About the Director

DEPARTMENT OF HEALTH AND HUMAN SERVICES

I am pleased to present the President's budget request for the National Institute of Allergy and Infectious Diseases (NIAID) for Fiscal Year 2000. The President proposes that the NIAID receive $789.2 million, an increase of 2.4 percent for NIAID non-AIDS research activities. Including the estimated allocation for AIDS research activities, total support proposed for the NIAID is $1.6 billion, an increase of 2.4 percent over the comparable FY 1999 appropriation. Funds for NIAID AIDS research efforts are included in the Office of AIDS Research budget request.

Domestic and Global Health: Reducing the Burden of Infectious Diseases

A central goal of NIAID is to reduce the burden of infectious diseases, which remain the leading cause of death worldwide and the third leading cause of death in the United States. This is a daunting challenge since newly recognized diseases such as AIDS are superimposed on old foes such as malaria and tuberculosis, which continue to exact a huge toll. In today's world, the enormous volume of international travel and trade has largely erased the distinction between domestic and global health problems. Americans are vulnerable to infectious diseases that emerge anywhere in the world: a virulent strain of influenza virus, for example, could reach our shores in less than a day from virtually anywhere on the globe. A bioterrorist's attack could impact wide geographical areas; microbes do not stop at borders.

Further compounding the problem of infectious diseases is the widespread emergence of drug-resistant pathogens. For example, the World Health Organization estimates that strains of the tuberculosis bacterium resistant to one or more drugs have infected up to 50 million people worldwide. Because of drug resistance, nearly 10 percent of invasive pneumococcal infections in the United States 1997 were untreatable with the three leading classes of antibiotics. Many other common diseases are increasingly resistant to standard drugs, including infections with common bacteria such as staphylococci, sexually transmitted diseases, and food-borne illnesses.

Against this backdrop, the Institute's multi-faceted efforts in understanding disease-causing microbes and how they develop drug resistance, delineating the human immune response to pathogens, and developing new diagnostics, interventions and vaccines, are critical to our ability to address current microbial threats, as well as those that will inevitably emerge in the future.

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HIV/AIDS In the United States

Considerable progress has been made against one of the world's leading infectious causes of death, the human immunodeficiency virus (HIV), the cause of AIDS. In the United States, the number of new AIDS cases and AIDS-related deaths has dropped dramatically. Among people aged 25 to 44, AIDS is now the fifth leading cause of death; just three years ago it was the leading cause of death in this age group. The recent decline in HIV-related mortality in the United States is due to several factors, particularly the increased use of potent combinations of anti-HIV drugs. The development of 15 licensed antiretroviral drugs has been facilitated by NIAID-supported basic research on HIV and the immune system. In addition, many of the pivotal clinical trials of these medications have been conducted within the NIAID network of clinical trials programs.

Despite the improved prognosis for HIV-infected individuals in the United States and other western countries, it is essential that we not become complacent with regard to the HIV/AIDS epidemic. The rate of new HIV infections in the United States -- approximately 40,000 per year -- continues at an unacceptably high level. In addition, many HIV-infected individuals have not responded adequately to currently available anti-HIV drugs, cannot tolerate their toxicities and side effects, or have difficulty adhering to complex dosing schedules.

These realities underscore the importance of NIAID's ongoing research into learning more about the HIV disease process and developing the next generation of antiretroviral therapies, including those aimed at targets in the viral replication cycle not addressed by current therapies.

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AIDS Vaccine and Prevention Research

Elsewhere in the world, the HIV epidemic continues to accelerate, notably in sub-Saharan Africa, Asia , the Indian sub-continent, and certain countries in the former Soviet Union. The expansion of the epidemic in the developing world, where expensive anti-HIV drugs are beyond the reach of all but the privileged few, underscores the urgent need for a safe and effective HIV vaccine. A sustained commitment to basic and applied HIV vaccine research is critical, as is the further development of topical microbicides and other approaches to HIV prevention.

As part of the NIAID effort in HIV vaccine development, the Institute has awarded more than 100 grants in a special program that fosters innovative research on HIV vaccines. Many novel approaches to an HIV vaccine are now being pursued, including vectored vaccines, which employ harmless viruses engineered to carry genes encoding one or more HIV proteins. Phase I and Phase II studies of this approach in the United States have yielded promising results. The Institute also is a partner in the NIH Vaccine Research Center (VRC), a new program involving NIH scientists with expertise in immunology, virology and vaccine development.

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Genomic Sequencing

Genomic sequencing technology has revolutionized medical research and is intimately linked to the Institute's mission. Although this technology is most often associated with the Human Genome Project, it is less widely known that numerous projects are underway to sequence the genomes of disease-causing microbes. These initiatives promise to speed vaccine and drug development, as well as to facilitate studies of disease pathogenesis and drug resistance. In 1998 alone, NIAID-supported researchers reported the complete genomic sequence of three important pathogens: the agents of chlamydia, syphilis and tuberculosis, as well as the sequence of one of the chromosomes of the malaria parasite Plasmodium falciparum. Significantly, no good vaccine exists for these four diseases. The new genomic sequence data promise to provide important insights regarding the components of these organisms that might be incorporated into candidate vaccines.

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NIAID Malaria Research

Malaria is one of the most devastating emerging and re-emerging diseases. It claims 1.5 to 2.7 million lives each year in tropical and subtropical regions of the world, according to the World Health Organization (WHO). Every 30 seconds, a child dies of malaria. As a partner in the Multilateral Initiative on Malaria (MIM), NIH is facing the challenges of malaria with laboratory, field-based and clinical research efforts within the NIAID intramural research program in Bethesda, Md., at grantee institutions elsewhere in the United States, and in collaboration with foreign colleagues in Africa, Asia, South America, and the Pacific region. In this endeavor, we and our colleagues in the MIM have an important new ally, World Health Organization (WHO) Director General Dr. Gro Harlem Brundtland, who recently launched the ambitious "Roll-Back Malaria" program.

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Vaccine Development

The importance of vaccines in the control of infectious diseases cannot be overstated -- they provide safe, cost effective and efficient means of preventing illness, disability and death from these diseases. Indeed, vaccines are the only human interventions that have actually eradicated diseases: the last case of smallpox anywhere on earth occurred in 1977, and polio has been eradicated from the western hemisphere, the western Pacific region, and virtually all of Europe. The complete elimination of polio, and perhaps other vaccine-preventable diseases, is within our grasp.

Each of the core scientific disciplines of NIAID – immunology, microbiology and infectious diseases – contributes to the development of new vaccines. Progress in basic research as well as technical advances have created opportunities for improving the safety and efficacy of existing vaccines as well as for developing vaccines for diseases for which no vaccines are currently available.

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Rotavirus Vaccine Licensed

NIAID intramural research spanning 25 years recently culminated in the licensure of a vaccine against rotavirus, a leading cause of life-threatening childhood diarrhea. Widespread use of the rotavirus vaccine promises to reduce the 160,000 emergency room visits and 50,000 hospitalizations necessitated by rotavirus infections each year in this country, according to the Centers for Disease Control and Prevention (CDC). Global use of the vaccine could significantly lessen the impact of rotavirus diarrhea, which affects 130 million infants and children each year, resulting in more than 870,000 deaths, according to the WHO.

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Conjugated Hib Vaccines: A Continuing Success Story

Another notable success in vaccinology is the development of conjugated vaccines to protect children under two years of age from Haemophilus influenzae type B (Hib), a microbe which can cause meningitis, deafness and mortality in young children. The success of Hib conjugate vaccines has been extraordinary: more than 35 countries have followed the lead of the United States and adopted these vaccines into their immunization programs, cutting the incidence of invasive Hib disease to negligible levels wherever the vaccine has been used. In the United States only 258 cases of invasive Hib disease among children younger than 5 years were reported in 1997, a 97 percent reduction from 1987. The Children's Vaccine Initiative has estimated that conjugated Hib vaccines, if used routinely and in the same proportion of children as other childhood vaccines, could prevent about 70 percent of the estimated 400,000 annual Hib-related deaths worldwide.

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Tuberculosis Vaccine Research

Last year, TB claimed the lives of nearly 3 million people, more than any other single infectious disease, according to the WHO. Clearly, an effective TB vaccine is needed, as well as new therapeutics. The Institute is working to develop a TB vaccine with a two-tiered approach: basic research into the pathogenesis of the disease and the host immune response to infection with the TB bacterium; and applied research into vaccine candidates. Several experimental vaccine approaches appear promising, and the NIAID recently joined forces with public and private sector health agencies to formulate a "blueprint" to speed TB vaccine development.

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Responding to the Threat of Bioterrorism

Recent terrorist attacks such as those in New York, Oklahoma City and Tokyo, the uncovering of advanced biological weapons in Iraq and the former Soviet Union, and other events have reinforced the urgent need to prepare for possible biological attack. As recently articulated by President Clinton, the NIH and NIAID have a central role is countering the threat of bioterrorism. The Institute has developed a bioterrorism research plan that consists of basic research into the pathogenesis and genetics of organisms which might be used in bioweapons, as well as the development of techniques for rapid identification of natural and bioengineered microbes, new therapies against these microbes, and vaccines to prevent infections with these agents. Our efforts are focused on four organisms known to be potential agents of bioterrorism: smallpox, anthrax, tularemia and plague. Important initiatives include collaborative research with the Department of Defense to identify antiviral drugs with the potential to treat or cure smallpox infections, and efforts to develop an improved anthrax vaccine.

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New Approaches to Immunologic Diseases

The immune response is central to human health. However, the immune system can go awry, as in the case of autoimmune diseases, in which a person's immune system targets their own organs or tissue. Collectively, autoimmune diseases afflict several million Americans, an estimated five percent of the population. The human and financial burden of these diseases is immense. To address the problem of autoimmune diseases, a trans-NIH working group has develop cross-cutting initiatives to address various aspects of autoimmunity, including the roles of environmental, infectious and genetic factors in these diseases, as well as innovative therapies such as islet cell transplantation. An important area of emphasis is the induction of tolerance. By blocking only those components of the immune system that attack healthy tissues, it may be possible to treat autoimmune diseases while avoiding immunosuppressive drugs that dampen not only the deleterious immune response, but also responses needed to protect a person from infections and cancers.

In addition to its applications in autoimmunity, tolerance induction holds extraordinary promise in transplantation biology. Researchers have shown that novel approaches to tolerance induction allow long-term, rejection free survival of transplanted kidneys and insulin-producing islet cells in monkeys, without immunosuppressive drugs. A comprehensive NIAID tolerance research plan has been developed to identify research gaps and opportunities, and to outline areas of future basic and clinical research in autoimmunity, transplantation, asthma and allergic diseases.

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Conclusion

The activities of NIAID are covered within the NIH-wide Annual Performance Plan required under the Government Performance and Results Act (GPRA). The FY 2000 performance goals and measures for NIH are detailed in this performance plan and are linked to both the budget and the HHS GPRA Strategic Plan which was transmitted to Congress on September 30, 1997. NIH's performance targets in the Plan are partially a function of resource levels requested in the President's Budget and could change based upon final Congressional Appropriations action. NIH looks forward to Congress' feedback on the usefulness of its Performance Plan, as well as to working with Congress on achieving the NIH goals laid out in this Plan.

The Institute is poised to take advantage of unprecedented scientific opportunities in immunology, microbiology and infectious diseases. With a strong research base, talented and committed investigators, and the availability of powerful new research tools, NIAID looks to the new millennium with confidence that new advances that will have significant impact on the health of our nation and the world are within our grasp. I will be happy to answer any questions.

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