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.)
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.
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 million in 2010. Of the deaths in 2010, 3.1 million (40%) occurred in the neonatal period. About one-third of these deaths among children <5 years old occurred in southern Asia and almost one-half in sub-Saharan Africa; <1% occurred in high-income countries.
Among persons 15–59 years of age, noncommunicable diseases accounted for more than one-half of all deaths in all regions except sub-Saharan Africa, where communicable diseases, maternal and perinatal conditions, and nutritional deficiencies together accounted for two-thirds of all deaths. Indeed, the HIVmortality rate among 15- to 59-year-olds in sub-Saharan Africa was higher than the mortality rate due to all causes among adults in high-income countries. In this age group, injuries accounted for 23% of all deaths worldwide. Overall, death rates in this age group declined between 1990 and 2004 in all areas except Europe and Central Asia, where cardiovascular diseases and injuries caused increased mortality rates, and sub-Saharan Africa, where the impact of HIV/AIDS in this age cohort was particularly devastating.
There is greater uncertainty in calculating years of life lived with disability for specific conditions than in calculating years of life lost. Best estimates from 2004 reveal that although 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. In most low- and middle-income countries, people lived shorter lives and experienced disability and poor health for a greater proportion of their lives. Indeed, >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.
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.
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.
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."
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 of 80%. Limited success in scaling up ITN coverage reflects the inadequately acknowledged economic barriers that prevent the destitute sick from accessing critical preventive technologies and the challenges in designing and implementing effective delivery platforms for these products.
IRS is one of the most common interventions for preventing the transmission of malaria in endemic areas. Vector control using insecticides approved by the WHO, including DDT, can effectively reduce or even interrupt malaria transmission. However, studies have indicated that spraying is effective in controlling malaria transmission only if most (~80%) of the structures in the targeted community are treated. Moreover, since a successful program is dependent on well-trained spraying teams as well as on effective monitoring and planning, IRS is difficult to employ and is often reliant on health systems with a strong infrastructure that renders the approach feasible. Regardless of the limitations of IRS, the WHO recommends its use in combination with ITNs. Neither intervention alone is sufficient to prevent transmission of malaria entirely.
Artemisinin-Based Combination Therapy
The emergence and spread of chloroquine resistance have increased the necessity for antimalarial combination therapy. To limit the spread of resistance, the WHO now recommends only the use of ACT for uncomplicated falciparum malaria. Like that of other antimalarial interventions, the use of ACT has increased in the last few years, but coverage remains very low in several countries in sub-Saharan Africa. In a 2007–2008 study, fewer than 15% of children under the age of 5 with a fever were receiving ACT in 11 of 13 countries surveyed, although the World Health Assembly's target is 80%. In response, the RBM partnership has focused significant investment on enhancing access to ACT by facilitating its delivery through the public-health sector and developing innovative funding mechanisms (e.g., the Affordable Medicines Facility—malaria) through which consumer prices for ACT can be reduced significantly and ineffective artemisinin monotherapies can be eliminated from the market.
In the last several years, resistance to antimalarial medicines and insecticides has become an even larger problem. In 2009, confirmation of artemisinin resistance was reported. Although the WHO has called for an end to the use of artemisinin monotherapy, the marketing of such therapies continues in many countries. Ongoing use of artemisinin monotherapy increases the likelihood of drug resistance, a deadly prospect that will make malaria far more difficult to treat.
Meeting the challenge of malaria control will continue to require careful study of appropriate preventive and therapeutic strategies in the context of an increasingly sophisticated molecular understanding of the pathogen, vector, and host. However, an appreciation of the economic and structural devastation wrought by malaria—like that inflicted by diarrhea, AIDS, and TB—on the most vulnerable populations should heighten the commitment to the critical analysis of ways to implement proven strategies for the prevention and treatment of these diseases.
Noncommunicable Chronic Diseases
Although 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, 60% of all deaths worldwide in 2004 were due to noncommunicable chronic diseases (NCDs). Moreover, 80% of deaths attributable to NCDs occurred in low- and middle-income countries, where 86% 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 out 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 already are carrying a "double burden" of communicable and noncommunicable diseases.
Unlike 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 flow of overseas development assistance to the health sector focused on the communicable causes that accounted for <1 in 20 excess deaths during that 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 along with 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 nonatherogenic pathologies.
The epidemiology of heart failure reflects inequalities in risk factorprevalence 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.
Among the 2.4 million annual cases of pediatric rheumatic heart disease, more than 40% 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 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 otherwise would have 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 beta blockers, angiotensin-converting enzyme (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 heart failure therapies.
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. Although 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." 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.
Low- and middle-income countries accounted for 54% and 60%, respectively, of the 12.4 million cases and 7.6 million deaths due to cancer in 2008. 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 also will have a profound impact on cancer-related mortality and morbidity rates. Whereas 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. Yet this need not be the future. Only a decade ago, MDR-TB and HIV infection were considered untreatable for all but the wealthiest among the world's population. The last decade has made clear the feasibility of creating innovative programs that reduce technical and financial barriers to the provision of care for complex diseases for the world's poorest populations.
The International Diabetes Federation reports that the number of diabetic patients in the world is expected to increase from 285 million in 2010 to 438 million by 2030. Already, more than 70% of diabetic patients live in developing countries where, because those affected are far more frequently under age 65, the complications of micro- and macrovascular disease take a far greater toll. In 2009, the Federation projected an estimated 4 million deaths from diabetes-related illnesses in 2010, with almost 80% of those deaths occurring in low- and middle-income countries.
In 2004, the WHO released its Global Strategy on Diet, Physical Activity and Health, which focused on the populationwide 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. Although 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 Prevention
The 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. Although 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 reversed in any population, including the populations 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 worldwide died 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 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.
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.
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.
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. Global primary care is examined in detail in Chap. e1.