Before the Committee on Government Reform
States House of Representatives
Medical Care for Bioterrorism Exposure - - Are We Making
Evidenced Based Decisions?
Division of Microbiology and Infectious Diseases, National
Institute of Allergy and Infectious Diseases
Institutes of Health
Release on Delivery
at 1:00 pm
Wednesday, November 14, 2001
and Members of the Committee, thank you for inviting me
here today to discuss the medical response to bioterrorism
as well as current efforts by the National Institutes
of Health (NIH) to accelerate basic and clinical research
related to bioterrorism agents.
In just the
last two months we have witnessed the deliberate mailing
of spores of anthrax bacterium, including the exposure
of members of this esteemed body to this deadly bacteria.
The recent misuse of microorganisms has shocked the scientific
and public health communities, but I can assure you that
we are all working tirelessly to advance our nation's
ability to respond to bioterrorism and to advance research
to address such threats.
agencies are evaluating and accelerating measures to protect
the public from the health consequences of such an attack.
Today I will describe one component of this national effort.
As part of the NIH, the National Institute of Allergy
and Infectious Diseases (NIAID) supports research on the
diagnosis, prevention and treatment of infections caused
by a wide variety of pathogens, including those that rarely
occur in the United States and that have otherwise received
relatively little attention. It is important to note that
much of our current knowledge about pathogens can be attributed
to many years of NIH-supported basic research. NIH-sponsored
studies are also yielding key insights into organisms
of bioterrorism including agents that cause anthrax, plague,
tularemia, botulism, smallpox, and viral hemorrhagic fevers
(diseases caused by agents on the Centers for Disease
Control and Prevention (CDC) Category A list of bioterrorist
agents). I would like to describe our current efforts
in pathogen research and plans to increase research in
to detect and counter bioterrorism depends to a large
degree on the state of biomedical science. Basic and applied
research supported by NIH complements the efforts of other
agencies by developing the essential tools -- diagnostic
tests, therapies and vaccines -- needed by physicians,
nurses, epidemiologists and other public health workers
to prevent and control a disease outbreak.
To meet the
challenges posed by bioterrorism, especially to civilians,
NIH supports research in four broad areas: basic research,
diagnostics, vaccines and therapeutics.
Research. Research into the basic biology
and disease-causing mechanisms of pathogens underpins
efforts to develop interventions against agents of bioterrorism.
NIH supports research to better understand the factors
that influence a pathogen's virulence and invasiveness,
as well as those that determine antibiotic resistance.
NIH also supports research on the host/pathogen interactions.
For example, NIAID and the NIH Office of Dietary Supplements
co-sponsored a workshop to draw attention to the scientific
gaps in our knowledge of the relationship between micronutrients,
such as vitamins and minerals, and infectious diseases.
The summary of this workshop can be found in a supplement
to the Journal of Infectious Diseases: 182; Sept, 2000.
Most recently, NIAID has co-sponsored a targeted solicitation
to the research community indicating our interest in further
understanding this relationship. In total, knowledge from
basic research findings is crucial to the development
of preventive and therapeutic strategies.
tool is our ability to rapidly obtain genome sequence
information of microbial pathogens, including potential
agents of bioterrorism. Some agents, such as smallpox
and other orthopoxviruses related to smallpox, have already
been sequenced; the sequences of others, such as Bacillus
anthracis (the anthrax bacterium), Enterococcus
faecalis, and Staphylococcus aureus and
the organisms that cause brucellosis, Q-fever, glanders,
cholera, and botulism are in progress. The fruits of genomics
research, coupled with other biochemical and microbiological
information, are expected to facilitate the achievement
of critical new goals, including the discovery of new
targets for drugs and vaccines. In particular, comparative
genomics (comparing the sequences of different strains
of particular organisms) will be an important component
of future research, helping us to understand what makes
a particular organism either harmful or benign.
to these activities, and as part of our broader research
agenda, other Institutes at NIH support research on new
and emerging infectious agents, the metabolic effects
of toxic agents, hazardous chemicals, and biological mechanisms
of action of certain organophosphate chemicals, which
mimic the effects of chemically similar nerve agents.
The overall goal of this research is to establish
methods for the rapid, sensitive, and specific identification
of natural and bioengineered microbes as well as the determination
of the microbe's sensitivity to drug therapy. These scientific
advances will allow health care workers to diagnose and
treat patients more accurately and quickly.
NIH-supported researchers are developing vaccines effective
against many infectious agents, including those considered
to be bioterrorism threats (brucellosis, tularemia, Q-fever,
dengue, ebola, anthrax, smallpox, and cholera), with the
goal of producing products that are safe and effective
in civilian populations of varying ages and health status.
Vaccines against pathogens are being developed using both
traditional and novel technologies. Some novel technologies
include the development of "DNA vaccines" and innovative
systems for the rapid creation of vaccines against unfamiliar
or genetically altered pathogens; these technologies are
in various stages of development. As one example, researchers
at the Vaccine Research Center of NIAID have developed
a DNA vaccine that has protected monkeys from infection
with Ebola virus; this vaccine could soon enter human
NIH therapeutics research focuses on the development
of new antimicrobials and antitoxins, as well as the screening
of existing antimicrobial agents to determine whether
they have activity against organisms that might be employed
by bioterrorists (activities include drug screening of
potential treatments for smallpox, plague, and hantavirus).
Knowledge gained from basic and applied research is helping
to identify additional targets for medications against
agents of bioterrorism.
of antimicrobial resistance is an important issue with
the treatment of most infectious diseases. The design
of therapeutic drugs active against known drug-resistant
variants of microbes and the development of broad-spectrum
agents are important NIH research priorities. For example,
NIAID is exploring an opportunity to sequence the genomes
of a variety of clinical isolates of Bacillus anthracis
in order to investigate the potential for antimicrobial
resistance in these strains. I have included in Appendix
D a copy of the Department of Health and Human Services
report entitled "A Public Health Action Plan to Combat
Antimicrobial Resistance," which outlines the Department's
efforts to address issues of antimicrobial resistance
I have just
described NIAID's overall agenda for pathogen research.
NIAID-funded research and a bibliography of published
research articles related to vaccines and treatments for
the potential agents of bioterrorism requested by this
committee are also included in Appendices A and B, respectively.
In addition, the current recommendations for medical care
for these agents are included in Appendix C.
Now I would
like to talk about how this agenda translates to research
on two specific pathogens that are of particular concern
as bioterrorist threats, smallpox and anthrax.
and Treatment of Smallpox
considered one of the most dangerous, potential biological
weapons because it is easily transmitted from person-to-person,
and few people carry full immunity to the virus. The mortality
of smallpox infection is approximately 30 percent; those
patients who recover frequently have disfiguring scars.
has proven to be highly effective in preventing infection.
In addition, the vaccine can lessen the severity of, or
even prevent, illness in unvaccinated people exposed to
smallpox, if given within a few days after exposure. Based
on its effectiveness in prevention and treatment of smallpox,
this vaccine was the essential factor in the global eradication
of smallpox in 1977. Vaccinations to prevent smallpox
have not been required in the United States since 1972.
In the near-term,
a bioterrorist attack involving smallpox would require
the utilization of stores of the existing smallpox vaccine
to protect those at immediate risk. The current stock
of DryvaxÒ vaccine, approximately 15 million doses,
clearly would not be enough to respond to a national smallpox
epidemic. Last year, NIAID initiated a study to determine
the feasibility of expanding the use of the existing stores
of the DryvaxÒ vaccine by testing various dilutions.
The results of this study showed that the full-strength
vaccine had maintained its potency, and that 70 percent
of people who received a single dose of a 1:10 dilution
of vaccine mounted a sufficient immune response. In the
first week of November, a new smallpox vaccine study began
that is designed to compare the use of a 1:5 dilution,
1:10 dilution, and undiluted vaccine in order to determine
if a diluted vaccine combined with an alternative vaccination
schedule could protect a greater number of people than
does the standard dose and regimen. This study will provide
data that will guide the use of the remaining stockpile
of smallpox vaccine if needed to protect the general population.
to support the clinical testing of new smallpox vaccines
that may be safely used in other segments of the population.
At the same time, we are looking into alternative vaccine
strategies, including the development of "DNA vaccines"
and other innovative systems, with the goal of designing
safer and more effective vaccines.
NIAID is also
accelerating efforts to identify antiviral drugs that
will be effective in treating smallpox and related viruses.
One of these agents is an antiviral called cidofovir,
which is approved by the Food and Drug Administration
(FDA) for treating certain AIDS-related viral infections.
Cidofovir has shown potent activity against smallpox and
related viruses in test tube studies and in animal models.
NIH has taken the lead in developing a protocol that would
allow cidofovir to be used in emergency situations for
the treatment of smallpox.
agents are also being investigated. For the past three
years, NIAID and the U.S. Army Medical Research Institute
of Infectious Diseases (USAMRIID) have screened approximately
500 compounds for potential antiviral activity against
and Treatment of Anthrax
of Bacillus anthracis, the agent that causes
anthrax, help to establish it as a formidable bioterrorist
threat, including its stability in spore form, its ease
of culture, and the absence of natural immunity in industrialized
has three major clinical forms: cutaneous, inhalation,
and gastrointestinal. If left untreated, anthrax in all
forms can lead to septicemia and death. Early treatment
of cutaneous and gastrointestinal anthrax with appropriate
antibiotics is usually curative, and early antibiotic
treatment of all forms is important for recovery. Although
case-fatality estimates for inhalational anthrax are based
on incomplete information, the historical rate is extremely
high, approximately 75%, even with all possible supportive
care including appropriate antibiotics.
adsorbed (AVA) is the only currently licensed anthrax
vaccine. At this time, AVA is recommended only for high-risk
populations such as veterinarians. The Department of Defense
(DOD) also uses this vaccine to protect U.S. military
personnel in high-threat areas. The current schedule for
receiving vaccine, 6 doses over the course of 18 months,
is cumbersome and efforts are underway to identify a simpler
safety of the very young, the aged, and immunocompromised
individuals requires a different approach to drug therapy
and vaccine prevention than would be applicable in a military
population. NIAID has been working with DOD to support
the development of the next generation of anthrax vaccines
that may be more appropriate than AVA for use in the civilian
population. NIAID is also exploring rapid diagnosis of
anthrax and the utility of alternative antimicrobial or
antitoxin therapies. Together with the Food and Drug Administration
(FDA), CDC, and USAMRIID, NIH is working to prioritize
and accelerate testing of promising candidates for use
as antimicrobial therapies for anthrax in order to increase
the pool of available treatments. NIAID-supported investigators
have recently published two studies in the scientific
journal Nature that help to explain how anthrax
toxin destroys cells. In the first study, researchers
have identified the site on the cell that binds the anthrax
toxin and have developed a compound that may disable it.
Another group of investigators has characterized the structure
of a major component of the anthrax toxin. The information
gained through these studies will likely hasten the development
of new drugs to treat anthrax.
our many research partners, NIH has made substantial progress
in the research effort that is critical to our Nation's
fight against terrorism. In addition to previously mentioned
collaborations with other government agencies, NIAID maintains
important partnerships with industry that are essential
to the development of new technologies and treatments
in the infectious diseases arena.
to be accomplished, however, and the challenges posed
by bioterrorism will require a protracted and sustained
commitment. NIH will announce in the next few weeks several
new initiatives to provide the academic and industrial
research communities with an opportunity to propose studies
targeting new approaches to research on agents of bioterrorism.
The submission, review, and funding of these proposals
will be expedited in order to facilitate the rapid advance
of these important research endeavors.
With a strong
research base, talented investigators throughout the country,
and the availability of powerful new research tools, we
fully expect that our basic and applied research programs
will provide the essential elements that will help enhance
our defenses against those who attempt to harm us with
my testimony. I would be happy to respond to any questions
you might have.
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Last revised: November 14, 2001