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108th Congress
Session I | Session II
Testimony Before the House Committee on Appropriations Subcommittee on Labor, HHS, and Education, United States House of Representatives
Anthony S. Fauci, M.D.
Director
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Department of Health and Human Services
Introduction
Mr. Chairman and Members of the Committee, thank you for the opportunity to discuss with you the
role of the National Institute of Allergy and Infectious Diseases (NIAID) in combating infectious
diseases worldwide. Infectious diseases pose a major global public health challenge. These diseases are
the second leading cause of death worldwide, accounting for 26 percent of all deaths. Furthermore,
because infectious diseases strike the young disproportionately, causing approximately two thirds of
deaths among children less than five years of age, the situation is even worse in terms of years of healthy
life lost. Infectious diseases also seriously undermine economic development, especially in developing
countries, and can cause serious political instability. Infectious diseases are both a cause and
consequence of poverty.
Infectious diseases have afflicted humanity throughout history, and will continue to do so for the
indefinite future. Moreover, the viruses, bacteria, and parasites that cause infectious diseases continually
and dramatically change over time as new pathogens emerge and familiar ones re-emerge with either
new properties or in unfamiliar settings. For example, since the Acquired Immunodeficiency Syndrome
(AIDS) was first recognized in 1981, this emerging disease has spread relentlessly throughout the
world. It now threatens to surpass in total fatalities both the “Black Death” of the 14th century and the
influenza pandemic of 1918-1919—two other emerging infections that each killed tens of millions of
people. In the past five years alone, we have seen the appearance of the West Nile and monkeypox
viruses in the United States, an unprecedented number of human infections with avian influenza viruses,
as well as the emergence of a new infectious disease, Severe Acute Respiratory Syndrome (SARS).
Finally, the anthrax bioterrorist attacks of 2001 confronted us with a disease resulting from the
deliberate release of an infectious agent.
Effective national and global responses to infectious disease threats, whether they are emerging, re-
emerging, or deliberately introduced, involve many different types of activities and many different
organizations. NIAID, a component of the National Institutes of Health (NIH), is the lead Federal
agency for conducting, supporting, and coordinating research on infectious diseases. NIAID’s research
activities include the basic and clinical research needed to understand these diseases, as well as the
application of knowledge gained to develop the relevant diagnostics, therapeutics, and vaccines. Today,
I will briefly highlight NIAID research activities on the three infectious diseases with highest global death
toll—malaria, tuberculosis, and HIV/AIDS, as well as three other emerging and re-emerging
infections—SARS, West Nile Virus, and influenza. I will close with a short discussion of NIAID
biodefense research to counter deliberately-emerging disease threats.
Malaria
Malaria is one of the major killers of humans worldwide, threatening the lives of more than one-third of
the world’s population. Caused by a single-celled parasite and transmitted by mosquitoes, malaria
causes an estimated 300 million acute illnesses each year, with more than 1 million deaths. It is a
substantial impediment to economic and social development in regions where it is endemic, especially in
sub-Saharan Africa. The threat posed by malaria is growing, primarily because of the spread of drug-
resistant strains and insecticide-resistant mosquitoes, changing weather patterns, and limitations of the
medical and public health infrastructure in many endemic areas.
The sequencing of the complete genomes of all three organisms involved in the malaria parasite’s life
cycle—human beings, Plasmodium falciparum, the most lethal malaria-causing parasite, and Anopheles
gambiae, a mosquito that transmits the parasite to humans—were recently completed. Scientists are
now mining this wealth of genomic data to gain new insights into malaria pathogenesis, and to uncover
new molecular targets for both drugs and vaccines. For example, genomic data have allowed scientists
to discover new parasite enzymes that are very promising targets for drug intervention; NIAID and the
pharmaceutical industry are currently collaborating in the development of drug candidates against these
enzymes. In addition, in 2003, NIAID launched its first clinical trial of a malaria vaccine in a malaria
endemic country: Mali, in west Africa.
Tuberculosis
The bacterium that causes tuberculosis (TB) currently infects about 2 billion people, or about one-third
of the world’s population; five to ten percent of infected people will develop active TB disease
sometime in their lifetime. Each year, approximately 8 million new cases of active TB occur, and
approximately 2 million people die of the disease. The problem is currently being exacerbated by two
major factors. First, the alarming global prevalence of HIV/AIDS has created a situation whereby many
more people today have a compromised immune system, which allows a latent TB infection to become
active and spread more easily. Second, drug resistant strains of the TB bacterium develop readily when
an infected individual does not take the entire course of standard antibiotic treatment, which typically
lasts for six to nine months. Strains of the TB bacterium that are resistant to the least expensive and
most effective anti-TB antibiotics have spread widely.
To address this problem, NIAID scientists are working to develop more effective drugs that would
allow for shorter and less complex drug treatments. A promising drug candidate developed by public
and private partners with contributions by NIAID is completing preclinical evaluation, and is expected
to undergo review by the U.S. Food and Drug Administration (FDA) later this year for approval to be
tested in humans. This candidate is a new member of a class of chemicals known as nitroimidazoles,
which have the potential to be effective against both the drug-resistant and drug-sensitive forms of TB.
The development of a new TB vaccine is also critical because the currently available TB vaccine only
offers protection against disseminated TB in infants and children, with limited effectiveness against TB of
the lung, the most contagious form of the disease among adults and children. This year, two new
engineered TB vaccines developed with NIAID support entered clinical trials in the United States, the
first to do so in 60 years. These studies also offer an opportunity to learn more about the protective
immune responses against the TB bacterium, which are currently not completely understood. In
addition, NIAID is supporting development of several promising TB diagnostic tests.
HIV/AIDS
HIV/AIDS is taking a terrible toll worldwide. Approximately 40 million people worldwide are infected
with the virus. In 2003 alone, 5 million new infections occurred—about 14,000 each day—and an
estimated 3 million people with HIV/AIDS died, 500,000 of whom were children. In the United States,
nearly one million people are living with HIV/AIDS, and by the end of 2002, more than 500,000
Americans with HIV/AIDS had died. As sobering as these numbers are, however, they do not
adequately convey the physical and emotional devastation to individuals, families, and communities
coping with HIV/AIDS, nor do they capture the devastating impact of the pandemic on national
economies and political stability.
Although the burden of HIV/AIDS continues to grow, biomedical research provides optimism that
those already infected can lead healthy lives and that improved prevention approaches to stop the
spread of HIV can be developed. Two decades of basic research into the mechanisms by which the
virus propagates itself and evades and destroys the immune system have led to the development of
more than 20 antiretroviral drugs, which can reduce the level of virus in an infected person, maintain the
health of the person for many years, and prevent mother-to-infant transmission of HIV. Four new
antiretroviral drugs were licensed in 2003 by the FDA, each of which was developed on the basis of
NIAID-sponsored research or tested in NIAID clinical trials networks. Many other new anti-HIV drug
candidates are in clinical trials.
A vaccine that prevents HIV infection, or at least slows the progression of disease, would be an
enormously powerful tool to control the pandemic, and is, therefore, a critical NIAID priority.
Development of such a vaccine presents many difficulties, including the genetic diversity of the virus and
the lack of a clear understanding of the immune responses that might protect against HIV infection.
Nonetheless, NIAID and its academic, industrial, international and philanthropic partners have made
significant progress, and several HIV vaccine candidates are in preclinical and clinical development.
Because of the international character of the AIDS pandemic, the President’s budget request for FY
2005 includes approximately $355 million for NIH HIV/AIDS research conducted at international
sites. The NIAID international HIV/AIDS research agenda includes development of vaccines,
microbicides and other prevention strategies to interrupt transmission of HIV, testing of therapeutic
approaches for HIV and common co-infections such as tuberculosis and malaria, and discovery of new
ways to prevent HIV transmission at birth and through breast-feeding. Furthermore, the President’s
Emergency Plan for AIDS Relief (PEPFAR)—a $15 billion initiative to treat, prevent, and care for HIV
infection in areas hardest hit by the pandemic—and the activities of the Global Fund to Fight
HIV/AIDS, Tuberculosis, and Malaria—an international effort organized with U.S. leadership and
currently chaired by HHS Secretary Tommy Thompson—will provide treatment, care, and prevention
services to those who need them most, and, together with continued advances in the biomedical
research arena, will help address the devastation caused by HIV/AIDS.
SARS
SARS is the first severe, newly emergent infectious disease of the 21st century. The prompt recognition
in the Spring of 2003 that SARS is caused by a new type of coronavirus and the rapid progress in
SARS research that followed reflect the dedication of and collaboration by the world's medical
researchers and public health experts, including NIAID-sponsored scientists in the United States and
abroad. Although only very few cases of SARS have occurred over the past several months, we must
remain vigilant to prevent another global outbreak. NIAID supports research to understand the
epidemiology and biology of the SARS virus and how it spreads, and to develop vaccines, diagnostic
tests and therapeutic agents to effectively address any future SARS outbreaks.
NIAID scientists and grantees are pursuing several parallel approaches to develop candidate SARS
vaccines. NIAID intramural scientists recently made two advances in SARS vaccine development. In
one study, they showed that the mouse immune system develops antibodies capable of neutralizing the
SARS virus. In a second study, NIAID researchers demonstrated that a DNA vaccine based on a
gene for a viral protein protected mice challenged with the virus by inducing the appropriate antibody
responses. A Phase I clinical trial of this candidate DNA vaccine is planned for late 2004. Although a
great deal of work remains to translate these findings into a safe and effective human vaccine, these
studies indicate that SARS vaccines that trigger antibodies to the SARS virus are a promising avenue to
pursue.
West Nile Virus
West Nile virus (WNV) first appeared in the Western Hemisphere in 1999, and by 2003 had spread to
46 states in the United States. NIAID has moved quickly to address this threat by expanding basic
research into how the virus causes diseases and how it is maintained in nature. NIAID also embarked
on the development of vaccines and treatments, and acted to provide reagents and other resources to
the research community. Several promising vaccine candidates against WNV are under development.
Two are genetically engineered combinations of WNV proteins added to a highly attenuated strain of
another virus. One candidate is based on the attenuated virus used in the Yellow Fever vaccine, the
other on the attenuated Dengue virus used in a Dengue vaccine. Both have been shown to be 100
percent protective in primates, and both will shortly enter Phase I human safety and immunogenicity
testing. Another vaccine candidate is DNA-based. A Phase I clinical trial is planned for late 2004 to
assess the safety and immunogenicity of this vaccine candidate in healthy volunteers.
Influenza
The influenza virus constantly changes, and therefore can be considered a classic example of a re-
emerging disease. In the United States, influenza infections cause an average of 36,000 deaths and
114,000 hospitalizations each year; the World Health Organization (WHO) estimates that the annual
average number of influenza-related deaths worldwide is approximately 500,000.
In most years, human influenza viruses undergo gradual changes in their antigenicity so that over time
viruses emerge that are no longer neutralized by the anti-influenza immune responses of most people.
This process is called antigenic drift and is the reason influenza vaccines must be re-evaluated and
usually updated every year. Influenza viruses are common in nature and infect many different animal
species especially migratory water fowl, pigs and horses. Occasionally, one of these animal influenza
viruses acquires the ability to infect other hosts and jumps from its normal host into humans, as has
occurred in the past months with avian influenza. Humans that become infected with avian influenza
viruses do not appear to transmit these animal viruses to other humans. However, if the animal virus
mutates sufficiently and/or recombines with a human virus and thereby acquires the capability to spread
efficiently from person to person, the result can be a fast-moving and deadly pandemic. For example,
the influenza pandemic that occurred in 1918-1919 after such a viral evolution killed 20-40 million
people worldwide, including more than half a million individuals in the United States. Influenza
pandemics that occurred following other such shifts in 1957 and 1968 killed approximately 2 million
and 700,000 people worldwide, respectively. These figures explain our current high level of concern
about the appearance of new forms of virulent H5N1 avian influenza viruses in Asia, which could
subsequently mutate or recombine with human influenza viruses to cause a pandemic. Given the poor
condition of public health systems in many underdeveloped regions and the speed of modern air travel,
the consequences of such an event, should it result in an influenza pandemic, would be severe.
The NIAID has responded to this situation with a comprehensive research program. The overall goal of
the NIAID Influenza Program is to support research that leads to more effective approaches for
controlling influenza virus infections. The program has two major components. The first component
reflects longstanding programs for interpandemic influenza—research to understand the pathogenesis,
transmissibility, evolution, epidemiology, and the immune response to influenza viruses, and to develop
new drugs and vaccines to combat it. The second component specifies NIAID’s several roles after the
emergence of influenza viruses with pandemic potential in humans. Foremost among these is to help
develop and produce an effective vaccine as rapidly as possible. NIAID also would work with industry
to produce and clinically test candidates at different doses and in different populations in our vaccine
clinical trials sites, and would coordinate closely with the Centers for Disease Control and Prevention
(CDC), FDA, and WHO to ensure that a safe and effective vaccine is available to the public as soon as
possible.
The use of reverse genetics—a genetic tool developed by NIAID-supported scientists—holds great
promise for rapid generation of vaccine candidates that could be used against a newly-emerged
pandemic strain. Laboratories around the world are using this technique to prepare vaccine candidates
against the H5N1 viruses emerging in Asia; NIAID is currently conducting negotiations for the
production of a 2004 H5N1 inactivated influenza vaccine for clinical trials.
Biodefense
Since the anthrax attacks of 2001 and the growing understanding of the serious threat posed by the
possibility of bioterrorist attacks with deadly pathogens, NIAID has significantly strengthened,
accelerated, and expanded its biodefense research program. NIAID-supported biodefense research
includes basic research into the disease-causing mechanisms of microbes that could be used by
bioterrorists, as well as translational research to turn this knowledge into safe and effective treatments,
diagnostics, and vaccines. Biodefense research on potential agents of bioterror promises to enhance not
only our preparedness for bioterrorism, but also for other naturally-occurring endemic, emerging, and
re-emerging infectious diseases.
Recent progress in biodefense research has been rapid. More than 50 major NIAID initiatives involving
intramural, academic and industrial partners have been undertaken. NIAID has also implemented a
large program to expand the infrastructure necessary for biodefense research. This includes funding of
eight Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases Research, and
the construction of two National Biocontainment Laboratories (NBLs) and nine Regional
Biocontainment Laboratories (RBLs). These high-level biosafety facilities will speed the development of
effective therapies, vaccines and diagnostics for infectious diseases.
The ultimate goal of all NIAID biodefense research is the development of medical countermeasures.
With respect to drug treatments, NIAID-supported scientists have recently identified antivirals that may
help treat smallpox or the complications of smallpox vaccination, and have identified several
approaches to blocking the toxins of the anthrax bacterium. New and improved vaccines against
smallpox, anthrax and other potential agents also are being developed. For example, NIAID has
sponsored the development of a next-generation anthrax vaccine known as rPA. Clinical trials of rPA
are under way; results to date suggest that the vaccine is safe and capable of evoking a robust immune
response. Researchers also will test whether the currently recommended course of antibiotic therapy for
individuals exposed to anthrax spores could be shortened by vaccinating with rPA after exposure.
NIAID-supported researchers also are testing several new smallpox vaccine candidates that may have
fewer side effects than the traditional Dryvax vaccinia virus. One of these, modified vaccinia Ankara
(MVA), is based on a strain of the vaccinia virus that replicates far less robustly than Dryvax in humans,
and is known to cause fewer side effects. Human trials of the potential efficacy of MVA vaccines are
under way at NIH and elsewhere; recent studies by NIAID intramural scientists and their colleagues
have shown that MVA protects monkeys and mice from smallpox-like viruses.
NIAID has launched the first human trial of a vaccine designed to prevent infection with Ebola virus.
The trial vaccine is made from parts of the viral DNA, and is similar in design to other investigational
vaccines that hold promise for controlling such diseases as AIDS, West Nile, and SARS.
Conclusion
Emerging, re-emerging, and deliberately emerging diseases pose a global public health challenge.
NIAID, the federal agency charged with the responsibility for conducting and coordinating basic and
clinical research to cope with infectious disease, plays a major role in our national response to these
serious global health issues. I would be pleased to answer any questions you may have.
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