Overview of NIAID
Global Health and Emerging Infectious Diseases
HIV/AIDS
Immune-Mediated Diseases
Vaccine Development
Conclusion

I am pleased to present the President's budget request for the National Institute of Allergy and Infectious Diseases (NIAID) for Fiscal Year (FY) 2002. Including the estimated allocation for the acquired immunodeficiency syndrome (AIDS) of $1,192,855,000, total support requested for NIAID is $2,355,325,000, an increase of $292,317,000 over the FY 2001 appropriation. The portion of the budget not related to AIDS is $1,162,470,000, which reflects an increase of $162,054,000 over the comparable FY 2001 appropriation. The NIH budget request includes the performance information required by the Government Performance and Results Act (GPRA) of 1993. Prominent in the performance data is NIH's second annual performance report which compares our FY 2000 results to the goals in our FY 2000 performance plan. As performance trends on research outcomes emerge, the GPRA data will help NIH to identify strategies and objectives to continuously improve its programs.

NIAID, the third largest NIH Institute, supports and conducts research to better understand, treat and prevent infectious, immunologic, and allergic diseases. The scope of the NIAID research portfolio is expanding continually in response to new challenges, such as the emergence of AIDS and other newly recognized diseases, and because of scientific opportunities facilitated by new technologies and progress in the core NIAID scientific disciplines of microbiology, immunology, and infectious diseases. Advances in these key fields, including progress in relatively new areas such as pathogen and human genomics, are driving the development of new treatments, vaccines, diagnostic tests, and technologies that improve the health of people in the United States and around the world.

In order to meet the many health challenges of the new millennium and take advantage of unprecedented scientific opportunities, the Institute has developed a strategic research plan for the 21st century centered around four major areas: 1) Global health and emerging infectious diseases; 2) HIV/AIDS; 3) Immune-mediated diseases, including allergy and asthma; and 4) Vaccines. The complete NIAID Strategic Plan is available on the World Wide Web at http://www.niaid.nih.gov/strategicplan2000.

NIAID has a long history of supporting research into diseases that transcend national boundaries and hence fall under the rubric of global health. Examples of such diseases include newly recognized conditions such as AIDS and liver disease due to hepatitis C virus; diseases that have spread to new geographical settings, such as West Nile fever and dengue; and resurgent endemic diseases such as malaria and tuberculosis, which are increasingly resistant to antimicrobial drugs. In addition, we now face the specter of a new kind of emerging disease: one deliberately spread by bioterrorists. These emerging and re-emerging diseases are superimposed on other major health problems such as acute respiratory infections, diarrheal diseases, and measles, which remain leading causes of illness and death worldwide.

To mitigate the burden of these diseases, NIAID supports numerous laboratory, field-based, and clinical research projects related to global health, both domestically and abroad. Among many projects, NIAID-supported studies on malaria in Mali, pneumococcal disease in the Gambia, tropical diseases in the International Centers for Tropical Disease Research, and HIV prevention through the HIV Prevention Trials Network, have achieved important results through coordinated partnerships with local governments and other agencies and organizations. Building on NIAID's longstanding commitment in global health, the Institute this month released a new Global Health Research Plan for HIV/AIDS, Malaria, and Tuberculosis, which outlines NIAID goals and plans for fighting infectious diseases by building sustained research capability domestically and internationally and enhancing international partnerships.

Many of the challenges posed by emerging infectious diseases lend themselves to research in a relatively new field: genomics. The sequencing of the entire human genome and the anticipated assignment, over the next few years, of function to the estimated 30,000 to 60,000 human genes will have an enormous impact on all of medicine, including our understanding of the host response to microbial pathogens. In addition, the genomic sequencing of microbial pathogens will be a critical component of 21st century strategies for the development of diagnostics, therapeutics, and vaccines for infectious diseases. NIAID has funded projects to sequence the genomes of more than 50 medically important pathogens, a dozen of which have been completed. These include the bacteria that cause tuberculosis, gonorrhea, chlamydia, and cholera, as well as individual chromosomes of the malaria parasite, Plasmodium falciparum. Most recently, investigators have reported the complete genomic sequence of Streptococcus pyogenes, a bacterium that causes diseases ranging from strep throat to the flesh eating disease known as necrotizing fasciitis, as well as that of Escherichia coli O157:H7, a worldwide public health threat that has triggered scores of recent outbreaks of hemorrhagic colitis and numerous fatalities from kidney failure. In the interest of global scientific cooperation, NIAID-supported scientists deposit pathogen sequence data in specialized public databases such as GenBank, where investigators around the world can access it via the World Wide Web.

AIDS, caused by the human immunodeficiency virus (HIV), has claimed 22 million lives since the disease was recognized 20 years ago. More than 36 million people are living with HIV infection, including approximately 800,000 to 900,000 individuals in the United States. 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. NIAID-supported investigators conducted research that was pivotal to the development of these drugs, and have helped define how best to use these medications in different clinical settings. Ongoing research promises to yield a new generation of drugs that may improve upon existing medications in terms of cost, effectiveness, and tolerability.

Until recently, expensive HAART regimens were considered to be beyond the reach of developing countries, where 95 percent of the world's HIV-infected people live. Now, with dramatic reductions in the price of antiretroviral drugs for developing nations and the commitment of world leaders to address the AIDS problem in southern Africa and other poor regions of the world, AIDS therapies will begin to reach more of the people in poor countries who could benefit from them. Building on the research infrastructure that NIAID has helped establish in Africa and elsewhere in the developing world, we intend to work with our international colleagues to link the provision of anti-HIV therapy to ongoing efforts in prevention research, with the goal of facilitating a comprehensive approach to the AIDS pandemic in poor countries. Two recently launched NIAID programs will be key to this effort: the HIV Prevention Trials Network (HPTN) and the HIV Vaccine Trials Network (HVTN), which have research sites in the United States, Latin America, Europe, Africa, Asia and the Caribbean.

The HPTN focuses on several key areas of prevention research, 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. The HVTN will conduct all phases of clinical vaccine trials, from evaluating candidate vaccines for safety and the ability to stimulate immune responses, to testing vaccine efficacy. In pre-clinical and clinical studies, NIAID-supported investigators are testing a diverse range of vaccine strategies, several of which in recent months have shown remarkable promise in tests in non-human primates. The best candidates will be moved rapidly into HVTN trials. We remain optimistic that a safe and effective vaccine can be found that will prevent HIV infection and/or slow the progression of disease in people who are already infected with the virus.

Immunologic diseases cause a considerable burden of illness and death and lead to medical costs that exceed $100 billion annually in the United States. Many immune-mediated diseases disproportionately affect women and members of minority groups. Autoimmune diseases such as type-one diabetes, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis collectively afflict approximately five per cent of the U.S. population. More than seven percent of American children are asthmatic, with poor children in inner city areas disproportionately affected by this serious disease. In addition, immune-mediated graft rejection remains a significant obstacle to the successful transplantation of potentially life-saving organs.

NIAID-funded research in basic and clinical immunology has led to many promising approaches for treating individuals with these and other immunologic conditions. For example, researchers are developing novel ways of selectively blocking inappropriate or destructive immune responses, while leaving protective immune responses intact. This approach, called tolerance induction, holds great promise for the treatment of many immune-mediated conditions, including autoimmune diseases and asthma and allergic diseases. The induction of tolerance to transplanted organs or tissues ultimately may allow transplant patients to forego long-term regimens of broadly immunosuppressive drugs. These drug regimens are costly and dampen not only destructive immune responses, but protective ones as well, thereby increasing a patient's risk of malignancies and infections. Among many projects in the field of immune tolerance, the Institute established the Immune Tolerance Network (ITN), an international consortium of more than 70 research groups. The ITN is implementing clinical trials in four areas: transplantation of islets (the insulin-producing cells of the pancreas), kidney transplantation, autoimmune diseases, and asthma and allergic diseases. The first ITN trial is testing a new approach to transplanting islets in diabetics who are unable to properly control their blood sugar levels. This international study builds on groundbreaking research at the University of Alberta that has resulted in long-term insulin independence for nearly 20 patients.

For more than a decade, NIAID has worked to reduce the burden of asthma, particularly among inner-city children. Investigators of NIAID's National Cooperative Inner-City Asthma Study developed a successful behavioral and educational intervention that substantially reduced asthma severity in these pediatric populations. Building on this success, NIAID and the Centers for Disease Control and Prevention (CDC) are collaborating to implement this proven intervention in a new four-year program that will reach 6,000 children in 23 inner-city health care delivery sites throughout the U.S. An ongoing NIAID intervention study, involving approximately 1,000 children nationwide, is testing the effectiveness of environmental control measures and physician education in reducing the burden of asthma. Preliminary results are showing substantial reductions in asthma symptoms and emergency room visits. In both of these studies, recruitment has exceeded the targeted levels and retention of patients has been extraordinarily high compared to other studies of other inner-city pediatric populations. Because of these successes, NIAID-supported inner-city asthma programs are now recognized as models for conducting clinical research in the inner city and have attracted partners in the public and private sectors to collaborate with NIH-funded researchers. These collaborations promise to bring new asthma interventions to minority populations whose access to such therapies might otherwise be diminished or delayed.

Vaccination has been recognized as the greatest public health achievement of the 20th century, and vaccine research has long been a cornerstone of the NIAID research portfolio. NIAID-supported research has led to the development of many new and improved vaccines now widely used, such as those against Haemophilus influenzae type b, pertussis, chickenpox, pneumococcal disease, and hepatitis A and B. The rapidly evolving science base in pathogen genomics, immunology and microbiology will facilitate further progress in developing new and improved vaccines. In particular, the availability of the genomic sequences of major microbial pathogens will facilitate the identification of a wide array of new antigens for vaccines. Because many pathogens gain entry to the body via mucosal sites, NIAID-supported scientists are developing new vaccines that target mucosal surfaces such as those in the intestine or respiratory tract. Vaccines that are easy to administer -- orally, nasally, or trans-dermally - will have great utility in resource-poor setting and for mass immunization programs. In addition to the development of vaccines against classic infectious diseases, NIAID is working to develop vaccines against chronic diseases with infectious origins, as well as potential agents of bioterrorism, and autoimmune diseases and other immune-mediated conditions.

In the 21st century, NIAID is poised to exploit unprecedented scientific opportunities in immunology, microbiology and infectious diseases. As has been the case for more than 50 years, a commitment to the best possible research -- basic science as well as clinical trials -- will drive our efforts to improve health in this country and abroad. With a strong research base, the commitment of talented investigators, and the availability of powerful new research tools, we are confident that our initiatives will help solve seemingly intractable clinical and public health problems and improve global health in the 21st century.