# 24 - PART 17 Global Medicine

# 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
27. Age-related hearing loss
29. Chronic kidney disease
30. HIV/AIDS
35. 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 

1. Neonatal disorders
2. Ischemic heart disease
3. Stroke
4. Lower respiratory infections
5. Diarrheal diseases
Global Issues in Medicine
CHAPTER 485
6. COPD
7. Road injuries
8. Diabetes
9. Low back pain
10. Congenital defects
11. HIV/AIDS
12. Tuberculosis
13. Depressive disorders
14. Headache disorders
15. Malaria
16. Cirrhosis
17. Lung cancer
18. Chronic kidney disease
19. Other musculoskeletal
20. Age-related hearing loss
21. Falls
22. Self-harm
40. Meningitis
41. Protein-energy malnutrition
46. Drowning
71. 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
1. Neonatal disorders
44.4
17.4
2. Lower respiratory infection
24.5
7.6
3. Malaria
23.3
7.2
4. Diarrheal disease
23.2
7.2
5. HIV/AIDS
14.5
4.5
6. Congenital defects
12.8
4.0
7. Tuberculosis
12.2
3.8
8. Stroke
8.6
2.7
9. Road injuries
6.2
2.3
10. Ischemic heart disease
7.4
2.3
High-Income Countriesa
1. Ischemic heart disease
26.8
7.6
2. Low back pain
17.7
4.9
3. Stroke
15.8
4.4
4. Lung cancer
13.7
3.9
5. Diabetes
13.3
3.7
6. COPD
12.0
3.4
7. Falls
9.7
2.7
8. Alzheimer’s disease
9.2
2.6
9. Other musculoskeletal
9.1
2.6
10. Depressive disorders
8.6
2.4
Sub-Saharan Africa
1. Neonatal disorders
70.5
13.8
2. Malaria
43.2
8.5
3. Diarrheal diseases
42.0
8.2
4. Lower respiratory infection
41.1
8.0
5. HIV/AIDS
35.6
7.0
6. Congenital defects
18.1
3.6
7. Tuberculosis
17.6
3.4
8. Road injuries
11.1
2.2
9. Stroke
10.8
2.1
10. 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
1. Neonatal disorders
0.5
9.7
2. Lower respiratory infection
0.4
8.3
3. Diarrheal diseases
0.3
6.8
4. Stroke
0.3
6.5
5. Ischemic heart disease
0.3
6.2
6. Malaria
0.3
6.1
7. Tuberculosis
0.3
5.5
8. HIV/AIDS
0.2
5.0
9. Congenital defects
0.1
2.8
10. COPD
0.1
2.5
High-Income Countriesa
1. Ischemic heart disease
1.8
16.4
2. Stroke
0.9
8.4
3. Lung cancer
0.7
6.4
4. Alzheimer’s disease
0.7
6.3
5. COPD
0.5
4.9
6. Lower respiratory infection
0.4
4.1
7. Colorectal cancer
0.4
3.8
8. Chronic kidney disease
0.3
3.0
9. Diabetes
0.3
2.3
10. Pancreatic cancer
0.2
2.1
Sub-Saharan Africa
1. Neonatal disorders
0.7
9.9
2. Lower respiratory infection
0.7
8.9
3. HIV/AIDS
0.6
8.4
4. Malaria
0.6
7.8
5. Diarrheal diseases
0.6
7.8
6. Stroke
0.4
5.3
7. Tuberculosis
0.4
5.1
8. Ischemic heart disease
0.4
5.0
9. Congenital defects
0.2
2.5
10. 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

# 02 - 486 Emerging and Re-Emerging Infectious Diseases

## 486 Emerging and Re-Emerging Infectious Diseases

high morbidity and mortality among those who cannot—grow in the 
absence of an equity plan to deliver the tools to those most at risk. 
Preventing such a future is among the most important goals of global 
health.
■
■FURTHER READING
Bukhman G et al: The Lancet NCDI Poverty Commission: Bridging 
a gap in universal health coverage for the poorest billion. Lancet 
396:991, 2020.
Cancedda C et al: Strengthening health systems while responding to 
a health crisis: Lessons learned by a nongovernmental organization 
during the Ebola virus disease epidemic in Sierra Leone. J Infect Dis 
214:S153, 2016.
Farmer P: Chronic infectious disease and the future of health care 
delivery. N Engl J Med 369:2424, 2013.
Farmer P: Fevers, Feuds, and Diamonds: Ebola and the Ravages of History. 
New York, Farrar, Straus and Giroux, 2020.
GBD 2019 Diseases and Injuries Collaborators: Global Burden of 
369 diseases and injuries in 204 countries and territories, 1990–2019: 
A systematic analysis for the Global Burden of Disease Study 2019. 
Lancet 396:1204, 2020.
GBD 2019 Risk Factors Collaborators: Global Burden of 87 
risk factors in 204 countries and territories, 1990–2019: A system­
atic analysis for the Global Burden of Disease Study 2019. Lancet 
396:1223, 2020. 
Institute for Health Metrics and Evaluation: Financing Global 
Health 2021: Global Health Priorities in a Time of Change. Seattle, 
Institute for Health Metrics and Evaluation, 2023.
Kim JY et al: Redefining global health-care delivery. Lancet 382:1060, 
2013.
Watkins DA et al: Alma-Ata at 40 years: Reflections from the Lancet 
Commission on Investing in Health. Lancet 392:1434, 2018.
David M. Morens, Anthony S. Fauci

Emerging and 

Re-Emerging 

Infectious Diseases
EMERGING INFECTIOUS DISEASES: 
DEFINITION AND CLASSIFICATION
Pathogenic microorganisms and viruses have existed in the environ­
ment and in numerous animal species for millions of years. Humans 
have presumably had endemic infectious diseases since the origins of 
the human species, about 2 million years ago. However, until about 
12,000 years ago, humans lived and moved about in small clans 
and tribal groups, experiencing limited contact with other humans 
or animals. During this pre-neolithic era, endemic infections were 
probably limited mostly to skin and gastrointestinal organisms. Even 
though contact with the environment and with animals undoubtedly 
led to sporadic infections with non-endemic pathogens, there was 
little opportunity for these pathogens to become widely spread among 
humans, i.e., to become epidemic.
This situation changed dramatically in the early neolithic age, about 
10,000 BCE, in association with domestication of animals for food and 
for labor, planting and fertilization of crops, storage of water, organized 
disposal or diversion of sewage, growth of large settled villages and 
towns, labor specialization, and an enormous increase in human crowd­
ing and animal–human contacts. These new elements of human societal 
existence were associated with the emergence and human adaptation 

of existing enzootic and environmental organisms within populations 
large enough to sustain human-to-human spread, i.e., to cause emerging 
epidemics. It is believed that in this period the first significant emerging 
infectious diseases (EIDs) appeared.
The likelihood that numerous pandemic emergences occurred 
between the onset of the neolithic era and the era of microbial iden­
tification (beginning in the nineteenth century) is suggested by the 
large number of human pathogens that are today found globally in 
genetic and phenotypic forms that are identical or highly similar to 
each other—e.g., skin organisms such as staphylococci (Chap. 152), 
streptococci (Chap. 153), pneumococci (Chap. 151), and corynebacte­
ria (Chap. 155); enteric pathogens like Escherichia coli (Chap. 166) and 
salmonellae (Chap. 171); latently infecting neural viruses like herpes­
viruses (Chap. 200); and sexually transmitted agents like human papil­
lomavirus (Chap. 203), gonorrhea (Chap. 161), and syphilis (Chap. 
187). In some cases, microbial/virologic phylogenetic data allow rough 
estimation of the times of pathogen emergences, but even without such 
data, it is obvious that pandemic spread had to have occurred at some 
time in the past if we are to explain the global prevalence of many 
human pathogens today. EIDs and indeed pandemic IDs are thus a very 
old human phenomenon that we have only recently begun to consider.
Emerging and Re-Emerging Infectious Diseases  
CHAPTER 486
EIDs have been defined and characterized as shown in Table 486-1. 
The importance of distinguishing between newly emerging IDs and 
re-emerging IDs (REIDs) has particular significance for clinicians, who 
usually are not only among the first to encounter the newly emerging 
group, but also among those with the greatest expertise in recogniz­
ing and dealing with the second group. It is also of note (Table 486-1) 
that subcategories of REIDs include accidental release of pathogens 
by human activities, e.g., vaccine-derived polioviruses or the sudden 
1977 pandemic appearance of a long-extinct 1950s-era H1N1 influenza 
virus, presumably a result of undisclosed vaccine or other virologic 
research that led to viral “escape.”
EMERGING INFECTIOUS DISEASES: THEIR 
IMPORTANCE
EIDs have been among the leading causes of death, disability, and 
social disruption throughout recorded human history (Table 486-2). 
For example, it is believed by some historians that at least two of the 
biblical pharaonic plagues (around the thirteenth century BCE) were 
EIDs. The regionally pandemic “Plague of Athens” (430–425 BCE) 
is said to have brought about the end of the “Golden Age” of Greece. 
TABLE 486-1  Emerging and Re-Emerging Infectious Diseases: 
Definitions, Categories, and Examples
Emerging infectious diseases (EIDs) are those recognized in humans for the first 
time, e.g., HIV/AIDS, Nipah virus infection, or severe acute respiratory syndrome 
(SARS) and COVID-19.
Re-emerging infectious diseases (REIDs) are those that have infected 
humans in the past and continue to reappear in new locations (e.g., West 
Nile virus in the United States and Russia in 1999), reappear in resistant or 
otherwise phenotypically different forms (e.g., influenza, methicillin-resistant 
Staphylococcus aureus, drug-resistant falciparum malaria), or reappear after 
apparent control or elimination (e.g., poliomyelitis in parts of Africa, cholera in 
Haiti in 2010 and elsewhere in association with natural disasters, wars, and mass 
migrations) or under unusual circumstances (e.g., deliberately released agents, 
including the 2001 anthrax bioterrorism attacks). Important subcategories of 
REIDs include the following:
REIDs related to accidental human release—e.g., vaccine-derived polioviruses, 
epizootic vaccinia virus, and the 1979 Sverdlovsk laboratory explosion releasing 
anthrax spores
REIDs caused by human intent to harm (bioterrorism)—e.g., the 1997 Oregon 
salad bar poisonings and the 2001 anthrax spore attacks in the United States
Established infectious diseases or endemic infectious diseases are those that 
have been prevalent for a sufficient period of time to allow for a relatively stable 
and predictable level of morbidity and mortality (e.g., many viral and bacterial 
respiratory and diarrheal diseases, including respiratory syncytial virus, endemic 
coronaviruses, noroviruses, pneumococcal disease, drug-susceptible malaria 
and tuberculosis, and many other tropical diseases such as helminthic and other 
parasitic diseases, many nosocomial infections).

TABLE 486-2  Selected Emerging Infectious Diseases of Note, 430 BCE to 2024 AD
YEAR
NAME
DEATHS
COMMENTS
430 BCE
“Plague of Athens”
~100,000
First identified transregional pandemic

Justinian plague (Yersinia pestis)
30–50 million
Pandemic; killed half of then-known world population
1340s
“Black Death” (Yersinia pestis)
~50 million
Pandemic; killed at least one-quarter of the known world population

Syphilis (Treponema pallidum)
>50,000
Pandemic brought to Europe from the Americas
c. 1500
Tuberculosis
High millions
Ancient disease; became pandemic in Middle Ages

Hueyzahuatl (Variola major)
3.5 million
Pandemic brought to New World by Europeans
1793–1798
“The American plague”
~25,000
Yellow fever terrorized colonial America

Second cholera pandemic (Paris)
18,402
Spread from India to Europe/Western Hemisphere
PART 17
Global Medicine 

“Spanish” influenza
~50 million
Led to additional pandemics in 1957, 1968, 2009
1976–2020
Ebola
More than 15,000 deaths
First recognized in 1976; 29 regional epidemics to 2020

Acute hemorrhagic conjunctivitis
Rare deaths
First recognized in 1969; pandemic in 1981

HIV/AIDS
> 40 million
First recognized in 1981; ongoing pandemic

SARS

Near-pandemic

H1N1 “swine flu”
284,000
Fifth influenza pandemic in less than 100 years

Chikungunya
Uncommon but high morbidity
Pandemic, mosquito-borne

Zika
~1000?*
Pandemic, mosquito-borne
*Zika mortality has not been fully established. Most deaths are fetal or related to outcomes of severe congenital infections.
Source: Reproduced with permission from DM Morens, AS Fauci: Emerging pandemic diseases: How we got to COVID-19. Cell 182:1077, 2020.
Both the Justinian plague (544 AD) and the Black Death pandemics of 
bubonic/pneumonic plague of 1347–1349 AD (Chap. 176) depopu­
lated large segments of Europe and surrounding regions. The cholera 
(Chap. 173) pandemic of 1831–1832 killed large numbers of Europeans 
and ushered in the first modern studies to characterize disease and 
death in modern epidemiologic terms.
The past century has featured three of the most highly fatal pan­
demics the world has ever experienced: the 1918 H1N1 influenza 
(Chap. 206) pandemic, thought to have been the deadliest pandemic 
in human history; the human immunodeficiency virus (HIV)/acquired 
immune deficiency syndrome (AIDS) pandemic (Chap. 208), which 
so far has killed more than 40 million people; and the COVID-19 
pandemic (Chap. 205), which is now (2024) in its fifth year, having 
killed more than 7 million people so far, and by some estimates as 
West Nile virus
Ebola virus
Cryptosporidiosis
Enterovirus D68
Heartland
virus
Powassan
virus
Antimicrobialresistant threats
 - CRE 
- C. difficile
 - MRSA - N. gonorrhoeae
H3N2v influenza
Cyclosporiasis
E. coli O157:H7
Hepatitis C
vCJD
Lyme
disease
Measles
Listeriosis
Adenovirus 14
Human mpox
Acute flaccid myelitis
Bourbon virus
2009 H1N1 influenza
Anthrax bioterrorism
Hantavirus pulmonary
syndrome
 Dengue
Chikungunya
Zika virus
Yellow fever
Human African trypanosomiasis Cholera
Plague
February 2020
Newly emerging
Re-emerging/resurging
“Deliberately emerging”
FIGURE 486-1  Selected newly emerging, re-emerging, and human-caused emergences over recent decades. (Reproduced with permission from DM Morens, AS Fauci: 
Emerging pandemic diseases: How we got to COVID-19. Cell 182:1077, 2020.)

many as 20 million. In addition to the highly fatal and the potentially 
fatal pandemics of the past century, recent decades featured a seeming 
Pandora’s box of EIDS (Fig. 486-1), including novel pathogenic agents, 
re-emerging agents, and agents that are known but have re-emerged in 
entirely new forms, e.g., dengue hemorrhagic fever (Chap. 215), Zika, 
and numerous antibiotic-resistant bacteria (Chap. 150). It appears that 
we have entered a new era in which emergences and re-emergences of 
IDs are increasing in frequency and impact.
RESPONSE OF THE MEDICAL COMMUNITY 
TO INFECTIOUS DISEASES
Acceptance of the concept of infection—almost complete before 
1890—quickly led to treatments such as antitoxins and immune plasmas, 
soon thereafter to non-vaccinia immunogens, by the 1930s to powerful 
Diphtheria
Drug-resistant malaria
Akhmeta virus
MERS-CoV
E. coli
O104:H4
Rift Valley fever
Typhoid fever
SFTSV bunyavirus
E. coli O157:H7
PNA syndrome
H5N6 influenza
Coronavirus
disease 2019
(COVID-19)
H10N8 influenza
H7N9 influenza
Lassa
fever
HIV
H5N1 influenza
SARS
Nipah virus
Hendra virus
Nipah virus
Enterovirus 71
Human mpox
Ebola virus
Zika virus
Marburg
virus
MDR/XDR
tuberculosis

antibiotics, and, by the 1950s, to antivirals. Ironically, however, these 
successes, which many considered miraculous, also led to significant 
overconfidence. By the 1960s, experts were predicting that infectious 
diseases would be conquered. In 1981 the U.S. Centers for Disease 
Control and Prevention was reorganized to pivot away from IDs and 
toward chronic and lifestyle-associated diseases that caused the great­
est U.S. mortality and years of productive life lost (YPLL). Then, before 
the year was out, the world was shocked by the appearance of the AIDS 
pandemic, caused by a previously unknown body fluid–transmitted 
virus: HIV.
Although the AIDS pandemic was an enormous challenge, the 
biomedical research community, together with the pharmaceutical 
industry, eventually responded, most importantly by developing effec­
tive combination antiretroviral therapies, as well as risk-reduction pro­
grams such as needle exchanges and education in safe sexual practices.
A 1992 report of the Institute of Medicine (IOM; now the National 
Academy of Medicine) drew attention to the enormous problem of 
emerging infections, coined the term and characterized the scope of 
EIDs, defined the variables associated with emergences, and made farreaching recommendations for preparedness, response, research, train­
ing, and medical and public health practice. Today, clinicians, scientists, 
public health officials, and government leaders work together within 
a global infrastructure of EID awareness, in which preparedness and 
response capacity have been increasingly successful. Such successes 
include stopping SARS from becoming globally pandemic and then 
eradicating its virus as a human pathogen; turning AIDS from an 
inevitably fatal disease to one associated with a normal lifespan for 
most patients who take antiviral medication; establishing the United 
States President’s Emergency Plan for AIDS Relief (PEPFAR) program 
to bring life-saving AIDS treatment to the poorest corners of the world; 
and success in controlling the 2014–2016 regional Ebola (Chap. 216) 
pandemic in West Africa, without a vaccine or proven treatment, using 
standard public health measures alone.
This modern global EID control infrastructure includes not only 
vigorous detection of and response to EIDs, including international 
health regulations and EID oversight by the World Health Organiza­
tion (WHO), but also controlling and even eradicating existing dis­
eases. Apart from SARS, mentioned above, in 1980 smallpox (Chap. 201) 
was declared eradicated, a feat considered by some to be the most sig­
nificant accomplishment in medical history, given the millions killed 
by the virus over many thousands of years. In 2011, the veterinary 
disease rinderpest was declared eradicated as well. A number of other 
important IDs now appear to be either close to eradication—e.g., polio­
myelitis (Chap. 210), dracunculiasis (Chap. 240)—or significantly 
controlled globally with eradication at least on the horizon—e.g., mea­
sles (Chap. 211), rubella (Chap. 212), yaws (Chap. 183). All aspects of 
ID control, including controlling and trying to eradicate old emerging 
and still-re-emerging IDs, as well as preventing and controlling the 
emergences of new ones, work toward the same goal of reducing the 
impact of IDs on global human morbidity and mortality.
MECHANISMS OF EMERGENCE
Pathogens that newly emerge into humans are acquired via several dif­
ferent mechanisms. Some emerging pathogens are dead-end infections, 
i.e., they are not usually transmitted onward to other humans, and thus 
are not likely to become epidemic. Common examples of such infec­
tions are those arising from environmental “point-source exposures,” 
in which many humans are exposed to a pathogen in one place over 
a very narrow window of time, e.g., coccidioidomycosis (Chap. 219) 
and histoplasmosis (Chap. 218) outbreaks associated with excavations, 
norovirus (Chap. 209) outbreaks aboard cruise ships (due to sewagecontaminated water), or bacterial/bacterial toxin contamination of 
foods in restaurants or at picnic or banquet events. Such point-source 
emergences tend to be sporadic, unpredictable, and of very short dura­
tion, the causative organisms being from the environment and usually 
well known and easily diagnosed, e.g., norovirus outbreaks identified 
by epidemiologic and clinical characteristics, or easily tested for, e.g., 
bacterial culture of enteric pathogens. They are typically short out­
breaks of high morbidity but low mortality.

A second category of disease emergence, animal-to-human host 
switching, is of relevance to both newly emerging and re-emerging dis­
eases and accounts for virtually all novel pandemics (e.g., the influenza 
pandemic of 1918, HIV/AIDS) and many re-emerging IDs as well (e.g., 
human mpox, human Rift Valley fever). In the past two decades there 
has been much theoretical and microbiologic and virologic research 
on how such zoonotic emergences occur. Current concepts are briefly 
summarized. Most animal and human pathogens, and especially 
viruses infecting mammals, are specifically adapted to a narrow host 
group, such as a single host species—e.g., the many New World hanta­
viruses, which tend to have been finely adapted to single rodent species 
over thousands of years. Such pathogens may have a limited ability to 
infect closely related species, and they are not normally highly trans­
missible between members of new host species they do infect. Measles, 
for example, is a human-adapted virus which can infect some primate 
species, but despite its extraordinary contagiousness for humans, it is 
not naturally transmitted between primates. How then do pathogen 
emergences into new host species, and most importantly into humans, 
occur?
Emerging and Re-Emerging Infectious Diseases  
CHAPTER 486
This is an extraordinarily difficult question to answer, since emer­
gences tend to occur in a “black box,” out of sight of scientists and epi­
demiologists, and indeed typically in remote locales. But it is theorized 
that such emergences result from uncommon constellations of other­
wise low-risk molecular genomic and ecologic events (Chaps. 125 and 
126), which include pathogens (particularly viruses) with high mutation 
rates, such as many RNA viruses; intense or unusual human–animal 
contact; and chance. A theoretical model (Fig. 486-2) posits that a 
virus well adapted to its primary host is likely to be non-adapted or at 
least far less adapted to other potential hosts, even closely related ones. 
But since viruses have high mutation rates, there will always be some 
virions that have mutated to become less well adapted to their own 
hosts and, by chance, some of these may “accidentally” have acquired 
an ability to adapt to a new host. Presumably, very few of these mutated 
viruses come into contact with potential new hosts before they are 
“purged,” but if one or more virions is (1) is not significantly de-adapted 
to its normal host, (2) is, at the same time, capable of adapting to a new 
host, and (3) is able to cross a “fitness valley” of de-adaptation to the 
old host and neo-adaptation to the new host, a host switch may occur 
(Fig. 486-2). This model attempts to explain why major emergences 
are relatively uncommon (e.g., despite countless billions of viral muta­
tions occurring daily, looking back over the past 500 years, there has 
only been about one new recognized influenza pandemic every 30 or 
so years). It might be said, teleologically, that pathogens are constantly 
“trying” to emerge, but almost always failing to do so.
A third category of disease emergence relates to mutations that 
occur in pathogens that are already human adapted, the best-known 
example being development of antibiotic resistance in a bacterial 
species previously susceptible to particular antibiotics. Although 
antibiotic-resistant pathogens live in the soil and other natural envi­
ronments and have done so since before human-developed antibiotics 
existed, bacteria are also capable of horizontally transmitting to other 
bacteria DNA-containing resistance genes, and these may be selected 
for in Darwinian fashion, e.g., by medical and hospital environments 
in which antibiotics are administered (Chap. 147). An analogous prin­
ciple even applies to viruses. Particularly as viruses gain access to larger 
human populations via crowding and human movement, mutation 
may lead to a fitness advantage, e.g., to a more transmissible phenotype 
that may escape natural and vaccine-induced immunity, and may even 
be associated with increased pathogenicity, as may have happened with 
the SARS-CoV-2 delta variant in 2022. A similar phenomenon was 
seen beginning in 2014 with the re-emergence of enterovirus D68 
(EV-D68) to cause global epidemics of acute flaccid myelitis.
VARIABLES ASSOCIATED WITH 

DISEASE EMERGENCE
Whatever the mechanisms of pathogen emergence may be, it has 
become clear that the determinants of emergence—i.e., variables 
that provide opportunities for pathogens in disturbed ecosystems to 
emerge, typically beginning with the host switch of an animal pathogen

Steep Fitness Valley
Shallow Fitness Valley
Fitness
Fitness
Donor
Species
Recipient
Species
Donor
Species
Recipient
Species
PART 17
Global Medicine 
Mutation frequency
Mutation frequency
A
B
Chance Transmission of Multiple
Advantageous Mutations
Progressive Adaptation in the
Recipient Species
Donor Species
Recipient Species
C
D
FIGURE 486-2  A theoretical model of how animal-to-human pathogen host-switching might occur, in this case the 
pathogen being a virus. The light-colored viruses represent those adapted to the transmitting host, and the darkcolored viruses represent those mutating in the direction of the host to which the virus is adapting. A and B compare 
two different situations in which there is a deep virus–host fitness valley (A) or a shallow fitness valley (B), 
the valleys representing the degree of challenges that mutable viruses need to overcome to be able to infect new 
host species. To be able to cross the steep fitness valley, a virus that is at peak adaptation to host 1 must mutate 
significantly in the direction of de-adaptation to be able to infect host 2, an event that is more likely if the virus has 
a high natural rate of mutations. In B, a narrow fitness valley is more easily crossed, resulting in a host switch. The 
phylogenetic trees in C and D show the adaptational mutations that necessarily occur for a virus that has crossed 
a steep fitness valley (shown in A) as it adapts to the new host (C). In D, a virus that has crossed a narrow fitness 
valley (as shown in B) does not “need to” adapt to the new host as significantly (C) to be able to initiate and sustain 
transmission between hosts of the new species. (Reproduced with permission from DM Morens, AS Fauci: Emerging 
pandemic diseases: How we got to COVID-19. Cell 182:1077, 2020.)
within a geographically identified global “hot spot”—are largely related 
to humans and human activities (Fig. 486-3). Most of the important 
variables associated with pathogen emergence are either activities of 
the human host—demographics and behavior including crowding, 
human movement, sexual practices, and occupation (Fig. 486-3, upper 
right)—or variables that reflect human degradation of the environment—
poverty and social ills, wars, displacements, land use practices, and 
inadequate public health infrastructure (Fig. 486-3, lower right). Even 
though HIV clades probably emerged separately and independently 
more than a century ago, AIDS did not become pandemic until signifi­
cant viral transmission could be sustained within a modern humandominated global environment, once composed of remote villages but 
more recently replaced by urban environments, transnational travel 
and commercial sex work, meeting places for men who have sex with 
men, IV drug use, and blood product transfusions. The emergence of 
hyperendemic dengue and dengue hemorrhagic fever after World War II 
was associated with urban crowding and domestic water storage. The 
United States epidemic of hepatitis C (Chaps. 350 and 352), which 
began in the 1960s, was associated with blood product transfusions 
and injection drug use. The emergence of hantavirus pulmonary syn­
drome was associated with construction of human-made peridomestic 
outbuildings and unfinished basements that housed infected reservoir 

rodents during the winter. The emergence 
of Nipah virus (Chap. 204) in Malaysia in 
1998 was associated with both deforesta­
tion and intensive pig farming practices. 
The 2003 United States mpox outbreak was 
associated with unregulated importation 
of rodent pets from enzootic areas. Emer­
gence in China of both H5N1 and H7N9 
poultry influenza A (“bird flu”) was associ­
ated with crowded live animal markets, and 
it stopped quickly when these markets were 
shut down. The 2010 cholera epidemic in 
Haiti followed a devastating earthquake 
associated with human displacement, loss 
of access to safe water, inadequate medi­
cal and social support, and the arrival of 
aid from foreign locales that inadvertently 
imported cholera organisms.
It should be noted that emergence vari­
ables are not always identical between the 
newly emerging and re-emerging IDs. Reemergences of known pathogens are more 
likely to result from societal failures to cre­
ate and sustain safe human environments, 
and to disruption of balanced ecosystems 
in the natural world. Emergences of new 
pathogens such as pandemic influenza, on 
the other hand, are sometimes unique and 
highly improbable events. It is noteworthy 
that for diseases like influenza, in which 
transmission is facilitated by crowding and 
human movement, the intervals between 
pandemics are about the same today as they 
were 500 years ago, despite an eightfold 
increase in the global population and the 
advent of modern rapid global travel. This 
suggests that influenza pandemics are rare 
stochastic events unrelated to the size of the 
population that spreads them, even though 
population growth spreads them more 
widely and more quickly than they once did.
EXAMPLES OF 
CHALLENGES OF DISEASE 
EMERGENCE AND HOW 
THEY ARE BEING MET
The complexities of potential control of pathogen emergence and 
re-mergence are noteworthy: each emergent disease presents a differ­
ent challenge, as briefly summarized below for three selected patho­
gens of global importance.
■
■INFLUENZA A
The reservoir of influenza A viruses is the global pool of wild waterfowl 
and shorebirds. All human, other mammalian, and poultry-associated 
influenza viruses are derived from this pool. The 1918 pandemic 
influenza H1N1 “founder” virus either was derived directly from a 
waterfowl or had a brief period in another mammalian host before 
becoming pandemic. Humans immediately transmitted it to domestic 
pigs in 1918; descendants of those human and pig viruses still exist in 
whole or in part, having devolved into separate and increasingly diver­
gent lineages over the past century. The three influenza pandemics that 
have occurred since 1918 were all caused by genetic descendants of the 
1918 virus, having been naturally modified by genetic changes of sev­
eral types. Such mutations make control and prevention difficult. The 
viruses have multiple mutational mechanisms to circumvent human 
immunity, including (1) genetic “drift” (point mutations); (2) “shift” 
(importation of different avian hemagglutinins with or without impor­
tation of neuraminidases); (3) intrasubtype reassortments (importation

• Cell tropism 
• Alternative and co-receptors 
• ADE and related phenomena 
• Genetic/inherent susceptibility
• Immune protection 
• Genetic diversity
• Genetic evolution and change
• Variable infectivity
• Immunodominant antigens
• Co-pathogenesis
ENVIRONMENT
AGENT
FIGURE 486-3  Infectious agents, hosts, and the environment: determinants of disease emergence, re-emergence and persistence. Factors most closely associated with 
re-emergences are highlighted, including accidental and purposeful human release of infectious pathogens. (Reproduced with permission from DM Morens, AS Fauci: 
Emerging pandemic diseases: How we got to COVID-19. Cell 182:1077, 2020.)
of whole human hemagglutinin or neuraminidase subtype variants), 
and (4) glycosylation of external protein sites that can alter viral struc­
ture and function. With a broad repertoire of mutational possibilities, 
a human-adapted virus may repeatedly escape population immunity 
elicited by natural infection and vaccination, as has been the case with 
the 1968 pandemic H3N2 virus, which is still causing infections and 
death, and escaping vaccine immunity, 56 years after its appearance. 
During this interval it has also periodically, and for unknown reasons, 
increased in pathogenicity.
Influenza control is further confounded by the fact that influenza 
A is a nonsystemic virus that replicates on a one-cell-deep layer of 
respiratory epithelium, without fully encountering the human systemic 
immune system. Because influenza has a very short incubation period, 
there is too little time for the virus to fully elicit memory immune cells, 
the virus only encountering the less specific innate immune system, 
as well as IgA and IgM antibodies secreted across the epithelium from 
the systemic circulation (only fully effective in high concentration). 
It also has an advantage in replicating only in an immune environ­
ment of the upper respiratory tract that tolerates multiple continuous 
antigenic exposures, including brief viral infections, without massive 
immune responses that could be harmful to the host. Thus, influenza 
vaccines are at best incompletely effective and protect for only a matter 
of months. This will be an important challenge in attempts to develop 
universal influenza vaccines.
It is also noteworthy that pandemic and postpandemic influenza 
viruses are increasingly better adapted to the modern world. Before 
1889, the predominant travel mechanism of influenza spread was by 
coach, globalization of spread taking as much as a year or more, or 
failing to occur at all. Until the 1700s, the Americas and Europe did 
not even appear to have been on the same influenza pandemic cycles. 
(Although the earliest genetically sequenced influenza viruses date 
to 1918, scholars have for several centuries presumptively identified 
influenza pandemics on the basis of characteristic clinical-pathologic 
signs and symptoms, epidemiologic patterns, and route and rapid­
ity of global spread). In the 1889 pandemic, presumed influenza was 
spread from East Asia to Europe by rail. The 1918 and 1957 pandemics 
were spread predominantly by ship, and the 1968 and 2009 pandem­
ics predominantly by air. Influenza spread is ideally suited to human 
movement and crowding. Furthermore, high rates of presymptomatic 
and subsymptomatic infection allow the virus to be transmitted by 

• Demographics and behavior 
 – International travel/trade/recreational 
 – Sex 
 – Occupation 
 – Antibiotic misuse
HOST 
Emerging and Re-Emerging Infectious Diseases  
CHAPTER 486
• Animal exposures
• Environmental degradation
• Climate and weather
• Economic development/land use
• Technology/industry/agriculture
• Poverty and social ills
• Wars, famines, natural disasters
• Lack of public health infrastructure
• Lack of political will
DISEASE
persons who do not know they are infectious or capable of transmitting, 
thwarting attempts to lower transmission by public health measures.
In short, influenza A is an avian virus emerging out of nature. It 
remains difficult to prevent or to identify in advance an avian influ­
enza virus with pandemic potential. At this point we have limited 
ability to control constantly mutating viruses once they have become 
human-adapted.
■
■SARS AND SARS-CoV2
The sarbecoviruses (SARS-like beta-coronaviruses) are similar to 
influenza in some respects and different in others. Their natural reser­
voir is not birds but bats, and the main human host receptor for viral 
infection is the angiotensin-converting enzyme 2 (ACE2) receptor, as 
opposed to respiratory tract sialic acid receptors for influenza. Because 
ACE2 receptors on bats, many other mammals, and humans are quite 
similar, sarbecoviruses can be thought of as potentially preadapted to 
humans. It is in part for this reason that many experts predict future 
emergences of these viruses.
Similar to influenza, SARS-CoV2 is a respiratory virus that does not 
produce true viremia, has a short incubation period and incomplete 
exposure to the systemic immune system, and often causes asymptom­
atic or subsymptomatic infection, bedeviling control with public health 
measures such as social distancing and isolation. Also similar to influ­
enza, and despite its moderate transmissibility, it can be “superspread” 
in crowded environments such as restaurants and bars, churches, 
sports venues, or any crowded place, especially if there is imperfect 
airflow and humidity. In addition, like influenza, SARS-CoV2 evolves 
continually (not however by genetic reassortment, but by mutation 
and recombination), continually escapes population immunity, and is 
imperfectly prevented by vaccines. As has been the case with influenza, 
control of emerging SARS-CoV2, and prevention of population spread 
and large-scale mortality, remains difficult.
■
■DENGUE
A third example of the complexities of emergence and response, in 
this case re-emergence, is dengue. An Aedes aegypti–borne flavivirus, 
“dengue virus” is actually four closely related viruses (DEN-1, DEN-2, 
DEN-3, and DEN-4) that interact with each other serologically and 
with respect to immunity and pathogenicity. Dengue is believed to 
have emerged more than 400 years ago, perhaps much earlier, and has

3858 been endemic and hyperendemic around the tropical belt ever since, 
re-emerging sporadically to cause high morbidity and sometimes high 
mortality. Emergences now occur repeatedly in the U.S. commonwealths 
of the Northern Mariana Islands and Puerto Rico, in the U.S. territories 
of Guam, American Samoa, and the United States Virgin Islands, and 
in the United States–affiliated Federated States of Micronesia. At one 
time, large-scale dengue epidemics were common in the continental 
United States, e.g., a major epidemic in Philadelphia in 1780; in recent 
years smaller outbreaks have occurred in southern states. Despite the 
fact that all dengue cases occur within a human-to-mosquito-to-human 
transmission cycle, without direct human-to-human transmission, den­
gue re-emergences can be so explosive that they mimic the most highly 
contagious respiratory viruses. During simultaneous 1977 outbreaks of 
dengue and influenza in Puerto Rico, within-household studies showed 
greater case-clustering of dengue than of influenza.
PART 17
Global Medicine 
Dengue is highly associated with peridomestic water storage (where 
vector mosquitoes oviposit), lack of sanitation, crowding, and lack of 
screens and air conditioning. It would seem a simple matter to control 
dengue by controlling water storage, but even Singapore—a developed 
country whose residences have screens, air conditioning, excellent 
sanitation, and public health mosquito police who constantly patrol 
residences and public places to examine for breeding sites, assessing 
fines for even minor breeding site violations—is unable to prevent 
dengue outbreaks from occurring. A difficult problem seems to be that 
mosquitoes can oviposit in the tiniest and most inconspicuous bits of 
water, e.g., the slight (several millimeter) indentations in the bases of 
porcelain toilets where they are bolted to the floor.
Although dengue was historically considered a nuisance disease, 
shortly after World War II (during which only 4 of more than 90,000 
dengue-infected servicemen/service women died) a new and highly 
fatal clinical form emerged in Southeast Asia and quickly became a 
significant killer of children. Studied by teams of Thai and American 
scientists, the new clinical form was classified as dengue hemorrhagic 
fever (DHF) and, in its most severe form, dengue shock syndrome 
(DSS), a result of sudden massive extravasation of intravascular fluids 
into the tissues. But the very same viruses that caused the mild form 
of dengue were also those that caused DHF and DSS, a puzzle that 
was unraveled by Halstead and others when it was learned that it was 
predominantly only with the second of four potential dengue infec­
tions (one with each of the four serotypes) that DHF/DSS occurred. 
Epidemiologic data were consistent with the belief that cross-reactive 
antibodies elicited by the first dengue infection, unable to neutralize 
the second virus, actually potentiate viral entry into cells via antibodydependent enhancement for the acute clinician, dealing with EIDS 
depends upon  ecologic perspectives on infectious disease occurrence.
Only in recent years have science and medicine begun to make an 
impact on severe dengue disease, including training of clinicians and 
parents, the widespread availability of oral rehydration solutions that 
reverse shock syndrome, and several recently developed vaccines. But 
fear remains that vaccines might potentiate more severe disease, and 
dengue remains among the greatest re-emerging disease problems for 
more than 3 billion people.
The three emerging disease examples noted above exemplify the 
complexity of disease emergence: the role of demographic and envi­
ronmental variables (live poultry markets in severe human influenza; 
human-made peridomestic environments in dengue), pathogen inter­
actions (partial immune crosses in influenza and dengue, related 
to both protection and disease severity, as well as to diagnostic dif­
ficulties), complete or partial immune escape (all three pathogens), 
immunopathogenesis (1918 influenza and dengue), inherent problems 
in vaccine prevention (all three diseases), animal reservoir hosts of 
progenitor viruses (all three diseases), viral evolution via mutations (all 
three diseases), and many other factors.
THE ROLE OF CLINICIANS AND 
LABORATORIANS IN EID CONTROL
Clinicians and laboratorians are on the front lines of EID control 
and response efforts, and they must continue to play a leading role in 
global pandemic preparedness and response. It is typically the astute 

clinician who first recognizes a new disease, usually because signs and 
symptoms, or complications, are not typical of similar diseases. For 
example, in the 1918 influenza pandemic there was never-before-seen 
pneumonia-associated case-fatality featuring viral infection and bacterial 
co-pathogenesis, the bacteria being normal oral flora and the pneumonia 
producing an anatomic pattern, diagnosed clinically or in some cases by 
x-ray, which was invariably bronchopneumonic. In the 1950s, emergence 
of dengue hemorrhagic fever was associated with never-before-seen 
complications, including shock and death, occurring in association with 
endemic dengue viruses and in epidemiologic patterns that were novel 
(shock occurring only in infants under one, and in older toddlers and 
school-aged children, but sparing children between these ages, as well as 
those in and beyond the older teenage years). In fact, it was the bizarre 
and unprecedented age-specific mortality patterns of DSS that suggested 
its pathogenetic mechanisms. That legionellosis (Chap. 164), first identi­
fied in 1976, must have been an unknown emerging disease was learned 
when clinicians were unable to make a pathogen-specific pneumonia 
diagnosis and laboratories were unable to isolate a pathogen. A similar 
profile was seen with SARS, emerging in 2002–2003, when adults with 
respiratory/constitutional symptoms typical of many respiratory viruses 
experienced an approximate 10% case-fatality rate.
It is not only primary care providers who are in a position to recognize 
newly emerging diseases. Both emerging acute hemorrhagic conjuncti­
vitis (AHC) in 1969–1970 and emerging human Rift Valley fever (RVF) 
in 1977 were largely identified by ophthalmologists who observed the 
unexpected: severe and explosively epidemic conjunctivitis with AHC, 
and blindness associated with macular infiltrates in RVF. In 1981, it 
was pathologists who identified Pneumocystis carinii (now jirovecii) 
pneumonia in autopsies of previously healthy young men, joining epi­
demiologists and clinicians in characterizing a new clinical-pathologic 
syndrome that was eventually recognized as AIDS. And it was pediatric 
neurologists who played a major role in identifying emergent enterovirus 
D68–associated acute flaccid myelitis beginning in about 2014. Even 
looking back in history to a time before the microbial era, we can identify 
the same phenomenon: it was a “proto-epidemiologist” who first imag­
ined that cervical cancer was the result of a contagious disease when he 
showed, in the 1840s, that nuns never suffered from it.
Among the skills of medical practitioners related to a key front-line 
role in dealing with EIDs are the following: (1) abiding curiosity; (2) the 
ability to sense something out of the ordinary and pursue suspicions, 
using the medical history, physical examination, and laboratory tests 
(Chaps. 8 and 505); (3) a sense of the epidemiology of different diseases 
that allows imagination of how an illness might have been acquired, of 
the mechanism of acquisition—environmental, respiratory, inocula­
tion (including sexual inoculation), gastrointestinal, occupational, etc. 
(Fig. 486-3); (4) whether there are family or other case clusters, and 
whether such clusters represent common-source exposure, zoonotic 
exposure, or person-to-person transmission; (5) determination of an 
approximate incubation period and duration of infectivity; (6) a close 
relationship with the diagnostic laboratory and knowledge of when to 
seek additional laboratory follow-up; (7) a close relationship with allied 
practitioners, including specialists, and with disease researchers; (8) a 
close relationship with public health workers, diligence in promptly 
reporting reportable diseases and reportable disease syndromes, and 
awareness of outbreaks that may be occurring in the community; (9) 
regular reading of the medical literature to stay grounded within and 
outside of one’s specialty; and (10) skill at communicating with and 
eliciting trust from patients, which appears to maximize the chance of 
finding clues that may be easily missed.
History tells us that EIDs will certainly continue to appear, includ­
ing some so novel that they cannot even be imagined. An important 
component of the biomedical and public health enterprise is the ability 
to recognize, diagnose, and begin to control EIDs at the earliest pos­
sible time, and to limit their spread so that emergences do not evolve 
into epidemics. This requires coordinated efforts of those in multiple 
disciplines, communicating with each other rapidly and effectively. It 
is a part of the significant responsibilities of medical, biomedical, and 
public health practitioners, who together have the critical skill sets 
needed to confront the existential threats of EIDs.

# 03 - 487 Primary Care and Global Health

## 487 Primary Care and Global Health

■
■FURTHER READING
Fauci AS, Morens DM: The perpetual challenge of infectious diseases. 
N Engl J Med 366:454, 2012.
Harper K: Plagues Upon the Earth: Disease and the Course of Human 
History. Princeton, Princeton University Press, 2023.
Keusch GT et al: Pandemic origins and a One Health approach to 
preparedness and prevention: Solutions based on SARS-CoV-2 and 
other RNA viruses. Proc Natl Acad Sci USA 119:e2202871119, 2022.
Lederberg J et al: Emerging Infections. Microbial Threats to Health in 
the United States. Washington, DC, National Academies Press, 1992.
Menachery VD et al: SARS-like WIV1-CoV poised for human emer­
gence. Proc Natl Acad Sci USA 113: 3048, 2016.
Morens DM, Fauci AS: Emerging pandemic diseases: How we got to 
COVID-19. Cell 182:1077, 2020.
Morens DM, Taubenberger JK: Pandemic influenza: Certain uncer­
tainties. Rev Med Virol 21:262, 2011.
Parrish C et al: Cross-species virus transmission and the emergence 
of new epidemic diseases. Microbiol Molec Biol Rev 72:457, 2008.
Wasik BR et al: Onward transmission of viruses: How do viruses 
emerge to cause epidemics after spillover? Philos Trans R Soc Lond B 
Biol Sci 374:20190017, 2019.
Wegner GI et al: Averting wildlife-borne infectious disease epidem­
ics requires a focus on socio-ecological drivers and a redesign of the 
global food system. EClinicalMedicine 47:101386, 2022.
Tim Evans, Kumanan Rasanathan

Primary Care and 

Global Health
The twentieth century witnessed the rise of an unprecedented global 
health divide. Industrialized or high-income countries experienced 
rapid improvement in standards of living, nutrition, health, and health 
care (Chap. 485). Meanwhile, in low- and middle-income countries 
with much less favorable conditions, health and health care progressed 
much more slowly. The scale of this divide is reflected in the cur­
rent extremes of life expectancy at birth, with Japan at the high end 
(84 years) and Chad at the low end (54 years). This 30-year shortfall 
in Chad reflects the daunting range of health challenges faced by 
low- and middle-income countries. These nations must deal not only 
with a complex mixture of diseases (both infectious and chronic) and 
illness-promoting conditions but also, and more fundamentally, with 
the fragility of the foundations underlying good health (e.g., sufficient 
food, water, sanitation, and education) and of the systems necessary 
for universal access to good-quality health care and public health. In 
the last decades of the twentieth century, the need to bridge this global 
health divide and establish health equity was increasingly recognized. 
The Declaration of Alma-Ata in 1978 crystallized a vision of justice in 
health, regardless of income, gender, ethnicity, or education, and called 
for “health for all by the year 2000” through primary health care. While 
progress since the declaration is remarkable, >45 years later and in the 
aftermath of a global pandemic of COVID-19, much remains to be 
done to achieve global health equity.
This chapter looks first at the nature of the health challenges that 
underlie the health divide in low- and middle-income countries. It then 
outlines the values and principles of a primary health care approach, 
with a focus on primary care services. Next, the chapter reviews the 
experience of low- and middle-income countries in addressing health 
challenges through primary care and a primary health care approach. 
Finally, the chapter identifies how current challenges and global 
context, in particular, the global pandemic, shape an agenda for the 

renewal of primary health care and primary care, allied to the move­
ment to achieve universal health coverage.
PRIMARY CARE AND PRIMARY HEALTH 
CARE
The term primary care has been used in many different ways: to 
describe a level of care or the setting of the health system, a set of treat­
ment and prevention activities carried out by specific personnel, a set 
of attributes for the way care is delivered, or an approach to organizing 
health systems that is synonymous with the term primary health care. 
In 1996, the U.S. Institute of Medicine encompassed many of these 
different usages, defining primary care as “the provision of integrated, 
accessible health care services by clinicians who are accountable for 
addressing a large majority of personal health care needs, developing 
a sustained partnership with patients, and practicing in the context 
of family and community.”1 We use this definition of primary care in 
this chapter. Primary care performs an essential function for health 
systems, providing the first point of contact when people seek health 
care, dealing with most problems, and referring patients onward to 
other services when necessary. As is increasingly evident in countries 
of all income levels, without strong primary care, health systems cannot 
function properly or address the health challenges of the communities 
they serve.
Primary Care and Global Health 
CHAPTER 487
Primary care is only one part of a primary health care approach. The 
Declaration of Alma-Ata, drafted in 1978 at the International Confer­
ence on Primary Health Care in Alma-Ata (now Almaty in Kazakhstan), 
identified many features of primary care as being essential to achieving 
the goal of “health for all by the year 2000.” However, it also identi­
fied the need to work across different sectors, address the social and 
economic factors that determine health, mobilize the participation of 
communities in health systems, and ensure the use and development of 
technology that was appropriate in terms of setting and cost. The decla­
ration drew from the experiences of low- and middle-income countries 
in trying to improve the health of their people following independence. 
Commonly, these countries had built hospital-based systems similar 
to those in high-income countries. This effort had resulted in the 
development of high-technology services in urban areas while leaving 
the bulk of the population without access to health care unless they 
traveled great distances to these urban facilities. Furthermore, much of 
the population lacked access to basic public health measures. Primary 
health care efforts aimed to move care closer to where people lived, to 
ensure their involvement in decisions about their own health care, and 
to address key aspects of the physical and social environment essential 
to health, such as water, sanitation, and education.
After the Declaration of Alma-Ata, many countries implemented 
reforms of their health systems based on primary health care. Most 
progress involved strengthening of primary care services; unexpect­
edly, however, much of this progress was seen in high-income coun­
tries, most of which constructed systems that made primary care 
available at low or no cost to their entire populations and that delivered 
the bulk of services in primary care settings. This endeavor also saw 
the reinforcement of family medicine as a specialty to provide primary 
care services. Even in the United States (an obvious exception to this 
trend), it became clear that the populations of states with more primary 
care physicians and services were healthier than those with fewer such 
resources.
Progress was also made in many low- and middle-income countries. 
However, the target of “health for all by the year 2000” was missed by 
a large margin. The reasons were complex but partly entailed a general 
failure to implement all aspects of the primary health care approach, 
particularly work across sectors to address social and economic fac­
tors that affect health and provision of sufficient human and other 
resources in order to make possible the access to primary care attained 
in high-income countries. Furthermore, despite the consensus in 
Alma-Ata in 1978, the global health community rapidly became frac­
tured in its commitment to the far-reaching measures called for by the 
1Institute of Medicine. Primary Care: America’s Health in a New Era (1996).

3860 declaration. Economic recession tempered enthusiasm for primary 
health care, and momentum shifted to programs concentrating on a 
few priority measures such as immunization, oral rehydration, breast- 
feeding, and growth monitoring for child survival. Success with these 
initiatives supported the continued movement of health development 
efforts away from the comprehensive approach of primary health care 
and toward programs that targeted specific public health priorities. 
This approach was reinforced by the need to address the HIV/AIDS 
epidemic. By the 1990s, primary health care had fallen out of favor 
in many global-health policy circles, and low- and middle-income 
countries were being encouraged to reduce public sector spending on 
health and to focus on cost-effectiveness analysis to provide a package 
of health care measures thought to offer the greatest health benefits.
PART 17
Global Medicine 
HEALTH CHALLENGES IN LOW- AND 
MIDDLE-INCOME COUNTRIES
Low- and middle-income countries, defined by a per-capita gross 
national income of <$12,535 (U.S.) per person per year, account for 
>85% of the world’s population. Average life expectancy in these coun­
tries lags far behind that in high-income countries: whereas the average 
life expectancy at birth for a girl in high-income countries is 83 years, it 
is only 65 years for a girl in low-income countries. This discrepancy has 
received growing attention over the past 50 years. Initially, the situation 
in poor countries was characterized primarily in terms of high fertility 
and high infant, child, and maternal mortality rates, with most deaths 
and illnesses attributable to infectious or tropical diseases among 
remote, largely rural populations. With growing adult (and especially 
elderly) populations and changing lifestyles linked to global forces of 
urbanization, a new set of health challenges characterized by chronic 
diseases, environmental overcrowding, and road traffic injuries has 
emerged rapidly (Fig. 487-1). The majority of tobacco-related deaths 
globally now occur in low- and middle-income countries, and the 

Deaths (millions)

Year/countries grouped by income per capita
FIGURE 487-1  Projections of disease burden to 2030 for high-, middle-, and low-income countries (left, center, and right, respectively). TB, tuberculosis. (Reproduced with 
permission from World Health Organization: The Global Burden of Disease 2004 Update, 2008.)

risk of a child’s dying from a road traffic injury in Africa is more than 
twice that in Europe. Thus, low- and middle-income countries in the 
twenty-first century face a full spectrum of health challenges—infectious, 
chronic, and injury-related—at much higher incidences and preva­
lences than are documented in high-income countries and with many 
fewer resources to address these challenges.
Addressing these challenges, however, does not mean simply waiting 
for economic growth. Analysis of the association between wealth and 
health across countries reveals that, for any given level of wealth, there 
is a substantial variation in life expectancy at birth that has persisted 
despite overall global progress in life expectancy during the past 40 years 
(Fig. 487-2). Health status in low- and middle-income countries varies 
enormously. Nations such as Cuba and Costa Rica have life expectan­
cies and childhood mortality rates similar to or even better than those 
in high-income countries; in contrast, countries in Sub-Saharan Africa 
and the former Soviet bloc have at times experienced significant reversals 
in these health markers, particularly in the 1990s.
As Angus Deaton stated in the World Institute for Development 
Economics Research annual lecture on September 29, 2006, “People in 
poor countries are sick not primarily because they are poor but because 
of other social organizational failures, including health delivery, which 
are not automatically ameliorated by higher income.” This analysis 
concurs with classic studies of the array of societal factors explaining 
good health in poor settings such as Cuba and Kerala State in India in 
the 1980s. Analyses conducted over the past 4 decades indeed show 
that rapid health improvement is possible in very different contexts. That 
some countries continue to lag far behind can be understood through 
a comparison of regional differences in progress in terms of life expec­
tancy over this period (Fig. 487-3).
As average levels of health vary across regions and countries, so 
too do they vary within countries (Fig. 487-4). Indeed, disparities 
within countries are often greater than those between high-income 
Intentional injuries
Other unintentional injuries
Road traffic accidents
Other noncommunicable
diseases
Cancers
Cardiovascular disease
Maternal, perinatal, and
nutritional conditions
Other infectious diseases
HIV/AIDS, TB, and malaria

Life expectancy at birth (years)

Namibia
South Africa

Botswana
Swaziland

10,000
15,000
20,000
25,000
30,000
35,000
40,000
GDP per capita, constant 2000 international $
FIGURE 487-2  Gross domestic product (GDP) per capita and life expectancy at birth in 169 countries, 1975 and 2005. Only outlying countries are named. (Reproduced with 
permission from World Health Organization: Primary Health Care: Now More Than Ever. World Health Report 2008.)
and low-income countries. For example, if low- and middle-income 
countries could reduce their overall childhood mortality rate to that of 
the richest one-fifth of their populations, global childhood mortality 
could be decreased by 40%. Disparities in health are mostly a result 
of social and economic factors such as daily living conditions, access 
to resources, and ability to participate in life-affecting decisions. In 
most countries, the health care sector actually tends to exacerbate 
health inequalities (the “inverse-care law”); because of neglect and 
discrimination, poor and marginalized communities are much less 
likely to benefit from public health services than those that are better 
off. Reforming health systems toward people-centered primary care 
provides an opportunity to reverse these negative trends.
Health services have failed to make their contribution to reducing 
these pervasive social inequalities by ensuring universal access to existing, 
scientifically validated, low-cost interventions such as insecticide-treated 
bed nets for malaria, taxes on cigarettes, short-course chemotherapy for 
tuberculosis, antibiotic treatment for pneumonia, dietary modification 
and secondary prevention measures for high blood pressure and high 
1970–1975
2000–2005
52.1
66.9
Arab states
60.5
70.4
East Asia and Pacific
Latin America and
Caribbean
61.1
71.7
50.1
63.2
South Asia
45.8
46.1
Sub-Saharan Africa

68.1
CEE and CIS
71.6
78.8
High-income OECD

Life expectancy (years)
FIGURE 487-3  Regional trends in life expectancy. CEE, Central and Eastern Europe; 
CIS, the Commonwealth of Independent States; OECD, Organization for Economic 
Cooperation and Development. (Reproduced with permission from World Health 
Organization: Closing the Gap in a Generation: Health Equity Through Action on the 
Social Determinants of Health. Commission on Social Determinants of Health Final 
Report, 2008.)

Primary Care and Global Health 
CHAPTER 487

Rural
Urban

Under 5 mortality rate per 1000

A
Haiti
Nigeria
Pakistan
Philippines
Rwanda
Lowest quintile
Quintile 2
Quintile 3
Quintile 4
Highest quintile

Bangladesh

Colombia

Indonesia
2002–2003
Mozambique

B
FIGURE 487-4  A. Mortality of children under 5 years old, by place of residence, in 
five countries. (Reproduced with permission from World Health Organization: Data 
from the World Health Organization.) B. Full basic immunization coverage (%), by 
income group. (Reproduced with permission from World Health Organization: 
Primary Health Care: Now More Than Ever. World Health Report 2008.)

3862 cholesterol levels, and water treatment and oral rehydration therapy for 
diarrhea. Despite decades of “essential packages” and “basic” health cam­
paigns, the effective implementation of what is already known to work 
with requisite scale and quality appears (deceptively) to be difficult.
Recent analyses have begun to focus on “the how” (as opposed to 
“the what”) of health care delivery, exploring why health progress is 
slow and sluggish despite the abundant availability of proven inter­
ventions for health conditions in low- and middle-income countries. 
Three general categories of reasons are being identified: (1) shortfalls 
in performance of health systems; (2) stratifying social conditions; and 
(3) skews in science.
PART 17
Global Medicine 
■
■SHORTFALLS IN PERFORMANCE 

OF HEALTH SYSTEMS
Specific health problems often require the development of specific health 
interventions (e.g., tuberculosis requires short-course chemotherapy). 
However, the delivery of different interventions is often facilitated by 
a common set of resources or functions: money or financing, trained 
health workers, and facilities with reliable supplies fit for multiple pur­
poses. Unfortunately, health systems in most low- and middle-income 
countries are largely dysfunctional across these core functions.
In the large majority of low- and middle-income countries, the 
level of public financing for health is woefully insufficient: whereas 
high-income countries spend, on average, >7% of the gross domestic 
product on health, middle-income countries spend <3%, and lowincome countries <2%. External financing for health through various 
donor channels grew rapidly in the first decade of the twenty-first 
century but has grown more slowly in the second decade to its current 
level of $37 billion. While these funds for health are significant, they 
represent <2% of total health expenditures in low- and middle-income 
countries and therefore are neither a sufficient nor a long-term solution 
to chronic underfinancing. In Africa, 70% of health expenditures 
come from domestic sources. The predominant form of health care 
financing—charging patients at the point of service—is the least 
efficient and the most inequitable, tipping millions of households 
into poverty annually. Health workers, who represent another critical 
resource, are often inadequately trained and supported in their work, 
especially in locations with the greatest needs. Recent estimates indi­
cate a shortage of >18 million health workers, constituting a crisis that 
is greatly exacerbated by the migration of health workers from low- 
and middle-income countries to high-income countries. Sub-Saharan 
Africa carries 24% of the global disease burden but has only 3% of the 
health workforce (Fig. 487-5).
Critical diagnostics and drugs often do not reach patients in need 
because of supply-chain failures. Moreover, facilities fail to provide 
good-quality and safe care: new evidence suggests much higher rates of 
adverse events among hospitalized patients in low- and middle-income 
countries than in high-income countries. Weak government planning, 

South-East Asia
% of global burden of disease
Africa

Western Pacific
Europe
Americas

Eastern Mediterranean

% of global workforce
FIGURE 487-5  Global burden of disease and health workforce. (Reproduced with 
permission from World Health Organization: Working Together for Health, 2006.)

regulatory, monitoring, and evaluation capacities are associated with 
rampant, unregulated commercialization of health services and cha­
otic fragmentation of these services as donors “push” their respective 
priority programs. With such fragile foundations, it is not surprising 
that low-cost, affordable, validated interventions are not reaching those 
who need them.
■
■STRATIFYING SOCIAL CONDITIONS
Health care delivery systems do not exist in a vacuum but rather are 
embedded in a complex of social and economic forces that often 
stratify opportunities for health unfairly. Most worrisome are the 
pervasive forces of social inequality that serve to marginalize popula­
tions with disproportionately large health needs (e.g., the urban poor; 
illiterate mothers). Why should a poor slum dweller with no income 
be expected to come up with the money for a bus fare needed to travel 
to a clinic to learn the results of a sputum test for tuberculosis? How 
can a mother living in a remote rural village and caring for an infant 
with febrile convulsions find the means to get her child to appropriate 
care? Shaky or nonexistent social security systems, dangerous work 
environments, isolated communities with little or no infrastructure, 
and systematic discrimination against racialized minorities are among 
the myriad forces with which efforts for more equitable health care 
delivery must contend.
■
■SKEWS IN SCIENCE
While science has yielded enormous breakthroughs in health in highincome countries, with some spillover to low- and middle-income 
countries, many important health problems continue to affect primar­
ily low- and middle-income countries whose research and develop­
ment investments are deplorably inadequate. The past two decades 
have seen growing efforts to right this imbalance with research and 
development investment for new drugs, vaccines, and diagnostics that 
effectively cater to the specific health needs of populations in low- and 
middle-income countries. For example, the TB Alliance has revitalized 
a previously “dry” pipeline for new tuberculosis drugs. In 2019, their 
new drug (pretomanid) received U.S. Food and Drug Administration 
approval as part of a triple oral regimen (bedaquiline, pretomanid, and 
linezolid [BPaL]) that treats extensively drug-resistant tuberculosis 
faster, better, and cheaper. Nevertheless, the global vaccine inequity 
witnessed during the COVID-19 pandemic is indicative of the need for 
further efforts to right the research and development balance globally.
As discussed above, the primary constraint on better health in 
low- and middle-income countries is related less to the availability of 
health technologies and more to their effective delivery. Underlying 
these health delivery challenges is a major bias regarding what consti­
tutes legitimate “science” to improve health equity. The lion’s share of 
health research financing is channeled toward the development of new 
technologies—drugs, vaccines, and diagnostics; in contrast, virtually 
no resources are directed toward research on how health care delivery 
systems can become more reliable and overcome adverse social condi­
tions. The complexity of systems and social context is such that this 
issue of delivery requires an enormous investment in terms not only 
of money but also of scientific rigor, with the development of new 
research methods and measures and the attainment of greater legiti­
macy in the mainstream scientific establishment.
These common challenges to low- and middle-income countries 
partly explain the resurgence of interest in the primary health care 
approach and the emergence of a global movement toward universal 
health coverage, now enshrined as one of the Sustainable Develop­
ment Goal targets adopted in Agenda 2030 by all countries at the 
United Nations in September 2015. In some countries (mostly middleincome), significant progress has been made in expanding coverage by 
health systems based on primary care and even in improving indicators 
of population health. More countries are embarking on the creation of 
primary care services despite the challenges that exist, particularly in 
low-income countries. Even when these challenges are acknowledged, 
there are many reasons for optimism that low- and middle-income 
countries can accelerate progress in building primary care as a key 
vehicle toward achieving universal health coverage.

PRIMARY HEALTH CARE IN THE 

TWENTY-FIRST CENTURY
The new millennium has seen a resurgence of interest in primary 
health care as a means of addressing global health challenges but also of 
familiar obstacles to its implementation. This interest has been driven 
by many of the same issues that led to the Declaration of Alma-Ata: 
rapidly increasing disparities in health between and within countries; 
spiraling costs of health care at a time when many people lack qual­
ity care; dissatisfaction of communities with the care they are able 
to access; and failure to address changes in health threats, especially 
noncommunicable diseases, pandemics, and challenges arising from 
accelerated climate change. These challenges require a comprehensive 
approach and strong health systems with effective primary care. Global 
health development agencies have partially recognized that sustaining 
gains in public health priorities such as HIV/AIDS and pandemic pre­
paredness requires not only robust health systems but also the tackling 
of social and economic factors related to disease incidence and progres­
sion. Weak health systems have proved a major obstacle to delivering 
new technologies, such as COVID-19 vaccines and antiretroviral 
therapy, to all who need them. We discuss experiences in low- and 
middle-income countries in relation to primary care in greater detail 
below. First, we consider the features of primary health care and pri­
mary care as currently understood.
■
■REVITALIZATION OF PRIMARY HEALTH CARE
At the 2019 World Health Assembly (an annual meeting of all coun­
tries to discuss the work of the World Health Organization [WHO]), a 
resolution was passed reaffirming the principles of the Declaration of 
Alma-Ata and the need for national health systems to be based on pri­
mary health care. This resolution reframed primary health care as three 
components: (1) primary care and essential public health functions as 
the core of integrated health services; (2) empowered people and com­
munities; and (3) multisectoral policy and action. This reframing itself 
drew on the 2008 WHO World Health Report, which asserted that a 
primary health care approach was necessary “now more than ever” to 
address global health priorities, especially in terms of disparities and 
new health challenges.
The 2008 World Health Report highlighted four broad areas for 
reform (Fig. 487-6). One of these areas—the need to organize health 
care so that it places the needs of people first—relates to the necessity 
SERVICE
DELIVERY
REFORMS
UNIVERSAL
COVERAGE
REFORMS
to make health systems
people-centered
to improve
health equity
LEADERSHIP
REFORMS
PUBLIC POLICY
REFORMS
to make health
authorities more
reliable
to promote and
protect the health of
communities
FIGURE 487-6  The four reforms of primary health care renewal. (Reproduced with 
permission from World Health Organization: Primary Health Care: Now More Than 
Ever. World Health Report 2008.)

for strong primary care in health systems and what this requirement 
entails. The other three areas also relate to primary care. All four areas 
require action to move health systems in a direction that will improve 
health, reduce disparities, and increase satisfaction.
Universal 
Coverage 
Reforms 
to 
Improve 
Health 
Equity  
Despite progress in many countries, most people in the 
world can receive health care services only if they can pay at the point 
of service. Disparities in health are caused not only by a lack of access 
to necessary health services but also by the impact of expenditure on 
health. More than 100 million people are still being driven into extreme 
poverty each year by health care costs, with countless others deterred 
from accessing services at all. Moving toward prepayment financing 
systems for universal coverage, which ensure access to a comprehensive 
package of services according to need without precipitating economic 
ruin, has therefore emerged as a major priority in low- and middleincome countries. Increasing coverage of health services can be consid­
ered in terms of three axes: the proportion of the population covered, 
the range of services underwritten, and the percentage of costs paid 
(Fig. 487-7). Moving toward universal health coverage requires ensur­
ing the availability of health care services to all, eliminating barriers to 
access, and organizing pooled financing mechanisms, such as taxation 
or insurance, to remove user fees at the point of service. It also requires 
measures beyond financing, including expansion of health services in 
poorly served areas, improvement in the quality of services provided 
to marginalized communities, and increased coverage of other social 
services that significantly affect health (e.g., education).
Primary Care and Global Health 
CHAPTER 487
Service Delivery Reforms to Make Health Systems PeopleCentered  
Health systems have often been organized around the 
needs of those who provide health care services, such as clinicians and 
policymakers. The result is a centralization of services or the provi­
sion of vertical programs that target single diseases. The principles of 
primary health care, including the development of primary care, reori­
ent care around the needs of the people to whom services cater. This 
“people-centered” approach aims to provide health care that is both 
more effective and appropriate.
The increase in noncommunicable diseases in low- and middleincome countries offers a further stimulus for urgent reform of service 
delivery to improve chronic disease care. As discussed above, large 
numbers of people currently fail to receive relatively low-cost interven­
tions that have reduced the incidence of these diseases in high-income 
countries. Delivery of these interventions requires health systems that 
can address multiple problems and manage people over a long period 
within their own communities, yet many low- and middle-income 
countries are only now starting to adapt and build primary care ser­
vices that can address noncommunicable diseases and communicable 
diseases requiring chronic care. Even some countries (e.g., Iran) that 
have had significant success in reducing communicable diseases and 
improving child survival have been slow to adapt their health systems 
to rapidly accelerating noncommunicable disease epidemics.
Total health expenditure
Height:
what
proportion
of the costs
is covered?
Reduce
cost
sharing
Include
other
services
Public expenditure
on health
Extend to
uninsured
Depth:
which benefits
are covered?
Breadth: who is insured?
FIGURE 487-7  Three ways of moving toward universal coverage.

People-centered care requires a safe, comprehensive, and integrated 
response to the needs of those presenting to health systems, with treat­
ment at the first point of contact or referral to appropriate services. 
Because no discrete boundary separates people’s needs for health 
promotion, curative interventions, and rehabilitation services across 
different diseases, primary care services must address all present­
ing problems in a unified way. Meeting people’s needs also involves 
improved communication between patients and their clinicians, who 
must take the time to understand the impact of the patients’ social 
context on the problems they develop. This enhanced understanding 
is made possible by improvements in the continuity of care so that 
responsibility transcends the limited time people spend in health care 
facilities. Primary care plays a vital role in navigating people through 
the health system; when people are referred elsewhere for services, 
primary care providers must monitor the resulting consultations and 
perform follow-up. All too often, people do not receive the benefit of 
complex interventions undertaken in hospitals because they lose con­
tact with the health care system once discharged. Comprehensiveness 
and continuity of care are best achieved by ensuring that people have 
an ongoing personal relationship with a care team.
PART 17
Global Medicine 
Public Policy Reforms to Promote and Protect the Health 
of Communities  
Public policies in sectors other than health 
care are essential to reduce disparities in health and to make progress 
toward global public health targets. The 2008 final report of the WHO 
Commission on Social Determinants of Health provided an exhaus­
tive review of the multisectoral policies required to address health 
inequities at the local, national, and global levels. Advances against 
major challenges such as HIV/AIDS, tuberculosis, emerging infec­
tions, cardiovascular disease, cancers, and injuries require effective 
collaboration with sectors such as transport, housing, labor, agricul­
ture, urban planning, trade, and energy. The COVID-19 pandemic has 
underscored the importance of multisectoral action to protect health; 
countries that have been most successful in managing the pandemic 
have been those best able to coordinate across their societies to imple­
ment nonpharmaceutical health measures and build social solidarity. 
Similarly, while tobacco control provides a striking example of what is 
possible if different sectors work together toward health goals, the lack 
of implementation of many evidence-based tobacco control measures 
in most countries just as clearly illustrates the difficulties encountered 
in such multisectoral work and the unrealized potential of public poli­
cies to improve health.
Leadership Reforms to Make Health Authorities More 
Reliable  
The Declaration of Alma-Ata emphasized the importance 
of participation by people in their own health care. In fact, participa­
tion is important at all levels of decision-making. Contemporary health 
challenges require models of leadership that acknowledge the role 
of government but also the many types of organizations involved in 
health care delivery. Governments need to engage, guide, negotiate, 
and regulate among these diverse actors, including but not limited 
to nongovernmental organizations (NGOs), the private sector, pro­
fessional societies, academia, and patient groups. This difficult task 
requires concerted investment in leadership and governance capacity, 
especially if action requires the engagement of different sectors such as 
local government and education. The complex landscape for leadership 
at the national level extends to the international level. The increasing 
transnational character of health as seen by the interdependence of 
countries with respect to pandemics, climate change, health worker 
migration, and food security emphasizes the need for more effective 
global health governance mechanisms.
EXPERIENCES WITH PRIMARY CARE IN 
LOW- AND MIDDLE-INCOME COUNTRIES
Aspects of the primary health care approach described above, with an 
emphasis on primary care services, have been implemented to varying 
degrees in many low- and middle-income countries over the past halfcentury. As discussed above, some of these experiences inspired and 
informed the Declaration of Alma-Ata, which itself led many more 

countries to attempt to implement primary health care. This section 
describes the experiences of a selection of low- and middle-income 
countries in improving primary care services that have enhanced the 
health of their populations.
Before Alma-Ata, few countries had attempted to develop pri­
mary care on a national level. Rather, most focused on expanding 
primary care services to specific communities (often rural villages), 
making use of community volunteers to compensate for the absence 
of facility-based care. In contrast, in the post–World War II period, 
China invested in primary care on a national scale, and life expectancy 
doubled within roughly 20 years. The Chinese expansion of primary 
care services included a massive investment in infrastructure for pub­
lic health (e.g., water and sanitation systems) linked to innovative use 
of community health workers. These “barefoot doctors” lived in and 
expanded care to rural villages. They received a basic level of training 
that enabled them to provide immunizations, maternal care, and basic 
medical interventions, including the use of antibiotics. Through the 
work of the barefoot doctors, China brought low-cost universal basic 
health care coverage to its entire population, most of which had previ­
ously had no access to these services.
In 1982, the Rockefeller Foundation convened a conference to 
review the experiences of China along with those of Costa Rica, Sri 
Lanka, and the state of Kerala in India. In all of these locations, good 
health care at low cost appeared to have been achieved. Despite lower 
levels of economic development and health spending, all of these juris­
dictions, along with Cuba, had health indicators approaching—or in 
some cases exceeding—those of developed countries. Analysis of these 
experiences revealed a common emphasis on primary care services, 
with expansion of care to the entire population free of charge or at 
low cost, combined with community participation in decision-making 
about health services and coordinated work in different sectors (espe­
cially education) toward health goals. During the more than three 
decades since the Rockefeller meeting, some of these countries have 
built on this progress, while others have experienced setbacks. Recent 
experiences in developing primary care services show that the same 
combination of features is necessary for success. For example, Brazil—
a large country with a dispersed population—made major strides in 
increasing the availability of health care from 1980 to 2010. The Brazilian 
Family Health Program expanded progressively across the country to 
reach universal coverage. This program provided communities with 
free access to primary care teams made up of primary care physicians, 
community health workers, nurses, dentists, obstetricians, and pedia­
tricians. These teams were responsible for the provision of primary 
care to all people in a specified geographic area—not only those who 
access health clinics. Moreover, individual community health workers 
were responsible for a named list of people within the area covered by 
the primary care team. Solid evidence indicated that the Family Health 
Program has contributed to impressive gains in population health, 
particularly in terms of childhood mortality and health inequities 
(Fig. 487-8). Nevertheless, systemic inequalities, magnified during the 
COVID-19 crisis, highlight how continued progress is not guaranteed, 
and efforts to implement and expand a primary health care approach 
need to adapt to new health and political challenges.
Chile has also built on its existing primary care services in the past 
two decades, aiming to improve the quality of care and the extent of 
coverage in remote areas, above all for disadvantaged populations. 
This effort has been made in concert with measures aimed at reducing 
social inequalities and fostering development, including social welfare 
benefits for families and disadvantaged groups and increased access 
to early-childhood educational facilities. As in Brazil, these steps have 
improved maternal and child health and have reduced health inequi­
ties. In addition to directly enhancing primary care services, Brazil 
and Chile have instituted measures to increase both the accountability 
of health providers and the participation of communities in decisionmaking. In Brazil, national and regional health assemblies with high 
levels of public participation are integral parts of the health policymaking process. Chile has instituted a patient’s charter that explicitly 
specifies the rights of patients in terms of the range of services to which 
they are entitled.

3.96
Mean annual change (since 1998)

–2
–2.08
–4
–4.24
–6
–6.82
–6.97
–6.77
–8
–10
0–20
21–50
51–70
71+
PSF coverage (% population covered)
FIGURE 487-8  Improvements in childhood mortality following the Family Health Program in Brazil. HDI, 
Human Development Index; PSF, Program Saúde da Família (Family Health Program). (Source: Ministry of 
Health, Brazil.)
Other countries that have made recent progress with primary 
health care include Bangladesh, once one of the poorest countries in 
the world. Since achieving its independence from Pakistan in 1971, 
Bangladesh has seen a dramatic increase in life expectancy, and child­
hood mortality rates are now lower than those in neighboring nations 
such as India and Pakistan. The expansion of access to primary care 
services has played a major role in these achievements. This progress 
has been spearheaded by a vibrant NGO community that has focused 
its attention on improving the lives and livelihoods of poor women and 
their families through innovative and integrated microcredit, educa­
tion, and primary care programs.
The above examples, along with others from the past 40 years in 
countries such as Thailand, Rwanda, Ethiopia, Turkey, Vietnam, and 
Oman, illustrate how the implementation of a primary health care 
approach, with a greater emphasis on primary care, has led to bet­
ter access to health care services—a trend that has not been seen in 
many other low- and middle-income countries. This trend, in turn, 
has contributed to improvements in population health and reductions 
in health inequities. However, as these nations have progressed, other 
countries have shown how previous gains in primary care can easily be 
eroded. In Sub-Saharan Africa, undermining of primary care services 
contributed to catastrophic reversals in health outcomes catalyzed by 
the HIV/AIDS epidemic. Countries such as Botswana and Zimbabwe 
implemented primary health care strategies in the 1980s, increasing 
access to care and making impressive gains in child health. Both coun­
tries were severely affected by HIV/AIDS, with pronounced decreases 
in life expectancy. However, Zimbabwe has also seen political turmoil, 

Percentage of total health expenditure

FIGURE 487-9  Changes in source of health expenditure in China over the past 40 years. (Reproduced with permission from World Health Organization: Primary Health Care: 
Now More Than Ever. World Health Report 2008.)

a decline of health and other social services, and 
the flight of health personnel, whereas Botswana 
has maintained primary care services to a greater 
extent and has managed to organize widespread 
access to antiretroviral therapy for people living 
with HIV/AIDS.
High HDI
Low HDI
China provides a particularly striking example 
of how changes in health policy relevant to the 
organization of health systems (Fig. 487-9) can have 
rapid, far-reaching consequences for population 
health. Even as the 1982 Rockefeller conference 
was celebrating China’s achievements in primary 
care, its health system was unraveling. The deci­
sion to open up the economy in the early 1980s 
led to rapid privatization of the health sector and 
the breakdown of universal health coverage. As 
a result, by the end of the 1980s, most people, 
especially the poorer segments of the population, 
were paying directly out of pocket for health care, 
and almost no Chinese had insurance—a dramatic 
transformation. The “barefoot doctor” schemes collapsed, and the 
population either turned to care paid for at hospitals or simply became 
unable to access care. This undermining of access to primary care ser­
vices in the Chinese system and the resulting increase in impoverish­
ment due to illness contributed to the stagnation of progress in health 
in China at the same time that incomes in that country increased at an 
unprecedented rate. Reversals in primary care have meant that China 
now increasingly faces health care issues similar to those faced by 
India, although the country has more recently implemented measures 
to restore universal health coverage, with significant success. In both 
countries, rapid economic growth has been linked to lifestyle changes 
and noncommunicable disease epidemics. The health care systems of 
the two nations share two negative features that are common when 
primary care is weak: a disproportionate focus on specialty services 
provided in hospitals and unregulated commercialization of health ser­
vices. China and India both saw expansion of private hospital services 
that cater to middle-class and urban populations who can afford care; at 
the same time, hundreds of millions of people in rural areas struggled 
to access basic services. Even in the wealthier groups, a lack of primary 
care services has been associated with late presentation with illness and 
with insufficient investment in primary prevention approaches. This 
neglect of prevention poses a risk of large-scale epidemics of cardio­
vascular disease, which could endanger continued economic growth. 
In addition, the health systems of both countries now depend for the 
majority of their funding on out-of-pocket payments by people when 
they use services. Thus, substantial proportions of the population must 
sacrifice other essential goods as a result of health expenditure and 
Primary Care and Global Health 
CHAPTER 487
–5.64
–8.38
Out-of-pocket
expenditure
Prepaid private
expenditure
Social security
expenditure
Other general
government
expenditure

3866 may even be driven into poverty by this cost. The commercial nature 
of health services with inadequate or no regulation has also led to the 
proliferation of charlatan providers, inappropriate care, and pressure 
for people to pay for expensive and sometimes unnecessary care.
Faced with these problems, China and India have implemented 
measures to strengthen primary health care. China has increased gov­
ernment funding of health care, has taken steps toward restoring health 
insurance, and has enacted a target of universal access to primary care 
services. India has similarly mobilized funding to greatly expand pri­
mary care services in rural areas and in urban settings. Both countries 
are increasingly using public resources from their growing economies 
to fund primary care services.
PART 17
Global Medicine 
These encouraging trends are illustrative of new opportunities to 
implement a primary health care approach and strengthen primary 
care services in low- and middle-income countries. Linked to goal 
number 3 of the UN Sustainable Development Goals, Over the past 
decade, nearly all countries have adopted universal health coverage—the 
provision of quality health services in a timely manner at affordable 
cost—and the primary health care approach remains key to achieving 
this.
■
■OPPORTUNITIES TO BUILD PRIMARY CARE IN 
LOW- AND MIDDLE-INCOME COUNTRIES
To reach global health targets, health systems must be strengthened. 
More money is currently being spent on health than ever before. In 
2020, global health spending totaled $9 trillion (U.S.)—more than 
double the amount spent a decade earlier. Although most expendi­
ture occurs in high-income countries, spending in many emerging 
middle-income countries has rapidly accelerated, as has the allocation 
of monies for this purpose by both governments in, and donors to, lowincome countries. These twin trends—greater emphasis on building 
health systems based on primary care and allotment of more money for 
health care—provide opportunities to address many of the challenges 
discussed above in low- and middle-income countries.
Accelerating progress requires a better understanding of how global 
health initiatives (GHIs) can more effectively facilitate the development 
of primary care in low-income countries. Recent reviews including the 
WHO Maximizing Positive Synergies Collaborative Group and the 
Wellcome Trust Future of GHIs have assessed the impact on coun­
try health systems of diverse GHIs such as the Global Fund to Fight 
AIDS, Tuberculosis and Malaria; the Global Alliance for Vaccines and 
Immunization; the U.S. President’s Emergency Plan for AIDS Relief; 
and the Global Financing Facility of the World Bank. While evidence 
of improved access to targeted health services is encouraging, systemic 
concerns related to increasing domestic resources for health and accel­
erating comprehensive primary care remain. If GHIs implement pro­
grams that work in tandem with other components of national health 
systems without undermining staffing and procurement of supplies, 
they have the potential to contribute substantially to the capacity of 
health systems to provide comprehensive primary care services.
In the context of the recent pandemic, GHIs appear even more 
important. The imperative of vaccinating the world’s population 
against SARS-CoV-2 led to the creation of the multi-billion-dollar 
COVAX facility that failed to ensure equitable access to COVID-19 
vaccines. After the pandemic, the need to recover essential health ser­
vices, particularly for mothers and children, underlines the importance 
of GHIs like the Global Financing Facility for every mother and child 
as catalysts for universal access to life-saving services. The general 
trend is to coordinate this funding in order to reduce fragmentation 
of national health systems and to concentrate more on strengthening 
these systems. Comprehensive primary care in low-income countries 
must inevitably deal with the rapid emergence of chronic diseases and 
the growing prominence of injury-related health problems; thus, inter­
national health development assistance must become more responsive 
to these needs.
Beyond funding for health services, other opportunities exist. 
Increased social participation in health systems can help build pri­
mary care services. In many countries, political pressure from com­
munity advocates for more holistic and accountable care as well as 

entrepreneurial initiatives to scale up community-based services 
through NGOs have accelerated progress in primary care without 
major increases in funding. Participation of the population in the 
provision of health care services and in relevant decision-making often 
drives services to cater to people’s needs as a whole rather than to nar­
row public health priorities.
Participation and innovation can help address critical issues related 
to the health workforce in low- and middle-income countries by estab­
lishing effective people-centered primary care services. Many primary 
care services do not need to be delivered by a physician or a nurse. 
Multidisciplinary teams can include paid community workers who 
have access to a physician if necessary but who can provide a range of 
health services on their own. In Ethiopia, >38,000 community health 
workers have been trained and deployed to improve access to primary 
care services, and there is increasing evidence that this measure is 
contributing to better health outcomes. In India, >600,000 community 
health advocates have been recruited as part of expanded rural primary 
care services. In Niger, the deployment of community health work­
ers to deliver essential child health interventions (as a component of 
integrated community case management) has had impressive results 
in reducing childhood mortality and decreasing disparities. After the 
Declaration of Alma-Ata, experiences with community health work­
ers were mixed, with particular problems regarding levels of training 
and lack of payment. Current endeavors are not immune from these 
concerns. However, with access to physician support and the deploy­
ment of teams, some of these concerns may be addressed. Growing 
evidence from many countries indicates that shifting appropriate tasks 
to primary care workers who have had shorter, less expensive training 
than physicians will be essential to address the human resources crisis.
Finally, recent improvements in information and communication 
technologies, particularly mobile phone and Internet systems, have cre­
ated the potential for systematic implementation of e-health, telemedi­
cine, and improved health data initiatives in low- and middle-income 
countries. These developments raise the tantalizing possibility that 
health systems in these countries, which have long lagged behind those 
in high-income countries but are less encumbered by legacy systems 
that have proved hard to modernize in many settings, could leapfrog 
their wealthier counterparts in exploiting these technologies. Although 
the challenges posed by poor or absent infrastructure and investment 
in many low- and middle-income countries cannot be underestimated 
and will need to be addressed to make this possibility a reality, the rapid 
rollout of mobile networks and their use for health and other social 
services in many low-income countries where access to fixed telephone 
lines was previously very limited offer great promise in building pri­
mary care services in low- and middle-income countries. To a partial 
extent, this potential has been demonstrated and even realized in many 
countries during the COVID-19 pandemic, with greatly increased 
uptake of the use of telemedicine and clinical support via digital means.
CONCLUSION
As concern continues to mount about glaring inequities in global 
health, there is a growing commitment to redress these egregious 
shortfalls, as exemplified by the central place of equity in the United 
Nations’ Sustainable Development Goals adopted in 2015, including 
a specific target on the achievement of universal health coverage in all 
countries by 2030. This commitment begins first and foremost with a 
clear vision of the fundamental importance of health in all countries, 
regardless of income. The values of health and health equity are shared 
across all borders, and primary health care provides a framework for 
their effective translation across all contexts.
The translation of these fundamental values has its roots in four 
types of reform that reflect the distinct but interlinked challenges of 
(re)orienting a society’s resources on the basis of its citizens’ health 
needs: (1) organizing health care services around the needs of people 
and communities; (2) harnessing services and sectors beyond health 
care to promote and protect health more effectively; (3) establishing 
sustainable and equitable financing mechanisms for universal health 
coverage; and (4) investing in effective leadership to steward change 
locally, nationally and across borders. This common primary health

care agenda highlights the striking similarity, despite enormous dif­
ferences in context, in the nature and direction of the reforms that 
national health systems must undertake to promote greater equity in 
health. This shared agenda is complemented by the growing reality of 
global health interconnectedness due, for example, to shared microbial 
threats, bridging of ethnolinguistic diversity, flows in migrant health 
workers, and mobilization of global funds to support the neediest 
populations. Embracing solidarity in global health while strengthening 
health systems through a primary health care approach is fundamental 
to sustained progress in global health.
The shortfalls in health system performance, stratification of social 
conditions leading to unfair differences in health, and skews in science 
that undermine the realization of “Health for All” have never been 
more glaringly visible than during the COVID-19 pandemic. But they 
also have never commanded such global political attention at the high­
est level. Out of this crisis, then, is a once-in-a-lifetime opportunity to 
recast global and national systems to enable the genuine implementa­
tion of the primary health care approach in all countries.
■
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