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Fiscal Year 2003 Budget Request
Witness Appearing Before the
House Subcommittee on Labor-HHS-Education Appropriations
Anthony S. Fauci, M.D.
Director
National Institute of Allergy and Infectious Diseases
March 13, 2002
Mr. Chairman and Members of the Committee:
I am pleased to present the President's budget request for the National Institute of Allergy and Infectious Diseases (NIAID) for Fiscal Year (FY) 2003, a sum of $3,999,379,000, which reflects an increase of $1,456,933,000 over the comparable Fiscal Year 2002 appropriation. The NIAID budget request includes the performance information required by the Government Performance and Results Act (GPRA) of 1993. Prominent in the performance data is NIAID's second annual performance report, which compared our FY 2001 results to the goals in our FY 2001 performance plan.
NIAID supports and conducts basic and applied research to better understand, treat and prevent infectious, immunologic, and allergic diseases. For more than fifty years, NIAID research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and around the world. The scope of the NIAID research portfolio has expanded considerably in recent years in response to new challenges such as bioterrorism; the emergence or re-emergence of diseases such as the acquired immunodeficiency syndrome (AIDS), West Nile fever, dengue, malaria and tuberculosis; and the increase in asthma among children in this country. The growth of NIAID programs also has been driven by unprecedented scientific opportunities in the core NIAID scientific disciplines of microbiology, immunology, and infectious diseases. Advances in these key fields have led to a better understanding of the human immune system and the mechanisms of infectious and immune-mediated diseases.
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The final four months of 2001 were among the most extraordinary -- and tragic -- in American history. The September 11 attacks on the World Trade Center and Pentagon have transformed society in ways that we are only now beginning to discern. Superimposed on that tragedy were the first recorded cases of anthrax in the United States to result from an intentional human act. Of 18 confirmed anthrax cases associated with bioterrorism in the eastern United States in 2001, 11 individuals suffered the inhalational form of the disease; 5 of these people died.
Homeland defense is a multifaceted endeavor. Defense against and response to bioterrorism is a critical component of homeland defense, and our ability to detect and counter bioterrorism depends to a large degree on the state of biomedical science. As the lead agency at NIH for infectious diseases and immunology research, NIAID has developed a Strategic Plan for Counter-Bioterrorism Research, as well as a detailed NIAID Counter-Bioterrorism Research Agenda, with short-, intermediate-, and long- term goals. The Strategic Plan and Research Agenda stress two over-arching and complementary components: basic research into agents with bioterrorism potential and the specific and non-specific host defense mechanisms against those agents, and applied research with pre-determined milestones for the development of new or improved diagnostics, vaccine and therapies. We focus on research in six key areas:
Microbial Biology. Research into the basic biology and disease-causing mechanisms of pathogens underpins all our efforts to develop interventions against agents of bioterrorism. NIAID supports research to better understand the factors that influence the virulence and invasiveness of a pathogen, as well as those that determine antibiotic resistance.
An important new tool in understanding all microbes is our ability to rapidly obtain microbial genome sequence information, including that of potential bioterror agents. Many such agents have already been sequenced; others, including different strains of Bacillus anthracis, the anthrax bacterium, are in the process of being sequenced. These efforts promise to facilitate the discovery of new medical interventions.
Host Response to Microbes. In order to develop potent, safe, and effective vaccines, accurate diagnostics, and immunotherapeutics against microbes that may be used as bioterrorist agents, research has been accelerated to improve our understanding of the complex parameters of two components of the human immune system: innate and adaptive immunity.
Vaccines. NIAID has bolstered research efforts on vaccines against many of the infectious agents considered to be bioterrorism threats, with an eye toward generating products that are safe and effective in civilian populations of varying ages and health status. For example, a three-tiered strategy for smallpox vaccine research has been developed. In the near-term, a clinical trial at several NIAID Vaccine and Treatment Evaluation Units suggests that it is possible to "stretch" the 15.4 million available doses of licensed smallpox vaccine 5- or 10-fold by dilution. A concurrent initiative is the development of a new smallpox vaccine: a safe, sterile product grown in cell cultures using modern technology. This vaccine will be rapidly tested in human clinical trials; more than 200 million doses will be produced and delivered to the federal government by the end of 2002. In the long-term, basic research promises to provide a third generation of smallpox vaccines that could be used in all segments of the population, including pregnant women and people with weakened immune system. Additional bioterrorism vaccines also are in development. For example, a new anthrax vaccine, based on a bioengineered component of the anthrax bacterium called recombinant protective antigen (rPA), will soon enter human trials. On the NIH campus, researchers at the NIAID Dale and Betty Bumpers Vaccine Research Center have developed a DNA vaccine that protected monkeys from infection with Ebola virus, and that will soon be tested in human volunteers.
Therapeutics. NIAID 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. For example, in collaboration with DOD and with support from CDC, NIAID has rigorously screened a large number of antiviral drugs against smallpox- related viruses. One of these agents is an antiviral drug 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 poxviruses related to smallpox in test tube studies and in animal models. NIAID has taken the lead in developing a protocol that would allow cidofovir to be used in emergency situations for the treatment of smallpox. Concurrently, other anti-smallpox agents are being investigated.
Diagnostics. The overall goal of NIAID bioterrorism research on diagnostics 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.
Research Resources. Basic research and the development of new vaccines, therapeutics, and diagnostics depend on the availability of research resources, such as genomics/proteomics information, appropriate animal models, standardized reagents, and appropriate laboratory facilities. Among many initiatives, NIAID plans to accelerate training of investigators specializing in bioterror agents, establish the first four to seven of what will be ten regional Centers of Excellence for Bioterrorism and Emerging Diseases Research, develop a centralized research reagent repository, and expand the national bioterrorism research infrastructure. The latter will include the construction/renovation of BioSafety Level (BSL) 3-4 laboratories, necessary to work with the most dangerous pathogens.
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We anticipate that the large investment in research on counter-bioterrorism will have many positive "spin-offs" for other diseases. The planned NIAID research on microbial biology and on the pathogenesis of organisms with bioterror potential will certainly lead to an enhanced understanding of other more common and naturally occurring infectious diseases that afflict people here and abroad. In particular, the advancement of knowledge should have enormous positive impact on our ability to diagnose, treat and prevent major killer-diseases such as malaria, tuberculosis, HIV/AIDS, and a spectrum of emerging and re-emerging diseases such as West Nile fever, dengue, influenza, and multi-drug resistant microbes. Furthermore, and importantly, the NIAID research agenda on counter-bioterrorism will greatly enhance our understanding of the molecular and cellular mechanisms of the innate immune system and its relationship to the adaptive immune system. This clearly will help in the search for new ways to treat and prevent a variety of immune-mediated diseases such as systemic lupus erythematosus, rheumatoid arthritis and other autoimmune diseases. In addition, new insights into the mechanisms of regulation of the human immune system will have positive spinoffs for diseases such as cancer, immune-mediated neurological diseases, allergic and hypersensitivity diseases, as well as for the prevention of rejection transplanted organs.
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Vaccine research, so important to our preparedness against future bioterrorism attacks, has long been a cornerstone of NIAID research. NIAID-supported research has led to the development of many new and improved vaccines that are now widely used; these vaccines have saved literally millions of lives and prevented untold illness and disability from infectious diseases. Success stories include the development of vaccines against Haemophilus influenzae type b, pertussis, chickenpox, pneumococcal disease, and hepatitis A and B. NIAID has three broad goals in vaccine research: identifying new vaccine candidates to prevent diseases for which no vaccines currently exist; improving the safety and efficacy of existing vaccines; and designing novel vaccine approaches, such as new vectors and adjuvants. To speed these efforts, NIAID has made a significant investment in the growing field microbial genomics, and has funded the genomic sequencing of more than 60 medically important microbes. Approximately 20 of these projects have been completed, including the bacteria that cause tuberculosis, gonorrhea, chlamydia, cholera, the parasite that causes malaria, as well as the mosquito that transmits malaria. The availability of the genomic sequences of these and other organisms will facilitate the identification of a wide array of new antigens for vaccine targets.
One of the important challenges for the 21st century is the development of safe and effective vaccines for the three greatest microbial killers worldwide: HIV/AIDS, malaria, and tuberculosis. These three diseases account for one-third to one-half of healthy years lost in less developed countries. NIAID has a robust portfolio of vaccine research and development for these and other diseases of global importance.
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Despite recent progress in treatment and prevention, human immune deficiency virus (HIV) disease and AIDS continue to exact an enormous toll throughout the world. An estimated 40 million people are living with HIV/AIDS, and another 22 million people with HIV/AIDS have died. More than 95 percent of these infections and deaths have occurred in developing countries, most of which are also burdened by other significant health challenges. In these nations, HIV/AIDS threatens not only human welfare, but social, political and economic stability as well. In the United States, approximately 850,000-950,000 people are living with HIV/AIDS; approximately 450,000 deaths among people with AIDS had been reported to the CDC as of the end of 2000. The rate of new HIV infections in this country has reached an unacceptable plateau of 40,000 per year, with minority communities disproportionately affected.
In the United States and other western countries, potent combinations of anti- HIV drugs (highly active antiretroviral therapy or "HAART") have dramatically reduced the numbers of new AIDS cases and AIDS deaths. Meanwhile, the toll of AIDS has accelerated elsewhere in the world, especially in poor countries where expensive HAART regimens are beyond the reach of all but a privileged few. Fortunately, this disparity in access to life-saving medications may be changing. Building on the research infrastructure NIAID has helped establish in Africa and elsewhere in the developing world, we are actively working with our international colleagues to link the provision of anti-HIV therapy to efforts in prevention research, with the goal of facilitating a comprehensive approach to the AIDS pandemic in poor countries. Concurrently, NIAID- supported investigators are testing a diverse range of HIV prevention and vaccine strategies. Prevention efforts in our country and abroad focus on several key areas, including behavioral modification, interventions to prevent mother-to infant transmission of HIV, and the development of topically applied microbicides that women could use to protect themselves against HIV and other sexually transmitted pathogens. Several vaccine candidates have recently shown remarkable promise in tests in non- human primates. The best candidates are rapidly being moved into human clinical trials at sites of NIAID's HIV Vaccine Trials Network in the United States and abroad, and at the NIAID Vaccine Research Center.
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NIAID-funded research in basic and clinical immunology has led to many promising approaches for treating individuals with immunologic conditions such as multiple sclerosis, type I diabetes and asthma. Researchers are developing novel ways of selectively blocking inappropriate or destructive immune responses, while leaving protective immune responses intact, an area of research known as tolerance induction. The NIAID-supported Immune Tolerance Network an international consortium of approximately 50 research groups, now has 16 clinical trials that are enrolling patients or will do so soon, in areas such as islet transplantation (for diabetics), kidney transplantation, autoimmune diseases, and asthma and allergic diseases.
For the past decade, NIAID also has focused on reducing the significant and growing burden of asthma among inner-city minority children. The current Inner-City Asthma Study has investigated novel interventions to improve the health of inner-city children with asthma. One approach, called a physician feedback intervention, involves periodic reports to the child's doctor about the status of the child's asthma. These reports, generated from bi-monthly phone interviews with parents, recommend changes in the child's treatment regimen according to National Heart, Lung, and Blood Institute (NHLBI) guidelines, if warranted. Another method is an environmental intervention that involves identifying and removing asthma triggers such as cigarette smoke or cockroaches from the child's home. Both interventions are reducing health care utilization, and the children receiving the environmental intervention gained an additional three weeks of symptom-free days during the intervention year. We are working to make such interventions available nationwide.
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With a strong research base, talented investigators in the United States and abroad, and the availability of powerful new research tools, we fully expect that our basic and applied research programs will provide the essential elements to enhance our defenses against those who would attempt to harm us with bioterrorism, to develop new tools in the fights against HIV/AIDS and other infectious diseases, and to improve therapies and management of immune-mediated diseases.
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