Introduction

Over the past four generations, public health tools and interventions resulting from research have dramatically improved life expectancy and quality of life. However, significant disparities continue to exist in global health status. Low- and middle-income nations suffer over ninety percent of the burden of premature mortality as measured in lost years of life. These countries, constituting three-quarters of the world's population, now share a double burden: The persistent cluster of infectious diseases and malnutrition that are responsible for 16 million deaths per year, of which many are children; and a growing incidence of chronic disease and disabilities due to increased life spans and new risk exposures that accompany the demographic transition.

In the United States, health disparities are evident within and among population groups. Genetic and environmental factors, nutrition, access to health education and services, behavior, and other factors are implicated in varying degrees as contributors to these disparities. Research advances made abroad may have a positive impact on U.S. populations through improvements in education or counseling strategies; development of diagnostics, drugs or intervention technologies; or through identification of new avenues of research that ultimately lead to health care interventions. In addition, basic knowledge gained through research studies conducted abroad contribute to the scientific foundation upon which U.S. and international medical studies are built.

Adapting research advances in biomedicine to populations at home and abroad requires a continuing commitment to basic science as well as rigorous clinical and applied studies. To address these needs, the Fogarty International Center (FIC) forges collaborations with a range of domestic and international partners in international research and training to pursue three core objectives. The first is to accelerate the pace of discovery and its application by enabling scientists worldwide to share conceptual insights, analytic methods, data sets, patient cohorts or special environments. The second is to engage and assist both young and established U.S. investigators to address scientific challenges related to global health. And the third is to help develop a cadre of highly capable young foreign investigators positioned to cooperate with U.S. scientists in areas of the world that, due to geography, population structure, or disease burdens, provide unique opportunities to understand disease pathogenesis, anticipate disease trends, or develop interventions.

These objectives form the conceptual basis for current FIC programs related to HIV/AIDS, emerging infectious diseases, maternal and child health, population research and demographic science, medical informatics, drug discovery from biodiversity, as well as fellowship programs for young Americans, with emphasis on underrepresented minorities. The disciplinary fields described are pursued through a range of funding mechanisms, including institutional training grants, cooperative agreements, small research grants, fellowships, and multilateral initiatives involving international organizations.

FIC Program Objectives: Building an Effective Support System for International Health

Pursue a systematic and comprehensive approach to capacity development through the creation of regional "centers of excellence" in Asia, Africa and Latin America, promoting research at all levels of the health system.

Build interdisciplinary skills required to meet the global health challenges, emphasizing modern analytic tools of cell and molecular biology, genetics, bioinformatics and rigorous clinical research methodologies.

Provide necessary material resources, including the infrastructure for communications and computing and dissemination of information.

Address the importance of equity and social justice and increase capabilities in bioethical reasoning and practice.

Promote intrasectoral alliances among research and development agencies, emphasizing partnerships for the application of research findings in-country.

Establish working relationships for national programs for disease control to help ensure the relevance of research priorities and application of findings.

Promote the capacity to assess multiple factors on incidence, severity and outcome of endemic problems, including behavioral and economic influences.

Deploy program strategies which limit the potential or "brain drain" in view of current economic constraints in many low- and middle-income countries.

Take long-term perspectives–conduct necessary research.

The following outlines FIC’s research and training priorities and objectives for FY 2000-2003. These are based on a calculus of planning considerations, including disease burden and public health urgency, scientific opportunities and emerging research tools and technologies, and research required to inform evidence-based health policy. These strategic plans were developed in consultation with counterpart NIH institutes, the FIC Advisory Board and ad hoc committee of public representatives.

Global Health Trends: The Challenges Ahead

Changing and Persistent Microbial Threats to Health

Our battle to prevent and cure HIV/AIDS is a dramatic example of the need to mobilize scientific resources to address disease threats and reduce health disparities. AIDS has exacted a profound humanitarian toll in the United States and abroad, reversed gains in child survival in many nations, and threatened the economic stability of emerging markets by reducing the number of working age men and women. Critical to reducing the impact of HIV/AIDS in resource-poor countries, which bear the disproportionate burden of this disease, are strong national commitments and international cooperation and research to develop effective prevention and control strategies. In addition to accelerating efforts to develop a vaccine, an evolving global strategy for HIV/AIDS is to deploy multiple prevention strategies based on successfully tested interventions: in concept, to prevent HIV at the population level through "combination" approaches. The international health R&D community is positioned to create lower cost "prevention algorithms" to contain HIV in highly impacted countries through the testing of combination interventions to include STD treatments, affordable anti-viral regimens to prevent mother-to-child transmission, topical microbicides, condoms, improved obstetrical practices and behavioral/social interventions.

HIV is a cautionary example. The rapid emergence of new pathogens presents a disturbing new chapter in the grim evolutionary battle between humans and microbes. This is the result of social and demographic trends, and changes in the genetic structure of microbes that increase virulence and transmission and weaken the efficacy of existing drugs. Among major disease pathogens which exhibit these characteristics, tuberculosis accounts for one-quarter of all preventable adult deaths in the developing world. Pneumococcal pneumonia carries almost as great a death toll as tuberculosis and a higher disease burden. Forty-three years after the World Health Assembly initiated a global eradication program, malaria has resurged due to resistance of the parasite to available drugs and resistance of vectors to insecticides. Preventive strategies to slow the emergence of microbial disease require research on factors that influence the spread of microbial resistance to anti-microbials and chemotherapeutic drugs and new technologies to monitor these occurrences.

Current Programs on Persistent and Changing Microbial Threats

• AIDS International Training and Research program
• HIV and Related Illness Collaboration Award
• International Training and Research Program in Emerging Infectious Diseases
• Tuberculosis International Training andRresearch program
• Actions for Building Capacity
• Multilateral Initiative on Malaria

Proposed initiatives

• International Vaccine Action Project
• Intramural Program in Population Biology

Program Development Goals

• Assist development of research infrastructure, cohorts of study volunteers, and field and laboratory skills to support international HIV vaccine and therapeutic trials.
• Identify prevention algorithms in resource-poor settings to reduce the risk of HIV infection, to include reduction of risk through blood transfusion.
• Establish "sentinel sites" to develop data and predictive models to anticipate future epidemics and devise corrective actions.
• Strengthen epidemiological research and clinical trials capacity at sites in low and middle-income nations that might serve to evaluate candidate vaccines for parasitic, bacterial and viral disease.
• Examine correlates of protection and surrogate markers to evaluate vaccine candidates and monitor vaccination.
• Develop and evaluate ways to increase efficiency of vaccines by simplifying delivery and maximizing use of opportunities for immunization.
• Pursue mathematical and computational approaches to study interactions between environment pathogen and host, the spread and persistence of genotypes within the pathogen population and the dynamics of transmission.

The Unfinished Health Agenda of Maternal and Child Health

Childhood infections, poor reproductive health and malnutrition account for over one-third of the entire global burden of disease, based on the metric of disability adjusted life years, or DALYs (an indicator of the state of global health introduced by the World Bank that measures the economic, social, and human impact of both premature death and lifelong disability). A root cause of this burden stems from demographic pressures in low- and middle-income nations. The world's population is now expanding at the unprecedented rate of nearly 1 billion per decade; virtually all of this growth is expected to occur in developing nations of Africa, Asia and Latin America. There is broad consensus that a reduction in rapid population growth in the developing world will enhance the prospects for improved living standards in the decades ahead. Yet ultimately, the effectiveness of family planning is dependent on the improvement of infant and child survival rates. Current child mortality rates in many low- and middle-income nations result in excess births to ensure that a desired number of children survive to adulthood. More than one quarter of the global disease burden is caused by diseases which primarily affect children in low-income nations, mainly childhood communicable diseases and inadequate dietary intake which exacerbate these conditions. These multiple and complex challenges require new medical technologies and social adaptations, presenting important international research and training needs.

Current Programs in Maternal and child health

• International Training and Research program in Population and Health
• International Maternal and Child Health Research Program

Proposed Initiatives

• International Nutrition Project

Program Development Goals

• Pursue new and improved contraceptive devices and agents, including natural or synthetic products to reduce transmission of sexually-transmitted diseases, and development of reversible sterilization techniques.
• Identify social and behavioral factors that influence population growth and change, including contraceptive use and choice and societal roles of women.
• Develop and evaluate packages of services for antenatal care delivery and reduction of the burden of neonatal morbidity and mortality.
• Develop research strategies for improved diagnostics and community prevention and control programs for meningitis, upper respiratory and enteric bacteria and viruses that cause severe diarrheal illness.
• Understand the relative importance of nutrient intake on control of infectious disease and chronic disease risk.
• Create capacity to evaluate and address the causes and impact of childhood developmental disabilities, including learning disabilities and school performance.

The Emerging Epidemics of Chronic Disease

In 1990, non-communicable diseases accounted for just over 40 percent of the global burden of disease and disability. By the year 2020, their share is expected to reach 60 percent, with the increase attributable to economic and demographic trends in low- and middle-income nations. By 2020 chronic diseases are expected to eclipse infectious diseases as major causes of lost years of health life. In principle, many of these burdens may be averted by adapting cost-effective interventions which have been applied in industrialized nations. These include, for example, primary prevention programs to modify environmental and behavioral risk factors as well as programs for secondary prevention. However, the appropriate transfer of these interventions to low- and middle-income nations requires expanded efforts to determine risk exposures and culturally-relevant interventions. Among risk factors accompanying industrialization, three conditions deserve special emphasis based on both health and economic consequences: mental health disorders; tobacco-related diseases and exposures to environmental toxins.

Current programs On Chronic Disease

• International Training and Research Program in Environmental and Occupational Health

Proposed initiatives

• International Training and Research Program on Mental Health Disorders
• International Training and Research Program on Tobacco Control

Program Development Goals

• Pursue epidemiological data on the incidence of mental health disorders and risk factors, including socio-cultural determinants of mental health in societies undergoing transition to industrialized economies.
• Identify mechanisms of toxicity, radiation damage and DNA repair through studies among populations with toxic environmental and occupational exposures, and strategies to mitigate their impact.
• Develop biomarkers of environmental exposure and effect.
• Pursue research on, the addictive nature of tobacco use and behavioral factors associated with smoking uptake in low- and middle-income countries.
• Pursue research into the adaptation of demand reducing measures such as tax schemes, and bans on advertising and promotion.

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Biodiversity and Health

Biologic diversity is being reduced by human activities, such as slash and burn agriculture, and may be one of the chief casualties of environmental changes. There is a tendency to assume that our increasing technological sophistication moves us further away from dependence on the natural world. However, it is likely that ecosystems maintained by diverse species are part of our protection against diseases. For example, loss of diversity due to deforestation has introduced new infectious agents into human populations; heavily-used nitrogen-based fertilizers in monocultural farming, releasing nitrous oxide, are a prime contributor to ozone depletion, eroding protection against the damaging effects of ultraviolet B radiation among other consequences. Moreover, the earth's biota also is a continuing resource for new therapeutics. Advanced bioassays and automation now make prospecting for bioactive compounds easier, faster and far more productive. It is estimated that in the United States, one-half of prescribed pharmaceuticals are substances extracted from plants or derived from microorganisms. The most effective new antimalarial, and the only agent that has prevented a disaster due to multidrug resistant falciparum malaria is derived from a Chinese herb. Yet only a tiny fraction of the world's biological wealth has been studied for possible therapeutic benefit at the same time species loss proceeds at an unprecedented pace.

Current Programs on Biodiversity and health

• International Cooperative Biodiversity Groups Program
• International Program on Ecology of Infectious Diseases

Proposed Initiatives

• Environment and Sustainable Development Project

Program Development Goals

• Identify bioactive properties of biological resources such as plants, invertebrates and marine organisms through partnerships that emphasize equitable distribution of intellectual property resulting from collaborative ventures and benefits for local communities.
• Establish inventories of biological resources and contribute toward documentation and recognition of biodiversity
• Identify strategies to enhance conservation management of biodiverse resources at study sites.
• Promote efforts to quantify the health and social cost of environmental degradation as part of ongoing economic monitoring.
• Examine how environmental variation influences distribution and adaptation of organisms and consequences for human health.

 

Interdisciplinary Training Needs in the New Millennium

FIC plays a major role in preparing the current and future generation of scientists to function and excel in a global environment, and to work interdependently to meet global health challenges that exceed the capabilities and resources of any one nation. With the emergence of molecular and cellular biology, recombinant DNA technology, computational biology and refinements of more classical techniques, biomedical science has become more complex and interdisciplinary. In response, FIC has identified four core areas as targets of training and infrastructural support to form the foundation of all of FIC’s program efforts.

First, many low- and middle-income nations are entering a period of technological change, which will result in a transition from a more traditional library system to reliance on electronic access to international data networks through individual workstations. Technologies such as fiber optics and satellite telecommunication networks ultimately will evolve as the technical backbone to the scientific and health care community in these countries. There is a prescient need to consider how these emergent technologies in low- and middle-income nations can be applied to such challenges as epidemiologic surveillance, improvements in clinical practice, distance learning, and the construction of scientific "collaboratories" to share information, software and computing capabilities and conduct electronic peer review. Second, advances in molecular genetics and medicine already demonstrate that the structure of individual genes and encoded proteins provide a new starting points for diagnosis and therapy to identify and correct defects in the regulation of cellular machinery. This shift has profound implications for our understanding of susceptibility and resistance to polygenic disorders and the maintenance of health in the community. This shift will require the transfer and adaptation of state-of-the-art analytic tools and technologies, such as polymerase chain reaction or new tools to probe cell architecture. Third, in complement with new techniques, competence is required in clinical research methods, including clinical trials and observational study design, epidemiology and outcomes research, pharmacokinetics and data management and analysis. And fourth, the scientific community and public are presented with complex questions concerning the social and ethical dimensions of research and the application of discoveries. In the first instance, there is need to deepen global capacity in bioethical theory and application and to support empirical studies on ethical theory and practice in biomedical and behavioral research in diverse cultural and economic settings. Emphasis will be placed on considerations arising from cross-cultural research. These issues have been raised most frequently in the conduct of HIV/AIDS research but extend to a broad range of potential interventions that require controlled field evaluations and human investigations.

Current programs on Interdisciplinary Training needs

• International Training program in Medical Informatics

Program Initiatives

• International Training Program in Molecular Genetics and Genomics
• International Training in Clinical Research Design and Methods
• International Bioethics Education and Career Development Award

Program Development Goals

• Initiate "collaboratory" projects to link experts internationally on a given scientific challenge or process, such as infectious disease research surveillance, distance learning or peer review.
• Improve international access to national information resources through available technologies. Expand programs to ensure access to on-line databases (e.g., MEDLINE, TOXLINE) and related information processing tools by scientists and health care professionals.

 

• Increase skills required to identify genes responsible for relative susceptibility and resistance to heritable, chronic and infectious disease burdens in low- and middle-income nations and test the predictive strength of particular polymorphisms with prospective community-based studies
• Prepare investigators to build the scientific bases for prevention of disease and management of established illness and improve methods of research, with attention to clinical variables essential to understanding the course of disease and the outcome of patient therapies.
• Increase skills and knowledge in bioethics at the level of the community (prospective study populations), research investigator and allied health professional, ethics committee reviewers and institutional stewards (e.g., ministries of health).
• Increase the cadre of professionals in low and middle-income nations capable of pursuing ethnographic studies of the practice of ethics in medical contexts–to deepen the empirical foundations of ethical practice and theory in transcultural research.

Building U.S. Capacity in Global Health Research

There is a recognized shortfall of biomedical researchers in the United States who are engaged in tropical medicine and other fields of global health. Previous reports of the Institute of Medicine have cited critical shortages in such fields as medical entomology, arboviruses and general parasitology. Given the magnitude of global health challenges, there is a need to provide opportunities for young US investigators to perform basic and applied research within endemic countries, as well as provide a substantive career structure in global health research within US institutions. Several scientific developments provide enormous incentive to pursue research on disease burdens which confront populations in tropical and sub-tropical regions. The first is the rapid sequencing of the genomes of pathogenic organisms which will yield new immunogens and drug targets. A second is the development of new assays which enable scientists to measure biological changes at the genetic and molecular levels, and have created a powerful armature for population based studies. Special attention must be paid to engaging underrepresented minorities in global health research, targeting the formative stages of their academic careers.

Current programs to build US capacity in Global health research

• Minority International Research and Training Program
• International Research Scientists Development Award for US Postdoctoral Scientists

Program Development Goals

• Increase the cadre of talented students at both majority and minority colleges and universities who participate in scientific projects in low-and middle-income nations.
• Develop linkages between these students and NIH international research protocols to provide exposure to the intellectual milieu of the research enterprise.
• Enhance the research skills of US postdoctoral scientists in laboratory-based, clinical and field investigation, including behavioral and ethnographic studies, through opportunities at foreign field sites.
• Promote stable career structures in global health research through US based "re-entry" awards to postdoctoral scientists pursuing research at foreign sites, and other measures.

 

Research to Inform Health and Economic Policy

Incentives for the Development and Deployment of Preventive Vaccines and Drugs of Priority to Low- and middle-income Nations.

Due to the expense of bringing a pharmaceutical to market (an estimated US $360 million on average), R&D expenditures are recaptured through pricing that considerably exceeds the marginal costs of production and packaging. As a result, little incentive exists to invest in products where the prime market is the developing world and the potential of recovering costs plus profits is uncertain. This is perceived to impede the development of products that primarily would benefit populations in poorer nations. It is instructive that among therapeutic interventions licensed from 1975-1997, only 1 percent are specific for tropical diseases. Economic constraints also affect the availability of essential drugs in many low- and middle-income nations. It is estimated that approximately 2 billion people lack access to essential drugs. There is a well-recognized need to address these market failures. In addition, there is a need to create a more enabling economic environment for the deployment of available vaccines for Haemophilus influenzae type b and hepatitis B, and to assess the potential to deliver additional vaccines within the DPT platform or Expanded Programme on Immunization. These challenges will call for innovative public-private partnerships, evaluative research and novel funding or cost recovery schemes.

Program Development Goals

• Examine incentives and disincentives for industrial investment in medical products of primary benefit to low- and middle-income nations. This may entail a deepened empirical review of proposed incentive structures in consultation with industry.
• Examine creative methods of leveraging new resources for global health research through debt conversion or other schemes in support of the Heavily Indebted Poor Countries Initiative.

 

Health and Economic Productivity: A Neglected Link

Correlates to economic development have been studied vigorously, but little attention has been paid to the relationship between health or demographic status and economic development. Recently, economists and the public health community have begun two broad avenues of investigation: Macroeconomic studies to examine the relationship between national growth indicators and health; and microeconomic studies that explore the dynamics of health and productivity at the individual or household levels. These studies suggest that our conceptual understanding of the long-term influences on economic development and the formulation of effective policies rely on a deepened understanding of the determinants and consequences of public health. If governments and donors are to effectively target their investment in health as a component of development plans, expanded research is required on the complex dynamics of health, poverty and productivity.

Proposed initiatives

• International Program in Health and Economic development

Program Development Goals

• Assess the effect of biomedical interventions on household and aggregate economic indicators, including agricultural and manufacturing productivity, literacy and social and environmental welfare.
• Assist in the development of a system of metrics that equips researchers and service providers with the information needed to effectively target public health interventions.

 

Conclusion

In commenting on the international commitments of the NIH, what is past is prologue. NIH began as a small laboratory on Staten Island, tending to the needs of merchant marines. At the turn-of-the century the Laboratory of Hygiene proved its worth after diagnosing cases of cholera among immigrant passengers on the steamship "Alesia" -- the first diagnosis of cholera in the western hemisphere. This landmark was made possible through collaboration with the laboratory of Robert Koch in Berlin, who pioneered methods to isolate bacteria. This early discovery presaged the very practical benefits of public investments in basic research. It also signaled our reliance on international scientific cooperation to accelerate the pace of discovery, which remains essential to improvements in health and medicine at the beginning of this new century, and which embodies the mission of FIC.