Aria

Contents
Forewords . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Copyright 2010 World Lung Foundation
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ISBN: 978-1-4507-3262-8
About the Author . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Acute Respiratory Infections: Making Inroads Against a Forgotten Pandemic . . . . . . . . . . . . . . . . 8

Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
The Forgotten Pandemic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Solutions within Reach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Part 1: Understanding Acute Respiratory Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
How Infection Occurs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Pathogens That Cause Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Preventing Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Treating Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
HIV and Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
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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
The designations employed and the presentation of the material in this publication do not imply the expression of any opinion
whatsoever on the part of World Lung Foundation concerning the legal status of any country, territory, city, or area of its authorities,
or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers products
does not imply that they are endorsed or recommended by World Lung Foundation in preference to others of a similar nature that are
not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. World
Lung Foundation does not warrant that the information contained in this publication is complete and correct and shall not be liable
for any damages incurred as a result of its use. World Lung Foundation alone is responsible for the views expressed in this publication.
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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Part 2: Drivers of Acute Respiratory Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Antibiotics and Antiviral Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
How Drug Resistance Develops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
How Nutritional Deficiencies Affect the Immune System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
The Research and Development Drought . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Linking ARIs and Malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Preventing Drug Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Access to Health Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Micronutrients: Zinc, Vitamin D, and Vitamin A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Gaps in Health Care Spending . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
How the International Community Can Help . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Primary Care in Rural and Urban Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Air Pollution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Growing the Health Workforce . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Particulates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Profile: Treating Severe Pneumonia in Malawi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
How Pollutants Affect the Body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

Indoor Air Pollution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Part 4: Making ARIs a Global Priority . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Home Cooking and Heating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Identifying and Meeting the Worldwide Challenge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Indoor Smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
ARIs Are Significantly Underfunded . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Outdoor Air Pollution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
More Information Is Needed About ARIs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Motor Vehicles Emissions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Health and Governance Infrastructure Is Often Weak . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Ozone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Global Initiatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Profile: Air Pollution in China . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

Tobacco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
appendices
Adult Smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Appendix A: World Regions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Environmental Tobacco Smoke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Appendix B: Mechanisms of Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Overcrowding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Pathogens:Agents of Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Profile: The Hajj . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
What Is a Virus? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

What Are Bacteria? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Part 3: Prevention, Diagnoses, and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
What Is a Fungus? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Preventing ARIs with Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
How the Body Defends Itself . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Immunization Disparities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Appendix C: Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Financing Immunization Campaigns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Appendix D: Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Promoting Wider Vaccine Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Appendix E: Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
Diagnoses and Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Diagnosing ARIs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Surveillance Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Profile: Integrated Approaches to Reduce ARIs in India . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
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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
The 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.
About the Author

Neil 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 programs 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.
Acknowledgments
World 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.
Dr. Nils Billo, MD, MPH

Executive Director
International Union Against Tuberculosis and Lung Disease
8/31/10 11:03 AM
World Lung Foundation Acute Respiratory Infections Atlas
Top Ten Causes of Death:

Developing World
Top Ten Causes of Death:

Worldwide
Percent of total deaths
Ischemic heart disease
12.2%
Cerebrovascular disease
9.7%
Lower respiratory infection

(accounts for most ARIs)
7.1%
Chronic obstructive pulmonary

disease
5.1%
Diarrheal diseases
3.7%
HIV/AIDS
3.5%
Tuberculosis
Lower respiratory infection

(accounts for most ARIs)
11.2%
Ischemic heart disease
9.4%
Diarrheal diseases
6.9%
HIV/AIDS
5.7%
Cerebrovascular disease
5.6%
Chronic obstructive pulmonary

disease
3.6%
2.5%
Tuberculosis
3.5%
Trachea, bronchus, lung cancers
2.3%
Neonatal infections
3.4%
Road traffic accidents
2.2%
Malaria
3.3%
10
Prematurity and low birthweight
2.0%
10
Prematurity and low birthweight
3.2%
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.
Acute Respiratory Infections:

Making Inroads Against a Forgotten Pandemic
8
Percent of total deaths
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.
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.
8/31/10 11:03 AM
ARI death rate,

per 100,000 (2004)
>200
101-200
51-100
31-50
21-30
11-20
Overview
0-10
no data
Acute respiratory infections (ARIs), a group of diseases that includes
ARI death rates are highest in sub-Saharan Africa and parts of Asia.
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
More than
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
Despite the tremendous public health
disproportionate impact of ARIs on developing countries and
burden, acute respiratory infections
vulnerable populations: The death rate from pneumonia is 215 times
are not generally recognized as a
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.
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.
4,250,000
people will die this year from ARIs.
Acute respiratory infections:

Sicken and kill children. Twenty to 40 percent of all hospitalizations
Burden health care systems. Acute respiratory infections are the
among children are due to acute respiratory infections. Pneumonia
most common reason that people access health services around
alone is responsible for almost 1.6 million deaths a year in children
the world.
under five, making it the leading global killer in that age group.
Threaten a global catastrophe. Bacteria and viruses can mutate, as
Sicken and kill adults. ARIs annually kill 1.65 million adults 60 or
the H1N1 influenza virus demonstrates, and new pathogens, such
older and more than half a million people from ages 15 to 59. Three to
as the one that caused severe acute respiratory syndrome (SARS),
five million severe influenza infections occur every year, killing some
can emerge to infect unprotected populations. Both have
250,000 to 500,000 people. More than three million people are hospi-
unpredictable consequences.
talized annually with illness caused by respiratory syncytial virus.
10
11
8/31/10 11:04 AM
Overview
DALYs lost to ARIs,

per 100,000 (2004)
Deaths per 1,000 live
births (2008)
>5,000
3,001-5,000
>150
1,001-3,000
101-150
401-1,000
51-100
201-400
11-50
101-200
0-10
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.
The burden of disease linked to ARIs

falls most heavily on the developing world.
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,
Death Rate from All Causes among Children under Five
Acute respiratory infections are
the leading killer of children under five.

Neonatal other 2%
Neonatal diarrheal diseases
1%
Neonatal tetanus
2%
Congenital anomalies
3%
and they draw only a fraction of the resources dedicated to other
Birth asphyxia
8%
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
Preterm birth
10%
tuberculosis accounted for 80 percent of that total.
Others
10%
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.
12
Diarrheal diseases
17%
Malaria
8%
Severe neonatal infections

(mainly pneumonia/sepsis)
10%
Pneumonia
19%
Measles
4%
Injuries
3%
HIV/AIDS
3%
More children under five die of pneumonia worldwide than any other cause.
13
8/31/10 11:04 AM
Overview
Rate per 1,000 child years
25
Influenza
pandemic
20
Solutions within Reach
Younger than age one

Ages one to four
Fortunately, cost-effective solutions are within reach (see Prevention,

Diagnoses and Treatment, p. 66). Wider use of existing vaccines can
15
prevent some acute respiratory infections altogether. Breastfeeding, im-
Antibiotics
introduced
10
proved nutrition, and pollution and tobacco controls are also essential
Haemophilus
influenzae type b
15%
Pneumococcal
diseases
28%
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
Pertussis
11%
Measles
21%
antibioticsif these are readily available, prescribed appropriately, and
0
1900
1920
1940
taken as directed.
1960
Tetanus
8%
Better access to health care, especially in poor urban communities
Declines in U.S. Child Mortality Rate from Influenza and Pneumonia
ARIs can be controlled with better housing, better nutrition, and antibiotics.
Proven strategies exist,

failing to act globally.
but we are
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
Rotavirus
16%
Other vaccinepreventable diseases
1%
Of 2.5 million child deaths preventable by

vaccines in 2002, more than half were caused
by ARI-related pathogens.
governments, industry, and the international public health community

(see Making ARIs a Global Priority, p. 88).
ARI-related deaths per 100,000 total deaths (2004)
500
450
400
Global Impact
Actions That Make a Difference
350
Acute respiratory infections are the leading cause of illness

worldwide and the leading killer of children. ARIs account for 30
Expanding access to vaccines, improving nutrition (including better
300
250
200
150
100
50
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
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.
18 percent, and TB 16 percent.
ID
AR
lM
ed
ia
n
lo
ba
G
percent of all hospitalizations among children.
ea
th
D Rat
jib e
ou
E
S
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r
To
Ke ea
m
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a
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nd H a
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.P
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-B o
ep
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he nd
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to 50 percent of pediatric visits to medical providers and 20 to 40
14
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
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.
15
8/31/10 11:04 AM
Part 1
Understanding Acute Respiratory Infections
Acute respiratory infections cause

at least six percent of the disability
and death around the globe,
affecting the most vulnerable
populations, especially the young,
the old, the ailing, and the poor.
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
Strategies to curb ARIs include:

Emphasizing acute respiratory infections as an interrelated package
of health challenges that can be addressed with low-cost prevention
and treatment strategies.
Stronger data collection and monitoring systems to measure the
incidence of acute respiratory infections and to evaluate prevention,
diagnostic, and treatment strategies.
Improving access to care, distributing effective vaccines more
widely, encouraging appropriate use of antimicrobials, and undertaking more vaccine development and drug research.
Public health education promoting breastfeeding, infection control,
tobacco control, and spreading knowledge about the warning signs
of serious disease.
Adequate resources for surveillance in order to identify new
pathogens quickly, when more opportunities exist to control them.
Initiatives that address global poverty, including malnutrition,
overcrowding, and other living conditions that are directly linked
to ARIs.
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.
16
17
8/31/10 11:04 AM
Percent of total deaths in children

under five caused by pneumonia
>19.9%
15-19.9%
10-14.9%
2-9.9%
<2%
Pneumonia
no data
Vaccines, breastfeeding, improved living

standards, and swift treatment can curb
pneumonia, the leading global killer of
children under five.
Pneumonia is responsible for nearly 20 percent of child deaths globally.

Pneumonia is the leading global killer of children under five, respon-
Global Impact
sible for almost 1.6 million deaths per year. In that vulnerable popula-
Almost 1.6 million deaths from pneumonia occur annually
still-developing defense system is weakened by malnutrition, air
tion, it is a disease of poverty and occurs most commonly when a childs
in children under five, about one-fifth of all pediatric deaths
pollution, coinfections with HIV/AIDS and measles, and low birth-
around the world (based on 8.8 million pediatric deaths from
weight. In wealthier nations, adults over 65 years old and people with
all causes in 2008). By contrast, 732,000 children die from
chronic health problems bear the greater burden of pneumonia.
malaria and 200,000 from HIV/AIDS each year.

Every year, an estimated 156 million new cases 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
occur, 97 percent of them in the developing world. Seventy-four
them severe enough to require hospitalization. Seventy-four percent of
percent of those cases occur in just 15 countries, mostly in South
those cases occur in just 15 countries, mostly in Asia and sub-Saharan
Asia and sub-Saharan Africa, with 43 million cases in India alone.
Africa, with 43 million cases in India alone.
Improved living standards and access to antibiotics transformed
Pneumonia occurs when the sacs of the lungs, known as alveoli, become
the trajectory of pneumonia in the developed world during the
filled with pus and fluid, limiting oxygen intake and making it hard
20 century. In the United States, pneumonia-related deaths
to breathe. A bacterial or viral pathogen can be the primary cause of
among children fell by 97 percent between 1939 and 1996.
pneumonia, or it can be a complication of other infections, including
th

Breastfeeding plays a key role in preventing pneumonia, providing
Prompt treatment of pneumonia is imperative. As many as
proteins, enzymes, and other cells with immunological properties,
20 percent of infected children will die if they are left untreated,
as well as all the nutrients an infant needs (see Breastfeeding,
sometimes within three days after symptoms first appear. Adequate
p. 50).
oxygen systems reduce mortality, but they are overlooked by the
Access to antibiotics and vaccines should be scaled up. Treating all
global health community as a key component of care.
children who need them with antibiotics could cure most cases of
Caregivers need to be educated about pneumonia. In the developing
bacterial pneumonia and save as many as 600,000 lives every year.
world about 20 percent of caregivers recognize its symptoms, and
Children in countries that do not have access to the Streptococcus
only about 54 percent respond to those symptoms by taking the
pneumoniae and Haemophilus influenzae type b vaccines are 40
child to a health care provider.
times more likely to die than those living in countries that

administer the vaccines routinely.
WHO says that a combination of vaccines, standard case

management, and breastfeeding counseling could prevent 5.3
million pneumonia deaths over five years.
influenza, measles, tuberculosis, or HIV.
18
19
8/31/10 11:04 AM
Pneumonia
0%
World
10%
20%
30%
40%
50%
19%
Industrialized world 3%
2%
Developing countries
20%
South Asia
21%
Sub-Saharan Africa
21%
Middle East and North Africa
15%
East Asia and Pacific
15%
Latin America and Caribbean

Central and Eastern Europe and the
Commonwealth of Independent States
14%
13%
Percent of total deaths in children under five from pneumonia
(excludes severe neonatal infections, some of which are pneumonia)
The burden of pneumonia in the developing world

is nearly ten times that of the developed world.
How Infection Occurs
Pathogens That Cause Pneumonia
Most severe cases of pneumonia, whether acquired in the community or
Bacteria: Streptococcus pneumoniae, usually called pneumococcus, is
the hospital, result from bacterial infections, although viruses or fungi
the most common cause of bacterial pneumonia worldwide, accounting
can sometimes be the cause. These pathogens may travel as airborne
for about 30 percent of the total pneumonia caseload and at least
particles or droplets, causing infection after they are inhaled, or they
half the cases in the developing world. In 2000, almost 14 million
clinical and public health measures can accomplish.
may colonize the nose or throat, where they reside harmlessly until
pneumococcal pneumonia cases occurred in children younger than five.
they have an opportunity to penetrate the bodys defense system and
Pneumococcus is also a leading cause of meningitis in that age group.
Vaccines: Vaccines to prevent diseases associated with Streptococcus
infected with tuberculosis.
causes Legionnaires disease). These infections are also increasing in the

community, especially antibiotic-resistant staph. Pneumonia can also
13 of the most common pneumococcal strains, known as serotypes (20

serotypes cause most pneumococcal infections worldwide). PCV13
result from tuberculosis, which is caused by Mycobacterium tuberculosis.
replaces PCV7, which has been available since 2000. Earlier generations
Viruses: If left untreated, influenza virus, respiratory syncytial virus,
younger than two years old.
parainfluenza virus, and the measles virus can all lead to pneumonia.
of vaccines, first distributed in the mid-1970s, were not safe for children
The potential benefit to developing countries is highlighted by the
Fungi: Individuals with compromised immune systems, especially those
effectiveness of a vaccine that was tested in Gambia and was designed
who are HIV-positive, are susceptible to Pneumocystis jiroveci pneumonia.
to provide protection against the nine pneumococcal serotypes most
Other types of fungus-linked pneumonia occur among individuals in
prevalent in the country. On the basis of a four-year study of
e
co
m
in
in the United States in 2010, protects infants, children and adults against
h-
coccus aureus or gram-negative bacteria (including Legionella spp, which
Hi
g
people living with HIV are 20 to 40 times more likely to become
co
m
children infected by measles every year, and within the same country,
0%
ein
Pneumococcus: The pneumococcal conjugate vaccine (PCV13), approved
dl
Hospital-acquired bacterial pneumonia is typically caused by Staphylo-
For example, pneumonia can cause death among the 30 to 40 million
id
ric pneumonia significantly.
the deaths of an estimated 300,000 children under age five.
5%
Up
pe
r-m
easier for other pathogens to cause secondary infection in the lungs.
three-quarters of the worlds children in 2004, could also lessen pediat-
co
m
responsible for 7.9 million cases of pneumonia in 2000, resulting in
ein
pathogen damages the bodys tissues or immune system, making it
dl
which also cause meningitis and other severe infections, were
id
routinely. Wider use of the measles vaccine, which covered
Often, pneumonia is the result of a coinfection process, in which one
10%
40 times more likely to die than those in countries that administer them
Lo
we
r-m
remarkably effective. Children in countries without these vaccines are
15%
co
m
20 percent of the worlds severe pneumonia cases. These bacteria,
pneumoniae (pneumococcus) and Haemophilus influenzae type b are
20%
in
Haemophilus influenzae type b (Hib) is implicated in as many as
97 percent between 1939 and 1996dramatic evidence of what effective
Lo
w-
microbes in the birth canal or during delivery.
In the United States, pneumonia-related deaths among children fell by
Percent of deaths in children

under five due to pneumonia
travel into the lungs. Newborns can also become infected by exposure to
Preventing Pneumonia
World Bank Income Group (2004)
The lower a countrys income, the more

child deaths from pneumonia.
certain geographic locations, including the American Southwest.
20
21
8/31/10 11:04 AM
Pneumonia
20
Case management of pneumonia
80%
15
Hib vaccine
60%
40%
Pneumococcal vaccine
20%
0%
10
Breastfeeding counseling
2009
2010
2011
Post-neonatal pneumonia deaths
2012
2013
2014
2015
Child deaths prevented annually

(x 100,000)
Average coverage of interventions

by year (%)
100%
No pathogen identified
S. pneumoniae
S. aureus
Gram-negative
bacteria
M. tuberculosis
RSV and other

respiratory viruses
H. influenzae
Neonatal pneumonia/sepsis deaths
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.
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.
Treating Pneumonia
17,000 children, researchers determined that the vaccine had lowered
Breastfeeding: Breastfeeding provides all the nutrients an infant needs
rates of X-ray-confirmed pneumonia by 37 percent and had reduced
in the first six months of life. It remains an essential nutritional source
mortality by 16 percent. Gambia, Rwanda and South Africa now include
until at least age two and contributes significantly to the development
Appropriate therapies, administered promptly, will cure most cases of
the vaccine as part of their routine vaccination programs.
of a healthy immune system, making it one of the most important tools
pediatric bacterial pneumonia. But many children go untreated, and as
available to prevent pneumonia (see Breastfeeding, p. 50).
many as 20 percent of them will die as a result, sometimes within three
Haemophilus influenzae type b (Hib): Ninety-two percent of children in
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.
days of the onset of illness.
developed countries received Hib conjugate vaccines in 2003, compared
Improved living standards: Like other acute respiratory infections,
with 42 percent in the developing world and just eight percent in
pneumonia targets the worlds most vulnerable children.
Diagnoses: A first step in treatment is to recognize the warning signs
Treatments: Antibiotics are the treatment of choice for bacterial pneumo-
the least-developed countries. The Hib vaccine is highly effective in
Malnutrition, crowded housing, smoking, and polluted air, especially in
and to seek immediate attention from a health care provider. But in
nia. They can cure most cases, and if they were given to all children under
reducing infections in countries where it is widely used, even among
households that cook with wood and other biofuels, have all been linked
the developing world, only 54 percent of caregivers recognize the
age five with pneumonia, as many as 600,000 lives could be saved annu-
unvaccinated people, presumably because it lessens the chance that
to higher incidences of pneumonia (see Drivers of Acute Respiratory
need to take a child who is breathing quickly, or with difficulty, to an
ally. Yet a 2008 report indicated that only about one-third of all children
people will be exposed to the bacteria (a phenomenon known as herd
Infections, p. 44).
appropriate provider, even though these are classic indicators
under five with suspected pneumonia received an antibiotic in the 68
of pneumonia.
countries that have the highest levels of childhood and maternal deaths
immunity). Broader use of the Hib vaccine could save 400,000 lives.
Improvements in health care, nutrition, and the environment are
(see Antibiotics and Antiviral Therapy, p. 78). Providing universal antibi-
The bottom line is clear: Vaccines can transform patterns of
independent interventions that can significantly reduce the
To provide optimal therapy, it is ideal for clinicians to identify the
pneumonia in developing countries, as they have in the developed
incidence of pneumonia. But a broad and integrated commitment on the
pathogen involved, but this is often impossible, especially in resource-
world. But increasing immunization depends on a strong vaccine
part of the international community to improving living standards world-
poor countries without adequate laboratories. Conventional diagnostic
delivery infrastructure, leadership and political will, and a much greater
wide is the true foundation of prevention (see Making ARIs a Global
techniques, including blood tests and cultures taken from blood and
Systems for delivering supplemental oxygen to children with
commitment from the international community (see Preventing ARIs
Priority, p. 88).
sputa, may not be available. Even if they are, these tests are less definitive
pneumonia can also save lives, but deficits in equipment, supplies, and
than using the much more costly tools of microbiology, such as DNA-
staff training have meant that this critical component of care is often
based techniques that identify specific pathogenic strains. If resources
unavailable in developing countries. Investments in oxygen systems
allow for an intensive investigation, multiple infectious agents can still
should be a more prominent priority of those concerned about
make the cause difficult to pinpoint.
treating pneumonia.
with Vaccines, p. 68).
22
otic treatment in sub-Saharan Africa and South Asia, where the great
majority of pediatric deaths occur, would cost US$200 million per year.
23
8/31/10 11:04 AM
Pneumonia
Fifty-five to 65 percent of African children

admitted to hospitals with very severe
pneumonia have HIV-1 infection, and up
to one-third of them will die of the disease.
That death rate is three to six times higher
than it is for children with pneumonia
who are not infected with HIV.
Total number of deaths from pneumonia
among children under five (2008)
20,000
5,000-19,999
HIV and Pneumonia
2,000-4,999
Common bacterial pneumonia, pneumonia associated with
100-499
tuberculosis, and fungal pneumonia caused by Pneumocystis jiroveci all
20-99
have a greater impact on HIV-infected people because their immune
<20
systems are so weakened. HIV-infected children are 40 to 50 times more
no data
500-1,999
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
antimicrobial agents also used in HIV treatment, helps to prevent

pneumonia as well. Its use may prove to be a double-edged sword,
however, because it threatens to cause resistance to other drugs used in
pneumonia treatment (see How Drug Resistance Develops, p. 78).
provided protection to 65 percent of HIV-infected children (compared
In HIV-infected populations, the higher toll of pneumonia and the
with 83 percent among uninfected people). The Haemophilus
greater difficulty of treating it underscore the importance of further
influenzae type b vaccine provided protection to 55 percent of infected
prevention efforts and more research. Measures to increase vaccination
children (compared with 91 percent among those without HIV).
rates are particularly urgent (see Preventing ARIs with Vaccines, p. 68).
HIV-infected populations are generally advised to have both vaccines,
Studies are also needed to determine whether the standard recommen-
as well as to be immunized against influenza.
dations for managing children with pneumonia should be revised for
Some of the clinical interventions used to treat HIV can also be effective
HIV-infected children.
in preventing pneumonia, including highly active antiretroviral
In addition to an increased focus on preventing pneumonia in
therapy (HAART). The combination of drugs used in HAART reduces
HIV-positive children, clinical guidelines need to be developed for
by fourfold the risk of opportunistic infectionsthose that can gain
uninfected children who live in close contact with infected populations.
a foothold in the body because the immune system is damaged
Because they are repeatedly exposed to pathogens, these children face
among HIV-infected children. Cotrimoxazole, a combination of two
greater pneumonia risks.
24
Pneumonia is responsible for almost 1.6 million deaths

a year in children under five.
25%
0%
Pneumococcal
vaccine
H. influenzae
tybe b vaccines
50%
75%
100%
65%
83%
55%
91%
HIV-infected children
HIV-uninfected children
Percent of Children under Five in Whom Pneumonia Vaccines Are Effective
Vaccines can prevent most childhood pneumonia,

but HIV lessens their effectiveness.
25
8/31/10 11:04 AM
The Influenza Virus

Influenza 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
ing counries, but it imposes a heavy

burden, especially among malnourished
and immunocompromised populations.
proteins on the viral surfacehemagglutinin (HA) and neuraminidase
Number of laboratoryconfirmed flu cases (2009)
(NA). There are 16 HA and nine NA subtypes, although relatively few
>10,000
cause human infection. The proteins largely define the behavior of
3,001-10,000
viruses, which are named according to the combinations of protein they
1,001-3,000
contain. For example, the influenza A viruses currently circulating in
101-1,000
the human population include the subtypes H1N1 and H3N2.
0-100
Once an influenza virus has invaded the body and attached itself to cells
no data
Influenza
Influenza has been overlooked in develop-
Most developing countries lack the ability

to diagnose and report influenza.
Surveillance, vaccines, and infection

control can curb influenza, which causes
three to five million severe
infections annually.
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
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).
Research is needed on more efficient ways to manufacture
systems might be capable of infecting others for weeks. Influenza can
vaccines, distribution systems to poor countries should be
survive for hours outside a human host, further aiding its capacity
strengthened, and more equitable access to a limited
to spread.
vaccine supply is essential (see Preventing ARIs with
The many types of influenza virus infect anywhere from five to 30 percent
primarily affecting the nasal passages, throat, and pharynx in the upper
Rigorous surveillance can send an early warning signal about
for ten days or longer, while individuals with compromised immune
HA
of the worlds population during a typical year. Most cases of flu are mild,
Vaccines, p. 68).
Public education about hand-washing techniques, cough and
sneeze safeguards, and limiting social contact are essential to
NA
curbing the spread of flu. In health care settings, compliance
Global Impact
respiratory tract. But every year three to five million severe infections
with proper infection control procedures is also crucial, so that
occur, generally in the lower respiratory tract (see The Airways and the
infections do not spread from patient to health care worker
Worldwide, three to five million severe influenza infections occur
Lungs, p. 103). Influenza kills 250,000 to 500,000 people annually.
to patient.
annually, killing between 250,000 and 500,000 people. While

influenza is a burden everywhere, it tends to be overlooked in developing countries, where inadequate laboratory facilities impede
diagnoses, and other health challenges compete for attention.
Vaccines are the most effective strategy available for preventing
influenza, but the wealthier nations dominate production, and
worldwide capacity is limited to 900 million doses.
Many influenza viruses are resistant to antiviral therapies, and
those that remain effective are not being manufactured in adequate volume.
Influenza tends to get more attention in wealthier countries, where
policies that restrict public interaction and minimize the spread
cause of their lessened immunity and underlying health conditions. In
of infection.
developing countries, where so many other health problems compete
New antiviral therapies are needed to counter growing drug
for attention, influenza is sometimes overlookedyet it imposes a heavy
resistance. For example, oseltamivir (Tamiflu) has largely lost
disease burden, especially among populations that are malnourished or
its value against a seasonal form of H1N1. Tamiflu remains
immunocompromised.
effective against the pandemic strain of H1N1 that arose in
The flu virus can travel on inhaled airborne particles, sprayed droplets
2009, but production capacity should be increased from the
that are projected onto mucous membranes, or a contaminated hand
220 million doses currently available around the world (see
that touches the nose or mouth. In temperate regions of both hemi-
Antibiotics and Antiviral Therapy, p. 78).
spheres, peak flu activity occurs in the winter season, while in the tropics, influenza occurs throughout the year.
26
In severe epidemics, it may become necessary to use public
infants and individuals over age 65 are typically at greatest risk be-
Structure of an Influenza Virus

27
8/31/10 11:04 AM
Influenza
Drift and Shift:

How Influenza Viruses Evolve
Influenza Pandemics
The Spanish flu pandemic may have involved an avian virus that
A pandemic is the widespread transmission of a pathogen to
Hong Kong pandemics were caused by a reassortment of human and
Influenza viruses can mutate swiftlyone million times faster than
populations around the world. Influenza pandemics are inevitable but
avian viruses. In each case, younger populations faced greater-than-
involved an avian virus that adapted to
vertebrates can mutateand can swap genetic components with other
unpredictable, and they generally occur with the emergence of a virus
usual risks, possibly because they had no exposure to earlier versions of
viruses. Many influenza viruses are believed to originate in the tropics
that is either novel or has not circulated for many decades. Pandemic flu
the pathogenindividuals younger than 65 were 20 times more likely to
become able to infect humans directly,
before being exported to the more temperate northern and southern
infects far more people than a typical seasonal flu, although the illness is
die during one of these pandemics than they were during a normal flu
while the Asian and Hong Kong
hemispheres, although this pattern is not fully understood.
not necessarily more severe.
season. Elderly populations, who are inherently more vulnerable, may
pandemics were caused by a reassortment
adapted to become able to infect humans directly, while the Asian and
In a process known as antigenic drift, the proteins on the surface of the
Pandemics of the past: Three influenza pandemics occurred in the 20th
flu virus make frequent minor changes in their genetic structure. The
century, each resulting from antigenic shifts in the influenza A virus.
resulting new strains can evade the human defense system, even among
populations previously infected by, or vaccinated with, a related strain.
have already built up some immunological protection and did not face
Spanish flu of 1918: The 1918 pandemic occurred in three waves

around the world. After a first round of mild infections in the spring,
history, infected between one-third and one-half the worlds population

and killed tens of millions of people. Milder pandemics occurred in
undergo antigenic shift, a more significant genetic alteration that
1957, when Asian influenza killed two million people, and in 1968,
typically results from a merger with viruses residing in reservoirs of
when the Hong Kong influenza was responsible for one million deaths.
of human and avian viruses.
special additional risks.
The Spanish flu of 1918, believed to be the most devastating in human
At unpredictable intervals, flu viruses with the power to infect humans
The Spanish flu pandemic may have
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
poultry, water fowl, pigs, or other mammals. If the recombined virus
million deaths occurred. Global population growth remained depressed
is zoonotic, or capable of traveling from animal to human populations,
for a decade afterward.
humans are unlikely to have any immunity.
Researchers have called the Spanish flu the mother of all pandemics
Influenza A and B viruses are subject to antigenic drift, while only
because the genetic structure of most subsequent influenza A viruses
influenza A undergoes antigenic shift. The H1N1 pandemic of 2009-10
can be traced back to it. Many of todays efforts to prepare for a potential
is an example of a significant viral antigenic shift.
new pandemic consider the severity of that event in their calculations,

although the vagaries of biology, coupled with todays ease of travel, access to health care, and improved nutrition, make extrapolation difficult.
Improved surveillance has
helped to identify emerging
influenza strains that did not
reach pandemic levels.
Antigenic
DRIFT
H1N1
Spanish flu
as many as 50 million deaths
H2N2
Asian flu
2 million deaths
H3N2
Hong Kong flu
1 million deaths
1918
1957
1968
H5N1
H7N3
H10N7
H7N2
H5N1
H9N2
H5N1
H7N7
H7N2
H9N2
H1N1
18,000
deaths
2009
Antigenic
SHIFT
1900
Antigenic Drift and Shift

28
1910
1920
1930
1940
1950
1960
1970
1980
1990
2000
2010
Human influenza pandemics are inevitable, but unpredictable, in the extent of the death they cause.
29
8/31/10 11:05 AM
Influenza
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.
Areas with confirmed H5N1 human cases,
since 2003
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 influenza 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
Avian Flu Watch: Will H5N1 cause the next epidemic?
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
At-risk groups: The majority of infections have occurred among
The burden on many local health systems was significant, with spikes
reported fewer than 500 laboratory-confirmed human infections,
individuals with an age range of 12 to 17 years, but the groups at
in the use of emergency rooms, hospitals, and outpatient care. Mexico,
although the death rate when infection does occur approaches 60
highest risk for complications have been the elderly, children under
where the virus was first reported, estimated the cost of the outbreak at 57
percent (and in Indonesia, 165 cases caused 136 deaths). Should the
five, pregnant women, and individuals with chronic health problems.
billion pesos in 2009 (US$4.29 billion), primarily from lost tourism. An
virus evolve to infect humans more readily, it could cause a devastating
As in a more traditional flu season, severe respiratory distress and
adequate vaccine supply was slow to become available: Near the end of
new pandemic.
coinfection with bacterial pneumonia can develop. As of May 2010,
2009, WHO said it would have 200 million donated doses available to 95
18,000 laboratory-confirmed deaths from the pandemic form of H1N1
countries that are home to one-third of the global population; by contrast,
had been reported. However, the total death toll is undoubtedly much
the U.S. had already purchased 250 million doses for its residents.
H1N1: The First 21 -Century Flu Pandemic

st
On June 11, 2009, two months after two cases of a new strain of in-
higher, as most cases are not confirmed.
Because the symptoms caused by the H1N1 pandemic have been
fluenza A H1N1 were confirmed in the United States, WHO officially
Are we prepared? H1N1 has been a test case for global preparedness.
relatively mild, at least thus far, global response capacity was not fully
declared the first flu pandemic of the 21 century. By then, some 30,000
WHO guided international surveillance efforts, and many nations
tested. Nonetheless, even an outbreak of limited virulence strained
cases had been confirmed in 74 countries. Although the circulating
declared the pandemic a public health emergency. Among those nations
public health resources.
virus was a novel combination of swine and avian influenza A viral
was the United States, which released stockpiles of antiviral medication
strains, some components had circulated in the past, giving many adults
and protective equipment but did not choose to exert the federal authority
born before 1956 a degree of immunity.
to impose border controls or mandate that public facilities be closed.
st
30
31
8/31/10 11:05 AM
Influenza
Influenza Surveillance
Preventing Influenza
Worldwide monitoring of influenza provides best-guess information
As part of this network, designated National Influenza Centres at 134
Vaccines: The best protection against influenza is a vaccine well
about the viral strains most likely to cause disease in a given year, so
institutions in 104 countries isolate and analyze some 175,000 viral
matched to the viral strains in circulation in any given season. Once
that a timely vaccine can be manufactured and distributed (some com-
samples every year and submit 2,000 of them to five WHO Collabo-
developed, access remains a challenge and coverage rates are generally
ponents of the vaccine change every year). Surveillance is also essential
ration Centers. These centers sequence the viruses to determine the
low, especially in less-developed countries. The vaccine supply is never
for alerting public health authorities to illness surges so that they can act
extent and direction of their evolution away from previously identi-
sufficient to reach all those who need it: Even without a pandemic, some
before a new, highly transmissible, or especially dangerous virus spreads
fied genetic structures. Through FluNet, the networks web-based data
1.2 billion people around the globe are considered at high risk for flu,
in human populations.
collection and reporting tool, tables, maps, graphs and reports are
and many more are likely to be affected during a pandemic.
available to the public.
Many surveillance strategies are available. These include case counts,
Only 900 million doses of vaccine can be produced worldwide, if all
based on specific laboratory tests and physician reports, monitoring do-
Many countries with the highest burden of acute respiratory infec-
manufacturing facilities are operating at maximum capacity. More
mestic and wild animal populations, emergency room records, and even
tions do not have their own National Influenza Centres because they
research is needed to overcome production bottlenecks, improve
Google Flu Trends, which tracks regional patterns of online flu-related
lack the resources and technology to provide the necessary data. For
vaccine technology, and identify more efficient immunization strategies.
queries (see Surveillance Techniques, p. 75).
example, of 46 countries in the WHO African region, only 18 have
Strengthening distribution systems and developing strategies to
centers, and only 10 have the laboratory capacity to conduct sophisti-
ensure more equitable access to limited vaccines are also essential, and
cated diagnostic testing.
manufacturers liability concerns may need to be addressed.
WHOs Global Influenza Surveillance Network, established in 1952,

is the primary vehicle for a coordinated, worldwide tracking effort.
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
385 million elderly
140 million infants
Several hundred million adults and

children with underlying chronic health
problems.
24 million health
care workers
countries with one-third of the worlds population.
communities. In severe epidemics, the principles of social distancing,

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.
400
600
800
1 billion
within 48 hours of the onset of illness. Treatment is generally

recommended only for individuals at risk of complications and for
the population can recover on its own.
such as canceling public events and closing recreational facilities, may
200 million
severity of some types of influenza, but only if they are administered
for example, a single dose of H1N1 vaccine generates a robust immune
essential to preventing flu outbreaks or reducing the viruss spread in
include zanamivir (Relenza) and oseltamivir (Tamiflu), can reduce the
those who have been hospitalized with flu symptoms, as the majority of
about hand-washing techniques and cough and sneeze safeguards is
Vaccine production capacity
A class of antiviral therapies known as neuraminidase inhibitors, which
Other prevention strategies: No vaccine confers 100 percent immunity

response in only 56 to 80 percent of adults 65 or older. Public education
At-risk populations
Treating Influenza
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.
Government mandates are another option for prevention. For example,

some Asian countries have used quarantine and medical detention to
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.
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.
32
33
8/31/10 11:05 AM
Respiratory
Syncytial Virus
RSV is the most common source of severe
respiratory illness in children worldwide,
but a vaccine is not yet available.
Respiratory syncytial virus (RSV), while far less familiar to most
In adults, the distinctive feature of RSV is its disproportionate impact
Because the infection is so common, RSV should be a priority for
people than pneumonia or influenza, is the most common source of
on vulnerable populations. Although three to seven percent of a healthy
immunization research. Advancing the science has been complicated
severe respiratory illness in infants and children worldwide. In the
elderly population had active RSV infections in one study, they had gen-
by the 1960s legacy of an RSV vaccine, which resulted in more severe
developed world, RSV is the most frequent reason that children are
erally milder symptoms than those who had influenza, and they rarely
disease among vaccinated children when they were subsequently
hospitalized during the winter months. Exposure to tobacco smoke
needed to be hospitalized. By contrast, in a high-risk populationsuch
exposed to the virus. Nonetheless, the U.S. National Institute for Allergy
and overcrowded living conditions heighten the risk (see Tobacco,
as adults over 21 who had been diagnosed with congestive heart failure
and Infectious Diseases and several vaccine manufacturers are engaged
p. 60, and Overcrowding, p. 62).
or chronic pulmonary diseaseRSV hospitalization and mortality
in clinical trials to evaluate several new vaccine designs.
No established treatment for RSV is available, and good data about
estimate of global mortality among older populations. In 2011,
Building immunity: RSV exposure in infancy does not provide full
More data about RSV is vital. Strategies for prevention and
WHO is expected to provide some of this data for the first time.
protection against subsequent infection, so children may have repeated
treatment cannot move forward without more information
symptoms, especially until about age three. Older children and adults
about the epidemiology of the disease.
Symptoms and risks: By the age of two, essentially all children have
children under five, and 3.4 million of them were severe enough
been infected by RSV, which is spread through close contact with an
to require hospitalization. RSV is the most frequent reason that
infected person or by touching a contaminated surface.
children in the developed world are hospitalized during the

winter months.
cold, RSV causes 3.4 million episodes of illness severe enough to
experience severe lower respiratory infections caused by RSV are at
among the over-65 population in the United States. (There
heightened risk for asthma and recurrent wheezing later in life.
is no comparable estimate of RSV in the elderly population

worldwide.)
1%
1.5%
2%
2.5%
0.7%
0.3%
2.1%
2.1%
Children <1 year
Seven times more children in the developing world die from RSV than in the developed world.
vulnerable populations will be essential.
40
30
20
Hib
Pneumococcal
10
RSV
Bacterial
pneumonia
600
3-5
million
2.8-4.3
million
3
2
1
Severe
influenza in
adults and
children
Severe RSV
in children
under 5
500
400
250,000500,000
300
200
66,000199,000
100
Influenza
deaths in
adults and
children
RSV deaths
in children
under 5
Children <5 years
Percent of Fatalities among RSV Cases
34
effective vaccine becomes available, strategies to immunize
Estimated annual deaths worldwide
severe pneumonia had RSV-associated pneumonia. Children who
An estimated 10,000 RSV-associated deaths occur every year
Developing
countries
Vaccines offer the best opportunity to prevent RSV. Once an
result in chronic lung-related problems.
Estimated severe cases in millions worldwide
19 percent of children admitted to the hospital with severe or very
supportive care less available.
Industrialized
countries
a significant factor in the disease, promoting inflammation that may
Annual estimated incidence in children <5 (in millions)
monia and bronchiolitis. Over a five-year period in Kenya, 15 to
oping countries, where the population is more vulnerable and
0.5%
elderly populations suggests that naturally acquired immunity to RSV is
require hospitalization and is the leading cause of both viral pneu-
children annually. Virtually all of these deaths occur in devel-
0%
are less vulnerable, but the recurrence of symptoms in at-risk and

only partial. Moreover, the immune systems response to RSV is in itself
While the symptoms are often mild, resembling those of a typical
RSV infection is estimated to kill between 66,000 and 199,000
pneumonia-related hospitalizations identified in this population over
range from 66,000 to 199,000 annually, and there is no reliable
In 2005, 33 million new cases of RSV infection occurred in
rates were comparable to those of influenza. More than 10 percent of all

four winter seasons were caused by RSV.
its impact remain sparse. Estimates of the death toll among children
Global Impact
RSV, while far less familiar than pneumonia or influenza, is the most common source of
severe respiratory illness in infants and children worldwide.
35
8/31/10 11:05 AM
Countries with highest

TB burden
Global Impact
TB causes nearly two million deaths a year, making it the worlds
more likely to have treatment-resistant forms of the disease, and

more likely to die of it.
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).
36
io
pi
a
In
di
a
In
do
ne
sia
But this reservoir of latent infections leads to more than
0%
Ke
ny
M
a
oz
am
bi
qu
e
M
ya
nm
ar
N
ig
er
ia
Pa
ki
sta
n
Ph
ili
Ru
p
pi
ss
ian
ne
s
Fe
de
ra
tio
So
n
ut
h
Af
ric
a
Th
ail
an
Un
d
ite
Ug
d
Re
an
p.
da
of
Ta
nz
an
ia
Vi
et
N
am
Zi
m
ba
bw
e
HIV-positive people are more likely to become infected with TB,
people infected with TB are symptom-free.
Et
h
In 2008, 1.4 million people living with HIV had active TB.
defenses and remain hidden within the body for decades, and most
20%
on
go
new TB cases in 2008.
infected with Mycobacterium tuberculosis. Tuberculosis can survive host
in
a
multidrug-resistant TB accounted for more than one-fifth of all
More than two billion peopleone-third of the worlds populationare
he
C
antibiotics, and in some republics of the former Soviet Union,
40%
Ch
Five percent of the global TB caseload is now resistant to multiple
60%
ep
.o
ft
study reported per-person costs of US$21,000.)
80%
.R
treatment costs can rise to US$5,000 or more. (A recent Kenyan
WHO target
em
personbut if the disease becomes resistant to those drugs,
100%
First-line therapies to cure TB can cost as little as US$20 per
TB, 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.
zil
Ca
m
bo
di
a
drivers are similar, as are some of the effective interventions.
Br
a
their lifetimes. Though TB is not a classic ARI, the symptoms and
Tuberculosis
ha
ni
sta
n
Ba
ng
lad
es
h
and ten percent of them will develop active TB symptoms over
Twenty-two countries incur 80 percent of all TB cases.
Af
g
people are currently infected with Mycobacterium tuberculosis,
Percent of DOTS success
seventh most common cause of mortality. More than two billion
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.
37
8/31/10 11:05 AM
Tuberculosis
The Stop TB Strategy

WHOs Stop TB Strategy, with its goal of dramatically reducing the
global burden of tuberculosis, was developed by a global partnership 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.
Though not traditionally considered an acute respiratory infection, TB
TB in children has been a neglected aspect of the disease, even though
can have similar symptoms and many of the same drivers (see Drivers
WHO estimates that 10 to 15 percent of the global caseload occurs in
of Acute Respiratory Infections, p. 44), and its huge global burden can
children under age 14. In some countries, pediatric TB represents as
be lessened with some of the same interventions. Once TB bacteria are
many as 40 percent of all cases.
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
Treating TB
Tuberculosis can generally be cured with a four-drug cocktail,

More funds need to be spent on diagnostic tools to ensure that
active TB infection is recognized quickly. An uninterrupted
drug supply is also essential to full and prompt treatment.
Health care systems should provide directly observed therapy,
administered over six months, that can cost as little as US$20 per
short course, in which drugs are administered to infected pa-
or another underlying illness.
person. But more bacterial strains are becoming resistant to therapy (see
tients under supervision. DOTS has an 85 percent success rate,
How Drug Resistance Develops, p. 78), leaving increasing numbers
and expansion is essential to ensure that patients complete their
While substantial resources are being dedicated to TB, numerous research
of patients with limited treatment options, or none at all. If the disease
drug regimens.
studies have documented the heightened vulnerability of poor, homeless,
becomes resistant to first-line therapies, medication and other treatment
immigrant, and prison populations to TB exposure. As with acute respira-
costs can rise to US$5,000, or much higher.
receive treatment, especially if they have HIV, severe malnourishment,
tory infections, greater risk for TB is associated with air pollution, tobacco
Empower people with TB and communities through partnerships.
smoke, overcrowded living conditions, and assaults against the immune
Enable and promote research.
nomic status and other social determinants that increase the probability
system linked to HIV, drug use, malnutrition, and stress. Lower socioecoof infection also tend to limit access to care and optimal therapy.
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.
More research is needed to develop new pharmaceuticals that

work against the growing problem of multidrug-resistant TB.
Health care priorities for the HIV-infected population with
TB are drugs to prevent latent infection from becoming active,
screening of at-risk individuals, and an emphasis on infection
control to limit the spread.
Directly observed therapy, short course: 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
First-line therapies to cure TB can cost as
85 percent success rate.
little as US$20 per person, but if the disease
Of course, a diagnosis is required before DOTS can be implemented,
becomes resistant to those drugs, treatment
and this is a significant gap: Only about two-thirds of active TB cases
costs can rise to US$5,000 or more.
are ever detected, mostly because modern diagnostic equipment is

lacking in regions where TB is most common.
Drug-resistant TB: 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
Eighty-five percent of MDR-TB cases occur in just the 22 countries that

have the highest overall tuberculosis burden. Fifteen of the heavily affected
countries are in the former Soviet Union. India and China together have
seems to be growing.
almost half the total caseload, a reflection of their vast populations, their
The rise of multidrug resistance originates in a patients inability or
MDR-TB is usually curable with a complex regimen of second-line drugs,
failure to complete a full course of drug therapy, coupled with the
but these must be taken longer than the six months of standard therapy, at
bacterias capacity to mutate. A number of barriers make it difficult for
greater cost, and with more side effects. WHO estimates that only 55,000
patients to complete therapy, including inadequate or distant health
MDR cases will be adequately treated in 2010.
overcrowded living conditions, and their significant levels of poverty.
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.
38
39
8/31/10 11:05 AM
Tuberculosis
More recently, extensively drug-resistant tuberculosis (XDR-TB), caused

by strains that do not respond to virtually any of the currently available
antibiotics, has emerged. At least one case had appeared in each of
57 countries by September 2009, and death rates rival those seen before
antibiotics were developed. Where treatment does exist, care is expensive because costly therapies must be administered by injection, often
for as long as 18 months. In the United States, caring for one hospital-
are infected with HIV.
those come from wildlife. Birds, pigs, horses, and bats are common
drugs to treat HIV and TB share toxicities, have potentially adverse

interactions, and may promote an inflammatory immune system
response. HIV-infected individuals who develop TB symptoms are also
more likely to have drug-resistant forms of the disease.
WHO has identified the three I public health action steps to reduce
the spread of TB that should be a central part of HIV care and
treatment in resource-limited countries. Local HIV initiatives should be
encouraged to own these measures, as they are recognized as crucial to
TB prevention and treatment efforts:
Infection control to limit spread of Mycobacterium tuberculosis.
This suggests a need to reconsider current immunization strategies

and schedules. In addition, the impact of an anti-vaccine movement
in Europe, Russia, Australia, Japan, and elsewhere has been well
countries that have curtailed the vaccine.
Other infectious agents are not new, but knowledge of their risks is
recent. The hantavirus, transmitted to human beings through rodent
droppings, may have caused respiratory illness for many years, but
immunity. Zoonotic diseases, those caused by pathogens capable of
it was recognized only in 1993, after a fatal outbreak on an Indian
traveling from animal to human populations, result from intensive
reservation in the American Southwest. Bacillus anthracis, the bacteria
agricultural practices, human encroachment into natural habitats,
that causes anthrax, was identified in 1875 but gained notoriety with
urbanization, deforestation, and climate change, while their rapid
an attack that killed five people in the United States and heightened
spread around the globe reflects patterns of migration, tourism, and
awareness of bioterrorism in the 21st century. Smallpox and plague are
commerce.
among other pathogens that could potentially be used in bioterrorism.
Drug resistance: Emerging infections can also be caused by pathogens
An ongoing battle: History and microbiology both warn that the battle
that have evolved to evade drug therapy. One example is methicillin-
against microbes will endure and evolve. Aggressive surveillance, public
resistant Staphylococcus aureus (MRSA), a bacterial strain that does not
education, and a commitment of global resources are essential to ensure
respond to first-line antibiotics.
that the human population maintains the upper hand.
Re-emerging infections: There are also signs that some familiar

infections are re-emerging with renewed vigor. Pertussis, a bacterial
infection of the lower respiratory tract that can lead to pneumonia,
affected 200,000 people in the United States in the 1940s, most of them
100
Number of emerging
infectious disease events
others at risk for TB.
of the immunity conferred by both the vaccine and prior infection.
reservoirs for these microbes, against which people have no established
Isoniazid drug therapy to prevent latent TB from becoming active.

Intensified case finding by screening HIV-infected individuals or
growth, but the rise in pertussis may also reflect a waning over time
documented, with pertussis infection rates 10 to 100 times higher in
humans have their origins in animals, and almost three-quarters of
incidence of active TB in HIV-infected patients. Unfortunately, the
Improved diagnostic techniques likely account for some of this
respiratory infections of unpredictable severity.
reach similar conclusions; the risk is 20 times higher among those who
The antiretroviral therapy used against HIV also helps to reduce the
among those over 20, compared with 1990-93 data.
pathogens will continue to evolve at an unknown pace to cause acute
Zoonotic diseases: Sixty percent of new pathogens capable of infecting
epidemic, with 80 percent of the worlds HIV-positive TB cases.
States increased nineteenfold among 10- to 19-year-olds and sixteenfold
left its swath of destruction, the H1N1 pandemic, avian influenza, and
who do not have HIV. Studies that have looked specifically at children
individuals in 2009. Sub-Saharan Africa is the epicenter of the dual
affected population changed as well: In 2004, pertussis in the United
Aggressive surveillance, public education,

and a commitment of global resources
can help curb new infections.
severe acute respiratory syndrome (SARS) are all recent reminders that
treat, and more likely to be fatal. Active TB killed 500,000 HIV-positive
access to care and optimal therapy.
1,000 cases were reported, but that number rose to 19,000 in 2004. The
Tuberculosis and HIV
In HIV-infected populations, TB is also harder to diagnose, harder to
probability of infection also tend to limit
children. By 1976, with a vaccine in widespread use, slightly more than
Although it has been almost a century since the Spanish flu of 1918
living with HIV are 20 to 40 times more likely to develop TB than those
social determinants that increase the
Future Threats
ized XDR-TB patient averaged US$483,000.
TB and HIV are inextricably linked. Within the same country, people
Lower socioeconomic status and other
80
60
Zoonotic
Non-zoonotic
40
20
0
1940
1950
1960
1970
1980
1990
2000
Most emerging infections originate in animals.

40
41
8/31/10 11:05 AM
Links from Index patient and Metropole Hotel in Hong Kong

METROPOLE HOTEL link to:
Singapore (238)
Canada (138)
United States
China
Viet Nam (16)
Phillippines to UK
INDEX PATIENT link to:

Kwong Wah Hospital (1)
METROPOLE HOTEL link to:

PRINCE OF WALES HOSPITAL (238) connected to:
Alice Ho Miu Ling Nethersole Hospital (156) to Tai Po Hospital (37)
Private Clinic (2)
Baptist Hospital (34)
Amoy Gardens (329):
TO: Princess Margaret Hospital (62) AND United Christian Hospital (26)
TO: Taiwan
TO: Beijing TO: Airplane
METROPOLE HOTEL
link to:
World Lung Foundation
Acute
Respiratory Infections Atlas
St. Paul Hospital (12)
Profile: The SARS Story

Severe acute respiratory syndrome (SARS) is an ARI that seems, at least
thus far, to have been contained successfully. Its trajectory is at once a public
How SARS Spread
Singapore, with 238 cases, required all health care workers to use
health triumphsurveillance, isolation, contact tracing, and infection
The index SARS case that appeared to trigger the global spread was an
suspected SARS and to have their temperature checked twice daily.
control prevented the spread of the deadly virusand a reminder of the
ailing physician who checked into a Hong Kong hotel in February 2003
The country also required the use of air purification respirators
importance of surveillance (see Surveillance Techniques, p. 75).
and died a few days later. At least 14 other visitors or guests at that hotel
for certain medical procedures, barred most hospital visitation,
quickly became infected, carrying the virus with them to health care
conducted telephone surveillance following a patients release from
settings in Canada, China, Singapore, and Viet Nam.
hospitals where SARS cases had occurred, and mandated home
SARS first appeared in November 2002 among market workers selling
Mainland China
Canada
x136
quarantine for discharged SARS patients.
United Kingdom
of China. The source was a new coronavirus, a viral family previously
Other superspreading events, made possible by combinations of host,
known only to cause the common cold in human beings. Characteristic
environmental, and viral features, also played a significant role in the
All of these control efforts might not have been adequate had the
early symptoms were those of the typical flu, including high fever and
pandemic. After an infected person was admitted to the Prince of Wales
character of the virus been different. In particular, SARS proved to
body aches, but most patients eventually developed pneumonia.
Hospital in Hong Kong, 238 SARS cases were reported there. One of the
be transmissible only after symptoms appeared, making isolation and
patients lived in or visited the Amoy Gardens apartment complex, also
quarantine more feasible. Despite the superspreading events, each
in Hong Kong, where 329 cases were eventually identified.
primary SARS infection caused an average of just two to four additional
x238
cases. But vigilance remains essentialcoronaviruses are experts at
By March 12, 2003, WHO had issued a global alert, the first ever for an
emerging infectious agent. Less than four months laterafter more than
8,000 SARS cases had occurred in 29 countries on six continents, killing
The SARS pandemic spread particularly swiftly in health care settings,
774 peoplethe pandemic was contained.
eventually infecting 1,700 health care workers, more than one-fifth the
total global caseload. Overall, China was hardest hit, with 5,327 cases,
Philippines
Viet Nam
x63
In
te
rn
at
H
io
on
na
gK
lc
on
lu
ste
gc
rs
lu
ste
r
exotic live animals for human consumption in the Guangdong province
United States
personal protective equipment when attending to any patient with
Hong Kong
Metropole Hotel
Singapore
mutating, and a related strain, perhaps in more virulent form, could

appear again.
Index patient
Kwong Wah
Hospital
x238
x12
Prince of Wales
Hospital
St. Paul
Hospital
and Hong Kong was second, with 1,755 cases.

x156
How SARS Was Contained
x34
Alice Ho Miu Ling

Nethersole Hospital
Hong Kong
The chain of SARS infections was successfully broken by effective public
Private
Clinic
Baptist
Hospital
Amoy Gardens
x26
x62
x37
Princess Margaret
Hospital
Tai Po Hospital
health measures that included infection control in health care settings,
x329
United Christian
Hospital
contact tracing, quarantines, bans on public gatherings, and travel

advisories. During the pandemic:
SARS Infections Resulting from Index Patient at Metropole Hotel
A single person can trigger a superspreading

event that travels across the globe.
WHO coordinated surveillance and reporting; issued guidance

pertaining to travel, mass gatherings, and patient care; promoted
scientific collaborations; and sent equipment and expertise to af-
Pathways of SARS Transmission
stations, roadways, and the airport, but out of 14 million people

screened, these uncovered just 12 probable SARS cases.
14
238
27
63
8096
Number of 0
deaths
43
349
299
37
33
774
Case fatality 0
ratio (%)
17
17
11
14
40
14
14 100
22
9.6%
Sp
ai
n
Sw
e
Sw de
itz n
er
lan
d
Un Tha
ila
ite
d K nd
in
Un gdo
m
ite
dS
ta
Vi tes
et
Na
m
Total
also implemented resource-intensive fever checks at major train
346
Ita
ly
Ku
wa
M it
ala
ys
ia
M
on
Ne go
li
w
Ze a
ala
nd
Re Ph
pu ilip
bl
pi
ic
ne
s
Re of
pu Ire
lan
bl
ic
of d
Ko
re
Ru
a
R
ss
ia oma
n
n
Fe
i
de a
ra
tio
Si
ng n
So apo
re
ut
h
Af
ric
a
individuals, and closed 3,500 public entertainment facilities. The city
M
ac
ao
Ta
iw
an
Fr
an
G e ce
rm
an
y
In
di
In
a
do
ne
sia
techniques, quarantined more than 30,000 close contacts of infected
1,755
in
a
Ho
ng
Ko
ng
hospitals for people with SARS, emphasized infection control
251 5,327
Ch
Beijing, where 2,521 cases were reported, designated specific
Cumulative 6
number of cases
Au
str
ali
Ca a
na
da
fected regions.
Number of SARS Cases and Deaths during the 200203 Outbreak
SARS was contained before it spread widelybut it killed almost 10 percent of those it infected.
42
43
8/31/10 11:05 AM
Part 2
Drivers of Acute Respiratory Infections
Although bacteria and viruses are

the immediate causes of most acute
respiratory infections, malnutrition, air pollution, smoking, and
overcrowding are the underlying
drivers of vulnerability.
Taking action against poverty, improving standards of living, and
addressing the environmental factors that create the conditions for the
spread of disease can dramatically reduce ARIs. Other, more targeted
strategies are emphasized in this section.
Malnutrition
Tobacco
Exclusive breastfeeding before six months.
Raise tobacco prices.
Breastfeeding and complementary foods until age two.
Enforce no-smoking policies.
Access to appropriate nutritional supplements.
Provide education about the harms of smoking and
Commitment from governments and the international community

to combat malnutrition.
secondhand smoke.
Ban all forms of tobacco advertising and marketing.
Air Pollution
Expand the use of health warnings on cigarettes.
Wider access to cleaner fuels for cooking and heating.
Overcrowding
Support and education to help people change their cooking habits.
Improve urban infrastructure and foster economic development.
More research into the relationship between indoor air pollution
Build housing that meets standards for ventilation and density.
and health.
Motor vehicle and industrial emission controls.
Promote community input on opportunities for improving

living conditions.
Improved public transportation systems to reduce motor vehicle use.
44
45
8/31/10 11:09 AM
Non-communicable
diseases
7%
Injuries
4%
Birth asphyxia
and trauma
8%
Pneumonia
17%
greatest benefit on child health during the period from fetal

5%
44%
development to the age of 24 months.
11%
Number of deaths
by WHO region (2004)
Taking zinc supplements routinely may prevent about one-
45%
457,400
quarter of the ARIs that occur in children under age five who
73%
Diarrhea
17%
36% 10%
Severe neonatal
infections
11%
155,100
47%
1,500
See p. 98 for the countries
in each WHO region.
Measles
4%
Nutritional deficiencies
2%
21,200
ARI Deaths Attributable to Undernutrition
Malaria
7%
Causes of Death in Children under Five (2004)

Shading represents contribution of undernutrition.
Malnutrition
Breastfeeding, nutritional supplements,
and international support curb
malnutrition, breaking the link to ARIs.
Other infections
12%
are zinc-deficient. Direct research on vitamin D supplementation

is not yet available, and vitamin A supplements, while
important in early childhood nutrition, have not demonstrated
36,900
23,400
Promoting breastfeeding, which provides essential nutrients

in infancy, saves lives. Nutritional interventions have the
Prematurity
11%
271,000
a significant preventive effect on ARIs specifically.

The international nutrition community can support countrylevel efforts to combat malnutrition by gathering more evidence
about programs that work, increasing targeted resources,
providing direct nutrition services in emergency situations, and
training more personnel.
Lack of food contributes to 44 percent of

deaths from pneumonia among children.
Inadequate nutritionin utero and during infancy and early childhood
is closely linked to lifelong immune deficiencies and acute respiratory
infections. Nutritional deficits may result from any combination of
insufficient caloric intake, lack of protein, and inadequate levels of
micronutrients.
ARIs generally occur more frequently, last longer, and are more severe
Global Impact
Thirty-six countries are home to 90 percent of the worlds
underweight or stunted children.
As many as one-quarter of all deaths associated with acute
respiratory infections in Africa and Asia can be traced to
childhood underweight.
Suboptimal breastfeeding is a factor in 44 percent of all ARI-
in malnourished children, typically because the mucous membranes

and other mechanical structures designed to keep the respiratory tract
clear are impaired, and the immune system has not developed properly
(see How the Body Defends Itself, p. 103). Being underweight is
especially dangerous: Worldwide, childhood underweight is responsible
for more poor health than any other single factor, and in low-income
The already critical problem of inadequate

nutrition has been dramatically worsened
by recent economic crises. According to
the World Bank, the slowdown in global
countries it is the leading risk factor for death.
growth in 2009 caused 41 million more
The already critical problem of adequate nutrition has been
people to become undernourished.
dramatically worsened by recent economic crises. One billion people
related deaths in the first 28 days of life and in 18 percent of
around the globe are now undernourished, reflecting the increase
those deaths in children under five (see Breastfeeding, p. 50,
in food prices in 2008 and the 2009 slowdown in global growth that
for WHOs recommendations).
caused 41 million more people to become undernourished, according

to the World Bank.
46
47
8/31/10 11:09 AM
Malnutrition
Percent of children under five

who are underweight
>30%
21-30%
How Nutritional Deficiencies Affect the

Immune System
11-20%
6-10%
0-5%
Increasingly sophisticated scientific tools continue to reveal more about
no data
the precise mechanisms by which malnutrition weakens the immune

systems ability to protect the body from acute respiratory infections.
Recent research reveals that:
Chronic food deficits impair the capacity of nutrients to regulate
cytokines, chemical messengers that coordinate communication
between the bodys immune cells and tissues.
Malnutrition is associated with atrophy of the thymus and other
lymphoid tissue, where a type of pathogen-fighting white blood cells
known as lymphocytes mature.
Without sufficient antioxidants, especially vitamins A, C, E, and
beta-carotene, the human body cannot counteract the oxidation
process. That process is a crucial component of the bodys defense
system, but one that is also damaging.
Zinc deficiencies accelerate the death of B and T immune cells.
They also weaken the bodys ability both to control inflammation
and to maintain the skin and mucous membranes that act as
microbial barriers.
Separate studies in Ethiopia, Kuwait, Scotland, and Yemen show
that children with vitamin D deficiencies are at significantly
increased risk of pneumonia. Insufficient vitamin D may also
reduce activation of genes programmed to respond to microbes.
Vitamin A deficiency diminishes the functioning of key immune system cells and impairs the protective function of the mucous barrier.
48
Linking ARIs and Malnutrition

The links among overlapping and interrelated nutritional deficits and
acute respiratory infections in children under five is supported by
these findings:
Most underweight children are in Africa and parts of Asia.
In the developing countries on the African and Asian continents,

as many as one-quarter of all childhood deaths associated with ARIs
can be traced to underweight.
Inadequate maternal nutrition is a major risk factor for later
childhood pneumonia and other ARIs, because it is linked to fetal
100%
8%
75%
6%
50%
4%
25%
2%
weight below the tenth percentile (relative to gestational age) and

low birthweight.
Suboptimal breastfeeding increases an infants risk of malnutrition
and vitamin deficiencies. During the first six months of life, infants
who are not breastfed at all are five times more likely to die from
pneumonia than those who are exclusively breastfed.
Over the past few years, rising food prices have exacerbated longstanding problems of malnutrition. The price of staple foods, including
the rice, wheat, and maize that feed so much of the worlds population,
are predicted to be 10-20 percent higher, on average, during the period
2009-2018, compared with actual prices during the 1997-2006 period.
0%
Burkina Faso
Tanzania
% increase in domestic price

of main staple food (2009)
Kenya
Mozambique
0%
% increase in undernourishment
incidence (since 2008)
When food prices rise, more people go hungry.

49
8/31/10 11:09 AM
Malnutrition
recommends breastfeeding as the sole source of food until an infant is
infants risk of death from infectious disease in the first two months of
six months old and a combination of breastfeeding and complementary
life. A shorter course of breastfeeding may help to balance the risks:
foods from six months to 24 months of age.
Women who breastfeed their babies for six months have one-third the
risk of transmitting HIV than women who do so for two years.
Rates of breastfeeding fell sharply in many countries during the middle

and latter parts of the 20 century, then rose modestly from 1990 to
Published research also suggests that the use of highly active
2000. Between one-quarter and one-third of infants are exclusively
antiretroviral therapy by pregnant and breastfeeding HIV-infected
breastfed in developing regions, and those percentages are lower in the
women may dramatically reduce HIV transmission rates.
th
developed world.
(For more on the link to acute respiratory infections, see HIV and
Barriers to exclusive breastfeeding include time constraints, cultural
Pneumonia, p. 24.)
risk that infants will ingest water and other liquids or formula that lack
Interventions designed to address micronutrient deficiencies tend to
essential nutrients and carry disease-causing microbes.
emphasize zinc and vitamin A because they have the greatest impact on
Suboptimal breastfeeding is a factor in 44 percent of all deaths

associated with acute respiratory infections among infants in the first
28 days of life and in 18 percent of ARI-related deaths in children under
five. During their first six months, infants who are not breastfed at all
are five times more likely to die from pneumonia than those who are
The international community can help with a commitment that

includes financing, direct nutrition services, training, and the sharing
40%
of expertise. International donors invested just US$300 million in basic

nutrition in low- and middle-income countries and US$1.4 billion in
food aid and food security from 2000 to 2005compared with US$5.7
20%
billion in donor aid for HIV during the same period.

To build capacity, governments, universities and donors should develop
0%
Being underweight is a significant

contributor to ARIs and other diseases.
child health. Adequate intake of vitamin D, which plays an important
associated with acute respiratory infections in children under age five.
role in synthesizing peptides that have antimicrobial properties within
Taking zinc supplements routinely may prevent about one-quarter of
the body, has more recently gained attention for its contributions to a
acute respiratory infections in children who are zinc-deficient, although
healthy immune system.
no significant effect is seen in infants younger than six months, and zinc
Zinc: About one-third of the worlds population is zinc-deficient. Lack
exclusively breastfed.
and political upheaval.
60%
fants, they often combine breast milk with bottle-feeding, increasing the
service and health care systems, competing health problems, and social
D
iar
Micronutrients: Zinc, Vitamin D,

and Vitamin A
While most women in Africa and parts of Asia do breastfeed their in-
shortages, absence of public sector commitment, fragmented social
rh
ea
norms, multiple births, ready access to formula, and lack of knowledge.
80%
in
f
di ecti
se ou
as s
es
more likely to transmit the virus, but they also decrease by sixfold an
th
er
enzymes, and other cells with immunological properties. WHO
National efforts to combat malnutrition are challenged by resource
M
ea
sle
s
HIV-infected mothers who breastfeed their children are considerably
How the International Community Can Help
100%
ia
Breast milk contains all the nutrients an infant needs, as well as proteins,
breastfeeding, and the policies designed to promote its use.
Pn
eu
m
on
HIV and breastfeeding: HIV has complicated decisions about
M
a la
r ia
Breastfeeding
Percent of each disease resulting from underweight
of zinc is a factor in seven percent of the total death and disease burden
10%
20%
30%
40%
50%
of undernutrition as an area for further research and grantmaking.

Through the Baby Friendly Hospital Initiative, a joint effort of WHO
and UNICEF, 15,000 facilities in 134 countries have been accredited
as meeting the criteria for promoting breastfeeding. These criteria
comprise ten specific steps, including staff training, efforts to help
women start and maintain breastfeeding, rooming-in policies that allow
mothers and infants to stay together, and support groups.
continues to be assessed, with a recent study confirming that zinc was a

useful preventive tool where specific diagnostic criteria for pneumonia
Vitamin D: Research has demonstrated a strong association between

vitamin D deficiencies and severe ARIs among hospitalized children.
World
38%
To date, however, the impact of either maternal or infant vitamin
Developing countries
38%
D supplementation as a strategy for preventing ARIs has not been
Least-developed countries
37%
established, although research is underway.
Sub-Saharan Africa
31%
Middle East/North Africa
26%
East Asia/Pacific
43%
Latin America/Caribbean
Central/Eastern Europe and the
Commonwealth of Independent States
N/A
Vitamin A: In regions where vitamin A deficiencies exist, children

who do not receive vitamin A supplements have a 25 percent greater
risk of death than those who do. WHO and UNICEF are among the
organizations that recommend vitamin A supplementation for children
20%
policy and program needs. They should also emphasize the importance
has not proved useful in treating pneumonia. The extent of the benefit
were applied.
0%
more nutrition-related training, especially training that emphasizes
International donors invested

US$300 million in basic nutrition in
low- and middle-income countries and
US$1.4 billion in food aid and food
security from 2000 to 2005compared
with US$5.7 billion in donor aid for HIV
during the same period.
under five in those locations.

Percent of Infants Who Are Exclusively Breastfed until Six Months Old (2000-07)
Far less than half of children are exclusively breastfed in any part of the world.
However, the hope that vitamin A supplementation might lessen the

toll of acute respiratory infections has not been borne out by research
thus far. One analysis of five major studies showed it did not reduce the
incidence of ARIs, or the deaths they cause.
50
51
8/31/10 11:09 AM
Total deaths from

childhood pneumonia
Total deaths from ARIs

499,800
37,600
217,900
22,800
108,100
17,600
22,900
16,200
12,300
13,800
10,500
8,700
4,100

in each WHO region.

in each WHO region.
Every year, 1.96 million people die from ARIs as a result of indoor air pollution.
Air Pollution
Cleaner cooking fuels, reduced tobacco
use, and vehicle emission controls reduce
pollution and ARIs.
Air pollutionindoors and outdoors, in both urban and rural areas
significantly increases the incidence of acute respiratory infections. The
risk depends on how toxic the pollutants are, how long and at what
concentration exposure occurs, and the adequacy of ventilation.
Children are particularly vulnerable for three reasons: their lungs,
respiratory defenses, and immune systems are not fully developed; they
wood, grasses, animal dung, agricultural wastes, and other biomass

fuels causes an estimated 871,500 deaths annually from childhood
pneumonia (and a total of 1.96 million deaths altogether). Half
the worlds population cooks with these fuels. Tobacco is also a
significant source of indoor air pollutionnearly half of the worlds
children are exposed to tobacco smoke in their daily lives.
Measures to reduce many of the indoor contaminants implicated in
ARIs include using cookstoves that burn biomass more cleanly or that
run on alternate fuels, using vented propane or kerosene stoves for
heating, improving ventilation in cooking areas, and tobacco control.
Outdoor air pollution, primarily from the particulates and chemical
toxins in motor vehicle exhaust and industrial processes, causes
spend more time in polluted home environments.
121,000 deaths a year from acute respiratory infections.
Although it is impossible to tease out the direct links between a specific
Reducing outdoor air pollution requires a mix of regulation,
pollutant and a specific infection, the association of air pollution with
incentives, and culture change aimed at tightening emission
acute respiratory infections is well established. At the same time,
standards for motor vehicles and industrial plants, promoting public
solutions are at hand:
transportation, and encouraging less polluting infrastructure.
Outdoor air pollution causes 121,000 ARI deaths annually.
Indoor air pollution associated with cooking and heating with
breathe more in proportion to their body size; and they are likely to
52
Global Impact
Indoor air pollution associated with using biomass fuels (such
From 1985 to 2007, only 44 studies were published focusing on
as wood and grasses) causes an estimated 871,500 deaths annu-
the link between indoor air pollution and ARIs in developing
ally from childhood pneumonia.
countries.
The release of particles and chemicals from tobacco use con-
Outdoor air pollution, mostly associated with motor vehicle
tributes significantly to indoor air pollution. Children living
and industrial emissions, causes 121,000 ARI-related deaths
in households with people who smoke are twice as likely to
annually.
develop ARIs severe enough to require hospitalization (see

Tobacco, p. 60).
Reducing outdoor air pollution in urban environments is typically the shared responsibility of central and local governments
and involves a mix of regulation, incentives, and culture change.
53
8/31/10 11:09 AM
Air Pollution

Air Pollution
Dust
>10 microns
The Particulate Danger Zone

Tobacco smoke
.01 micron
How Pollutants Affect the Body
Fine beach sand

90-100 microns
Among the reported links between pollutants and acute respiratory
Ozone can increase the permeability of the alveoli, the air sacs deep
within the lungs, easing the entry of foreign invaders.
infections:
Spiderweb
3-5 microns
Car exhaust
.01-.1 micron
The bodys innate and acquired systems of immunity can be dam-
Human hair
50-70 microns
Wood smoke
.02-.2 micron
Pollutants can inflame the alveoli and the tissue lining the lower
aged by a long and overlapping list of pollutants, including particu-
respiratory tract. This inflammation can narrow the airways and
lates, nitrogen dioxide, sulfur dioxide, and ozone.
exacerbate the severity of an infection.
Exposure to tobacco smoke impairs the bodys capacity to keep the
Exposure to pollutants during pregnancy can increase the risk
respiratory tract clear and allows particles to penetrate normally
of low-birthweight babies, which in turn is a risk factor for acute
sterile areas of the lungs.
respiratory infections in childhood.
Nitrogen dioxide has an adverse effect on the actions of the upper and
lower respiratory tracts designed to keep microbes away from the lungs.
0.01
0.1
2.5
10
100
Size in microns. Particles enlarged for comparison.
1,000
10,000
The greatest lung damage results from particulate matter smaller than 2.5 microns.
Particulates
Indoors, particulates generated by incomplete combustion are the primary pollutant associated with acute respiratory infections. The concentration of particulates in homes that use wood and other biomass
fuels can be 10 to 50 times higher than WHO-established guidelines.
Outdoors, particulates generated by fossil-fuel consumption are the
most significant component of air pollution in urban areas. They are
also the primary cause of pollution-related mortality and a leading
factor in childhood ARIs.
Particles suspended in the air are generally distinguished by size:

Coarse particles, which are between 2.5 and 10 microns in
aerodynamic diameter (PM2.5-PM10), can be inhaled into the upper
respiratory tract, bypassing the defenses of the nose and mouth.
(For example, dust and pollen can be about 10 microns.)
Fine particles, which are smaller than 2.5 microns (PM2.5), are
generally considered the most harmful particle size because they
can travel deeper into the lungs. The particles released with the
burning of wood and motor vehicle fuels are generally smaller
than 1 micron.
Ultra-fine particles, measuring less than 0.1 micron, have recently
been linked to asthma, inflammatory disease, and reduced oxygen
intake. Some components of tobacco smoke are ultra-fine particles.

Indoor Pollution
Outdoor Pollution
Greater use of alternate cooking fuels, stoves designed to burn bio-
Government strategies to reduce outdoor air pollution should include:
mass more cleanly, and vented propane or kerosene stoves for heating
would have a significant impact on indoor air pollution, but they
require equipment and an affordable fuel supply.
After examining indoor air quality in Bangladeshi households,
researchers offered these ideas for reducing contamination:
Encourage bulk purchases of cleaner fuel at the village level to
reduce costs.
Relocate cooking facilities to peripheral areas of the home
so that pollutants can more readily disperse outside.
Use more permeable construction materials to
enhance ventilation.
Share cooking responsibilities to reduce individual exposure.
The challenges and successes of Chinas National Improved Stove
Program and Indias National Biomass Cook-Stoves Initiative merit
attention (see Profile: Air Pollution in China, p. 59, and Profile:
Integrated Approaches to Reduce ARIs in India, p. 77).
More research is needed to understand the nature and extent of the
association between indoor air pollution and ARIs.
54
Ongoing efforts to meet the air quality targets set by WHO for
particulates, ozone, and nitrogen and sulfur dioxides. These targets are
continually revised to reflect the most current scientific thinking.
Setting fuel quality and vehicle emission standards at realistic
levels and rigorously enforcing and tightening them over time.
Requirements should include inspection systems to ensure that
motor vehicles are in compliance.
Appropriate, affordable public transportation systems that allow
people and goods to move efficiently and discourage the use of
private cars, especially in congested areas.
Financial incentives, tax penalties, and infrastructure design that
encourage conservation and favor both less polluting transportation
and industrial development strategies.
Monitoring and publicizing outdoor air quality, including early
warning systems that allow vulnerable individuals to minimize
exposure by staying indoors, using masks, or moving to other
locations, as necessary.
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8/31/10 11:09 AM
Air Pollution

Air Pollution
Home Cooking and Heating

About half the worlds population cooks daily with biomass fuels: twigs
and grass, animal dung, firewood, and crop residue such as plant stalks.
While these are inefficient and highly polluting sources of energy, they
are cheap and readily available, especially in poor rural communities.
Unvented heating with biomass fuels is also a common practice in the
cooler climates of impoverished highland areas around the world.
The resulting particulate concentrations dramatically exceed standards
Percent of people using

solid fuels for cooking
>95%
set in the developed world. In the United States, for example, the
75-95%
acceptable standard for coarse particulates (PM10) in the air is no more
50-75%
than a concentration of 150 ug/m3 (micrograms per cubic meter) within
20-50%
a 24-hour period, and that level can be reached no more than once a
5-20%
year, averaged over three years.
5%
By contrast, indoor air particulate concentrations well in excess of 1,000

ug/m3 have been consistently reported over 24 hours in developing
countries, and those measures soar when shorter periods of time are
Indoor Air Pollution
measured. For example, a series of studies in several Indian villages
Most acute respiratory infections associated with indoor air pollu-
in Nepal, a summary of five studies found concentrations on the order
burning biomass fuels for cooking and heat or from environmental

tobacco smoke. Among the pollutants generated by these activities are
particulate matter, carbon monoxide, nitrogen and sulfur dioxides,
and volatile organic compounds. Another source of nitrogen dioxide
is unvented gas stoves. While many nations have set outdoor exposure
limits for these pollutants, there are no international standards for
indoor exposure.
Despite the scope of the problem, the link between indoor air pollution
and acute respiratory infections in developing countries is markedly
under-researched. An electronic search conducted over 22 years (1985
to 2007) yielded only 44 relevant studies, and just 25 of those actually
involved empirical research. Although existing data clearly establish an
association, more data are urgently needed.
Solid fuels include wood, dung, agricultural waste and other biomass fuels, as well as charcoal.
of 4,700 ug/m3 at mealtime.
Half of the worlds population cooks with solid fuels.
In Zimbabwe, children diagnosed with recurrent pneumonia were more

likely to live in households that use wood fuel indoors. Likewise, a series
of studies in Nepal demonstrated that infants and children suffering life-
3.5
threatening respiratory infections had spent more time near cooking

stoves. The developed world is not immune: Children in Arizona
were four times more likely to be diagnosed with an acute respiratory
infection in homes that used woodstoves for heating and cooking.
Indoor Smoking
Tobacco use releases particulates and chemical toxins into the air,
and smoking indoors endangers not only the smoker, but also others
present in the home or workplace. The risk of acute respiratory tract
infections linked to secondhand smoke is especially heightened among
children, and the more a parent smokes, the greater the risk. A child is
twice as likely to be hospitalized with an ARI if a parent smokes (see
Environmental Tobacco Smoke, p. 61).
PM10 relative to mean daily PM10
tion are the result of incomplete combustion in the home, either from
showed exposure levels of between 900 and 1,100 ug/m3 at mealtime;
3.0
2.5
2.0
1.5
1.0
0.5
0
12 am
4 am
8 am
12 pm
4 pm
8 pm
12 am
Daily PM10 pattern for cooking and living areas

Daily ambient (outdoor) pollution pattern in rural villages
Indoor Air Pollution Spikes during Mealtimes, Bangladesh

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8/31/10 11:09 AM
Air Pollution
Profile: Air Pollution in China
A significant amount of outdoor air pollution can be prevented, yet it

is sometimes mistakenly viewed as the cost of progress. That cost is
high: Every year, particulates and chemical toxins in outdoor air cause
121,000 deaths from acute respiratory infections (and approximately
one million deaths from other respiratory diseases, lung cancer,
and cardiovascular disease). Although the developed worlds cities
are generally far cleaner than those of the developing world, fine
particulates in outdoor air reduce life expectancy for the average
European by 8.6 months.
Rural areas are not immune to outdoor air pollution. Traditional
Chinas enormous air pollution challenges highlight a situation unique
Although the principal aim of the initiative was to improve fuel effi-
to a nation straddling the traditional and modern worlds. More than
ciency, the new stoves also helped to reduce particles in indoor air. But
60 percent of the population still lives in rural areas, where about
the health threat has not adequately diminished, because older stoves
80 percent of energy consumption is generated by biomass fuels and an
are still in use and the new stoves, while cleaner, are not optimal. One
additional 10 percent by coal. At the same time, soaring motor vehicle
study of rural areas published in 2007 found that the concentrations of
use, rapid industrialization, and coal consumption that exceeds the
particles smaller than four microns surpassed the standards set by the
combined use of the worlds next seven largest consumers are generating
Chinese government for coarser particles.
a deadly mix of particulate and chemical emissions.
agricultural practices, including land-clearance fires and the burning of
Indoor air pollution caused by biomass fuels and burning coal leads
The rapid rise in motor vehicle use, coupled with weak or absent
to 420,000 deaths every year.
emission standards, are major contributors to air pollution. Significant

sources of particulates include automobiles without functioning
catalytic converters and diesel-fueled and two-stroke gasoline engines,
such as those in motorcycles and tuk-tuks.
Together, outdoor and indoor air pollution account for almost five
sion standards. Vehicles with odd and even license plate numbers were
studies of the relationship are designed with proxy exposure measures,
A nation in transition, China has invested heavily in environmental

improvement. Its National Improved Stove Program, in place during the
exposure is a more precise way to capture the health impact on a
1980s and 1990s, was termed the largest and most successful improved
given population.
stove program ever implemented anywhere in the world. An estimated
of the world, is formed when sunlight reacts with chemicals in motor
most common pollutants associated with the burning of fossil fuels.
vehicle exhaust, industrial emissions, and solvents, notably nitrogen oxide
Industrial operations, coal-burning power plants, and solid waste also
and volatile organic compounds. While ozone is principally a problem of
generate considerable outdoor burdens.
urban areas, rural areas are not spared because wind can carry ozone and
pollutants hundreds of miles away from their original sources.
controls have lagged, allowing air pollution in some places to rival that
The concentration of ground-level ozone is rising in many developing
of the industrialized world 60 years ago. Twenty of the worlds 30 most
countries. Health effects, especially in the respiratory tract and lungs,
polluted cities, based on coarse particulate count, are in China, according
are well established and include increased susceptibility to ARIs and
to the World Bank; not coincidentally, that nation also uses more coal than
irritation and inflammation of the airways.
the next seven largest consumers combined and is opening one new coalburning power plant every week. Kolkata, Jakarta, Delhi and Cairo are also
on the list of most polluted cities.
58
185 million rural Chinese households added at least one chimney stove
during that period.
nearby provinces of Tianjin and Hebei provinces in the final weeks be-
Air quality in Beijing improved substantially as a result, with concentrations

of sulfur dioxide, nitrogen dioxide, and coarse particles dropping to half
their levels over the previous year. Some of this reflects enduring changes in
China and some were temporary measures, but together they demonstrate
what can be accomplished with advocacy and political will.
100%
Percent decrease in pollutant
Ozone, the primary constituent of the smog that hangs over many cities
the Olympics, some factories and construction sites were closed in the
fore the games, and indoor smoking in public places was briefly banned.
per-capita automobile ownership. Directly monitoring individual
around the world, fine particles, nitrogen dioxide, and ozone are the
relocating highly polluting factories, and imposing strict vehicle emisalternately barred from Beijing for two months prior to the start of
such as living near areas with heavy traffic or census data on
environments. With leaded gasoline either banned or being phased out
In the region surrounding Beijing, large-scale initiatives launched

ing scrubbers and other pollution control devices on industrial plants,
from one month to 11 months of age.
Ozone
event for an environmental intervention of unprecedented scale.
Outdoor air pollution is linked to some 470,000 deaths annually.
Pneumonia accounts for nearly half the deaths that occur in infants
infections is well-established, better data are needed. To date, most
pace of urban growth. The 2008 Beijing Olympics was the galvanizing
years before the games included shifting toward cleaner fuels, install-
percent of the nations burden of disease.
Although the link between motor vehicle use and acute respiratory
As cities have increasingly grown in developing countries, pollution
sures on many fronts, although these have not entirely kept up with the
The nation is home to 20 of the worlds 30 most polluted cities.
Motor Vehicle Emissions
Motor vehicles remain a primary source of pollution in urban
China has also taken aim at outdoor air pollution with aggressive mea-
The health effects in China are clear:
crop waste, are contributors, as is biomass combustion in the home.
Outdoor Air Pollution
75%
50%
25%
0
Sulphur
dioxide
Carbon
monoxide
Nitrogen
dioxide
Particulate matter
of 10m or less
China cut Beijings air pollution in half

during the Olympics.
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8/31/10 11:09 AM
Adult Smoking
As tobacco burns, it releases an aerosol of vaporized chemicals and particles into the body. Smoking weakens the many mechanisms in place
to defend the respiratory system, damaging the mechanical structures
designed to expel particles, allowing particles to penetrate the normally
sterile air sacs of the lungs, and depressing the pathogen-fighting capacARI deaths attributable to
tobacco, by WHO region (2004)
ity of white blood cells (see How the Body Defends Itself, p. 103).
Among the research linking acute respiratory infections and smoking:
84,900
75,800
Influenza occurs from 50 to 100 percent more often among smokers,
22,500
and smokers have more complications and more severe disease.
19,900
Influenza antibodies wane more rapidly in smokers, making them
14,400
more susceptible to reinfection.
13,300
Smokers are more likely to develop community-acquired pneumonia,
10,400
in each WHO region.
Tobacco use increases the risk of death from ARIs.
Global Impact
Tobacco use is associated with some 241,000 deaths from
acute respiratory infections annually. Adult smokers are
more vulnerable to pneumonia, influenza, and TB, and their
infections are generally more severe.
Smoking in the household can impair the lung function of
children. If a parent smokes, a child is approximately twice as
likely to develop an acute respiratory infection severe enough to
require hospitalization.
The burden of disease associated with tobacco will shift as
smoking declines in developed countries and continues to
increase in the developing world.
Tobacco
Tobacco control reduces smoking,
exposure to secondhand smoke, and the
risk of ARIs.
Tobacco use, the leading cause of preventable deaths worldwide, is
associated with some 241,000 ARI-related deaths annually. Adults who
smoke are more likely to develop pneumonia, influenza, and TB, and the
course of their infections is generally more severe. Children who live in
households with smokers are twice as likely to develop acute respiratory
a risk that increases with the number of cigarettes smoked per day and
WHOs MPOWER strategy provides an evidence-based road
the years of smoking. Individuals who smoke more than 20 cigarettes
map to policymakers, advocates, and public health practitioners
daily are almost three times more likely to develop pneumonia than
promoting tobacco control:
those who have never smoked, while smoking more than 25 cigarettes
a day nearly triples the risk of dying from pneumonia.
Most individuals with chronic obstructive pulmonary disease (COPD)
are smokers, and COPD, in turn, increases the risk of pneumonia.
Smokers are also more likely to be infected with Mycobacterium
tuberculosis and more likely to develop active tuberculosis. The risk of
developing active TB symptoms doubles among heavy smokers and those
who have smoked for at least 20 years, compared with nonsmokers.
Environmental Tobacco Smoke
Monitor tobacco use and prevention policies

Protect people from tobacco smoke
Offer help to quit tobacco use
Warn about the dangers of tobacco
Enforce bans on tobacco advertising, promotion,
and sponsorship
Raise taxes on tobacco
infections severe enough to require hospitalization. Strict tobacco control
Also known as secondhand smoke, environmental tobacco smoke
measures reduce smoking and secondhand smoke and help to break
is a mixture of sidestream smoke from the burning tip of a cigarette
these links.
and mainstream smoke exhaled by a smoker. It is more toxic, per unit
The unique vulnerability of children, especially under the age of
of tobacco, than mainstream smoke alone. There is no safe level of
two, reflects the amount of time they spend in the home and the fact
secondhand smoke and no way to adequately ventilate the air.
that their physical and immunological defense systems are not fully
Because ARIs are so often associated with poverty, the cost of smoking
Smokers are significantly more likely to
can also have an impact on health. In developing countries, smokers
develop a variety of respiratory illnesses,
spend disproportionate sums on cigarettes relative to their incomes,
In both developed and developing countries, nearly half the worlds
lessening the household resources available for food, health care, safer
children are exposed to tobacco smoke in their daily lives, and in much of
including pneumonia, influenza, and
cooking fuels, and other necessities. For example, the poorest 20 percent
southern Europe, including Greece, Romania, and Turkey, that figure is
tuberculosis, and their cases are more
of households in Mexico spend more than 10 percent of their total
Adults also face danger from secondhand smoke. Nonsmokers who are
above 80 percent. Children living in households with smokers are twice as
income on tobacco.
exposed in the workplace or at home face a 25 to 30 percent greater risk
likely to be hospitalized for an acute respiratory infection, and the more
of heart disease and a 20 to 30 percent greater risk of lung cancer. As
a parent smokes, the greater a childs risk of ARIs. In the United States,
smoking declines in developed countries yet continues to increase in the
environmental tobacco smoke contributes to 150,000 to 300,000 lower
developing world, the disease burden is certain to shift.
likely to be severe.
developed. Fetuses are at special risk, and abnormal lung function at

birth may result in more severe infections during infancy.
respiratory infections annually among children younger than 18 months.
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8/31/10 11:09 AM
Overcrowding
ARIs are less likely to spread in
communities with well-ventilated housing
that meets density standards.
Global Impact
By 2015, more than 75 percent of the worlds slum dwellers will
live in sub-Saharan Africa and parts of Asia, in conditions that
promote the spread of ARIs.
By 2050, almost 70 percent of the worlds population will live
in cities.
Alleviating overcrowding is closely tied to broader efforts to
address poverty, manage growth, improve urban infrastructure,
and foster economic development.
Annual average growth in

urban population (2000-08)
>7%
5-7%
3-5%
1-3%
1% or less
Urban population has declined
Oceania
0.06%
Western Asia
4.88%
In an increasingly urban world, ARIs can spread rapidly.
Europe
2.63%
Other 1.87%
Northern Africa
1.61%
Southeast Asia
5.22%
South-central Asia
27.23%
Living in close proximity to others, typically in overcrowded urban
As of 2007, 3.3 billion people lived in cities, just over half the global
housing, is associated with higher levels of acute respiratory infections.
population, and the trend toward urbanization is projected to continue.
In the sprawling megacities of developing countries, slum communities
China alone will add 425 million more people to its urban regions by
that stack neighbors closely together allow pathogens to spread rapidly,
2030, and Africa is urbanizing at the most rapid pace in history. By
especially in combination with inadequate ventilation, poor sanitation,
2050, almost 70 percent of the worlds people are expected to be urban
and other toxic effects of poverty. Conditions within individual homes
dwellers, most of them in Asia (with a projected 3.5 billion city resi-
add further risk: A body of research has identified links to ARIs based
dents) and Africa (projected at 1.23 billion).
on number of residents, number of siblings, and number of people who

share a bed or a room.
62
Eastern Asia
20.55%
Sub-Saharan Africa
24.14%
Latin America and

the Caribbean
11.75%
Distribution of Slum Population (2015 projections)
More than 75 percent of the worlds slum dwellers will soon live in
sub-Saharan Africa and parts of Asia, where ARIs are already rampant.
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8/31/10 11:09 AM
Overcrowding
Among the research documenting a link between overcrowding and

acute respiratory infections:
A study in So Paulo found that when four or more children shared
Profile: The Hajj

The Hajj, the largest mass gathering in the world, brings together an
a bedroom, they were 2.5 times more likely to have acute respiratory
estimated two to three million pilgrims from more than 160 countries
infections. Similar findings were reported in another Brazilian study,
to Saudi Arabia every year, and many stay as long as a month. Muslims,
which correlated an increase in pneumonia with an increase in
who are duty-bound to journey to Mecca once in their lifetimes, follow
household size, and in Kenya, where children in households
a prescribed circular route to reach a series of destinations a
with more than five siblings were at greater risk of ARIs.
few kilometers apart. At times, the Hajj brings as many as seven people
Children living in the urban slums of developing countries have ARI
together in a single square meter of space.
rates similar to those of children in rural areas, even though urban
The risk that Hajj pilgrims can spread infectious diseases when they
populations tend to be healthier overall.
return to their countries of origins is well established. In the 19th
Instead, Saudi Arabia urged high-risk individualsthe elderly, pregnant
century, returning pilgrims contributed to a global cholera outbreak,
women, people with chronic diseases, and childrento postpone their
and Hajj-related outbreaks of meningococcal disease have occurred
Hajj. Public officials also took steps to promote hygiene, provide ad-
repeatedly over the past two decades. Tens of thousands of seasonal
equate surveillance, create facilities at ports of entry to isolate pilgrims
influenza cases also occur during the typical Hajj. Crowded conditions,
with influenza-like illnesses, establish systems for laboratory testing and
followed by journeys through airports, long flights, and celebrations
mandatory reporting, and treat patients with antiviral therapies.
Overcrowded housing is not solely an urban phenomenon. Among

the Nunavut people living in Canadas remote Arctic region, pandemic H1N1 influenza has spread rapidly. Despite the isolation, as
many as 18 people share houses in some of Nunavut communities,
sometimes sleeping in shifts.
upon returning home, help pathogens to move readily around

the world.
Persuading vulnerable populations to stay home may well have been

Saudi Arabias single most effective approach to limiting the spread of
In June 2009, with the H1N1 influenza pandemic underway, the
infection, although the absence of published comprehensive surveillance
Saudi Arabian Ministry of Health convened a meeting with global
data makes success somewhat difficult to measure. WHO, however,
public health experts to develop a plan to control disease spread. They
reported 9,355 cases and 81 fatalities in 2009, the largest caseload in the
recognized that most visitors would not be vaccinated and that other
region. Sharing country and regional data is fundamental to worldwide
safety measures, including airport screening to identify passengers
infection control.
with fever and isolate them, could not prevent all transmission,
especially since there was no way to identify asymptomatic individuals

To improve housing conditions and strengthen communities:
Build housing that meets appropriate standards for ventilation,
density, and habitable space per person. The American Society
of Heating, Refrigeration and Air-Conditioning Engineers and the
International Society of Indoor Air Quality are among those
recommending and evaluating healthy standards.
Provide resources that allow the urban poor to own land and build
incubating the virus.

Promote community input and collective efforts to improve living
conditions. Non-governmental organizations with proven track
records in engaging affected populations need resources, technical
assistance, and other support to manage these efforts.
Develop creative planning, land-use, and transportation policies
that accommodate sustainable growth. Effective leadership, broadbased participation, and partnerships are essential tools for success.
or improve their own housing. Efforts to organize and strengthen

communities should emphasize local assets and resiliency.
The Pilgrimage to Mecca
Number of Pilgrims Arriving for Hajj from Abroad (2005)
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8/31/10 11:09 AM
Part 3
Prevention, Diagnoses and Treatment
Many acute respiratory infections can be

prevented, and others can be cured, if they are
identified early and treated promptly.
But children continue to die from diseases that are preventable by vaccine, some once-effective
antibiotics are losing their power, and access to health care remains limited in many regions.
Adequate resources, effective partnerships, and national and international commitments can
help to reverse all of that.
Strategies to prevent, diagnose, and treat ARIs include:

Strengthen the vaccine delivery infrastructure, integrate immunizations with other health
care services, and provide resources to distribute existing vaccines more widely.
Implement educational campaigns to inform families about the importance of vaccines and
the early warning signs of acute respiratory infections that indicate the need to seek care.
Support state-of-the-art surveillance systems that allow new infectious agents to be
identified as they emerge.
Combat antimicrobial drug resistance with multifaceted educational initiatives, aggressive
policy interventions, and rigorous clinical practice guidelines.
Provide incentives to engage the pharmaceutical industry in antibiotic research
and development.
Scale up primary care and community case management.
Expand, train, and support the health workforce while offering incentives to locate workers
where needs are greatest.
66
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8/31/10 11:11 AM
Pneumococcal deaths per

100,000 children under five* (2000)
Pneumococcal vaccine status (2008)

Vaccine introduced nationwide
500
Vaccine introduced in part of the country
300-500
Applied for GAVI support to introduce vaccine
100-300
No vaccine
10-100
<10
* HIV-negative only
Most of the world still lacks the pneumococcal vaccine.
Preventing ARIs
with Vaccines
Wider use of inexpensive vaccines can
prevent millions of deaths over the next
decade from pneumonia, influenza,
and pertussis.
Pneumococcal death rates are much higher where the vaccine is unavailable.
Vaccines are one of the most cost-effective preventive tools available,
countries. Almost three-quarters of the children who have not received
Still, with global immunization campaigns reaching ever-larger popula-
and in recent years, meaningful progress has been made in using
the three recommended doses of the DTP vaccine live in just ten coun-
tions in the 21st century, there is cause for hope. By the end of 2008:
them to reduce acute respiratory inspections. The Global Alliance for
tries, all of them in Asia and Africa.
Vaccines and Immunisation (GAVI), a partnership of international

health agencies, donors, industry, and governments of developed and
developing countries that has been operating since 2000, has made
pneumonia one of its two highest priorities (the other is diarrhea) (see
Financing Immunization Campaigns, p. 71).
The opportunity to transform patterns of ARIs is evident in the developed
world, where widespread vaccination has dramatically reduced death
from pediatric pneumonia and pertussis, has lessened the risk of
influenza, and has almost eradicated measles. (Pneumonia is a common
complication of both pertussis and measles.) Streptococcus pneumoniae
vaccine alone reduces hospital admissions linked to pneumonia by almost
40 percent. Immunization against pertussis, via the primary diphtheriatetanus-pertussis (DTP) series, has eliminated 78 percent of the deaths
that would have otherwise occurred from the disease.
More than 31 countries had introduced the pneumococcal vaccine,
In 2008, 735,000 deaths from pneumococcal diseases and 363,000 from
and 15 others, including 11 in Africa, had applied for GAVI support
Hib could have been avoided in HIV-negative children, mostly in the
to fund that vaccine. WHO predicts the pneumococcal vaccine
developing world. (In addition to pneumonia, these figures include
could prevent some 262,000 deaths a year in 72 of the worlds
deaths from meningitis and sepsis, which are caused by the same
poorest countries.
bacteria but are not ARIs.) An estimated 254,000 deaths from pertussis
also could have been prevented.
One hundred thirty-six countries had introduced vaccines against

Haemophilus influenzae type b, either nationwide or in part of the
Much more can be done to distribute existing vaccines, develop new
country, compared with just 26 countries in 1997. Forty-two million
ones, and close the so-called vaccine gap, reflecting the average 15 to
children had received the vaccination. The vaccine was available in
20 years separating access to a vaccine by developed and developing
Central and South America and much of Africa, but not in India,
countries. A stronger vaccine delivery infrastructure, guided by
China, or many other Asian countries.
effective leaders and greater commitment from governments and the

international community, can reach more children and save millions of
lives. But it will take resources, and right now GAVI says it is facing a
A record 106 million infants, or 82 percent of the worlds children,

had been vaccinated against pertussis.
US$4.3 billion shortfall to meet its goals.
But acute respiratory infections continue to kill children who do not get
preventive vaccinesand those children are generally poor. In low-income countries, pneumonia kills 7,320 out of 100,000 children younger
than age five every year, compared with just 34 children in high-income
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8/31/10 11:11 AM
Preventing ARIs
with Vaccines
Global Impact
Ninety-three percent of the worlds children121 million
peoplehad not received a pneumococcal vaccine, and
71 percent, or 93 million children, had not received the
Hib vaccine, as of 2008.
The burden of vaccine-preventable diseases, which are responsible for one-quarter of global childhood deaths every year, falls
on the poor. In low-income countries, pneumonia kills 7,320
out of 100,000 children under age five, compared with just
34 children in high-income countries.
A system to regulate vaccines, such as that overseen by the
U.S. Food and Drug Administration, exists in all developed
countries but in only one-quarter of developing countries, yet
vaccine production increasingly occurs in Brazil, China, India,
and other developing countries.
Immunization Disparities
Influenza: Routine seasonal influenza vaccinations are generally
The GAVI campaign: The Global Alliance for Vaccines and Immunisation
available for at-risk populations only in developed countries, and
is spearheading international efforts to increase access to pneumonia
Poverty remains a persistent barrier to immunization at both the country
equitable distribution seems unlikely under pandemic conditions. The
vaccines. This partnership brings together WHO, UNICEF, the World
and household levels. The starkest disparities exist between vaccine rates
United States purchased 250 million doses of a vaccine against the
Bank, governments of donor countries, governments of developing
in developed and developing countries, but even in wealthier countries,
H1N1 influenza virus for its population in 2009, while WHO, relying on
countries, philanthropy, and private industry. The bulk of the financial
with their generally high rates of immunization, income has an influence.
donated vaccines, was able to secure only about 200 million doses for 95
support comes from seven donor countries, with additional resources
countries representing one-third of the global population.
provided by the European Commission, the Bill & Melinda Gates
Pneumonia: Vaccines to safeguard against the bacterial strains of
Foundation, and other private donors.
Streptococcus pneumoniae prevalent in the developing world began to
Pertussis: By the end of 2008, 82 percent of the worlds infants had
be distributed in 2009, making it too soon to measure their impact.
been vaccinated against pertussis, as part of the diphtheria-tetanus-
GAVI currently funds immunization campaigns in 72 low-income
(Effective pneumococcal vaccines were routinely available almost a
pertussis series given before the age of one. But substantial vaccination
countries, such as Afghanistan, Bangladesh, Cambodia, Haiti, Kenya,
decade earlier in the wealthier nations that were more able to pay for
disparities remain: Pertussis causes 40 deaths per 1,000 cases in
Mozambique, Nicaragua, Pakistan, Rwanda, and Zimbabwe. As of
them.) In 2010, two drug companies agreed to supply 600 million doses
developing countries, compared with one death per 1,000 cases in the
2011, eligible countries will be required to have annual, per-capita gross
of deeply discounted pneumococcal vaccine over ten years to poor
developed world.
national incomes of less than US$1,500, with annual increases designed
countries.
to keep up with inflation.
Likewise, the impact of a recent international commitment to distribute
Financing Immunization Campaigns
Haemophilus influenzae type b vaccine has yet to be fully felt. In 2003,
Substantial resources are available to provide vaccines in low-income
US$7 billion campaign to distribute three vaccines: a five-in-one vaccine
countriesbut more are needed. As of 2008, low-income countries were
that provides protection against Hib disease, diphtheria, tetanus, pertus-
paying 39 percent of the total cost of their own immunization programs,
sis, and hepatitis B, as well as vaccines to prevent pneumococcal disease
up from 35 percent in 2000, but this still underscores the need for
and rotavirus diarrhea. But as of March 2010, the organization had only
donor support.
US$3 billion in hand for that effort, and the shortfall jeopardizes its goals.
92 percent of children in developed countries were vaccinated against

Hib, compared with just eight percent in the worlds poorest countries.
But in 2006, WHO recommended that the Hib vaccine become part of
all routine immunization programs, and its use is increasing. Where
they are administered, Hib vaccines virtually eliminate the diseases
Million of lives could be saved by 2015 if GAVI is able to implement its
associated with the bacteria.
Percent of population covered by

Hib vaccine (2008)
Hib death rates per 100,000

children under five* (2000)
Hib 80%
200
Hib <80%
Hib vaccine introduced but no coverage
data reported
Hib vaccine not introduced
100-200
25-100
10-25
The Hib vaccine has been widely

introduced in 102 countries.
70
<10
* HIV-negative only
Hib death rates are much higher in countries

where the vaccine is unavailable.
71
8/31/10 11:12 AM
Preventing ARIs
with Vaccines
The Vaccine Gap:

National income is a key influence on how quickly a vaccine is introduced.
Rate of Cumulative Introduction
Cumulative country introductions
50
Herd immunity: Vaccines do more than protect those who actually

receive them; if enough people are immunized, they can also protect a
community. Infectious pathogens are less able to gain a foothold in a
resistant population so that individuals who are too young, medically

More financial resources are needed to distribute vaccines.
High-income
Hib
Pneumococcal
ineligible, or otherwise unable or unwilling to be vaccinated derive
Despite significant donor commitments and innovative
benefit from those who do get the vaccines.
funding mechanisms, the Global Alliance for Vaccines and
30
Upper-middle-income
Hib
Pneumococcal
The benefits of herd immunity were apparent both in the United
20
Lower-middle-income
Hib
Pneumococcal
significantly among vaccinated and non-vaccinated populations after
40
10
0
Lower-income
Hib
Pneumococcal
1
11
13
15
17
19
21
Years after first introduction
Innovative financing: GAVI uses two innovative financial mechanisms

to supplement donor pledges:
The International Finance Facility for Immunization builds on
long-term donor commitments to GAVI programs to issue bonds
on international capital markets. This mechanism raised more than
US$2.3 billion in financing from 2006 to 2009, leveraging sixfold the
legally binding pledges made by donors.
Advance Market Commitment, launched in 2009, is a contract that
guarantees pharmaceutical companies a market for their vaccines
in exchange for pricing them at a fraction of what they charge in
developed countries. (For example, with an advance market commitment, the existing pneumococcal vaccine sold at US$70 per dose
in the developed world will cost US$3.50 in developing countries.)
Some advocates believe the arrangement is too generous to the drug
industry and should be overhauled to promote competition.
The availability of a vaccine does not

ensure its use. Strengthening local access
to health care, training providers, and
educating families about the importance
of vaccinations also play a role.
72
Promoting Wider Vaccine Use

The availability of a vaccine does not ensure its use. Strengthening local
States and the Gambia, where the incidence of disease dropped
vaccine delivery infrastructure, effective leadership, national

commitment, efforts to integrate immunization programs
as an appropriate social norm.
with other health care services, and engaged communities that
The anti-vaccine movement: In 1998, the British medical journal The

Lancet published an article linking the measles, mumps and rubella vaccluded the author had acted dishonestly and irresponsibly and with
antivaccine movement has been built on the discredited fear
callous disregard, and The Lancet retracted the article soon afterward.
that vaccines are linked to autism. And in some developing
educating families about the importance of vaccinations also play a role.
stream medicine and the Internets remarkable capacity to spread
Communications campaigns that inform families about the

availability of vaccines.
Outreach to target populations with low coverage rates.
Engagement with communities to increase demand for vaccines.
unsubstantiated ideas. One researcher counted more than 180 anti-
health workers who deliver immunizations, and involve communities
New vaccines are needed to combat RSV and other acute

the effectiveness of existing vaccines, reducing the required
promulgating conspiracy theories.
immunization dose, and developing all-in-one combinations.
Responding to lingering concerns, the Institute of Medicine, the U.S.

Centers for Disease Control and Prevention, WHO, and a number of
peer-reviewed studies examined the possibility of a cause-and-effect
relationshipand determined there was none.
Nonetheless, the anti-vaccine movement has had an impact. In the U.S.,
requests have grown for exemptions from state vaccine requirements on
the vaccine. And in countries where DTP immunization was disrupted
ensure the availability of vaccines even in remote locations, supervise
children and destroy the tribe.
respiratory infections. Research should also focus on improving
The Reaching Every District (RED) campaign organized by WHO,
engage in data-driven efforts to identify difficult-to-reach populations,
peoples believe that vaccines are being used to sterilize their
the purported link between vaccines and autism, others dedicated to
religious or personal belief grounds. In South Africa, a 2010 measles
approach provides resources and support to help local health officials
countries, other fears hold sway: In one region of Nigeria, tribal
vaccine advocacy websites, some of them sober calls for research into
Better integration of immunization with other health care services.
UNICEF, and others is an example of outreach at the district level. This
Efforts are needed to combat misunderstanding and lack of

information about vaccines. In some developed countries, an
driven not only by falsified research but by skepticism about main-
immunization campaigns.
understand the value of vaccines.
cine to autism. In 2010, medical authorities in the United Kingdom con-
ers to routinely remind patients that they are due for immunizations, and
Leadership and a national commitment to strong
Immunizing more children and adults depends on a strong
results helps people understand the value of immunization and accept it
In the intervening years, an influential anti-vaccine movement arose,
delivery infrastructure and emphasizing:
goals for reducing the toll of vaccine-preventable diseases.
the pneumococcal vaccine was introduced. Highlighting these kinds of
access to health care (see Access to Health Care, p. 82), training provid-
Immunization rates can be increased by strengthening a nations vaccine
Immunisation does not have the resources to meet its 2015
outbreak appears to have been linked to fears of autism associated with

by antivaccine movements (including Russia, Australia, Japan, and some
in Europe), the incidence of pertussis was 10 to 100 times higher than
in countries that maintained high rates of DTP vaccination coverage
(including Hungary, the former East Germany, and Poland).
in planning and delivering services. A 2005 evaluation of five African
The choice not to be vaccinated goes beyond the personalby lessening
countries that had implemented RED found that the number of children
herd immunity, it puts others at risk, and that is a message that public
who had not been immunized had fallen from three to 1.9 million.
health officials need to communicate more clearly.
73
8/31/10 11:12 AM
Diagnoses and
Surveillance
More resources for diagnostic tools and
surveillance will lessen the toll of ARIs.
Global Impact
Identifying acute respiratory infections quickly is an urgent matter. At the

level of the individual patient, early diagnosis allows for prompt treat-
Surveillance Techniques
ment, while at the community level, ongoing surveillance is essential for
Surveillance, conducted by public health entities at the local, national,
detecting new pathogens and unusual disease patterns, possibly while an
and international levels, is the foundation of preparedness, providing
outbreak can still be contained. The tools of both clinical care and public
essential information about new pathogens, patterns of infection,
health are essential here, as is communication between these two fields.
and local disease outbreaks. Key data help to describe the pace of an
infections spread, the severity of the illness it causes, and who is at
Diagnosing ARIs
risk. WHOs Global Influenza Surveillance Network, which relies on
Diagnosing acute respiratory infections is often complicated by the
example of how local surveillance can be aggregated to detect
presence of symptoms common to many different illnesses (such as
larger patterns.
fever), the presence of multiple medical conditions in an individual
reporting from National Influenza Centres in 104 countries, is an
patient, and the way in which an infection changes course over time.
By sounding an early warning, effective surveillance allows time to pre-
the infrastructure to support optimal approaches to diagnoses
If local resources are plentiful, gold-standard diagnostic tools can be put
and surveillance is unavailable in many locations.
the H1N1 influenza virus first appeared, and to implement public health
to use. These may include chest X-rays, pulmonary biopsies, bacterial
measures that can slow the spread of an infection or even stop it alto-
and viral cultures, and polymerase chain reaction assays (a DNA-based
gether, as appears to have occurred with SARS. (See H1N1: The First
technique used to identify a specific strain of pathogen). But laboratory
21st-Century Flu Pandemic, p. 30, and Profile: The SARS Story, p. 42.)
Infection can spread quickly in an interconnected world, and
Barriers to a timely diagnosis can include delays in obtaining

test results, lack of supplies or equipment, lack of familiarity
with testing protocols, inconvenience, and cost.
Surveillance alerts public health authorities to illness surges so
that they can act before a new, highly transmissible, or especially dangerous virus spreads to the human population.
testing is not available in many developing countries, and even where

lab resources are adequate, treatment for a worsening infection cannot
In resource-poor countries, surveillance may be patchy, nonexistent,

or of poor quality. Workers often lack the skills to conduct on-site
Education and training: Family members, community health workers,
to communicate their findings may not be available. Investments in
investigations and analyses, and the infrastructure allowing them
and clinicians all have roles to play in diagnosing ARIs accurately
communications (including Internet connections and geographic
enough to start treatment, even if the diagnosis is only on the basis
information systems) and rigorous worker training are essential.
breathing characteristic of pneumonia, so caregivers can be educated

to know when to bring a child into the health system, and community
health workers can be alert to danger. Medical associations, public
health entities, and advocacy groups can arm providers with clinical
decisionmaking guidelines to help them ask the right questions,
recognize warning signs, make rapid assessments, and begin
timely therapy.
Community laboratories: The Community Laboratory Initiative is a
pioneering idea to develop a bottom-up strategy for increasing access
to diagnostic tools, especially in remote and rural regions of developing
countries. The concept, under discussion by WHO, the U.S. Centers
for Disease Control and Prevention, the Earth Institute at Columbia
University, and the Foundation for Innovative New Diagnostics, is to
build a network of decentralized community-based laboratories that
would complement a national laboratory infrastructure. Administered
Sentinel
surveillance
Syndromic
surveillance
Zoonotic
surveillance
In a laboratory-based surveillance
model, the appropriate authorities are
notified if the lab-confirmed diagnosis
appears on a list of reportable diseases.
This targeted approach draws on data

from sentinel sites, typically hospitals,
ambulatory settings, or nursing homes,
which mirror the general population.
pare an adequate response, as many nations did when the novel form of
always wait until results become available.
of a best guess. Certain signs are highly specific, such as the rapid
Laboratory
surveillance
Rather than identify a specific infectious

disease, syndromic surveillance gathers
information about trends that suggest
case spikes or a new outbreak.
Trends in animal diseases may be observed,

since many pathogens implicated in human
ARIs have been identified previously in
animals (especially influenza viruses,
which tend to originate in swine and birds).
Effective surveillance targeted at acute respiratory infections can be

used to:
Determine the distribution and spread of infection and estimate
its impact.
Detect outbreak spikes and sound an early warning
about pandemics.
Inform prevention and response strategies.
Describe the infections natural history and identify high-risk groups.
Develop population-based interventions.
Evaluate control measures.
Generate research questions and facilitate planning.

Community-based initiatives to improve diagnoses and
track the course of an infection include educating family
members, arming clinicians with decision-making tools, and
developing diagnostic techniques that are feasible in resourcepoor environments.
Two-way communication between clinicians and public health
agencies can call attention to unusual patterns of disease.
Laboratory diagnoses and reporting should be combined with
less resource-intensive surveillance approaches such as sentinel
and syndrome surveillance, which can produce data quickly.
by community health workers, these labs would provide a baseline

package of testing services at the village level. The model has not been
fully developed and there are no strategies yet in place for funding it.
74
75
8/31/10 11:12 AM
Diagnoses and
Surveillance
Sentinel surveillance: This targeted approach draws on data from

sentinel sites, typically hospitals, ambulatory settings, or nursing homes,
which mirror the general population. Patterns of diseases are identified
by a combination of clinical and laboratory reports collected from these
sites, which should reflect the ethnic and socioeconomic composition
of the country, be located in different climates and regions, and have the
resources, communication networks, and transportation infrastructure
necessary for timely reporting.
disease, syndromic surveillance gathers information about trends that

suggest case spikes or a new outbreak. Potential data sources, typically
available electronically, include logs of emergency room visits, school or
work absenteeism, calls to medical hotlines, sales of over-the-counter
medication, and patterns of online queries.
A number of surveillance strategies may be appropriate, depending on
Zoonotic surveillance: Many pathogens implicated in human ARIs
the public health issue of concern, the nature and immediacy of the
have been identified previously in animals (especially influenza viruses,
information needed, and the available resources:
which tend to originate in swine and birds). Animals are also considered
infections have overlapping symptoms, testing blood or tissue samples

in the laboratory is the only sure way to identify a specific diseasecausing pathogen. In a laboratory-based surveillance model, the
appropriate authorities are notified if the diagnosis appears on a list
Profile: Integrated
Approaches to Reduce
ARIs in India
More than one million people die from acute respiratory infections in India
every year, about one-quarter of the worldwide total, and 43 million cases of
Syndromic surveillance: Rather than identify a specific infectious
Laboratory-based surveillance: Since many acute respiratory
the likely source of emerging infectious diseases. Recognizing the

interconnections among humans, pets, wildlife, agricultural animals,
and the environment, zoonotic surveillance requires an integrated
approach that draws on data and expertise in all of the
associated disciplines.
pneumonia occur. The death toll from ARIs among Indians is higher than
all deaths from HIV/AIDS, malaria, and tuberculosis combined.
All of the basic ARI drivers play a role, with indoor air pollution a primary culprit (wood- or coal-burning stoves are used by 826 million Indians)
Along with emphasizing immunizations and feeding advice, components
and malnutrition a close second. Tobacco, used by some 241 million
of this strategy include strengthening infrastructure and the skills of
Indians, also contributes significantly to ARI mortality, as does over-
health care workers, and involving the community.
crowding, a situation certain to worsen as the urban slum population

doubles over the next decade, to as much as 200 million.
The Work Ahead
WHO calculates total deaths associated with acute respiratory infections
Declining childhood mortalityfrom 116 deaths per 1,000 children
by region (see World Regions p.98). Estimates in the lower- and
under age five in 1990 to 69 deaths per 1,000 children in 2008suggest
middle-income countries of South/East Asia are as follows (Indias
that some combination of strategies is working in India. But the
1.1 billion residents represent two-thirds of this population):
magnitude of the problem continues to demand attention.
217,900 ARI deaths attributable to indoor air pollution
Immunization coverage is a particular concern: Only 44 percent of all
171,000 ARI deaths attributable to underweight
of reportable diseases. Though laboratory testing is a core component

of comprehensive surveillance, collecting and aggregating this data is
75,800 ARI deaths attributable to tobacco
resource-intensive and time-consuming, and complementary strategies

are needed to identify trends more quickly.
37,600 ARI deaths attributable to outdoor air pollution

For each risk factor, the region of South/East Asia has roughly twice
the number of ARI deaths, compared with the average among all
Reasons given for

not testing for pertussis 0%
25%
Delay in obtaining
test results
52%
Inconvenience of
sample collection
29%
Lack of testing supplies
29%
Lack of familiarity
with testing protocols
28%
Cost
22%
50%
75%
Sixteen percent of American doctors sampled said they did not test adolescents for pertussis.
As with many ARIs, pertussis often goes undiagnosed.
100%
seven WHO regions.
ARI Control Programs

Beginning in 1990, India established a program to standardize case
management of pneumonia with antimicrobial agents, yet cases continued to be misclassified and inadequately treated.
Subsequently, India took a more holistic approach, integrating ARI control with other strategies to improve the overall health status of women
and children. Indias model builds on findings that ailing children under
age five are likely to have more than one health problem, and that focusing on a single disease may result in missed prevention opportunities.
76
children under five were fully immunized, and coverage is lower in

urban slums and rural areas. With research showing that living within
two kilometers of an urban health center doubles the likelihood that
a child will be fully immunized, expanding access to primary care is
essential. Also important is increasing the availability of community
health workers, called anganwadi workers in India.
Distributing new stoves: Through the National Biomass Cook-Stoves
Initiative, launched in 2009, India has begun distributing low-emissions
stoves to rural households. Although the government has not yet
established targets for this initiative, researchers have estimated that 87
percent of Indian households could gain access to clean stoves over the
next ten years. The result could be that 240,000 fewer children under
age five would die from acute respiratory infections.
Scaling up interventions: Scaling up breastfeeding, vaccinations, and
case management, as outlined in the WHO/UNICEF Global Action
Plan for Prevention and Control of Pneumonia (GAPP), could save
1.2 million post-neonatal pneumonia deaths worldwide by 2015. The
cost to execute that plan on a global scale is estimated at US$39 billion,
including US$13 billion for China and US$7 billion for India.
77
8/31/10 11:12 AM
Antibiotics and
Antiviral Therapy
ARIs can be sharply reduced with
appropriate use and careful stewardship
of antimicrobial therapies.
Antimicrobialsantibiotics, antivirals, and antifungalsare lifesaving
therapies for treating acute respiratory infections. Many types of
bacterial pneumonia and a significant proportion of TB cases can be
cured when the correct antibiotics are administered promptly, at an
Over time, microbes often evolve to evade the pharmaceuticals that once
acted so effectively against them. WHO has called this antimicrobial
resistance one of the three greatest threats to human health. Unless new
Practices in both developed and developing countries highlight the issues:

In the United States, antibiotics are the second most commonly
prescribed class of drugs, and as much as half of those prescriptions
therapies are developed, tested, approved, manufactured and distributed,
are unnecessary or inappropriate.
once-treatable diseases will once again become untreatable.
How Drug Resistance Develops
A so-called antibiotic culture exists in some Latin American

countries, promoting a careless assumption that any unidentified fever
and many other symptoms should promptly be treated with the drugs.
Most acute respiratory infections can no longer be cured by at least some of

the drugs that were once effective. For example, 40 percent of Streptococcus
A survey of almost 5,400 people (mostly in Europe, but also on
pneumoniae has some degree of resistance to penicillin, and as much as
three other continents) found antibiotics widely available without a
one-third of it can resist the macrolide class of drugs. Almost all seasonal
prescription. Twenty-five percent of respondents indicated that they
H1N1 influenza has ceased to be treatable with oseltamivir (Tamiflu).
saved leftover drugs for later use.
appropriate dose, and for the right period of time. Antivirals can reduce
Biological bases: Even when antimicrobial drugs are used correctly,
The lack of office-based diagnostic tools to distinguish bacterial and
the severity of influenza or prevent it altogether. Coupled with accurate
resistance tends to occur over time as microbes adapt to their
viral infections, along with the inaccessibility of laboratory facilities in
diagnoses and appropriate access to care, these medicines are the
environment. Biological mechanisms that promote resistance include:
many regions, worsens the problem because a clinician may think it
foundation of effective treatment.
Selective pressure: While a drug may be generally effective against

a class of microbes, some members of that class typically have a
genetic structure that enables them to survive. As drugs kill off
the nonresistant microbes, the survivors reproduce and become
Global Impact
Only about one-third of all children under five with suspected
pneumonia received an antibiotic in the 68 countries that bear
the worlds highest burden of childhood and maternal mortality.
Making antibiotics available to children who need them could
save as many as 600,000 lives every year.
Drug resistance is one of todays most pressing public health
challenges, especially resistance to the antibiotics used to treat
Streptococcus pneumoniae, Haemophilus influenzae type b, and
tuberculosis, and resistance to the antivirals that once worked
against influenza.
Very few new antimicrobials are in the pharmaceutical
(see Diagnoses and Surveillance, p. 74). In many developing countries,

overcrowded living conditions add further pressure by allowing microbes
to mingle and transfer resistant genes (see Overcrowding, p. 62).
dominant and harder to eliminate.

Mutation: Microbes reproduce quickly and mutations arise as they
do, including mutations that resist targeted drugs. These mutations
then prevail through selective pressure.
Gene transfer: Microbes can transfer genes to one another,
including genes that are programmed to resist drug therapy.
5%
uninformed patients exacerbate the natural causes of drug resistance.
4%
confidence in their health providers, and costs. In some cultures, people

also insist on antibiotics for influenza and sore throats of viral origin,
even though antibiotics are completely ineffective against viruses.
Responding to patient pressure or their own practice habits, doctors,
existing drugs, but many companies have stopped developing
community health workers, pharmacy technicians, and traditional
alternatives because they fear the useful life of new products
healers often dispense antibiotics too freely.
which occurs even when antimicrobials are used appropriately

and intensifies when they are not. Altering prescribing and drug
use practices requires aggressive education, sweeping policy
4
3%
3
Individuals often fail to complete a full course of therapy for a host of

reasons that include lack of knowledge about proper dosing, lack of

There is no magic bullet to the problem of drug resistance,
Societal contributors: Antibiotic overuse and misuse by clinicians and
industry pipeline. Microbes continue to develop resistance to
will be short and the market limited.
prudent to prescribe antibiotics until a definitive diagnosis can be made
2%
2
interventions, and rigorous practice guidelines targeted at

patients, clinicians, and the general public.
National and local policies should bar the sale of antibiotics
without prescription, and mechanisms to enforce those policies
should be in place.
1%
A long-term sustainable commitment to stimulate antimicrobial

research should be guided by leaders in government, medicine,
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998
Number of fluoroquinolone
antibiotic prescriptions per
100 persons in Canada
0%
Percent of pneumococci with reduced

susceptibility to fluoroquinolones
among patients ages 15-64 in Canada
industry, academia and public health. The Infectious Disease

Society of America is spearheading the 10 x 20 initiative, a
collaborative venture to develop 10 new systemic antibacterial
drugs by 2020.
As prescriptions for antibiotics increase,

so does resistance.
78
79
8/31/10 11:12 AM
Antibiotics and
Antiviral Therapy
The Research and Development Drought
The Infectious Disease Society of America has made a number of
As resistant microbial strains emerge, new therapies are needed to
may be useful to other nations as well:
research priorities.
new drugs. That number has dropped steadily, and only five big firms
now have major antibiotic discovery programs in place, although
Consider incentives that encourage drug companies to develop new
many smaller biotechnology firms do so as well. The pipeline for new
therapeutics and rapid diagnostic tests, including extended patent
antibiotics currently contains fewer investigational drugs than it has in
protections, tax breaks, limited liability, and a guaranteed market.
decades.
Modify policies at research and regulatory entities, notably the
Despite a US$25 billion annual market for antibiotics, the industrys
National Institute of Allergy and Infectious Diseases and the Food
declining interest reflects concerns that resistance will limit the length
and Drug Administration, to expand clinical trials, encourage
of time that a drug remains useful. Industry officials may also expect
creative designs, and reach conclusions more quickly.
public health officials to discourage widespread use of any new drug in

order to maintain its effectiveness for as long as possible.
Number of approved new antibiotics
Establish an independent commission to identify antimicrobial
flourishing, with 15 major pharmaceutical companies searching for
In many instances, the push for antibiotics by individual patients clashes
because patients typically take these drugs for only a few weeks
with the pull of the public health community toward restraint. Given
(compared with the lifetime use of blood pressure and cholesterol
the dangers of drug resistance and the absence of drugs in the pipeline,
medicines, for example), and because the pathogens of concern may
clinicians, public health practitioners, and the general public share an
change considerably during the 10 to 12 years it takes to move a new
obligation to become better stewards of existing antimicrobial therapy.
drug from discovery to regulatory approval.
Misuse of Antibiotics
Among the research documenting a widespread misuse of
16
antibiotics:
14
12
Self-medication with antibiotics is common in parts of Europe.
10
On the basis of more than 15,500 responses from 19 countries,

self-medication is practiced by as few as one respondent per
1,000 (in the Netherlands) and as many as 210 per 1,000 (in
Lithuania). On average, antibiotics were used for five days, but

the shortest use was one day, the longest 100 days.
4
2
0
In Sudan, half the 1,750 adults surveyed indicated they had self1983-87
1988-92
1993-97
1998-2002
2003-07
Preventing Drug Resistance
Antibiotic research is also less appealing to pharmaceutical companies
medicated with antibiotics in the previous month, primarily

because it was less costly than seeking other health care.
In Mexico, poorly trained clinicians, poor-quality drugs, easy
Although no single strategy will alter all of the factors that influence
access to antibiotics without a prescription, and overcrowded
misuse, a combination of approaches can make a difference:
living conditions are all likely contributors to bacterial
Culturally appropriate education, presented in a range of venues

and formats, should be targeted at audiences with various levels of
knowledge and literacy. Public health campaigns should emphasize
resistance problems that exceed global averages. Seventy

percent of S. pneumoniae cases in Mexico are resistant
to penicillin.
that not all infections require antimicrobials and should underscore
35%
Percent of S. pneumoniae resistant to antibiotics
The number of new antibiotics approved

for sale in the U.S. is declining.
proposals to stimulate new research in the United States, many of which
treat acute respiratory infections. In the 1980s, antibiotic research was
the broad health risks of drug resistance.
30%
Drug recommendations should be modified as appropriate after a

laboratory diagnosis is made. Broad-spectrum antibiotics are often
prescribed when doctors do not know exactly which pathogens
25%
are causing an infection, but a more targeted prescription may be

appropriate once they do.
20%
Packaging drugs to highlight the correct dosage and duration of use

can help to improve patient compliance.
15%
Hospitals, clinics, and nursing homes should develop diagnostic

and prescribing guidelines, formularies that limit drug choices,
10%
and hygienic practices that reduce infection. Physicians could be

required to seek prior approval from an infectious disease specialist
5%
0%
before writing antimicrobial prescriptions.

1992
1993
1994
1995
1996
Penicillin-resistant
1997
1998
1999
Partially penicillin-resistant
2000
2001
2002
2003
2004
Macrolide-resistant
Antibiotic-resistant strains of S. pneumoniae threaten to undermine treatment for pneumonia.

80
National and local policies should bar the sale of antimicrobials

without prescription, and those policies should be enforced. Developing treatment guidelines and lists of essential drugs at the national
level, with allowances made for local modifications, also helps to
establish a baseline of appropriate use.
81
8/31/10 11:12 AM
A study of children in the slums of India found that those who lived
within two kilometers of an urban health center were twice as likely
to have been fully immunized as those living farther away.
Nicaragua introduced community-based care provided by lay
health workers in four remote rural areas in 2006. Rather than
having to travel to distant, facility-based services, families gained
24-hour access to brigidistas who were trained to diagnose and treat
Physicians per
10,000 people
common infections.
>20
The result: In a country where only 57 percent of children under age
11-20
five receive appropriate treatment for suspected pneumonia, use of
6-10
curative services increased at least fivefold in the pilot communities.
2-5
1
Despite these replicable models, lack of primary care, resource gaps,

workforce shortages, and caregiver behavior remain significant barriers
to care.
In some parts of the world there is only one physician for every
10,000 peopleand sometimes not even one.
Global Impact
The availability of good medical care tends to vary inversely
with the need for it in the population served, wrote British
physician-advocate Julian Tudor Hart 40 years ago. The
comment remains valid todayin both developed and
developing countries, health workers disproportionately serve
the wealthy and the urban.
Thirty WHO member states currently spend less than US$20
per person per year on basic lifesaving health care services
(including spending by government, households, the private
sector, and external donors). Minimum spending should be
US$35-50, according to WHO.
The global health care workforce is short 4.25 million people,
according to WHO. Fifty-seven countries, most of them in
Africa and Asia, face the most severe worker shortages.
Access to Health Care

A strengthened health system and a
well-trained workforce are essential for
preventing, diagnosing, and treating ARIs.
An accessible and efficient health care system is a cornerstone in
the effort to lessen the toll of acute respiratory infections. Timely
prevention, ongoing surveillance, accurate diagnoses, and effective
treatment all require that a combination of public health and clinical
care tools be made available to the broadest possible population.
Models of access: The health advantages conferred by timely access to
care are illustrated by these examples:
In rural Tanzania, village health workers were trained to make
home visits to each family in their district every six to eight
weeks. These visits were opportunities to provide education on
recognizing and preventing acute respiratory infections, on-thespot treatment, and referrals if necessary. Two years after the
programs launch, deaths from pneumonia among children under
five had fallen 30 percent.
82
Gaps in Health Care Spending

WHO estimates that countries need to spend a minimum of
US$35-50 per person per year to provide basic, lifesaving services

Scaling up community case management guided by lay health
workers reduces acute respiratory infections and saves lives.
Various studies estimate that this approach can cut mortality
rates from ARIs by 50 to 70 percent.
Substantial investments are essential to expand, train, and
support the health workforce and to offer incentives for
locating workers in the rural and poor urban communities
where disease burdens are greatest. The unchecked flow
of health workers from developing to developed countries
undermines access to care.
Caregivers in the home should be educated about preventing
acute respiratory infections and recognizing signs that they
should seek care from an appropriate health provider.
High-income countries:
Annual health expenditure per capita (2008): US$4,704
(including spending by government, households, the private sector, and

external donors). Sixty-four WHO member states currently spend less
than US$50, and 30 states spend less than US$20.
US$651
out of pocket
(14%)
The wide gap separating the resources dedicated to health care in

developed and developing countries is apparent in these data:
In high-income countries, annual spending on health care averages
US$4,704 per person, compared with US$30 per person in
low-income countries.
Despite poverty that is sometimes extreme, individuals in lowincome countries pay a substantially higher proportion of their own
health care costs: more than 50 percent of total costs (a per-capita
annual average of US$16), compared with 14 percent of total costs
(a per-capita annual average of US$651) in high-income countries.
Together, North and South America account for more than half
of all global health expenditures. By contrast, sub-Saharan Africa
spends less than one percent of the total.
US$16
out of pocket
(53.3%)
Low-income countries:
Annual health expenditure per capita (2008): US$30
Far less is spent on health care for the worlds

poorest people, yet they pay proportionately far
more out of pocket.
83
8/31/10 11:12 AM
Also called promotoras, brigidistas, anganwadi workers, and peer
Educating caregivers: Protecting family members from acute
health educators in various countries, community health workers are
respiratory infections and accessing timely health care as necessary
trained to recognize symptoms of pneumonia and other illnesses,
begins in the home. An effective health care system includes strategies
administer antimicrobial therapy, refer severe cases to higher levels
for educating adults about prevention (including the value of proper
of care, and educate families about their roles in prevention and
breastfeeding, adherence to immunization schedules, and reducing
support. Community health workers are also indispensable in influenza
exposure to indoor pollutants) and knowing when to seek care
surveillance because they have regular contact with families and may be
(especially for the early signs of pneumonia, since the illness can be fatal
the first health providers to observe a local outbreak.
within a few days). Community health workers are uniquely suited to
Selecting, training, and supervising community health workers, defining
serve as educators.
their roles, and maintaining their commitment is often challenging.
Percent of children under five with

suspected pneumonia taken to a
health care provider (2005-08)
Nonetheless, studies in Asia have shown that this approach can cut
mortality from acute respiratory infections in half, and a number
>75%
of countries have successfully scaled up their projects to a national
51-75%
level, including Bangladesh, Bhutan, Nepal, and Sri Lanka. The use of
26-50%
community health workers is not confined to developing countries: In
0-25%
the United States, the Health Resources and Services Administration
no data
estimates there were 86,000 community health workers in 2000.
Many children with suspected pneumonia

do not see a health care provider.
Primary Care in Rural and Urban Settings
Even in wealthier countries, significant portions of the population
Acute respiratory infections take particular aim at populations in
United States are medically disenfranchised, according to the National
underdeveloped rural areas and in urban slums, yet poverty and
Association of Community Health Centers, either because they lack
provider shortages are especially likely to limit access to primary care
insurance or live in underserved areas. Without a consistent source
in these environments. Long distances, poor transportation, and other
of primary care, this population is more likely to have multiple health
infrastructure limitations are added barriers in rural settings, as is the
problems that leave them vulnerable to infections.
bias of providers toward urban practice. In Ghana, two-thirds of the

countrys population lives in rural communities, yet 87 percent of its
do not have timely access to primary care. Sixty million people in the
Community case management: One of the most widely recommended
general physicians work in urban settings.
strategies for building the primary care infrastructure is community
In many countries, a primary-care safety nettypically, public
services. Because they come from the same background as those they
hospitals and clinicshave at least some capacity to provide preventive,
serve, and live among them, community health workers have easy
diagnostic and treatment services for ARIs. But even if care is accessible
access to families and are knowledgeable about the traditional beliefs
and affordablea big if the capacity to handle infectious disease
and cultural practices that can influence willingness to seek care or to
surges is often lacking, as was evident at the peak of the H1N1 influenza
comply with medical recommendations.
case management, which uses local people to provide targeted health
Percent of children under five

with suspected pneumonia who
receive antibiotics (2005-08)
>60%
41-60%
21-40%
0-20%
no data
pandemic. Safety-net facilities may also face significant financial strains,

especially if they are not reimbursed for much of the care they provide.
Many children with suspected pneumonia do not receive antibiotics.

84
85
8/31/10 11:12 AM
Profile: Treating
Severe Pneumonia
in Malawi
Growing the Health Workforce

Workforce shortfalls threaten to undermine strategies for addressing
acute respiratory infections. WHO says the global health workforce
lacks an estimated 4.25 million people, specifically 2.36 million
health service providers (such as physicians, nurses, pharmacists, and
laboratory technicians) and 1.9 million managers and support staff.
Twenty percent of the children of Malawi, one of the poorest countries

in the world, will die before their fifth birthday, and the countrys death
Disparities: Fifty-seven countries, most of them in Africa and Asia,
rate from acute respiratory infections is exceptionally high
face the most severe worker shortages. Regions with the greatest health
227 deaths per 100,000 people (of 192 nations for whom ARI death rates
care needs have the fewest people available to meet them, as is apparent
are available, only 15 others have death rates above 200 per 100,000).
by comparing the WHO region of the Americas (North and South

America, plus the countries of the Caribbean) with sub-Saharan Africa:
The government of Malawi has made a commitment to change that with a

package of interventions that includes boosting vaccination rates, provid-
The Americas, with 14 percent of the global population, has

10 percent of the global burden of disease and 42 percent of the
A brain drain resulting from the growing migration of health care
worlds health workers.
providers from developing to developed countries is intensifying
Sub-Saharan Africa, with 11 percent of the global population, has

25 percent of the disease burden and just three percent of the worlds
health workers.
disparities and becoming an enormous barrier to care. This shift

reflects, in part, a desire among health care workers to pursue better
economic prospects and avoid the stress of providing care in resourcepoor environments. It is also significantly driven by the demand for
workers in developed countries that have aging populations and hightech health care, and that have underinvested in worker education.
The International Organization for Migration estimates that poor
countries spend US$500 million a year to educate health workers who
100%
subsequently leave for other opportunities.

Actions to meet workforce needs: Developing an adequate workforce
75%
means increasing investments designed to:

Provide continuous education and support for the current
workforce.
50%
Train more health workers while offering incentives for them to

locate where the need is greatest, typically in rural and poor urban
25%
0%
areas.
Use community health workers or other staff with lesser levels of
Global burden
of disease
Worlds health
workers
The Americas
Global health
expenditure
Sub-Saharan Africa
Sub-Saharan Africa has more disease and

fewer health care workers, and spends less on
health care, compared with the Americas.
86
training to provide some health care services.
ing vitamin supplements, empowering village health workers to provide

services, and developing protocols to improve pneumonia care.
One component of its ambitious intervention strategy is the Child Lung
Health Programme, a health service delivery strategy launched in 2000
to provide hospital-based, standardized case management for severe
pneumonia in children. The Paris-based International Union Against
Tuberculosis and Lung Disease developed the model, which each
host government integrates into its primary health care system. It was
implemented and evaluated in Malawi in collaboration with the Malawi
Ministry of Health (MoH).
The MoH initially covered 70 percent of the cost through existing services,
with the remainder provided by the Bill & Melinda Gates Foundation.
The program is now included in the MoHs essential health package and
is supported with both internal resources and donor contributions.
Training health workers: Pediatric wards in 22 district hospitals and

three central hospitals began participating in the Child Lung Health
Programme after a gradual scale-up. Hundreds of health workers have
received five days of training, guided by a Malawi-specific curriculum that
covers the sometimes-interrelated childhood lung diseases of pneumonia,
TB, asthma, and HIV-related lung disease. The curriculum also offers
guidelines on managing malnutrition, diarrhea, meningitis, malaria, and
other health challenges that may be present in vulnerable children.
Providing oxygen: Half the childhood deaths from pneumonia in
Malawi could be prevented with oxygen therapy, yet hospitals do not
always have oxygen available on pediatric wards, and health workers
often do not know how or when to administer it. Through the Child
The Child Lung Health Programme addresses three key barriers to care
Lung Health Programme, oxygen concentrators have been supplied to
the absence of appropriate health worker skills, the unreliable supply of
all pediatric wards of the participating district hospitals, and clinical
antibiotics and oxygen therapy, and the lack of routine information sys-
personnel have been trained in their use.
tems. The program includes diagnostic and treatment guidelines, training

for clinical staff, logistics for ensuring an uninterrupted drug supply, and a
framework for reporting outcomes and evaluating impact.
Success and expansion: From 2000 to 2005, the 25 participating hospitals

treated almost 49,000 pneumonia cases and saw death rates drop by more
than half, from 18.6 percent to 8.4 percent. Challenges remain, but the
program continues and is expanding into private-sector hospitals.
Structure care more efficiently, for example, by piggybacking

services so that a childs immunization schedule is routinely checked
at any medical visit.
87
8/31/10 11:12 AM
Part 4
Making ARIs a Global Priority
With adequate resources and global

commitment, the epidemic of acute respiratory
infections can be halted.
But the public health and donor communities have yet to make the same commitment to
pneumonia, influenza, and other ARIs that they have made to HIV/AIDS, malaria,
and tuberculosis.
Acute respiratory infections are in part a problem of poverty and put at special risk the
worlds most vulnerable populations, especially children. But pathogens do not always respect
geographic and economic boundaries, and many dangers are common to all. Reducing the
burden of ARIs worldwide must be a shared responsibility, and it demands better data, more
resources, and targeted prevention and treatment strategies of proven value. It also requires
broad and systemic changes built on a foundation of good governance, political will,
effective leadership, and policies that strengthen the health system infrastructure.
88
89
UN Photo/Evan Schneider
WLF_Part4_SH_0823.indd 88-89
8/31/10 11:19 AM
Identifying and
Meeting the
Worldwide Challenge
Reducing the deadly toll of ARIs
demands worldwide commitment,
recognition of the shared drivers,
and investments in proven solutions.
Global Impact
Donor priorities are heavily focused on HIV/AIDS, malaria
Gross national income,

US$ per capita (2008)
and TB, rather than ARIs. For every lost disability-adjusted
$10,001
life year, US$18.53 is spent on HIV/AIDS-related R&D for
$4,001-10,000
pharmaceuticals and related products, compared to just

US$0.31 for acute lower respiratory infections (meningitis, also
caused by pneumococcus, is included in this figure).
Researchers tend to track diseases when resources are targeted
$2,001-4,000
$1,001-2,000
<$1,000
no data
at them, leading to better data, interventions that can be

measured, and replicable results that encourage further
Many of the greatest challenges in addressing ARIs occur

in the poor countries of the world.
funding. The absence of dedicated funding for acute respiratory

infections is self-reinforcing.
Acute respiratory infections remain a neglected disease group.
and community case management are underutilized, despite their
The challenges have yet to capture the full attention of governments,
proven value in preventing pneumonia. Research on other cost-effective
donors, the global health community, the pharmaceutical industry, or
interventions, such as reducing exposure to air pollution, is in its
the public, certainly not to the same degree as HIV/AIDS, malaria
infancy. Resources dedicated to distributing lifesaving antibiotics and
or tuberculosis.
developing new ones are inadequate.
Making ARIs a global priority begins with the gathering of basic data.
Without curbing acute respiratory infections, there is little hope of
Pneumonia is almost certainly undercounted because many of the
reaching U.N. Millennium Development Goals, especially the goal of
worlds poorest nations, where child mortality rates are highest, lack
reducing the deaths of children under five by two-thirds by 2015. Gaps
national registries for recording causes of death. Surveillance systems
in funding, data and capacity are all limiting factors, and ARIs need to
for tracking influenza and other emerging infections are patchy, non-
become more of a priority within the global health community in order
existent or of poor quality in many developing countries.
to fill them. Keys to making a difference include expanded donor com-
The neglect of ARIs is also apparent in the failure to reach broad

segments of the worlds population with effective, low-cost
interventions. As this Atlas demonstrates, vaccinations, breastfeeding,
90
mitments, greater efforts to gather core information on which action

can be based, and a broad-based commitment to strengthening good
governance and the health system infrastructure.
1,500
0
Pneumonia
(in children under five)
Rotavirus diarrhea
(in children under five)
HIV/AIDS
3,000
4,500
6,000
7,500
7,320
34
1,770
15
1,197
21
Low-income countries
High-income countries
Deaths per 100,000 (2008)
In low-income countries, the average death rate from pneumonia is

215 times greater than in high-income countries.
91
8/31/10 11:19 AM
Making ARIs
a Global Priority
Other
0.8%
Cannot be allocated to one disease

4.72%
Other R&D
2.02%
Bacterial pneumonia and meningitis

1.27%
Helminths (worms and flukes)
2.02%
Dengue
3.2%
Diarrheal diseases
4.45%
Official Development
Assistance, US$ per capita
(2008)
Kinetoplastids
4.89%
HIV/AIDS
42.3%
>$300
$100-300
Tuberculosis
16.03%
$75-100
$50-75
$25-50
Malaria
18.3%
$10-25
<$10
no data
Distribution of Development Aid
R&D Funding for Pharmaceuticals and Related Products by Disease (2007)
Pneumonia research is poorly funded, compared with

other communicable diseases of global health concern.
ARIs Are Significantly Underfunded
As these data show, no apparent correlation exists between the

allocation of R&D funds and the loss of DALYs caused by each disease.
92
HIV/AIDS
Donor aid heavily favors HIV/AIDS.
0
s
Food aid/
food security
he
rla
nd
lost DALYsjust US$0.31 in R&D funds per lost DALY.
Basic nutrition
N
et
included in this figure). Yet together, these account for 106 million
da
respiratory infections (meningitis, also caused by pneumococcus, is
$0.5
Ca
na
By contrast, US$32 million was spent for R&D on acute lower
$1.0
ay
is, US$18.53 per lost DALY.
N
or
w
responsible for 58.5 million lost disability-adjusted life yearsthat
$1.5
St
at
es
US$1.1 billion was spent on HIV-related R&D, which was
$2.0
Un
ite
d
that disproportionately affect the developing world, as follows:
$2.5
ly
ticals and related products. In 2007, US$2.56 billion was spent on diseases
$3.0
Ita
illustrated by the use of research and development funds for pharmaceu-
Aid in US$ in billions (2000-05)
The shortfall in dedicated resources for acute respiratory infections is
centrated on three major killers: HIV/AIDS, malaria, and tuberculosis.
Fr
an
c
1990 to US$21.8 billion in 2007. But these resources remain highly con-
$3.5
Ki Un
ng ite
do d
m
has grown significantly over the past decade, from US$5.6 billion in
Contributions and commitments in US$ in billions
Donor assistance dedicated to improving health in developing countries
Nearly 80 percent of contributions to the Global Alliance for Vaccines

and Immunisation comes from just seven countries.
93
8/31/10 11:19 AM
Making ARIs
a Global Priority
Percent of deaths reported

to vital registries (2000-08)
75%
Research on indoor air pollution (5,587 studies)

Research on child ARIs (1,251 studies)
Research on child ARIs in low-income countries (287 studies)
(Based on a 2007 review)
25-49%
<25%
no data
Adequate death records are essential for surveillance,

but many countries do not maintain them.
The 10/90 Gap
The Global Forum on Health Research coined the term 10/90 gap
to highlight the mismatch between how health research funds are
allocated and where they are most needed. The suggestion that just
10 percent of the investment in global health research is targeted
at 90 percent of the worlds health problems offers a way to frame a
fundamental inequity.
The disparity is illustrated by the problem of indoor air pollution
(see Indoor Air Pollution, p. 56). Although cooking and heating
with biomass fuels is associated with an estimated 871,500 deaths
annually from pediatric pneumonia (and some 1.96 million deaths
from all causes), very little original research has explored the key
issues. Among almost 5,600 articles dealing with indoor air
pollution and published between 1985 and 2007, just 44 dealt with
childhood acute respiratory infections in developing countries and
More Information Is Needed About ARIs

Basic data about the populations most affected by acute respiratory
infections and the interventions that work best are incomplete in many
parts of the world. Without core statistics, there is no rigorous basis for
setting health priorities, implementing programs, or measuring success.
Resource limitations and an inadequate surveillance infrastructure have
meant that:
Surveillance data are inconsistently collected and analyzed, because
many countries have not invested in the necessary training and
infrastructure. For example:
Seventy percent of countries do not collect systematic data on
the number of children under five who receive antibiotics
for pneumonia.
Forty-six percent of countries do not collect systematic data on
many of those reviewed other studies, rather than reporting on
the number of children with pneumonia who are taken to an
new ones. Only a single randomized, controlled trial measuring the
appropriate health care provider.
impact of cleaner woodstoves on ARIs has been published (in 2009,

based on 534 households in 23 Guatemalan communities).
94
44 studies
approximately 10 studies
50-74%
Some countries do not collect any data on influenza, making it
There is a paucity of research on indoor air pollution and its impact on

children in developing countries.
ARIs may be grouped with other infectious diseases (for example,

data on pneumococcal diseases may not distinguish between
pneumonia and meningitis), making it difficult to track specifically
Health and Governance Infrastructure

Is Often Weak
how donor aid is used or why a particular infection is escalating or
Good governance, political will, effective leadership, and national
declining in a given location.
commitment are the foundation of a systematic and sustained approach
Data are also aggregated across regions so that, for example, all of
sub-Saharan Africa tends to be treated as a single location. Data can
be especially misleading when significant variations exist within a
country, as in Burkina Faso, where one study of 32 villages found as
few as 36 deaths and as many as 563 deaths per 1,000 live births.
Reliable mortality data is often scarce. In many African and Asian
countries with the highest levels of ARIs, fewer than 25 percent of
deaths are recorded through a centralized vital statistics registry.
Cause of death is even more difficult to determine. In countries
where most deaths occur outside the health care system, verbal
autopsies, in which trained personnel ask structured questions
of family members, may be the only way to establish cause. This
approach tends to be unreliable, especially where pneumonia and
difficult to assess regional differences or patterns of transmission
malaria are endemic. Because both involve respiratory distress, the
from tropical to temperate regions.
distinction can be hard to recognize.
to reducing the burden of acute respiratory infections. Without them,

it is impossible to strengthen and support a nations health care system,
and without a strong health care systemone that is adequately
staffed, well supplied and capable of delivering care even in remote and
impoverished settingsadequate progress against ARIs is impossible.
In many regions, response capacity is impeded by fragmented
policymaking, lack of community participation, a weak or poorly
administered health infrastructure, and corruption. Global
health workforce shortages, estimated at 4.25 million people,
disproportionately affect Africa and Asia and are a major barrier to
delivering proven interventions on a broad scale. Offering incentives to
locate trained workers where needs are greatest, providing continuous
education and support to clinicians, and training more community
health workers will help sustain and build workforce capacity (see
Growing the Health Workforce, p. 86).
95
8/31/10 11:19 AM
Making ARIs
a Global Priority
PneumoAction, a project of the International Vaccines Access

Center at Johns Hopkins Bloomberg School of Public Health,
Surveillance, developed in partnership between the CDC and
provides data, tools, maps, case studies, action guides, and other
WHO, in consultation with many nations around the world,
at least two percent of national health expenditures and
information resources to galvanize interest in pneumococcal disease
describes the strategies necessary to build vaccine-preventable-
five percent of health-related development aid to be committed to
(which includes both pneumonia and meningitis) from advocates,
disease surveillance programs and monitor immunization strategies.
building research capacity and to conducting research.
policymakers, and donors.
The framework emphasizes the importance of building a scientific

ARI-related R&D is needed to produce reliable and inexpensive
diagnostic tests in resource-scarce locations, to advance research
into new vaccines and antibiotics, and to develop and distribute
technologies to combat air pollution. Other global funding priorities
include disease surveillance, disseminating and evaluating proven
interventions, and building health system capacity.
Good governance, political will, strong leadership, and community
participation are essential to expanding health system capacity and
addressing workforce shortages.
Expanding local research helps to identify challenges on the ground
and makes it more likely that interventions will be relevant for local
Global Framework for Immunization Monitoring and
Improving data collection helps ensure that funding is properly

targeted, interventions are well designed, evidence builds for the
immunization campaigns in 72 countries with gross national
value of specific prevention, control, and treatment strategies, and
income, per capita, between US$1,000 and US$3,000 per year.
changes in the epidemiological profile of disease are recognized as
Support comes from seven donor countries, the European
they emerge.
Commission, the Bill & Melinda Gates Foundation, and others.
Despite funding, data, and capacity gaps, numerous global initiatives

targeted at acute respiratory infections are underway and should be
dramatically scaled up to increase their impact.
database through which to make informed decisions and take
The Global Alliance for Vaccines and Immunisation funds
appropriate public health action.
(For more information on GAVI, see Financing Immunization

Campaigns, p. 71.)
The Hib Initiative, a collaboration of the Johns Hopkins Bloomberg
School of Public Health, the U.S. Centers for Disease Control and
conditions. WHO has established a global health policy that calls for
Prevention, the London School of Hygiene and Tropical Medicine,

and WHO, guides countries in making evidence-based decisions
about use of the Haemophilus influenzae tybe b vaccine. Supported
Global Initiatives
Global Action Plan for Prevention and Control of Pneumonia

(GAPP) is a joint WHO and UNICEF initiative to build a broad
Global initiatives offer the best hope of overcoming funding, data, and
coalition of global and national policymakers, donor agencies, and
capacity gaps, and many efforts are underway to curb acute respiratory
institutions of civil society committed to scaling up pneumonia
infections and childhood mortality, increase vaccine use, strengthen
interventions. If GAPP could meet its 2010 goal of securing a
surveillance, and promote pharmaceutical research and development.
US$39 billion global commitment to breastfeeding, vaccinations,
CARE, Save the Children, the U.S. Agency for International

Development (USAID), the World Bank, WHO, and countless
pneumonia deaths annually could be averted by 2015.

The Global Coalition Against Pneumonia launched the first
partners guide the many global health and development initiatives that
annual World Pneumonia Day in April 2009, supported by
have implications for acute respiratory infections. While too numerous
more than 100 governmental, non-governmental, academic, and
to list comprehensively, these include:
community-based partners. In 36 countries on six continents, 167
and disseminate country-level progress toward Millennium

Development Goals 4 and 5 (to reduce child mortality and improve
maternal health). Among the two dozen partners are the Bill &
Melinda Gates Foundation, Save the Children, UNICEF, USAID,
WHO, and the World Bank. Over the past five years, the initiative
the vaccine; strengthening surveillance systems to demonstrate

Hib disease burden and vaccine impact; and coordinating with
international and national government partners.
and case management, an estimated 1.2 million post-neonatal
governmental, academic, industry, and non-governmental organization
The Countdown to 2015 Initiative formed in 2005 to track
by GAVI, its activities focus on communicating the benefits of
activitiesfrom rallies to symposia, football matches to radio

call-inswere held to direct attention to pneumonia as a public
health issue.
International code of marketing

of breast milk substitutes
25
Maternity protection in accordance

with ILO* convention 183
20
Community management of
pneumonia with antibiotics
18
New oral rehydration salts formula

and zinc for management of diarrhea
34
IMCI** adapted to cover

newborns up to one week old
39
Specific notification
of maternal deaths
23
Midwives authorized to administer

a core set of lifesaving interventions
27
28
13
48
11
31
8
17
10
3
14
21
Yes
18
13
25
* International Labour Organization

** Integrated Management of Childhood Illness
Partial
5
No
11
No data
has reported on the extent to which 60 countries are implementing

proven interventions.
Uptake by the 68 Countdown to 2015 Priority Countries
Limited progress is being made in adoption of key maternal, newborn, and child health policies.
96
97
8/31/10 11:19 AM

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Contents

About the Author . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Acute Respiratory Infections: Making Inroads Against a Forgotten Pandemic . . . . . . . . . . . . . . . . 8

Part 1: Understanding Acute Respiratory Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Produced for World Lung Foundation by

Part 2: Drivers of Acute Respiratory Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Antibiotics and Antiviral Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

How Drug Resistance Develops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

How Nutritional Deficiencies Affect the Immune System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

The Research and Development Drought . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

Linking ARIs and Malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

Preventing Drug Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

Access to Health Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

Micronutrients: Zinc, Vitamin D, and Vitamin A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

Gaps in Health Care Spending . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

How the International Community Can Help . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

Primary Care in Rural and Urban Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

Growing the Health Workforce . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

Profile: Treating Severe Pneumonia in Malawi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

How Pollutants Affect the Body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

Part 4: Making ARIs a Global Priority . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

Home Cooking and Heating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

Identifying and Meeting the Worldwide Challenge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

ARIs Are Significantly Underfunded . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

Outdoor Air Pollution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

More Information Is Needed About ARIs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

Motor Vehicles Emissions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

Health and Governance Infrastructure Is Often Weak . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

Profile: Air Pollution in China . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

Appendix A: World Regions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98

Environmental Tobacco Smoke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

Appendix B: Mechanisms of Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

Pathogens:Agents of Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

Profile: The Hajj . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

What Is a Virus? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

Part 3: Prevention, Diagnoses, and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

What Is a Fungus? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

Preventing ARIs with Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

How the Body Defends Itself . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

Appendix C: Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

Financing Immunization Campaigns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Appendix D: Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

Promoting Wider Vaccine Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

Appendix E: Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

Diagnoses and Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

Reducing ARIs begins with increased knowledge,

The drivers of ARIs can be largely addressed through poverty

About the Author

Dr. Nils Billo, MD, MPH

World Lung Foundation Acute Respiratory Infections Atlas

Top Ten Causes of Death:

Top Ten Causes of Death:

Ischemic heart disease

Lower respiratory infection

Chronic obstructive pulmonary

Lower respiratory infection

Ischemic heart disease

Chronic obstructive pulmonary

Trachea, bronchus, lung cancers

Road traffic accidents

Prematurity and low birthweight

Prematurity and low birthweight

This Atlas offers an in-depth look

Acute Respiratory Infections: