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Thứ Hai, 26 tháng 4, 2010

Chapter 002. Global Issues in Medicine

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Harrison's Internal Medicine > Chapter 2. Global Issues in MedicineWhy Global Health?Global health, it has been noted, is not a discipline; it is, rather, a collection of problems. No single review can do much more than lay out the leading problems faced in applying evidence-based medicine in settings of great poverty or across national boundaries. In this chapter, we first introduce the major international bodies engaged in addressing these problems; identify the more significant barriers to improving the health of people who to date have not, by and large, had access to modern medicines; and summarize population-based data regarding the most common health problems faced by people living in poverty. Examining specific problems—notably AIDS (Chap. 182), but also tuberculosis (TB, Chap. 158), malaria (Chap. 203), severe acute respiratory syndrome (SARS; Chap. 179), and key noncommunicable diseases—helps to sharpen the discussion of barriers to prevention, diagnosis, and care as well as means of overcoming them. We next discuss global health equity, drawing on notions of social justice that once were central to international public health but have fallen out of favor over the past several decades. We close by acknowledging the importance of cost-effectiveness analysis linked to national economic data, while at the same time underlining the need to address disparities of disease risk and access to care.History of Global Health InstitutionsConcern about health across national boundaries dates back many centuries, predating the Black Plague and other pandemics. Before the advent of germ theory, when epidemic disease began to be understood to be the result of microbes rather than of "miasmas" or the wrath of a divine being, the chief social responses to such epidemics often included accusations that this or that human group was responsible for propagating the affliction in question. Similarly inaccurate and ineffective beliefs abounded when the arrival of European colonists led to catastrophic outbreaks of communicable diseases among indigenous populations in the Americas, and these viewpoints continued to hold sway during subsequent pandemics of cholera. Many historians trace modern public health and epidemiology to the day in 1851 when Dr. John Snow, having discerned the link between cholera outbreaks in London and water sources used by the afflicted populace, removed the handle of the Broad Street water pump. Thus one cholera epidemic was stopped, but it would still be years before the etiology of cholera was discovered.A proper understanding of etiology was necessary to the birth not only of epidemiology but also of efforts to apply public health measures across administrative boundaries; indeed, without agreement upon etiology and case definitions, there could be no sound metrics upon which to base either assessments of disease burden or effective interventions. The close of the nineteenth century marked the birth and rapid growth of microbiology and the development of some of the first effective vaccines, which, along with measures to promote sanitation, were for decades the mainstay of modern public health. Before the development of effective antibiotics in the mid-twentieth century, international health endeavors consisted largely of the transnational application of a small number of lessons learned from local or regional campaigns. Perhaps the first organization founded explicitly to tackle cross-border health issues was the Pan American Sanitary Bureau, which was formed by 11 countries in the Americas in 1902. The primary goal of what was later to become the Pan American Health Organization was the control of infectious diseases across the Americas. Of special concern was yellow fever, which had been running a deadly course through much of South and Central America and posed a threat to the construction of the Panama Canal. The identification of a mosquito vector in 1901 led public and private health authorities to focus on mosquito control; a vaccine was developed in the 1930s.Even in the early heyday of vaccine development, no global institutions tackled the health problems of the world's poor. Colonial powers did address (with varying degrees of effectiveness and sources of motivation) the ranking infectious killers in regions now known as the developing world, but universal standards or even aspirations for international public health and medicine were still far in the future. Although the League of Nations concerned itself with health issues such as malaria in the early twentieth century, and although various organs of the nascent United Nations—including the United Nations Development Program and the United Nations Children's Fund (UNICEF)—also addressed health issues, the World Health Organization (WHO) was the first truly global health institution. Since its founding in 1948, the WHO has witnessed dramatic shifts in population health and in its own stature as the premier global health institution. In line with a long-standing focus on communicable diseases that readily cross administrative and political borders, leaders in global health, under the aegis of the WHO, initiated the effort that led to what some see as the greatest success in international health: the eradication of smallpox. Historians of the smallpox campaign note the preconditions that made eradication possible: international consensus regarding the potential for success, an effective vaccine, and the apparent lack of a nonhuman reservoir for the often-lethal and highly infectious etiologic agent. The primary obstacle was the lack of effective delivery mechanisms for the vaccine in settings of poverty, where health personnel were scarce and health systems weak. Close collaborations across administrative and political borders were clearly necessary. Naysayers were surprised when the smallpox eradication campaign, which engaged public health officials throughout the world, proved successful at the height of the Cold War.The optimism born of the world's first successful disease-eradication campaign invigorated the international health community, if only briefly. Global consensus regarding the right to primary health care for all was reached at the International Conference on Primary Health Care in Alma-Ata (in what is now Kazakhstan) in 1978. However, the declaration of this collective vision was not followed by substantial funding, nor did the apparent consensus reflect universal commitment to the right to health care. Moreover, as is too often the case, success paradoxically weakened commitment. Basic-science research that might lead to effective vaccines and therapies for TB and malaria faltered in the latter decades of the twentieth century after these diseases were brought under control in the affluent countries where most such research is conducted. U.S. Surgeon General William H. Stewart declared in the late 1960s that it was time to "close the book on infectious diseases," and attention was turned to the main health problems of countries that had already undergone an "epidemiological transition"; that is, the focus shifted from premature deaths due to infectious diseases toward deaths from complications of chronic noncommunicable diseases, including malignancies and complications of heart disease.In 1982, the visionary leader of UNICEF, James P. Grant, frustrated by the lack of action around the Health for All initiative announced in Alma-Ata, launched a "child survival revolution" focused on four inexpensive interventions collectively known by the acronym GOBI: growth monitoring; oral rehydration; breast-feeding; and immunizations for TB, diphtheria, whooping cough, tetanus, polio, and measles. GOBI, which was later expanded to GOBI-FFF (to include female education, food, and family planning), was controversial from the start, but Grant's advocacy led to enormous improvements in the health of poor children worldwide. The Expanded Programme on Immunization was especially successful and is thought to have raised the proportion of children worldwide who were receiving critical vaccines by more than threefold—i.e., from <20% to almost 80% (the target level).For many reasons (including, perhaps, the success of the UNICEF-led campaign for child survival), the influence of the WHO waned during the 1980s. In the early 1990s, many observers argued that, with its vastly superior financial resources and close if unequal relationships with the governments of poor countries, the World Bank had eclipsed the WHO as the most important multilateral institution working in the area of health. One of the stated goals of the World Bank was to help poor countries identify "cost-effective" interventions worthy of international public support. At the same time, the World Bank encouraged many of these nations to reduce public expenditures in health and education as part of (later discredited) structural adjustment programs (SAPs), which were imposed as a condition for access to credit and assistance through international financial institutions such as the Bank and the International Monetary Fund (IMF). One trend related, at least in part, to these expenditure-reduction policies was the resurgence in Africa of many diseases that colonial regimes had brought under control, including malaria, trypanosomiasis, and schistosomiasis. Tuberculosis, an eminently curable disease, remained the world's leading infectious killer of adults. Half a million women per year died in childbirth during the last decade of the twentieth century, and few of the world's largest philanthropic or funding institutions focused on global health.AIDS, first described in 1981, precipitated a change. In the United States, the advent of this newly described infectious killer marked the culmination of a series of events that discredited the grand talk of "closing the book" on infectious diseases. In Africa, which would emerge as the global epicenter of the pandemic, HIV disease further weakened TB control programs, while malaria continued to take as many lives as ever. At the dawn of the twenty-first century, these three diseases alone killed an estimated 6 million people each year. New research, new policies, and new funding mechanisms were called for. Some of the requisite innovations have emerged in the past few years. The leadership of the WHO has been challenged by the rise of institutions such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria; the Joint United Nations Program on HIV/AIDS (UNAIDS); and the Bill & Melinda Gates Foundation and by bilateral efforts such as the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Yet with its 193 member states and 147 country offices, the WHO remains preeminent in matters relating to the cross-border spread of infectious and other health threats. In the aftermath of the SARS epidemic of 2003, the International Health Regulations—which provide a legal foundation for the WHO's direct investigation of a wide range of global health problems, including pandemic influenza, in any member state—were strengthened and brought into force in May 2007. Even as attention to and resources for health problems in resource-poor settings grow, the lack of coherence in and among global health institutions may seriously undermine efforts to forge a more comprehensive and effective response. While UNICEF had great success in launching and sustaining the child survival revolution, the end of James Grant's term at UNICEF upon his death in 1995 was followed by a lamentable shift of focus away from immunizations; predictably, coverage dropped. The WHO has gone through two recent leadership transitions and is still woefully underfunded despite the ever-growing need to engage a wider and more complex range of health issues. In another instance of the paradoxical impact of success, the rapid growth of the Gates Foundation, while clearly one of the most important developments in the history of global health, has led other foundations to question the wisdom of continuing to invest their more modest resources in this field. We may indeed be living in what some have called "the golden age of global health," but leaders of major organizations such as the WHO, the Global Fund, UNICEF, UNAIDS, and the Gates Foundation must work together to design an effective architecture that will make the most of the extraordinary opportunities that now exist. To this end, new and old players in global health must invest heavily in discovery (relevant basic science); in the development of new tools (preventive, diagnostic, and therapeutic); and in a new science of implementation, or delivery.
The Economics of Global Health
Political and economic concerns have often guided global health interventions. As mentioned previously, early efforts to control yellow fever were tied to the completion of the Panama Canal. However, the precise nature of the link between economics and health remains a matter for debate. Some economists and demographers argue that economic development is the key to improving the health status of populations, while others maintain that ill health is the chief barrier to development in poor countries. In either case, investment in health care, and especially in the control of communicable diseases, should lead to increased productivity. The question is where to find the necessary resources to start the predicted "virtuous cycle."International financial institutions, including the World Bank and the IMF, have counseled limited investments and the capping of social expenditures in health and education. The socioeconomic argument was that a balanced budget and a "friendly investment climate"—that is, privatization, deregulation, decreased trade barriers, devalued currencies, and debt repayment—would favor development and thus improve health outcomes. The limitations on social-sector spending recommended for many poor countries by the World Bank and the IMF from the 1970s through the 1990s tended to confirm the opposite view. In the poorest countries, already-tiny health-sector budgets were further constricted. Moreover, health-sector spending in many poor countries channeled a majority of resources toward city hospitals that served mostly élites who were able to pay; consequently, in the past quarter-century, little spending went toward addressing the problems that most affected poor people in poor countries.Since 1999, spurred by the leadership of the Gates Foundation and the growing interest in addressing novel and persistent challenges such as AIDS, spending on health in poor countries has increased, with $40 billion in new funds earmarked for the discovery and development of drugs and diagnostics targeting diseases of the poor; for comprehensive responses to the AIDS, TB, and malaria epidemics; for vaccine development and delivery; and even for improved methods of data collection in resource-poor settings. Nevertheless, in order to reach the United Nations' Millennium Development Goals, which include targets for poverty reduction, universal primary education, and gender equality, spending in the health sector will have to be further increased and sustained. To determine by how much and for how long, it is imperative that we improve our ability to assess the global burden of disease (GBD) and to plan interventions that more precisely match the need, which is glaring but often poorly understood. Refining metrics is an important task for global health: only recently have we had solid assessments of the GBD. Such assessments may serve as preliminaries or as correctives to effective interventions among the poor.Life Expectancy and Global Burden of DiseaseSince the late 1980s, serious efforts have been made to calculate the GBD. The first GBD study, conducted in 1990, laid the foundation for the first report on Disease Control Priorities in Developing Countries (DCP1) and for the World Bank's 1993 World Development Report entitled Investing in Health. These efforts represented a major advance in our understanding of health status in developing countries. Investing in Health has been especially influential: it familiarized a broad audience with cost-effectiveness analysis for specific health interventions and with the notion of disability-adjusted life years (DALYs). The DALY, which has become a standard measure of the impact of a specific health condition on a population, combines in a single measure both absolute years of life lost and years lost due to disability for incident cases of a condition.The second GBD analysis was carried out on health data from 2001. The latter report reflects growth in the available data on health in the poorest countries and in our capacity to measure the impact of specific conditions on a population. Yet, even in 2001, only 107 of 192 nations surveyed had reliable information on the causes of deaths within their own borders. It is essential to expand efforts to collect the most basic health data; this task falls to the WHO, national governments, and certain academic institutions. The lack of complete data has led to considerable uncertainty in estimates of overall mortality. The level of uncertainty ranges from as low as 1% for estimates of all-cause mortality in developed countries to well over 50% for disability resulting from diseases for which surveillance mechanisms are incomplete. As analytic methods and data quality have improved, however, important trends can be identified in a comparison of GBD estimates from 1990 and 2001.Of the 56 million deaths worldwide in 2001, one-third were due to communicable diseases, maternal and perinatal conditions, and nutritional deficiencies. While the proportion of all deaths attributable to these causes was unchanged from 1990, the share of all deaths due to the communicable disease HIV/AIDS grew from just 2% to an astonishing 14%. If these deaths were excluded, the fraction of all deaths related to communicable diseases, maternal and perinatal conditions, and nutritional deficiencies dropped from one-third to one-fifth. Of the deaths making up that one-fifth of the total figure, 97% occurred in middle- and low-income countries. The leading cause of death among adults in 2001 was ischemic heart disease, accounting for 17.3% of all deaths in high-income countries and for 11.8% in middle- and low-income countries. In second place was cerebrovascular disease, which accounted for 9.9% of deaths in high-income countries and for 9.5% of deaths in middle- and low-income countries. While the third leading cause of death in high-income countries was tracheal, bronchial, and lung cancers (which accounted for 5.8% of all deaths), these conditions do not even register in the top 10 places in middle- and low-income countries. Of the 10 leading causes of death in poorer countries, 5 were communicable diseases; in high-income countries, however, only 1 communicable disease—lower respiratory infection—was ranked among the top 10 causes of death.Nearly 20% (10.6 million) of the 56 million dead in 2001 were children <5 years of age who died of acute respiratory infections, measles, diarrhea, malaria, and HIV/AIDS (Fig. 2-1). Of these deaths, 99% occurred in middle- and low-income countries, and fully 40% occurred in sub-Saharan Africa. If stillbirths are counted, the number of childhood deaths rises to 13.5 million worldwide (~25% of all deaths worldwide), of which more than half (i.e., one-eighth of all deaths) occurred before the first birthday. Between 1990 and 2001, under-five childhood mortality dropped by 30% in high-income countries, Latin America, the Caribbean, the Middle East, North Africa, and the middle- and low-income countries of Europe and Central Asia. Notably, the total number of deaths from diarrheal diseases dropped from 2.4 million in 1990 to 1.6 million in 2001, probably as a result of the increased use of oral rehydration therapy in poor countries. Malaria and HIV infection were the only two conditions for which childhood death rates increased between 1990 and 2001.Among persons 15–59 years of age (Fig. 2-2), noncommunicable diseases accounted for more than half of all deaths in all regions except South Asia and sub-Saharan Africa, where communicable diseases, maternal and perinatal conditions, and nutritional deficiencies together accounted for one-third and two-thirds of all deaths, respectively. The 15- to 59-year-olds with noncommunicable conditions in low- and middle-income countries faced a 30% greater risk of death from their conditions than did their peers in high-income countries. In this age group, injuries accounted for 25% of all deaths; Europe and Central Asia registered even higher rates, with injuries accounting for one-third of all deaths. Overall, death rates in this age group declined between 1990 and 2001 in all regions except Europe and Central Asia, where cardiovascular diseases and injuries have caused increased mortality, and sub-Saharan Africa, where the impact of HIV/AIDS in this age cohort has been particularly devastating.Noncommunicable diseases accounted for almost 60% of all deaths in 2001 but, because of the later onset of these diseases, accounted for only 40% of years of life lost. In contrast, because they occur more often in younger people, injuries accounted for 12% of years of life lost but for only 9% of deaths. Overall, males had an 11% higher death rate than females as well as a 15% higher rate of years of life lost; these figures reflect the earlier age of death of males worldwide. Notably, almost half of the disease burden in middle- and low-income countries in 2001 derived from noncommunicable disease—an increase of 10% since 1990.Compared with years of life lost, there is greater uncertainty in calculating years of life lived with disability for specific conditions. Best estimates from 2001 reveal that, while the prevalence of diseases common in older populations (e.g., dementia and musculoskeletal disease) was higher in high-income countries, the disability experienced as a result of cardiovascular diseases, chronic respiratory diseases, and the long-term impact of communicable diseases was greater in low- and middle-income countries. Thus, predictably, in most low- and middle-income countries, people both lived shorter lives and experienced disability and poor health for a greater proportion of their lives. Indeed, 45% of the overall burden of disease occurred in South Asia and sub-Saharan Africa, which together comprise only one-third of the global population.In its analysis of risk factors for ill health, the GBD project found that undernutrition was the leading cause of loss of DALYs in both 1990 and 2001. In an era that has seen obesity become a major health concern in so many developed countries, the persistence of undernutrition is surely cause for great consternation. Our inability to feed the hungry indicts many years of failed development projects and must be addressed as a problem of the highest priority. Indeed, no health care initiative, however generously funded and scientifically justified, will be effective without adequate nutrition.The GBD analysis was used as the basis for the second edition of Disease Control Priorities in Developing Countries (DCP2). Published in 2006, DCP2 is a document of stunning breadth and ambition, providing cost-effectiveness analyses for >100 interventions and including 21 chapters focused on strategies for strengthening health systems. Cost-effectiveness analyses that compare two relatively equal interventions and facilitate the best choices under constraint are important; however, as both resources and ambitions for global health grow, cost-effectiveness analyses (particularly those based on past conditions) must not hobble the increased worldwide commitment to provide resources and accessible services to all who need them. To illustrate this point, we turn in greater detail to AIDS, which has become, in the course of the last three decades, the world's leading infectious cause of death during adulthood.AIDSChapter 182 provides an overview of the AIDS epidemic in the world today. Here we will limit ourselves to a discussion of AIDS in the developing world. Lessons learned in tackling AIDS in resource-constrained settings are highly relevant to discussions of other chronic diseases, including noncommunicable diseases, for which effective therapies have been developed. We highlight several of these lessons below.In the United States, the availability of highly active antiretroviral therapy (ART) for AIDS has transformed this disease from an inescapably fatal destruction of cell-mediated immunity into a manageable chronic illness. In developing countries, treatment has been offered more broadly only since 2003, and only in the summer of 2006 did the number of patients receiving treatment exceed 25% of the number who currently need it. (It remains to be seen how many of these fortunate few are receiving ART regularly and with the requisite social support.) Before 2003, many arguments were raised to justify not moving forward rapidly with ART programs for people living with HIV/AIDS in resource-limited settings. The standard litany included the price of therapy compared to the poverty of the patient, the complexity of the intervention, the lack of infrastructure for laboratory monitoring, and the lack of trained health care providers. Narrow cost-effectiveness arguments that created false dichotomies—prevention or treatment, rather than both—too often went unchallenged. The greatest obstacle at the time was the ambivalence, if not outright silence, of political leaders and experts in public health. The cumulative effect of these factors was to condemn to death tens of millions of poor people in developing countries who had become ill as a result of HIV infection.The inequity between rich and poor countries in access to HIV treatment has rightly given rise to widespread moral indignation. In several middle-income countries, including Brazil, visionary programs have bridged the access gap. Other innovative projects pioneered by international nongovernmental organizations (NGOs) in diverse settings have clearly established that a very simple approach to ART, based on intensive community engagement and support, can achieve remarkable results. In 2000, the United Nations Accelerating Access Initiative finally brought the research-based and generic pharmaceutical industries into play, and AIDS drug prices have since fallen significantly. At the same time, easier-to-administer fixed-dose combination drugs have become more widely available.Building on these lessons, the WHO advocated a public health approach to the treatment of people with AIDS in resource-limited settings. This approach, which was derived from models of care pioneered by the NGO Partners In Health and other groups, proposed standard first-line treatment regimens based on a simple five-drug formulary, with a more complex (and, up to now, more expensive) set of second-line options in reserve. Common clinical protocols were standardized, and intensive training packages for health and community workers were developed and implemented in many countries. These efforts were supported by unprecedented funding through the World Bank, the Global Fund, and PEPFAR. In 2003, the lack of access to ART was declared a global public-health emergency by the WHO and UNAIDS, and the two agencies launched the "3 by 5 initiative," setting an ambitious target: having 3 million people in developing countries on treatment by the end of 2005. Many countries have since set corresponding national targets and have worked to integrate ART into their national AIDS programs and health systems and to harness the synergies between HIV/AIDS treatment and prevention activities. The G8 (Gleneagles) 2005 communiqué endorsing universal access to HIV treatment by 2010 was another major step forward.It is clear by now that the claims made for the efficacy of ART are well founded: in the United States, such therapy has prolonged life by an estimated 13 years per patient on average—a success rate that would compare favorably with that of almost any treatment for cancer or for complications of coronary artery disease. Further lessons with implications for policy and action have come from efforts that are now under way in the developing world. During the past decade, through experiences in >50 countries thus far, the world has seen that ambitious policy goals, adequate funding, and knowledge about implementation can dramatically transform the prospects of people living with HIV infection in developing nations.TuberculosisChapter 158 offers a concise overview of the pathophysiology and treatment of TB, which is closely linked to HIV infection in much of the world. Indeed, a substantial proportion of the resurgence of TB registered in southern Africa may be attributed to HIV co-infection. Even before the advent of HIV, however, it was estimated that fewer than half of all cases of TB in developing countries were ever diagnosed, much less treated.Primarily because of the common failure to diagnose and treat TB, international authorities devised a single strategy to reduce the burden of disease. The DOTS strategy (directly observed therapy using short-course isoniazid- and rifampin-based regimens) was promoted in the early 1990s as highly cost-effective by the World Bank, the WHO, and other international bodies. Passive case-finding of smear-positive patients was central to the strategy, and an uninterrupted drug supply was, of course, deemed necessary for cure. DOTS was clearly effective for most uncomplicated cases of drug-susceptible TB, but it was not long before a number of shortcomings were identified. First, the diagnosis of TB based solely on smear microscopy—a method dating from the late nineteenth century—is not sensitive. Many patients with pulmonary TB and all patients with exclusively extrapulmonary TB are missed by smear microscopy, as are most children with active disease. Second, passive case-finding relies on the availability of health care services, which is uneven in settings where TB is most prevalent. Third, patients with multidrug-resistant (MDR) TB are by definition infected with strains of Mycobacterium tuberculosis resistant to isoniazid and rifampin; thus exclusive reliance on these drugs is ineffective in settings in which drug resistance is an established problem.The crisis of antibiotic resistance registered in U.S. hospitals is not confined to the industrialized world or to bacterial infections. In some settings, a substantial minority of patients with TB are infected with strains resistant to at least one first-line anti-TB drug. As an effective DOTS-based response to MDR TB, global health authorities adopted DOTS-Plus, which adds the diagnostics and drugs necessary to manage drug-resistant disease. Even before DOTS-Plus could be brought to scale in resource-constrained settings, however, new strains of extensively drug-resistant (XDR) M. tuberculosis began to threaten the success of TB control programs in already-beleaguered South Africa, for example, where high rates of HIV infection have led to a doubling of TB incidence over the past decade.Tuberculosis and AIDS as Chronic Diseases: Lessons LearnedStrategies effective against MDR TB have implications for the management of drug-resistant HIV infection and even drug-resistant malaria, which, through repeated infections and a lack of effective therapy, has become a chronic disease in parts of Africa. Indeed, examining AIDS and TB together as chronic diseases allows us to draw a number of conclusions, many of them pertinent to global health in general (Fig. 2-3). First, charging fees for AIDS prevention and care will pose insurmountable problems for people living in poverty, many of whom will always be unable to pay even modest amounts for services or medications. Like efforts to battle airborne TB, such services might best be seen as a public good for public health. Initially, this approach will require sustained donor contributions, but many African countries have recently set targets for increased national investments in health—a pledge that could render ambitious programs sustainable in the long run. Meanwhile, as local investments increase, the price of AIDS care is decreasing. The development of generic medications means that ART can now cost <$0.50 (U.S.) per day, and costs continue to decrease to affordable levels for public health bodies in developing countries.Second, the effective scale-up of pilot projects will require the strengthening and sometimes rebuilding of health care systems, including those charged with delivering primary care. In the past, the lack of health care infrastructure has been cited as a barrier to providing ART in the world's poorest regions; however, AIDS resources, which are at last considerable, may be marshaled to rebuild public health systems in sub-Saharan Africa and other HIV-burdened regions—precisely the settings in which TB is resurgent.Third, a lack of trained health care personnel, most notably doctors, is invoked as a reason for the failure to treat AIDS in poor countries. The lack is real, and the "brain drain," which is discussed below, continues. However, one reason doctors leave Africa is that they lack the tools to practice their trade there. AIDS funding provides an opportunity not only to recruit physicians and nurses to underserved regions but also to train community health workers to supervise care for AIDS and many other diseases within their home villages and neighborhoods. Such training should be undertaken even in places where physicians are abundant, since community-based, closely supervised care represents the highest standard of care for chronic disease, whether in the First World or the Third.Fourth, extreme poverty makes it difficult for many patients to comply with therapy for chronic diseases, whether communicable or not. Indeed, poverty in its many dimensions is far and away the greatest barrier to the scale-up of treatment and prevention programs. It is possible to remove many of the social and economic barriers to adherence, but only with what are sometimes termed "wrap-around services": food supplements for the hungry, help with transportation to clinics, child care, and housing. In many rural regions of Africa, hunger is the major coexisting condition in patients with AIDS or TB, and these consumptive diseases cannot be treated effectively without adequate caloric intake.Finally, there is a need for a renewed basic-science commitment to the discovery and development of vaccines; of more reliable, less expensive diagnostic tools; and of new classes of therapeutic agents. This need applies not only to the three leading infectious killers—against none of which an effective vaccine exists—but also to many other neglected diseases of poverty. MalariaWe turn now to the world's third largest infectious killer, which has taken its greatest toll among children, especially African children, living in poverty.The Cost of MalariaMalaria's human toll is enormous. An estimated 250 million people suffer from malarial disease each year, and the disease annually kills between 1 million and 2.5 million people, mostly pregnant women and children under the age of 5. The poor disproportionately suffer the consequences of malaria: 58% of malaria deaths occur in the poorest 20% of the world's population, and 90% are registered in sub-Saharan Africa. The differential magnitude of this mortality burden is greater than that associated with any other disease. Likewise, the morbidity differential is greater for malaria than for diseases caused by other pathogens, as documented in a study from Zambia that revealed a 40% greater prevalence of parasitemia among children under 5 in the poorest quintile than in the richest.Despite suffering the greatest consequences of malaria, the poor are precisely those least able to access effective prevention and treatment tools. Economists describe the complex interactions between malaria and poverty from an opposite but complementary perspective: they delineate ways in which malaria arrests economic development both for individuals and for whole nations. Microeconomic analyses focusing on direct and indirect costs estimate that malaria may consume up to 10% of a household's annual income. A Ghanaian study that categorized the population by income group highlighted the regressive nature of this cost: the burden of malaria represents only 1% of a wealthy family's income but 34% of a poor household's income.At the national level, macroeconomic analyses estimate that malaria may reduce the per capita gross national product of a disease-endemic country by 50% relative to that of a nonmalarial country. The causes of this drag include high fertility rates, impaired cognitive development of children, decreased schooling, decreased saving, decreased foreign investment, and restriction of worker mobility. Given this enormous cost, it is little wonder that an important review by the economists Sachs and Malaney concludes that "where malaria prospers most, human societies have prospered least."Rolling Back MalariaIn part because of differences in vector distribution and climate, resource-rich countries offer few blueprints for malaria control and treatment that are applicable in tropical (and resource-poor) settings. In 2001, African heads of state endorsed the WHO Roll Back Malaria (RBM) campaign, which prescribes strategies appropriate for sub-Saharan African countries. RBM recommends a three-pronged strategy to reduce malaria-related morbidity and mortality: the use of insecticide-treated bed nets (ITNs), combination antimalarial therapy, and indoor residual spraying.ITNs are an efficacious and cost-effective public health intervention. A meta-analysis of controlled trials indicates that malaria incidence is reduced by 50% among persons who sleep under ITNs compared with that among those who do not use nets at all. Even untreated nets reduce malaria incidence by one-quarter. On an individual level, the utility of ITNs extends beyond protection from malaria. Several studies suggest that all-cause mortality is reduced among children under 5 to a greater degree than can be attributed to the reduction in malarial disease alone. Morbidity (specifically that due to anemia) predisposing children to diarrheal and respiratory illnesses and pregnant women to the delivery of low-birth-weight infants is also reduced in populations using ITNs. In some areas, ITNs offer a supplemental benefit by preventing transmission of lymphatic filariasis, cutaneous leishmaniasis, Chagas' disease, and tick-borne relapsing fever. At the community level, investigators suggest that the use of an ITN in just one household may reduce the number of mosquito bites in households up to several hundred meters away. The cost of ITNs per DALY saved is estimated at $10–$38 (U.S.), which qualifies ITNs as a "very efficient use of resources and [a] good candidate for public subsidy."1Some RBM programs have had limited success, but overall the burden of malarial disease has continued to grow. In fact, annual malaria-attributable mortality increased between 1999 and 2003. While the RBM campaign's own report from that year is quick to note that morbidity and mortality data-collection methods in sub-Saharan Africa are inadequate and indicators may thus lag behind actual outcomes of ongoing campaigns, they nevertheless acknowledge that "RBM is acting against a background of increasing malaria burden."Limited success in scaling-up ITN coverage reflects the inadequately acknowledged economic barriers that prevent the destitute sick from accessing critical preventive technologies. Despite proven efficacy and what are considered "reasonable costs," the 2003 RBM report reveals disappointing levels of ITN coverage. In 28 African countries surveyed, only 1.3% (range, 0.2–4.9%) of households owned at least one ITN, and <2% of children slept under an ITN. Why has the RBM campaign failed to achieve its goals? Do Africans not want to use bed nets? Do they not recognize malaria as a health risk? Or have project managers and donors miscalculated most Africans' ability to obtain bed nets?These are not rhetorical questions. The RBM strategy initially emphasized the importance of commercial markets as sources of ITNs for African populations. A precedent supporting this emphasis is the prior existence in countries such as Madagascar and Mali of local markets for untreated bed nets. Presumably, therefore, a demand for bed nets existed prior to the RBM campaign, as did a distribution system with points of sale. However, even with the application of subsidized social marketing strategies, this market approach has not resulted in large increases in coverage during the first years of the RBM campaign. Several studies have attempted to define willingness to pay (WTP) and actual payment for ITNs in African countries and thereby to determine why market-based strategies have been unsuccessful. Policy-makers often use WTP figures to determine appropriate pricing for social marketing projects and to project revenue and demand. A cross-sectional study in a rural Nigerian community administered two questionnaires, 1 month apart, to examine community members' WTP for ITNs, actual purchase of ITNs (with the second questionnaire accompanied by the opportunity to buy a subsidized ITN), and factors (such as socioeconomic status and recent history of malarial illness) contributing to hypothetical and actual ITN purchase. Among the 453 persons answering both surveys, the poorest quintile perceived a greater risk of malaria than the other quintiles (27.3% vs. 12.9–21.6%, p < .05). However, the poorest quintile was least likely to own a net, purchase a net, or express a hypothetical WTP. Even the most well-off quintile was willing to pay only 51% of the government-set price for an ITN. This finding suggests that even the relatively well-off may not be willing or able to pay for bed nets at set prices. The authors of this study concluded that reliance on the sale of nets alone may prove inadequate and that further studies are needed to define the degrees to which costs can be lowered and/or demand increased.A 2002 study in highland Kenya compared the attitudes of people living in homesteads provided with heavily subsidized ITNs (n = 190) with those of residents of households that had no ITNs and had not been targeted by other health care initiatives (n = 200). Of all households, 97% expressed willingness to pay for ITNs. However, only 4% of those willing to pay offered spontaneously to meet the suggested price of 350 Kenyan shillings. After being prompted that "nets are expensive," 26% of respondents expressed willingness to pay the full price. This study did not offer nets for sale; therefore, the number of nets that would actually have been purchased is unknown. However, the study did contextualize the hypothetical WTP for ITNs by comparing their cost with other household costs: the price of one ITN is equal to the cost of sending three children to primary school for a year. By placing the nets' relative cost in context, the authors of this study call into question the likelihood that families in this district, over half of whom fall below the Kenyan poverty line, would actually be able to purchase ITNs.Given the documented barriers to purchasing ITNs, especially among the poorest of the poor, many researchers and development professionals involved in malaria programs have called for the free distribution of ITNs, comparing their importance as a public health measure with that of childhood vaccination. The adoption of free ITN distribution strategies has been limited, however, by concerns about their feasibility and potential ITN misuse (for example, as nets for fishing). Evidence from a targeted free-distribution program discounts both concerns. In 2001, a Kenyan program sponsored by UNICEF sought to distribute 70,000 ITNs to pregnant women through antenatal clinics. Within 12 weeks, >50% of the ITNs had reached their intended recipients. A 1-year follow-up evaluation of 294 women who had received bed nets while pregnant—152 women from a high-transmission area and 142 from a low-transmission area—revealed that 84% of women in the high-transmission area used the ITNs throughout pregnancy. One year later, 77% continued to use the bed nets. In the low-transmission area, 57% of women used the ITNs during pregnancy, and 46% continued to use them a year later. These results contradict suppositions that free nets may not be used because recipients do not value them.Given the scope and magnitude of the challenge posed by malaria, it is unlikely that any one strategy will work for every region or population within a country or across the world. Encouraging results from an employer-based ITN distribution system in Kenya highlight the potential role of public-private partnerships. Potential synergies between antimalaria programs and measles vaccine campaigns or possibly lymphatic filariasis eradication campaigns have been reported or suggested. Concerns about discomfort associated with sleeping under ITNs or about insecticide toxicities must be addressed through educational campaigns.Meeting the challenge of malaria control will continue to require careful study of appropriate preventive and therapeutic strategies in the context of our increasingly sophisticated molecular understanding of the pathogen, vector, and host. However, an appreciation for the economic and structural devastation wrought by malaria—like that inflicted by diarrhea, AIDS, and TB—on the most vulnerable populations should heighten our commitment to the critical analysis of ways to implement proven strategies for the prevention and treatment of these diseases.1Nuwaha F: The challenge of chloroquine-resistant malaria in sub-Saharan Africa. Health Policy Plan 16:1, 2001.Chronic Noncommunicable DiseasesWhile the burden of communicable diseases—especially HIV infection, tuberculosis, and malaria—still accounts for the majority of deaths in resource-poor regions such as sub-Saharan Africa, close to 60% of all deaths worldwide in 2005 were due to chronic noncommunicable diseases (NCDs). Moreover, 80% of deaths attributable to NCDs occurred in low- and middle-income countries, where 85% of the global population lives. In 2005, 8.5 million people in the world died of an NCD before their 60th birthday—a figure exceeding the total number of deaths due to AIDS, TB, and malaria combined. By 2020, NCDs will account for 80% of the GBD and for 7 of every 10 deaths in developing countries. The recent rise in resources for and attention to communicable diseases is both welcome and long overdue, but developing countries are already carrying a "double burden" of communicable and noncommunicable diseases.Cardiovascular DiseaseUnlike TB, HIV infection, and malaria—diseases caused by single pathogens that damage multiple organs—cardiovascular diseases reflect injury to a single organ system downstream of a variety of insults. The burden of chronic cardiovascular disease in low-income countries represents one consequence of decades of health system neglect; furthermore, cardiovascular research and investment have long focused on the ischemic conditions that are increasingly common in high- and middle-income countries. Meanwhile, despite awareness of its health impact during the early twentieth century, cardiovascular damage in response to infection and malnutrition has fallen out of view until recently.The perception of cardiovascular diseases as a problem of elderly populations in middle- and high-income countries has contributed to their neglect by global health institutions. Even in Eastern Europe and Central Asia, where the collapse of the Soviet Union was followed by a catastrophic surge in cardiovascular disease deaths (mortality rates from ischemic heart disease nearly doubled between 1991 and 1994 in Russia, for example), the modest flows of overseas development assistance to the health sector focused on the communicable causes that accounted for <1 in 20 excess deaths during this period.Predictions of an imminent rise in the share of deaths and disabilities due to NCDs in developing countries have led to calls for preventive policies to restrict tobacco use, improve diet, and increase exercise alongside the prescription of multidrug regimens for persons with high levels of vascular risk. Although this agenda could do much to prevent pandemic NCD, it will do little to help those with established heart disease stemming from non-atherogenic pathologies.The epidemiology of heart failure reflects inequalities in risk factor prevalence and treatment. Heart failure as a consequence of pericardial, myocardial, endocardial, or valvular injury accounts for as many as 1 in 10 admissions to hospitals around the world. Countries have reported a remarkably similar burden of this condition at the health system level since the 1950s, but the causes of heart failure and the age of the people affected vary with resources and ecology. In populations with a high human-development index, coronary artery disease and hypertension among the elderly account for most cases of heart failure. Among the world's poorest billion people, however, heart failure reflects poverty-driven exposure of children and young adults to rheumatogenic strains of streptococci and cardiotropic microorganisms (e.g., HIV, Trypanosoma cruzi, enteroviruses, M. tuberculosis ), untreated high blood pressure, and nutrient deficiencies. The mechanisms of other causes of heart failure common in these populations—such as idiopathic dilated cardiomyopathy, peripartum cardiomyopathy, and endomyocardial fibrosis—remain unclear.Of the 2.3 million annual cases of pediatric rheumatic heart disease, nearly half occur in sub-Saharan Africa. This disease leads to more than 33,000 cases of endocarditis, 252,000 strokes, and 680,000 deaths per year—almost all in developing countries. Researchers in Ethiopia have reported annual death rates as high as 12.5% in rural areas. In part because the prevention of rheumatic heart disease has not advanced since the disappearance of this disease in wealthy countries, no part of sub-Saharan Africa has yet eradicated rheumatic heart disease despite examples of success in Costa Rica, Cuba, and some Caribbean nations.Strategies to eliminate rheumatic heart disease may depend on active case-finding confirmed by echocardiography among high-risk groups as well as efforts to extend access to surgical interventions among children with advanced valvular damage. Partnerships between established surgical programs and areas with limited or nonexistent facilities may help develop capacity and provide care to patients who would otherwise suffer an early and painful death. A long-term goal is the establishment of regional centers of excellence equipped to provide consistent, accessible, high-quality services.In stark contrast to the extraordinary lengths to which patients in wealthy countries will go to treat ischemic cardiomyopathy, young patients with nonischemic cardiomyopathies in resource-poor settings have received little attention. These conditions account for as many as 25–30% of admissions for heart failure in sub-Saharan Africa and include poorly understood entities such as peripartum cardiomyopathy (which has an incidence in rural Haiti of 1 per 300 live births) and HIV cardiomyopathy. Multidrug regimens that include heart failure beta-blockers, ACE inhibitors, and other neurohormonal antagonists can dramatically reduce mortality risk and improve quality of life for these patients. Lessons learned in the scale-up of chronic care for HIV infection and TB may be illustrative as progress is made in establishing means to deliver cardiac therapies over a background of careful fluid management with diuretic drugs.Because systemic investigation of the causes of stroke and heart failure in sub-Saharan Africa has begun only recently, little is known about the impact of elevated blood pressure in this portion of the continent. Modestly elevated blood pressure in the absence of tobacco use in populations with low rates of obesity may confer little risk of adverse events in the short run. In contrast, persistently elevated blood pressure above 180/110 goes largely undetected, untreated, and uncontrolled in this setting. In the Framingham cohort of men 45–74 years old, the prevalence of blood pressures above 210/120 declined from 1.8% in the 1950s to 0.1% in the 1990s with the introduction of effective antihypertensive agents. While debate continues about appropriate screening strategies and treatment thresholds, rural health centers staffed by nonphysicians must quickly gain access to essential antihypertensive medications.In 1960, Paul Dudley White and colleagues reported on the prevalence of cardiovascular disease in the region near the Albert Schweitzer Hospital in Lambaréné, Gabon. Although the group found little evidence of myocardial infarction, they concluded that "the high prevalence of mitral stenosis [sic] is astonishing. . . . We believe strongly that it is a duty to help bring to these sufferers the benefits of better penicillin prophylaxis and of cardiac surgery when indicated. The same responsibility exists for those with correctable congenital cardiovascular defects."2 Leaders from tertiary centers in sub-Saharan Africa and elsewhere have continued to call for prevention and treatment of the cardiovascular conditions of the poor. The reconstruction of health services in response to pandemic infectious disease offers an opportunity to identify and treat patients with organ damage and to undertake the prevention of cardiovascular and other chronic conditions of poverty. 2Miller DC et al: Survey of cardiovascular disease among Africans in the vicinity of the Albert Schweitzer Hospital in 1960. Am J Cardiol 19:432, 1962. CancerLow- and middle-income countries accounted for 53% and 56%, respectively, of the 10 million cases and 7 million deaths due to cancer in 2000. By 2020, the total number of new cancer cases will rise by 29% in developed countries and by 73% in developing countries. Also by 2020, overall mortality from cancer will increase by 104%, and the increase will be fivefold higher in developing than in developed countries. "Western" lifestyle changes will be responsible for the increased incidence of cancers of the breast, colon, and prostate, but historic realities, sociocultural and behavioral factors, genetics, and poverty itself will also have a profound impact on cancer-related mortality and morbidity. While infectious causes are responsible for <10% of cancers in developed countries, they account for 25% of all malignancies in low- and middle-income countries. Infectious causes of cancer such as human papillomavirus (cervical cancer), hepatitis B virus (liver cancer), and Helicobacter pylori (stomach cancer) will continue to have a much larger impact in developing countries. Environmental and dietary factors, such as indoor air pollution and high-salt diets, also help account for increased rates of certain cancers (e.g., lung and stomach cancers). Tobacco use (both smoking and chewing) is the most important source of increased mortality from lung and oral cancers. In contrast to decreasing tobacco use in many developed countries, the number of smokers is growing in developing countries, especially among women and young people. For many reasons, outcomes of malignancies are far worse in developing countries than in developed nations. Overstretched health systems in poor countries simply are not capable of early detection; 80% of patients already have incurable malignancies at diagnosis. Treatment of cancers is available for only a very small number of mostly wealthy citizens in the majority of poor countries, and, even when treatment is available, the range and quality of services are often substandard. DiabetesThe International Diabetes Federation reports that the number of diabetics in the world is expected to increase from 194 million in 2003 to 330 million by 2030, when 3 of every 4 sufferers will live in developing countries. Because diabetics are far more frequently under the age of 65 in developing nations, the complications of micro- and macrovascular disease take a far greater toll. In 2005, an estimated 1.1 million people died of diabetes-related illnesses, and >80% of these deaths occurred in low- and middle-income countries. Obesity and Tobacco UseIn 2004, the WHO released its Global Strategy on Diet, Physical Activity and Health, which focused on the population-wide promotion of healthy diet and regular physical activity in an effort to reduce the growing global problem of overweight and obesity. Passing this strategy at the World Health Assembly proved difficult because of strong opposition from the food industry and from a number of WHO member states, including the United States. While globalization has had many positive effects, one negative aspect has been the growth in both developed and developing countries of well-financed lobbies that have aggressively promoted unhealthy dietary changes and increased consumption of alcohol and tobacco. Foreign direct investment in tobacco, beverage, and food products in developing countries reached $327 million in 2002—a figure nearly five times greater than the amount spent during that year to address NCDs by bilateral funding agencies, the WHO, and the World Bank combined.The Three Pillars of PreventionThe WHO estimates that 80% of all cases of cardiovascular disease and type 2 diabetes as well as 40% of all cancers can be prevented through the three pillars of healthy diet, physical activity, and avoidance of tobacco. While there is some evidence that population-based measures can have some impact on these behaviors, it is sobering to note that increasing obesity levels have not been successfully reversed in any population, including those of high-income countries with robust diet industries. Nonetheless, in Mauritius, for example, a single policy measure that changed the type of cooking oil available to the population led to a fall in mean serum cholesterol levels. Tobacco avoidance may be the most important and most difficult behavioral modification of all. In the twentieth century, 100 million people died worldwide of tobacco-related diseases; it is projected that >1 billion people will die of these diseases in the twenty-first century, with the vast majority of these deaths in developing countries. Today, 80% of the world's 1.2 billion smokers live in low- and middle-income countries, and, while tobacco consumption is falling in most developed countries, it continues to rise at a rate of ~3.4% per year in developing countries. The WHO's Framework Convention on Tobacco Control was a major advance, committing all of its signatories to a set of policy measures that have been shown to reduce tobacco consumption. However, most developing countries have continued to take a passive approach to the control of smoking. Environmental HealthIn a recent publication that examined how specific diseases and injuries are affected by environmental risk, the WHO determined that ~24% of the total GBD, one-third of the GBD among children, and 23% of all deaths are due to modifiable environmental factors. Many of these factors lead to deaths from infectious diseases; others lead to deaths from malignancies. Increasingly, etiology and nosology are difficult to parse. As much as 94% of diarrheal disease, which is linked to unsafe drinking water and poor sanitation, can be attributed to environmental factors. Risk factors such as indoor air pollution due to use of solid fuels, exposure to second-hand tobacco smoke, and outdoor air pollution account for 20% of lower respiratory infections in developed countries and for as many as 42% of such infections in developing countries. Various forms of unintentional injury and malaria top the list of health problems to which environmental factors contribute. Some 4 million children die every year from causes related to unhealthy environments, and the number of infant deaths due to environmental factors in developing countries is 12 times that in developed countries.Mental HealthThe WHO reports that some 450 million people worldwide are affected by mental, neurologic, or behavioral problems at any given time and that ~873,000 people die by suicide every year. Major depression is the leading cause of lost DALYs in the world today. One in four patients visiting a health service has at least one mental, neurologic, or behavioral disorder, but most of these disorders are neither diagnosed nor treated. Most low- and middle-income countries devote <1% of their already-paltry health expenditures to mental health.Increasingly effective therapies exist for many of the major causes of mental disorder. Effective treatments for many neurologic diseases, including seizure disorders, have long been available. One of the greatest barriers to delivery of such therapies is the paucity of skilled personnel. Most sub-Saharan African countries have only a handful of psychiatrists, for example; most of them practice in cities and are unavailable within the public sector or to patients living in poverty. Of the few patients who are fortunate enough to see a psychiatrist or neurologist, fewer still are able to adhere to treatment regimens: several surveys of already-diagnosed patients ostensibly receiving daily therapy have revealed that, among the poor, few can take their medications as prescribed. The same barriers that prevent the poor from having reliable access to insulin or ART also prevent them from benefiting from antidepressant, antipsychotic, and antiepileptic agents. To alleviate this problem, some authorities are proposing the training of health workers to provide community-based adherence support, counseling services, and referrals for patients in need of mental health services.World Mental Health: Problems and Priorities in Low-Income Countries offers a comprehensive analysis of the burden of mental, behavioral, and social problems in low-income countries and relates the mental health consequences of social forces such as violence, dislocation, poverty, and the disenfranchisement of women to current economic, political, and environmental concerns.Health Systems and the "Brain Drain"A significant and oft-invoked barrier to effective health care in resource-poor settings is the lack of medical personnel. In what is termed the brain drain, many physicians and nurses emigrate from their home countries to pursue opportunities abroad, leaving behind health systems that are understaffed and ill-equipped to deal with the epidemic diseases that ravage local populations. The WHO recommends a minimum of 20 physicians and 100 nurses per 100,000 persons, but recent reports from that organization and others confirm that many countries, especially in sub-Saharan Africa, fall far short of those target numbers. More than half of these countries register fewer than 10 physicians per 100,000 population. In contrast, the United States and Cuba register 279 and 596 doctors per 100,000 population, respectively. Similarly, the majority of sub-Saharan African countries do not have even half of the WHO-recommended minimum number of nurses. In addition to these appalling national aggregates, further inequalities in health care staffing exist within countries. Rural-urban disparities in health care personnel mirror disparities of both wealth and health. In 1992, the poorest districts in southern Africa reported 5.5 doctors, 188.1 nurses, and 0.5 pharmacists per 100,000 population. The same survey found, in the richest districts, 35.6 doctors, 375.3 nurses, and 5.4 pharmacists per 100,000 population. Nearly 90% of Malawi's population is rural, but >95% of clinical officers were at urban facilities, and 47% of nurses were at tertiary care facilities. Even community health workers, trained to provide first-line services to rural populations, often transfer to urban districts. In 1989 in Kenya, for example, there were only 138 health workers per 100,000 persons in the rural North Eastern Province, whereas there were 688 per 100,000 in Nairobi.In addition to inter- and intranational transfer of personnel, the AIDS epidemic contributes to personnel shortages across Africa. Although data on the prevalence of HIV infection among health professionals are scarce, the available numbers suggest substantial and adverse impacts on an already-overburdened health sector. In 1999, it was estimated that 17–32% of health care workers in Botswana had HIV disease, and this number is expected to increase in the coming years. A recent study that examined the fates of a small cohort of Ugandan physicians found that at least 22 of the 77 doctors who graduated from Makerere University Medical School in 1984 had died by 2004—most, presumably, of AIDS. Similar numbers have been registered in South Africa, where a small study by the Human Sciences Research Council found an HIV seroprevalence among health professionals similar to that among the general population—in this case, 15.7% of all health care workers surveyed. The shortage of medical personnel in the areas hardest hit by HIV has profound implications for prevention and treatment efforts in these regions. The cycle of health-sector impoverishment, brain drain, and lack of personnel to fill positions when they are available conspires against ambitious programs to bring ART to persons living with both AIDS and poverty. The president of Botswana recently declared that one of his country's main obstacles to rapid expansion of HIV/AIDS treatment is "a dearth of doctors, nurses, pharmacists, and other health workers."3 In South Africa, the departure of nearly 600 pharmacists in 2001, coupled with standing vacancies for 32,000 nurses, has put continued strain on that relatively affluent country's ability to respond to calls for expanded treatment programs. In Malawi, only 28% of established nursing posts are filled. Furthermore, the education of medical trainees is jeopardized as the ranks of the health and academic communities continue to shrink as a result of migration or disease. The long-term implications are sobering.A proper biosocial analysis of the brain drain reminds us that the flight of health personnel—almost always, as most reviews suggest, from poor to less-poor regions—is not simply a question of desire for more equitable remuneration. Epidemiologic trends and access to the tools of the trade are also relevant, as are working conditions in general. In many settings now losing skilled health personnel, the advent of HIV has led to a sharp rise in TB incidence; in the eyes of health care providers, other opportunistic infections have also become insuperable challenges. Together, these forces have conspired to render the provision of proper care impossible, as the comments of a Kenyan medical resident suggest: "Regarding HIV/AIDS, it is impossible to go home and forget about it. Even the simplest opportunistic infections we have no drugs for. Even if we do, there is only enough for a short course. It is impossible to forget about it. . . . Just because of the numbers, I am afraid of going to the floors. It is a nightmare thinking of going to see the patients. You are afraid of the risk of infection, diarrhea, urine, vomit, blood. . . . It is frightening to think about returning."4 Another resident noted, "Before training we thought of doctors as supermen. . . . [Now] we are only mortuary attendants."5 Nurses and other providers are, of course, similarly affected.Given the difficult conditions under which these health care personnel work, is it any surprise when the U.S. government's appointed Global AIDS Coordinator notes that there are more Ethiopian physicians practicing in Chicago than in all of Ethiopia? In Zambia, only 50 of the 600 doctors trained since the country's independence in 1964 remain in their home country. Nor is it surprising that a 1999 survey of medical students in Ghana in their final year of training revealed that 40 of 43 students planned to leave the country upon graduation. When providing care for the sick becomes a nightmare for those at the beginning of clinical training, physician burn-out soon follows among those who carry on in settings of impoverishment. In the public-sector institutions put in place to care for the poorest people, the confluence of epidemic disease, lack of resources with which to respond, and unrealistically high user fees has led to widespread burn-out among health workers. Patients and their families are those who pay most dearly for provider burn-out, just as they bear the burden of disease and—with the introduction of user fees—much of the cost of responding, however inadequately, to new epidemics and persistent plagues.3Dugger C: Botswana's brain drain cripples war on AIDS. New York Times A10 (13 November 2003).4Raviola G et al: HIV, disease plague, demoralization, and "burnout": Resident experience of the medical profession in Nairobi, Kenya. Cult Med Psychiatry 26:55, 2002.5Ibid.Conclusion: Toward a Science of ImplementationPublic-health strategies draw largely on quantitative methods—from epidemiology and biostatistics, but also from economics. Clinical practice, including internal medicine, draws on a rapidly expanding knowledge base but remains focused on individual patient care; clinical interventions are rarely population-based. In fact, neither public-health nor clinical approaches alone will prove adequate in addressing the problems of global health. There is a long way to go before evidence-based internal medicine is applied effectively among the world's poor. Complex infectious diseases such as AIDS and TB have proven difficult but not impossible to manage; drug resistance and a lack of effective health systems have further complicated such work. Beyond communicable disease, in the arena of chronic diseases (e.g., cardiovascular disease), global health is a nascent endeavor. Efforts to address any one of these problems in settings of great scarcity need to be integrated into broader efforts to strengthen failing health systems and to alleviate the growing personnel crisis within these systems.For these reasons, scholarly work and practice in the field once known as international health and now often designated global health equity are changing rapidly. Such work is still informed by the tension between clinical practice and population-based interventions, between analysis and action. Once metrics are refined, how might they inform efforts to lessen the premature morbidity and mortality registered among the world's poor? As in the nineteenth century, human rights perspectives have proven helpful in turning attention to the problems of the destitute sick; such perspectives may also inform strategies of delivering care equitably. A number of university hospitals are developing training programs for physicians with interests in global health. In medical schools across the United States and in other wealthy countries, interest in global health has been exploding. An informal survey at Harvard Medical School in 2006 revealed that nearly one-quarter of the 160 entering students either had significant global health experience or were planning a career in global health. A similar sea-change among trainees has been reported at other medical schools. Half a century or even a decade ago, such high levels of interest would have been unimaginable.Persistent epidemics, improved metrics, and growing interest have only recently been matched by an unprecedented investment in addressing the health problems of poor people in the developing world. Ours is a moment of opportunity. To ensure that the opportunity is not wasted, the basic facts need to be laid out for specialists and laypeople alike. More than 12 million people die each year simply because they live in poverty. An absolute majority of these premature deaths occur in Africa, with the poorer regions of Asia not far behind. Most of these deaths occur because the world's poorest do not have access to the fruits of science. They include deaths from vaccine-preventable illness; deaths during childbirth; deaths from infectious diseases that might be cured with access to antibiotics and other essential medicines; deaths from malaria that would have been prevented by bed nets and access to therapy; and deaths from water-borne illnesses. Other excess mortality is attributable to the inadequacy of efforts to develop new tools. Those funding the discovery and development of new tools typically neglect the concurrent need for strategies to make them available to the poor. Indeed, some would argue that the biggest challenge facing those who seek to address this outcome gap is the lack of practical means of distribution in the regions most heavily affected.The development of tools must be followed in short order by their equitable distribution. When new preventive and therapeutic tools are developed without concurrent attention to delivery or implementation, we face what are sometimes termed perverse effects: even as new tools are developed, inequalities of outcome—less morbidity and mortality among those who can afford access, with sustained high morbidity and mortality among those who cannot—will grow in the absence of an equity plan to deliver the tools to those most at risk. Preventing such a future is the most important goal of global health.Further Readings

Cohen J: The new world of global health. Science 311:162, 2006 [PMID: 16410496]
Desjarlais R et al (eds): World Mental Health: Problems and Priorities in Low-Income Countries. New York, Oxford University Press, 1995
Farmer PE: Infections and Inequalities: The Modern Plagues, 2d ed. Berkeley, University of California Press, 2001
———: From "marvelous momentum" to healthcare for all. Response to Garrett L: The challenge of global health. Foreign Affairs 86:155, 2007 
Fauci AS et al: Emerging infectious diseases: A 10-year perspective from the National Institute of Allergy and Infectious Diseases. Emerg Infect Dis 11:519, 2005 [PMID: 15829188]
Garrett L: The challenge of global health. Foreign Affairs 86:14, 2007 
Hotez PJ et al: Neglected tropical diseases and HIV/AIDS. Lancet 368:1865, 2006 [PMID: 17126708]
Jamison DT et al (eds): Disease Control Priorities in Developing Countries, 2d ed. Washington, DC, Oxford University Press and The World Bank, 2006
Kim JY et al (eds): Dying for Growth: Global Inequality and the Health of the Poor. Monroe, ME, Common Courage Press, 2000
Lopez AD et al: Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet 367:1747, 2006 [PMID: 16731270]
Murray CJL, Lopez AD (eds): The global burden of disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge, MA, Harvard University Press, 1996 
Sachs J, Malaney O: The economic and social burden of malaria. Nature 415:680, 2002 [PMID: 11832956]
World Bank: World Development Report 1993: Investing in Health. New York, Oxford University Press, 1993
World Health Organization: Macroeconomics and Health: Investing in Health for Economic Development. Geneva, Commission on Macroeconomics and Health, 2001
———: World Health Report 2006: Working Together for Health. Geneva, World Health Organization, 2006

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