Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page R1
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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
OCR for page R2
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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.
OCR for page R3
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
“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.
OCR for page R4
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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
OCR for page R5
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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.
OCR for page R6
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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.
OCR for page R7
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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
OCR for page R8
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
This page intentionally left blank.
OCR for page R9
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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-
OCR for page R10
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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.
OCR for page R11
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
Contents
ACRONYMS
xv
SUMMARY
1
1
INTRODUCTION
15
Obstacles to Treatment,
16
Workshop Objectives,
17
Organization of This Report,
18
2
THE GLOBAL SPREAD OF MULTIDRUG-RESISTANT AND EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS
19
Scope of the Problem,
19
Underreporting of MDR TB in Africa,
25
The Threat of Totally Drug-Resistant TB,
33
Importance of Better Data,
33
3
MDR TB TRANSMISSION, HIV COINFECTION, AND TRANSMISSION CONTROL
35
Coinfection with HIV,
35
Treatment,
36
Transmission of XDR TB,
37
Perspective from Russia,
43
Mitigating Transmission,
43
Implications for Health Care Workers,
49
OCR for page R12
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
4
DIAGNOSIS
51
Actual Need,
51
Diagnostic Quality,
53
Currently Available Diagnostics,
53
Point-of-Care (POC) Diagnostics,
54
5
INFRASTRUCTURE AND HEALTH CARE DELIVERY SYSTEMS
59
Vertical Versus Horizontal Programs,
59
Approaches to Addressing Infrastructure Problems,
62
Role of Information Technology,
63
6
GLOBAL SYSTEMS FOR THE PURCHASE AND DELIVERY OF TB DRUGS
67
Procurement Problems,
68
The Drug Quality Issue,
69
Need for Accurate Demand Forecasting,
73
7
RESEARCH ON THE GLOBAL CONTROL OF TB: UNDERSTANDING THE ROLE OF DRUGS, VACCINES, AND FUNDING
81
The Pipeline for New Drugs,
82
Probability of Success,
85
Economic Incentives for Drug Development,
93
8
STRATEGIES FOR CONFRONTING THE GLOBAL MDR AND XDR TB CRISIS
97
Recommendations Presented by Dr. Keshavjee,
97
Lessons Learned from the President’s Emergency Plan for AIDS Relief (PEPFAR),
102
Policy Focus on Drug-Resistant Versus Non-Drug-Resistant TB,
104
The Level of Response,
105
Summary of Key Points,
107
Closing Remarks,
108
REFERENCES
109
APPENDIXES
A
Agenda
113
B
Participant Biographies
117
C
Partners In Health White Paper—Stemming the Tide of Multidrug-Resistant Tuberculosis: Major Barriers to Addressing the Growing Epidemic
139
OCR for page R13
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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
OCR for page R14
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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
OCR for page R15
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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
OCR for page R16
Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge - Workshop Summary
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
