-
Forewords . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . 6
About the Author . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . 7
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . 7
Acute Respiratory Infections: Making Inroads Against a Forgotten
Pandemic . . . . . . . . . . . . . . . . . 8Overview . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . 10
The Forgotten Pandemic . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 12
Solutions within Reach . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 15
Part 1: Understanding Acute Respiratory Infections . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . 16Pneumonia .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
How Infection Occurs . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 20
Pathogens That Cause Pneumonia . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
20
Preventing Pneumonia . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 21
Treating Pneumonia . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 23
HIV and Pneumonia . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 24
Influenza . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . 26
The Influenza Virus . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 27
Drift and Shift: How Influenza Viruses Evolve . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
28
Influenza Pandemics . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 28
H1N1: The First 21st-Century Flu Pandemic . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
30
Influenza Surveillance . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 32
Preventing Influenza . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 33
Treating Influenza . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 33
Respiratory Syncytial Virus . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 34
Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . 36
Treating TB . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 39
Tuberculosis and HIV . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 40
Future Threats . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . 41
Profile: The SARS Story . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . 42
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Contents
WLF_Part1_BH_0824.indd 2-3 8/31/10 11:03 AM
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Antibiotics and Antiviral Therapy . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 78
How Drug Resistance Develops . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
78
The Research and Development Drought . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
80
Preventing Drug Resistance . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 80
Access to Health Care . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . 82
Gaps in Health Care Spending . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
83
Primary Care in Rural and Urban Settings . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
84
Growing the Health Workforce . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
86
Profile: Treating Severe Pneumonia in Malawi . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
87
Part 4: Making ARIs a Global Priority . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
88Identifying and Meeting the Worldwide Challenge . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
90
ARIs Are Significantly Underfunded . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
92
More Information Is Needed About ARIs . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
94
Health and Governance Infrastructure Is Often Weak . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
95
Global Initiatives . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 96
APPendICeS Appendix A: World Regions . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . 98
Appendix B: Mechanisms of Infection . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
100
Pathogens:Agents of Disease . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
100
What Is a Virus? . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 100
What Are Bacteria? . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
101
What Is a Fungus? . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 101
How the Body Defends Itself . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
103
Appendix C: Glossary . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 104
Appendix d: Tables . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 106
Appendix e: Sources . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 114
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . 123
Part 2: drivers of Acute Respiratory Infections . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 46
How Nutritional Deficiencies Affect the Immune System . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
48
Linking ARIs and Malnutrition . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 48
Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 50
Micronutrients: Zinc, Vitamin D, and Vitamin A . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
50
How the International Community Can Help . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
51
Air Pollution . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . 52
Particulates . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 54
How Pollutants Affect the Body . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 55
Indoor Air Pollution . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 56
Home Cooking and Heating . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
56
Indoor Smoking . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
56
Outdoor Air Pollution . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 58
Motor Vehicles Emissions . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
58
Ozone . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 58
Profile: Air Pollution in China . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . 59
Tobacco . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . 60
Adult Smoking . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 61
Environmental Tobacco Smoke . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
61
Overcrowding . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 62
Profile: The Hajj . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . 65
Part 3: Prevention, diagnoses, and Treatment . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Preventing ARIs with Vaccines . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
68
Immunization Disparities . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 70
Financing Immunization Campaigns . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
71
Promoting Wider Vaccine Use . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
72
diagnoses and Surveillance . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 74
Diagnosing ARIs . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 74
Surveillance Techniques . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 75
Profile: Integrated Approaches to Reduce ARIs in India . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
77
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6The drivers of ARIs can be largely addressed through poverty
reduction strategies, evidence-based public policies, medical
knowledge, and funding.Three themes have consistently emerged
during my 30 years fighting lung disease across the globe . The
first: Lung diseases take a much greater toll than is recognized .
Ten million people around the world will die this year alone, some
from ancient diseases such as tuberculosis, others from
21st-century strains of influenza .
The second theme is that the worlds poorest people bear an
overwhelming share of the lung disease burden . Acute respiratory
infections thrive where people go hungry, live in overcrowded
conditions, earn less than two dollars a day, and have inadequately
funded health systems . Many who die could not afford a doctor or
medicine .
The third theme is that so much of this death and suffering is
preventable . The drivers of ARIs, such as malnutrition, air
pollution, and tobacco use, can be largely addressed through
poverty reduction strategies, evidence-based public policies,
medical knowledge, and funding .
That is why this Atlas is vitally important . It is the first
scientific publication to weave together all of these themes in
ways that motivate action by those who can make a difference .
The team behind the Atlas and ARIAtlas .org has made an
important contribution to the need to address ARIs, and I
congratulate its members on this tremendous accomplishment . For
more than a century, the Union has been on the frontlines of global
lung health issues . We hope that those who pick up this book will
feel compelled to join us in our work .
Dr . Nils Billo, MD, MPHExecutive Director
International Union Against Tuberculosis and Lung Disease
Reducing ARIs begins with increased knowledge, global
commitment, and partnerships.Advances in medical knowledge and
technology, though considerable, have not rid the world of age-old
respiratory infections such as pneumonia and influenza, which are
especially devastating in poverty-stricken countries . Increasing
the availability of public health and health care services is part
of the solution, but the perspectives of sociology, urban planning,
nutrition, environmental sciences, and economics are also essential
.
This Atlas offers a new way of understanding and tackling this
global problem by presenting these diseases as a group of acute
respiratory infections (ARIs) with common symptoms, drivers, and
methods of prevention and treatment . Dramatic reductions in ARIs,
which claim 4 .25 million lives every year, can be achieved by
raising living standards and addressing malnutrition, pollution,
and overcrowding, especially in low- and middle-income nations
.
With this Atlas, World Lung Foundation (WLF) takes an important
step to inform and empower policymakers, journalists, and other
public health advocates, presenting the most up-to-date data in the
most accessible manner . Accompanying this book is ARIAtlas .org, a
dynamic and interactive resource for advancing discussions on ARI
research and policy issues .
WLF is pleased to introduce this Atlas to the public health,
policy, journalism, and philanthropic communities . Through global
commitment and partnerships, we can dramatically reduce the toll of
ARIs and help to better the lives of people around the world .
Peter Baldini Chief Executive Officer and President World Lung
Foundation
About the AuthorNEIL W . SCHLUGER, MD, is the Chief Scientific
Officer of World Lung Foundation . Dr . Schluger received his
undergraduate degree from Harvard University and his medical degree
from the University of Pennsylvania School of Medicine . He
completed training in pulmonary and critical care medicine at the
Cornell University Medical Center in New York City, with research
training at Rockefeller University and the National Institutes of
Health .
Dr . Schluger began his academic career at the New York
University School of Medicine and Bellevue Hospital Center, where
he directed the Tuberculosis Clinic and led research programs
designed to develop new diagnostics and treatments for tuberculosis
. He also led innovative pro-grams designed to improve delivery of
services to patients with tuberculosis . In 1998 Dr . Schluger was
recruited to Columbia University, where he is currently Professor
of Medicine, Epidemiology and Environmental Health Sciences, and
Chief of the Division of Pulmonary, Allergy and Critical Care
Medicine . He has an active research career in lung disease and is
the Steering Committee Chairman of the Tuberculosis Trials
Consortium, an international research collaboration supported by
the U .S . Centers for Disease Control and Prevention . He has long
been involved in advocacy for lung health and has served as
President of the American Lung Association of the City of New York
. Dr . Schluger is author of more than 100 scientific publications
about lung disease and is an internationally recognized authority
on lung infections .
AcknowledgmentsWorld Lung Foundation (WLF) is grateful for the
generous contributions of many individuals who made the Acute
Respiratory Infections Atlas possible . Karyn Feiden masterfully
synthesized reams of complex research into clear narrative and was
a core part of the team assembled to tell the ARI story . Kimberly
Sebek dedicated countless hours to the collection and analysis of
global lung health data and was unwavering in her commitment to
accuracy and thoroughness .
We would also like to thank our peers who lent their expertise
and guidance to the Atlas:
Otto Braendli, MD, President, Swiss Lung Foundation; E . Jane
Carter, MD, Associate Professor, Alpert School of Medicine, Brown
University; Penny Enarson, MD, Head of Child Lung Health Division,
International Union Against Tuberculosis and Lung Disease (The
Union); Paula I . Fujiwara, MD, MPH, Senior Technical Advisor, The
Union; Patrick Kinney, ScD, Professor of Environmental Health
Sciences, Columbia University Mailman School of Public Health;
Keith Klugman, MB BCh, PhD, FRCPath, Professor of Global Health,
Rollins School of Public Health, Emory University; Ram Koppaka, MD,
MPH, Senior Advisor, Epidemiology and Analysis Program Office, U .S
. Centers for Disease Control and Prevention .
We gratefully acknowledge the support of these individuals, yet
we do not hold them responsible for the views expressed within
.
Additional acknowledgment goes to the World Health Organization
for providing a large portion of the data that appears in this book
.UNICEF, the World Bank, the Stop TB Partnership, and others also
provided essential data .
A special thanks to Mego Lien for her meticulous editing of the
manuscript, and to Stephen Hamill for his invaluable art direction
. WLF is also grateful to its many other colleagues who contributed
their talent and expertise to the review, editing, and design of
the Atlas, as well as those who oversaw project management,
promotion, and distribution of the book: Jorge Alday, Yvette Chang,
Chun-Yu Huang, Alexey Kotov, Sandra Mullin, Rebecca Perl, and
Stephan Rabimov . We would also like to thank other team members at
WLF for their unwavering support of this project: Peter Baldini,
Jos Castro, and Joanna Thomas .
We also extend our appreciation to Sarah Fedota, Rob Levin, and
the staff of Bookhouse Group, Inc . for their hard work on the
design, layout, and printing of the Atlas .
7
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8Acute Respiratory Infections:Making Inroads Against a Forgotten
Pandemic
World Lung Foundation Acute Respiratory Infections Atlas
9
This Atlas offers an in-depth look at a forgotten pandemic that
kills more than four million people every year. And yet the core
message is hopeful: Progress lies within reach.Acute respiratory
infections, or ARIs, are a group of diseases that impose an
enormous burden on vulnerable populations around the world, yet
they have rarely risen to the top of the global health priority
list . This Atlas seeks to change that .
Pneumonia need not claim the lives of 1 .6 million children
every year . The toll of influenza, which causes three to five
million severe infections annually, and respiratory syncytial virus
(RSV), which results in three million hospitalizations, can be
dramatically reduced . All it takes is adequate resources,
collaborative partnerships, and broad global commitment .
Part 1: Understanding Acute Respiratory Infections describes
three major ARIspneumonia, influenza, and RSVas well as the
emerging infections that loom as further threats . It also provides
an overview of tuberculosis (TB), which has many characteristics of
ARIs . This section includes information about the bacterial and
viral pathogens that cause these infections and how they evolve,
the risk of coinfections, the role of the health system, and the
opportunities to intervene at every disease stage .
1 Ischemic heart disease 12 .2%
2 Cerebrovascular disease 9 .7%
3 Lower respiratory infection (accounts for most ARIs)
7 .1%
4 Chronic obstructive pulmonary disease
5 .1%
5 Diarrheal diseases 3 .7%
6 HIV/AIDS 3 .5%
7 Tuberculosis 2 .5%
8 Trachea, bronchus, lung cancers 2 .3%
9 Road traffic accidents 2 .2%
10 Prematurity and low birthweight 2 .0%
Top Ten Causes of Death: Worldwide
1 Lower respiratory infection (accounts for most ARIs)
11 .2%
2 Ischemic heart disease 9 .4%
3 Diarrheal diseases 6 .9%
4 HIV/AIDS 5 .7%
5 Cerebrovascular disease 5 .6%
6 Chronic obstructive pulmonary disease
3 .6%
7 Tuberculosis 3 .5%
8 Neonatal infections 3 .4%
9 Malaria 3 .3%
10 Prematurity and low birthweight 3 .2%
Top Ten Causes of Death: Developing World
Part 2: drivers of Acute Respiratory Infections examines the
environmental conditions that foster ARIs and considers how they
can be altered . Poverty, malnutrition, air pollution, tobacco, and
overcrowding allow pathogens to flourish, while improved standards
of living can vanquish many of them . The Atlas gives special
emphasis to proven interventions, such as the use of cleaner
cooking fuels, emissions controls, breastfeeding and other
nutritional strategies, tobacco regulations, and community
development .
Part 3: Prevention, diagnoses, and Treatment reviews the
therapeutic and policy tools that can halt the spread of ARIs or
control them when they occur: a strong vaccine infrastructure, the
widespread availability of diagnostic tools, comprehensive
surveillance, strategies to maintain the effectiveness of existing
antibiotics, research to develop new ones, and improved access to
health care, especially in poor urban and rural areas .
Part 4: Making ARIs a Global Priority is a call to action for
governments and the international community . Far less funding is
dedicated to ARIs than to HIV/AIDS or malaria, relative to their
global burden . A lack of basic data limits the ability to set
program priorities and measure success . Weak health systems,
workforce shortages, fragmented policymaking, and governance
challenges further delay progress . But the good news is that
strategic, carefully planned changes can have a dramatic impact
.
Appendices provide an overview of illness-causing pathogens and
the bodys defenses, a glossary, extensive country-level and
regional data about the ARI burden and its drivers, and source
lists .
Percent of total deaths Percent of total deaths
WLF_Part1_BH_0824.indd 8-9 8/31/10 11:03 AM
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10
World Lung Foundation Acute Respiratory Infections Atlas
11
Acute respiratory infections (ARIs), a group of diseases that
includes pneumonia, influenza, and respiratory syncytial virus
(RSV), result in 4 .25 million deaths worldwide every year . ARIs
are also the leading cause of illness in children and their leading
killer . These diseases are responsible for at least six percent of
the worlds disability and death .
While the immediate bacterial or viral triggers of ARIs are
unique, the underlying drivers are often the same and can include
some combination of malnutrition, pollution, overcrowding, and
tobacco use . Poverty is also an underlying risk factor, as
evidenced by the disproportionate impact of ARIs on developing
countries and vulnerable populations: The death rate from pneumonia
is 215 times higher in low-income countries than in high-income
countries .
Despite the tremendous public health burden, acute respiratory
infections are not generally recognized as a collective global
threat, and far too little is being done to prevent or treat them .
Yet the good news is that many solutions lie within reach .
Overview
despite the tremendous public health burden, acute respiratory
infections are not generally recognized as a collective global
threat, and far too little is being done to prevent or treat them.
Yet the good news is that many solutions lie within reach.
More than 4,250,000 people will die this year from ARIs. Acute
respiratory infections: Sickenandkillchildren. Twenty to 40 percent
of all hospitalizations
among children are due to acute respiratory infections .
Pneumonia alone is responsible for almost 1 .6 million deaths a
year in children under five, making it the leading global killer in
that age group .
Sickenandkilladults. ARIs annually kill 1 .65 million adults 60
or older and more than half a million people from ages 15 to 59 .
Three to five million severe influenza infections occur every year,
killing some 250,000 to 500,000 people. More than three million
people are hospi-talized annually with illness caused by
respiratory syncytial virus.
Burdenhealthcaresystems.Acute respiratory infections are the
most common reason that people access health services around the
world .
Threatenaglobalcatastrophe.Bacteria and viruses can mutate, as
the H1N1 influenza virus demonstrates, and new pathogens, such as
the one that caused severe acute respiratory syndrome (SARS), can
emerge to infect unprotected populations . Both have unpredictable
consequences .
>200
101-200
51-100
31-50
21-30
11-20
0-10
no data
ARI death rates are highest in sub-Saharan Africa and parts of
Asia .
ARI death rate, per 100,000 (2004)
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12 13
World Lung Foundation Acute Respiratory Infections
AtlasOverview
The Forgotten Pandemic Despite their toll, acute respiratory
infections have been called the forgotten pandemic because they
have not attracted sufficient attention from governments, the
global health community, donors, the pharmaceutical industry, or
the public .
The clinical conditions that comprise ARIs are not uniformly
defined, and they draw only a fraction of the resources dedicated
to other global health challenges . For example, only about one
percent of the funds dedicated to pharmaceutical research and
development in 2007 were spent on bacterial pneumonia, while
HIV/AIDS, malaria, and tuberculosis accounted for 80 percent of
that total .
In part, this skewed resource allocation reflects a tendency to
view every acute respiratory infection discretely, rather than as
an interrelated group of diseases with similar clinical
presentation and a degree of common cause . This Atlas brings the
package of ARIs together in a single volume for the first time so
that the many linked challenges and opportunities can be considered
comprehensively .
Acute respiratory infections are
the leading killer of children under five.
More children under five die of pneumonia worldwide than any
other cause .
Diarrheal diseases 17%
Others 10%
Pneumonia 19%
Severe neonatal infections (mainly pneumonia/sepsis)
10%
Birth asphyxia 8%
Malaria 8%
Measles 4%
Injuries 3%
HIV/AIDS 3%
Preterm birth 10%
Congenital anomalies 3%
Neonatal tetanus 2%
Neonatal other 2%Neonatal diarrheal diseases
1%
The burden of disease linked to ARIs falls most heavily on the
developing world .
>5,000
3,001-5,000
1,001-3,000
401-1,000
201-400
101-200
0-100
no data
Disability-adjusted life years, or DALYs, are a measure of the
burden of disease, calculated both by lost years of life and lost
years of healthy life .
Death Rate from All Causes among Children under Five
>150
101-150
51-100
11-50
0-10
Deaths per 1,000 live births (2008)
DALYs lost to ARIs, per 100,000 (2004)
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World Lung Foundation Acute Respiratory Infections Atlas
15
Overview
14
Global Impact Acute respiratory infections are the leading cause
of illness
worldwide and the leading killer of children . ARIs account for
30 to 50 percent of pediatric visits to medical providers and 20 to
40 percent of all hospitalizations among children .
ARIs are a forgotten pandemic . They have not attracted the
global attention that would enable proven low-cost interventions to
be implemented on a scale that could transform patterns of disease
and death .
ARIs garner considerably less funding, relative to their impact
on health, than HIV/AIDS, malaria or tuberculosis . In 2007,
bacterial pneumonia received about one percent of the US$2 .56
billion invested in pharmaceutical R&D in developing countries
. By comparison, HIV/AIDS received 42 percent, malaria received 18
percent, and TB 16 percent .
Solutions within ReachFortunately, cost-effective solutions are
within reach (see Prevention, Diagnoses and Treatment, p . 66) .
Wider use of existing vaccines can prevent some acute respiratory
infections altogether . Breastfeeding, im-proved nutrition, and
pollution and tobacco controls are also essential tools of
prevention . Close surveillance and timely diagnosis allow acute
respiratory infections to be recognized and curbed before they
spread or become more severe . When ARIs do occur, they can often
be cured with antibioticsif these are readily available, prescribed
appropriately, and taken as directed .
Better access to health care, especially in poor urban
communities and remote rural areas, is crucial to prevention and
treatment . Other priorities are public health education, research
and development to bring more vaccines and new antibiotics to
market, drug-use practices that minimize antibiotic resistance, and
reliable studies to inform interventions .
Significant progress to reduce or prevent ARIs is also
possiblebut it demands more awareness and commitment from donors,
national governments, industry, and the international public health
community (see Making ARIs a Global Priority, p . 88) .
0
Declines in U .S . Child Mortality Rate from Influenza and
Pneumonia
ARIs can be controlled with better housing, better nutrition,
and antibiotics .
5
10
15
20
25
1900 1920 1940 1960
Rate
per
1,0
00 ch
ild ye
ars
Influenza pandemic
Younger than age oneAges one to four
Antibiotics introduced
In parts of the developing world, the death rate from ARIs alone
is ten times higher than the global median death rate from all
causes .
500
450
400
350
300
250
200
150
100
50
0
Glob
al Med
ian AR
I deat
h Rate
Proven strategies exist, but we are failing to act globally.
Of 2 .5 million child deaths preventable by vaccines in 2002,
more than half were caused
by ARI-related pathogens .
Other vaccine-preventable diseases
1%
Tetanus 8%
Pertussis 11%
Haemophilus influenzae type b
15%
Pneumococcal diseases
28%
Measles 21%
Rotavirus 16%
ARI
-rel
ated
dea
ths p
er 1
00,0
00 to
tal d
eath
s (20
04)
Actions That Make a Difference Expanding access to vaccines,
improving nutrition (including better
breastfeeding practices), mitigating air pollution, and
controlling tobacco use can prevent many acute respiratory
infections, and pharmaceutical therapies can cure others .
Reducing global poverty would lessen some of the key drivers of
acute respiratory infections while also improving access to care .
These drivers include malnutrition, air pollution associated with
wood-burning cookstoves and motor vehicles, and overcrowding in
urban areas .
Fostering broad-based commitment from governments, increased
donor funding, and more engagement by the public, the global health
community, and the pharmaceutical industry are crucial to lessen
the toll of acute respiratory infections .
Djibo
uti
Eritre
aKe
nya
Haiti
So To
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Tajiki
stan
Myan
mar
Gamb
ia
Dem .
Peop
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p . of K
oreaYem
enTo
go
Mauri
tania
Mozam
bique
Tanz
ania
Camb
odia
Ugan
da
Mada
gascar
Came
roonGu
inea
Centr
al Afric
an Re
publi
c
Zamb
iaBe
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Senega
l
Cte d
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Niger
ia
Malaw
i
Ethiop
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ad
Equa
torial
Guine
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Burki
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Guine
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Rwan
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Rep . o
f the C
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Burun
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Ango
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Afgh
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Sierra
Leon
eNi
ger
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16
Acute respiratory infections cause
atleastsixpercentofthedisabilityanddeatharoundtheglobe,affectingthemostvulnerablepopulations,especiallytheyoung,theold,theailing,andthepoor.
Pneumonia is the leading global killer of children under five,
responsible for almost 1 .6 million deaths a year, most of them in
developing nations .
Influenza causes three to five million severe infections in a
typical year and could create a global emergency if a new and
virulent influenza virus were to spread rapidly.
Respiratory syncytial virus (RSV) is the most common source of
severe respiratory illness in infants and children worldwide.
Acute respiratory infections can occur in either the upper or
lower respiratory tract (see Appendix B, p . 100, for more
information on infectious agents and the bodys defense system) .
Lower respiratory tract infections, which include pneumonia,
influenza, and RSV and typically involve the lungs, are the primary
focus of this Atlas .
Because tuberculosis (TB) can be mistaken for pneumonia and
affects the lower respiratory tract, it is included in this Atlas,
even though symptoms tend to develop more gradually and it is not a
classic ARI . TB causes nine million symptomatic cases and two
million deaths annually .
Pertussis, which is preventable with vaccines, is another
potentially dangerous ARI . In developing countries, 40 deaths
occur for every 1,000 pertussis cases (compared with one death in
the developed world) . The overall ARI-related data collected by
the World Health Organization (WHO) and others, and presented in
this Atlas, do not include pertussis, but it is mentioned in
several sections of this book .
Strategies to curb ARIs include:
Emphasizingacuterespiratoryinfectionsasaninterrelatedpackage
of health challenges that can be addressed with low-cost
prevention and treatment strategies .
Strongerdatacollectionandmonitoringsystemstomeasurethe
incidence of acute respiratory infections and to evaluate
prevention, diagnostic, and treatment strategies .
Improvingaccesstocare,distributingeffectivevaccinesmore
widely, encouraging appropriate use of antimicrobials, and
under-taking more vaccine development and drug research .
Publichealtheducationpromotingbreastfeeding,infectioncontrol,
tobacco control, and spreading knowledge about the warning signs
of serious disease .
Adequateresourcesforsurveillanceinordertoidentifynew
pathogens quickly, when more opportunities exist to control them
.
Initiativesthataddressglobalpoverty,includingmalnutrition,
overcrowding, and other living conditions that are directly
linked to ARIs .
Part 1Understanding Acute Respiratory Infections
World Lung Foundation Acute Respiratory Infections Atlas
17
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World Lung Foundation Acute Respiratory Infections Atlas
Pneumonia is the leading global killer of children under five,
respon-sible for almost 1 .6 million deaths per year. In that
vulnerable popula-tion, it is a disease of poverty and occurs most
commonly when a childs still-developing defense system is weakened
by malnutrition, air pollution, coinfections with HIV/AIDS and
measles, and low birth-weight. In wealthier nations, adults over 65
years old and people with chronic health problems bear the greater
burden of pneumonia .
An estimated 156 million new cases of pneumonia occur each year,
97 percent of them in the developing world, and seven to 13 percent
of them severe enough to require hospitalization . Seventy-four
percent of those cases occur in just 15 countries, mostly in Asia
and sub-Saharan Africa, with 43 million cases in India alone.
Pneumonia occurs when the sacs of the lungs, known as alveoli,
become filled with pus and fluid, limiting oxygen intake and making
it hard to breathe . A bacterial or viral pathogen can be the
primary cause of pneumonia, or it can be a complication of other
infections, including influenza, measles, tuberculosis, or HIV
.
Pneumonia is responsible for nearly 20 percent of child deaths
globally .
PneumoniaVaccines, breastfeeding, improved living standards, and
swift treatment can curb pneumonia, the leading global killer of
children under five.
Global Impact
Almost1.6milliondeathsfrompneumoniaoccurannually
in children under five, about one-fifth of all pediatric deaths
around the world (based on 8 .8 million pediatric deaths from all
causes in 2008) . By contrast, 732,000 children die from malaria
and 200,000 from HIV/AIDS each year .
Everyyear,anestimated156millionnewcasesofpneumonia
occur, 97 percent of them in the developing world . Seventy-four
percent of those cases occur in just 15 countries, mostly in South
Asia and sub-Saharan Africa, with 43 million cases in India alone
.
Improvedlivingstandardsandaccesstoantibioticstransformed
the trajectory of pneumonia in the developed world during the
20th century . In the United States, pneumonia-related deaths among
children fell by 97 percent between 1939 and 1996 .
>19 .9%
15-19 .9%
10-14 .9%
2-9 .9%
-
20 21
World Lung Foundation Acute Respiratory Infections Atlas
How Infection OccursMost severe cases of pneumonia, whether
acquired in the community or the hospital, result from bacterial
infections, although viruses or fungi can sometimes be the cause .
These pathogens may travel as airborne particles or droplets,
causing infection after they are inhaled, or they may colonize the
nose or throat, where they reside harmlessly until they have an
opportunity to penetrate the bodys defense system and travel into
the lungs . Newborns can also become infected by exposure to
microbes in the birth canal or during delivery.
Often, pneumonia is the result of a coinfection process, in
which one pathogen damages the bodys tissues or immune system,
making it easier for other pathogens to cause secondary infection
in the lungs . For example, pneumonia can cause death among the 30
to 40 million children infected by measles every year, and within
the same country, people living with HIV are 20 to 40 times more
likely to become infected with tuberculosis.
Pathogens That Cause PneumoniaBacteria: Streptococcus
pneumoniae, usually called pneumococcus, is the most common cause
of bacterial pneumonia worldwide, accounting for about 30 percent
of the total pneumonia caseload and at least half the cases in the
developing world . In 2000, almost 14 million pneumococcal
pneumonia cases occurred in children younger than five .
Pneumococcus is also a leading cause of meningitis in that age
group.
Haemophilus influenzae type b (Hib) is implicated in as many as
20 percent of the worlds severe pneumonia cases. These bacteria,
which also cause meningitis and other severe infections, were
responsible for 7 .9 million cases of pneumonia in 2000, resulting
in the deaths of an estimated 300,000 children under age five.
Hospital-acquired bacterial pneumonia is typically caused by
Staphylo-coccus aureus or gram-negative bacteria (including
Legionella spp, which causes Legionnaires disease) . These
infections are also increasing in the community, especially
antibiotic-resistant staph . Pneumonia can also result from
tuberculosis, which is caused by Mycobacterium tuberculosis .
Viruses: If left untreated, influenza virus, respiratory
syncytial virus, parainfluenza virus, and the measles virus can all
lead to pneumonia .
Fungi: Individuals with compromised immune systems, especially
those who are HIV-positive, are susceptible to Pneumocystis
jiroveci pneumonia . Other types of fungus-linked pneumonia occur
among individuals in certain geographic locations, including the
American Southwest .
Preventing PneumoniaIn the United States, pneumonia-related
deaths among children fell by 97 percent between 1939 and
1996dramatic evidence of what effective clinical and public health
measures can accomplish .
Vaccines: Vaccines to prevent diseases associated with
Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae
type b are remarkably effective . Children in countries without
these vaccines are 40 times more likely to die than those in
countries that administer them routinely . Wider use of the measles
vaccine, which covered three-quarters of the worlds children in
2004, could also lessen pediat-ric pneumonia significantly .
Pneumococcus: The pneumococcal conjugate vaccine (PCV13),
approved in the United States in 2010, protects infants, children
and adults against 13 of the most common pneumococcal strains,
known as serotypes (20 serotypes cause most pneumococcal infections
worldwide) . PCV13 replaces PCV7, which has been available since
2000 . Earlier generations of vaccines, first distributed in the
mid-1970s, were not safe for children younger than two years old
.
The potential benefit to developing countries is highlighted by
the effectiveness of a vaccine that was tested in Gambia and was
designed to provide protection against the nine pneumococcal
serotypes most prevalent in the country . On the basis of a
four-year study of
3%
21%21%15%15%14%13%
20%
19%2%
0% 10% 20% 30% 40% 50%
South Asia
Sub-Saharan Africa
Middle East and North Africa
East Asia and Pacific
Latin America and CaribbeanCentral and Eastern Europe and
the
Commonwealth of Independent States
Developing countries
Industrialized world
World
Percent of total deaths in children under five from
pneumonia(excludes severe neonatal infections, some of which are
pneumonia)
World Bank Income Group (2004)
The lower a countrys income, the more child deaths from
pneumonia .
20%
15%
10%
5%
0%
Low-i
ncome
Lowe
r-midd
le-inc
ome
Upper
-midd
le-inc
ome
High-i
ncome
Perc
ent o
f dea
ths i
n ch
ildre
n
unde
r five
due
to p
neum
onia
The burden of pneumonia in the developing world is nearly ten
times that of the developed world .
Pneumonia
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World Lung Foundation Acute Respiratory Infections
AtlasPneumonia
17,000 children, researchers determined that the vaccine had
lowered rates of X-ray-confirmed pneumonia by 37 percent and had
reduced mortality by 16 percent . Gambia, Rwanda and South Africa
now include the vaccine as part of their routine vaccination
programs .
Haemophilus influenzae type b (Hib): Ninety-two percent of
children in developed countries received Hib conjugate vaccines in
2003, compared with 42 percent in the developing world and just
eight percent in the least-developed countries . The Hib vaccine is
highly effective in reducing infections in countries where it is
widely used, even among unvaccinated people, presumably because it
lessens the chance that people will be exposed to the bacteria (a
phenomenon known as herd immunity). Broader use of the Hib vaccine
could save 400,000 lives.
The bottom line is clear: Vaccines can transform patterns of
pneumonia in developing countries, as they have in the developed
world . But increasing immunization depends on a strong vaccine
delivery infrastructure, leadership and political will, and a much
greater commitment from the international community (see Preventing
ARIs with Vaccines, p . 68) .
Projected Lives Saved with Proven Pneumonia Interventions among
Countdown to 2015Countries (see Countdown to 2015 Initiative p . 96
.)
Deaths from childhood pneumonia can be dramatically reduced with
a package of proven interventions .
100%
80%
60%
40%
20%
0%2009 2010 2011 2012 2013 2014 2015
Aver
age c
over
age o
f int
erve
ntio
nsby
year
(%)
Child deaths prevented annually(x 100,000)
20
15
10
5
0
Post-neonatal pneumonia deaths Neonatal pneumonia/sepsis
deaths
Pathogens That Cause Pneumonia
Half the severe cases of pneumonia among children in developing
countries are caused by
pathogens that can be stopped by vaccines .
S. pneumoniae
H. influenzaeRSV and other
respiratory viruses
No pathogen identified
S. aureus
Gram-negativebacteria
M. tuberculosis
Breastfeeding:Breastfeeding provides all the nutrients an infant
needs in the first six months of life . It remains an essential
nutritional source until at least age two and contributes
significantly to the development of a healthy immune system, making
it one of the most important tools available to prevent pneumonia
(see Breastfeeding, p . 50) .
Improved living standards: Like other acute respiratory
infections, pneumonia targets the worlds most vulnerable children .
Malnutrition, crowded housing, smoking, and polluted air,
especially in households that cook with wood and other biofuels,
have all been linked to higher incidences of pneumonia (see Drivers
of Acute Respiratory Infections, p . 44) .
Improvements in health care, nutrition, and the environment are
independent interventions that can significantly reduce the
incidence of pneumonia . But a broad and integrated commitment on
the part of the international community to improving living
standards world-wide is the true foundation of prevention (see
Making ARIs a Global Priority, p . 88) .
Treating PneumoniaAppropriate therapies, administered promptly,
will cure most cases of pediatric bacterial pneumonia . But many
children go untreated, and as many as 20 percent of them will die
as a result, sometimes within three days of the onset of
illness.
Diagnoses: A first step in treatment is to recognize the warning
signs and to seek immediate attention from a health care provider .
But in the developing world, only 54 percent of caregivers
recognize the need to take a child who is breathing quickly, or
with difficulty, to an appropriate provider, even though these are
classic indicators of pneumonia .
To provide optimal therapy, it is ideal for clinicians to
identify the pathogen involved, but this is often impossible,
especially in resource-poor countries without adequate laboratories
. Conventional diagnostic techniques, including blood tests and
cultures taken from blood and sputa, may not be available . Even if
they are, these tests are less definitive than using the much more
costly tools of microbiology, such as DNA-based techniques that
identify specific pathogenic strains . If resources allow for an
intensive investigation, multiple infectious agents can still make
the cause difficult to pinpoint.
Treatments: Antibiotics are the treatment of choice for
bacterial pneumo-nia . They can cure most cases, and if they were
given to all children under age five with pneumonia, as many as
600,000 lives could be saved annu-ally. Yet a 2008 report indicated
that only about one-third of all children under five with suspected
pneumonia received an antibiotic in the 68 countries that have the
highest levels of childhood and maternal deaths (see Antibiotics
and Antiviral Therapy, p . 78) . Providing universal antibi-otic
treatment in sub-Saharan Africa and South Asia, where the great
majority of pediatric deaths occur, would cost US$200 million per
year .
Systems for delivering supplemental oxygen to children with
pneumonia can also save lives, but deficits in equipment, supplies,
and staff training have meant that this critical component of care
is often unavailable in developing countries . Investments in
oxygen systems should be a more prominent priority of those
concerned about treating pneumonia .
Most caregivers dont know when to seek care for child pneumonia.
Just 17 percent know that fast breathing is a sign to seek
immediate care, and just 21 percent recognize that difficult
breathing demands the same attention.
Case management of pneumonia
Hib vaccine
Breastfeeding counseling
Pneumococcal vaccine
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World Lung Foundation Acute Respiratory Infections Atlas
HIV and PneumoniaCommon bacterial pneumonia, pneumonia
associated with tuberculosis, and fungal pneumonia caused by
Pneumocystis jiroveci all have a greater impact on HIV-infected
people because their immune systems are so weakened. HIV-infected
children are 40 to 50 times more likely than children without HIV
infection to develop pneumonia and are less likely to respond to
treatment . Likewise, the fungus may reside harmlessly in the lungs
of healthy people, but it causes one-quarter of all deaths among
HIV-positive infants younger than six months and is often the first
indication that an infant is carrying the virus.
Prevention and treatments: Vaccines designed to prevent
bacterial pneumonia are less effective in HIV-infected populations,
but they still have the power to save lives . For example, under
the controlled conditions of a clinical trial, the conjugate
pneumococcal vaccine provided protection to 65 percent of
HIV-infected children (compared with 83 percent among uninfected
people) . The Haemophilus influenzae type b vaccine provided
protection to 55 percent of infected children (compared with 91
percent among those without HIV). HIV-infected populations are
generally advised to have both vaccines, as well as to be immunized
against influenza.
Some of the clinical interventions used to treat HIV can also be
effective in preventing pneumonia, including highly active
antiretroviral therapy (HAART) . The combination of drugs used in
HAART reduces by fourfold the risk of opportunistic infectionsthose
that can gain a foothold in the body because the immune system is
damagedamong HIV-infected children. Cotrimoxazole, a combination of
two
Pneumonia
20,000
5,000-19,999
2,000-4,999
500-1,999
100-499
20-99
-
26 27
World Lung Foundation Acute Respiratory Infections Atlas
InfluenzaSurveillance, vaccines, and infection control can curb
influenza, which causes three to five million severe infections
annually.
The Influenza VirusInfluenza can be caused by three major
classes of RNA viruses grouped by their genetic characteristics .
Influenza A and B are associated primarily with diseases in humans,
while influenza C primarily infects animals .
These classes are further delineated by the nature of the two
large proteins on the viral surfacehemagglutinin (HA) and
neuraminidase (NA) . There are 16 HA and nine NA subtypes, although
relatively few cause human infection. The proteins largely define
the behavior of viruses, which are named according to the
combinations of protein they contain . For example, the influenza A
viruses currently circulating in the human population include the
subtypes H1N1 and H3N2 .
Once an influenza virus has invaded the body and attached itself
to cells lining the respiratory tract, it incubates for one to
seven days before symptoms appear . An infected individual may be
able to infect others prior to and during the symptomatic period .
One study of the pandemic H1N1 virus showed that children and young
adults remained infectious for ten days or longer, while
individuals with compromised immune systems might be capable of
infecting others for weeks . Influenza can survive for hours
outside a human host, further aiding its capacity to spread.
The many types of influenza virus infect anywhere from five to
30 percent of the worlds population during a typical year . Most
cases of flu are mild, primarily affecting the nasal passages,
throat, and pharynx in the upper respiratory tract . But every year
three to five million severe infections occur, generally in the
lower respiratory tract (see The Airways and the Lungs, p . 103) .
Influenza kills 250,000 to 500,000 people annually .
Influenza tends to get more attention in wealthier countries,
where infants and individuals over age 65 are typically at greatest
risk be-cause of their lessened immunity and underlying health
conditions . In developing countries, where so many other health
problems compete for attention, influenza is sometimes
overlookedyet it imposes a heavy disease burden, especially among
populations that are malnourished or immunocompromised .
The flu virus can travel on inhaled airborne particles, sprayed
droplets that are projected onto mucous membranes, or a
contaminated hand that touches the nose or mouth . In temperate
regions of both hemi-spheres, peak flu activity occurs in the
winter season, while in the trop-ics, influenza occurs throughout
the year.
Global Impact
Worldwide,threetofivemillionsevereinfluenzainfectionsoccur
annually, killing between 250,000 and 500,000 people . While
influenza is a burden everywhere, it tends to be overlooked in
de-veloping countries, where inadequate laboratory facilities
impede diagnoses, and other health challenges compete for attention
.
Vaccinesarethemosteffectivestrategyavailableforpreventing
influenza, but the wealthier nations dominate production, and
worldwide capacity is limited to 900 million doses .
Manyinfluenzavirusesareresistanttoantiviraltherapies,and
those that remain effective are not being manufactured in
ad-equate volume .
Most developing countries lack the ability to diagnose and
report influenza .
Actions That Make a Difference
Rigoroussurveillancecansendanearlywarningsignalabout
the emergence of new viral strains, providing a window of
opportunity for control . Effective surveillance requires adequate
resources and international cooperation (see Surveillance
Techniques, p . 75) .
Researchisneededonmoreefficientwaystomanufacture
vaccines, distribution systems to poor countries should be
strengthened, and more equitable access to a limited vaccine supply
is essential (see Preventing ARIs with Vaccines, p . 68) .
Publiceducationabouthand-washingtechniques,coughand
sneeze safeguards, and limiting social contact are essential to
curbing the spread of flu . In health care settings, compliance
with proper infection control procedures is also crucial, so that
infections do not spread from patient to health care worker to
patient .
Insevereepidemics,itmaybecomenecessarytousepublic
policies that restrict public interaction and minimize the
spread of infection .
Newantiviraltherapiesareneededtocountergrowingdrug
resistance . For example, oseltamivir (Tamiflu) has largely lost
its value against a seasonal form of H1N1 . Tamiflu remains
effective against the pandemic strain of H1N1 that arose in 2009,
but production capacity should be increased from the 220 million
doses currently available around the world (see Antibiotics and
Antiviral Therapy, p . 78) .
Influenza has been overlooked in develop-ing counries, but it
imposes a heavy burden, especially among malnourished and
immunocompromised populations.
>10,000
3,001-10,000
1,001-3,000
101-1,000
0-100
no data
Number of laboratory- confirmed flu cases (2009)
Structure of an Influenza Virus
HA
NA
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1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010
Drift and Shift: How Influenza Viruses EvolveInfluenza viruses
can mutate swiftlyone million times faster than vertebrates can
mutateand can swap genetic components with other viruses . Many
influenza viruses are believed to originate in the tropics before
being exported to the more temperate northern and southern
hemispheres, although this pattern is not fully understood.
In a process known as antigenic drift, the proteins on the
surface of the flu virus make frequent minor changes in their
genetic structure . The resulting new strains can evade the human
defense system, even among populations previously infected by, or
vaccinated with, a related strain.
At unpredictable intervals, flu viruses with the power to infect
humans undergo antigenic shift, a more significant genetic
alteration that typically results from a merger with viruses
residing in reservoirs of poultry, water fowl, pigs, or other
mammals . If the recombined virus is zoonotic, or capable of
traveling from animal to human populations, humans are unlikely to
have any immunity .
Influenza A and B viruses are subject to antigenic drift, while
only influenza A undergoes antigenic shift. The H1N1 pandemic of
2009-10 is an example of a significant viral antigenic shift.
Influenza PandemicsA pandemic is the widespread transmission of
a pathogen to populations around the world . Influenza pandemics
are inevitable but unpredictable, and they generally occur with the
emergence of a virus that is either novel or has not circulated for
many decades . Pandemic flu infects far more people than a typical
seasonal flu, although the illness is not necessarily more severe
.
Pandemics of the past: Three influenza pandemics occurred in the
20th century, each resulting from antigenic shifts in the influenza
A virus .
The Spanish flu of 1918, believed to be the most devastating in
human history, infected between one-third and one-half the worlds
population and killed tens of millions of people . Milder pandemics
occurred in 1957, when Asian influenza killed two million people,
and in 1968, when the Hong Kong influenza was responsible for one
million deaths .
Human influenza pandemics are inevitable, but unpredictable, in
the extent of the death they cause .
H1N1Spanish flu
as many as 50 million deaths
H2N2 Asian flu
2 million deaths
H3N2Hong Kong flu
1 million deaths
H5N1
H7N2
H9N2H5N1H7N7H7N2H9N2
H5N1H7N3
H10N7
H1N118,000 deaths
Antigenic DRIFT
Antigenic SHIFT
Antigenic Drift and Shift
The Spanish flu pandemic may have involved an avian virus that
adapted to become able to infect humans directly, while the Asian
and Hong Kong pandemics were caused by a reassortment of human and
avian viruses. In each case, younger populations faced
greater-than-usual risks, possibly because they had no exposure to
earlier versions of the pathogenindividuals younger than 65 were 20
times more likely to die during one of these pandemics than they
were during a normal flu season . Elderly populations, who are
inherently more vulnerable, may have already built up some
immunological protection and did not face special additional risks
.
Spanishfluof1918: The 1918 pandemic occurred in three waves
around the world. After a first round of mild infections in the
spring, the Spanish flu returned with deadly power in the late
summer, causing acute lung inflammation and progressing rapidly to
lethal pneumonia . A third wave in early 1919 was also deadly,
although less so . Mortality data are inconsistent, but most
sources estimate that between 20 and 50 million deaths occurred .
Global population growth remained depressed for a decade afterward
.
Researchers have called the Spanish flu the mother of all
pandemics because the genetic structure of most subsequent
influenza A viruses can be traced back to it . Many of todays
efforts to prepare for a potential new pandemic consider the
severity of that event in their calculations, although the vagaries
of biology, coupled with todays ease of travel, ac-cess to health
care, and improved nutrition, make extrapolation difficult .
The Spanish flu pandemic may have involved an avian virus that
adapted to become able to infect humans directly, while the Asian
and Hong Kong pandemics were caused by a reassortment of human and
avian viruses.
1918 1957 1968 2009
Improved surveillance has helped to identify emerginginfluenza
strains that did not reach pandemic levels .
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The burden on many local health systems was significant, with
spikes in the use of emergency rooms, hospitals, and outpatient
care . Mexico, where the virus was first reported, estimated the
cost of the outbreak at 57 billion pesos in 2009 (US$4 .29
billion), primarily from lost tourism. An adequate vaccine supply
was slow to become available: Near the end of 2009, WHO said it
would have 200 million donated doses available to 95 countries that
are home to one-third of the global population; by contrast, the U
.S . had already purchased 250 million doses for its residents.
Because the symptoms caused by the H1N1 pandemic have been
relatively mild, at least thus far, global response capacity was
not fully tested . Nonetheless, even an outbreak of limited
virulence strained public health resources .
Avian flu watch: Aware that other influenza pandemics are
inevitable, public health officials around the world conduct
surveillance in order to identify new viral strains as soon as
possible . A strain of H5N1 avian in-fluenza virus, first isolated
in Asia in 2003, remains worrisome. As many as 150 million birds
were culled to reduce transmission of the highly contagious virus,
which is often fatal in domestic stocks of poultry, cats, and wild
birds, but the virus nonetheless remains endemic in many parts of
Asia .
To date, the H5N1 virus has had limited ability to cross the
species barrier into human populations . From 2003 to May 2010, WHO
reported fewer than 500 laboratory-confirmed human infections,
although the death rate when infection does occur approaches 60
percent (and in Indonesia, 165 cases caused 136 deaths). Should the
virus evolve to infect humans more readily, it could cause a
devastating new pandemic .
H1N1: The First 21st-Century Flu PandemicOn June 11, 2009, two
months after two cases of a new strain of in-fluenza A H1N1 were
confirmed in the United States, WHO officially declared the first
flu pandemic of the 21st century . By then, some 30,000 cases had
been confirmed in 74 countries . Although the circulating virus was
a novel combination of swine and avian influenza A viral strains,
some components had circulated in the past, giving many adults born
before 1956 a degree of immunity.
Areas with confirmed H5N1 human cases, since 2003
Avian Flu Watch: Will H5N1 cause the next epidemic?
A strain of H5n1 avian influenza virus, first isolated in Asia
in 2003, is particularly worrisome. As many as 150 million birds
were culled to reduce transmission of the highly contagious virus,
but it nonetheless remains endemic in many parts of Asia.
At-risk groups: The majority of infections have occurred among
individuals with an age range of 12 to 17 years, but the groups at
highest risk for complications have been the elderly, children
under five, pregnant women, and individuals with chronic health
problems . As in a more traditional flu season, severe respiratory
distress and coinfection with bacterial pneumonia can develop. As
of May 2010, 18,000 laboratory-confirmed deaths from the pandemic
form of H1N1 had been reported . However, the total death toll is
undoubtedly much higher, as most cases are not confirmed .
Are we prepared? H1N1 has been a test case for global
preparedness . WHO guided international surveillance efforts, and
many nations declared the pandemic a public health emergency. Among
those nations was the United States, which released stockpiles of
antiviral medication and protective equipment but did not choose to
exert the federal authority to impose border controls or mandate
that public facilities be closed .
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Preventing Influenza Vaccines: The best protection against
influenza is a vaccine well matched to the viral strains in
circulation in any given season . Once developed, access remains a
challenge and coverage rates are generally low, especially in
less-developed countries . The vaccine supply is never sufficient
to reach all those who need it: Even without a pandemic, some 1 .2
billion people around the globe are considered at high risk for
flu, and many more are likely to be affected during a pandemic
.
Only 900 million doses of vaccine can be produced worldwide, if
all manufacturing facilities are operating at maximum capacity .
More research is needed to overcome production bottlenecks, improve
vaccine technology, and identify more efficient immunization
strategies . Strengthening distribution systems and developing
strategies to ensure more equitable access to limited vaccines are
also essential, and manufacturers liability concerns may need to be
addressed .
Because the vaccine designed for the 2009-10 flu season did not
confer protection against the H1N1 virus that emerged to cause a
pandemic, a new vaccine had to be developed, licensed and
distributed in the months after its appearance . With supplies
scarce, public health agencies in many countries initially limited
immunization to first-responders and other priority populations .
By the end of 2009, the United States had purchased adequate
supplies for most of its residents, but WHO, relying on donated
vaccines, had only 200 million vaccine doses for 95 countries with
one-third of the worlds population.
Other prevention strategies: No vaccine confers 100 percent
immunityfor example, a single dose of H1N1 vaccine generates a
robust immune response in only 56 to 80 percent of adults 65 or
older. Public education about hand-washing techniques and cough and
sneeze safeguards is essential to preventing flu outbreaks or
reducing the viruss spread in communities . In severe epidemics,
the principles of social distancing, such as canceling public
events and closing recreational facilities, may also be necessary .
Compliance with proper infection-control procedures in health care
settings limits spread among patients and staff, and prophylactic
antiviral drugs may be appropriate for health care workers and
others at high risk of complications .
Government mandates are another option for prevention . For
example, some Asian countries have used quarantine and medical
detention to curb H1N1 transmissionaggressive but controversial
measures that appear to have slowed the spread of disease . Many
other nations have developed pandemic preparedness plans, with
containment strategies that include travel restrictions and
prohibitions against mass gatherings .
Influenza Surveillance Worldwide monitoring of influenza
provides best-guess information about the viral strains most likely
to cause disease in a given year, so that a timely vaccine can be
manufactured and distributed (some com-ponents of the vaccine
change every year) . Surveillance is also essential for alerting
public health authorities to illness surges so that they can act
before a new, highly transmissible, or especially dangerous virus
spreads in human populations .
Many surveillance strategies are available . These include case
counts, based on specific laboratory tests and physician reports,
monitoring do-mestic and wild animal populations, emergency room
records, and even Google Flu Trends, which tracks regional patterns
of online flu-related queries (see Surveillance Techniques, p . 75)
.
WHOs Global Influenza Surveillance Network, established in 1952,
is the primary vehicle for a coordinated, worldwide tracking
effort.
As part of this network, designated National Influenza Centres
at 134 institutions in 104 countries isolate and analyze some
175,000 viral samples every year and submit 2,000 of them to five
WHO Collabo-ration Centers. These centers sequence the viruses to
determine the extent and direction of their evolution away from
previously identi-fied genetic structures . Through FluNet, the
networks web-based data collection and reporting tool, tables,
maps, graphs and reports are available to the public .
Many countries with the highest burden of acute respiratory
infec-tions do not have their own National Influenza Centres
because they lack the resources and technology to provide the
necessary data . For example, of 46 countries in the WHO African
region, only 18 have centers, and only 10 have the laboratory
capacity to conduct sophisti-cated diagnostic testing.
Treating Influenza A class of antiviral therapies known as
neuraminidase inhibitors, which include zanamivir (Relenza) and
oseltamivir (Tamiflu), can reduce the severity of some types of
influenza, but only if they are administered within 48 hours of the
onset of illness . Treatment is generally recommended only for
individuals at risk of complications and for those who have been
hospitalized with flu symptoms, as the majority of the population
can recover on its own .
Certain influenza strains have become resistant to an older
class of antivirals known as adamantanes, and Tamiflu is no longer
effective against a form of H1N1 influenza that circulates
seasonally . While Tamiflu generally remained effective for the
2009 pandemic strain of H1N1, scattered reports of resistance raise
concern (see How Drug Resistance Develops, p . 78) . Even if
Tamiflu does retain its effectiveness, supplies are limited: In
2009, only about 220 million doses were available around the
world.
24 million health care workers
Several hundred million adults and children with underlying
chronic health
problems.
385 million elderly 140 million infants
As many as one billion people are at high risk for severe
influenza outcomes, yet the worlds total vaccine production
capacity is only 900 million doses .
0 200 million 400 600 800 1 billion
At-risk populations
Vaccine production capacity
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World Lung Foundation Acute Respiratory Infections Atlas
In adults, the distinctive feature of RSV is its
disproportionate impact on vulnerable populations . Although three
to seven percent of a healthy elderly population had active RSV
infections in one study, they had gen-erally milder symptoms than
those who had influenza, and they rarely needed to be hospitalized.
By contrast, in a high-risk populationsuch as adults over 21 who
had been diagnosed with congestive heart failure or chronic
pulmonary diseaseRSV hospitalization and mortality rates were
comparable to those of influenza . More than 10 percent of all
pneumonia-related hospitalizations identified in this population
over four winter seasons were caused by RSV.
Buildingimmunity: RSV exposure in infancy does not provide full
protection against subsequent infection, so children may have
repeated symptoms, especially until about age three . Older
children and adults are less vulnerable, but the recurrence of
symptoms in at-risk and elderly populations suggests that naturally
acquired immunity to RSV is only partial . Moreover, the immune
systems response to RSV is in itself a significant factor in the
disease, promoting inflammation that may result in chronic
lung-related problems .
Respiratory Syncytial VirusRSV is the most common source of
severe respiratory illness in children worldwide, but a vaccine is
not yet available.
0.7%0.3%
0% 0.5% 1% 1.5% 2% 2.5%
Industrializedcountries
Children
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World Lung Foundation Acute Respiratory Infections Atlas
TuberculosisTB, which kills two million people annually, is not
a classic ARI because it progresses more slowly, but many of the
root causes, symptoms, and effective interventions overlap.
Countries with highest TB burden
Twenty-two countries incur 80 percent of all TB cases .
Global Impact
TBcausesnearlytwomilliondeathsayear,makingittheworlds
seventh most common cause of mortality . More than two billion
people are currently infected with Mycobacterium tuberculosis, and
ten percent of them will develop active TB symptoms over their
lifetimes . Though TB is not a classic ARI, the symptoms and
drivers are similar, as are some of the effective interventions
.
First-linetherapiestocureTBcancostaslittleasUS$20per personbut
if the disease becomes resistant to those drugs, treatment costs
can rise to US$5,000 or more . (A recent Kenyan study reported
per-person costs of US$21,000 .)
FivepercentoftheglobalTBcaseloadisnowresistanttomultiple
antibiotics, and in some republics of the former Soviet Union,
multidrug-resistant TB accounted for more than one-fifth of all new
TB cases in 2008 .
In2008,1.4millionpeoplelivingwithHIVhadactiveTB. HIV-positive
people are more likely to become infected with TB, more likely to
have treatment-resistant forms of the disease, and more likely to
die of it .
More than two billion peopleone-third of the worlds
populationare infected with Mycobacterium tuberculosis .
Tuberculosis can survive host defenses and remain hidden within the
body for decades, and most people infected with TB are symptom-free
.
But this reservoir of latent infections leads to more than nine
million symptomatic cases of tuberculosis every year, and two
million TB deaths annually . Eighty percent of active TB cases are
found in 22 countries, most of them developing nations in Asia
(with 55 percent of the worlds cases) and Africa (with 30
percent).
Directly observed therapy, short course, or DOTS, cures most TB
in high-burden countries but only about two-thirds of active cases
are ever detected .
100%
80%
60%
40%
20%
0%
Afgh
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n
Bang
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Brazil
Camb
odia
China
Dem .
Rep . o
f the C
ongo
Ethiop
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ia
Indon
esia
Keny
a
Mozam
bique
Myan
mar
Niger
ia
Pakis
tan
Philip
pines
Russi
an Fe
derati
on
South
Afric
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Thail
and
Ugan
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of Ta
nzan
ia
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am
Zimbab
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WHO target
Perc
ent o
f dO
TS su
cces
s
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TB in children has been a neglected aspect of the disease, even
though WHO estimates that 10 to 15 percent of the global caseload
occurs in children under age 14 . In some countries, pediatric TB
represents as many as 40 percent of all cases .
Treating TBTuberculosis can generally be cured with a four-drug
cocktail, administered over six months, that can cost as little as
US$20 per person . But more bacterial strains are becoming
resistant to therapy (see How Drug Resistance Develops, p . 78),
leaving increasing numbers of patients with limited treatment
options, or none at all . If the disease becomes resistant to
first-line therapies, medication and other treatment costs can rise
to US$5,000, or much higher .
Treating TB effectively requires more investment in the
diagnostic tools used to identify active infection, greater use of
directly observed therapy, short course (DOTS)the proven technique
of monitoring patients as they take their drugsand more
pharmaceutical research to replace drugs that have stopped working
.
Directlyobservedtherapy,shortcourse:One of the most important
strategies for curing TB, and curbing the development of drug
resistance, is a short course of directly observed therapy, in
which patients take their drugs under supervision . More than half
the worlds population lives in a region that has adopted DOTS,
which has an 85 percent success rate .
Of course, a diagnosis is required before DOTS can be
implemented, and this is a significant gap: Only about two-thirds
of active TB cases are ever detected, mostly because modern
diagnostic equipment is lacking in regions where TB is most common
.
Drug-resistantTB:Five percent of the worlds tuberculosis cases
are now multidrug-resistant (MDR-TB) and can no longer be treated
effectively with rifampicin and isoniazid, two of the first-line
therapies . In 2007, some 510,000 cases of MDR-TB occurred, and the
problem seems to be growing.
The rise of multidrug resistance originates in a patients
inability or failure to complete a full course of drug therapy,
coupled with the bacterias capacity to mutate . A number of
barriers make it difficult for patients to complete therapy,
including inadequate or distant health care, coexisting social and
medical challenges, cost, and the stigma associated with TB . A
further complication is that patients must continue treatment after
their symptoms subside .
Tuberculosis
The Stop TB StrategyWHOs Stop TB Strategy, with its goal of
dramatically reducing the global burden of tuberculosis, was
developed by a global partner-ship of governmental and private
organizations, donors, and individuals . The six features of this
strategic framework:
Pursue high-quality DOTS expansion and enhancement .
Address TB-HIV, multidrug-resistant TB, and the needs of poor
and vulnerable populations .
Contribute to health-system strengthening based on primary care
.
Engage all health care providers .
Empower people with TB and communities through partnerships
.
Enable and promote research .
Though not traditionally considered an acute respiratory
infection, TB can have similar symptoms and many of the same
drivers (see Drivers of Acute Respiratory Infections, p . 44), and
its huge global burden can be lessened with some of the same
interventions . Once TB bacteria are activated, usually because the
immune system is depressed, they can quickly cause serious illness
. Symptoms include a long-lasting cough, which can produce blood or
phlegm, fever, fatigue, weight loss, and chest or breathing pain .
The majority of patients will die if they do not receive treatment,
especially if they have HIV, severe malnourishment, or another
underlying illness .
While substantial resources are being dedicated to TB, numerous
research studies have documented the heightened vulnerability of
poor, homeless, immigrant, and prison populations to TB exposure .
As with acute respira-tory infections, greater risk for TB is
associated with air pollution, tobacco smoke, overcrowded living
conditions, and assaults against the immune system linked to HIV,
drug us