Senator Frist and members of the Subcommittee, I am pleased to appear before you today to discuss the role of the National Institute of Allergy and Infectious Diseases (NIAID) and the
National Institutes of Health (NIH) in developing better means of
preventing, diagnosing and treating infectious diseases, and the
importance of basic and clinical research to our preparedness
for emerging and re-emerging infections.
As you know, in this century vaccines, drugs, improved sanitation
and control of disease-transmitting insects have made
enormous contributions to the public health. Smallpox has been
eradicated. Polio has been eliminated from the western
hemisphere, and the goal of worldwide polio eradication is
within our grasp. Diseases such as rubella, measles, cholera,
typhoid fever and diphtheria, once major killers in this country,
are now rare.
The burden of infectious diseases
Despite significant progress, infectious diseases remain the
world's leading cause of death, and the third leading cause of
death in the United States. In 1996 alone, an estimated 3 million
deaths worldwide were attributed to tuberculosis (TB), 2.5 million
to diarrheal diseases, 1.5 to 3.0 million to malaria (including one
million children under age five), and 1.2 million to chronic
hepatitis B virus infection. In addition to their human toll, the
financial and psychological burdens of infectious diseases on
families and communities are enormous.
Drug resistance: a growing problem
Many serious infections are becoming increasingly resistant to
standard antibiotics, making treatment difficult and in some
cases impossible. For example, drug-resistant tuberculosis has
now been found in virtually every country surveyed. Worldwide,
more than ten percent of TB cases are resistant to one or more
of the four first-line anti-TB drugs. In the United States, more than
one-third of hospital-acquired infections with Staphylococcus
aureus are resistant to penicillin-like drugs, leaving vancomycin
as the only available drug that reliably eradicates them. We were
given pause in recent months when S. aureus isolates with
increased resistance to vancomycin were identified for the first
time in Japan and the United States. Many other diseases,
including enterococcal infections and pneumococcal pneumonia,
are increasingly problematic because of the development of
drug resistance.
Emerging and re-emerging diseases
Superimposed on these concerns are more than three dozen
diseases and syndromes newly recognized since the
mid-1970s. This list, which includes AIDS; liver disease due to
hepatitis C virus; a new form of cholera; tick-transmitted Lyme
disease and ehrlichiosis; foodborne illness caused by E. coli
0157:H7 and Cyclospora; waterborne disease due to
Cryptosporidium; and the hantavirus pulmonary syndrome,
continues to grow. For example, in 1997 the first known cases
of human influenza caused by a virulent bird virus known as
H5N1 avian influenza were identified in Hong Kong.
The link between microbes and chronic diseases
In recent years, it also has become clear that many cancers and
other chronic conditions can be attributed to infectious diseases.
For example, both hepatitis B virus and hepatitis C virus can
lead to liver cancer, and human papilloma virus is responsible
for most cases of cervical cancer. Chlamydia pneumoniae has
been implicated as a cause of atherosclerosis, and we now
know that the bacterium Helicobacter pylori causes ulcers and
stomach cancer. In addition, certain autoimmune diseases,
including Reiter's syndrome, are linked to infectious microbes.
The importance of research
Clearly, we remain vulnerable to infectious diseases, old and
new. We face a difficult challenge: coping with ongoing
problems, and preparing for the inevitable emergence of
diseases that are currently unknown or under control. In this
regard, the early detection and tracking of pathogens, a function
primarily of the Centers for Disease Control and Prevention
(CDC), is critical. Equally important is the basic and clinical
research conducted by NIH and our sister agencies. Historically,
basic research has led to important, often unpredictable,
advances that have illuminated the etiology of sometimes
mysterious diseases and facilitated the development of
diagnostics, therapies and vaccines.
Basic research and HIV/AIDS
Rapid advances in HIV/AIDS research have been possible
because of the foundation in basic science developed over the
past decades. In the 1960s and 1970s, before the identification
of HIV as the cause of AIDS, a number of top cancer
researchers were working on viruses known as RNA tumor
viruses. Among this group were two investigators who
discovered the reverse transcriptase enzyme, an
accomplishment for which they later won the Nobel Prize. This
discovery facilitated the identification in 1983 of HIV, which also
contains reverse transcriptase. Without basic research, we
might still be wondering what caused the AIDS epidemic.
More recently, fundamental research into the structure and
function of the HIV protease enzyme led to the development of a
powerful new class of anti-HIV medications that block this
enzyme and hence the replication of the virus. Protease
inhibitors are now widely prescribed as part of combination
treatment regimes for HIV-infected people, and have helped
dramatically reduce the number of deaths due to HIV in this
country.
The development of diagnostic tools also is closely linked to
basic research, and critically important in this era of economic
constraint and emphasis on cost-effective technologies. Thanks
largely to research by virologists at the NIH, we have had a useful
diagnostic kit for HIV since 1985. The development of a
technology called the polymerase chain reaction, based on
fundamental research into the bacterium Thermus acquaticus,
has led to sensitive and non-invasive diagnostic tools for many
diseases, including chlamydia and other sexually transmitted
diseases. These tests can help clinicians detect and treat
asymptomatic infections before they cause serious health
problems.
A rapid response to avian H5N1 influenza
As mentioned above, an outbreak of an avian influenza in people
in Hong Kong recently alarmed the medical community.
Fortuitously, as part of NIAID's long-standing research into
respiratory viruses, we had in our reagent repository the specific
antisera needed to quickly develop test kits for detecting the
avian influenza virus. We also have supported the rapid
production of a recombinant vaccine against the avian influenza
virus for use in at-risk laboratory and health care personnel.
Thus, building on years of research, we were able to move
quickly in concert with our colleagues at the CDC, the World
Health Organization (WHO) and other agencies to address the
critical public health needs associated with the outbreak.
New initiatives in NIAID's 50th year
This year, as the NIAID prepares to celebrate our 50th
anniversary, we have enhanced our efforts in finding new tools
for the diagnosis, treatment, prevention and control of infectious
diseases, especially emerging diseases and those with
potential for re-emergence. For instance, the Institute is
developing research and training programs to build a critical
mass of scientists with expertise in diseases of importance to
global health. NIAID also supports numerous studies --
domestically and internationally -- on topics related to disease
emergence, such as the molecular basis of drug resistance and
the mechanisms of pathogen virulence. The Institute sponsors
five international programs in tropical infectious diseases, most
of which have components both in the United States and at
institutions in developing countries.
Defining priorities
With the help of our advisory panels, we have defined infectious
disease priorities in three broad areas:
- Expanding basic and applied research to advance our
understanding of infectious agents, our susceptibility and
immune responses to them, and the environmental factors
that influence their emergence and spread.
- Strengthening our ability to develop and validate new tools,
including therapies, diagnostics, and vaccines, to prevent
and control infectious diseases.
- Ensuring that support for training and research is sufficient
for building and maintaining the scientific expertise and
resources needed to control emerging infectious
diseases.
Malaria research
An important focus of these efforts is research into malaria, a
disease of enormous importance, particularly to the 40 percent
of the world's population living in malaria-endemic regions. The
WHO estimates that approximately 300 to 500 million cases of
malaria occur worldwide each year; every 20 seconds, a child
dies of the disease. In the past year, we have worked with
research organizations and donor agencies from around the
world to form a coalition called the Multilateral Initiative on
Malaria to enhance international collaborations, encourage the
involvement in malaria research of scientists from
malaria-endemic countries, and identify additional malaria
research resources.
In addition, we have bolstered 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.
Hepatitis C
Another priority of the NIH is research into the hepatitis C virus
(HCV), 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. Annual HCV-related deaths
number approximately 8,000 to 10,000 people in this country, a
figure projected to reach 24,000 deaths/year by 2017 if effective
therapies are not found. To combat this epidemic, NIH 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 critical
to the development of effective therapies and a vaccine.
The importance of vaccines
With malaria, hepatitis C and many other diseases, an important
goal of the NIH is the development of vaccines. The impact and
importance of vaccines cannot be overstated -- these powerful
public health tools provide safe, cost effective and efficient
means of preventing illness, disability and death from infectious
diseases. Perhaps the greatest triumph of public health -- the
global eradication of smallpox -- resulted from widespread
immunization programs with an inexpensive, effective, easily
administered vaccine.
Basic research drives vaccine development
Historically, scientific advances in microbiology and related
disciplines have led to the development of new vaccines. For
example, the identification of microbial toxins, as well as
methods to inactivate them, allowed the development of some of
our earliest vaccines, including those for diphtheria and tetanus.
In the 1950s, new tissue culture techniques ushered in a new
generation of vaccines, including those for measles, mumps and
rubella. In recent years we have seen rapid advances in our
understanding of the immune system and the complex
interactions between pathogens and the human host, as well as
extraordinary technical advances such as recombinant DNA
technology, gene sequencing and peptide synthesis. These
developments 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.
Vaccines: recent successes
Widespread use of vaccines based on technology developed by
NIH-supported researchers has resulted in the virtual elimination
of meningitis caused by Haemophilus influenza type B (Hib)
wherever the vaccine has been used. Prior to the availability of
an effective Hib vaccine, at least 10,000 U.S. infants suffered
invasive Hib disease annually, 10 percent of whom died and 20
to 30 percent of whom were left with long-term neurologic
sequelae. Today, Hib meningitis is virtually unknown in the
United States, and the Hib vaccine saves $400 million for each
cohort of children vaccinated. Building on the precedent set with
vaccines against smallpox and polio, widespread use of the Hib
vaccine could one day eradicate Hib meningitis in this country.
We now have a safe and effective hepatitis A vaccine developed
by NIH researchers, which has reduced the burden of this food-
and water-borne disease. Another vaccine developed by NIH
scientists has proven safe and effective in preventing the severe
diarrheal illnesses caused by rotavirus, which kill over 870,00
children worldwide every year. The successful development of
these vaccines exemplifies the synergy between basic and
applied research, as well as the fruitful collaborations that are
possible between the private and public sectors.
HIV vaccine development
Although recent treatment advances have led to an encouraging
downturn in the number of new AIDS cases and AIDS-related
deaths in this country, the epidemic continues to accelerate
elsewhere in the world. In 1997 alone, approximately 5.8 million
people globally were newly infected with HIV, including
approximately 590,000 children under age 15. More than 90
percent of these new infections -- approximately 16,000 each
day -- occurred in developing countries. By the end of 1997, an
estimated 30.6 million people were living with HIV/AIDS, a figure
projected to reach 40 million by the year 2000. These trends
underscore the importance of vigorously pursuing HIV vaccine
research and other prevention efforts to slow the spread of the
epidemic, in addition to finding new and better ways to treat
those already infected with HIV.
Last year, the participants in the Denver Summit of Eight
stressed their shared commitment to developing an HIV vaccine.
President Clinton, through the President's Vaccine Initiative, has
made HIV vaccine development a top priority, with the goal of
having a useful HIV vaccine within ten years. At NIH, we have
increased our support for a range of basic, preclinical and
clinical research activities to improve upon the vaccine
candidates that were the first to reach clinical trials. As part of
our expanded effort in HIV vaccine research, we recently
awarded 58 grants to foster innovative research on HIV
vaccines. In addition, the NIH has begun development of a
Vaccine Research Center (VRC) within the intramural research
program, co-sponsored by NIAID and the National Cancer
Institute, to stimulate multidisciplinary research into basic and
clinical immunology and virology, and ultimately vaccine design
and production. Concomitant with efforts in HIV vaccine
development, the NIH and our sister agencies within DHHS have
taken a leadership role in developing other approaches to HIV
prevention, such as behavioral modification, the development of
topical microbicides that women can use to protect themselves
from HIV and other infections, and new ways to prevent
maternal-fetal transmission. Such interventions promise to have
an important impact in fighting HIV in both the developed and
developing world.
Toward a tuberculosis vaccine
As noted above, TB exacts an enormous toll worldwide.
Resistance to TB drugs is widespread; even when effective, four
of these drugs generally must be taken for at least six months in
order to cure the disease, often in the setting of directly
observed therapy. Clearly, an effective TB vaccine is needed.
NIH is working to develop a TB vaccine with a two-tiered
approach: basic research into the mechanisms of the disease
and the response of the immune system to the infection; and
applied research into developing vaccine candidates. Several
candidates appear promising in pre-clinical studies, including
live-but-weakened strains of the TB bacterium, vaccines based
on components of the organism, and so-called "naked DNA
vaccines"
Improving current vaccines
Substantial NIH resources are also devoted to developing
improved vaccines that are more effective or easier to
administer than current vaccines while having fewer side effects.
The prototype of this kind of research is the NIH program to
develop acellular pertussis vaccines. In two seminal
NIH-sponsored trials in Italy and Sweden, researchers
conclusively demonstrated that acellular pertussis vaccines were
highly effective in protecting infants against whooping cough,
with fewer side-effects than a whole-cell pertussis vaccine that
had been in use for many years. The positive results of these
trials, the culmination of more than 15 years of NIH efforts in the
development of acellular pertussis vaccines, have helped define
acellular vaccines as the new "gold standard" in pertussis
immunization. We anticipate that the availability of acellular
pertussis vaccines will break down a significant barrier to
pertussis immunization --the reactogenicity of the whole cell
vaccine by improving vaccine coverage and thereby reducing
pertussis-related disease and death.
In the past few months, researchers in NIAID's Vaccine and
Treatment Evaluation Units have reported promising results with
a new influenza vaccine, given as a nasal spray. The new
vaccine promises to be easier to administer and more
acceptable than injections, thereby increasing vaccine coverage.
The nasal flu vaccine has proven safe and effective in children;
large-scale trials, now underway, will determine whether it
protects older people most at risk of serious influenza disease
and if, as hoped, it reduces influenza-related health care costs
and absenteeism in adults.
Developing research infrastructure
As we proceed with our efforts to conduct research on infectious
diseases with global impact, it is essential to engage scientists
in other countries and work collaboratively. Particularly in
developing countries where the burden of infectious diseases
has extraordinary impact, the development of research
infrastructure is an important component of our efforts. To
address this need, the Fogarty International Center and the
NIAID collaborate to carry out training and research programs
intended to enhance the skills of developing country scientists
and foster collaborations with our foreign partners.
The promise of new technologies
We now have at our disposal remarkably fast and accurate
methods for sequencing the genomes of disease-causing
microbes, tools that are a boon to vaccine development, studies
of drug resistance, and many other areas of research. The
success of the first microbe sequencing project -- the delineation
of the complete Haemophilus influenzae genome in 1995 --
encouraged our current efforts to sequence the full genomes of
several other medically important pathogens.
Other technologies of great importance to our mission fall
outside the disciplines traditionally associated with infectious
disease research. For example, in partnership with the National
Aeronautics and Space Administration, NIH-funded scientists
are using satellite-based remote sensing technology and
geographic information systems to identify ecologic conditions
associated with infectious disease outbreaks. This approach
could help predict potential disease outbreaks and identify
regions where intervention programs should be targeted.
Conclusion
Using modern technologies, NIH continues to build a solid
research foundation in immunology, microbiology and related
disciplines that drive the development of new treatments,
vaccines and diagnostic tools for infectious diseases.
With a strong research infrastructure in these areas, our ability to
do battle with infectious microbes -- known and unknown -- is
greatly enhanced.
