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Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

Addressing the Threat of Drug-Resistant Tuberculosis

A Realistic Assessment of the Challenge

WORKSHOP SUMMARY

Robert Giffin and Sally Robinson, Rapporteurs

INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.
www.nap.edu

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

THE NATIONAL ACADEMIES PRESS

500 Fifth Street, N.W. Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.

This project was supported by the American Diabetes Association; the American Society for Microbiology; Amgen, Inc.; the Association of American Medical Colleges; AstraZeneca Pharmaceuticals; Blue Cross Blue Shield Association; the Burroughs Wellcome Fund; Celtic Therapeutics Management, LLLP; the Critical Path Institute; the Doris Duke Charitable Foundation; Eli Lilly and Company; Entelos Inc.; Genentech; GlaxoSmithKline; Johnson & Johnson; the March of Dimes Foundation; Merck & Co.; the National Institutes of Health—HHS Contract No. N01-OD-4-2139 (National Cancer Institute, National Center for Research Resources, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, Office of Rare Disease Research); Pfizer Inc.; UnitedHealth Group; and the U.S. Food and Drug Administration—HHS Contract No. 223-01-2460. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

International Standard Book Number-13: 978-0-309-13044-8

International Standard Book Number-10: 0-309-13044-1

Additional copies of this report are available from the

National Academies Press,

500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.

For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu.

Copyright 2009 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.

Suggested citation: IOM (Institute of Medicine). 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press.

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

“Knowing is not enough; we must apply.

Willing is not enough; we must do.”

—Goethe

INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES


Advising the Nation. Improving Health.

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine


The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.


The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.


The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.


The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.


www.national-academies.org

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

PLANNING COMMITTEE FOR ADDRESSING CHALLENGES IN DRUG DISCOVERY, DEVELOPMENT, AND DISTRIBUTION FOR MULTIDRUG-RESISTANT TUBERCULOSIS: A WORKSHOP SERIES1

Donald M. Berwick,

Institute for Healthcare Improvement

Enriqueta C. Bond,

Burroughs Wellcome Fund

Gail H. Cassell,

Eli Lilly and Company

Anthony S. Fauci,

National Institute of Allergy and Infectious Diseases, National Institutes of Health

Gerald H. Friedland,

Yale University School of Medicine

Elaine Gallin,

Doris Duke Charitable Foundation

Stephen Groft,

Office of Rare Disease Research, National Institutes of Health

Margaret A. Hamburg,

Nuclear Threat Initiative

Jim Yong Kim,

Harvard Medical School

Nancy Sung,

Burroughs Wellcome Fund

Roy Widdus,

Global Forum for Health Research

IOM Staff

Robert B. Giffin, Director

Rebecca A. English, Research Associate

Yeonwoo Lebovitz, Program Associate

Sally Robinson, Program Officer

Andrea Knutsen, Senior Program Assistant

Genea S. Vincent, Senior Program Assistant

Rona Briere, Consulting Editor

1

IOM planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION1

Gail H. Cassell (Co-Chair),

Eli Lilly and Company, Indiana

Jeffrey M. Drazen (Co-Chair),

New England Journal of Medicine, Massachusetts

Barbara Alving,

National Center for Research Resources, Maryland

Hal Barron,

Genentech, California

Leslie Z. Benet,

University of California, San Francisco

Catherine Bonuccelli,

AstraZeneca Pharmaceuticals, Delaware

Linda Brady,

National Institute of Mental Health, Maryland

Robert M. Califf,

Duke University Medical Center, North Carolina

Scott Campbell,

American Diabetes Association, Virginia

C. Thomas Caskey,

University of Texas-Houston Health Science Center

Peter B. Corr,

Celtic Therapeutics, New York

James H. Doroshow,

National Cancer Institute, Maryland

Paul R. Eisenberg,

Amgen, Inc., California

Gary L. Filerman,

Atlas Research, Virginia

Garret A. FitzGerald,

University of Pennsylvania School of Medicine

Elaine K. Gallin,

The Doris Duke Charitable Foundation, New York

Steven K. Galson,

Office of the Surgeon General, U.S. Department of Health and Human Services, Maryland

Mikhail Gishizky,

Entelos, Inc., California

Stephen Groft,

National Institutes of Health, Maryland

Edward W. Holmes,

National University of Singapore

Peter K. Honig,

Merck & Co., Inc., Pennsylvania

A. Jacqueline Hunter,

GlaxoSmithKline, United Kingdom

Michael Katz,

March of Dimes Foundation, New York

Jack D. Keene,

Duke University Medical Center, North Carolina

Ronald L. Krall,

GlaxoSmithKline, Pennsylvania

Freda Lewis-Hall,

Pfizer, Inc., New York

William D. Matthew,

National Institute of Neurological Disorders and Stroke, Maryland

Musa Mayer,

AdvancedBC.org, New York

Mark B. McClellan,

Brookings Institution, Washington, DC

Carol Mimura,

University of California, Berkeley

John Orloff,

Novartis Pharmaceuticals Corporation, New Jersey

Amy P. Patterson,

National Institutes of Health, Maryland

Janet Shoemaker,

American Society for Microbiology, Washington, DC

1

IOM forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

Lana Skirboll,

National Institutes of Health, Maryland

Nancy S. Sung,

Burroughs Wellcome Fund, North Carolina

Irena Tartakovsky,

Association of American Medical Colleges, Washington, DC

Jorge A. Tavel,

National Institute of Allergy and Infectious Diseases, Maryland

Joanne Waldstreicher,

Johnson & Johnson, New Jersey

Janet Woodcock,

U.S. Food and Drug Administration, Maryland

Raymond L. Woosley,

Critical Path Institute, Arizona

Page viii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
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Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

Reviewers

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We wish to thank the following individuals for their review of this report:

Richard E. Chaisson, Center for Tuberculosis Research, Johns Hopkins School of Medicine

Ann M. Ginsberg, Clinical Development, Global Alliance for TB Drug Development

Ruth Levine, Center for Global Development

Fuad Mirzayev, TB/HIV and Drug Resistance, Stop TB Department, World Health Organization

Lee B. Reichman, Global Tuberculosis Institute, New Jersey Medical School

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the final draft of the report before its release. The review of this report was over-

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

seen by Barry R. Bloom, Harvard School of Public Health. Appointed by the Institute of Medicine, he was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authors and the institution.

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×
Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×
Page xiii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

Tables, Figures, and Boxes

TABLES

S-1

 

Estimated Number of TB Cases and Number of Deaths, by Type, 2006,

 

3

2-1

 

Estimated Number of TB Cases and Number of Deaths, by Type, 2006,

 

21

2-2

 

Performance of National TB Programs,

 

27

4-1

 

Laboratory Capacity in High-Burden Countries, 2006, 52aboratory Capacity in High-Burden Countries, 2006,

 

52

6-1

 

Green Light Committee Projects and Patients, 2006–2009,

 

68

7-1

 

Four of the Eight TB Vaccine Candidates in Clinical Trials That Have Moved into Phase II Studies,

 

91

FIGURES

S-1

 

MDR TB burden and patients in treatment,

 

7

2-1

 

Global incidence of TB,

 

20

2-2

 

Per capita incidence of TB,

 

21

2-3

 

Two-thirds of the MDR TB burden is located in just three countries,

 

22

2-4

 

Percentage of MDR TB among new TB cases (1994–2007), 26MDR TB among new TB cases (1994–2007),

 

26

2-5

 

African countries with a known MDR TB rate,

 

28

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

2-6

 

Numbers of MDR TB and XDR TB patients in Tugela Ferry, 2005–2007,

 

30

2-7

 

A representation of the limited knowledge of the extent of MDR TB in KwaZulu-Natal Province, 2006,

 

31

2-8

 

High mortality due to MDR and XDR TB in Tugela Ferry (2005–2007),

 

32

3-1

 

MDR TB burden and patients in treatment,

 

37

3-2

 

Facilities in KwaZulu-Natal Province where at least one XDR TB case was described or diagnosed from June 2005 to March 2007,

 

39

3-3

 

Genotypes of 17 patients with MDR and XDR TB relapse,

 

41

3-4

 

Four TB strains in a single patient,

 

42

3-5

 

Partners In Health’s community-based TB treatment triage strategy in Haiti,

 

47

6-1

 

Commodity logistics system in Kenya (as of April 2004),

 

74

6-2

 

Artemisinin combination therapy (ACT) supply chain risk map,

 

77

6-3

 

Artemisinin combination therapy (ACT) supply chain incentives map,

 

78

7-1

 

Discovery timeline of currently available TB drugs,

 

83

7-2

 

Distribution of TB drug targets,

 

84

7-3

 

Global clinical portfolio of TB drugs in development,

 

86

7-4

 

Federal funding for HIV/AIDS, 1982–2008,

 

89

7-5

 

Funding for TB from the National Institute of Allergy and Infectious Diseases in fiscal year 2007,

 

90

8-1

 

A patient being carried by a family member to a clinic,

 

100

BOXES

3-1

 

Transmission of MDR and XDR TB in Shanghai,

 

44

5-1

 

Universal Access for MDR Care: The Cambodian and Ethiopian Perspectives,

 

60

7-1

 

Examples of Push and Pull Mechanisms for Stimulating Drug and Vaccine Development,

 

94

8-1

 

Specific Recommendations from the Report Stemming the Tide of Multidrug-Resistant Tuberculosis: Major Barriers to Addressing the Growing Epidemic,

 

98

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

Acronyms

ACH air changes per hour

ACT artemisinin combination therapy

ACTG AIDS Clinical Trial Group

AFRO African regional office

AIDS acquired immune deficiency syndrome

ANRS French National Agency for AIDS Research

ATP adenosine triphosphate

CDC U.S. Centers for Disease Control and Prevention

CGD Center for Global Development

DOTS directly observed treatment, short course

DST drug susceptibility testing

EMEA European Medicines Agency

FDA U.S. Food and Drug Administration

FIND Foundation for Innovative New Diagnostics

GDF Global Drug Facility

GLC Green Light Committee

GLI Global Laboratory Initiative

HIV human immunodeficiency virus

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×

IDA International Dispensary Association

IHR International Health Regulations

IOM Institute of Medicine

IT information technology

IUATLD International Union Against Tuberculosis and Lung Disease

LIMS laboratory information management system

MDR TB multidrug-resistant tuberculosis

MEND Medicine in Need

MIRU mycobacterial interspersed repetitive unit

MRSA methicillin-resistant Staphylococcus aureus

MSH Management Sciences for Health

NGO nongovernmental organization

NIAID National Institute of Allergy and Infectious Diseases

NIH National Institutes of Health

PCR polymerase chain reaction

PEPFAR U.S. President’s Emergency Plan for AIDS Relief

PETT CDC’s Preserving Effectiveness of TB Treatment study

PHLIP Public Health Laboratory Interoperability Project

POC point of care

PRV priority review voucher

R&D research and development

RFLP restriction fragment length polymorphism

SA Staphylococcus aureus

SRL Global Supranational Reference Laboratory

TB tuberculosis

UNICEF United Nations Children’s Fund

USAID U.S. Agency for International Development

UV ultraviolet

WHO World Health Organization

XDR TB extensively drug-resistant tuberculosis

Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×
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Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
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Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
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Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
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Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
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Page xiii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
×
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Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
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Suggested Citation:"Front Matter." Institute of Medicine. 2009. Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/12570.
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Tuberculosis is one of the leading causes of death in the world today, with 4,500 people dying from the disease every day. Many cases of TB can be cured by available antibiotics, but some TB is resistant to multiple drugs--a major and growing threat worldwide. The Institute of Medicine's Forum on Drug Discovery, Development, and Translation hosted a workshop on November 5, 2008, to address the mounting concern of drug-resistant TB. The session brought together a wide range of international experts to discuss what is known and not known about this growing threat, and to explore possible solutions.

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