Dr. Fauci's testimony to the House
Appropriations Subcommittee
Date posted on the Web: April 3,
1998
Accompanying posters will be available
on the NIAID homepage http://www.NIAID.nih.gov (go
to "Director's Page").
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Statement by Anthony S. Fauci, M.D.
Director, National Institute of Allergy and Infectious Diseases
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 1999. The President proposes
that the NIAID receive $702 million, an increase of 8.0 percent
for NIAID non-AIDS research activities. Including the estimated
allocation for AIDS research activities, total support proposed
for the NIAID is $1.47 billion, an increase of 8.6 percent
over the comparable FY 1998 appropriation. Funds for NIAID
AIDS research efforts are included in the Office of AIDS Research
budget request.
The activities of the NIAID are
covered by the NIH-wide Annual Performance Plan required under
the Government Performance and Results Act (GPRA). The FY 1999
performance goals and measures for NIH are detailed in this
performance plan and are linked to the HHS GPRA Strategic Plan
which was transmitted to Congress on September 30, 1997. The
NIAID is anxious to meet the challenges set forth in this plan
and we look forward to continued support from Congress that
will facilitate our achieving these goals.
FIFTY YEARS: ADVANCING KNOWLEDGE,
IMPROVING HEALTH
This year, the NIAID celebrates fifty years of progress in understanding,
treating and preventing infectious and immunologic diseases. During the past
five decades, NIAID-supported research in fields such as microbiology and
immunology has led to new therapies, vaccines and diagnostic tools that have
profoundly benefitted global health. Capping this remarkable half-century
are recent advances and initiatives that promise to further reduce the burden
of disease in this country and around the world. Meanwhile, new challenges
to the public health continue to emerge, underscoring the need for continued
progress in our fight against infectious microbes and diseases of the immune
system.
IMMUNOLOGIC TOLERANCE
A long-standing goal of NIAID-supported immunology research is the development
of new and better ways to prevent the rejection of transplanted organs
and tissue "grafts" by the immune system. While current immunosuppressive
drugs have greatly reduced graft rejection, these agents are highly toxic
and increase a patient's risk of infection, cancer and other complications.
In addition, despite major improvements in immunosuppressive therapy,
10 to 50 percent of transplanted organs and tissues are rejected by patients'
immune systems within the first year.1 Even with the latest immunosuppressive
drugs, approximately 60 percent of transplanted kidneys, the organ most
often transplanted, are rejected within 10 years.
As we work to improve
this record, we are encouraged by new findings, underpinned
by years of
basic immunology research, that show the feasibility of a totally
new approach to preventing graft rejection. NIAID-supported
researchers have demonstrated that it is possible to induce
immunologic "tolerance" to a graft by turning off
the specific immune responses that would otherwise attack it.
Promising results in animal models have been achieved with
transplanted kidneys and livers; early human studies suggest
that long-term tolerance of transplanted bone marrow may be
achieved with appropriate therapy.
One approach to inducing tolerance
is to block the second of two signals needed by T cells to
become activated and orchestrate an attack on a foreign tissue
or organ. In this regard, several different blocking molecules
have shown considerable promise. Other approaches to inducing
tolerance involve manipulating immune system molecules called
cytokines, or inducing the suicide of the immune cells that
otherwise would attack a graft. The refinement of strategies
for inducing tolerance could revolutionize the field of transplantation
and benefit the tens of thousands of patients whose lives could
be saved or improved by a donated organ. In addition, our growing
knowledge of immune tolerance will help in understanding and
treating other conditions such as cancer, autoimmune conditions,
and allergic and infectious diseases.
THE BURDEN OF INFECTIOUS DISEASES
It is underappreciated that infectious diseases remain the leading killer
of people globally and the third leading cause of death in the United
States.3,4 Of the approximately 52 million deaths worldwide in 1996,
more than 17 million were due to infectious diseases, including approximately
9 million among children.5 In addition, a growing number of cancers and
other chronic conditions have been attributed to infectious agents. For
example, the bacterium Helicobacter pylori causes ulcers and stomach
cancer, and Chlamydia pneumoniae has been implicated as a cause of artery-clogging
plaques. Both hepatitis B virus and hepatitis C virus (HCV) can lead
to liver cancer, and human papillomavirus is responsible for most cases
of cervical cancer. In addition to their human toll, the financial burdens
of infectious diseases are enormous. In the United States alone, costs
associated with infectious diseases exceed an estimated $120 billion
annually.
In the face of the enormous challenges
posed by infectious diseases, the sustained commitment of NIAID
to basic and applied research has paid enormous dividends against
newly recognized pathogens--such as human immunodeficiency
virus (HIV) and HCV--and scourges which have long plagued humanity,
including malaria, tuberculosis and life-threatening infant
diarrhea.
PROGRESS AGAINST HIV/AIDS HIV, the
cause of the acquired immunodeficiency syndrome (AIDS), remains
one of the greatest threats to global health. More than 30
million people worldwide are living with HIV/AIDS, a number
expected to reach 40 million by the year 2000. In the 17 years
since AIDS was recognized, an estimated 11.7 million people
with HIV worldwide have died,7 including approximately 380,000
in the United States.8 Despite the mounting toll of HIV, recent
developments have provided a measure of optimism. In the United
States, AIDS deaths dropped 44 percent from the first six months
of 1996 to the first six months of 1997; new AIDS diagnoses
declined by 12 percent during the same period.9 These encouraging
trends are probably due to several factors, notably the increased
use of potent combinations of anti-HIV drugs, and our growing
ability to prevent and treat the many secondary infections
associated with HIV disease.
Basic research into the structure
of HIV and how it interacts with the immune system led to the
development of the 12 antiretroviral drugs now licensed in
this country. Various combinations of these drugs, as well
as several investigational drugs now in clinical trials, have
helped restore the health of many patients, dramatically reducing
the amount of HIV in their bodies and lowering their risk of
secondary infections, hospitalizations and death. In addition,
new insights into the pathogens that prey on the weakened immune
systems of HIV-infected individuals have led to improved prophylactic
and curative therapies.
Unfortunately, many HIV-infected
individuals have not benefitted from the currently available
drugs, cannot tolerate their side effects, or have difficulty
complying with complex treatment schedules that may require
them to take 30 or more pills a day. In addition, the ability
of HIV to mutate and become resistant to the current drugs
is a persistent threat. Therefore, the development of the next
generation of therapies--well-tolerated, effective drugs that
can be administered with a minimum of doses for prolonged periods--remains
a priority. Together with partners in academia and industry,
NIAID-supported scientists are pursuing many new treatment
strategies and exploring ways to boost an HIV-infected person's
immune system.
HIV VACCINE RESEARCH
In many developing countries, where health care spending may be only a few
dollars per person each year, such therapies will probably remain beyond
the reach of all but the most privileged. Therefore, continued research
into an HIV vaccine and other means of preventing HIV infection is crucial
to slowing the epidemic in these settings, as well as in our own country.
To speed the pace of discovery, NIAID has strengthened its efforts in
HIV vaccine research. Among recent initiatives are 58 new grants to foster
innovative research on HIV vaccines and the establishment of a Vaccine
Research Center within the NIH intramural research program.
HEPATITIS C
Another recently recognized pathogen of great concern is hepatitis C virus
(HCV), identified in 1989. HCV is a leading cause of cirrhosis, liver
cancer, and a major reason for liver transplants. Worldwide, more than
170 million people are chronically infected with HCV, including 4 million
individuals in the United States.10 Annual HCV-related deaths number
approximately 8,000 to 10,000 people in this country,11 a figure projected
to reach 24,000 deaths/year by 2017 if effective therapies are not found.
To combat this epidemic, NIAID recently established a network of Hepatitis
C Research Centers to study the virus and how it causes disease. In the
past year, researchers at one of the new centers reported a major breakthrough:
the construction of functional, infectious clones of HCV, using genetic
engineering techniques. This advance has facilitated HCV studies in cell
cultures and animal models.
RESPONSE TO THE THREAT OF H5N1 AVIAN
INFLUENZA
We have come to understand that the emergence of previously unrecognized
pathogens such as HIV and HCV is a continual process. As further evidence
of this, the first known cases of human influenza caused by a virulent bird
virus known as H5N1 avian influenza were identified in Hong Kong in 1997.
Given the possibility that this avian virus might combine with a human influenza
strain and become more readily transmissible, possibly resulting in a pandemic,
NIAID moved quickly with our colleagues at the Centers for Disease Control
and Prevention, World Health Organization and other agencies in addressing
research questions and public health needs associated with the outbreak.
Fortuitously, as part of our long-standing research into respiratory viruses,
we had in our repository the specific antisera needed to quickly develop
test kits for detecting the avian influenza virus. NIAID has also supported
the production of a recombinant vaccine for use in at-risk laboratory and
health care personnel, as well as a surveillance effort in Hong Kong to identify
and characterize the source of the avian virus.
A COMMITMENT TO MALARIA RESEARCH
More than 40 percent of the world's population lives in areas
at risk for malaria transmission.12 Approximately 300 to 500
million cases of malaria occur worldwide each year; every 20
seconds, a child dies of the disease.13 In the past year, the
National Institutes of Health, together with research organizations
and donor agencies from around the world, have worked to mobilize
the scientific resources and political will needed to control
this dread disease. The extraordinary interest among scientists,
political leaders, the media and the general public in this
new partnership, called the Multilateral Initiative on Malaria,
is strong evidence that the global community has recognized
the magnitude of the malaria problem.
At NIAID, we have strengthened our
long-term commitment to malaria research. NIAID-supported malaria
projects--many in collaboration with other government and international
agencies--include a new repository of malaria research materials
that are available to researchers worldwide; basic, field-based
and clinical research on all phases of malaria research; and
projects to determine the genetic sequences of important malaria
species. In addition, new collaborations between intramural
and extramural scientists on malaria vaccine research, production
and evaluation are underway.
DIARRHEAL DISEASES
Like malaria, diarrheal diseases are leading killers of children, resulting
in about 2.5 million childhood deaths each year.14 At least a third of
these deaths are probably due to rotavirus, a disease for which NIAID
researchers have developed an effective, orally administered vaccine.
As recently reported in The New England Journal of Medicine, this vaccine,
the culmination of more than 20 years of research, reduced severe diarrheal
illness by 88 percent in a study of infants in Venezuela, a country where
rotavirus circulates year round.15 The vaccine is nearing licensure in
the United States and other countries, and promises to have a major impact
on the health of children worldwide. In the United States alone, widespread
use of the NIAID-developed rotavirus vaccine could greatly reduce the
500,000 doctor visits16 and 100,000 hospitalizations related to rotavirus
each year,17 as well as the $1.4 billion in direct and indirect costs
associated with the illness.
THE PROMISE OF NEW TECHNOLOGIES
Many of the advances I have described have been facilitated by rapid advances
in molecular biology, notably the development of fast and accurate methods
for sequencing the genomes of disease-causing microbes. Sequence information
can be used in many ways, such as finding targets for therapies, identifying
antigens to incorporate into vaccines, detecting mutations that cause
drug resistance, and determining the factors that influence the virulence
of a microbe.
Great progress has been made in
the field of pancreas transplantation and now simultaneous
kidney/pancreas transplant offers greater survival at five
years than kidney alone, and the majority of patients no longer
need insulin. However, most insurance companies do not cover
this combined transplant because definitive prospective studies
have not been conducted. The NIDDK needs to sponsor a trial
to document the superior benefit of combined kidney/pancreas
transplant to convince third party payers and Medicare to cover
this procedure, and further fund research to assess the comparative
benefit of whole organ (pancreas) versus islet cell transplantation.
The success of the first microbe
sequencing project--the delineation of the complete Haemophilus
influenzae genome in 1995--encouraged the Institute's current
efforts to sequence the full genomes of eight other medically
important bacteria. NIAID also supports projects to provide
complete or partial genome sequences of large parasitic protozoa.
MAINTAINING A RESEARCH BASE
The burden of infectious and immunologic diseases, in human and economic
terms, is enormous. It is critical that we maintain a strong scientific
infrastructure in core disciplines such as infectious diseases, immunology
and microbiology to meet the challenges of these diseases. With skillful
use of the increasingly powerful tools of molecular biology, by identifying
research opportunities and priorities and vigorously pursuing them, and
by sustaining a strong research base, we will be well-positioned to make
further progress against current disease threats as well as the new diseases
that will inevitably emerge.
1 United Network
for Organ Sharing. "The
1997 Report of Center-Specific Graft and Patient Survival Rates." Richmond,
VA.
2 Cecka, J.M. 1996. The UNOS scientific renal transplant registry. Clinical
Transplants. p. 1-14.
3 World Health Organization. 1997. "The World Health Report 1997." Geneva:
World Health Organization.
4 Pinner, R.W. et. al. 1996. Trends in infectious diseases mortality in the
United States. JAMA. 275:189-193.
5 World Health Organization. 1997. "The World Health Report 1997." Geneva:
World Health Organization.
6 Institute of Medicine. 1997. "America's Vital Interest in Global Health." Washington,
DC.: National Academy Press.
7 UNAIDS: "Report on the Global HIV/AIDS Epidemic." Geneva, December,
1997.
8 Centers for Disease Control. 1996. "HIV/AIDS Surveillance Report." 8(no.
2): 1-40.
9 DeCock, Kevin. 1998. Presentation: Fifth Conference on Retroviruses and
Opportunistic Infections, February 2, Chicago, IL.
10 World Health Organization. 1997. "Weekly Epidemiological Record:
March. 7, 1997." Geneva: World Health Organization.
11 National Institutes of Health. 1997. Consensus Statement: Management of
Hepatitis C. Bethesda, MD.
12 World Health Organization. 1997. "Weekly Epidemiological Record:
September 5, 1997." Geneva: World Health Organization.
13 World Health Organization. 1997. "The World Health Report 1997." Geneva:
World Health Organization.
14 World Health Organization. 1997. "The World Health Report 1997." Geneva:
World Health Organization.
15 Perez-Schael, I. et. al. 1997. Efficacy of the rhesus rotavirus-based
quadrivalent vaccine in infants and young children in Venezuela. N Engl J
Med. 337(17):1181-1187.
16 Glass, R.I. et. al. 1996. The epidemiology of rotavirus diarrhea in the
Untied States: surveillance and estimates of disease burden. J. Infect Dis.
174 (suppl 1): S5-S11.
17 Institute of Medicine. 1985. "New vaccine development: establishing
priorities," p.410-423. In Diseases of importance in developing countries
(Vol I). Washington, DC.: National Academy Press.
18 Smith, J. et. al. 1995. Cost effectiveness analysis of a rotavirus immunization
program for the United States. Pediatrics. 96: 856-15.
