform prospective use.
November 2005.--National Institute of Allergy and Infectious
Disease (NIAID)/Office of Clinical Research is pursuing a clinical
trials agreement with Biocryst Pharmaceuticals, Inc. and jointly
developing a protocol for Phase I clinical trials testing peramivir
intramuscular and intravenous administration. Investigational New Drug
Application (IND) submission is expected by late 2005, with study
initiation expected in winter 2006.
November 2005.--HHS plans to issue Request for Proposals # ODC V&B
05-08 entitled ``Antigen-Sparing Pandemic Influenza Vaccine Advanced
Development and Licensure.''
November 2005.--Manufacturing begins of H5N1 vaccine formulated
with alum adjuvant at sanofi pasteur under HHS/OS contract for clinical
evaluation by National Institute of Allergy and Infectious Disease
(NIAID) in early 2006.
Senator Specter. My red light just went on, Senator Harkin.
You're up.
Senator Harkin. No response to that last one?
Senator Specter. No, I want it in writing.
Senator Harkin. Okay.
Senator Specter. Others may come back to it, but I want to
stop on time.
STATE AND LOCAL PANDEMIC FLU PREPAREDNESS
Senator Harkin. Well, thank you very much, Mr. Chairman.
I just wanted to follow up a little bit, Mr. Secretary, on
this situation with State and local governments. This morning's
newspaper, Washington Post, said that you're planning for $644
million: ``to help local governments make your own preparations
for a flu pandemic.'' In your testimony, which I just looked
at, it carves out $100 million, directed to State and local
public health agencies. What is the correct figure? Is it $100
million or is it more than that?
Secretary Leavitt. The $100 million, Senator, goes to help
them with the development of plans and to exercise the plans--
specifically, the larger number, the $555 million, depending on
what you add into that category--would go, in general to help
enhance public health infrastructure and international
collaboration.
Senator Harkin. Well, if that's the case, Mr. Secretary, I
think that that needs to be re-examined. That $100 million, as
I figure it, is about 1 percent--less than 1 percent of the
entire package. State and local governments--we're already
hearing from them, by the way.
Also, I want to clear up one other thing. It is my
understanding that the President's proposal has a provision
that States will be required to pay for their own stockpile of
anti-virals, up to 75 percent--or 75 percent will have to come
from the States--and that HHS will subsidize up to 25 percent.
Is that correct?
Secretary Leavitt. Senator, we feel, as I believe you do,
that the State and local governments have to be deeply involved
in this process. What makes a pandemic a unique disaster is, as
I indicated earlier, it is not confined by geography. It is
quite likely that if a pandemic were to blossom, that we would
be dealing with pandemic conditions in virtually every State in
the country simultaneously. The capacity of any central
government to manage every one of those areas simultaneously is
nonexistent. So, we want to develop very strong commitments and
involvement. This is going to require all of us. It does
involve some cost sharing on the anti-virals, for a number of
reasons. One is that we want to make certain that they are
buying into pandemic preparation and not just looking for a
check from the Federal Government to put into a Federal
stockpile. The second is that we believe it is going to take
the mutual efforts of all of us to get this done. I am
persuaded that, in order for us to actually distribute these
anti-virals, that the stockpiles are going to have to be kept
in the States, for the most part, and distributed according to
protocols. at are developed on a State-by-State basis that
would be based on their own priorities and protocols. We would
make recommendations, but, nevertheless, customize to the
State.
Senator Harkin. Mr. Secretary, I don't think I tracked that
too much. It seems to me, then, we're going to allocate scarce
resources. We're only talking about 20 million, going up to 81
million by the summer of 2007. It almost seems, then, that they
will be allocated based upon a State's ability to pay. How are
you going to ask Louisiana, right now, to come up with money
for that? Take Mississippi, I mean, they've been hit hard. I
just don't mean to single those two States out. Other States
are having problems, too. Right now, the Federal Government
stockpiles smallpox vaccine, but we don't ask the States to
contribute to that.
Secretary Leavitt. We, very clearly, believe the States
should contribute to this. The actual percentage that they
contribute, we're open to discussions on how we do that.
Senator Harkin. Well----
Secretary Leavitt. We think, just like in a co-pay for a
prescription, that there's a need for co-pay with the States on
this.
Senator Harkin. Then why don't we asking them to pay for
smallpox vaccine?
Secretary Leavitt. Well, I--that opens up a discussion of
the broad stockpile issues that I'm anxious to have.
Senator Harkin. It just seems to me this is a national
emergency. It seems to me that the States are going to be
involved, obviously, through their State public health agencies
and things like that, which we need to help them beef up. But,
in terms of the stockpiling of the anti-virals and stuff, I
don't think it's right to ask the States to come up with
approximately $500 million to stockpile them. I just--right
now, I'm informed that State public health agencies have
obligated 89 percent, already, of their fiscal year 2005 funds.
So, the money that we have sent out there already has already
been basically used up. I really do think we're going to have
to re-examine this. There may be ways for the States to buy in
and be active in this program. Obviously, we want them to buy
into this. You do that through the collaboration between the
Centers for Disease Control and Prevention and public health--
and their State public health agencies, and you get those
meshed. But it just--in terms of paying for the anti-virals, to
stockpile them, seems to me you ought to have the same basis
there as we would for smallpox or anything else; that this is a
national emergency, it should not be allocated on a State's
ability to pay. That means some States, poorer States, they
don't get it? More wealthy States get it? I don't think that's
the correct message to be sending out. I think we have to
examine that.
I have more questions, but my time has run out.
Senator Specter. Senator Cochran.
PANDEMIC PREPARATION
Senator Cochran. Mr. Chairman, the request before us is
described as an emergency. Can it also be described as urgent,
in terms of the need for Congress to act quickly to make these
funds available, as requested by the administration?
Secretary Leavitt. Senator, we find ourselves in a
vulnerable position were this virus to become a person-to-
person transmittable virus. We are not alone in the world on
that measure, but we are clearly in a place--with the virus
moving across continents. The troubling signs are that we have
people who are getting the disease from birds, and we are also
seeing wild birds travel across the planet in the natural
flyways, carrying the virus. We have now seen it go from
Southeast Asia, into Europe. There's no reason to believe that
those birds will discontinue. There's no reason to believe that
the virus won't continue to follow the pattern that others
have. We don't know whether it will achieve person-to-person
sustainable status, but, if it does, it would be a serious
matter, and one that we should have responded to.
Senator Cochran. In our use of vaccines for influenza,
generally, there is almost a rationing kind of system that we
have. We prefer that older members of the population get the
vaccine, and then if there is enough available, then other
members of the population are eligible or encouraged to take
the vaccine. Is this true in this kind of potential challenge?
I noticed that children are considered vulnerable. Is this flu
different in that respect? Is it no respecter of age or
location?
Secretary Leavitt. I'll ask Dr. Gerberding to respond to
that.
Dr. Gerberding. First of all, the big picture here is that
we can finally think about a future where we can take flu off
the table, because we will modernize our vaccine, and we
shouldn't ever have to face these shortages or this rationing
of the seasonal flu again. In the context of the potential H5N1
influenza, right now it's disproportionately affecting children
and young people. That may be because those are the people who
are having contacts with the affected chickens, and they are
coming into direct exposure to the virus. It is really too soon
to say how a pandemic would affect the population. We can look
back to 1918 and recognize that in that devastating pandemic it
was the young people who were disproportionately affected and
killed.
Senator Cochran. In our State, we've had good success in
making sure that vaccinations against other illnesses and
diseases are available to children. We had 100 percent. I think
we're the first State in the Union to achieve that goal of
childhood immunizations. I wonder what kind of program, if any,
we will have. Will it be patterned on the experiences that
States like ours have had in achieving success in getting the
vaccine to the people who need it?
Dr. Gerberding. The seasonal influenza program obviously
affects a broader population than just children. Right now, we
don't have those kinds of programs for the adolescent vaccines
or for the adult vaccines. We have to give a lot of
consideration to what is the most sensible way for delivering
vaccines to adults. With children, it's somewhat easy, because
they see their pediatrician, and they need to see their
pediatrician anyway, and they all start school at a certain
age. But, you know, adults are all over the map. So, in
addition to using the healthcare system in its traditional
format, we are increasingly aware of how important the private
sector has been in this--the Wal-Marts, the Targets, the
grocery stores that are immunizing increasing proportions of
our populations. With the health information technology system
that allowed us to track those people using computers and
electronic health records, we really could create a very modern
system for delivering this product to people. That's not what
we're asking for in our emergency budget, but, separate from
that, that kind of planning is going on at HHS and CDC.
Senator Cochran. Okay. Thank you very much.
Senator Specter. Thank you, Senator Cochran.
Senator Murray.
FDA APPROVAL PROCESS
Senator Murray. Thank you very much, Mr. Secretary, for
testifying before us today. I think we all know that the
American people are putting a lot of faith and hope in you, and
the agencies that you oversee, in implementing a plan that will
protect them. I just have to say that that really makes me
pretty uneasy. I'll tell you why. As you well know, for 2
years, FDA dragged its feet and took some really unusual steps
in handling the application for the Plan B emergency
contraceptives being available over the counter. And, in fact,
the FDA overruled its own scientific advisory panel and appears
to be putting politics and ideology ahead of drug safety and
effectiveness, which is their mission.
As you well know, Senator Clinton and I put a hold on the
confirmation of Lester Crawford over this issue. As you also
know, in July you write to Chairman Enzi and Senator Kennedy
and said, and I quote, ``The FDA will act on this application
by September 1, 2005.'' Well, Senator Clinton and I relied on
your word and your letter, and we accepted what you told us,
and we lifted that hold. In fact, in a subsequent Budget
Committee hearing I thanked you for your getting involved in
this and moving it forward and bringing us a decision by that
date. But what you told us didn't happen. The FDA didn't make a
decision. Instead, they issued another delay and, I believe,
put science on the back burner and really gave the Agency a
black eye.
I have to tell you that that is why I am concerned about
the Department's handling this new challenge. As I shared with
you, as I talked with you after that happened, this is far
bigger than Plan B. It's about the American public's confidence
in the agencies that oversee our public health, and
particularly FDA, and why it's especially important for this
conversation is that this national strategy calls for knocking
down regulatory barriers in the approval process so that
critical vaccines can reach the public sooner.
We know there have been problems with the FDA. We've seen
drugs being recalled, because they threaten public health, and
we've seen other drugs, as I just talked about, Plan B, being
held up even though the FDA's own scientific panel said it was
safe and effective.
So, I want to know how we can be confident now in the FDA,
when you plan to speed up approval of vaccines, while still
protecting the public health, while treatments that are known
to be safe and effective are still being held up at the FDA.
Secretary Leavitt. Senator, I know how important this issue
is to you. You've made----
Senator Murray. It's not just important to me. It's
important to the American public and their confidence in this
critical agency when they go to the store to purchase a drug.
Secretary Leavitt. The FDA did act, on September 15. They
put forward a notice of rulemaking to examine some very
important public policy issues that are new. Yesterday, the
period closed--we have had nearly 10,000 comments.
Senator Murray. Highly unusual to ask for public input to
the FDA, adding to the erosion of confidence.
Secretary Leavitt. Well, it must have been important to the
public if they put forward 10,000 comments, which they have. We
will now analyze them and move it forward in the way that we
said we would.
Senator Murray. Well, Mr. Secretary, the point is, we are
now being asked, in a very serious public health question, to
have confidence in an FDA that we have seen confidence be--
erode dramatically, including by pharmaceutical companies who
have talked to me, and the American public. I think that it
calls into question--as I told you, we've got to have
confidence. This decision needs to be made. We expect an answer
soon.
You know, especially now, when we are urging FDA to approve
new vaccines quickly. I would just ask you, are you urging the
approval of these new vaccines that--and anti-viral treatments
that do not meet current FDA safety standards for approval?
What are we going to see happen?
Secretary Leavitt. We're going to use the FDA to do what it
does well, and that is to protect the American people. Every
vaccine that we put forward has to go through FDA clinical
trials in a way that I'm sure Dr. Fauci would be very pleased
to describe.
ROLE OF STATE AND LOCAL GOVERNMENTS
Senator Murray. Well, let me just re-emphasize that if we
can't have confidence in FDA following its own scientific
panels in the mission that it has to approve drugs, not on
politics, but on safety and effectiveness, and it erodes our
confidence, it is going to make it very hard for the public, in
a public health crisis like this, to have confidence in the
agencies that you oversee.
But, having said that, I know I have got 20 seconds, and I
know we're going to have this conversation again. I will keep
working on it. It is critical. But I want to add to what
Senator Harkin said. This morning, in my hometown newspaper,
Seattle Post-Intelligencer, the headline is, ``Bush's Plan to
Fight Flu Doesn't Thrill States.'' As Senator Harkin said, the
States are extremely nervous about what is going to be required
of them. I would say that the public health officials--and
you're all sitting at the table--know that a flu pandemic
doesn't sit within a State boundary, and if one State doesn't
have the financial resources to be able to deal with this on
the ground, it will create severe danger and hazards.
So, I am very concerned, as Senator Harkin pointed out, Mr.
Chairman, about a plan that relies on public health agencies to
come up with the majority of the money, particularly when many
of our States are struggling today, and particularly because
the administration budget has already reduced funding for State
and local health departments by $130 million. They are already
struggling. So, if we add this on top of them and say, ``If you
want to participate, come up with 75 percent of the funding,''
we are going to have a public health crisis. That concerns me
greatly.
Secretary Leavitt. Senator, I would like to clarify that.
The plan does call for the Federal Government to pay for the
majority of the anti-virals. It also should be made clear that
we do not see anti-viral strategies being synonymous with
preparation. We do believe that the States have a
responsibility in the development of their plans and in the
decision on how they should deploy anti-virals. We're looking
forward to working with the States in developing a level of
preparedness. This cannot be managed by the National
Government. It is too wide. There is no person skilled enough
at logistics that they could manage a pandemic in 500 locations
or 1,000 locations at a time. If we have a full pandemic,
that's likely what we'll see.
Senator Murray. Well, I'm positive we'll be pursuing both
of those conversations again.
FUNDING PRIORITIES
Senator Specter. Thank you, Senator.
I was informed this morning, during the course of the
hearing, that our other witness, Mr. John Barry, has some
travel restrictions and has to leave by about 10:10, but I
don't want to keep this panel waiting, so, let's proceed now
with 4 minute rounds on the second round to give Mr. Barry an
opportunity to testify before he has to go.
Secretary Leavitt, we have a disconnect on what information
comes to the Congress from the administration. That occurs
because matters are transmitted through OMB, and they not only
superintend the requests for money where various secretaries
have to fight it out there, but also in what you say. I've
found that to be a very serious limiting factor on having
Congress discharge its constitutional duty to establish
priorities and decide what funding there ought to be.
One illustration which was very emphatically brought to
bear was the construction at the Centers for Disease Control
and Prevention. This goes back before your watch. This goes
back to 1999. And I had heard tales about the terrible
facilities in CDC, but not from the Secretary of HHS, not from
anybody in the administration. I went to a wedding in the
proximity of Atlanta, in April 2000, and went on down to
Atlanta and took a look, and was just astounded at what I saw.
Senator Harkin joined the visit. Immediately, on the budget
then in process, we put up $175 million, and then $250, $266,
$260, and $269 million. The administration's request came in
this year for $30 million, which is preposterous. We had world-
class scientists in hallways and had toxic materials not
subject to proper supervision. We have, by reassessing
priorities, come up with $239 million. We've got to finish
that.
CDC, the request is down by $475 million this year. Instead
of going down by $475 million, we've tried to increase funding.
We do that, because of the magic of ``Senator Taylor'' and
``Senator Ellen'' to find the money. But we need to find some
better way to know what the hell's going on, because the
executive branch won't tell us. We need some whistleblowers,
starting with the Secretary.
I know it's pretty tough to do, but I want to take a look
at what you're going to provide us, Dr. Fauci, on the
chronology of events. I've been involved in enough
investigations and enough oversight to have an instinct that
the scientists knew a lot more about the problem than the
subcommittee did. We've proved our willingness to buck the
system on NIH, where Senator Harkin, Senator Cochran, this
subcommittee, have taken the lead at increasing funding from
$12 to $28 billion, up to $29 billion this year, if they can
hold it. We have very high regard for what you people do. But
you've got to help us help you.
Finally, the alarms have been sounded, and we're prepared
to go forward. I'm going to yield back my final 6 seconds.
Senator Cochran, round two?
Senator Cochran. Senator Harkin should go first.
VACCINE LIABILITY
Senator Harkin. Thank you, Mr. Chairman.
I just want to join with you on that, and I was just
thinking that perhaps, Mr. Chairman, what we need is, because
of the importance of us getting the proper information from the
basic science community, whether that's NIH, all of NIH, or
CDC, perhaps we need to expand the concept of the pass-through
budget from the NCI--that is the only one we have now--if we
get that pass-through the budget from the National Cancer
Institute. Perhaps we need a pass-through budget from other
Institutes, or maybe even CDC. That may be one thing we might
explore.
Mr. Secretary, I wonder if I could maybe shift on a couple
of things. One, we're hearing a lot of talk about liability and
how we're going to handle the liability of drug manufacturers
and things like that. Congress is going go have to wrestle with
that. I hope that--and I just make this statement for the
public record, that I hope we also start thinking about the
liability aspect that pertains to public health workers that
are out on the front lines that are administering the drugs,
the vaccines, anti-virals, that type thing. How about their
liability protection? We've got to be thinking about them, too.
So, I just throw that out there so that we don't forget as we
think about that.
I wonder if I might just perhaps ask Dr. Gellin this
question, if I might, Mr. Secretary.
Dr. Gellin, we've talked about cell-based vaccines. The
Secretary mentioned that we are moving ahead in that area. I've
spent a great deal of time talking to drug manufacturers about
this new technology. But there's something else that came up on
the scope as we began looking at this, this summer, and that's
something called ``synthetic vaccines,'' which may even hold
more promise. Now, I don't know about the timeframes of this.
We have got cell based, we have got synthetic vaccines. Could
you just briefly explain the two and whether or not this is
something also that we're going to be investing resources in--
synthetic vaccines?
SYNTHETIC AND CELL-BASED VACCINES
Dr. Gellin. Yeah, thank you very much. I'll start, and
maybe Dr. Fauci will fill in, as well.
The concept here is that we have a tried-and-true
methodology to make vaccines, in that we know, at the end of
the line, that it is the component of the vaccine that
stimulates an immune response. Currently, we grow viruses in
eggs that can grow up that amount of----
Senator Harkin. Yes, right.
Dr. Gellin [continuing]. Antigen. The conversion to a cell-
based system is essentially to do the same thing in a more
modern way, using cells to grow virus.
Senator Harkin. Right.
Dr. Gellin. At the end of the line, you still have that
same antigen. There are a whole range of other vaccine
technologies that Dr. Fauci's groups are already looking into
that are new ways to stimulate the immune system. You would
have to look at the immune system in a different way.
Currently, we will use a vaccine and measure the antibody
response to those proteins. With newer vaccines, we have to
have new ways to evaluate how well the immune system is
responding, because it will not just be the equivalent. But
there are a range of these technologies. I think the dream is
that someday there will be a vaccine--a flu vaccine that would
protect all--against all of the flu viruses. It is clearly the
Holy Grail. If it was easy, it would be done. But someday, if
we are there, then these discussions will be much simpler.
Senator Harkin. Dr. Fauci, you tell us about synthetic
vaccines.
Dr. Fauci. It is less synthetic, Senator Harkin, that it is
getting away from the technology which we have now with flu,
which is either a killed vaccine, which is what we have used
with the Sanofi and Chiron group, or a live, attenuated, which
is the MedImmune version.
When you're talking about being more specific, it is more
of the recombinant DNA technology. There are components of the
influenza virus that are very constant from flu strain to flu
strain. We've not been able to utilize that to get our, quote,
``universal vaccine,'' because many of those proteins are not
highly immunogenic, which means they do not stimulate the
immune system very well.
Several companies, with and without collaboration from us
in the Department--and many times it is in collaboration--are
developing vaccine approaches toward influenza, which are
trying to look at some of those constant regions. One of them
is the M2 protein of influenza, where you make it in a way that
when you present it to the immune system, it's highly
immunogenic and would hopefully induce an immune response that
would really be very beneficial to all of our projects, because
what it will do is cover a broad range of different strains of
influenza. So, if you really look at the future, that is where
we want to be several years from now, where you can actually
make a vaccine that covers all the bases of a potential flu.
So, I think that's what you're referring to.
Senator Harkin. Tony, that may have been over my head. I
have to think about that.
But this--the briefing I had on synthetic vaccines, is some
of this money going to be used for that? I know we're going
into cell-based. Is some of this money going into that area?
Secretary Leavitt. Our purpose is to identify a large range
of new, promising technologies. We'll begin to invest in those
technologies in the first round. When--then we'll go back and
say which of them continue to show promise after our first
investments, and we'll begin to narrow the--our investments. We
are programming to have multiple providers and to utilize the
best technologies that come from a wide range of starts.
Senator Harkin. Would you send me some stuff on synthetics,
so I can read it?
Dr. Fauci. Will do.
Senator Harkin. It might take me a little while.
Dr. Fauci. Okay.
[The information follows:]
National Institutes of Health Research on Synthetic Vaccines
Question. ``Synthetic Vaccines:'' What research is NIAID supporting
on cell culture technology, and recombinant and DNA vaccine
development, and what promise/advantage do they hold?''
Answer. The term ``synthetic vaccines'' technically refers to
vaccines such as peptide vaccines that are artificially synthesized
through chemical reactions. NIAID is not currently pursuing the
development of a synthetic vaccine against influenza.
However, the development of other types of influenza vaccines has
been a major focus of the National Institute of Allergy and Infectious
Diseases (NIAID) Influenza Program. NIAID supports strategies to foster
the development of new influenza vaccine candidates and manufacturing
methods that are simpler and more reliable, yield more broadly cross-
protective products, and provide alternatives to the egg-based
technology currently used to grow vaccine viruses.
Influenza vaccine production technology using recombinant DNA or
cell culture could potentially enable vaccine manufacturers to respond
more quickly to public health needs by allowing the rapid scale-up of
vaccine production and manufacture to meet demand. For example, the
technique of reverse genetics, developed by NIAID-supported scientists,
allows scientists to manipulate the genomes of influenza viruses and to
transfer genes between viral strains. The technique allows the rapid
generation of seed viruses for vaccine candidates that exactly match
the anticipated epidemic strain. By removing or modifying certain
virulence genes, reverse genetics also can be used to convert highly
pathogenic influenza viruses into vaccine candidates that are safer for
vaccine manufacturers to handle.
In another approach, NIAID and MedImmune, Inc. are working under a
cooperative agreement to produce and test multiple vaccines against
potential pandemic flu strains, including the H5N1 avian influenza
virus. The agreement specifies that the scientists will select genes
from avian flu viruses with pandemic potential and add them into a
weakened human flu virus to create multiple live, attenuated virus
vaccine candidates. An attenuated vaccine can potentially stimulate a
broader and more potent immune response than a killed vaccine
formulation. For example, live attenuated virus vaccines for measles,
mumps, and rubella stimulate life-long immunity and have a long history
of safety and effectiveness. A live attenuated virus vaccine may also
stimulate effective immunity to a circulating pandemic virus that
differs significantly from the vaccine strain, which would be a major
advantage given both the biology of influenza viruses and the lengthy
flu vaccine production process. In addition, an intranasal live
attenuated virus-based pandemic flu vaccine could be easily
administered by non-medical personnel, self-administered, or given as a
booster to a killed vaccine.
Although still in the proof-of-concept stage, the ability to
manipulate DNA vaccine antigens by recombinant means is a powerful tool
against viruses such as influenza and HIV, which have a tendency to
mutate rapidly. Recombinant DNA technology allows for the relatively
easy addition or deletion of antigens in new combinations. An example
of a gene-based method of production is the genetic engineering of
baculovirus, an insect virus not related to influenza, to express a
gene that encodes an influenza coat protein such as hemagglutinin or
neuraminidase. The engineered baculovirus is then grown in insect cell
cultures, and the influenza protein that the virus produces is purified
for use as a ``recombinant subunit'' influenza vaccine.
The NIAID Vaccine Research Center (VRC) is developing a candidate
``prime-boost'' vaccine against influenza, an approach that has also
been used to develop a candidate HIV vaccine. The VRC ``prime-boost''
vaccine is composed of two vaccine components, both of which contain
influenza genes, given at different times. The two vaccine components
differ in how the genes are packaged. One contains only the naked gene
fragments, which cannot reconstitute into an infectious virus. The
other uses a weakened type of respiratory virus known as adenovirus as
a vector to shuttle the non-infectious influenza gene fragments into
the body. This approach may result in enhanced cellular and humoral
immunity. The NIAID Vaccine Research Center is also constructing and
has pre-clinically tested a number of DNA plasmids which contain
proteins from the influenza virus (hemagglutinin, neuraminidase, ion
channel M2, and the nucleocapsid protein). VRC studies of vaccines
expressing these proteins will serve as the proof of concept basis for
a gene-based influenza vaccine.
Senator Harkin. Thank you.
Senator Specter. Thank you, Senator Harkin.
Senator Cochran.
PANDEMIC FLU BUDGET
Senator Cochran. Mr. Secretary, I am assuming that this
request, as it recommends basic research, infrastructure
improvements, and expansion, includes the traditional role
that's been played in this area by the Departments of Health
and Human Services, as well as Homeland Security and the
Department of Agriculture, animal research--where animal
research is involved. Do you suggest that funding for basic
research in these traditional areas should be increased across
these departments as part of this request?
Secretary Leavitt. The request that you have seen focuses
on vaccines in the Department of Health and Human Services.
There is a part of this budget--the difference between the $6.7
billion and $7.1 billion--that would be contained in budgets of
the other departments outside of HHS, for other tasks.
USE OF ANTI-VIRALS
Senator Cochran. I understand that anti-virals play an
important role during annual flu outbreaks. They are used in
nursing homes to prevent the spread of flu, and also given to
people who, for health reasons, should not take the flu
vaccine. How can we ensure that anti-viral supplies are used
correctly and in accordance with normal flu needs?
Secretary Leavitt. I'm going to ask Dr. Gerberding, from
the Centers for Disease Control and Prevention to respond to
that. We've recently been issuing guidance on that subject.
Dr. Gerberding. Thank you.
On October 21, CDC issued some updated guidance on
management of seasonal influenza. That guidance emphasizes the
importance of using anti-virals. First of all, for treatment
for people who identify flu-like symptoms and see a clinician
within 48 hours, these drugs can reduce the severity and the
duration of their symptoms. For people who have risk factors
that put them at high risk for complicated flu, they should see
their doctor anytime they suspect influenza, because those
drugs may be indicated for them, as well.
We do also use anti-viral drugs in cases that you
mentioned--nursing homes, for example--where either the people
are not vaccinated or we don't have confidence that the vaccine
will be 100 percent protective. So, by treating the people in
the nursing home for many days, we can often reduce the impact
and the death rate among those senior citizens. So, there are
specific indications where we use it for preventing flu, but it
is important that people recognize that, unlike the situation,
you know, 10 years ago, we really do have drugs now that are
widely useful for reducing flu complications. Those are the
same drugs that we are putting into our stockpile.
VACCINE PRODUCTION
Senator Cochran. Thank you.
Much of the request deals with the need to increase
manufacturing capacity of vaccines and anti-virals. Can you
describe how the President's initiative will address this
deficiency?
Secretary Leavitt. Yes, Senator. We intend to do three
basic avenues of research. The first is expanding our existing
egg-based production. It is tried, it is true. We know it is
there. We think particularly with new adjuvant technology, that
we can expand the yield of our egg-based production and that it
should continue.
Second, we are going to pursue cell-based technologies.
There will be a number of different technologies that we will
pursue. We have put an RFP out asking for providers to give us
ideas where we could pursue the development of a new
technology. We intend to pursue those. Then, last, there will
be some retrofitting of existing facilities that will be
necessary in order to get additional capacity needed to produce
300 million courses of vaccine in a 6-month period.
Senator Cochran. Thank you.
Senator Specter. Thank you very much, Senator Cochran.
We do want to move ahead and give Mr. Barry his round of--
opportunity to testify.
We applaud what the President did yesterday. We applaud
what you're doing. We thought it important to have this hearing
so that the American people would know that the President is
moving, the Secretary is moving, his key people are moving, and
so is the Congress.
We did have some problems, Mr. Secretary, in getting
information to prepare for this hearing. I'd like to correct--
see if those channels of communications are corrected. We
understood the New York Times had information 2 weeks ago that
we couldn't have access to. They have a louder bullhorn than we
do. But they don't have as much money for you as we do.
We need to have a better line of communication so that we
find out what's going on, because we can't help you unless we
know.
Do you care to make any closing comments, Mr. Secretary?
Secretary Leavitt. Well, it might not surprise you to know
that those aren't always intended, for them to have information
before you do. We'll do our best to remedy that situation.
Senator Specter. Okay, we'd appreciate it.
Dr. Fauci, any last word?
Dr. Fauci. No, thanks. I will get you the information you
have asked for.
Senator Specter. Okay.
Dr. Gerberding, any final words?
Dr. Gerberding. Just thank you.
Senator Specter. We have all this talent here. It's a waste
of talent not to have them speak.
Anything further, Dr. Gellin, you'd like to say?
Dr. Gellin. We look forward to ongoing discussions with
you.
Senator Specter. Dr. Raub, anything?
Dr. Raub. No, sir, other than we are available to assist,
as we can.
Senator Harkin. Can I just make one statement?
Senator Specter. Senator Harkin, you're called upon for one
statement.
HOSPITAL SURGE CAPACITY
Senator Harkin. Now, would you please get back to me, Dr.
Leavitt. We're just out--or, Secretary Leavitt--we're just out
of time here. But, in looking through the plan and asking my
staff, there's nothing in there about hospital surge capacity.
We never--we don't have time, I guess, to get into that now,
but that needs to be addressed. Could you somehow correspond
with us on this and let us know what you're doing on that end
of it?
Secretary Leavitt. Yes, sir.
Senator Harkin. Thank you.
[The information follows:]
Hospital Surge Capacity
Increasing hospital and health care system surge capacity has been
the cornerstone of the National Bioterrorism Hospital Preparedness
Program (BHPP) since the program's inception in 2002. State departments
of public health, the recipients of BHPP awards, have been directed to
work closely with hospitals and supporting health care system to
address the various aspects of surge capacity that would allow the
system to increase its ability to triage and treat an influx of
patients during a bioterrorism event or other public health emergency.
Specifically, States have been directed to establish systems to
increase bed availability beyond current daily staffed capacity in
BHPP-supported hospitals and community-based clinics; upgrade and
expand airborne infectious disease isolation capacity within individual
hospital facilities and across intrastate health care regions; develop
systems to recruit, identify, and deploy volunteer health professional
to supplement hospital and health care system personnel, including
behavioral health providers; establish hospital and intrastate regional
pharmaceutical caches; obtain and maintain sufficient amounts of
personal protective equipment to protect daily and surge personnel and
train personnel in the proper us of the equipment; and develop and
enhance redundant communications systems that ensures connectivity
between the health care system, public health, and other first
responders.
States departments of public health have supported hospitals and
the health care system in greatly enhancing surge capacity in each of
these areas, which will certainly improve local, regional, and
statewide response to pandemic influenza. In addition, departments of
public health and health care communities nationwide have taken
additional steps to prepare for a pandemic influenza outbreak. Namely,
public health and medical communities nationwide have developed
statewide pandemic influenza plans. These plans were initiated in
fiscal year 2004, and final plans were submitted to the Centers for
Disease Control and Prevention for review in fiscal year 2005. In
addition, State departments of public health and health care systems
have begun to explore other means of further increasing surge
capability to achieve the levels of care necessary to support a
pandemic influenza response, including the identification of alternate
care facilities and the provision of home health care, delivery of
prescription drugs, and delivery of meals. The pandemic influenza
supplemental will allow public health, hospitals, and supporting health
care systems to build upon the plans that have been developed and
ensure sufficient hospital and community surge capacity to respond to
an influenza pandemic in many communities across the Nation.
Senator Specter. We were joined by the distinguished
Senator from Ohio, Senator DeWine. We have one more witness,
Senator DeWine, I have said earlier, who has a plane to catch
at 10:10, but----
Senator DeWine. You can proceed, Mr. Chairman.
Senator Specter [continuing]. But Senators take preference
over--over anything.
Senator DeWine. I'm fine, Mr. Chairman.
Senator Specter. Okay. Thank you all very much.
I'll now call on Mr. John Barry, the author of ``The Great
Influenza: The Epic Story of the Deadliest Plague in History,''
author of other award-winning books, Brown University graduate.
We welcome you here, Mr. Barry. It is our custom to limit
witnesses to 5 minutes. You have a full allocation before you
have to leave, and we might hold your plane just a little bit
for you to respond to a question or two, if you have any
flexibility.
Thank you for joining us, and the floor is yours.
STATEMENT OF JOHN M. BARRY, AUTHOR
Mr. Barry. Thank you very much. I am not quite--I've got
a--probably 10:20, maybe even squeeze to 10:25. So, I
appreciate your comments and courtesy.
Senator Specter. Well, I wanted to bring you on after--I
don't want to keep those scientists here a minute longer than
necessary--to interrupt their testimony, because they have a
lot of important work to do. But now we want to hear from you.
Mr. Barry. I thank you very much for the opportunity to
testify and give you some background on a disease that,
according to the CDC, kills 36,000 Americans in a normal year.
By definition, a pandemic would not be a normal year. As you
heard, another pandemic is virtually inevitable, because of the
nature of the virus. We have no idea when it will occur. It
could have started 2 weeks ago, and we don't know it. It might
not come for another 20 years. But for the last 500 years, they
have occurred, at least the 500 years. The greatest duration
between pandemics in the past was 42 years. We're now at 37
years, and counting.
They don't need air travel to spread. In the 1690s,
influenza made it from Europe to the American Colonies, when it
took 8 weeks to cross the ocean. We have substantial
information only about the last four pandemics: in 1989, 1918,
1957, and 1968. 1918, of course, is the one that gets all the
press, because the most people died. No one knows exactly how
many died, but a Nobel Prize winner, MacFarlane Burnett, who
spent most of his life studying the disease, put the estimate
at a minimum of 50 million dead, possibly 100 million dead. And
that, of course, was in a world only 28 percent the population
of today's. In other words, even without adjusting for
population, influenza in 1918 killed more people in 24 weeks
than AIDS has killed in 24 years.
Even then, though, in the developed world, the overwhelming
majority of victims had what we would regard as a normal
influenza attack. The mortality rate in the United States was
no higher than 2 percent, but so many people are attacked that,
in the United States alone, 675,000 people died in a population
roughly one-third of today's.
Symptoms could be horrific. People turned so dark blue from
lack of oxygen that physicians reported they had difficulty
distinguishing between black patients and white patients.
People could bleed from their eyes, ears, as well as nose and
mouth. The impact on the society was immense.
Part of the problem came from false reassurances from the
Federal Government, which were repeated by local governments.
The Surgeon General actually said, ``There is no cause for
alarm.'' Of course, there was cause for alarm. People would die
in less than 24 hours.
This enormous disconnect between horrific symptoms,
terrible death tolls, and constant false reassurances from
officials, national and local, and reinforced by the media,
which, then, was totally passive, led, ultimately, to a
breakdown in trust in all authority, and people became
alienated. The Red Cross reported that people were starving to
death, quote, ``not from lack of food, but because the well are
afraid to help the sick,'' unquote.
One very sober scientist not given to overstatement said
that if the epidemic continued, quote, ``for a few more weeks,
civilization could easily disappear from the face of the
Earth.'' That is how serious this impacted the society.
But a 1918-like scenario is not necessary to justify the
full attention of the Government to influenza. A best-case
scenario will do that. This is because recently, despite
antibiotics that would cut deaths from secondary bacterial
infections, we have actually become more vulnerable to
influenza, not less vulnerable. This is largely because medical
science has improved in so many other areas, but lagged in
influenza. As a result, the demographics of the population have
changed. We now have a much larger segment of the population
with impaired immune systems. Most obviously, the elderly, but
also, anyone who survived cancer and had radiation therapy or
chemotherapy has an impaired immune system, not to mention
people with HIV or transplant recipients and some others. As a
result, a mild virus would kill far more Americans than in the
past, not less.
The 1968 pandemic killed 34,000 Americans. If you adjust
for population, that's about 55,000 today. Yet, CDC currently
estimates that if a virus similar to the 1968 pandemic struck,
between 89,000 and 207,000 Americans today would die.
Deaths are, however, only one measure of the impact of the
pandemic. We are also more vulnerable economically, because
of--everything's more efficient--just-in-time inventories,
people's habits have changed about eating out, going to the
supermarket. There are actually far fewer canned goods sold
today than used to be the case. Businesses are more vulnerable
to supply disruptions.
There is just the one bright spot, and that is, in all the
four pandemics that we know about, there was a lag time between
6 months and 1 year when it seems that the virus first surfaced
in human populations and became serious. All of those prior
four pandemics that we know about had a mild first wave that
was barely distinguishable, and sometimes not distinguishable,
from a normal course of influenza. So, there does seem to be
some time to do something, and a window of opportunity to get
things produced, particularly, obviously, vaccine.
I'd like to make one comment that's not in my prepared
remarks. The first responders are the public. I think that
public information is extremely important. I also think it's
important to exercise the plans. I'm from New Orleans. People
don't realize that one thing that worked in Katrina very well
was the pre-storm evacuation, when, when 80 percent of the city
was evacuated. The reason that worked, particularly compared to
Rita and the Texas gulf coast was because of Hurricane Ivan,
which the city evacuated the year before, and it was a
disaster. The--of course, that hurricane missed New Orleans,
but the planners looked at what happened, made adjustments,
and, in Katrina, those adjustments worked very well on the pre-
storm.
PREPARED STATEMENT
One other point, I gave a talk to the Pennsylvania Public
Health Association last week and was informed that the State of
Pennsylvania considers its pandemic preparedness plan so
sensitive that it is not releasing it to the public, which I
find rather ironic and a little bit strange.
On that, I thank you.
[The statement follows:]
Prepared Statement of John M. Barry
I thank you for the opportunity to testify, and to provide you with
some background on a disease that, according to the Center for Disease
Control and Prevention, kills 36,000 Americans in a normal year. By
definition, an influenza pandemic would not be a normal year and kill
far more Americans than that. And although I will tell you about what
happened during the pandemic of 1918 and 1919, which killed more people
than any other disease outbreak in history, a worst case scenario is
not necessary to justify far more expenditures on influenza. The best
case scenario is bad enough to get the attention of any American.
Another pandemic is virtually inevitable because of the nature of
the influenza virus. It is one of a group of viruses that mutate so
rapidly that virologists refer to them as ``mutant swarms'' or ``quasi-
species.'' All influenza viruses originate as bird viruses, but their
mutation rate allows them to jump species, from birds to humans. It can
jump directly, as happened in 1918, by mutation. It can also jump
indirectly when an avian influenza virus infects the same cell as an
influenza virus that earlier adapted to humans; the two viruses can
swap genes and create a new hybrid virus capable of infecting people.
This gene-swapping can occur not only in humans, but in other mammals.
Whenever a new avian influenza virus does transform itself into one
that can pass easily from one person to another, human immune systems
will not recognize it. This allows it to spread explosively through the
world causing a worldwide epidemic--a pandemic.
We have no idea when the next pandemic will occur. It may have
started two weeks ago and we just don't know it yet, or it may not come
for twenty years. But for at least the last five hundred years,
pandemics have occurred three to five times a century, with the
greatest duration between pandemics of 42 years. We are now at 37 years
and counting.
Pandemics do not need air travel to spread. In the 1690s, when it
took six to eight weeks to cross the Atlantic, influenza crossed from
England to the colonies. In Virginia one report said ``the people dyed
. . . as in a plague.'' In Massachusetts Cotton Mather wrote, ``All
conditions of persons were attacked . . . The sickness extended to
allmost all families. Few or none escaped, and many dyed especially in
Boston, and some dyed in a strange or unusual manner, in some families
all weer sick together, in some towns allmost all weer sick so that it
was a time of disease.''
We have substantial information only about the last four pandemics,
which occurred in 1889, 1918, 1957, and 1968. Of these, by far the most
lethal was the one in 1918, but there are some indications that
similarly lethal influenza outbreaks occurred in the past as well. In
1580, according to one account, some Spanish cities reportedly were
``nearly entirely depopulated by the disease.''
No one knows with certainty how many people died in the 1918
pandemic, but according to Nobel laureate Frank MacFarlane Burnett,
that pandemic killed at least 50 million people, and possibly 100
million. It did this in a world whose population was only 28 percent as
large as today's. That is the equivalent of 175 to 350 million today.
Yet even without adjusting for population and using Burnet's lower
estimate, the 1918 influenza pandemic killed more people in 24 weeks
than AIDS has killed in the 24 years that disease has been known. Well
over half the deaths occurred in an incredibly short span of about 10
weeks, between late September and early December, 1918.
In the developed world, the overwhelming majority of victims
suffered what we would today regard as a typical attack of the disease.
For example, the case mortality rate in the United States was no more
than 2 percent. But influenza attacks so many people that the U.S.
death toll was an estimated 675,000, the equivalent of about 1.8
million today.
We were of course at war when the pandemic erupted, and some people
have theorized that the war contributed to the lethality of the
disease. This reminds me of what Thomas Huxley called the great tragedy
of science, when a beautiful theory is slain by an ugly fact. This
theory is entirely inconsistent with the actual course of the disease.
There are several other points worth making about 1918. Influenza
normally behaves like a bully, killing people with the weakest immune
systems, particularly the elderly and the very young. This is true not
only with the endemic disease that occurs every year, but in the 1889,
1957, and 1968 pandemics.
This was not true in 1918. The people most likely to die in 1918
were healthy young adults, aged 20 to 35, people with the strongest
immune systems.
Symptoms could be horrific. People turned so dark blue from lack of
oxygen a physician reported he had difficulty distinguishing between
black and white patients. Victims could bleed from their mouth, nose,
ears, and eyes.
The impact on society was immense. Part of the problem came from
false reassurances from all levels of government. The Surgeon General
said, ``There is no cause for alarm.''
There was cause for alarm. Every city, town, and village ran out of
coffins. People could die less than 24 hours after their first
symptoms. This enormous disconnect between what people saw for
themselves and what they were being told destroyed all trust in
authority. People became alienated. In city and country victims starved
to death ``not from lack of food but because the well are afraid to
help the sick.'' Streets emptied. In Philadelphia in a city of almost
two million people, one medical student who was in charge of an
emergency hospital saw so few cars on his way home every night over a
drive of 12 miles that he started counting them; one night he saw not a
single other car on the road, and wrote, ``The life of the city has
almost stopped.'' Doctors and nurses were kidnapped. A confidential Red
Cross report noted ``a fear and panic akin to the terror of the Middle
Ages of the plague.'' One sober scientist, not given to overstatement,
wrote that if the epidemic had continued ``for a few more weeks,
civilization could disappear from the face of the earth.''
But as I said before, a 1918-like scenario is not needed to justify
the full attention of the government to influenza. A best case scenario
serves well enough.
This is because in recent years, despite antibiotics would cut
deaths from complicating secondary bacterial infections, we have become
more vulnerable to influenza, not less vulnerable, both in its economic
impact and in the death toll.
Ironically, medical science has increased our vulnerability by its
enormous advances that have increased the number of people living with
impaired immune systems. These include not only many more elderly, but
cancer survivors who have undergone chemotherapy or radiation therapy--
which weakens the immune system--transplant recipients, people infected
with HIV, and others.
As a result, a mild virus would kill more Americans than in the
past, not less. The 1968 influenza pandemic was the mildest that we
know of, with approximately 34,000 deaths in the United States,
equivalent to about 55,000 in today's population. By comparison, the
CDC projects that a pandemic caused by even such a mild virus would
today most likely kill between 89,000 and 207,000 in the United States
alone.
Deaths are, however, only one measure of the impact of a pandemic.
A pandemic will also cause massive economic losses and social
disruption. Increased efficiencies and just-in-time inventory
management in business and health care have both cut into the surge
capacity to make needed goods and exposed much of the economy to supply
disruptions.
There is however one bright spot. Although in past decades, the
nation has paid too little attention to influenza, and therefore we
have made little progress on improving our ability to make vaccines, or
in finding real solutions that can only come from basic research, such
as developing a vaccine that works against conserved portions of the
virus, or in finding effective anti-viral drugs. But if we pay
attention to influenza now, even in the relatively short term of the
next few years, it may be possible to improve our vaccine production
capacity enough to make a real difference.
Influenza pandemics seem to come in waves. Certainly that was the
case in 1889, 1918, 1957, and 1968. The first wave, which in 1918
probably lasted six to eight months, was mild. In 1957 the first
isolate was identified in February, and the pandemic did not really
erupt until September. In 1968 there seems to have been a year between
identification of the first isolate as a new virus and serious pandemic
disease. And in the 1889-1890 pandemic, the third wave was the most
deadly.
So a window of opportunity does exist. If surveillance and vaccine
production capacity improve enough, we do have a chance to intervene
successfully and cut the death toll significantly.
How much our ability to fight this disease improves is largely up
to the appropriations committee.
Thank you.
Senator Specter. Thank you very much for joining us, Mr.
Barry. What are your time constrictions?
Mr. Barry. I need to leave about 10:25, I think.
PENNSYLVANIA PLAN
Senator Specter. Okay. We will proceed, then, with 4 minute
rounds.
When you mentioned Pennsylvania, a couple items of your
testimony attracted my specific attention: ``Pennsylvania'' and
``chemotherapy.'' Let me start with Pennsylvania.
When they won't reveal the plan, do you think there's the
slightest suggestion that they either don't have one, or it
would be embarrassing to be revealed?
Mr. Barry. Well, I have no details on this, other than, as
I said, I talked last week at the Pennsylvania Public Health
Association, and they told me this. They said that the State
considers it, sort of, a national security issue, which--it
just seems very odd to me.
CHEMOTHERAPY PATIENTS
Senator Specter. Well, we'll pursue that. We had a little
trouble getting the plan of our own administration, so maybe
it's not out of line.
When you talk about the people who have had chemotherapy,
as I say, that rings a bell close to home. Immune systems down.
Any special advice for that category of individual?
Mr. Barry. Not that I know of. When you undergo either
chemotherapy or radiation therapy, it takes a long time for the
immune systems to fully rebound.
Senator Specter. How long?
Mr. Barry. It can be years. In some cases, never. It, sort
of, depends on the course of chemotherapy and your own
individual body. So, any individual can consult his physician
as to what kind of shape their immune system is.
VACCINE DEVELOPMENT
Senator Specter. When you say the first wave is not too
bad, so that there's a window of opportunity, what window of
opportunity to do you see here, where we are so far behind on
developing a vaccine?
Mr. Barry. Well, by ``window,'' I meant that you do have
some time once the virus surfaced.
Senator Specter. Well, you have some time, too, before----
Mr. Barry. That--right.
Senator Specter [continuing]. Before it surfaces.
Mr. Barry. Right, exactly.
Senator Specter. Where we are now.
Although you can't really tell how much it has surfaced.
Mr. Barry. I applaud, you know, your earlier amendments,
and I am glad that the administration is now spending the
money. You create a vaccine infrastructure that is capable of
responding within a matter of months, with a new vaccine. If
your surveillance is good enough, you will likely catch it very
soon after it becomes a human virus. These past four pandemics
have shown between 6 months and 1 year before that virus
becomes serious. So, depending on how much investment, how well
things go, it is plausible that--3 years from now, 5 years from
now--that in 6 or 8 months we might well be able to produce
large doses of vaccine. We certainly could not do that today,
but you are making the investment. This committee, of course,
has a lot to say over what the investment is--in creating just
the infrastructure that will allow us to respond. Again,
whether it would take 3 years or 10 years before we are really
ready, that depends on how long it takes to develop the cell
culture techniques.
FEDERAL, STATE, AND LOCAL COMMUNICATION
Senator Specter. Let me interrupt you, Mr. Barry, because I
have one more question and my time is about to expire. Your
full statement will be made a part of the record. As you saw
Secretary Leavitt put, high on the list, communications. This
subcommittee would be interested in your expertise on what
ought to be communicated, and how. For example, your
suggestions on radiation or chemotherapy. If you could
supplement your testimony with what you think we ought to do
about communications, we'd appreciate it.
[The information follows:]
Dear Senator Specter: Thank you for the opportunity to testify, and
for your graciousness in accommodating my travel schedule. I'm writing
now to reply to the two questions you asked me to address.
The first involved the effect of chemotherapy and radiation therapy
on the immune system. Chemotherapy is the most common cause of
immunosuppression (a weakened immune system) and myelosuppression
(insufficient production of blood cells) in people receiving cancer
treatment. It's impossible to generalize about how severe these impacts
will be, since they depend on the drugs used, the dosage, the schedule,
previous treatments for cancer, age, nutritional status, type of
cancer, and the stage of the cancer. White blood cell production tends
to be most sensitive to chemotherapy drugs. Radiation therapy has a
similar impact. How long it takes a person's immune system to recover
depends on many factors as well.
No doubt you would prefer a better answer than the generalities
above. In that case, may I suggest you contact Dr. Steven Rosenberg,
chief of the Surgery Branch at the National Cancer Institute, whom you
may know since he has often testified. Dr. Rosenberg is best known for
being the first to develop a way to stimulate the immune system to cure
a cancer, and his combined expertise on clinical medicine, laboratory
research, immunology, and cancer make him one of the best people in the
world to answer your question in greater detail.
Your second question involved something closer to my own area--
communicating with the public. I have studied in considerable detail
what are probably two of the three greatest natural disasters (the 1927
flood and the 1918 influenza pandemic) ever to strike the country, and,
given that my home is in New Orleans, have lived through the third,
Katrina. I hope I have learned something from those experiences.
I believe firmly that the first responders are not firemen or
health care workers or police, but the public. This means that
considerable effort should be expended to get information to the public
sooner rather than later, and people should be given more information--
even if incomplete--rather than less. Information of course is power,
and when people have information they have some control and can make
their own informed decisions. Some of those decisions, even when fully
informed, will be bad ones. But without information, both bad
individual decisions and panic are more likely to ensue.
On influenza specifically, I'm not sure of the best way to get
information out in advance of an actual outbreak. A highly skilled
writer might be able to put useful information into a brief public
service announcement (or some notice on mass transit), while
simultaneously referring people to places where they could get more
facts about the disease itself, its progress, what individuals and
their families should do, and on what's being done. People should be
able to easily access this information, and they should be able go deep
into subject if they choose to.
The most obvious place for the kind of thing I am suggesting is a
website; that's necessary but insufficient since too many people don't
have access to them. Perhaps pamphlets for distribution not only in
doctors' & dentists' offices, etc., but in churches and temples, move
theaters and schools. (This of course means the information has to be
out there well in advance of any decisions to close public places.)
Again, since the real first responders are the public, the more the
public knows, the better off everyone is. Should a pandemic actually
strike, we need the most forthright statements.The parts of the book
that Secretary Leavitt took most to heart related to the false
reassurances given to the public, which caused the loss of trust and
threatened the very fiber of the society. I would not even issue such
statements as: ``Don't panic,'' or ``Stay calm,'' I believe that most
people's natural response is, ``Wow. I didn't know things were that
bad.''
The message also has to fit the pandemic. If the pandemic is like
1968, that calls for one message. If it looks like it will resemble
1918, it requires another. In the latter case, I think the message
should resemble Churchill's ``blood, sweat, and tears'' speech. ``This
is serious. Many Americans will die no matter how well we respond. But
we will do all that is humanly possible, it will pass, and we will get
through this.''
To keep public trust, we need to hold nothing back from either the
general public or the media. Holding information close is almost as
destructive of trust as lying. People usually think you know more than
you are saying anyway. We need to fight that preconception by flooding
people with information. Get everything out. Explain that we don't know
when we don't know, and explain why we don't know--we're conducting
tests x,y,z, and part x takes 14 hours for a result, part y takes 22
hours, etc.
In terms of the course of the disease, if we don't know we should
perhaps give a range of the most likely scenarios, from best case to
worst case. The idea that we somehow best protect the public by keeping
bad news from them is counter-productive. Yes, the media will hype any
statements and spark fear and even panic that might otherwise not
exist. Nonetheless, in the long run I think society is better served by
being told best case, worst case, and points in between, as well as
what those in authority are doing about it both nationally and locally.
Thanks again for the opportunity to testify. I hope you find this a
suitable reply.
Senator Specter. Senator Harkin.
HOSPITAL SURGE CAPACITY
Senator Harkin. Thank you, Mr. Chairman.
Mr. Barry, your book, in my reading of it, brought back
to--memories of my father, who was born in 1886, died in 1967.
But during my formative years growing up, he talked about his
early years. The two things that made the biggest impression on
his lifetime, I think, was the flu of 1918, which I never
really thought about that much, in which many members of his
own family and communities died, and the Great Depression. I
thought, how could those two be equal? But, in reading your
book, I can see now that the great flu really was kind of
equivalent in its impact on people's lives.
Now, having said that, one of the things I said to
Secretary Leavitt before he left was--had to do with hospital
surge capacity not addressed. In your book, you talk about some
of these scenes, about 4,000-8,000 cases coming into these
hospitals, they are in the corridors, and you describe, in your
book, the accounts of the nurses and others about what was
happening. Talking about what you see out there today, I mean,
are we--what would happen today if this kind of pandemic were
to hit, and we are looking at millions of people in America
seeking hospital help?
Mr. Barry. Well, I think that is part of our increased
vulnerability. Hospitals, like everything else, have become
more efficient. There are no vacant, or much fewer vacant, beds
than there used to be. Even in 1957, I have seen photographs
of, essentially, emergency hospitals, like 1918, basically look
like airplane hangars filled with cots. Back in 1957, I do not
know the exact numbers of hospital beds compared to population,
but I would, offhand, guess that there were more than there are
today. So, that is a very real problem, and a very good
question for you to ask. Of course, I'm not capable of
answering it, but I--it is a good question.
Senator Harkin. But it's your sense, your feel, that----
Mr. Barry. I mean, yeah, we would be overwhelmed. The
healthcare system today, without any question, would be
overwhelmed by a major pandemic. I mean, even in the normal
course of a flu season--I was on a book tour in Kansas City,
and I turn on the news, and eight hospitals closed their
emergency rooms because of influenza season, just normal
influenza. A pandemic is multiplied many-fold.
Senator Harkin. Thank you.
Thank you, Mr. Chairman.
Senator Specter. Thank you, Senator Harkin.
Senator Cochran.
Senator Cochran. Well, welcome, Mr. Barry. It is a pleasure
to get to see you here before our subcommittee.
Mr. Barry. Thank you.
Senator Cochran. I think ``Rising Tide'' was one of the
most interesting books I have ever read.
Mr. Barry. Thank you.
Senator Cochran. I congratulate you for that, and I will
have to read ``The Great Influenza.'' I will.
But, thank you for being here today and helping us get the
big picture on the impact that such an influenza outbreak in
our country would have and the things we can do to prepare for
it.
You have looked at the request that the administration has
submitted, in terms of the priorities, better international
surveillance, domestic surveillance, vaccines, anti-virals,
developing of greater capacity for production, communications,
and State and local preparedness. Is there anything that you
think that the administration has failed to request, in terms
of emergency funding, that we should also consider?
Mr. Barry. No, I think the basics of the plan are sound. I
would share the comments about the idea that the States have to
put out money when they are already pressed, as compared to
smallpox or some of the other things. But, basically, you know,
it is a sound plan and a very good place to begin.
Senator Cochran. In your research for----
Mr. Barry. Of course, I have not seen any details. I mean,
like you----
Senator Cochran. Yes. Sure.
Mr. Barry [continuing]. I mean, all I have heard was the
Secretary's testimony.
Senator Cochran. Sure. In your research for the book, ``The
Great Influenza,'' did you come across any parallel with the
bird flu and the question of whether or not transmission,
instead of just going between birds and humans who have had
close contact, whether there is a natural evolution for man-to-
man communication of a disease like that?
Mr. Barry. Actually, in the full prepared comments, I
mention that all influenza viruses are bird viruses. All of
them are. Historically, it is one of the most rapidly mutating
viruses in existence, and that gives it the opportunity to jump
species. It can do that one of two ways, either directly
mutating a virus, a bird virus becoming a human virus, which
happened in 1918, or it can do it indirectly. A bird virus can
infect the same cell that an existing human virus that, once
upon a time, was a bird virus also infects, and then they trade
genes and create a new virus. That happened in 1957 and 1968.
There very recently has been some scientific work that
confirmed 1918 was completely a bird virus that went straight
to man through mutation, and they have tracked and identified
several points of mutation, and they are comparing that to H5N1
right now. There are some points of similarity, where H5 has
seemed to make progress along those lines. It does give us a
good way to monitor H5, but we are not certain that even if it
makes all those mutation points similar to what happened in
1918, that does not automatically mean it will become a human
virus.
Senator Cochran. Well, thank you very much for being here.
You have added to our hearing, and we appreciate your
cooperation with our subcommittee.
Mr. Barry. Thank you very much.
Senator Specter. Thank you, Senator Cochran.
Senator DeWine.
Senator DeWine. Mr. Barry, thank you very much. You
describe some horrible symptoms in 1918, the flu. Would the
symptoms of today's bird flu be similar in any way, or can you
tell?
Mr. Barry. Some of them are. I have read pathology reports
from H5 victims and, in fact, noted that in those pathology
reports, they say, ``These findings have never before been
described in influenza.'' In fact, all of those findings had
been described in 1918. Chiefly, that the virus can get into
other organs besides the lung, including the brain, which is
quite unusual, but--normally, in birds, it is an intestinal
virus, and, in people, normally it is respiratory virus. But
both the 1918 flu and--I believe H5 variety can infect other
organs and cause other symptoms.
Senator DeWine. In your book, you state that, in 1918,
members of the American medical research community really
expected such a situation, but thought they were prepared for
it.
Mr. Barry. Right.
Senator DeWine. Any similarities between now and then, you
know, that we think maybe we're prepared, or we're getting
prepared, and that we are not?
Mr. Barry. Well, I don't think----
Senator DeWine. You've touched on this a little bit
already, but----
Mr. Barry. I don't think anyone--and I think Secretary
Leavitt would be among the first to tell you--I don't think
anybody thinks we're prepared today. Again, it would have been
nice if this had happened a few years ago, but it would have
been even nicer if, in the last 40 years, a lot more energy had
been devoted to influenza, in which case maybe we would have
the virus against the concerned portion--I mean, the vaccine
against the concerned portions of the virus, one vaccine that
worked against all influenza viruses. But for--you know, a few
years ago, we were spending more on West Nile than we were
spending on influenza, and West Nile, this year, has killed
about 55 people. If we had not spent a penny on West Nile this
year--in my opinion, this year, it would have killed about 55
people. Whereas, influenza is killing 36,000 Americans a year
anyway. I mean, every year.
Senator DeWine. Every year.
Mr. Barry. Yeah. Yeah.
Senator DeWine. Yeah.
Mr. Barry. So, it had--it has been a disease that has not
been taken seriously over a long time. Now it is being taken
seriously. We don't know when the next pandemic is going to
come. If it comes next year, we are in serious trouble. If it
waits 10 years, chances are pretty good we will be able to
handle it, certainly a lot better than we could today.
Senator DeWine. Good. Thank you very much.
Thank you, Mr. Chairman.
Senator Specter. Thank you, Senator DeWine.
CONCLUSION OF HEARING
Thank you very much, Mr. Barry. Your book is certainly a
big red flag and something we need. If you would follow up with
some specific suggestions on communications, you have got a
background to give us some special expertise and insights on
that.
I thank you all very much, and that concludes our hearing.
[Whereupon, at 10:25 a.m., Wednesday, November 2, the
hearing was concluded, and the subcommittee was recessed, to
reconvene subject to the call of the Chair.]
-