By 1986, there were 5,833 reported AIDS cases in the United States and the 1-year
mortality was 51 percent. Efforts were being made to find something—anything—that would slow disease
progression. A seminal discovery, made in 1970, was that an
enzyme called reverse transcriptase was necessary for retroviruses like HIV to replicate. Based on this understanding, scientists
began to screen existing agents to find candidate drugs that inhibited the enzyme. Drs. Robert
Yarchoan, Hiroaki Mitsuya, and Samuel Broder found that zidovudine (AZT) had this property.
AZT was then quickly placed in a placebo-controlled clinical trial in patients with
late-stage disease. The first review of data in September 1986 showed 19 deaths in
the placebo group compared with 1 death in the AZT treatment group. The study was
stopped and the FDA approved the drug in record time. It was 21 months from trial
initiation to drug approval—an FDA record that has never been surpassed.
Introduction
The goals of NIH-supported research on infectious diseases and biodefense rest on
two core components. NIH builds and maintains a base of fundamental knowledge about
infectious and immune-related diseases and uses that knowledge to develop new and
improved diagnostics, therapeutics, and preventive measures, including vaccines.
At the same time, NIH continues to develop a flexible domestic and international
infrastructure that allows it to respond to newly emerging and re-emerging threats
wherever they occur, thereby protecting public health in the United States and abroad.
Infectious Diseases
Infectious diseases are caused by microbial pathogens—bacteria, viruses, fungi, protozoa,
and helminths (worms)—that invade the body and multiply, causing physiological damage and illness.
Pathogens cause a range of diseases from nonserious to life-threatening and can be transmitted in
many ways. Influenza and TB can be transmitted from person to person via airborne inhalation; HIV,
which causes AIDS, is transmitted through exposure to blood or other body fluids, during sexual
intercourse, and from mother to child at birth or during breast-feeding; and malaria is caused by
a microscopic parasite that is transmitted by an insect “vector,” in this case a mosquito. Unlike
chronic and degenerative illnesses, transmissible infectious diseases can rapidly devastate large
human populations and easily cross international borders
Biodefense and Emerging and Reemerging Infectious Diseases
Public health threats that could cause large-scale disruption and devastation include the deliberate
or accidental release of pathogenic agents such as anthrax or smallpox, biological toxins, chemical
weapons such as nerve gas, or radioactive substances. The NIH biodefense strategy is designed to protect
all civilian populations and integrates basic, applied, and clinical research knowledge and capabilities
into a flexible and adaptable “network.” Other threats to public health change continually as new pathogens
emerge and as familiar microbes reemerge with new properties or in unusual settings. Examples of recent
emerging and reemerging public health threats include naturally occurring infectious diseases such as
Ebola hemorrhagic fever and severe acute respiratory syndrome (SARS). The overall goal of research on
biodefense and emerging and reemerging infectious diseases is to develop the knowledge and tools to
respond quickly and effectively as public health threats emerge, whether they occur naturally,
accidentally, or deliberately.
Although NIAID has primary responsibility for infectious diseases and biodefense research, many other NIH ICs
play critical roles, including FIC, NICHD, NINDS, and the NIH Office of AIDS Research (OAR). Nearly every
NIH IC supports AIDS-related research activities, consistent with their individual missions. The ICs that
conduct most of the research on AIDS and related co-infections, malignancies, cardiovascular and metabolic
complications, and behavioral and social science issues are NIAID, NIDA, NCI, NIMH, the National Center for
Research Resources (NCRR), NICHD, and NHLBI. All NIH AIDS research is coordinated by OAR.
In addition, the NIH Office of Science Policy manages and supports the National Science Advisory
Board for Biosecurity (NSABB). The NSABB provides advice on strategies for the efficient and
effective oversight of dual-use biological research—research that has a legitimate scientific purpose
but could be misused to pose a threat to public health or national security—taking into consideration
both national security concerns and the needs of the research community.
NIH-wide research on infectious diseases and biodefense includes basic research to understand
fundamental mechanisms by which microorganisms cause disease, the host response to pathogens,
and mechanisms by which insects and other vectors transmit infectious diseases. Translational
research builds on basic research findings with the aim of developing new and improved diagnostics,
therapeutics, vaccines, and other preventive measures. NIH conducts and supports clinical research to
assess the efficacy and safety of new drugs, vaccines, and other products. As NIH pursues these goals,
an overarching priority is to reduce health disparities and improve health for all people.
Infectious diseases and biodefense are inherently global concerns. NIH engages in international
partnerships to improve means for detecting and controlling the spread of infectious diseases and
supports international programs to foster research and research capacity in low- and middle-income
countries. Within the United States, NIH seeks strategic partnerships with other governmental
and nongovernmental organizations.
NIH supports research on HIV/AIDS, TB, malaria, emerging and reemerging infectious diseases
(such as hemorrhagic fevers caused by Ebola and other viruses, West Nile virus, SARS, Lyme
disease, prion diseases, and H5N1, a virus that causes avian influenza), sexually transmitted
infections, and influenza and other respiratory infections. In addition, NIH funds research on
many less familiar but still important diseases that exact an enormous global toll24.
NIH research on biodefense and emerging and reemerging infectious diseases is necessarily intertwined
and includes the development of infrastructure and capacity-building, that is, facilities and human
resources needed to conduct research on dangerous pathogens safely and effectively; basic research
on microbes and host immune defenses; and the targeted development of medical countermeasures,
including vaccines, therapeutics, and diagnostics that would be needed in the event of a
biological, chemical, or radiological weapons attack.
Burden of Illness and Related Health Statistics
Infectious diseases cause approximately 26 percent of all deaths worldwide. Each year, more
than 11 million people die from infectious diseases, the vast majority of deaths occurring in
low- and middle-income countries. The top infectious disease killers in those countries for
people ages 15 to 59 are HIV/AIDS, TB, and lower respiratory infections. HIV causes nearly 2.1
million total deaths each year25, TB kills 1.6 million each year, and lower respiratory infections
in 2005 caused an estimated 3.7 million deaths.26, Malaria is a serious problem, especially in Africa,
where one in every five childhood deaths is due to the effects of the disease.27 The infectious
diseases that today cause the greatest number of human deaths worldwide are (in order) lower
respiratory infections, HIV/AIDS, diarrheal diseases, malaria, and TB.28
Each year infectious diseases kill approximately 6.5 million children, most of whom live in
developing countries. For children younger than age 14, infectious diseases account for 7
of the top 10 causes of death. In this age group, the leading infectious diseases are lower
respiratory infections, diarrheal diseases, and malaria. Among children younger than age 5,
infectious diseases cause about two-thirds of all deaths.29
The burden of infectious diseases is not evenly shared, even among developing nations.
People who live in sub-Saharan Africa are most affected, particularly by HIV/AIDS, which
accounts for one in five deaths in that region. Africa and the most populous countries of
Asia harbor the largest number of TB cases. Together, Bangladesh, China, India, Indonesia,
and Pakistan account for half of new TB cases each year.30
In the United States, infectious diseases add significantly to the overall burden of illness.
Together, influenza and pneumonia account for more than 60,000 deaths annually.31 More than
a million cases of sexually transmitted diseases occur each year, and more than 42,000
new cases of AIDS were reported in 2004.32
Also, many infectious diseases are increasingly difficult to treat because pathogens
are developing resistance to antimicrobial drugs. For example, in recent years there have
been dramatic increases in antiretroviral drug resistance in HIV, chloroquine resistance in
malaria, the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant
TB (XDR-TB), and methicillin-resistant Staphylococcus aureus (MRSA) infection.
NIH Funding for Infectious Disease and Biodefense Research
FYs 2006 and 2007, NIH funding for infectious diseases research was $3.132 billion and $3.059 billion
respectively. Funding for biodefense research was $1.766 billion and $1.735 billion. There is substantial
overlap in these funding figures. The table at the end of this chapter indicates some of the research
areas involved in this investment (see “Estimates of Funding for Various Diseases, Conditions,
and Research Areas”).
Summary of NIH Activities
NIH programs on infectious diseases and biodefense encompass a broad range of basic, translational,
preclinical, and clinical research. These activities include developing critical research resources
and infrastructure domestically and abroad that allow NIH to respond effectively to existing and
emerging infectious diseases wherever they occur.
Basic Research
Basic research on infectious diseases and biodefense seeks to increase understanding of how pathogens
cause disease and how hosts respond to infection; it provides the foundation for improvements in the
prevention, diagnosis, and treatment of infectious diseases. For example, NIH researchers recently
discovered how a surface protein of the virus that causes chicken pox and shingles attaches to a
host cellular protein. That finding, in turn, has opened the door to designing and developing new
treatments that block the virus-attachment process.
Many challenges remain in basic research on infectious diseases. These include further definition
of the mechanisms by which the immune system protects against infection and of the intricate
interactions that occur between pathogens and their hosts; more precise identification of the
driving forces behind changing global patterns of infectious diseases; uncovering additional
links between infectious diseases (and the immune responses to them) and the development of
some cancers, as well as some autoimmune, cardiovascular, and neurological disorders; and
discovering how and why genetic changes arise that make pathogens more dangerous. For example,
HIV, H5N1 influenza, and Ebola virus originated in animals but mutated and acquired the ability
to infect humans. Also, microbes that cause TB, AIDS, and influenza are mutating and acquiring
resistance to antimicrobial drugs, which has prompted NIH to develop research initiatives and
programs to expand investigations of the basis of antimicrobial resistance, including how bacteria
develop and share resistance genes.
Many advances in understanding infectious diseases are the result of the revolution in genomic
sequencing that has occurred in the past decade. In FYs 2006 and 2007, NIH-funded researchers
and their collaborators completed a range of genome-sequencing projects that help reveal how
microbes evolve, infect host cells, cause disease, develop drug resistance, and spread. The
studies include sequencing the complete or partial genomes of 54 different samples of the
malaria parasite, Plasmodium falciparum; a common sexually transmitted parasite,
Trichomonas vaginalis; an oral bacterium; and more than 2,800 samples of avian and human
influenza viruses.33
Several of the genome-wide association studies funded by NIH examine
genetic variations and explore susceptibility to infection or responses to smallpox,
anthrax, typhoid, and cholera vaccinations (see also the section “Genomics” in Chapter 3).
Major Infectious Diseases
NIH conducts research on hundreds of infectious diseases, placing special emphasis on those
that claim large numbers of lives each year and cause widespread suffering. NIH also explores
how human behaviors as well as social, cultural, economic, and geographic factors affect
disease transmission. Additionally, NIH conducts studies to evaluate and ensure the health
of special populations, including minorities, individuals who are immunocompromised, the
elderly, adolescents, young children, and infants. The ultimate goal is to translate knowledge
gained through basic research into interventions that improve public health.
Tuberculosis
TB is an old disease but still ranks high among the foremost microbial killers of the 21st century
and is particularly common among people with HIV. NIH supports a large portfolio of research to
develop new drugs, vaccines, and diagnostics for TB and to evaluate improved treatment and
prevention regimens. New drugs currently in clinical trials include SQ-109, a promising
candidate therapy being developed in a private-public partnership. After a hiatus of 60
years in which no new TB vaccines were clinically tested, at least 9 candidates are now in
human trials and at least 10 more are in preclinical development.
The rapid emergence of drug-resistant forms of TB poses an increasing and dangerous public
health threat. Both MDR-TB and XDR-TB are classified as emerging infectious diseases and
are increasingly difficult to treat. NIH supports the development of new and improved
diagnostic tools to more accurately diagnose early TB disease, help optimize therapy
by identifying drug-resistant strains, and track the spread of TB in communities.
To ensure that research continues to contribute effectively to the global response to
the increasing TB threat, in 2007 NIH developed a comprehensive
TB research agenda.
The plan incorporates NIH collaborations with other U.S. Government agencies and
multilateral organizations worldwide and supports public-private partnerships to benefit
people who have TB, including individuals who are co-infected with HIV.
Malaria
The age-old scourge of malaria claims millions of lives every year, mostly among children. The
broad NIH malaria research portfolio and the malaria research agenda currently under development
are designed to improve understanding of malaria parasites, host responses, and vector biology,
thereby accelerating the development of new and improved public health interventions, including
vaccines, therapeutics, and vector management. NIH is collaborating with strategic partners to
develop vaccines for malaria and is currently testing several candidate vaccines in malaria-endemic
areas. In 2007, NIAID began a new initiative entitled “NIAID Partnerships with Public-Private
Partnerships.” This initiative seeks to support the role of public-private partnerships in the
development of new drugs, vaccines, and diagnostics for diseases such as malaria, trypanosomiasis,
leishmaniasis, and other neglected tropical diseases.
HIV/AIDS
In the countries hardest hit by HIV/AIDS, the disease has lowered life expectancy, orphaned millions of
children, lowered family income, reduced worker productivity, and diminished the supply of teachers and
health care workers.34
NIH plays many critical roles in the global effort to conquer HIV. Antiretroviral
therapies made possible by NIH-supported research have resulted in improved quality of life and life
expectancy for people who have access to these drugs. A recent study concluded that, since 1996,
these antiretroviral medications have saved at least 3 million years of life in the United States
alone. Worldwide, more than 2 million people receive antiretroviral therapy, more than half of them
with support from the President's Emergency Plan for AIDS Relief (PEPFAR). However, the use of these
antiretroviral therapies is associated with a range of side effects and long-term complications that
may have a negative impact on mortality rates. The appearance of multidrug-resistant strains of HIV
presents an additional serious public health concern. NIH AIDS research programs are addressing these
and other complications.
The broad effort to extend the availability and use of anti-HIV drugs to regions most affected by HIV/AIDS
continues. NIH is funding research to develop therapeutic regimens that are easier to use in resource-limited
settings, as well as new antiretroviral drugs that target HIV in novel ways. In one of the largest HIV/AIDS
treatment trials ever conducted, NIH-funded scientists participating in an international collaboration
involving 318 clinical sites in 33 countries showed that HIV-positive individuals who receive episodic
treatment with anti-HIV drugs have twice the risk of disease progression, including death from AIDS,
than do those who receive continuous therapy with antiretroviral drugs. In addition, the recently
Children with HIV Early Antiretroviral Therapy study
in South Africa showed that treating HIV-infected children early with antiretroviral drugs helps them live longer.
Another key research priority is prevention and treatment of HIV-associated co-infections,
such as TB and hepatitis C, and comorbidities, such as HIV-associated malignancies, cardiovascular
disease, and neurological complications. Studies are evaluating the incidence and treatment of
metabolic and cardiovascular disease in people who receive long-term antiretroviral therapy.
In addition, the AIDS Malignancy Consortium has launched several clinical studies to identify
appropriate treatment regimens for HIV-infected individuals with cancer.
Successful efforts to prevent the spread of HIV and improve adherence and access to treatment
are also driven by research in behavioral and social sciences that extends understanding of
decision-making, drug abuse, and sexual behavior. As people changed risky behaviors, new AIDS
cases in the United States were nearly halved from a peak of over 80,000/year in 199335,
to 42,000/year in 200536.
Previously 1,650 babies were born infected with HIV each year but
today that number is less than 5037.
Whether preventing transmission, engendering trust to
encourage testing and early treatment, or increasing adherence and access to the latest
medications and health services, slowing the spread of HIVAIDS involves understanding
(basic behavioral and social science) and changing human behavior at individual,
group and community levels.
NIH continues to place a high priority on HIV prevention research, including research to develop vaccines,
microbicides, strategies to prevent mother-to-child transmission, antiretroviral therapy as a pre-exposure
prophylaxis strategy, treatment for drug addiction, and behavioral interventions. NIH-sponsored studies
recently demonstrated that the use of antiretroviral prophylaxis can reduce the rate of mother-to-child
transmission of HIV from approximately 25 percent to less than 2 percent. NIH also supports research
to develop and test other prevention strategies, such as circumcision. For example, NIH-supported
clinical trials in Kenya and Uganda showed that medically supervised circumcision of adult males
can significantly lower their risk of contracting HIV through heterosexual intercourse by approximately 50
percent. In countries hit hard by HIV, adult male circumcision serves as another prevention strategy that
could result in fewer HIV infections.
Topically applied microbicides for women and men are another promising avenue for preventing HIV
transmission. Several microbicides have entered large-scale efficacy trials, the results of
which are expected in the next few years. In 2006, NIH established the
Microbicide Trials Network
to develop safe and effective microbicides to prevent HIV transmission. In addition to
basic and clinical research, studies of cultural and behavioral factors related to
acceptability and adherence of prevention interventions are under way.
The ultimate prevention tool, and what is considered the best hope to end the HIV/AIDS pandemic, is a
safe and effective vaccine that could prevent HIV infection. NIH-supported researchers around the
world have developed candidate vaccines against HIV, some of which are now being tested in various
phases of clinical trials. One example is the large-efficacy HIV vaccine trial in Thailand that is
being conducted with support from NIH. The
NIH Vaccine Research Center,
as well as the NIH-supported
HIV Vaccine Trials Network,
is also dedicated to developing and testing new HIV vaccine candidates, including some that target different
HIV types (called clades). To overcome key scientific roadblocks to HIV vaccine development and facilitate
the design and testing of HIV vaccine candidates, NIH established the
Center for HIV/AIDS Vaccine Immunology,
an international consortium of scientists. NIH is a member of the Partnership for AIDS Vaccine
Evaluation, a consortium of U.S. Government agencies and key U.S. Government-funded organizations
involved in the development and evaluation of HIV vaccines. NIH also recently reissued a notice of
program project awards for the HIV Vaccine Research and Design Program, which supports multiproject,
multidisciplinary HIV/AIDS vaccine-related studies.
Emerging Infectious Diseases and Biodefense
NIH has mounted a comprehensive and vigorous research program to address critical challenges posed by
naturally emerging and reemerging infectious diseases, as well as to mitigate the threats of
biological, chemical, or nuclear/radiological terrorism.
The goals of these overlapping programs are to develop the capacity
to respond rapidly to public health threats; better understand the patterns and means by
which pathogens spread and how they cause disease; decipher the mechanisms by which
pathogens that infect animals mutate and acquire the ability to infect humans; and develop
safe and effective medical countermeasures against naturally occurring, accidental, and deliberately
introduced public health threats.
Influenza is a classic example of a reemerging infectious disease. The influenza viruses that caused the
pandemic World War I-era Spanish flu and the current avian flu (caused by the H5N1 influenza virus) began
in birds, mutated and spread to mammals (pigs, cats, etc.), and then mutated further and acquired the
ability to infect humans. Thus, the spread of H5N1 from birds to humans underscores the urgent need to
develop better vaccines and drugs to protect against pandemic influenza, as well as the seasonal epidemics
that claim an average of 36,000 lives per year in the United States alone.
In 2006, NIH undertook a comprehensive examination of its influenza portfolio and convened a
Blue Ribbon Panel on Influenza Research
to identify areas of influenza research in which progress is needed. To help implement the panel's
recommendations and facilitate a broad spectrum of influenza research, NIH has adopted several
strategies. In 2007, NIH made multiple awards to support innovative influenza research to advance
the development of promising vaccines, adjuvants, therapeutics, immunotherapeutics, and diagnostics.
NIH also established six
Centers of Excellence for Influenza Research and Surveillance
to expand its ability to conduct research on different strains of animal and human influenza
viruses collected in other countries or the United States. NIH researchers are collaborating
extensively with other Department of Health and Human Services (HHS) agencies, across other
Federal agencies, with private industry, and internationally and are working with strategic
partners to develop DNA-, recombinant virus-, and recombinant protein-based candidate influenza
vaccines. NIH also leads an international collaborative effort to analyze national and global
epidemiological patterns associated with influenza virus circulation.
To date, NIH research has laid the foundation for improved influenza vaccine manufacturing
methods, new categories of vaccines that may work against multiple influenza strains, and the
next generation of anti-influenza drugs. The inactivated-virus H5N1 vaccine currently stockpiled
by HHS has been shown in NIH-sponsored clinical trials to be safe and capable of inducing an immune
response predictive of being protective against the H5N1 virus in healthy adults, children, and seniors.
To date, NIH research has laid the foundation for improved influenza vaccine manufacturing methods,
new categories of vaccines that may work against multiple influenza strains, and the next generation
of anti-influenza drugs. The inactivated-virus H5N1 vaccine currently stockpiled by HHS has been
shown in NIH-sponsored clinical trials to be safe and capable of inducing an immune response predictive
of being protective against the H5N1 virus in healthy adults, children, and seniors.
Biological Countermeasures Research
NIH supports research on a range of emerging and reemerging pathogens that are also considered potential
agents of bioterrorism, including Marburg and Ebola hemorrhagic fever viruses, smallpox, and anthrax.
NIH-supported researchers are probing the ecology of how these infections arise, identifying the
natural hosts and modes of natural transmission of pathogens and developing safe and effective
vaccines and treatments. For example, NIH-funded scientists recently developed promising candidate
vaccines for Ebola and Marburg hemorrhagic fever viruses. The Marburg vaccine has been tested in
rhesus monkeys and helped all of them survive a later challenge with live virus. An
experimental Ebola vaccine
has entered human clinical trials.
Chemical Countermeasures
Within HHS, NIH is leading the development of new and improved medical countermeasures designed
to prevent, diagnose, and treat the conditions caused by chemical agents that could be released
either accidentally or deliberately. To guide this research, NIH has prepared the “Strategic
Plan and Research Agenda on Medical Countermeasures Against Chemical Threats.” Under this plan
and in collaboration with DoD, NIH has established the trans-agency
CounterACT Research Network.
The network has established four Centers of Excellence in Medical Chemical Research; funded
more than two dozen research projects focusing on nerve agents, sulfur mustard and other
blister-causing agents, cyanide and other metabolic poisons, and pulmonary agents; and awarded
several Small Business Innovation Research grants for therapeutics and diagnostics development.
Nuclear/Radiological Countermeasures
To enhance readiness in the event of a radiological or nuclear threat, NIH has developed a
strategic plan and research agenda.
To help implement the plan, NIH has issued an RFA to conduct research
to validate existing biodosimetry tools that evaluate radiation doses to which individuals have
been exposed and to develop new
biodosimetry assays and tools.
NIH also issued RFAs to support the research and development of
medical countermeasures to enhance survival after radiation exposure.
NIH works closely with HHS to periodically update and prioritize the research development
activities of its strategic plan and ensure its integration as a key component of the larger
national biodefense research agenda. The
Radiation Event Medical Management Program
(REMM) provides online guidance to health care providers about diagnosis and treatment for
radiation-induced injuries. Further, in collaboration with the HHS Office of the Assistant
Secretary for Preparedness and Response, NIH has prepared a downloadable, online diagnostic
and treatment tool kit to guide health care providers during a mass casualty radiation event.
Infrastructure and Research Resources
NIH continues to develop the infrastructure necessary to carry out pioneering research on
infectious diseases. As research capabilities (e.g., genomics, proteomics, microarray technology)
have evolved and research needs have changed, new facilities and research resources have been
designed, implemented, and enhanced. However, since the U.S. anthrax attacks of 2001, the
emergence of severe acute respiratory syndrome (SARS) in southeast Asia, repeated outbreaks
of hemorrhagic fever viruses in Africa, the threat of pandemic influenza, and other actual
and potential public health emergencies, there is an increased need to develop the ability
to respond rapidly to public health threats. To this end, NIH has established or expanded
reagent and tissue repositories, data centers, and centralized analytical laboratories and is
expanding the number of extramural research facilities nationwide. The latter include the 6
Centers of Excellence for Influenza Research and Surveillance mentioned above, 10 Regional
Centers of Excellence for Biodefense and Emerging Infectious Diseases Research, 2 National
Biocontainment Laboratories (with BSL-4 capacity, the highest level of containment), 13
Regional Biocontainment Laboratories with BSL-3 capacity, 8 Human Immunology Centers, 10 centers
to study host immunity in special populations (children, pregnant women, elderly, immunosuppressed
individuals), clinical trials networks at domestic and international sites, and nonhuman primate
research centers. In addition, three intramural biocontainment laboratories—on the NIH campus in
Bethesda, Maryland (BLS-3); on the National Interagency Biodefense Campus at Fort Detrick in
Frederick, Maryland (BSL-4); and at the NIAID Rocky Mountain Laboratories in Hamilton, Montana
(BSL-4)—are operational or nearing completion.
International Collaboration
Much of NIH infectious disease and biodefense research is collaborative, interdisciplinary,
and—increasingly—international. NIH supports research and training programs to develop and
test safe and effective interventions for preventing and treating infectious diseases,
exchanging scientific information, and building research capacity in other countries (see
also the section “Research Training and Career Development” in Chapter 3). These efforts
include programs to establish research resources and infrastructure, for example, to help
train scientists from developing countries to engage in infectious disease research, including
clinical, operational, and health services research, and to help establish sustainable research
capacity in those countries. Because HIV/AIDS and TB take such an enormous global toll, NIH
is strengthening the capacity for clinical, operational, and health services research in low-
and middle-income countries where HIV/AIDS, TB, or both are significant problems. NIH has
established critical global partnerships with the World Health Organization and other United
Nations agencies, governmental and nongovernmental organizations, international foundations,
and private-sector organizations. Additionally, NIH is establishing international collaborations
to develop a safe, effective vaccine against malaria and to gather and analyze national
and global epidemiological patterns associated with influenza virus circulation, including
data on mortality, virus surveillance, genomics, and control strategies.
Notable Examples of NIH Activity
Key for Bulleted Items:
|
E = Supported through Extramural research
I = Supported through Intramural research
O = Other (e.g., policy, planning, and communication)
COE = Supported through a congressionally mandated Center of Excellence program
GPRA Goal = Concerns progress tracked under the Government Performance and Results Act
|
|
Basic Research
Microbial Genomics: NIH has made significant investments in large-scale, whole-genome
sequencing of pathogens over the last decade. Sequenced pathogens include hundreds of bacteria,
fungi, parasites, invertebrate vectors of diseases, and viruses (including the pathogens that
cause anthrax, influenza, aspergillosis, TB, gonorrhea, chlamydia, and cholera and many that
are potential agents of bioterrorism). NIH also provides comprehensive genomic, bioinformatic,
and proteomic resources and reagents to the scientific community. These include the (1) Microbial
Genome Sequencing Centers, which rapidly produce high-quality genome sequences of human pathogens
and invertebrate vectors of diseases; (2) Pathogen Functional Genomics Resource Center, which
provides functional genomic resources; (3) Bioinformatics Resource Centers, which provide access
to genomic and related data in a user-friendly format; and (4) Proteomics Research Centers,
which support research on the full set of proteins encoded in a microbial genome. The NIH
Influenza Genome Sequencing Project has sequenced more than 2,800 human and avian isolates
(as of November 28, 2007); NIH scientists recently exploited these data to explain the global
spread of resistance to adamantanes, a first-generation class of anti-influenza drug.
Scientists Complete Full Sequence of Opportunistic Oral Bacterium: Over the last decade,
scientists have assembled the complete DNA sequences of several important oral bacteria.
Now NIH-funded investigators have decoded and added another important bacterium,
Streptococcus sanguinis, a key player in the formation of the oral biofilm, to the list.
Although not regarded as a pathogen in the mouth, S. sanguinis is known to enter the
bloodstream, where it can colonize heart valves and contribute to bacterial endocarditis,
a condition that kills an estimated 2,000 Americans each year. With the bacterium's genetic
blueprint now publicly available online, scientists can better study the dynamics of biofilm
formation and possibly tease out new leads to prevent tooth decay and periodontal disease.
They can also now systematically identify and target sequences within the DNA of S. sanguinis
that are critical to the infectious process, invaluable information in designing more effective
treatments for endocarditis.
Major Infectious Diseases
Malaria Vaccine Research: Malaria continues to be one of the most devastating diseases
throughout the world today. The number of cases of the disease ranges from 350 million to 500
million each year, resulting in more than 1.1 million deaths, primarily among young children in
Africa (World Health Organization [WHO]). To address this important public health issue, the WHO
Initiative for Vaccine Research reports that, as of August 2005, there are at least 45 candidate
vaccines in preclinical development and 26 in clinical trials. NIH plays a valuable role in funding
a number of these activities, supporting 15 of the candidates in preclinical development and 5 of
the candidates in clinical trials. Examples of NIH-supported activities include the following:
- NIH researchers have applied an innovative technology, tested in mice, that may prompt an individual's
immune system to eliminate the malaria parasite from the mosquito. Because the vaccine targets the parasite
instead of conferring protection to the individual, it has the potential to eradicate malaria from large
geographic regions.
- NIAID, in collaboration with the Walter Reed Army Institute of Research, GlaxoSmithKline Biologicals,
the U.S. Agency for International Development, and others, has completed a Phase I adult trial in Mali of
a novel candidate vaccine that works by blocking the replication of malaria parasites in the blood. Additional
studies in children (who have the highest death toll among malaria cases) are under way.
Value of Early HIV Screening, Testing, and Counseling: HIV/AIDS disproportionately affects
several minority groups, particularly African Americans. Although adult and adolescent African
Americans make up approximately 13 percent of the population, they accounted for half of the
new HIV/AIDS diagnoses in 2001-2005. This disparity is particularly striking because African
Americans do not have higher rates of addiction or intravenous drug use than Whites. One
contributing factor is that African Americans are often diagnosed with HIV infection at a
later point in the illness, increasing their likelihood of progressing to AIDS and of transmitting
the disease. As part of efforts to prevent late diagnosis and HIV spread, NIH is working to
identify and address the cultural barriers to making HIV screening more acceptable and to strengthen
the links among education, testing and counseling, and treatment within all ethnic groups. Indeed,
NIH-supported modeling research has shown that routine HIV screening, even among populations
with prevalence rates as low as 1 percent, is as cost-effective as screening for other conditions
such as breast cancer and high blood pressure. The CDC has recognized that these findings have
important public health implications and has called for increased HIV screening as part of its
recommended guidelines. NIH is eager to advance new HIV rapid-screen technologies and counseling
in community drug treatment programs and in criminal justice settings.
Special Journal Issue: “Cultural Dynamics in HIV Prevention Among Young People”: Twenty-five years of
behavioral and biomedical research have led to breakthroughs in the prevention and treatment of HIV disease;
however, young people have not fully benefited from these advances. In September 2005, NIH held a workshop,
“Cultural Dynamics in HIV/AIDS Biobehavioral Research Among Young People.” In March 2007, a special issue of
the Journal of the Association of Nurses in AIDS Care presented a series of papers developed from this
workshop. These papers are focused on current research into preventing the spread of HIV infection
among youths from many cultures across the United States and around the world.
Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN): Although one-third to one-half
of new HIV infections occur among adolescents and young adults, researchers know little about how
the complex physiological changes associated with adolescence impact the transmission dynamics
and course of HIV infection. NIH is supporting a national clinical research network to address
the unique challenges and clinical management needs of HIV-positive youth and those at risk
of infection. Researchers in this network are building the capacity to develop and conduct
selected biomedical, behavioral, and community-based studies, including vaccine and microbicide
trials to ensure that the needs of high-risk teens (e.g., alcohol- or drug-abusing adolescents)
have access to the most promising treatment and prevention interventions as they are being developed.
- For more information, see http://www.atnonline.org
- This example also appears in Chapter 2: Life Stages, Human Development, and Rehabilitation.
- (E) (NICHD, NIDA, NIMH)
Diagnosis of Malaria by Microscopy: Virtually all clinical decisions, epidemiological
surveys, field trials of drugs and vaccines, and evaluations of intervention programs in
malaria depend on diagnoses made by microscopy. NIH has undertaken the first systematic
analysis of errors and sources of error in malaria microscopy. This multiyear study
includes the best malaria clinics in the tropical world and found 13 percent false-negative
and 24 percent false-positive rates. Follow-up work is analyzing the accuracy and effect
of different microscopy techniques, using different blood samples from the same patient,
different microscope slides from the same blood sample, aspects of parasite and patient
biology, microscopist training, and other factors.
Microbicides: With more than 19.2 million women worldwide living with HIV/AIDS
and more than 80 percent of HIV infections spread through heterosexual activity, NIH
collaborative research is developing new ways to help women protect themselves from
the virus. This includes the development and testing of agents that, if applied
topically to genital areas, inactivate the virus or otherwise prevent susceptible
cells from being infected with HIV. Scientists are working to develop, standardize,
and validate innovative ways to rapidly screen large numbers of potential antimicrobial
agents for irritation and safety. In addition, work is under way to examine the
behavioral and social factors influencing whether individuals or couples would adopt
and use new antimicrobial products consistently and effectively.
Culturally Appropriate Research to Prevent HIV Infection: Great strides have been made in
the past 25 years in treatment and prevention strategies to combat the spread of HIV/AIDS
in the United States. However, many populations in the United States and around the world
have not benefited from these developments, and this is especially true for young people.
One possible reason for such disparities is the influence of cultural differences on the
effectiveness of prevention and treatment strategies. In fall 2006, NIH solicited proposals
for innovative research to design and test interventions to prevent HIV transmission among
young people. Areas of research interest include developing prevention/treatment interventions
for young people with HIV/AIDS that take into account the cultural differences of those infected,
determining the influence of cultural differences on how young people view living with HIV/AIDS
and how these differences affect their views on preventing the spread of the disease, and
examining challenges in transferring successful interventions across cultures, especially
to other parts of the world.
The Program in HIV/AIDS < Cancer Virology: The mission of this program is to facilitate
and rapidly communicate advances in the discovery, development, and delivery of antiviral
and immunologic approaches for the prevention and treatment of HIV infection, AIDS-related
malignancies, and cancer-associated viral diseases. This includes basic laboratory, translational,
and clinical studies of disease pathogenesis and the development of novel targeted treatment
approaches for cancers in HIV-infected individuals, as well as HIV infection itself, and
drug resistance. Recent advances include a new prophylactic vaccine for HPV and promising
candidates for prophylactic and therapeutic vaccines for HIV.
The NCI Vaccine Program: NCI's vaccine program develops novel vaccines for cancer immunotherapy
and prevention and HIV. The program encourages collaborations, identifies organizational and reagent
needs for the community, and develops the optimal infrastructure for vaccine development and novel
clinical trial approaches. Gardasil®, the first vaccine to prevent cervical cancer induced by HPV,
is now available and can potentially save more than 5,000 U.S. women's lives each year. This
FDA-approved vaccine resulted from the basic research performed at NIH that produced a prototype
vaccine and the observation that linked HPV and cervical cancer.
- This example also appears in Chapter 2: Cancer and Chapter 3: Clinical and Translational Research
- (E/I) (NCI)
Retrovirus Epidemiology Donor Study (REDS): REDS was begun by NIH in 1989 to determine
the prevalence and incidence of HIV infection among blood donors and the risks of transmitting
HIV and other viruses via transfusions. In 2004, NIH launched REDS-II to monitor the appearance
of newly discovered infectious agents in the blood supply, evaluate the characteristics and
behaviors of voluntary blood donors, determine the causes of transfusion reactions of unknown
etiology, assess the results of new donor screening methods, assess the effects of new blood-banking
technologies, and evaluate the donation process. In 2005, an international component was added
to REDS-II to conduct research on blood donors in selected countries seriously affected by
the AIDS epidemic to ensure the safety and availability of blood for transfusion.
Improved Management of Antiretroviral Therapy for Adults and Children: Two recent NIH studies transformed
the management of antiretroviral therapy by extending the survival of adults and children with HIV/AIDS.
Results from the Strategies for Management of Antiretroviral Therapy (SMART) study, one of the largest
HIV/AIDS treatment trials ever conducted, showed that episodic use of antiretroviral therapy based on CD4+
cell levels is inferior to the use of continuous therapy for treatment-experienced patients and that deliberately
interrupting antiretroviral therapy more than doubles the risk of developing AIDS or dying from any cause.
The Children with HIV Early Antiretroviral Therapy (CHER) Study examined early antiretroviral therapy in
South African children. Interim data showed a 96 percent increase in survival among infants who received
immediate antiretroviral therapy compared with infants who received therapy later.
New Approaches to Diagnostics: Recognizing the urgent need for rapid, highly sensitive, and
specific clinical diagnostics that can diagnose individuals exposed to or infected by human
pathogens, NIH has developed a comprehensive research program that is taking advantage of
genomic information and emerging technologies, such as nanotechnology, to develop new and improved
diagnostic tools. The program covers a broad range of activities, including the development of
improved sample preparation and processing, platform development, enhanced detection methods,
and clinical validation. Program priorities include development of tools that can distinguish
between a variety of pathogens or that can determine pathogen subtypes and their sensitivity to
drug treatments.
NIAID HIV Vaccine Research Education Initiative (NHVREI): This new national initiative is designed
to educate the public about HIV vaccine research, especially at-risk populations such as African Americans,
Hispanics, men who have sex with men, and women at high risk of HIV infection. The goal is to increase
awareness about the urgent need for an HIV vaccine within the communities that are most affected by HIV/AIDS,
create a supportive environment for current and future volunteers in HIV vaccine trials, and improve the public's
perceptions and attitudes toward HIV vaccine research. The NHVREI Local Partnership Program provides support to
partner organizations in targeted communities to help achieve the initiative's goals.
Research Agenda for MDR-TB/XDR-TB: Diagnosing, treating, and controlling the spread of TB has
become increasingly complicated by the HIV/AIDS co-epidemic and the emergence of MDR-TB and XDR-TB,
which together threaten to set TB control efforts back to the pre-antibiotic era. In response to
this urgent situation, in June 2007, NIH released its research agenda, Multidrug-Resistant and
Extensively Drug-Resistant Tuberculosis. The research priorities identified in the agenda build
on a foundation of ongoing NIH-supported TB research, which currently comprises more than 300
research projects worldwide. This Web-based “living document,” identified as such because of NIH's
ability to modify, amend, or update it as scientific and public health needs and opportunities
evolve, was prepared in close collaboration with other Government and non-Government organizations
and reviewed by TB specialists in academia, advocacy groups, international organizations, and
other Government agencies. It identifies six critical areas for additional investigation: (1)
new TB diagnostic tools, (2) improved therapies for all forms of TB, (3) basic biology
and immunology of TB, (4) MDR-TB and XDR-TB epidemiology, (5) clinical management of MDR-TB
and XDR-TB in people with and without HIV infection, and (6) TB prevention, including vaccines.
The Evolving HIV Epidemic: Beyond Intravenous Drug Use: The nature of the HIV epidemic in
this country is changing. Effective medications and HIV risk reduction interventions in intravenous
drug abusers have helped to curb the spread of HIV though injection drug use to a point
where it now accounts for a smaller percentage of new infections. However, drug abuse
continues to play a major role in the spread of HIV through other mechanisms: drug
abusers proffer sexual behaviors to obtain drugs or money to support their addiction,
and drugs of abuse can worsen the course of the illness and produce intoxication,
which can alter judgment and decision-making and lead to impulsive and risky sexual behaviors.
Recognition of this link is critical for developing more integrated and effective prevention strategies.
A critical aspect of this message is that treatment of drug abuse is HIV prevention, an idea
being furthered by NIH in concert with other Federal agencies, such as CDC.
Understanding Factors Affecting the Use of Microbicides: NIH is planning an initiative
on research directed toward understanding the complex interplay among individual, dyadic,
social, and other contextual factors that may influence the initiation and sustained use
of microbicides that are proven to be efficacious in reducing the risk of acquiring or
transmitting HIV. In addition, the initiative will address research on prevention
strategies that incorporate the use of microbicides and on the development of behavioral
and social tools to assess product acceptability, initiation, and sustained use in a
manner that will directly inform microbicide product development and improvement.
OAR-Sponsored Initiatives Targeting Scientific Needs in AIDS Research: OAR, through its
planning process, identifies scientific areas that require focused attention and facilitates
innovative, cross-institute, multi-institute, multidisciplinary activities to address those needs.
OAR fosters these efforts by designating resources to jump-start program areas through funds for
grant supplements to the ICs, establishing working groups or committees, sponsoring workshops or
conferences to highlight a particular research topic, and sponsoring reviews or evaluations of
research program areas. Examples include a Microbicide Innovation Program to accelerate the
discovery of single and/or combination microbicides against HIV and STDs and a Prevention
Science Initiative to foster innovative research in HIV prevention. OAR also supports initiatives
to enhance dissemination of research findings, including sponsorship of a group of scientific
panels that develop AIDS treatment and prevention guidelines, and the distribution of those
guidelines through AIDSinfo, a Web-based service to provide up-to-date information for
caregivers and patients about AIDS treatment and prevention.
Trans-NIH Management and Coordination of HIV/AIDS Research: NIH is the world's leader in
AIDS research, representing the largest and most significant public investment in AIDS
research in the world. Our response to the pandemic requires a unique and complex multi-institute,
multidisciplinary, global research program. NIH supports a comprehensive program of basic, clinical,
and behavioral research on HIV infection and its associated co-infections, opportunistic infections,
malignancies, and other complications. Perhaps no other disease so thoroughly transcends every area
of clinical medicine and basic scientific investigation, crossing the boundaries of nearly every NIH IC.
This diverse research portfolio demands an unprecedented level of scientific coordination and management
of research funds. OAR, located within the NIH Office of the Director, coordinates the scientific,
budgetary, and policy elements of NIH AIDS research. Through its unique, trans-NIH planning, budgeting,
and portfolio assessment processes, OAR ensures that AIDS research dollars are invested in the highest
priority areas of scientific opportunity, allowing NIH to pursue a united research front against the pandemic.
Development of New TB Diagnostic Tool: By detecting TB as early as possible, health providers
can more effectively treat and control the disease in a population. An NIH-funded investigator
working in Lima, Peru, has developed a new assay for TB. This simple and relatively inexpensive
diagnostic test offers faster, more sensitive detection of TB and drug-resistant TB than the
currently used method and cuts diagnostic time from an average of 28 days
to 7 days. The new, inexpensive method is appropriate for countries with limited resources,
and several countries are in the process of incorporating it into TB control protocols.
Adult Male Circumcision Significantly Reduces Risk of Acquiring HIV: NIH-supported scientists announced an early
end to two clinical trials of adult male circumcision because an interim review of trial data revealed that
medically performed circumcision, with appropriate care in the postoperative period, significantly reduces a
man's risk of acquiring HIV through heterosexual intercourse. The trials, which enrolled 2,784 men in Kisumu,
Kenya, and 4,996 men in Rakai, Uganda, showed that HIV acquisition in circumcised men relative to uncircumcised
men was reduced by roughly half. Although the initial benefit will be fewer HIV infections in men, ultimately
adult male circumcision could lead to fewer infections in women in those areas of the world where HIV is spread
primarily through heterosexual intercourse. Circumcision remains only part of a broader HIV prevention research
agenda that includes development of vaccines, microbicides, behavioral interventions, and prevention of
mother-to-child transmission.
Emerging Infectious Diseases and Biodefense
Biodefense Vaccines: NIH is the lead Federal agency within HHS for conducting research on
potential agents of bioterrorism that directly affect human health. The terrorist attacks of September 11, 2001,
and the deliberate exposure of civilians to anthrax spores prompted HHS to emphasize the importance of advancing
vaccines for specific pathogens that could be used in bioterrorist attacks. In response, in February 2002, NIH
convened the Blue Ribbon Panel on Bioterrorism and Its Implications for Biomedical Research. This panel was
brought together to provide objective expertise on NIH's future biodefense research agenda in both the short
and the long term. As expected, one of the identified areas of research emphasis was the development of new
and improved vaccines against agents of bioterrorism, with the initial focus on smallpox and anthrax. Since
that time, substantial progress has been made in biodefense vaccine research and development, which has
resulted in the following advances:
- Modified Vaccinia Ankara, a new, safer smallpox vaccine that is the outcome of several
years of NIH-sponsored research and development, has been purchased for the Strategic National Stockpile.
- An Ebola vaccine has been developed and is currently being tested in humans at NIH.
- A promising new anthrax vaccine candidate made with a purified protein has been developed
and will enable researchers to determine the minimum level of protein needed to confer protection and minimize side effects.
Microneedle-Based Immunization Against Pandemic Influenza: NIH is supporting a team of
investigators under the Bioengineering Research Partnership grant mechanism to develop a
low-cost, room temperature-stable, microneedle-based transdermal vaccine patch against
pandemic influenza that could be rapidly distributed through pharmacies, fire stations,
or the U.S. mail and painlessly self-administered. This dose-sparing delivery system
will not produce any sharp, biohazardous waste and would avoid the expensive and time-consuming
hypodermic vaccination process administered by medical personnel, thus allowing for a rapid
response to pandemic influenza. This innovative application impacts the “HHS Pandemic
Influenza Plan” and NIH's directives on high-priority influenza research areas.
Probes and Cell Arrays for Detection of Bacterial Toxins: Microarray technology offers an
opportunity for simultaneous monitoring the behavior of multiple markers within a mammalian cell
and ultimately could be used for detection and elucidation of mechanisms of action of different
biologically active agents, including those that are considered a threat in the biodefense area.
The ultimate goal of this research project is to provide a general and robust approach for the
detection of biologically active agents, especially when these agents have been engineered to
elude currently available immunoassays. Cell arrays offer a new opportunity for sensitive and
precise monitoring of biologically active substances. The goal of this project is to develop
a system for the identification of regulatory elements that will allow a substantial extension
of the discriminative abilities of cell arrays and the creation of cell arrays that are capable
of detection and identification of potential biowarfare agents.
Antimicrobial Resistance Research: Antimicrobial resistance, which is caused by factors
such as overuse of antibiotics, is severely jeopardizing the utility of many “first-line”
antimicrobial agents and has emerged as a major public health threat. NIH supports a robust
basic research portfolio on antimicrobial resistance, including studies of how bacteria develop
and share resistance genes. NIH is also pursuing translational and clinical research in this area,
including clinical studies to test interventions for community-acquired MRSA infection, and to
evaluate the efficacy of off-patent antimicrobial agents. NIH will continue to address high-priority
research questions regarding resistance to help public health officials hold the line against
drug-resistant microbes.
Ecology of Infectious Diseases (EID): Jointly administered by NIH and the National Science
Foundation (NSF), the EID program uniquely fills a critical gap in our national effort to protect
public health against the threat of emerging infectious diseases. Most emerging diseases are initially
transmitted from animals to humans, and some are capable of becoming pandemics. This program supports
the discovery of the principles that govern the relationships between ecological disturbances and
transmission of infectious agents, and the use of those principles to develop predictive models of
epidemics. Potential benefits of the program include an increased capacity to forecast outbreaks and
to improve understanding of how diseases emerge and reemerge.
Biodefense Therapeutics Development: Treatments against NIAID Category A-C priority pathogens,
microbes, and toxins, which are considered to be the most significant threats to the Nation's well-being,
are either nonexistent, of limited utility, or threatened by the emergence of antimicrobial resistance or
intentional engineering to increase virulence or decrease drug susceptibility. Given the absence of a
substantial commercial market, regulatory hurdles, and extensive clinical trial requirements, the private
sector has little incentive to invest in antimicrobial countermeasures. To remedy this situation, NIH
supports unique partnerships among Government, industry, small businesses, and academia to facilitate
the movement of promising products through all stages of the drug research and development pipeline,
with the goal of developing therapeutics against diseases such as smallpox, botulism, and Ebola and
West Nile virus infection. These projects range from preclinical services (such as performing medicinal
and analytical chemistry, custom drug synthesis, formulation, clinical manufacturing, microbiology and
virology screening, pharmacokinetics, and safety testing) to the development and testing of DAS 181 (Fludase),
which is potentially a broad-spectrum therapeutic agent for use against all annual and pandemic
variations of influenza.
Developing New Adjuvants to Boost Vaccine Effectiveness: The NIH Innate Immune Receptors and
Adjuvant Discovery initiative encourages the discovery of novel adjuvants to meet the growing need
to boost the effectiveness of vaccines against potential agents of bioterrorism and emerging
infectious diseases. Adjuvants activate the body's innate immune system—microbe-engulfing phagocytes
and soluble immune stimulators—leading to effective adaptive immune responses by B cells, which make
antibodies, and T cells, which can directly kill infected cells. Using high-throughput screening,
several groups of researchers have identified, optimized, and developed adjuvants that are now in
preclinical development.
- This example also appears in Chapter 3: Molecular Biology and Basic Sciences.
- (E) (NIAID)
Medical Countermeasures Against Nuclear and Radiological Threats: NIH is leading the HHS effort to
sponsor and coordinate research to develop a means to counter the detrimental effects of a range of
radiological threats. Most medical countermeasures to treat radiation injury are still in the early
stages of development but are progressing. NIH-funded researchers recently (1) screened more than 40,000
candidate compounds and identified 52 candidates for evaluation as protective agents against the toxic
effects of ionizing radiation, (2) developed improved forms of the chelating agent diethylenetriaminepentaacetic
acid (DTPA), which animal testing data suggest can effectively clear the radionuclide americium-241 from
the blood, and (3) studied 29 candidate drugs that are active against a broad range of radionuclides
and might be useful in treating victims of radiological dispersion devices (“dirty bombs”).
Pandemic and Seasonal Influenza Vaccine Research: In FYs 2006 and 2007, NIH made significant progress
toward the development of new and more effective vaccines for the control of both seasonal and pandemic
influenza. For example, an NIH-supported clinical trial provided the scientific data on which the FDA
based its recent licensure of the first pandemic influenza vaccine against H5N1 virus (“bird flu”) in the
United States. NIH also developed and conducted clinical trials of whole-inactivated and live-attenuated
vaccines against H5N1 influenza and developed DNA, recombinant virus, and recombinant protein-based influenza
vaccines. NIH also supports activities to expand and accelerate the development of additional manufacturing
methods; evaluate various strategies to optimize a limited vaccine supply, including intradermal vaccines
and the use of adjuvants; and explore the concept of developing a vaccine that raises immunity to parts of
the influenza virus that vary little from season to season and from strain to strain, thereby potentially
reducing or eliminating the need for annual immunization against seasonal influenza. Such a vaccine might
also strengthen protective immunity against an emerging pandemic strain of influenza virus.
Radiation Event Medical Management (REMM): As a part of an effort to improve public health emergency
preparedness and response, NIH and the HHS Office of the Assistant Secretary for Preparedness and Response
announced in 2007 a new downloadable online diagnostic and treatment toolkit to guide health care providers
during a mass casualty radiation event. The REMM toolkit includes easy-to-follow procedures for diagnosis
and management of radiation contamination and exposure, guidance for the use of radiation medical
countermeasures, and a variety of other features to facilitate medical responses to radiation emergencies.
- For more information, see http://remm.nlm.gov
- This example also appears in Chapter 3: Disease Registries, Databases, and Biomedical Information Systems.
- (I) (NLM)
Infrastructure and Research Resources
Biodefense Research Infrastructure: NIH has invested substantially in the intellectual and physical infrastructure
needed to build the Nation's capacity for research on biodefense and emerging infectious diseases. This effort
draws scientists from many disciplines to conduct research and development activities and to train future researchers.
It also provides facilities that will greatly enhance the safe and efficient conduct of research on infectious agents.
The NIH-funded infrastructure includes (1) 10 Regional Centers of Excellence for Biodefense and Emerging Infectious
Diseases Research, which use a multidisciplinary approach to research and development, (2) two National Biocontainment
Laboratories (with BSL-4 capacity, the highest level of containment) and (3) 13 Regional Biocontainment Laboratories
with BSL-3 capacity.
The National Science Advisory Board for Biosecurity (NSABB): NSABB was established to advise the U.S.
Government on strategies for the efficient and effective oversight of dual-use biological research, taking into
consideration both national security concerns and the needs of the research community. The term “dual use” in
conjunction with life sciences research is an acknowledgment that some of the information and technologies
used to advance human, animal, and plant health can also be used to threaten public health and safety.
NSABB brings together 25 voting non-Federal members who represent the scientific, biosafety, security, legal,
ethics, scientific publishing, and intelligence communities. In addition, there is active participation
by 14 major Federal departments, agencies, and offices across the Government. NSABB has issued two
sets of reports and recommendations. The first is focused on the biosecurity issues raised by the
rapidly increasing ability to synthesize select agents and other dangerous pathogens. The report
identifies a number of biosecurity considerations; assesses whether the current Federal regulations,
policies, and guidelines afford adequate oversight in this arena; and provides recommendations for
addressing the issues. The second report is a proposed framework for local and Federal oversight of
dual-use research. It is intended as a springboard for the development of Federal guidelines and procedures
for oversight of dual-use research and includes guidance for identifying dual-use research of concern,
considerations for developing codes of conduct for life scientists, and considerations and tools for
the responsible communication of dual-use research. NSABB is currently developing strategies for
fostering international engagement of dual-use life sciences issues and for education and outreach
regarding these issues.
HIV/AIDS Research Network Restructuring: To better address the evolving scientific challenges of
the HIV/AIDS epidemic, in FY 2006 NIH restructured its HIV/AIDS clinical research infrastructure into
six research networks: the AIDS Clinical Trials Group (ACTG), the HIV Prevention Trials Network (HPTN),
the HIV Vaccine Trials Network (HVTN), the International Maternal Pediatric Adolescent AIDS Clinical Trials
(IMPAACT) Group, the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), and the
Microbicide Trials Network (MTN). Each network consists of a leadership group that provides administrative
and technical support, as well as a number of the 73 HIV/AIDS Clinical Trials Units NIH funds in the United
States and abroad (some Clinical Trials Units belong to more than one network). The reorganization will
improve the efficiency, flexibility, and coordination of HIV/AIDS clinical research.
Translational Research at Primate Research Centers: Nonhuman primates are critical components for
translational research because of their close physiological similarities to humans. Nonhuman primates
are widely used for both hypothesis-based and applied research directly related to human health, such
as the development and testing of vaccines and therapies. The NIH-supported National Primate Research
Centers and other primate resources provide investigators with the animals, facilities, specialized assays,
and expertise to perform translational research using nonhuman primates. In FY 2007, more than 1,000 research
projects used nonhuman primates from these resources. Highlights of research activities include:
- Use of the simian immunodeficiency virus for AIDS-related research, including development of novel microbicides to
prevent infection by the AIDS virus and testing of AIDS vaccines
- Identification of the central role of specific genes and molecules in drug addiction and neurological
conditions and diseases, studies of the biochemistry and physiology of drug and alcohol addiction, and
development of stem cell-based therapies for neurodegenerative diseases
- Sponsored scientific workshops in FYs 2006 and 2007 that further defined the genetic tools necessary for
translational research using nonhuman primates
Centers of Excellence for Influenza Research and Surveillance: Six Centers of Excellence for Influenza Research
and Surveillance, established in 2007, significantly expand the ability of NIH to conduct research on different
strains of animal and human influenza viruses collected internationally or in the United States. The centers will
lay the groundwork for the development of new and improved control measures for emerging and reemerging influenza
viruses, help determine the prevalence of avian influenza viruses in animals in close contact with humans, and
extend understanding of how influenza viruses evolve, adapt, and are transmitted. The centers will also bolster
research on questions such as how influenza viruses cause disease and how the human immune system responds to
infection and will inform public health strategies to control and minimize the impact of seasonal and pandemic influenza.
Urinary Tract Infections: NIH supports a Specialized Center of Research on Sex and Gender Factors Affecting
Women's Health. This program advances new understanding of host-pathogen interactions that occur throughout the
infectious cycle, including host defense response in the bladder and the virulence mechanisms by which bacterial
pathogens subvert the defenses.
NIH Countermeasures Against Chemical Threats (CounterACT) Research Network: CounterACT, as reflected in
an NIH GPRA goal, develops medical countermeasures to prevent, diagnose, and treat conditions caused by
chemical agents that might be used in a terrorist attack or released by industrial accidents or natural
disaster. The network, which has collaborated with DoD from its inception in 2006, includes Research
Centers of Excellence, individual research projects, small business research grants, contracts, and
other programs that conduct basic, translational, and clinical research. One promising countermeasure,
midazolam, which DoD researchers identified as a potential countermeasure against chemical agent-induced
seizures, is entering clinical trials in epilepsy patients through the NINDS Neurological Emergency Clinical
Trials Network, and NIH is collaborating with DoD to complete animal studies necessary for its FDA approval
as a nerve agent treatment.
Influenza Virus Resource: This database of more than 40,000 influenza virus sequences
allows researchers around the world to compare different virus strains, identify genetic factors
that determine the virulence of virus strains, and look for new therapeutic, diagnostic and vaccine
targets. The resource was developed by NCBI using data obtained from NCBI's Influenza Virus Sequence
Database and from NIAID's Influenza Genome Sequencing Project, which has contributed sequences of the
complete genomes from more than 2,500 influenza samples. In FY 2006 more than 11,000 influenza virus
sequences were entered into the database, and new search and annotation tools were added to assist
researchers in their analyses.
- Wolf YI, et al. Biol Direct 2006;1:34, PMID: 17067369
- Chang S, et al. Nucleic Acids Res 2007;35:D376-80, PMID: 17065465
- For more information, see http://www.ncbi.nlm.nih.gov/genomes/FLU/FLU.html
- For more information, see http://www.niaid.nih.gov/dmid/genomes/mscs/influenza.htm
- This example also appears in Chapter 3: Disease Registries, Databases, and Biomedical Information Systems, Chapter 3: Genomics, and Chapter 3: Molecular Biology And Basic Sciences
- (I) (NLM)
Wireless Information System for Emergency Responders (WISER®): WISER is a system designed to assist first responders
in hazardous material incidents by providing a wide range of information on hazardous substances, including
substance identification support, physical characteristics, human health information, and containment and
suppression advice. In 2007, several important features were added to WISER, including radiological support
with data for more than 20 isotope substances and tools/reference materials for radiological incidents. A
new partnership with the U.S. Department of Transportation (DoT) enabled integration of the DoT's Emergency
Response Guidebook (ERG) 2004 with WISER and the development of a stand-alone ERG 2004 Mobile version.
Widely used by first responders, WISER is available for downloading onto electronic handheld devices and
Windows-based platforms or for browsing on the Web.
- For more information, see http://wiser.nlm.nih.gov
- This example also appears in Chapter 3: Technology Development.
- (I) (NLM)
HIV/AIDS Epidemiological and Long-Term Cohort Studies: NIH supports epidemiological HIV research through a
wide range of cohort studies that contribute to our understanding of risk factors that lead to HIV transmission
and disease progression. Established in 2005, the International Epidemiologic Databases to Evaluate AIDS (IeDEA)
compiles data from NIH-funded international HIV research to answer population-level questions about HIV variants
and resistance, HIV pathogenesis in different settings, success of antiretroviral therapy, treatment history of
HIV in different populations, success of prevention strategies, and vaccines. The Pediatric HIV/AIDS Cohort
Study (PHACS), established in 2005, addresses two critical pediatric HIV research questions: the long-term
safety of fetal and infant exposure to prophylactic antiretroviral chemotherapy and the effects of perinatally
acquired HIV infection in adolescents. The Women's Interagency HIV Study (WIHS) and the Multicenter AIDS
Cohort Study (MACS) are the two largest observational studies of HIV/AIDS in women and homosexual or bisexual
men, respectively, in the United States. These studies exceed standard clinical care diagnostics and laboratory
analysis on both HIV-infected, and, importantly, HIV-negative controls, which allows for novel research on how HIV
spreads, how the disease progresses, and how it can best be treated. The studies focus on contemporary
questions such as the interactions among HIV infection, aging, and long-term treatment; cardiovascular
disease; and host genetics and their influence on susceptibility to infection, disease progression,
and response to therapy.
National NeuroAIDS Tissue Consortium (NNTC): The NNTC is a repository of brain tissue and fluids from
highly characterized HIV-positive individuals. Established as a resource for the research community, NNTC
includes information from more than 2,000 individuals, including approximately 641 brains, thousands of plasma
and cerebrospinal fluid samples, and additional organs and nerves of interest.
International Collaboration
Success in Treating Drug Addiction Internationally: International efforts to disseminate effective
drug abuse treatments have seen success in countries with epidemic opiate addiction/HIV problems.
Because of NIH research demonstrating that addiction is a chronic, relapsing disease that can be
effectively treated, a culture change is starting to occur in these countries. For example, despite
experiencing severe drug problems, Malaysia lagged behind in the treatment of drug addiction and related
disorders, even as it coped with having the second-highest HIV prevalence rate among adult populations
and the highest proportion of HIV cases from injection drug use. Historically, drug abusers were “rehabilitated”
involuntarily in correctional facilities. Although 60 percent of prisoners had drug-related offenses, no or
minimal treatment was available in prison, and no medications were permitted. This primarily criminal
treatment approach had limited effectiveness, which led to widespread public dissatisfaction and the
recent introduction of medications for addiction. These include naltrexone (1999), buprenorphine (2001),
and methadone (2003). These drug treatment programs, which were rapidly embraced by the country's medical
community, have resulted in tens of thousands of opiate-dependent patients receiving medical treatment.
Now, the Ministry of Health rather than the Ministry of Security has authority for providing medical
treatment for heroin addiction. This shift signals a remarkable change in Malaysian policies and approaches
to addiction and an important opportunity to develop, implement, and disseminate effective treatments. A similar
success story is starting to unfold in China as well.
Multinational Influenza Seasonal Mortality Study: NIH is leading an international collaborative effort to
analyze national and global epidemiological patterns associated with influenza virus circulation. Twenty countries
have contributed data on mortality, virus surveillance, genomics, and control strategies. The goals of this
large-scale collaboration are to evaluate and compare public health strategies to alleviate the impact of
seasonal influenza in different countries and to understand the global circulation patterns of influenza
and their impact on populations. A better understanding of influenza epidemiology worldwide can inform
vaccine strain selection and strategies to mitigate future influenza pandemics.
- For more information, see http://origem.info/misms
- This example also appears in Chapter 3: Epidemiological and Longitudinal Studies.
- (O) (FIC)
HIV Vaccine Development: NIH supports research around the world to find a safe and effective
vaccine against HIV. Since the first HIV vaccine trial in 1987, NIH has worked with its partners in
academia, Government, the private sector, and non-Government organizations to conduct more than 100
HIV vaccine clinical trials that have enrolled more than 26,000 volunteers. In 2005, NIH formed the
Center for HIV/AIDS Vaccine Immunology (CHAVI), a consortium of scientists committed to overcoming
key scientific roadblocks to HIV vaccine development and to designing and testing HIV vaccine candidates.
NIH is also involved in the Global HIV Vaccine Enterprise and the Partnership for AIDS Vaccine Evaluation
(PAVE). Several clinical trials are testing vaccine candidates around the globe. Recently, however, two
large vaccine trials stopped immunizations upon recommendation of a Data Safety Monitoring Board review.
However, the new large-scale trial, called PAVE 100, is still under discussion and may begin in 2008.
This trial will test whether an NIH-developed candidate vaccine can prevent acquisition of infection
or progression of disease (using viral load as a surrogate marker) in those who become infected.
Global Infectious Disease Research Training: A major barrier to improved treatment and control of
infectious diseases is the scarcity in endemic countries of scientists with expertise in infectious
disease research. This program supports institutions in the United States and developing countries to
train scientists from developing countries to engage in research on infectious disease other than HIV/AIDS.
The program is contributing to the long-term goal of building sustainable research capacity in endemic
infectious diseases in institutions in developing countries to enhance prevention, treatment, and control
of infectious diseases that cause major morbidity and mortality in the developing world.
HIV Research Training Programs: The AIDS International Training and Research Program (AITRP) builds
institutional, national, and regional HIV research capacity in low- and middle-income countries. Over the
past 19 years, this program has been responsible for many of the first generation of research scientists
from these countries, with many more in the pipeline. The program offers multidisciplinary biomedical,
behavioral, and social science research training to a wide range of professionals. Building on the AITRP,
the Clinical, Operational and Health Services Research Training Program for HIV/AIDS and TB (ICOHRTA AIDS/TB)
began in 2002 to strengthen the capacity for clinical, operational, and health services research in low- and
middle-income countries where AIDS, TB, or both are significant problems. Through training health professionals
that reach across the spectrum of clinical and public health research, this program is strengthening the
capacity of scientists, program managers, and policymakers to evaluate and better implement large-scale
prevention, treatment, and care interventions that are locally relevant and effective. Many local leaders
of programs supported by the President's Emergency Plan for AIDS Relief have received or are receiving
their research training through the AITRP and the ICOHRTA AIDS/TB programs.
- For more information, see http://www.fic.nih.gov/programs/training_grants/aitrp/index.htm
- For more information, see http://www.fic.nih.gov/programs/training_grants/icohrta/aids_tb.htm
- This example also appears in Chapter 3: Clinical and Translational Research and Chapter 3: Research Training and Career Development.
- (E) (FIC, NCI, NIAID, NHLBI, NIDA, NIDCR, NIMH, NINDS, NINR, OAR, ORWH)
Mechanisms of HIV Neuropathogenesis: Domestic and Global Issues: Neurological manifestations,
including HIV dementia and opportunistic infections and tumors, are among the most threatening complications
of HIV infection. Emerging data indicate that the prevalence of HIV-related neurological disease differs
across regions of the world, suggesting that different subtypes of HIV may be more or less capable of
causing neuropathology or that genetic variance among people in various regions of the world could affect
susceptibility to HIV's neuropathological effects. NIH sponsored a meeting in the spring of 2007 to address
these issues, resulting in the release of a funding announcement.
HIV Virus Transmission From Primates to Humans: Through the International Research Scientist Development
Award (IRSDA), FIC provides career development and research support to U.S. postdoctoral scientists in the
formative stages of their careers to solidify their commitment to global health research. For example, under
this program, FIC supported the career development of Dr. Nathan Wolfe, whose work in Cameroon advanced our
understanding of how retroviruses enter into human populations and determined that the likely point of transmission
of the HIV occurred between primates and bushmeat hunters. Dr. Wolfe has now received the NIH Director's Pioneer Award.
Co-funded by FIC and NIAID, this award builds on Dr. Wolfe's IRSDA-supported research and is enabling the establishment
of the first global network to monitor the transmission of new viruses, including those causing pandemic disease threats
such as Ebola, anthrax, and monkeypox, from animals into human populations. This hunter cohort distributed throughout
key habitats will provide a framework for a range of research projects aimed at predicting and preventing disease
emergence, including studies of risk factors associated with primary and secondary infections with zoonotic microorganisms,
anthropological studies of hunting and meat processing practices that lead to exposure, and ecological studies of the
animal and human populations that influence transmission among and between groups.
NIH Strategic Plans Pertaining to Infectious Diseases and Biodefense Research
National Institute of Allergy and Infectious Diseases (NIAID)
Infectious Diseases (non-biodefense, non-AIDS)
Biodefense and Emerging Infectious Diseases
National Institute of Dental and Craniofacial Research (NIDCR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Branch Reports to Council with Future Scientific Directions
National Institute on Drug Abuse (NIDA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Center for Complementary and Alternative Medicine (NCCAM)
John E. Fogarty International Center (FIC)
Office of AIDS Research (OAR)
- FY 2008 Trans-NIH Plan for HIV-Related Research
CC, CSR, FIC, NCCAM, NCI, NCMHD, NCRR, NEI, NHGRI, NHLBI, NIA, NIAAA, NIAID, NIAMS, NIBIB, NICHD,
NIDA, NIDCD, NIDCR, NIDDK, NIEHS, NIGMS, NIMH, NINDS, NINR, NLM, OAR, OBSSR, OIR, ORD, ORWH
Other Trans-NIH Strategic Plans
24 For more information, see http://www3.niaid.nih.gov/Biodefense
25 For more information, see http://www.unaids.org/en/KnowledgeCentre/HIVData/EpiUpdate?epiUpdArchive/2007default.asp
26 For more information, see http://www.dcp2.org/main/Home.html; http://www.who.int/entity/mediacentre/factsheets/fs310.pdf
27 For more information, see http://www.who.int/features/factfiles/malaria/en/index.html
28 For more information, see http://www.dcp2.org/pubs/GBD/3/Table/3.14
29 For more information, see http://www.dcp2.org/main/Home.html
30 For more information, see http://www.dcp2.org/main/Home.html
31 For more information, see http://www.cdc.gov/nchs/fastats/deaths.htm.
32 For more information, see http://www.cdc.gov/nchs/fastats/infectis.htm
33 For more information, see http://www.niaid.nih.gov/dmid/genomes/mscs/influenza.htm
34 For more information, see http://www.kff.org/hivaids/7661.cfm
35 For more information, see http://www.cdc.gov/hiv/topics/surveillance/resources/reports/2004report/pdf/2004SurveillanceReport.pdf
36 For more information, see http://www.cdc.gov/hiv/topics/surveillance/resources/reports/2005report/
37 For more information, see http://www.cdc.gov/hiv/topics/perinatal/resources/factsheets/perinatal.htm |
