01 - 485 Global Issues in Medicine

485 Global Issues in Medicine

Joseph J. Rhatigan, Paul E. Farmer*

Global Issues in Medicine WHY GLOBAL HEALTH? Global health has emerged as an important field within medicine. Some scholars have defined global health as the field of study and practice concerned with improving the health of all people and achiev­ ing health equity worldwide, with an emphasis on addressing trans­ national problems. 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. However, this is a moment of opportunity: only relatively recently have persistent calls for global health equity been matched by an unprecedented invest­ ment in addressing the health problems of poor people worldwide. To ensure that this opportunity is not wasted, we must strengthen health systems and improve health care delivery to address the true burden and distribution of disease. This chapter introduces the major interna­ tional bodies that address global health problems; identifies the more significant barriers to improving the health of people who to date have not, by and large, had access to modern medicine; and summarizes population-based data on the most common health problems faced by people living in poverty. Examining specific problems—notably HIV/ AIDS (Chap. 208) but also tuberculosis (Chap. 183), malaria (Chap. 231), Ebola (Chap. 216), COVID-19 (Chap. 205) and key “noncommunicable” chronic diseases (NCDs)—helps sharpen the discussion of barriers to prevention, diagnosis, and care as well as the means of overcoming them. This chapter closes by discussing global health equity, drawing on concepts of social justice. A BRIEF HISTORY OF GLOBAL HEALTH INSTITUTIONS Concern about illness across national boundaries dates back many centuries, predating the Black Plague and other pandemics. One of the first organizations founded explicitly to tackle cross-border health issues was the Pan American Sanitary Bureau, which was formed in 1902 by 11 countries in the Americas. 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 halted 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 communi­ cable 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 despite Cold War tensions. Even as attention to and resources for health problems in poor coun­ tries grow, the lack of coordination among global health institutions remains an issue. The global response to the COVID-19 pandemic revealed both strengths and fundamental flaws in the current state of global health governance. The WHO remains underfunded despite the ever-growing need to engage a wider and more complex range of health issues. This may be what some have called “the golden age of global health,” but leaders of major global health organizations must work together to design an effective architecture that will make the most of opportunities to link new resources for and commitments to global health equity with the emerging understanding of disease bur­ den and the unmet need to create robust and resilient national health systems. To this end, new and old players in global health must invest heavily in discovery (relevant basic science), development of new tools (preventive, diagnostic, and therapeutic), and modes of delivery that *Deceased. At the International Conference on Primary Health Care in AlmaAta (in what is now Kazakhstan) in 1978, public health officials from around the world agreed on a commitment to “Health for All by the Year 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 for the provision of selective primary health care emerged. This strategy included four inexpensive interventions collectively known as GOBI: growth monitoring, oral rehydration, breast-feeding, and immunizations for diphtheria, whooping cough, tetanus, polio, tuberculosis, and measles. GOBI later was expanded to GOBI-FFF,

Global Medicine PART 17 which also included female education, food, and family planning. Some public health figures saw GOBI-FFF as an interim strategy to achieve “health for all,” but others criticized it as a retreat from the bolder com­ mitments of Alma-Ata. In 1982, UNICEF, led by James Grant, helped usher in a period of sustained and coordinated efforts to reduce childhood mortality using a similar set of interventions among other measures. Over the ensuing two decades, it is estimated that 25 million children’s lives were saved in what is often called “The Child Survival Revolution.” The influence of the WHO waned during the 1980s. In the early 1990s, many observers argued that, with its vastly superior financial resources and its close—if unequal—relationships with the govern­ ments of poor countries, the World Bank had eclipsed the WHO as the most important multilateral institution working in global health. One of the stated goals of the World Bank was to help poor countries identify “cost-effective” interventions worthy of public funding and international support. At the same time, international financial institu­ tions encouraged many of those nations to reduce public expenditures in health and education in order to stimulate economic growth as part of (later discredited) policies, generally referred to as “structural adjust­ ment,” that imposed restrictions on social sector government spending as a condition for access to credit and assistance through the World Bank, the International Monetary Fund, and regional development banks. There was a resurgence of many diseases—including malaria, trypanosomiasis, and 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 equity. HIV/AIDS, first described in the medical literature in 1981, precipi­ tated a change. In the United States, the advent of this newly described infectious killer marked the culmination of a series of events that dashed previous hopes of “closing the book” on infectious diseases. In Africa, which would emerge as the global epicenter of the pandemic, HIV disease strained tuberculosis control programs, and malaria continued to claim as many lives as ever: at the dawn of the twentyfirst century, these three diseases alone killed nearly 6 million people each year. New research, new policies, and new funding mechanisms were called for. The past two decades have seen the rise of important multilateral global health financing institutions such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria; 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. With its 194 member states and 150 country offices, the WHO remains important in matters relating to the cross-border spread of infectious diseases and other health threats. In the aftermath of the epidemic of severe acute respiratory syndrome in 2003, the WHO’s International Health Regulations—which provide a legal foundation for that organization’s direct investigation into a wide range of global health problems, including pandemic influenza, in any member state— were strengthened and brought into force in May 2007.

3844 will ensure the equitable provision of health products and services to all who need them. The adoption of the Sustainable Development Goals (SDGs) in 2015 by the United Nations serves as an example of effective cooperation. The SDGs articulate 17 overarching goals across several domains to be achieved by 2030. Goal 3 specifically relates to global health and contains 13 distinct targets to be met, including reducing maternal and child mortality; ending the epidemics of HIV, tuberculosis, and malaria; and reducing the burden of NCDs. Included in the SDGs is a commitment to achieve universal health coverage (UHC), providing universal access to high-quality essential health services at an affordable cost worldwide. Championed by the WHO, the World Bank, and many civil society organizations, Goal 3 will measure coverage of 16 essential health services and assess the financial burden of health spending by households in every country. PART 17 Global Medicine THE ECONOMICS OF GLOBAL HEALTH Political and economic concerns have often guided global health inter­ ventions. 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, there is increasing consensus that investments in health care delivery and the control of communicable diseases lead to increased productivity. The question is where to find the necessary resources to start the predicted “virtuous cycle.” During the past two decades, spending on health in poor countries has increased dramatically. According to a study from the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, before the COVID-19 pandemic, total development assistance for health (DAH) worldwide (essentially a measure of “health aid”) grew to $38.9 billion in 2018—up from $5.6 billion in 1990—and seemed to reach a plateau. However, the global response to COVID-19 saw the largest yearly increases in DAH ever recorded. Between 2020 and 2021, DAH grew by 86%. It is estimated that in 2021 DAH reached $64.7 billion. In 2021, the leading contributors included the United States, the United Kingdom, Germany, and private foundations. MORTALITY AND THE GLOBAL

BURDEN OF DISEASE Refining metrics is an important task for global health: only relatively recently have there been solid assessments of the global burden of disease. The first study to look seriously at this issue, conducted in 1990, laid the foundation for the first report on Disease Control Pri­ orities in Developing Countries 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 famil­ iarized 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 absolute years of life lost and years lost due to disability for incident cases of a condition. (See Fig. 485-1 and Table 485-1 for an analysis of the global disease burden by DALYs.) In 2012, the IHME and partner institutions began publishing results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) study. The GBD study is the most comprehensive effort to date to pro­ duce longitudinal, globally ambitious, and comparable estimates of the burden of diseases, injuries, and risk factors. This report reflects the expansion of the available data on health in the poorest countries and of the capacity to quantify the impact of specific conditions on a popu­ lation. It measures current levels and recent trends for major diseases, injuries, and risk factors worldwide. Since its original publication, the GBD study team has revised and improved the health-state severity weight system, collated published data, and used household surveys to enhance the breadth and accuracy of disease burden data. Updated

reports were released in 2013, 2015, 2017, and 2019. The report now includes fact sheets that examine 386 diseases and injuries in depth. As analytic methods and data quality improve, important trends can be identified in a comparison of global disease burden estimates from 1990 to 2019. ■ ■GLOBAL MORTALITY Although the COVID-19 pandemic has led to significant excess deaths, it is instructive to look at the last GBD study’s data as a comprehensive baseline of disease burden before the pandemic. In 2019, before the COVID-19 pandemic, of the 56.5 million deaths worldwide, 17% (9.6 million) were due to communicable diseases, maternal and neonatal conditions, and nutritional deficiencies—a marked decrease compared with figures for 1990, when these conditions accounted for 32% of global mortality. Among the fraction of all deaths related to commu­ nicable diseases, maternal and neonatal conditions, and nutritional deficiencies, 78% occurred in Sub-Saharan Africa and southern Asia. While the proportion of deaths due to these conditions has decreased significantly in the past decade, there has been a dramatic rise in the number of deaths from NCDs. The leading cause of death worldwide in 2019 was ischemic heart disease, accounting for 9.1 million deaths (16% of total deaths). In high-income countries, ischemic heart disease accounted for 16% of total deaths, and in low-income countries, it accounted for 16%. It is noteworthy that ischemic heart disease was responsible for just 5% of total deaths in Sub-Saharan Africa (Table 485-2). In second place—causing 11% of global mortality—was stroke, which accounted for 8% of deaths in high-income countries, 6% in lowincome countries, and 5% in Sub-Saharan Africa. Although chronic obstructive pulmonary disease (COPD) was the third leading cause of death globally and was the fifth leading cause in high-income coun­ tries (accounting for 5% of all deaths), this condition did not figure among the top 15 causes in Sub-Saharan Africa. Among the 10 leading causes of death in Sub-Saharan Africa, five were infectious diseases, with HIV/AIDS, lower respiratory infections, diarrheal diseases, and malaria ranking as dominant contributors to disease burden. In highincome countries, however, only 1 infectious disease—lower respira­ tory infection—ranked among the top 10 causes of death. The number of deaths among children under 5 years dropped from 16.4 million in 1970 to 11.8 million in 1990 and to 5.0 million in 2019—a decrease that far surpassed predictions. Of childhood deaths in 2021, 2.3 million (46%) occurred in the neonatal period. Just under one-third of deaths among children under 5 years old occurred in southern Asia and slightly more than one-half in Sub-Saharan Africa, but only ~1% occurred in high-income countries. The global burden of death due to HIV/AIDS and malaria was on an upward slope until 2004, but significant progress has been made since then. Global deaths from AIDS fell from 2.0 million in 2006 to 630,000 in 2022, while malaria deaths dropped from 1.2 million to 608,000 over the same period. Despite these improvements, malaria and HIV/AIDS continue to be major burdens in particular regions, with global impli­ cations. Although it has only a minor impact on mortality outside SubSaharan Africa and Southeast Asia, malaria is the fifth leading cause of death of children under 5 years of age worldwide. HIV infection ranked 30th in global DALYs in 1990 but was the 11th leading cause of disease burden in 2019, with Sub-Saharan Africa bearing the vast majority of this burden (Fig. 485-1). The world’s population is living longer: global life expectancy has increased significantly over the past 50 years from 58.8 years in 1970 to 73.5 years in 2019. This demographic change, accompanied by the fact that the prevalence of NCDs increases with age, is dramatically shifting the burden of disease toward NCDs, which have surpassed communi­ cable, maternal, nutritional, and neonatal causes. By 2019, 74% of total deaths at all ages and 63% of all DALYs were due to NCDs. Increas­ ingly, the global burden of disease comprises conditions and injuries that cause disability rather than death. Worldwide, although both life expectancy and years of life lived in good health have risen, years of life lived with disability also have increased. Globally, the total burden of disability increased by 50% between 1950 and 2019. Despite the higher prevalence of diseases

Global Both sexes, all ages, DALYs 1990 Rank 2019 Rank

1. Neonatal disorders

2. Lower respiratory infections

3. Diarrheal diseases

4. Ischemic heart disease

5. Stroke

6. Congenital defects

7. Tuberculosis

8. Road injuries

9. Measles

10. Malaria

11. COPD

12. Protein-energy malnutrition

13. Low back pain

14. Self-harm

15. Cirrhosis

16. Meningitis

17. Drowning

18. Headache disorders

19. Depressive disorders

20. Diabetes

21. Lung cancer

22. Falls

23. Age-related hearing loss

24. Chronic kidney disease

25. HIV/AIDS

26. Other musculoskeletal Communicable, maternal, neonatal, and nutritional diseases Noncommunicable diseases Injuries FIGURE 485-1  Global disability-adjusted life-year (DALY) ranks for the top causes of disease burden in 1990 and 2019. COPD, chronic obstructive pulmonary disease. (From the Institute for Health Metrics and Evaluation [IHME]. GBD Compare. Seattle, WA: IHME, University of Washington, 2023. Available at http://vizhub.healthdata.org/ gbd-compare. Accessed Dec 15, 2023.) common in older populations (e.g., dementia and musculoskeletal disease) in developed and high-income countries, best estimates from 2019 reveal that disability resulting from cardiovascular diseases, chronic respiratory diseases, and the long-term impact of communi­ cable diseases was greater in low- and middle-income countries. In most developing countries, people lived shorter lives and experienced disability and poor health for a greater proportion of their lives. ■ ■HEALTH AND WEALTH Clear disparities in burden of disease (both communicable and noncom­ municable) across country income levels are strong indicators that pov­ erty and health are inherently linked. Numerous studies have documented the link between poverty and health within nations as well as across them. 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 8 billion persons alive in 2023, 9% (700 million) lived on less than $2.15 per day—a standard measurement of extreme poverty— and half of these individuals lived in Sub-Saharan Africa. While children make up 31% of the overall global population, they account for 50% of persons living in poverty. The extreme poverty rate declined steadily between 1990 and 2019. Before the COVID-19 pandemic, compared

27. Neonatal disorders

28. Ischemic heart disease

29. Stroke

30. Lower respiratory infections

31. Diarrheal diseases Global Issues in Medicine CHAPTER 485

32. COPD

33. Road injuries

34. Diabetes

35. Low back pain

36. Congenital defects

37. HIV/AIDS

38. Tuberculosis

39. Depressive disorders

40. Headache disorders

41. Malaria

42. Cirrhosis

43. Lung cancer

44. Chronic kidney disease

45. Other musculoskeletal

46. Age-related hearing loss

47. Falls

48. Self-harm

49. Meningitis

50. Protein-energy malnutrition

51. Drowning

52. Measles with 1990, there were more than 1 billion fewer people living in poverty despite growth in the global population of more than 2 billion during that time. The COVID-19 pandemic led to significant increases in pov­ erty, especially in low- and middle- income countries. The poorest bore the brunt of the economic shocks of COVID-19. The global poorest lost twice as much income as the richest between 2020 and 2022. ■ ■RISK FACTORS FOR DISEASE BURDEN The GBD study found that the three leading risk factors for global dis­ ease burden in 2019 were (in order of frequency) high systolic blood pressure, smoking, and high fasting plasma glucose—a substantial change from 1990, when childhood malnutrition was ranked first. Although its prevalence has declined, maternal and childhood malnu­ trition remain the leading risk factors for death among children < 5 years of age. In an era that has seen obesity become a major health concern in many developed countries, the persistence of undernutrition is cause for consternation. In its rural reaches, no health care initiative, however generously funded, will be effective or comprehensive without address­ ing undernutrition. In an analysis that examined how specific diseases and injuries are affected by environmental risk, the WHO estimates that 24% of all

TABLE 485-1  Leading Causes of Burden of Disease (DALYs), 2019 DALYS (MILLIONS) PERCENTAGE OF TOTAL DALYs DISEASE OR INJURY World 2540.0

1. Neonatal disorders 185.9 7.3
2. Ischemic heart disease 182.0 7.2
3. Stroke 143.2 5.7
4. Lower respiratory infection 97.2 3.8
5. Diarrheal diseases 80.9 3.2
6. COPD 74.4 2.9 PART 17 Global Medicine
7. Road injuries 72.9 2.9
8. Diabetes 70.9 2.8
9. Low back pain 63.7 2.5
10. Congenital defects 52.8 2.1 Low-Income Countriesa
11. Neonatal disorders 44.4 17.4
12. Lower respiratory infection 24.5 7.6
13. Malaria 23.3 7.2
14. Diarrheal disease 23.2 7.2
15. HIV/AIDS 14.5 4.5
16. Congenital defects 12.8 4.0
17. Tuberculosis 12.2 3.8
18. Stroke 8.6 2.7
19. Road injuries 6.2 2.3
20. Ischemic heart disease 7.4 2.3 High-Income Countriesa
21. Ischemic heart disease 26.8 7.6
22. Low back pain 17.7 4.9
23. Stroke 15.8 4.4
24. Lung cancer 13.7 3.9
25. Diabetes 13.3 3.7
26. COPD 12.0 3.4
27. Falls 9.7 2.7
28. Alzheimer’s disease 9.2 2.6
29. Other musculoskeletal 9.1 2.6
30. Depressive disorders 8.6 2.4 Sub-Saharan Africa
31. Neonatal disorders 70.5 13.8
32. Malaria 43.2 8.5
33. Diarrheal diseases 42.0 8.2
34. Lower respiratory infection 41.1 8.0
35. HIV/AIDS 35.6 7.0
36. Congenital defects 18.1 3.6
37. Tuberculosis 17.6 3.4
38. Road injuries 11.1 2.2
39. Stroke 10.8 2.1
40. Meningitis 10.4 2.0 aThe World Bank classifies high-income countries as those whose gross national income (GNI) per capita is ≥$14,005. Low- and middle-income countries are categorized as low income (GNI per capita, <$1,145), lower-middle income (GNI per capita, $1,146–$4,515), and upper-middle income (GNI per capita, $4,516–$14,005) (https://datahelpdesk.worldbank.org/knowledgebase/articles/906519). Abbreviations: COPD, chronic obstructive pulmonary disease; DALYs, disabilityadjusted life-years. Source: Institute for Health Metrics and Evaluation, University of Washington (2023). Data available at https://vizhub.healthdata.org/gbd-compare/. Accessed

December 15, 2023. deaths and 28% of deaths among children <5 years of age in 2019 were due to modifiable environmental factors: some 17 million children die every year from causes related to unhealthy environments, including the nearly 500,000 deaths stemming from a lack of access to clean water

TABLE 485-2  Leading Causes of Death Worldwide, 2019 DEATHS (MILLIONS) PERCENTAGE OF TOTAL DEATHS DISEASE OR INJURY World 56.5

1. Ischemic heart disease 9.1 16.1
2. Stroke 6.6 11.7
3. COPD 3.3 5.8
4. Lower respiratory infection 2.5 4.4
5. Lung cancer 2.0 3.6
6. Neonatal disorders 1.9 3.3
7. Alzheimer’s disease 1.6 2.9
8. Diabetes 1.6 2.7
9. Diarrheal diseases 1.5 2.7
10. Cirrhosis 1.5 2.6 Low-Income Countriesa
11. Neonatal disorders 0.5 9.7
12. Lower respiratory infection 0.4 8.3
13. Diarrheal diseases 0.3 6.8
14. Stroke 0.3 6.5
15. Ischemic heart disease 0.3 6.2
16. Malaria 0.3 6.1
17. Tuberculosis 0.3 5.5
18. HIV/AIDS 0.2 5.0
19. Congenital defects 0.1 2.8
20. COPD 0.1 2.5 High-Income Countriesa
21. Ischemic heart disease 1.8 16.4
22. Stroke 0.9 8.4
23. Lung cancer 0.7 6.4
24. Alzheimer’s disease 0.7 6.3
25. COPD 0.5 4.9
26. Lower respiratory infection 0.4 4.1
27. Colorectal cancer 0.4 3.8
28. Chronic kidney disease 0.3 3.0
29. Diabetes 0.3 2.3
30. Pancreatic cancer 0.2 2.1 Sub-Saharan Africa
31. Neonatal disorders 0.7 9.9
32. Lower respiratory infection 0.7 8.9
33. HIV/AIDS 0.6 8.4
34. Malaria 0.6 7.8
35. Diarrheal diseases 0.6 7.8
36. Stroke 0.4 5.3
37. Tuberculosis 0.4 5.1
38. Ischemic heart disease 0.4 5.0
39. Congenital defects 0.2 2.5
40. Cirrhosis 0.2 2.5 aThe World Bank classifies high-income countries as those whose gross national income (GNI) per capita is ≥$14,005. Low- and middle-income countries are categorized as low income (GNI per capita, <$1,145), lower-middle income (GNI per capita, $1,146–$4,515), and upper-middle income (GNI per capita, $4,516–$14,005) (https://datahelpdesk.worldbank.org/knowledgebase/articles/906519). Abbreviation: COPD, chronic obstructive pulmonary disease. Source: Institute for Health Metrics and Evaluation, University of Washington (2023). Data available at https://vizhub.healthdata.org/gbd-compare/. Accessed December 15, 2023. and sanitation. Many of these modifiable factors lead to child and adult deaths from infectious pathologies; others lead to deaths from malig­ nancies. Risk factors such as indoor air pollution due to use of solid fuels account for 25% of DALYs due to lower respiratory infections

globally. Various forms of unintentional injury and malaria top the list of health problems to which environmental factors contribute. The third edition of Disease Control Priorities (DCP3), published as a set of serial volumes based on content area, provides evidencebased recommendations and cost-effectiveness analyses for numerous interventions, with attention to strategies for strengthening health systems. Cost-effectiveness analyses that compare relatively equivalent interventions in order to facilitate sound decisions under constraint are necessary; however, these analyses, as the DCP3 authors acknowledge, are unreliable when based on an incomplete knowledge of cost and evolving evidence of effectiveness. As both resources and objectives for global health initiatives grew, cost-effectiveness analyses (particularly those based on older evidence) sometimes steered policy makers and public health experts toward low-cost but ultimately ineffective inter­ ventions or away from higher-priced but effective ones. Thus, we use the term global health equity to emphasize the need to ensure equitable access to high-value health interventions. To illustrate these points, it is instructive to look to HIV/AIDS, which in the course of the last four decades has become one of the world’s leading infectious causes of adult death. ■ ■HIV INFECTION/AIDS Chapter 208 provides an overview of the global HIV epidemic today. Approximately 39 million people worldwide were living with HIV infection in 2022, and it was the underlying cause of death for 630,000 people that year. Approximately 67% of all people living with HIV live in Sub-Saharan Africa. Here the discussion will be limited to HIV/ AIDS in the developing world. Lessons learned from tackling HIV/ AIDS in low-resource settings are highly relevant to discussions of other chronic diseases, including NCDs, for which effective therapies have been developed. In the United States, after the mid-1990s, ART transformed HIV infection from an inescapably fatal disease into a manageable chronic illness. Across high-income countries, improved ART has dramatically prolonged life expectancy for people living with HIV infection, which now approaches that of the general population. This success rate exceeds that obtained with almost any treatment for adulthood cancer or for complications of coronary artery disease. In developing countries, treatment has been offered broadly only since 2003. Before 2003, many arguments were raised to justify not mov­ ing 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 patients, 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 their synergistic integration—too often went unchal­ lenged by policy makers, public health experts, and health economists. As a cumulative result of these delays in the face of health disparities both old and new, there were mil­ lions of premature deaths. Disparities in access to HIV treatment did give rise to widespread moral indignation and a new type of health activism. In several middle-income countries, including Brazil, public programs have helped bridge the global access gap. Other innovative projects pioneered by interna­ tional nongovernmental organizations (NGOs) in diverse settings such as Haiti and Rwanda have established that a simple approach to ART based on intensive community engagement and social and economic support for patients and their community-based health workers can achieve remarkable results (Fig. 485-2). During the past decade, the availability of ART has increased sharply in the low- and middle-income coun­ tries that have borne the greatest burden of the HIV/AIDS pandemic. In 2000, few people living with HIV/AIDS in these nations had access to ART, whereas by 2022, 76% of people living with HIV infection were receiving ART. In light of these dramatic gains, coverage targets have grown

more ambitious; for example, in 2014, UNAIDS set the 90-90-90 tar­ gets, which aimed to have 90% of people living with HIV know their status, 90% of those with HIV treated with ART, and 90% of those on treatment achieving viral load suppression by 2020. Five countries met these ambitious goals: Botswana, Eswatini, Rwanda, the United Republic of Tanzania, and Zimbabwe. These goals were updated to “95-95-95” targets for 2030, and by 2023, these same five countries had already achieved them.

This scale-up was made possible by several developments: a stagger­ ing drop in the cost of generically manufactured ART, the development of a standardized approach to treatment, substantial investments by funders, and the political commitment of governments to afford ART as a public good. Civil-society AIDS activists spurred many of these efforts. Global Issues in Medicine CHAPTER 485 Starting in the early 2000s, a combination of factors, including work by the Clinton HIV/AIDS Initiative (now known as the Clinton Health Access Initiative) and Médecins Sans Frontières, led to the availability of generic ART medications. While first-line ART cost

$10,000 per patient per year in 2000, first-line regimens in low- and middle-income countries are now available for <$45 per year. At the same time, fixed-dose combinations made multidrug regimens easier to administer. Also, around this time, the WHO began advocating a public health approach to the treatment of people with AIDS in low-resource settings; this approach promised—thanks to dropping viremia—to lower transmission rates and, if universally available, to end almost all mother-to-child transmission. Derived from models of care pioneered by the NGO Partners In Health and other groups, this approach proposed the use of standard first-line treatment regimens based on a simple five-drug formulary, with a more complex (and more expensive) set of second-line options in reserve. Clinical protocols were standardized, and intensive training packages for health professionals and community health workers were developed and implemented in many countries. Early rollout efforts were supported by new funding from the Global Fund and PEPFAR. In 2003, 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 ambi­ tious target: to have 3 million people in developing countries on treat­ ment by the end of 2005. Many countries 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. External funding to FIGURE 485-2  An HIV and tuberculosis (TB)–co-infected patient in Rwanda before (left) and after (right) 6 months of treatment.

3848 fight HIV/AIDS in low- and middle-income countries increased dra­ matically during this period and beyond, rising from $332 million in 1996 to $9.9 billion in 2021. The integration of prevention and care led to a sharp drop in transmission—a 96% decline according to one review of the impact of ART rollout in heavily burdened countries in Africa and the Caribbean. Further lessons with implications for policy and action have come from efforts now under way among lower-income countries. Rwanda provides an example: since 2000, mortality from HIV disease has fallen by 85% as the country—despite its relatively low gross national income—has provided almost universal access to ART. The reasons for this success include strong national leadership, evidence-based policy, cross-sector collaboration, community-based care, and a deliberate focus on a health-systems approach that embeds HIV/AIDS treatment and prevention in the primary health care service delivery platform. As we will discuss later in this chapter, these principles can be applied to other conditions, including NCDs. PART 17 Global Medicine ■ ■TUBERCULOSIS Chapter 183 provides a concise overview of the pathophysiology and treatment of tuberculosis. In 2022, an estimated 1.3 million people died from Mycobacterium tuberculosis infection; this figure made tuber­ culosis the second leading single infectious killer after COVID-19 of adults globally. The disease is closely linked to HIV infection in much of the world: of the 10.6 million estimated new cases of tuberculosis in 2022, 890,000 occurred among people living with HIV. A much more substantial proportion of the resurgence of tuberculosis registered in southern Africa is attributed to HIV co-infection. Even before the advent of HIV, however, it was estimated that fewer than one-half of all cases of tuberculosis in developing countries were ever diagnosed. Primarily because of the common failure to diagnose and treat tuber­ culosis, international authorities devised a single strategy to reduce the burden of disease. In the early 1990s, the World Bank, the WHO, and other international bodies promoted the DOTS strategy (directly observed therapy using short-course isoniazid- and rifampin-based regimens) as highly cost-effective. Passive case-finding of smearpositive patients was central to the strategy, as was an uninterrupted drug supply. DOTS was clearly effective for most uncomplicated cases of drugsusceptible tuberculosis, but several shortcomings were soon identi­ fied. First, the diagnosis of tuberculosis based solely on sputum smear microscopy—a method dating from the late nineteenth century—is not sensitive. Many cases of pulmonary tuberculosis and all cases of exclu­ sively extrapulmonary tuberculosis are missed by smear microscopy, as are most cases of active disease in children. Second, passive case-find­ ing relies on the availability of health care services, which is uneven in the settings where tuberculosis is most prevalent. Third, patients with multidrug-resistant tuberculosis (MDR-TB) are by definition infected with strains of M. tuberculosis resistant to isoniazid and rifampin; thus, exclusive reliance on these drugs is unwarranted 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 common bacterial infec­ tions. While the great majority of patients sick with and dying from tuberculosis are afflicted with strains susceptible to all first-line drugs, a substantial minority of patients with tuberculosis in some settings are infected with strains of M. tuberculosis resistant to at least one first-line antituberculosis drug. Globally in 2021, an estimated 4% of all patients with new M. tuberculosis infections and 18% of all previously treated patients were infected with rifampin-resistant or MDR strains; most of these cases resulted from primary transmission. It was clear that poor infection control in hospitals and clinics in the face of delays in the initiation of effective therapy led to explosive and lethal epidemics due to these strains. To improve DOTS-based responses to MDR-TB, global health authorities adopted DOTS-Plus, which adds the diagnostics and drugs necessary to manage drug-resistant disease. Even as DOTSPlus was being piloted in resource-constrained settings, however, new strains of extensively drug-resistant (XDR) M. tuberculosis (resistant to isoniazid and rifampin, any fluoroquinolone, and at least one injectable

second-line drug) had already threatened the success of tuberculosis control programs in beleaguered South Africa, for example, where high rates of HIV infection had led to a doubling in the incidence of tuber­ culosis over the preceding decade. Genetic fingerprinting of cultures of infected sputum and tissues suggest that patients may be infected by more than one strain. Despite the poor capacity for detection of MDR- and XDR-TB in most resource-limited settings, an estimated 450,000 cases of MDR-TB were thought to have occurred in 2021. Approxi­ mately 8% of these cases were caused by XDR strains. ■ ■TUBERCULOSIS AND AIDS AS CHRONIC DISEASES: LESSONS LEARNED Strategies effective against MDR-TB have implications for the manage­ ment 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 (see “Malaria,” below). As new therapies, whether for tuberculosis or for hepatitis C infection, become available, many of the problems encountered in the past will recur. Indeed, examining AIDS and tuberculosis as chronic diseases— instead of simply communicable ones—makes it possible to draw several conclusions, many of them pertinent to global health equity in general. First, the chronic infections discussed here are best treated with multidrug regimens to which the infecting strains are susceptible. This is true of chronic infections due to many bacteria, fungi, parasites, or viruses; even acute infections such as those caused by Plasmodium spe­ cies are not reliably treated with a single drug. Second, charging fees for AIDS prevention and care poses insur­ mountable problems for persons living in poverty, many of whom are unable to pay even modest amounts for services or medications. Like efforts to battle airborne tuberculosis, such services might best be seen as a public good promoting public health. Initially, a subsidy approach will require sustained donor contributions, but many African coun­ tries have set targets for increased national investments in health—a pledge that could render ambitious programs sustainable in the long run, as the Rwanda experience suggests. Meanwhile, as local invest­ ments increase, the price of AIDS care continues to decrease. The use of generic medications means that ART can now cost <$0.13 per day. Third, the effective scale-up of pilot projects requires strengthen­ ing and sometimes rebuilding of health care systems, including those charged with delivering primary care. In the past, the lack of health care infrastructure has been cited as a barrier to providing ART in the world’s poorest regions; however, AIDS resources, which are at last considerable, may be marshaled to rebuild public health systems in Sub-Saharan Africa and other HIV-burdened regions—precisely the settings in which tuberculosis is resurgent. Failure to pursue such a health-systems approach after civil wars ended in Sierra Leone and Liberia accounts for much of their extreme vulnerability to Ebola a decade later. Fourth, the lack of trained health care personnel, most notably doctors and nurses, still must be addressed. The WHO recommends a minimum of 1 physician per 1000 persons, but many countries, especially in Sub-Saharan Africa, fall far short of that target. Specifi­ cally, ~45% of WHO member states report not achieving that target. In Sub-Saharan Africa, there were 0.3 physicians per 1000 people. In contrast, the United States and Cuba report 2.5 and 8.4 doctors per 1000 population, respectively. Similarly, ~50% of WHO member states report having fewer than 3 nurses and midwives per 1000 population. Sub-Saharan Africa bears >20% of the global burden of disease but has access to only 3% of the world’s health workers. 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, in Sierra Leone, an estimated 75% of the national health workforce is concentrated in urban areas, where just 44% of the population lives. Even community health workers trained to provide first-line services to rural populations often transfer to urban districts. 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 either emergencies like Ebola or the usual burden of disease.

One reason doctors and nurses leave Sub-Saharan Africa and other low-income areas is that they lack the tools to practice there. Fund­ ing for “vertical” (disease-specific) programs can be used not only to strengthen health systems but also to recruit and train physicians and nurses to underserved regions where they, in turn, can help to train and then work with community health workers in supervising care for patients with AIDS and many other diseases within their communi­ ties. Such training should be undertaken even where physicians are abundant, since close community-based supervision represents the highest standard of care for chronic disease, whether in developing or developed countries. The United States, which has a dearth of health care providers in many of its poor and rural communities, has much to learn from Rwanda in this regard. Fifth, the many barriers to adequate health care and patient adherence that are raised by extreme poverty can be removed only with the deploy­ ment of “wrap-around services”: food supplements for the hungry, help with transportation to clinics, childcare, and housing. Extreme poverty makes it difficult for many patients to comply with therapy for chronic diseases, whether communicable or not. Experience shows, however, that these many barriers can be more readily surmounted than the extreme poverty itself to which chronic disease and acute infection contribute substantially. Indeed, poverty in its many dimensions is far and away the greatest obstacle to the scale-up of treatment and prevention services. 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 HIV, tuberculosis, and malaria—against none of which there is a highly effective vaccine—but also to most other neglected diseases of poverty. ■ ■MALARIA Chapter 231 reviews the etiology, pathogenesis, and clinical treat­ ment of malaria, the world’s fifth-ranking infectious killer. In 2022, there were 249 million cases of malaria, and the disease killed 608,000 people; 77% of these deaths occurred among children <5 years old. The poor disproportionately experience the burden of malaria. SubSaharan Africa was home to about 94% of all malaria cases and 95% of all deaths. Just 4 countries—Nigeria, the Democratic Republic of the Congo, Uganda, and Mozambique—account for more than half of total malaria deaths globally. Malaria’s human cost has been enormous, with the highest toll among children—especially African children—living in poverty. In 2022, $4.3 billion was spent on malaria worldwide, but the WHO target is more than twice that sum. 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 non–malaria-endemic country. The causes of this drag include impaired cognitive development of children, decreased schooling, decreased savings, decreased foreign investment, and restriction of worker mobility. Microeconomic analyses focusing on direct and indirect costs estimate that malaria may consume >10% of a household’s annual income in malaria endemic regions. 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 SubSaharan African countries. In 2008, the RBM partnership launched the Global Malaria Action Plan (GMAP). This strategy integrates pre­ vention and care and calls for the avoidance of single-dose regimens and an awareness of existing drug resistance; the use of insecticidetreated bed nets (ITNs); indoor residual spraying; artemisinin-based combination therapy (ACT); intermittent preventive treatment during pregnancy; prompt diagnosis; and other vector control measures such as larviciding and environmental management. Over the past two decades, these efforts have dramatically reduced the global burden of malaria resulting in the prevention of 1.7 billion cases and saving 10.6 million lives. 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 pathogen, vector, and host. However, an appreciation of the economic and social devastation wrought by malaria—like that inflicted by diar­ rhea, AIDS, and tuberculosis—on the most vulnerable populations should heighten the level of commitment to critical analysis of ways to implement proven strategies for prevention and treatment. Funding from the Global Fund, the Gates Foundation, the World Bank’s International Development Association, and the U.S. President’s Malaria Initiative, along with leadership from public health authorities, is critical to sustain the benefits of prevention and treatment. Building on the growing momentum of the last decade with adequate financial support, innovative strategies, and effective tools for prevention, diag­ nosis, and treatment, we may yet achieve the goal of a world largely free of malaria. Global Issues in Medicine CHAPTER 485 ■ ■EBOLA Chapter 216 provides an overview of the epidemiology, pathogenesis, and clinical manifestations of Ebola virus and Marburg virus infec­ tions. The 2013–2016 outbreak of Ebola virus disease in West Africa was the largest documented Ebola epidemic to date, with >28,000 recorded cases and 11,000 recorded deaths. Prior to the outbreak, the health systems of the three most affected countries—Liberia, Guinea, and Sierra Leone—were among the world’s weakest. Histories of extractive colonial and postcolonial commerce, the conditional aid policies of international financial institutions, recent civil conflict, and underresourced health ministries left this part of West Africa bereft of the means to deliver modern medicine and promote public health. In 2013, Sierra Leone had the world’s highest maternal mortality ratio, with 1180 deaths per 100,000 live births. According to one estimate, Liberia had just 51 physicians working in the entire coun­ try before the Ebola epidemic, or roughly one physician per 100,000 persons. Clinics and hospitals were scarce across the region, especially in rural areas, and routinely lacked drugs, supplies, electricity, running water, laboratories, and personal protective equipment for the prevention of nosocomial infection. Such deficits were not surprising given these countries’ meager public and private expenditures on health. The unprecedented scale of the West African Ebola epidemic was largely a symptom of these chronically weak health systems. As a result, clinicians, patients’ families, and other caregivers—tasked with nursing the sick and interring the dead but lacking the means to do so safely— faced disproportionately high risks of Ebola infection. Health facilities with poor infection control and unsafe burials served as amplifiers of transmission. The quest to contain Ebola in West Africa was one of the largest global public health efforts at that time, but it was far from ambitious clinically. As in previous Ebola outbreaks, preventing new infections was often prioritized over improving survival among those already infected, leading to substandard care for most West African patients and high case-fatality rates—by WHO estimates, ~70%. However, in settings in which quality supportive and critical care could be provided, clinical outcomes among Ebola-infected patients affirmed that Ebola virus disease is treatable, even in the absence of specific antiviral thera­ pies and experimental drugs. As with efforts to combat AIDS and tuberculosis, the global response to Ebola reveals the unintended consequences of pitting preventive strategies against therapeutic ones—and the pull of debates about scarcity. Misguided (and often contradictory) public health messaging, distrust of disease-control and social mobilization teams, punitive containment measures, and the unavailability of safe Ebola treatment units capable of delivering effective clinical care deterred individuals from presenting to health facilities, reporting symptomatic patients and their contacts, and cooperating with epidemic response activities. The resulting epidemic of mistrust facilitated the further spread of new infections by impeding surveillance, timely diagnosis, contact tracing, and patient isolation. In August 2018, a new Ebola outbreak was detected in eastern Dem­ ocratic Republic of the Congo (DRC) and soon became the world’s sec­ ond largest on record. In June 2020, when it was declared over, it had sickened ~3500 persons and killed two-thirds of them. Containment

3850 was complicated by armed conflict in the affected region, which had long experienced strife, impoverishment, and colonial and postcolonial extraction, feeding a well-founded suspicion of foreign intervention. Despite these challenges, responders benefitted from the arrival of new tools to prevent, diagnose, and treat Ebola. A new vaccine was extensively deployed using a ring vaccination strategy. There was sig­ nificant progress in the quality of supportive care provided to patients in DRC, with more routine monitoring, improved access to clinical laboratory services, better staffing of treatment centers, and more aspi­ rational clinical protocols. Nevertheless, the overall case-fatality rate in DRC reveals that these welcome medical innovations did not reach everyone in need of them. PART 17 Global Medicine ■ ■COVID-19 Chapter 205 provides an overview of the epidemiology, pathogenesis, and clinical manifestations of COVID-19 infection. As we near the end of the fourth year of the pandemic, there have been more than 7 million confirmed deaths due to COVID-19 infection and 780 million con­ firmed cases. Reasonable estimates suggest that the true total of deaths is likely ~18 million. During this period, COVID-19 was among the top five causes of death worldwide. In the early months of the COVID-19 pandemic, many health systems in high-income countries were strained to treat the surge of patients afflicted by it. The pandemic revealed deep structural deficiencies in our collective global ability to recognize and contain such “novel” pathogens. Although SARS-CoV-2 is “novel” in relation to our human immune systems, its rapid march across the globe followed the familiar pattern of many pandemic pathogens before it, such as HIV, tuberculosis, and cholera. It has particularly high attack rates among vulnerable populations, such as those experiencing home­ lessness and nursing home residents, and in poor communities where insufficient housing, food insecurity, and marginal employment in low-paid service jobs have resulted in inability to safely social distance and quarantine. The United States suffered during the early parts of this pandemic from underinvestment in public health systems that can provide surveillance testing at scale and perform robust contact tracing. On the global level, profound inequities occurred in access to vaccines and therapeutics. The COVID-19 Vaccines Global Access (COVAX) initiative had broad global support and ambitious goals but was unable to meet its targets. This was due, in part, to lack of access to sufficient vaccine doses as a result of excess procurement by high-income coun­ tries for their own use. COVAX successfully delivered 2 billion doses of vaccine and is thought to have averted 2.7 million deaths. We share a deep hope that this pandemic may catalyze a broader recognition about the effects of poverty on health, about the need to achieve universal access to health care for all the world’s people, and about the urgency of strengthening global public health systems. ■ ■“NONCOMMUNICABLE” CHRONIC DISEASES Although the burden of communicable diseases—especially HIV infec­ tion, tuberculosis, and malaria—still accounts for the majority of deaths in resource-poor regions within Sub-Saharan Africa and in the poorest reaches of several first-world cities, 74% of all deaths worldwide in 2022 were attributed to NCDs. Although we use this term to describe cardiovascular diseases, cancers, diabetes, and chronic lung diseases, this usage masks important distinctions. For instance, two significant NCDs in low-income countries, rheumatic heart disease (RHD) and cervical cancer, represent the chronic sequelae of infections with group A Streptococcus and human papillomavirus, respectively, and it is in these countries that the burden of disease due to NCDs is rising most rapidly. A little more than three-quarters of deaths attributable to NCDs occur in low- and middle-income countries, which also account for 85% of all early NCD-related deaths—a figure representing ~17 million persons and exceeding the total number of deaths due to AIDS, tuberculosis, and malaria combined. By 2030, NCDs will account for 52 million deaths annually worldwide if no additional action is taken. The recent increase in resources for and attention to communicable diseases is both welcome and long overdue, but developing countries are already carrying a “double burden” of communicable and noncom­ municable diseases.

Diabetes, Cardiovascular Disease, and Cancer: A Global Perspective  In contrast to tuberculosis, 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, both infectious and noninfectious. Some of these insults result from rapid changes in diet and labor conditions; others are of a less recent vintage. The burden of cardio­ vascular disease in low-income countries represents one consequence of decades of neglect of health systems. Furthermore, cardiovascular research and investment have long focused on the ischemic conditions that are increasingly common in high- and middle-income countries. Predictions of an imminent rise in the share of deaths and disabili­ ties due to NCDs in developing countries have led to calls for preven­ tive policies to improve diet, increase exercise, and restrict tobacco use, along with the prescription of multidrug regimens for persons at highlevel vascular risk. Although this agenda could do much to prevent pandemic NCDs, it will do little to help persons with established heart disease stemming from nonatherogenic pathologies. The misperception of cardiovascular diseases as a problem primar­ ily of elderly populations in middle- and high-income countries has contributed to the neglect of these diseases by global health institu­ tions, including regionally focused ones. 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 assis­ tance to the health sector during these troubled years focused on the communicable causes that accounted for <1 in 20 excess deaths during that period. DIABETES  The International Diabetes Federation reports that the number of diabetic adult patients in the world is expected to increase from 537 million in 2022—~1 in 11 adults—to 783 million by 2045. Already, a significant proportion of patients with diabetes, 3 in 4 adults with the condition, live in developing countries where, because those affected are often younger, the complications of micro- and macrovas­ cular disease take a far greater toll. Globally, these complications are a major cause of disability and reduced quality of life: a high fasting plasma glucose level ranks third among risks for disability and global mortality. The GBD 2017 study estimates that diabetes accounted for 1.6 million deaths in 2019; 84% of these deaths occurred in low- and middle-income countries. CARDIOVASCULAR DISEASE  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 term. In contrast, persis­ tently elevated blood pressure goes largely undetected, untreated, and uncontrolled in this part of the world. In the cohort of men assessed in the Framingham Heart Study, the prevalence of blood pressures above 210/120 mmHg—severe hypertension—declined from 1.8% in the 1950s to 0.1% by the 1960s with the introduction of effective antihypertensive agents. Although debate continues about appropriate screening strategies and treatment thresholds, Africa’s rural health cen­ ters, run largely by nurses, must quickly gain access to antihypertensive medications. The epidemiology of heart failure also reflects inequalities in risk factor prevalence and in access to therapy. The reported burden of this condition has remained unchanged since the 1950s, but the causes of heart failure and the age of the people affected vary across the globe. Heart failure as a consequence of pericardial, myocardial, endocardial, or valvular injury is a leading cause of hospitalization in the United States and Europe, representing ~3% of all hospitalizations, and is estimated to account for a substantial proportion of medical admissions in hos­ pitals in low-income countries as well. In high-income countries, coro­ nary artery disease and hypertension among the elderly account for most cases of heart failure. Among the world’s poorest 1 billion people, however, heart failure reflects poverty-driven exposure of children and

young adults to rheumatogenic strains of streptococci and cardiotro­ pic microorganisms (e.g., HIV, Trypanosoma cruzi, enteroviruses, M. tuberculosis), untreated high blood pressure, and nutrient deficiencies. The mechanisms underlying other causes of heart failure common in these populations—such as idiopathic dilated cardiomyopathy, peripartum cardiomyopathy, and endomyocardial fibrosis—remain unclear. In stark contrast to the extraordinary lengths to which clinicians in wealthy countries will go to treat ischemic cardiomyopathy among elderly patients, little attention has been paid to young patients with nonischemic cardiomyopathies in resource-poor settings. Nonisch­ emic cardiomyopathies, such as those due to hypertension, RHD, and chronic lung disease, account for >90% of cases of cardiac 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-associated cardiomyopathy. Lessons learned in the scale-up of chronic care for HIV infection and tubercu­ losis may be illustrative as progress is made in establishing the means to deliver heart-failure medications to these patients. Some of the lessons learned from the chronic infections discussed above are, of course, relevant to cardiovascular disease, especially those classified as NCDs but caused by infectious pathogens. Integration of prevention and care remains as important today as in 1960 when Paul Dudley White and his colleagues found little evidence of myocardial infarction in the region near the Albert Schweitzer Hospital in Lambaréné, Gabon, but reported that “the high prevalence of mitral stenosis is astonishing.” They termed it a duty to integrate prevention with penicillin prophylaxis and care, including medical management and surgery, when indicated. “The same responsibility,” they agreed, “exists for those with correctable congenital cardiovascular defects.” RHD affects almost 40 million people worldwide, with ~2.8 million new cases each year. A meta-analysis of data on heart failure in SubSaharan Africa found that RHD was the third most common cause of heart failure in the region. This disease, which may cause endocarditis or stroke, leads to >300,000 deaths per year—almost all occurring in developing countries. Results from 14 low- and middle-income countries included in the Global Rheumatic Heart Disease Registry showed that mortality was significantly higher among patients living in low-income countries and among the less educated. Recent studies in Rwanda and Ethiopia have confirmed a high prevalence of RHD among schoolchildren, including those that are asymptomatic. In part because the prevention of RHD has not advanced since the disease’s disappearance in wealthy countries, no part of Sub-Saharan Africa has eradicated RHD despite examples of success in Costa Rica, Cuba, and some Caribbean nations. Strategies to eliminate RHD may depend on active case-finding, with confirmation by echocardiography, among high-risk groups as well as on efforts to expand access to surgical interventions among children with advanced valvular damage. Partnerships between estab­ lished surgical programs and areas with limited or nonexistent facilities may help expand the capacity to provide lifesaving interventions to patients who otherwise would die early and painfully. Such partner­ ships can speed the further development of regional centers of excel­ lence equipped to provide consistent, accessible, high-quality services to those now without them. CANCER  Low- and middle-income countries accounted for ~70% of the 10 million deaths due to cancer worldwide in 2020. By 2040, annual mortality from cancer is expected to increase to >16 million deaths— with developing countries experiencing a sharper increase than devel­ oped nations. “Western” lifestyle changes may be responsible for the increased incidence of cancers of the breast, colon, and prostate among populations in low- and middle-income countries, but historic realities, sociocultural and behavioral factors, genetics, and poverty itself already have a profound impact on cancer-related mortality and morbidity rates. Cancer-causing infections, such as human papillomavirus, hepa­ titis B virus, and Helicobacter pylori, are responsible for up to 50% of cancer cases in some countries in Sub-Saharan Africa. Infectious causes of cancer will continue to have a much larger impact in developing

countries. Environmental and dietary factors, such as indoor air pol­ lution and high-salt diets, also contribute to increased rates of certain cancers (e.g., lung and gastric cancers). Tobacco use (both smoking and chewing) is the most important source of increased mortality rates from lung, bladder and oral cancers. In contrast to decreasing tobacco use in many developed countries, the number of smokers is growing in devel­ oping countries, especially among women and young persons. For many reasons, outcomes of malignancies are far worse in developing countries than in developed nations. As currently funded, overstretched health systems in poor countries are not capable of early detection; at the time of tissue diagnosis, the majority of patients already have incurable malignancies. Treatment of cancers is available for only a very small number of mostly wealthy citizens in most poor countries, and even when treatment is available, the range and qual­ ity of services are often substandard. Yet this need not be the future. Twenty years ago, MDR-TB and HIV infections were widely deemed untreatable in settings of great poverty. The feasibility of creating innovative programs that reduce technical and financial barriers to the provision of care for treatable malignancies among the world’s poorest populations is now clear (Fig. 485-3). Several middle-income countries, including Mexico, have expanded publicly funded cancer care to reach poorer populations. This commitment of resources has dramatically improved outcomes for cancers, from childhood leukemia to cervical cancer. Global Issues in Medicine CHAPTER 485 Prevention of Noncommunicable Diseases  False dichotomies, including those pitting prevention against care, persist in global health and reflect, in part, outmoded paradigms or a limited understanding of shifts in disease burden and causality as well as the dramatic variations in risk within a single nation. Moreover, such dichotomies or debates are sometimes politicized as a result of vested interests. Although globalization has had many positive effects, one negative effect has been the growth in both developed and developing countries of wellfinanced lobbies that have aggressively promoted unhealthy dietary changes and increased consumption of alcohol and tobacco. The WHO’s 2003 Framework Convention on Tobacco Control represented a major advance, committing all of its signatories to a set of policy measures shown to reduce tobacco consumption. 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 healthier diets, increased physical activity, and avoidance of tobacco. These estimates mask large local variations. Although some evidence indicates 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. 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 1.1 billion smokers live in low- and middle-income countries. In 2019, tobacco use caused 8.7 million deaths, including deaths due to second-hand smoke. The majority of these deaths occurred in low- and middle-income countries. However, there is well-proven evidence that changes in policy, such as taxes on tobacco and indoor and workplace smoking bans, are effective in decreasing the number of people using tobacco, reducing the amount of tobacco consumed, and preventing young people from starting to use tobacco. ■ ■MENTAL AND NEUROLOGIC HEALTH In 2019, 1 in every 8 people, ~970 million people worldwide, lived with a mental health disorder, including >580 million people suffering from depression and anxiety disorders. One in 4 patients visiting a health service has at least 1 mental, neurologic, or behavioral disorder, but most of these disorders are neither diagnosed nor treated. More than 700,000 people die by suicide every year, and depressive disorders are the second leading cause of years lost to disability in the world today. Most low- and middle-income countries devote <1% of their health expenditures to mental health.

PART 17 Global Medicine A B FIGURE 485-3  An 11-year-old Rwandan patient with embryonal rhabdomyosarcoma before (left) and after (right) 48 weeks of chemotherapy plus surgery. Fifteen years later, she is healthy with no evidence of disease. Increasingly effective therapies exist for many of the major causes of mental disorders. 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, and almost all of them 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, multiple barriers prevent patients from taking their medications as prescribed. In one study from Kenya, no patients being seen in an epilepsy clinic had therapeutic blood levels of anti­ seizure medications, even though all had been prescribed these drugs. Moreover, many patients in this study had no detectable blood levels of these agents at all. 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. One such program instituted in Goa, India, used lay counselors and resulted in a significant reduction in symptoms of common mental disorders among the target population. CONCLUSION: TOWARD GLOBAL

HEALTH EQUITY There is a long way to go before evidence-based internal medicine is applied effectively and equitably among the world’s poor. Public health strategies typically operate on the population level, while clini­ cal practice, including the practice of internal medicine, often remains focused on individual patient care. However, global health equity depends on avoiding the false dichotomies of the past: neither public health nor clinical approaches alone are adequate to address the prob­ lems of global health. The integration of prevention and care, along with adequate funding, has shown that complex infectious diseases such as HIV/AIDS and tuberculosis are not impossible to manage, even though drug resistance and lack of effective health systems have complicated such work. Beyond what is usually termed communicable disease—i.e., in the arena of chronic diseases such as cardiovascular disease and mental illness—global health is still a nascent, but growing, 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. Such efforts must include the building of platforms for care delivery that are robust enough to incorporate new preventive, diagnostic, and therapeutic technologies rapidly in response to changes both in the burden of disease and in the needs not met by existing paradigms and systems of care delivery. Academic medical centers have tried to address this gap as new technologies are introduced and assessed through clinical trials, but the reach of these institutions into settings of poverty is limited in rich and poor countries alike. When such centers link their capacities effec­ tively to the public institutions charged with the delivery of health care to the poor, great progress can be made. 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 scholarship and practice is still informed by the tension between clinical practice and population-based interventions, between analysis and action, and between prevention and care. A number of university hospitals have developed training programs for physicians with an interest in global health. These programs pro­ vide training not only in the clinical problems encountered in settings of poverty, but also instruction in public health, health care service delivery, and strategies of health systems strengthening. At least half of the world’s population lacks reliable access to essen­ tial health services; the consequence is millions of preventable deaths each year. An absolute majority of these premature deaths occur in Africa, with the poorer regions of Asia not far behind. They include deaths from vaccine-preventable illness, deaths during childbirth, deaths from infectious diseases that might be cured with access to anti­ biotics and other essential medicines, deaths from malaria that would have been prevented by ITNs and access to therapy, and deaths from waterborne illnesses—in short, from failures of health care delivery. Other excess mortality is attributable to the inadequacy of efforts to develop new preventive, diagnostic, and therapeutic tools. The development of these tools must be followed quickly by their equitable distribution. 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 delivery in the most heavily affected regions. When new preventive and therapeutic tools are developed without concurrent attention to delivery or implementation, one encounters what are sometimes 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