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 (FY) 2001. The non-AIDS portion of the budget request is $935,166,000, which reflects an increase of $54,019,000 over the comparable FY 2000 appropriation. Including the estimated allocation for AIDS, total support requested for NIAID is $1,906,213,000, an increase of $109,582,000 over the FY 2000 appropriation. Funds for NIAID efforts in AIDS research are included within the Office of AIDS Research budget request. I would note that the National Institutes of Health (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 first performance report, which compares our FY 1999 results to the goals in our FY 1999 performance plan.

Global Health

The NIAID research program is predicated on the view that we live in an interconnected, global community. Because of the enormous volume of international travel and trade, we cannot separate the health problems of the United States from those of the rest of the world. Clearly, it is folly to think that we are somehow isolated from diseases that are public health challenges elsewhere. In 1999 alone, we witnessed the first known appearance of West Nile fever in the western hemisphere (in New York City and surrounding areas), as well as alarming reports of dengue fever outbreaks in Texas and Florida. The yearly U.S. epidemic of influenza, which originates in Asia, is the prototypic example of the maxim "microbes do not recognize borders." Indeed, the memory of three recent influenza pandemics (1918, 1957 and 1968), as well as the ever-present threat of another flu pandemic is perhaps the best reminder of humanity's shared vulnerability to disease.

As a nation, our interest in global health stems both from humanitarian concerns and what has been called "enlightened self-interest." In addition to our obligation to ameliorate human suffering wherever possible, history tells us that healthy, stable countries make strong allies and trading partners. Conversely, poor health status can have a profound negative impact on social and economic development, and frequently contributes to political instability. Significantly, this year the United Nations Security Council for the first time devoted an entire session to a health issue - AIDS in Africa - recognizing the enormous threat that the disease poses to the security not only of that continent but the world.

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Infectious Diseases: Challenges and Opportunities

The World Health Organization (WHO) estimates that 1,500 people die each hour from an infectious disease. Half of these deaths occur in children under five years of age, and most of the rest are working adults who frequently are breadwinners and parents. Virtually every year one or more newly recognized diseases add to the burden of known infectious conditions; in 1999, for example, the deadly Nipah virus emerged in Malaysia and Singapore. Because of the emergence of microbial drug resistance, many infectious diseases are increasingly difficult to treat. In addition, it is now clear that many chronic diseases have an infectious etiology: approximately 20 percent of all cancers are related to infections, and mounting evidence indicates that pathogenic organisms may be the underlying causes of chronic diseases such as coronary artery disease, diabetes, multiple sclerosis, and chronic lung diseases.

NIAID's Strategic Plan, available on the World Wide Web at http://www.niaid.nih.gov/strategicplan outlines the progress made in infectious disease research, including advances in HIV treatment, prevention and vaccine development, and delineates the scientific opportunities to strengthen our preparedness for infectious threats, known and unknown.

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The Promise of Pathogen Genomics

Many of the challenges posed by infectious diseases lend themselves to research in a relatively new field: pathogen genomics, or sequencing of the genes of microbes, a central focus of the Institute. Pathogen genomics, coupled with data from the Human Genome Project, as well as the use of new tools such as microarray and DNA "chip" technologies to delineate the functional expression of these microbial genes, will likely underpin infectious diseases research for the coming decades and will be critical to the development of new vaccines, therapies and diagnostics

In an important technical achievement, researchers have determined the complete genetic sequence of chromosomes 2 and 3 of P. falciparum, the most deadly malaria parasite. This new information will help to identify virulence factors and proteins involved in the parasite's lifecycle that may serve as targets for the development of drugs and vaccines. Researchers also have determined the complete genomic sequence of two strains of M. tuberculosis, the TB bacterium. These sequencing efforts are central to NIAID's detailed plans for the development of malaria and TB vaccines.

NIAID-supported researchers have also published complete or partial genomic sequences of the agents of the sexually transmitted diseases chlamydia and syphilis, as well as the leishmaniasis parasite Leishmania major. The Institute also supports the genetic sequencing of many other important pathogens that exact an enormous toll and are increasingly drug-resistant. Examples include important species of enterococci, streptococci, and staphylococci, including Stapyhlococcus aureus, which in some cases has become virtually untreatable because of drug resistance.

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Vaccine Development

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 been instrumental in the development of many new and improved vaccines, such as those against hepatitis A and B, Haemophilus influenzae type b, pertussis, typhoid, varicella, and pneumococcal disease. A new vaccine against Streptococcus pneumoniae, the leading cause of morbidity and mortality in children worldwide, shows particular promise. Widespread use of this vaccine could greatly reduce the 1.2 million child deaths worldwide attributed to S. pneumoniae each year, according to WHO. The domestic potential of this new vaccine is also significant: pneumococcal disease causes 40,000 deaths, 500,000 cases of pneumonia, and 7 million middle ear infections in this country every year, according to CDC.

The rapidly evolving science base in pathogen genomics, immunology and microbiology will facilitate further progress in developing new and improved vaccines. In particular, vaccines that target mucosal surfaces such as those in the intestine or respiratory tract are of great importance, because many pathogens gain entry to the host via mucosal sites. Vaccines administered orally, nasally or transdermally are easy to administer and therefore have potentially great utility in developing countries and for mass immunization programs. The development of new adjuvants, which boost the immune response to vaccines, is another important area of research that has progressed rapidly in recent years. In addition to the development of vaccines against classic infectious diseases, vaccines are being pursued to fight potential agents of bioterrorism; chronic diseases with infectious origins; and autoimmune diseases and other immune-mediated conditions.

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Acquired Immune Deficiency Syndrome (AIDS)

AIDS, caused by the human immunodeficiency virus (HIV), is one of the greatest threats to global health and one of the most destructive scourges in human history. Since the beginning of the HIV pandemic, more than 50 million people worldwide have been infected with HIV, of whom more than 16.3 million have died, according to UNAIDS. In the United States, approximately 650,000-900,000 people are living with HIV/AIDS; an additional 420,200 people with AIDS had died as of June 30, 1999, according to the Centers for Disease Control and Prevention (CDC). UNAIDS estimates that the global HIV-infected population continues to expand: in 1999 alone, there were 5.6 million new infections worldwide, half of which occurred among people younger than 25 years of age. In the United States, the rate of new HIV infections has reached an unacceptable plateau of 40,000 per year, with minority communities disproportionately affected.

Although potent combinations of anti-HIV drugs have reduced the number of AIDS deaths and new AIDS cases in many western countries, the utility of these medications is limited by their substantial cost, toxicities, complicated and disruptive dosing regimens, and the development of drug resistance. Many patients do not respond adequately to current regimens; even in patients who are successfully treated, the virus persists in sanctuaries where the drugs cannot penetrate and in a latent form on which the drugs have no effect. Therefore, the development of a new generation of therapies remains a major priority. In addition, approaches to purging the virus from its sanctuaries in certain cells and tissues are being vigorously pursued, as are methods to boost the body's immune defenses so they can better fight the virus.

In developing countries in which per capita health care spending may be only a few dollars a year, and where health care infrastructures are weak, anti-HIV therapies are invariably beyond the reach of all but the privileged few. This situation, coupled with the upward trajectory of the global HIV/AIDS epidemic, underscores the urgent need for effective and affordable tools of HIV prevention. Notable progress has been made. For example, an NIAID-supported study in Uganda found that two doses of the drug nevirapine, one given to the mother at the onset of labor and one given to the infant within 72 hours after birth, can markedly reduce perinatal HIV transmission. The entire regimen costs $4.00, making it feasible in resource-poor settings. Other methods of preventing HIV transmission, such as education and behavior modification and the social marketing and provision of condoms have also proven effective, both in the United States and in developing countries such as Uganda, Senegal and Thailand.

Approximately 46 percent of people living with HIV/AIDS are women. An important NIAID focus is developing interventions that will empower women to protect themselves in situations where they are unable to avoid sex with HIV-infected partners or cannot persuade their partners to use a condom. A critical effort is the development and testing of products for vaginal use - called topical microbicides - that may protect women (and their partners) from HIV and other sexually transmitted diseases. Promising microbicide candidates are now in various stages of testing in animal models and in humans.

The development of a safe and effective vaccine for HIV infection is a central goal of AIDS research, and a necessary tool to bring the HIV epidemic under control. In addition to the Institute's substantial commitment to pre-clinical HIV vaccine research, NIAID has conducted more than 50 clinical studies of HIV vaccines. Among these is the first HIV vaccine trial in Africa, a study initiated in Uganda last year in a growing effort to collaborate with scientists from developing countries to identify safe and effective vaccines suitable for worldwide use. Last year also marked the dedication of the Dale and Betty Bumpers Vaccine Research Center, a program within the NIH intramural research program to stimulate multidisciplinary vaccine research.

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Immune-Mediated Diseases

The burden of immune-mediated diseases is staggering; these conditions, like infectious diseases, are important global health concerns. For example, 100 to 150 million people worldwide suffer from asthma; in this country alone, 15 million people are asthmatics. Asthma-related deaths worldwide number approximately 180,000 annually and are increasing both in the United States and abroad.

The past two decades of intense and highly productive research on the immune system have resulted in a wealth of new information and extraordinary growth in conceptual understanding. These accomplishments now provide realistic opportunities for major advances in the diagnosis, treatment, and prevention of a broad range of immunologic conditions.

Among the most exciting developments is our growing understanding of tolerance induction. By blocking only those components of the immune system that attack healthy tissues, it may be possible to prevent graft rejection in transplant patients without immunosuppressive drugs that dampen protective immune responses as well as deleterious ones. The ability to selectively block the immune response also holds great promise for treatment of many immune-mediated conditions, including autoimmune diseases such as juvenile (type 1) diabetes, rheumatoid arthritis and multiple sclerosis, as well as asthma and allergic diseases. In addition, understanding the mechanisms of immune tolerance will likely prove important for efforts to prevent unresponsiveness to vaccines, and for enhancing natural host responses and defenses to infection.

In October 1999, NIAID launched a major initiative to develop new ways of inducing immune tolerance, in partnership with the Juvenile Diabetes Foundation International and the National Institute of Diabetes and Digestive and Kidney Diseases. The Collaborative Network for Clinical Research on Immune Tolerance involves more than 40 research institutions. Network researchers will conduct clinical trials to improve the success of kidney transplants using tolerogenic approaches and clinical trials are planned for patients receiving transplanted human islets to treat type 1 diabetes. Network investigators will test similar therapeutic approaches for other autoimmune diseases, such as systematic lupus erythematosus, rheumatoid arthritis and multiple sclerosis, and will pursue better ways to measure immune tolerance in humans. In addition, the network plans to conduct clinical trials in immune modulation to treat asthma and allergic diseases.

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Addressing Health Disparities

Virtually all of NIAID's research efforts address the health disparities that exist in our country, as well as the growing gap in health status between developed and developing countries. Perhaps the best example of this is the development of vaccines to prevent infectious diseases, which disproportionately affect the poor, both at home and abroad. Other efforts, such as HIV treatment and prevention research, hepatitis C research, asthma research, tissue typing and other transplantation research, and autoimmunity research, address conditions that exact a significant toll in minority communities. In addition, NIAID has a long-standing commitment to increasing the cadre of minority investigators involved in biomedical research.

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Conclusion

The United Nations, in the International Declaration of Health Rights, asserted that "The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being. It is not a privilege reserved for those with power, money or social standing." As the NIAID faces the new millennium, we anticipate that our research efforts will result in new and improved vaccines, diagnostics, and treatments that will make "the highest attainable standard of health" a global reality.

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