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Fiscal Year 2004 Budget Request
Anthony S. Fauci, M.D.
Director
National Institute of Allergy and Infectious Diseases
National Institutes of Health
April 8, 2003
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) of the National Institutes of Health (NIH). The Fiscal Year (FY) 2004 budget includes $4,335,255,000, an increase of $631,126,000 over the FY 2003 enacted level of $3,704,129,000 comparable for transfers proposed in the President's request. 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 third annual performance report, which compares our FY 2002 results to the goals in our FY 2002 performance plan.
Since 1948, NIAID has conducted and supported basic research into the etiology and pathogenesis of allergic, immunologic, and infectious diseases, as well as targeted research to develop new and improved interventions to prevent, diagnose, and treat these illnesses. Over the past half century, and in the past decade in particular, progress in the core disciplines of the Institute -- immunology, microbiology, and infectious diseases -- has been extraordinary. The rapid growth in scientific knowledge and the availability of new research tools has facilitated the development of numerous vaccines, therapies and other interventions that have saved or improved the lives of millions of individuals. For example, NIAID-supported scientists helped develop many of our most useful vaccines, including new or improved vaccines that protect against invasive Haemophilus influenzae type b (Hib) disease, pneumonia and meningitis caused by pneumococcal bacteria, pertussis, influenza, measles, mumps, rubella, chickenpox, and hepatitis A and B. These and other vaccines helped reduce infectious disease mortality in the Unites States more than 14-fold in the 20th century.
The scientific advances realized during 55 years of NAID research have been applied to long-standing global health problems such as asthma, autoimmune diseases, diarrheal diseases, malaria, and tuberculosis, as well as to diseases and pathogens that have recently emerged or re-emerged. Examples of the latter include the acquired immunodeficiency syndrome (AIDS), highly virulent influenza viruses, West Nile virus, drug-resistant microbes, severe acute respiratory syndrome (SARS), and a new kind of emerging disease - one spread deliberately by bioterrorists. As has been the case with AIDS and other emerging health crises, the NIAID response to the threat of bioterrorism has been swift and comprehensive, resulting already in important progress both in basic science and in the development of biodefense countermeasures.
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The anthrax attacks in the fall of 2001, which occurred soon after the horror of the September 11 terrorist assaults on the World Trade Center and the Pentagon, starkly exposed the vulnerability of the United States and the rest of the world to bioterrorism. Since the fall of 2001, NIAID has rapidly accelerated basic and clinical research devoted to the prevention, diagnosis, and treatment of diseases caused by potential agents of bioterrorism. Indeed, biodefense research spending now accounts for approximately one-third of the NIAID research portfolio. Our efforts have focused both on "Category A" agents considered to be the worst bioterror threats (smallpox, anthrax, botulinum toxin, plague, tularemia, and hemorrhagic fever viruses such as Ebola), as well as on a longer list of Category B and C priority pathogens agents that also pose significant threats to human health. The NIAID biodefense program is guided by the NIAID Strategic Plan for Biodefense Research, as well as by detailed research agendas for Category A agents and Category B and C priority pathogens. Each of these documents was prepared in consultation with blue-ribbon panels of experts, and delineates immediate, intermediate, and long-range NIAID plans for biodefense research and countermeasures development. Using the roadmap outlined in these agendas, NIAID has developed a total of 46 biodefense initiatives to stimulate research in Fiscal Years 2002 and 2003: 30 are new initiatives and 16 are significant expansions. During this same time period, NIAID has seen a 30 percent increase in the number of grant applications; the vast majority of these are in response to our biodefense initiatives.
The NIAID biodefense research program is anchored in the traditional NIH processes of basic biomedical research; concurrently, we are aggressively pursuing the goal of translating the findings of basic research into definable and quantifiable endpoints such as diagnostics, therapeutics, and vaccines. NIAID historically has sought to translate basic research findings into "real-world" interventions, as with the vaccines noted above. Until now, however, the path to product development has not been central to our research strategy. The attacks of September 11, 2001, and the subsequent anthrax incidents have compelled us to modify somewhat the way we do business, with an increased focus on translational research and product development. This applied research is based on the strongest possible foundation of fundamental knowledge of pathogenic microbes and the host immune response.
As we pursue innovative biodefense countermeasures, we have strengthened our interactions with the private sector, including biotechnology companies and pharmaceutical manufacturers. Many biodefense products do not provide sufficient incentives for industry to develop them on their own, because a profitable market for these products cannot be guaranteed. Therefore, NIAID has developed public-private partnerships with industry to overcome such obstacles so that new and improved interventions against bioterror threats can quickly be developed.
A number of significant advances in understanding, treating, and preventing potential agents of bioterror already have been realized. For example, NIAID-supported scientists have identified antivirals that may play a role in treating smallpox or the complications of smallpox vaccination, as well as new antibiotics and antitoxins against other major bioterror threats. Investigators have demonstrated that existing stores of smallpox vaccine can be diluted five-fold and still retain their potency, greatly increasing the Nation's available stock of smallpox vaccine. These studies of diluted smallpox vaccine helped fulfill an immediate goal delineated in our strategic plan for biodefense. In the intermediate-term, new and improved vaccines against smallpox, anthrax, and other potential bioterror agents are being developed and evaluated at NIAID intramural facilities, as well as by our grantees and contractors in academia and industry. One of these is a smallpox vaccine based on a strain of the vaccinia virus that replicates less robustly than the traditional smallpox vaccine virus, and is known to be less reactogenic than the current smallpox vaccine. In the long-term, we will develop even safer vaccines against smallpox virus and other pathogens.
Advances in biodefense, as well in other areas of infectious diseases research, are being facilitated by the detailed information about pathogens that now can be rapidly gleaned by determining their genomic sequence. The field of pathogen genomics has made remarkable progress: sequencing of the genomes of more than 100 pathogens is complete or nearing completion. Among them are approximately 30 different Category A, B and C agents, including multiple strains of the anthrax bacterium. This genomic information is being used to inform the development of new antimicrobials, vaccines, and diagnostics.
Progress in biodefense research depends on the availability of research resources, such as animal models, standardized reagents, and appropriate laboratory facilities, as well as on human capital, that is, well-trained investigators. Among many initiatives to improve the biodefense research infrastructure, NIAID will establish in fiscal year 2003 a nationwide network of Regional Centers of Excellence for Biodefense and Emerging Infectious Disease Research, and design, build, and renovate a system of Regional and National Biocontainment Laboratories. These facilities will include a small number of Biosafety Level-4 (BSL-4) laboratories, which have the containment safeguards necessary to study highly pathogenic organisms. The new Centers and laboratories will serve as national resources for biodefense research and product development, as well as for the study of other emerging diseases such as influenza and West Nile virus.
The many new NIAID initiatives in biodefense research will provide benefits far beyond protection from deliberate acts of bioterrorism. After all, the general philosophy and strategy of biodefense is essentially the same as that for defense against naturally emerging and re-emerging infectious diseases that threaten global public health. With the careful NIAID planning process, new biodefense resources will unquestionably have enormous benefits in our struggle against other diseases, endemic and emerging, that far transcend the specter of bioterrorism.
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Another major focus of the Institute, accounting for approximately one-third of NIAID spending, is research devoted to finding interventions to slow the pandemic of the human immunodeficiency virus (HIV), the cause of AIDS. HIV/AIDS is the defining health crisis of our generation, having claimed well over 20 million lives since the beginning of the pandemic. Another 42 million people worldwide are living with the virus. Most of the world's HIV-infected people live in resource-poor countries, where HIV frequently is superimposed on other significant health challenges, including endemic diseases such as malaria and tuberculosis, and malnutrition. By 2010, more than 45 million new infections will occur, for a cumulative total of 105 million infections, according to estimates of the Joint United Nations Programme on HIV/AIDS.
Despite these grim numbers, significant progress has been made against the HIV/AIDS, much of it due to the research and prevention efforts of NIAID and other NIH Institutes, the Centers for Diseases Control and Prevention, and other agencies of the Department of Health and Human Services. In this country, prevention efforts have reduced the annual number of new HIV infections in the United States from approximately 150,000 per year to about 40,000 annually. In recent years, we have seen the positive impact of advances in HIV therapeutics for many living with HIV/AIDS in the United States and other western countries, and more recently the promise these medicines offer for those in the developing world. All but one of the 19 antiretroviral drugs licensed in the United States target one of two viral targets: the HIV protease enzyme or the HIV reverse transcriptase enzyme. Over the past few years, NIAID-supported scientists and their collaborators have identified new targets for HIV therapy and novel drugs that block other stages of the virus replication cycle. Among them are agents that block viral genes from entering the host cell nucleus, and drugs that keep the virus from attaching to or entering the cell in the first place. In the latter category, a drug known as Fuzeon or T-20 that blocks the fusion of HIV to the host cell membrane was recently approved and holds great promise for the many HIV-infected patients who harbor HIV that is resistant to current therapies.
To help turn the tide of the global HIV/AIDS pandemic, NIAID has established research collaborations with international colleagues to develop comprehensive approaches to the HIV pandemic in poor countries, encompassing prevention activities, antiretroviral therapy when feasible, and care of the HIV-infected person. These collaborations have yielded extraordinary results, notably in developing methods to reduce mother-to-child transmission of HIV. However, a rate-limiting factor in HIV/AIDS research efforts in developing countries has been a lack of funds for the purchase of antiretroviral drugs and for improving existing healthcare infrastructure. In January 2003, the Institute's international AIDS program received a substantial boost with the announcement of the President's Emergency Plan for AIDS Relief. This plan commits $15 billion over 5 years ($10 billion of which is new money), starting with $2 billion in fiscal year 2004, for HIV/AIDS prevention, treatment, and care in 14 of the hardest-hit countries in sub-Saharan Africa and the Caribbean. This lifesaving effort will not only reduce the suffering caused by HIV/AIDS in countries that account for 50 percent of the world's HIV infections, but will provide a framework that will facilitate NIAID research efforts to develop new and improved tools of treatment and prevention.
Many approaches to HIV prevention are being developed or refined, but the "holy grail" of HIV prevention remains the development of a safe and effective HIV vaccine. Numerous vaccine candidates have shown promise in monkey models of HIV infection, and the most promising ones are rapidly being moved into human trials on the NIH campus and in the domestic and international sites of the NIAID HIV Vaccine Trials Network.
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In addition to developing HIV and biodefense vaccines, NIAID continues to make significant progress in the quest for new and improved vaccines for other diseases of global health importance. The NIH 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, substances that improve vaccine performance.
More than 100 vaccines currently are being developed by NIAID-funded researchers, including promising candidates against emerging diseases such as Ebola virus, West Nile virus, dengue, and dangerous strains of influenza virus. Of particular note are novel tuberculosis vaccines, which soon will enter clinical trials. These trials will mark the first time in more than 60 years that new approaches to TB vaccination have been assessed in humans. These vaccines are a tangible "payoff" of research funded by NIAID and others that led to the availability of the complete genomic sequence of the tuberculosis bacterium. The quest for a malaria vaccine received a significant boost in 2002 when researchers funded by NIAID and others published the genomic sequences of the malaria parasite Plasmodium falciparum, and one of its main mosquito vectors, Anopheles gambiae. Together, these projects are probably the most significant pathogen genome sequencing effort to date. With the availability of the human genome sequence, scientists now have detailed genomic information for each of the organisms involved in human malaria: the human host, the mosquito vector and the malaria parasite itself. This groundbreaking malaria research promises to provide new targets for vaccine development and other interventions against a disease that claims the lives of more than a million people each year, most of them children in sub-Saharan Africa.
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Immune-mediated diseases such as autoimmune diseases, allergic diseases, and asthma are important health challenges here and abroad. Autoimmune diseases, for instance, afflict 5 to 8 percent of the U.S. population; asthma and allergic diseases combined represent the sixth leading cause of chronic illness and disability in the United States. The past two decades of fundamental research in immunology have resulted in a wealth of new information and extraordinary growth in our conceptual understanding of the immune system and the pathogenesis of immune-mediated diseases. Researchers now know a great deal about the effector molecules that contribute to many immunological conditions, knowledge that has led to the design and discovery of drugs to block those molecules. For instance, we now have powerful treatments that selectively target several of the immune system molecules that cause inflammation, a hallmark of many autoimmune diseases. Blockers of an immune system molecule called tumor necrosis factor-alpha are now routinely used in patients with rheumatoid arthritis and other immunologic conditions.
A relatively new avenue of research suggests that it may be possible to interrupt deleterious immune responses, without dampening protective ones, and provide patients with long-term clinical benefit. The ability to induce "immune tolerance" by selectively blocking deleterious immune response holds great promise for treatment of many immune-mediated conditions, including type 1 diabetes, rheumatoid arthritis and multiple sclerosis, as well as asthma and allergic diseases. For example, researchers have shown in a small trial conducted by the NIAID-sponsored Immune Tolerance Network (ITN) that antibodies to the CD3 molecule on T-cells, given for two weeks soon after patients were diagnosed with Type 1 diabetes, appeared to halt the destruction of the patients' insulin-producing cells for at least a year, preserving their ability to produce some of their own insulin. Further follow-up is underway to determine the long-term benefits of this experimental therapy; a larger trial is currently recruiting patients.
Induction of immune tolerance is also one our highest priorities in organ transplantation research. The ability to selectively block the immune response to a transplanted organ would diminish or eradicate the risk of rejection, as well as the risks and morbidities associated with current methods of immunosuppression. A trial currently underway in the ITN is using a unique approach involving simultaneous bone marrow and kidney transplantation in patients with multiple myeloma. Although only a very small number of patients have undergone the procedure, early results are encouraging, as they have tolerated their transplanted kidneys without immunosuppressive medications for up to three years.
Another important NIAID research focus is the development of new interventions to reduce the burden of asthma. NIAID has long been at the forefront of discoveries leading to the characterization of asthma and allergic diseases and is now vigorously pursing the translation of basic knowledge into more effective treatment and prevention strategies. The NIAID-sponsored Inner-City Asthma Study, completed in 2002, evaluated the effects of a home-based environmental intervention on asthma symptoms and health care utilization in inner-city children with moderate to severe asthma. The intervention led to an additional three weeks of symptom-free days and a 14 percent reduction in unscheduled emergency room or clinic visits in the first year of the intervention; these effects largely persisted for a year following the intervention phase. The improvement in symptoms was correlated with a reduction in levels of key allergens in the home. Building on these results, the NIAID in 2002 launched the Inner-City Asthma Consortium, to conduct clinical trials of novel immune-based agents to treat or prevent asthma.
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The role of NIAID in fighting infectious and immunologic diseases has never been more important, particularly in the post 9-11 world. Working with our many collaborators in the public and private sectors, we hope to further reduce the burden of diseases endemic in the United States and abroad, to enhance our preparedness against bioterrorism, and to continue to prepare for new threats to public health that will inevitably emerge in the future.
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