Facing the Reality of Drug-Resistant Tuberculosis in India
Challenges and Potential Solutions
SUMMARY OF A JOINT WORKSHOP
by the Institute of Medicine,
the Indian National Science Academy, and
the Indian Council of Medical Research
Steve Olson, Rebecca A. English, Rita S. Guenther, and
Anne B. Claiborne, Rapporteurs
Forum on Drug Discovery, Development, and Translation
Board on Health Sciences Policy
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW 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 study was supported by contracts between the National Academy of Sciences and Department of Health and Human Services (Contract Nos. N01-OD-4-2139 and 223001003T), U.S. State Department (S-LMAQM-08-GR-071), American Society for Microbiology, Amgen Inc., Association of American Medical Colleges, Bristol-Myers Squibb, Burroughs Wellcome Fund, Celtic Therapeutics, LLLP, Critical Path Institute, Doris Duke Charitable Foundation, Eli Lilly & Co., FasterCures, Foundation for the NIH, Friends of Cancer Research, GlaxoSmithKline, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, and Pfizer Inc. The views presented in this publication do not necessarily reflect the views of the organizations or agencies that provided support for the project.
International Standard Book Number-13: 978-0-309-21966-2
International Standard Book Number-10: 0-309-21966-3
ISBN 0-309-21966-3
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Suggested citation: IOM (Institute of Medicine). 2012. Facing the Reality of Drug-Resistant Tuberculosis in India: Challenges and Potential Solutions: Summary of a Joint Workshop. Washington, DC: The National Academies Press.
“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.
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
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PLANNING COMMITTEE ON FACING THE REALITY
OF DRUG-RESISTANT TUBERCULOSIS IN INDIA:
CHALLENGES AND POTENTIAL SOLUTIONS1
GAIL H. CASSELL (Chair), Harvard Medical School (visiting)
BARRY R. BLOOM, Harvard School of Public Health
ENRIQUETA C. BOND, QE Philanthropic Advisors
RICHARD E. CHAISSON, Johns Hopkins University
PAUL E. FARMER, Partners In Health, Harvard Medical School
ANTHONY S. FAUCI, National Institute of Allergy and Infectious Diseases
GARY L. FILERMAN, Atlas Health Foundation
GERALD H. FRIEDLAND, Yale University School of Medicine
ELAINE K. GALLIN, QE Philanthropic Advisors
STEPHEN GROFT, National Center for Advancing Translational Sciences
NANCY SUNG, Burroughs Wellcome Fund
IOM Staff
ANNE B. CLAIBORNE, Forum Director
RITA S. GUENTHER, Program Officer
REBECCA A. ENGLISH, Associate Program Officer
ELIZABETH F. C. TYSON, Research Associate
ANDREW M. POPE, Director, Board on Health Sciences Policy
ROBIN GUYSE, Senior Program Assistant
RONA BRIERE, Consulting Editor
Indian National Science Academy (INSA) Staff
KRISHAN LAL, President
PRAKASH N. TANDON, Past President
A. K. JAIN, Inter Academy Officer
____________________
1 Institute of Medicine 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.
Indian Council of Medical Research (ICMR) Staff
VISHWA MOHAN KATOCH, Director General
LALIT KANT, Head, Division of Epidemiology and Communicable Diseases
MANJULA SINGH, Scientist C
HARPREET SANDHU, Scientist D
MUKESH KUMAR, Scientist E and Head
FORUM ON DRUG DISCOVERY,
DEVELOPMENT, AND TRANSLATION1
JEFFREY M. DRAZEN (Co-Chair), New England Journal of Medicine, Boston, Massachusetts
STEVEN K. GALSON (Co-Chair), Amgen Inc., Thousand Oaks, California
MARGARET ANDERSON, FasterCures, Washington, DC
HUGH AUCHINCLOSS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
LESLIE Z. BENET, University of California, San Francisco
ANN BONHAM, Association of American Medical Colleges, Washington, DC
LINDA BRADY, National Institute of Mental Health, Bethesda, Maryland
ROBERT CALIFF, Duke University Medical Center, Durham, North Carolina
C. THOMAS CASKEY, Baylor College of Medicine, Houston, Texas
GAIL H. CASSELL, Harvard Medical School (visiting), Carmel, Indiana
PETER B. CORR, Celtic Therapeutics, LLLP, New York, New York
ANDREW M. DAHLEM, Eli Lilly & Co., Indianapolis, Indiana
TAMARA DARSOW, American Diabetes Association, Alexandria, Virginia
JAMES H. DOROSHOW, National Cancer Institute, Bethesda, Maryland
GARY L. FILERMAN, Atlas Health Foundation, McLean, Virginia
GARRET A. FITZGERALD, University of Pennsylvania School of Medicine, Philadelphia
MARK J. GOLDBERGER, Abbott Pharmaceuticals, Rockville, Maryland
HARRY B. GREENBERG, Stanford University School of Medicine, California
STEPHEN GROFT, National Center for Advancing Translational Sciences, Bethesda, Maryland
LYNN HUDSON, Critical Path Institute, Tucson, Arizona
THOMAS INSEL, National Center for Advancing Translational Sciences, Bethesda, Maryland
MICHAEL KATZ, March of Dimes Foundation, White Plains, New York
PETRA KAUFMANN, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland
____________________
1 Institute of Medicine 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.
JACK D. KEENE, Duke University Medical Center, Durham, North Carolina
RONALD L. KRALL, University of Pennsylvania, Center for Bioethics, Steamboat Springs, Colorado
FREDA LEWIS-HALL, Pfizer Inc., New York, New York
MARK B. MCCLELLAN, The Brookings Institution, Washington, DC
CAROL MIMURA, University of California, Berkeley
ELIZABETH (BETSY) MYERS, Doris Duke Charitable Foundation, New York, New York
JOHN ORLOFF, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
AMY PATTERSON, National Institutes of Health, Bethesda, Maryland
MICHAEL ROSENBLATT, Merck & Co., Inc., Whitehouse Station, New Jersey
JANET SHOEMAKER, American Society for Microbiology, Washington, DC
ELLEN SIGAL, Friends of Cancer Research, Washington, DC
ELLIOTT SIGAL, Bristol-Myers Squibb, Princeton, New Jersey
ELLEN R. STRAHLMAN, GlaxoSmithKline, Research Triangle Park, North Carolina
NANCY SUNG, Burroughs Wellcome Fund, Research Triangle Park, North Carolina
JANET TOBIAS, Ikana Media and Mount Sinai School of Medicine, New York, New York
JOANNE WALDSTREICHER, Janssen Research & Development, LLC, Raritan, New Jersey
JANET WOODCOCK, Food and Drug Administration, White Oak, Maryland
IOM Staff
ANNE B. CLAIBORNE, Forum Director
RITA S. GUENTHER, Program Officer
REBECCA A. ENGLISH, Associate Program Officer
ELIZABETH F. C. TYSON, Research Associate
ANDREW M. POPE, Director, Board on Health Sciences Policy
ROBIN GUYSE, Senior Program Assistant
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 clarity, objectivity and responsiveness to the 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:
Digambar Behera, Lala Ram Sarup Institute of TB and Respiratory Diseases
Vishwa Mohan Katoch, Indian Council of Medical Research
P. R. Narayanan, National Institute for Research in Tuberculosis, Chennai
K. Srinath Reddy, Public Health Foundation of India
Christine F. Sizemore, National Institute of Allergy and Infectious Diseases
Soumya Swaminathan, National Institute for Research in Tuberculosis, Chennai
Prakash N. Tandon, Indian National Science Academy
Kristina Wallengren, KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal
Although the reviewers listed above provided many constructive comments and suggestions, they did not see the final draft of the report before its release. The review of this report was overseen by Melvin Worth. 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.
Contents
History and Dimensions of the Problem
The Burden of Drug-Resistant TB
Overview of TB and MDR TB in India
The Burden of TB and MDR TB in India
Plans of the Revised National TB Control Program
Involvement of the Private Sector
Challenges to the Revised National TB Control Program
Treatment of Drug-Resistant TB
Improving Health System Performance to Address the Challenge of Drug-Resistant TB
Potential Innovations and Action Items
3 THE GLOBAL BURDEN OF DRUG-RESISTANT TB
Overview of the Global Burden of TB and MDR TB
Global Challenges and Potential Solutions
Potential Innovations and Action Items
4 PREVENTING TRANSMISSION OF DRUG-RESISTANT TB
India’s Program Efforts to Prevent Transmission of Drug-Resistant TB
The Impact of Treatment on MDR TB Transmission
The Genetic Evolution of M.tb.
The Molecular Epidemiology of M.tb.
Potential Innovations and Action Items
5 DETECTING DRUG RESISTANCE AND STRENGTHENING LABORATORY CAPACITY
Diagnosis of Drug-Resistant TB
Quality Assurance Considerations in the Development of New Diagnostics
The Supranational Reference Laboratory Network
Expanding Laboratory Capacity in India for the Diagnosis of Drug-Resistant TB
Potential Innovations and Action Items
6 ADDRESSING TB AND DRUG-RESISTANT TB IN VULNERABLE POPULATIONS
Drug-Resistant TB in Pediatric Populations
The Burden of Pediatric TB in Households of Patients with MDR TB
Drug Resistance in HIV-Infected Populations
Drug-Resistant TB in Migrant and Refugee Populations
Case Studies in Cambodia and Ethiopia
Potential Innovations and Action Items
7 COMBATING DRUG-RESISTANT TB THROUGH PUBLIC–PRIVATE COLLABORATION AND INNOVATIVE APPROACHES
Operation ASHA: “Going the Last Mile,”
Engaging the Private Sector in India
8 CONFRONTING CHALLENGES TO THE SUPPLY CHAIN FOR SECOND-LINE DRUGS
Challenges in Drug Supply Chain Logistics
India’s Second-Line Drug Supply Chain
Improving the Availability and Reducing the Cost of MDR TB Drugs
Moving Toward a Functional Market for Second-Line TB Drugs
Potential Innovations and Action Items
9 CREATING A BLUEPRINT FOR ACTION
Preventing Transmission of Drug-Resistant TB
Strengthening Laboratory Capacity
Addressing TB and Drug-Resistant TB in Vulnerable Populations
Combating Drug-Resistant TB Through Public–Private Collaboration and Innovative Approaches
Strengthening the Second-Line Drug Supply Chain
APPENDIXES
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Tables, Figures, and Boxes
TABLES
2-1 Drug Resistance Surveillance in Three Indian States
3-1 Estimated Versus Reported MDR TB Cases in 2009
3-2 Reduced Prices of Second-Line TB Drugs (1997–2000)
3-3 Prices for Green Light Committee-Approved Drugs
6-1 Profile of XDR TB in India
FIGURES
2-1 India has the highest TB burden of any country in the world
6-1 TB incidence rates are highest in young adults in the African and Southeast Asian regions
AIDS | acquired immune deficiency syndrome | |
AIIMS | All India Institute of Medical Sciences | |
API | active pharmaceutical ingredient | |
CAS | Central Asian | |
CDC | U.S. Centers for Disease Control and Prevention | |
CHW | community health worker | |
CPC | cetyl-pyridinium chloride | |
CRI | colorimetric redox indicator | |
DOT | directly observed treatment | |
DOTS | Directly Observed Treatment-Short course | |
DST | drug susceptibility testing | |
EAI | East African-Indian | |
EXPAND-TB | Expanding Access to New Diagnostics for TB | |
FIND | Foundation for Innovative New Diagnostics | |
GDF | Global Drug Facility | |
GLC | Green Light Committee | |
GLI | Global Laboratory Initiative | |
GMP | Good Manufacturing Practice | |
GP | general practitioner |
HIV | human immunodeficiency virus | |
ICMR | Indian Council of Medical Research | |
INSA | Indian National Science Academy | |
IOM | Institute of Medicine | |
IRD | Interactive Research and Development | |
IRIS | immune reconstitution inflammatory syndrome | |
ISO | International Organisation for Standardization | |
IUATLD | International Union Against Tuberculosis and Lung Disease (“the Union”) | |
K-RITH | KwaZulu-Natal Research Institute for Tuberculosis and HIV | |
LAM | lipoarabinomannan | |
LED | light-emitting diode | |
LMIS | logistics management information systems | |
LPA | line probe assay | |
LRS | Lala Ram Sarup | |
MDR TB | multidrug-resistant tuberculosis | |
MGIT | mycobacteria growth indicator tube | |
MIRU | mycobacterial interspersed repetitive units | |
MODS | microscopic observation drug susceptibility | |
M.tb. | Mycobacterium tuberculosis | |
NAAT | nucleic acid amplification testing | |
NGO | nongovernmental organization | |
NIAID | National Institute of Allergy and Infectious Diseases | |
NIH | National Institutes of Health | |
NRA | nitrate reductase assay | |
PAS | P-aminosalicylic acid | |
PCR | polymerase chain reaction | |
PEPFAR | U.S. President’s Emergency Plan for AIDS Relief | |
PETTS | Preserving Effective TB Treatment Study | |
PKR | Pakistan rupees | |
PPM | public–private mix | |
RCC | Rolling Continuation Channel | |
RNTCP | Revised National Tuberculosis Control Program | |
SSCP | single-strand conformational polymorphism | |
TB | tuberculosis | |
TDR TB | totally drug-resistant tuberculosis | |
TLA | thin layer agar | |
TRC | Tuberculosis Research Centre (India)1 | |
TST | tuberculin skin test | |
USAID | U.S. Agency for International Development | |
VNTR | variable number of tandem repeats | |
WHO | World Health Organization | |
XDR TB | extensively drug-resistant tuberculosis |
____________________
1 Since the workshop, the Tuberculosis Research Centre (TRC) in Chennai, India, was renamed the National Institute for Research in Tuberculosis.
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