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Why Global Health? Global health, it has been noted, is not a discipline; it is, rather, a collection of problems. A leading group of scholars have defined global health as the study and practice concerned with improving the health of all people and achieving health equity worldwide, with an emphasis on addressing problems that are transnational. No single review can do much more than identify the leading problems in applying evidence-based medicine in settings of great poverty or across national boundaries. This chapter introduces the major international bodies that address these problems; identifies the more significant barriers to improving the health of people who to date have not, by and large, had access to modern medicines; and summarizes population-based data on the most common health problems faced by people living in poverty. Examining specific problems—notably AIDS (Chap. 189) but also tuberculosis (TB, Chap. 165), malaria (Chap. 210), and key noncommunicable diseases—helps sharpen the discussion of barriers to prevention, diagnosis, and care as well as the means of overcoming them. The chapter then discusses the role of health systems and the problem of “brain drain” on those systems. It closes by discussing 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 last several decades. Brief History of Global Health Institutions Concern about health across national boundaries dates back many centuries, predating the Black Plague and other pandemics. 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 later became 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. In 1948, the United Nations formed the first truly global health institution: the World Health Organization (WHO). In 1958, under the aegis of the WHO and in line with a long-standing focus on communicable diseases that cross borders, leaders in global health initiated the effort that led to what some see as the greatest success in international health: the eradication of smallpox. Naysayers were surprised when the smallpox eradication campaign, which engaged public health officials throughout the world, proved successful in 1979 during the Cold War. 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 those nations to reduce public expenditures in health and education as part of later discredited structural adjustment programs that were imposed as a condition for access to credit and assistance through international financial institutions such as the World Bank and the International Monetary Fund (IMF). At the same time, there was a resurgence of many diseases, including malaria, trypanosomiasis, are schistosomiasis, in Africa.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 talk of “closing the book” on infectious diseases. In Africa, which would emerge as the global epicenter of the pandemic, HIV disease strained TB control programs, and 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. The last decade has seen the rise of important multilateral global health institutions such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM) and the Joint United Nations Programme on HIV/AIDS (UNAIDS); bilateral efforts such as the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR); and private philanthropic organizations such as the Bill & Melinda Gates Foundation. Yet with its 193 member states and 147 country offices, the WHO remains preeminent in matters relating to the cross-border spread of infectious diseases and other health threats. In the aftermath of the severe acute respiratory syndrome (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 poor countries grow, the lack of coherence in and among global health institutions may undermine efforts to forge a more comprehensive and effective response. The WHO 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, which is 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. This indeed may be what some have called “the golden age of global health,” but leaders of major organizations such as the WHO, the GFATM, the United Nations Children’s Fund (UNICEF), UNAIDS, PEPFAR, and the Gates Foundation must work together to design an effective architecture that will make the most of the opportunities that now exist. To this end, new and old players in global health must invest heavily in discovery (relevant basic science), the development of new tools (preventive, diagnostic, and therapeutic), and delivery to ensure the equitable provision of health products and services to all who need them. The Economics of Global Health Political and economic concerns have often guided global health interventions. As mentioned, 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 improving the health status of populations must begin with economic development; others maintain that addressing ill health is the starting point for development in poor countries. In either case, investment in health care, especially 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.” 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 over $80 billion in new funds earmarked for the discovery and development of drugs and diagnostics targeting diseases of the poor; comprehensive responses to the AIDS, TB, and malaria epidemics; vaccine development and delivery; and even improved methods of data collection in resource-poor settings. Nevertheless, to reach the United Nations Millennium Development Goals, that include targets for poverty reduction, universal primary education, and gender equality, spending in the health sector must be increased further. To determine by how much and for how long, it is imperative to improve the ability to assess the global burden of disease (GBD) and plan interventions that more precisely match the need. Refining metrics is an important task for global health: only recently have there been solid assessments of the GBD. Mortality and the Global Burden of Disease Since 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 Investing in Health. Those efforts represented a major advance in the 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. (See Fig. 2-1 and Table 2-1 for an analysis of the GBD by DALYs.) Burden of disease, by broad cause and region, 2004. Table 2-1 Leading Causes of Burden of Disease (DALYs), with Countries Grouped by Income, 2004 Disease or Injury DALYs (millions) Percent of total DALYs Disease or Injury DALYs (millions) Percent of total DALYs World Middle-income countries 1 Lower respiratory infections 94.5 6.2 1 Unipolar depressive disorders 29.0 5.1 2 Diarrheal diseases 72.8 4.8 2 Ischemic heart disease 28.9 5.0 3 Unipolar depressive disorders 65.5 4.3 3 Cerebrovascular disease 27.5 4.8 4 Ischemic heart disease 62.6 4.1 4 Road traffic accidents 21.4 3.7 5 HIV/AIDS 58.5 3.8 5 Lower respiratory infections 16.3 2.8 6 Cerebrovascular disease 46.6 3.1 6 COPD 16.1 2.8 7 Prematurity and low birth weight 44.3 2.9 7 HIV/AIDS 15.0 2.6 8 Birth asphyxia and birth trauma 41.7 2.7 8 Alcohol use disorders 14.9 2.6 9 Road traffic accidents 41.2 2.7 9 Refractive errors 13.7 2.4 10 Neonatal infections and otherb 40.4 2.7 10 Diarrheal diseases 13.1 2.3 High-income countries Low-income countriesa 1 Unipolar depressive disorders 10.0 8.2 1 Lower respiratory infections 76.9 9.3 2 Ischemic heart disease 7.7 6.3 2 Diarrheal diseases 59.2 7.2 3 Cerebrovascular disease 4.8 3.9 3 HIV/AIDS 42.9 5.2 4 Alzheimer’s and other dementias 4.4 3.6 4 Malaria 32.8 4.0 5 Alcohol use disorders 4.2 3.4 5 Prematurity and low birth weight 32.1 3.9 6 Hearing loss, adult onset 4.2 3.4 6 Neonatal infections and otherb 31.4 3.8 7 COPD 3.7 3.0 7 Birth asphyxia and birth trauma 29.8 3.6 8 Diabetes mellitus 3.6 3.0 8 Unipolar depressive disorders 26.5 3.2 9 Trachea, bronchus, lung cancers 3.6 3.0 9 Ischemic heart disease 26.0 3.1 10 Road traffic accidents 3.1 2.6 10 Tuberculosis 22.4 2.7 aCountries grouped by gross national income per capita. bThis category also includes other noninfectious causes arising in the perinatal period apart from prematurity, low birth weight, birth trauma, and asphyxia. These noninfectious causes are responsible for about 20% of the DALYs shown in this category. Abbreviation: COPD, chronic obstructive pulmonary disease The most recent WHO analysis of the GBD was based on health data from 2004. This report reflects growth in the available data on health in the poorest countries and in the capacity to measure the impact of specific conditions on a population. Yet even in 2004, only 112 of 192 nations surveyed had reliable information on the causes of deaths within their 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 rates. The level of uncertainty ranges from as low as ± 1% for estimates of all-cause mortality in developed countries to ± 20% for all-cause mortality in the WHO’s African Region. The level of uncertainty in regional prevalence estimates ranges from ± 10% to ± 90%, with a median value of ± 41%. As analytic methods and data quality have improved, however, important trends can be identified in a comparison of GBD estimates from 1990 and 2004. Of the 58.8 million deaths worldwide in 2004, 30% were due to communicable diseases, maternal and perinatal conditions, and nutritional deficiencies. Although the proportion of all deaths attributable to these causes has decreased marginally since 1990, the share of all deaths due to HIV/AIDS grew from just 2% to >3.5%. Among the fraction of all deaths related to communicable diseases, maternal and perinatal conditions, and nutritional deficiencies, 97% occurred in middle- and low-income countries. The leading cause of death among adults in 2004 was ischemic heart disease, accounting for 16.3% of all deaths in high-income countries, 13.9% in middle-income countries, and 9.4% in low-income countries (Table 2-2). In second place was cerebrovascular disease, that accounted for 9.3% of deaths in high-income countries, 14.2% in middle-income countries, and 5.6% in low-income countries. Although the third leading cause of death in high-income countries was tracheal, bronchial, and lung cancers (that accounted for 5.9% of all deaths), those conditions did not even register in the top 10 places in low-income countries. Among the 10 leading causes of death in low-income countries, 6 were communicable diseases; in high-income countries, however, only one communicable disease—lower respiratory infection—ranked among the top 10 causes of death. Table 2-2 Leading Causes of Death Worldwide, by Income Group, 2004 Disease or Injury Deaths (millions) Percent of Total Deaths Disease or Injury Deaths (millions) Percent of Total Deaths World Middle-income countries 1 Ischemic heart disease 7.2 12.2 1 Cerebrovascular disease 3.5 14.2 2 Cerebrovascular disease 5.7 9.7 2 Ischemic heart disease 3.4 13.9 3 Lower respiratory infections 4.2 7.1 3 COPD 1.8 7.4 4 COPD 3.0 5.1 4 Lower respiratory infections 0.9 3.8 5 Diarrheal diseases 2.2 3.7 5 Trachea, bronchus, lung cancers 0.7 2.9 6 HIV/AIDS 2.0 3.5 6 Road traffic accidents 0.7 2.8 7 Tuberculosis 1.5 2.5 7 Hypertensive heart disease 0.6 2.5 8 Trachea, bronchus, lung cancers 1.3 2.3 8 Stomach cancer 0.5 2.2 9 Road traffic accidents 1.3 2.2 9 Tuberculosis 0.5 2.2 10 Prematurity and low birth weight 1.2 2.0 10 Diabetes mellitus 0.5 2.1 High-income countries Low-income countriesa 1 Ischemic heart disease 1.3 16.3 1 Lower respiratory infections 2.9 11.2 2 Cerebrovascular disease 0.8 9.3 2 Ischemic heart disease 2.5 9.4 3 Trachea, bronchus, lung cancers 0.5 5.9 3 Diarrheal diseases 1.8 6.9 4 Lower respiratory infections 0.3 3.8 4 HIV/AIDS 1.5 5.7 5 COPD 0.3 3.5 5 Cerebrovascular disease 1.5 5.6 6 Alzheimer’s and other dementias 0.3 3.4 6 COPD 0.9 3.6 7 Colon and rectum cancers 0.3 3.3 7 Tuberculosis 0.9 3.5 8 Diabetes mellitus 0.2 2.8 8 Neonatal infectionsb 0.9 3.4 9 Breast cancer 0.2 2.0 9 Malaria 0.9 3.3 10 Stomach cancer 0.1 1.8 10 Prematurity and low birth weight 0.8 3.2 aCountries grouped by gross national income per capita: low income ($825 or less), high income ($10,066 or more). Note that these high-income groups differ slightly from those used in the Disease Control Priorities Project. bThis category also includes other noninfectious causes arising in the perinatal period, that are responsible for about 20% of the deaths shown in this category. Abbreviation: COPD, chronic obstructive pulmonary disease. A recent study found that the worldwide mortality figure among children <5 years of age dropped from 11.9 million deaths in 1990 to 7.7 2010. Of the 2010, 3.1 (40%) occurred neonatal period. About one-third these among children <5 old southern Asia and almost one-half sub-Saharan Africa; <1% high-income countries. Among persons 15–59 age, noncommunicable diseases accounted for more than all regions except Africa, where communicable diseases, maternal perinatal conditions, nutritional deficiencies together two-thirds deaths. Indeed, HIVmortality rate 15- 59-year-olds Africa was higher mortality due causes adults countries. In this group, injuries 23% worldwide. Overall, death rates group declined between 2004 areas Europe Central Asia, cardiovascular caused increased rates, impact HIV AIDS cohort particularly devastating. There is greater uncertainty calculating life lived with disability specific conditions lost. Best estimates reveal that although prevalence common older populations (e.g., dementia musculoskeletal disease) countries, experienced as a result chronic respiratory long-term low- middle-income most people shorter lives poor health proportion their lives.>50% of the GBD occurred in southern Asia and sub-Saharan Africa, which together account for only one-third of the world’s population. Noncommunicable diseases accounted for almost 60% of all deaths in 2004 but, because of the later onset of those diseases, accounted for only 48% of years of life lost. In contrast, because they more often involve younger people, injuries accounted for 12% of years of life lost but for only 10% of deaths. Notably, 45% of the disease burden in middle-income countries in 2004 resulted from noncommunicable conditions; in 1990, the figure was 35%. Poverty remains one of the most important root causes of poor health worldwide, and the global burden of poverty continues to be high. Among the 6.8 billion people alive today, 43% (~2.7 billion) live on <$2 per day and 17% (~1.1 billion) live on <$1 per day. Comparison of national health indicators with gross domestic product per capita among nations shows a clear relationship between higher gross domestic product and better health, with only a few outliers. Numerous studies also have documented the link between poverty and health within countries. The Global Burden of Disease Study found that undernutrition was the leading risk factor for poor health. In an era that has seen obesity become a major health concern in many developed countries, the persistence of undernutrition is surely cause for great consternation. Inability to feed the hungry provides evidence of 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 second edition of Disease Control Priorities in Developing Countries (DCP2), published in 2006, 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, it is instructive to look to AIDS, that in the course of the last three decades has become the world’s leading infectious cause of adult death. AIDS Chapter 189 provides an overview of the AIDSepidemic in the world today. Here the discussion will be limited to 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. Several of these lessons are highlighted 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 fall of 2008 did the number of patients receiving treatment exceed 40% of the number who 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 with 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 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 that is 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 prices of AIDS drugs have fallen significantly. At the same time, fixed-dose combination drugs that are easier to administer 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, 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 far more expensive) set of second-line options in reserve. Common clinical protocols were standardized, and intensive training packages for health and community health workers were developed and implemented in many countries. Those efforts were supported by new funding from the World Bank, the GFATM, and PEPFAR. In 2003, the lack of access to ART was declared a global public health emergency by the WHO and UNAIDS, and those two agencies launched the “3 by 5 initiative,” setting an ambitious target: to have 3 million people in developing countries in 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 efficacy of ART is well documented: in the United States, such therapy has prolonged life by an estimated average of 13 years per patient—a better success rate than that obtained with almost any treatment for cancer or for complications of coronary artery disease. Further lessons with implications for policy and action have come from efforts now underway in the developing world. During the last 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. Tuberculosis Chapter 165 provides 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 one-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 a number of shortcomings soon 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, that is uneven in the settings where TB is most prevalent. Third, patients with multidrug-resistant TB (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, that 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 last decade. Tuberculosis and AIDS as Chronic Diseases: Lessons Learned Strategies 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 makes it possible to draw a number of conclusions, many of them pertinent to global health in general (Fig. 2-2). An HIV/TB co-infected patient in Rwanda, before (above) and after (below) 6 months of treatment. 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 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 <$0.25 per day, and costs continue to decrease to affordable levels in developing countries. Second, the effective scale-up of pilot projects will require strengthening and sometimes rebuilding 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 (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 strengthen health systems by building infrastructure, providing diagnostic and therapeutic resources, and training community health workers to supervise care for AIDS and many other diseases within their communities. 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 sometimes are 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 those 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; more reliable, less expensive diagnostic tools; and new classes of therapeutic agents. This need applies not only to the three leading infectious killers—against none of which is there an effective vaccine—but also to many other neglected diseases of poverty. Malaria Chapter 210 reviews the etiology, pathogenesis, and clinical treatment of malaria, the world’s third-ranking infectious killer. Malaria’s human cost is enormous, with the greatest toll among children, especially African children, living in poverty. An estimated 250 million people have malarial disease each year, and the disease annually kills 1 million people, mostly children under age 5. The poor disproportionately experience 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 age 5 in the poorest quintile than in the richest. Despite experiencing the greatest consequences of malaria, the poor are 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. In light of 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 Malaria In 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. In 2008, the RBM partnership launched the Global Malaria Action Plan (GMAP). This global strategy has set out a coordinated approach to control and eliminate the disease and to ensure that gains in one nation are not lost because of failed control measures in neighboring countries. The GMAP recommends a number of key tools to reduce malaria-related morbidity and mortality rates: the use of insecticide-treated bed nets (ITNs), indoor residual spraying (IRS), and artemisinin-based combination therapy (ACT) as well as intermittent preventive treatment during pregnancy, prompt diagnosis, and other vector control measures such as larviciding and environmental management. Insecticide-Treated Bed Nets 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 the incidence 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 age 5 to a greater degree than can be attributed to the reduction in malarial disease alone. Morbidity (specifically that due to anemia), which predisposes 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, which qualifies ITNs as a “very efficient use of resources and [a] good candidate for public subsidy.” The WHO recommends that all individuals living in malaria-endemic areas sleep under protective ITNs. About 140 million long-lasting ITNs were distributed in high-burden African countries in 2006–2008, and rates of household ownership of ITNs in high-burden countries increased to 31%. Although the RBM partnership has seen modest success, the WHO’s 2009 World Malaria Report states that the percentage of children <5 years of age using an ITN (24%) remains well below the World Health Assembly’s target 80%. Limited success in scaling up coverage reflects inadequately acknowledged economic barriers that prevent destitute sick from accessing critical preventive technologies and challenges designing implementing effective delivery platforms for these products. Indoor Residual Spraying IRS is one most common interventions preventing transmission malaria endemic areas. Vector control insecticides approved by WHO, including DDT, can effectively reduce or even interrupt transmission. However, studies have indicated spraying controlling only if (~80%) structures targeted community are treated. Moreover, since a successful program dependent on well-trained teams as monitoring planning, IRS difficult to employ often reliant health systems with strong infrastructure renders approach feasible. Regardless limitations IRS, WHO recommends its use combination ITNs. Neither intervention alone sufficient entirely. Artemisinin-Based Combination Therapy The emergence spread chloroquine resistance increased necessity antimalarial therapy. To limit resistance, now ACT uncomplicated falciparum malaria. Like other interventions, has last few years, but very low several countries sub-Saharan Africa. In 2007–2008 study, fewer than 15% children under 5 fever were receiving 11 13 surveyed, although response, RBM partnership focused significant investment enhancing access facilitating through public-health sector developing innovative funding mechanisms (e.g., Affordable Medicines Facility—malaria) which consumer prices be reduced significantly ineffective artemisinin monotherapies eliminated market. In medicines become larger problem. 2009, confirmation was reported. Although called end monotherapy, marketing such therapies continues many countries. Ongoing monotherapy increases likelihood drug deadly prospect will make far more treat. Meeting challenge continue require careful study appropriate therapeutic strategies context increasingly sophisticated molecular understanding pathogen, vector, host. appreciation structural devastation wrought malaria—like inflicted diarrhea, AIDS, TB—on vulnerable populations should heighten commitment analysis ways implement proven prevention treatment diseases. Noncommunicable Chronic Diseases Although burden communicable diseases—especially HIV infection, tuberculosis, malaria—still accounts majority deaths resource-poor regions Africa, 60% all worldwide 2004 due noncommunicable chronic diseases (NCDs). 80% attributable NCDs occurred low- middle-income countries, where 86% global population lives. 2005, 8.5 million people world died NCD before their 60th birthday, figure exceeding total number TB, combined. By 2020, account GBD 7 out every 10 The recent rise resources attention both welcome long overdue, already carrying “double burden” diseases. Cardiovascular Disease Unlike malaria—diseases caused single pathogens damage multiple organs—cardiovascular reflect injury organ system downstream variety insults. cardiovascular disease low-income represents consequence decades neglect; furthermore, research ischemic conditions high- Meanwhile, despite awareness impact during early twentieth century, response infection malnutrition fallen view until recently. The perception problem elderly middle- high-income contributed neglect institutions. Even Eastern Europe Central Asia, collapse Soviet Union followed catastrophic surge (mortality rates heart nearly doubled between 1991 1994 Russia, example), modest flow overseas development assistance causes accounted <1 20 excess period. Predictions imminent share disabilities led calls policies restrict tobacco use, improve diet, increase exercise along prescription multidrug regimens persons high levels vascular risk. this agenda could do much pandemic NCD, it little help those established stemming nonatherogenic pathologies. The epidemiology failure inequalities risk factorprevalence treatment. Heart pericardial, myocardial, endocardial, valvular 1 admissions hospitals around world. Countries reported remarkably similar condition at level 1950s, affected vary ecology. human-development index, coronary artery hypertension among cases failure. Among world’s poorest billion people, however, poverty-driven exposure young adults rheumatogenic strains streptococci cardiotropic microorganisms HIV, Trypanosoma cruzi, enteroviruses, M. tuberculosis), untreated blood pressure, nutrient deficiencies. populations—such idiopathic dilated cardiomyopathy, peripartum endomyocardial fibrosis—remain unclear. Among 2.4 annual pediatric rheumatic disease, 40% occur This leads 33,000 endocarditis, 252,000 strokes, 680,000 per year—almost Researchers Ethiopia death 12.5% rural part because not advanced disappearance wealthy no Africa eradicated examples Costa Rica, Cuba, some Caribbean nations. Strategies eliminate may depend active case finding confirmed echocardiography high-risk groups efforts extend surgical damage. Partnerships programs areas limited nonexistent facilities develop capacity provide care patients who otherwise would painful death. A long-term goal establishment regional centers excellence equipped consistent, accessible, high-quality services. In stark contrast extraordinary lengths go treat nonischemic cardiomyopathies settings received attention. These 25–30% include poorly understood entities cardiomyopathy (which incidence Haiti 300 live births) cardiomyopathy. Multidrug beta blockers, angiotensin-converting enzyme (ACE) inhibitors, neurohormonal antagonists dramatically mortality quality life patients. Lessons learned scale-up TB illustrative progress made establishing means deliver therapies. Because systemic investigation stroke begun recently, known about elevated pressure portion continent. Modestly absence obesity confer adverse events short run. contrast, persistently above 180 110 goes largely undetected, untreated, uncontrolled setting. Framingham cohort men 45–74 old, prevalence pressures 210 120 declined 1.8% 1950s 0.1% 1990s introduction antihypertensive agents. debate screening thresholds, staffed nonphysicians must quickly gain essential medications. In 1960, Paul Dudley White colleagues region near Albert Schweitzer Hospital Lambaréné, Gabon. group found evidence myocardial infarction, they concluded “the mitral stenosis [sic] astonishing. . We believe strongly duty bring sufferers benefits better penicillin prophylaxis cardiac surgery when indicated. same responsibility exists correctable congenital defects.” Leaders tertiary elsewhere continued call poor. reconstruction services infectious offers opportunity identify undertake poverty. Cancer Low- 54% 60%, respectively, 12.4 7.6 cancer 2008. new 29% developed 73% Also overall 104%, fivefold higher “Western” lifestyle changes responsible cancers breast, colon, prostate, historic realities, sociocultural behavioral factors, genetics, poverty itself also profound cancer-related morbidity rates. Whereas <10% 25% malignancies Infectious human papillomavirus (cervical cancer), hepatitis B virus (liver Helicobacter pylori (stomach cancer) Environmental dietary factors indoor air pollution high-salt diets certain lung stomach cancers). Tobacco (both smoking chewing) important source oral cancers. decreasing smokers growing especially women people. For reasons, outcomes worse nations. Overstretched poor simply capable detection; incurable diagnosis. Treatment available small mostly citizens available, range substandard. Yet need future. Only decade ago, MDR-TB considered untreatable wealthiest population. clear feasibility creating technical financial provision complex populations. Diabetes The International Diabetes Federation reports diabetic expected 285 2010 438 2030. Already, 70% where, frequently 65, complications micro- macrovascular take greater toll. projected estimated 4 diabetes-related illnesses 2010, almost occurring countries. Obesity Use In 2004, released Global Strategy Diet, Physical Activity Health, populationwide promotion healthy diet regular physical activity effort overweight obesity. Passing strategy Assembly proved opposition food industry member states, United States. globalization had positive effects, negative aspect been growth well-financed lobbies aggressively promoted unhealthy consumption alcohol tobacco. Foreign direct tobacco, beverage, products reached $327 2002—a five times amount spent year address bilateral agencies, Bank combined. The Three Pillars Prevention The estimates type 2 diabetes prevented three pillars activity, avoidance there population-based measures behaviors, sobering note increasing reversed any population, robust industries. Nonetheless, Mauritius, example, policy measure changed cooking oil fall mean serum cholesterol levels. modification all. 100 tobacco-related diseases;>1 billion people will die of these diseases in the twenty-first century, with the vast majority of those deaths in developing countries. Today, 80% of the world’s 1.2 billion smokers live in low- and middle-income countries, and although 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 2003 Framework Convention on Tobacco Control represented 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 Health In 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 secondhand tobacco smoke, and outdoor air pollution account for 20% of lower respiratory infections in developed countries and 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 Health The 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 years lost to disability 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 health expenditures to mental health. Increasingly effective therapies exist for many of the major causes of mental disorders. 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 practice in cities and are unavailable within the public sector or to patients living in poverty. Among 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 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 disenfranchisement of women to current economic, political, and environmental concerns. Primary Care At the International Conference on Primary Health Care in Alma-Ata (in what is now Kazakhstan) in 1978, public health officials from around the world agreed on a commitment to “Health for All by 2000,” a goal to be achieved by providing universal access to primary health care worldwide. Critics argued that the attainment of this goal by the proposed date was impossible. In the ensuing years, a strategy of selective primary health care emerged that included four inexpensive interventions collectively known as GOBI: growth monitoring, oral rehydation, breast-feeding, and immunizations for diphtheria, whooping cough, tetanus, polio, TB, and measles. GOBI later was expanded to GOBI-FFF, which also included female education, food, and family planning. Some public health figures saw this as an interim strategy to achieve “health for all,” but others criticized it as a retreat from the commitments of Alma-Ata. Similar debates still rage, with “vertical” disease-specific programs for HIV, TB, and malaria often seen as competing with primary health care efforts for critical economic, human, and political resources. Health Systems and the Brain Drain A significant and frequently 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 one-half of those 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. For instance, nearly 90% of Malawi’s population is rural, but more than 95% of clinical officers work at urban facilities, and 47% of nurses work at tertiary care facilities. Even community health workers trained to provide first-line services to rural populations often transfer to urban districts. 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. A 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. The shortage of medical personnel in the areas hardest hit by HIV has profound implications for prevention and treatment efforts in those 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. 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 confirms 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 also have become insuperable challenges. Together, these forces have conspired to render the provision of proper care almost impossible. One Kenyan medical resident noted, “Before training we thought of doctors as supermen. . . . [Now] we are only mortuary attendants.” In light of the difficult conditions under which these health care personnel work, is it any surprise that the U.S. government’s Global AIDS Coordinator remarked in 2004 that there were more Ethiopian physicians practicing in Chicago than in all of Ethiopia? When providing care for the sick becomes a nightmare for those at the beginning of clinical training, physician burnout 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 burnout among health workers. Patients and their families are those who pay most dearly for provider burnout, 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. Conclusion: Toward a Science of Implementation Public-health strategies draw largely on quantitative methods—epidemiology, biostatistics, and 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 proved difficult but not impossible to manage; drug resistance and a lack of effective health systems have 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 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. That 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 premature morbidity and mortality rates among the world’s poor? As in the nineteenth century, human rights perspectives have proved helpful in turning attention to the problems of the destitute sick; such perspectives also may inform strategies of delivering care equitably. A number of university hospitals are developing training programs for physicians with an interest 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. This is a moment of opportunity. To ensure that the opportunity is not wasted, the 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 waterborne illnesses. Other excess mortality is attributable to the inadequacy of efforts to develop new preventive, diagnostic, and therapeutic 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 most heavily affected regions. The development of tools must be followed quickly by their equitable distribution. When new preventive and therapeutic tools are developed without concurrent attention to delivery or implementation, one encounters what sometimes are termed perverse effects: even as new tools are developed, inequalities of outcome—lower morbidity and mortality rates 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.
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