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Textbook of
TUBERCULOSIS AND NONTUBERCULOUS
MYCOBACTERIAL DISEASES
Textbook of
TUBERCULOSIS AND NONTUBERCULOUS
MYCOBACTERIAL DISEASES
Third Edition
Editor
Surendra K Sharma
Former Senior Professor and Head
Department of Internal Medicine
[WHO Collaborating Centre for Research and
Training in Tuberculosis
Centre of Excellence for Extrapulmonary TB
Ministry of Health and Family Welfare, Government of India]
All India Institute of Medical Sciences
New Delhi, India
Adjunct Professor
Department of Molecular Medicine
Jamia Hamdard Institute of Molecular Medicine
Jamia Hamdard [Deemed to be University]
New Delhi, India
Adjunct Professor
Departments of General Medicine and Respiratory Medicine
Jawaharlal Nehru Medical College
Datta Meghe Institute of Medical Sciences [Deemed to be University]
Wardha, Maharashtra, India
Assistant Editor
Alladi Mohan
Chief, Division of Pulmonary and Critical Care Medicine
Professor and Head
Department of Medicine
Sri Venkateswara Institute of Medical Sciences
Tirupati, Andhra Pradesh, India
Foreword
Mario C Raviglione
JAYPEE BROTHERS MEDICAL PUBLISHERS

The Health Sciences Publisher
New Delhi | London
Jaypee Brothers Medical Publishers (P) Ltd.
Headquarters
Jaypee Brothers Medical Publishers (P) Ltd
4838/24, Ansari Road, Daryaganj
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Phone: +91-11-43574357
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Website: www.jaypeebrothers.com
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© 2020, Jaypee Brothers Medical Publishers
The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent
those of editor(s) of the book.
All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic,
mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers.
All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of
their respective owners. The publisher is not associated with any product or vendor mentioned in this book.
Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the
subject matter in question. However, readers are advised to check the most current information available on procedures included and
check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and
duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety
precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property
arising from or related to use of material in this book.
This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or
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The CD/DVD-ROM (if any) provided in the sealed envelope with this book is complimentary and free of cost. Not meant for sale.
Inquiries for bulk sales may be solicited at: [email protected]
Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases
First Edition: 2001
Second Edition: 2009
Third Edition: 2020
ISBN: 978-93-89129-21-2
Dedicated to
Our late parents for their encouragement
Our teachers and students for their inspiration
Anju and Himabala for their moral support
Abhishek, Animesh and Vikram Chandra for their cheerful enthusiasm
Contributors
SK Acharya VH Balasangameshwara Abha Chandra

Former Professor and Head Former Chief Medical Officer Professor and Head
Department of Gastroenterology and National Tuberculosis Institute Department of Cardiovascular and
Human Nutrition Directorate General of Health Services Thoracic surgery
All India Institute of Medical Sciences Bengaluru, Karnataka, India Sri Venkateswara Institute of Medical
New Delhi, India Sciences
D Behera Tirupati, Andhra Pradesh, India
Professor
SK Agarwal
Department of Pulmonary Medicine Rohan Chawla
Professor and Head
Postgraduate Institute of Medical Associate Professor
Department of Nephrology
Education and Research Dr Rajendra Prasad Centre for
All India Institute of Medical Sciences Chandigarh, India Ophthalmic Sciences
New Delhi, India
S Bhan New Delhi, India
AN Aggarwal Former Professor and Head
Professor and Head Department of Orthopaedics Vatsla Dadhwal
Department of Pulmonary Medicine All India Institute of Medical Sciences Professor
Postgraduate Institute of Medical New Delhi, India Department Obstetrics and Gynaecology
Education and Research All India Institute of Medical Sciences
Chandigarh, Punjab, India Deepali K Bhat New Delhi, India
Department of Transplant Immunology
and Immunogenetics
Gautam Ahluwalia Chandan J Das
Professor Associate Professor
New Delhi, India
Department of Medicine Department of Radiodiagnosis
Dayanand Medical College and Hospital All India Institute of Medical Sciences
Rajesh Bhatia
Ludhiana, Punjab, India New Delhi, India
Former Director
Department of Communicable Diseases
Vineet Ahuja WHO Regional Office for South-East Asia Prasenjit Das
Professor New Delhi, India Additional Professor
Department of Gastroenterology and Department of Pathology
Human Nutrition Vineet Bhatia All India Institute of Medical Sciences
All India Institute of Medical Sciences Medical Officer–MDR-TB New Delhi, India
New Delhi, India Department of Communicable Diseases
World Health Organization Malika Davids
Regional Office for South-East Asia Lung Infection and Immunity Unit
Jason Andrews
New Delhi, India Division of Pulmonology and
Assistant Professor
University of Cape Town Lung Institute
Department of Medicine-Infectious
Gregory Calligaro Department of Medicine
Diseases University of Cape Town
Pulmonologist
Stanford University Cape Town, South Africa
Groote Schuur Hospital
Stanford, California, USA
Researcher at Lung Infection and
Immunity Unit Rodney Dawson
Minu Bajpai Division of Pulmonology and University Professor and Head
Professor and Head of Cape Town Lung Institute UCT Lung Institute
Department of Paediatric Surgery Department of Medicine Department of Medicine
All India Institute of Medical Sciences University of Cape Town University of Cape Town
New Delhi, India Cape Town, South Africa Cape Town, South Africa
viii Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases
Sajal De Gaurav PS Gahlot Sanjay Gupta

Associate Professor Assistant Professor Chief Medical Officer
Department of TB and Department of Pathology Department of Tuberculosis and
Respiratory Diseases Army Hospital RR Respiratory Diseases
Mahatma Gandhi Institute of Medical New Delhi, India National Institute of Tuberculosis and
Sciences Respiratory diseases
Wardha, Maharashtra, India New Delhi, India
SP Garg
Former Professor
Surendran Deepanjali Dr Rajendra Prasad Centre for Siddhartha Datta Gupta
Associate Professor Professor
Ophthalmic Sciences
Department of Medicine Department of Pathology
Jawaharlal Institute of Postgraduate All India Institute of Medical Sciences
New Delhi, India
Medical Education and Research New Delhi, India
Puducherry, India
Haileyesus Getahun
Coordinator Nicola A Hanania
B Dey
TB/HIV and Community Engagement Associate Professor of Medicine
Center for Tuberculosis Research
[THC] Section of Pulmonary and Critical Care
Johns Hopkins School of Medicine
Global TB Programme [GTB] Medicine
Baltimore, MD, USA
World Health Organization [WHO] Baylor College of Medicine
Geneva, Switzerland Houston, Texas, USA
Keertan Dheda
Professor of Respiratory Medicine
Head of the Lung Infection and J Harikrishna
Marzieh Ghiasi
Immunity Unit Associate Professor
McGill International TB Centre
Division of Pulmonology and Department of Medicine
McGill University
University of Cape Town Lung Institute Sri Venkateswara Institute of
Montreal, Quebec, Canada
Department of Medicine Medical Sciences
University of Cape Town Tirupati, Andhra Pradesh, India
Cape Town, South Africa Ankur Goyal
Assistant Professor
CV Harinarayan
Department of Radiodiagnosis
Samjot S Dhillon Director
Associate Professor of Oncology Institute of Endocrinology, Diabetes,
New Delhi, India
Roswell Park Cancer Institute Thyroid and Osteoporosis Disorders
Assistant Professor of Medicine Sakra World Hospitals
Department of Medicine KK Guntupalli Bengaluru, Karnataka, India
Pulmonary Medicine and Thoracic Professor of Medicine
Oncology Chief, Pulmonary AK Hemal
State University of New York [SUNY] Critical Care and Sleep Former Professor
Buffalo, New York, USA Medicine Section Department of Urology
Baylor College of Medicine All India Institute of Medical Sciences
Alisgar Esmail Houston, Texas, USA New Delhi, India
Lung Infection and Immunity Unit
Division of Pulmonology and
University of Cape Town Lung Institute Arun K Gupta Md Khurshid Alam Hyder
Department of Medicine Professor and Head Public Health Administrator
University of Cape Town Department of Radiodiagnosis UN House Pulchowk
Cape Town, South Africa All India Institute of Medical Sciences Lalitpur
New Delhi, India Kathmandu, Nepal
Dennis Falzon
Medical Officer Alisha Gupta R Jain
Global TB Programme Department of Paediatric Surgery Center for Tuberculosis Research
World Health Organization All India Institute of Medical Sciences Johns Hopkins School of Medicine
Geneva, Switzerland New Delhi, India Baltimore, Maryland, USA
Contributors ix
Manisha Jana DR Karnad Amitabh Kumar

Associate Professor Professor and Chief Chest Specialist
Department of Radiodiagnosis Medical-Neuro Intensive Care Unit New Delhi Municipal Corporation
All India Institute of Medical Sciences Department of Medicine [NDMC] Charak Palika Hospital
New Delhi, India Seth GS Medical College and New Delhi, India
KEM Hospital
Mumbai, Maharashtra, India Arvind Kumar
Babban Jee Former Professor
Scientist C Department of Surgical Disciplines
Department of Health Research VM Katoch All India Institute of Medical Sciences
Ministry of Health and Family Welfare Former Secretary New Delhi, India
Government of India Department of Health Research [DHR]
New Delhi, India Ministry of Health and Family Welfare Rajeev Kumar
Government of India Professor
Former Director General Department of Urology
SK Jindal
Indian Council of Medical Research All India Institute of Medical Sciences
Former Professor and Head
New Delhi, India New Delhi, India
Department of Pulmonary Medicine
Postgraduate Institute of Medical NASI—ICMR Chair
Shaji Kumar
Education and Research Public Health Research
Professor
Chandigarh, India Rajasthan University of Health Sciences
Division of Hematology
Jaipur, Rajasthan, India
Mayo Clinic
Thomas Joseph Rochester, Minnesota, USA
Global TB programme Sunil D Khaparde
World Health Organization Former Deputy Director General- Sunesh Kumar
Geneva, Switzerland Tuberculosis Professor
Central TB Division Department of Obstetrics and
Ministry of Health and Family Welfare Gynaecology
Shalini Joshi All India Institute of Medical Sciences
Government of India
Consultant New Delhi, India
New Delhi, India
Department of Internal Medicine
Fortis Hospitals and Health Care T Mohan Kumar
Bengaluru, Karnataka, India Saurav Khatiwada Head of the Department and Chief
Department of Endocrinology and Consultant
Metabolism Institute of Pulmonary Medicine and
SK Kabra
All India Institute of Medical Sciences Research
Professor
New Delhi, India Sri Ramakrishnan Hospital
Department of Paediatrics
Coimbatore, Tamil Nadu, India
New Delhi, India
MPS Kohli Jason Limberis
National Consultant Lung Infection and Immunity Unit
Tamilarasu Kadhiravan Public Private Mix [Union SEA Office] Division of Pulmonology and
Additional Professor Central TB Division University of Cape Town Lung Institute
Department of Medicine Directorate General of Health Services Department of Medicine
Jawaharlal Institute of Postgraduate Ministry of Health and Family Welfare University of Cape Town
Medical Education and Research Government of India Cape Town, South Africa
Puducherry, India New Delhi, India
Rakesh Lodha
Professor
Arvind Kumar Kairo SS Kothari Division of Pulmonology, Intensive Care
Assistant Professor Professor and Tuberculosis
Department of ENT and Neck Surgery Department of Cardiology Department of Paediatrics
All India Institute of Medical Sciences All India Institute of Medical Sciences All India Institute of Medical Sciences
New Delhi, India New Delhi, India New Delhi, India
x Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases
Knut Lönnroth SP Munigoti John Porter

Professor of Social Medicine Consultant Professor
Karolinska Institutet Department of Endocrinology and London School of Hygiene and Tropical
Senior Consultant Metabolism Medicine
Centre for Epidemiology and Fortis Hospitals and Health Care London, UK
Community Health Bengaluru, Karnataka, India
Stockholm County Council Jagdish Prasad
Department of Public Health Sciences Former Director General of Health
Social Medicin Y Mutheeswaraiah
Services
Stockholm, Sweden Professor and Head
Ministry of Health and Family Welfare
Department of General Surgery
Government of India
Sri Venkateswara Institute of Medical
New Delhi
Govind K Makharia Sciences
Head of Cardiothoracic and
Professor Tirupati, Andra Pradesh, India
Vascular Surgery Department
Department of Gastroenterology and
Safdarjung Hospital
Human Nutrition
HL Nag New Delhi, India
New Delhi, India Professor
Department of Orthopaedics Kurupath Radhakrishnan
All India Institute of Medical Sciences Former Senior Professor
NK Mehra New Delhi, India Department of Neurology and Director
Dr CG Pandit National Chair Sree Chitra Tirunal Institute for Medical
Former Dean [Research] Sciences and Technology
Former Professor and Head Sreenivas Achutan Nair Thiruvananthapuram, Kerala, India
Department of Transplant Immunology Stop TB Partnership
Senior Consultant
and Immunogenetics Geneva, Switzerland
Avitis Institute of Medical Sciences
All India Institute of Medical Sciences Palakkad, Kerala, India
New Delhi, India
Jai P Narain
Former Director AK Rai
DK Mitra Department of Communicable Diseases Assistant Professor
Professor and Head WHO Regional Office for South-East Asia Department of Biotechnology
Department of Transplant Immunology New Delhi, India Motilal Nehru National Institute of
and Immunogenetics Technology
All India Institute of Medical Sciences Allahabad, Uttar Pradesh, India
New Delhi, India
Madhukar Pai
Director
M Ramam
McGill Global Health Programs
Professor
Alladi Mohan Associate Director
Department of Dermatology and
Chief, Division of Pulmonary and McGill International TB Centre
Venereology
Critical Care Medicine Professor of Epidemiology All India Institute of Medical Sciences
Professor and Head McGill University New Delhi, India
Department of Medicine Montreal, Quebec, Canada
Sri Venkateswara Institute of Medical
Mario C Raviglione
Sciences
CN Paramasivan Professor
Tirupati, Andhra Pradesh, India
Senior Scientific Advisor Department of Biomedical Sciences for
FIND, India Health
Prasanta Raghab Mohapatra University of Milan
Professor and Head Milan, Italy
Department of Pulmonary Medicine and Tania Di Pietrantonio Former Director
Critical Care McGill University Health Center Global TB Programme
All India Institute of Medical Sciences McGill University World Health Organization
Bhubaneswar, Odisha, India Montreal, Quebec, Canada Geneva, Switzerland
Contributors xi
Ruma Ray Erwin Schurr K Aparna Sharma

Professor Leader Associate Professor
Department of Pathology Infectious Diseases and Immunity in Department of Obstetrics and
All India Institute of Medical Sciences Global Health Gynaecology
New Delhi, India McGill University Health Centre All India Institute of Medical Sciences
McGill University New Delhi, India
Montreal, Quebec, Canada
Divya Reddy
Pulmonary Division
Aparna Singh Shah Kusum Sharma
Albert Einstein College of Medicine/
Regional Advisor Professor
Montefiore Medical Center
Blood Safety and Laboratory Technology Medical Microbiology
Bronx, New York, USA WHO Regional Office for South-East Asia Postgraduate Institute of Medical
New Delhi, India Education and Research
BB Rewari Chandigarh, India
Scientist–HIV/STI/HEP N Sarita Shah
World Health Organization Regional Associate Chief
Office for South-East Asia Science International Research and SC Sharma
New Delhi, India Programs Branch Professor and Head
Division of Tuberculosis Elimination Department of ENT and Neck Surgery
National Center for HIV, Viral Hepatitis, All India Institute of Medical Sciences
A Roy STD and TB Prevention New Delhi, India
Professor Centers for Disease Control and
Department of Cardiology Prevention
All India Institute of Medical Sciences Atlanta, Georgia, USA Surendra K Sharma
New Delhi, India Former Senior Professor and Head
Aman Sharma Department of Internal Medicine
KS Sachdeva Professor [WHO Collaborating Centre for Research
Deputy Director General–TB Rheumatology Services and Training in Tuberculosis
Central TB Division Department of Internal Medicine Centre of Excellence for Extrapulmonary
Postgraduate Institute of Medical TB, Ministry of Health and Family Welfare,
Directorate General of Health Services
Education and Research Government of India]
Ministry of Health and Family Welfare
Chandigarh, India All India Institute of Medical Sciences
Government of India
New Delhi, India
New Delhi, India
Amit Sharma Adjunct Professor
Chest Specialist
Department of Molecular Medicine
Pournamy Sarathchandran Department of Tuberculosis and
Jamia Hamdard Institute of Molecular
Former Assistant Professor Respiratory Diseases
Medicine
Department of Neurology National Institute of Tuberculosis and
Jamia Hamdard [Deemed to be University]
Sree Chitra Tirunal Institute for Medical Respiratory Diseases
New Delhi, India
Sciences and Technology New Delhi, India
Thiruvananthapuram, Kerala, India Adjunct Professor
Gaurav Sharma Departments of General Medicine and
Scientist I Respiratory Medicine
Kavitha Saravu
Department of Transplant Immunology Jawaharlal Nehru Medical College
Additional Professor
and Immunogenetics Datta Meghe Institute of Medical
All India Institute of Medical Sciences Sciences [Deemed to be University]
Kasturba Medical College
New Delhi, India Wardha, Maharashtra, India
Manipal, Karnataka, India
JB Sharma
Jussi Saukkonen Professor Amar Singh
Director Department of Obstetrics and Department of Transplant Immunology
Medical Intensive Care Unit Gynaecology and Immunogenetics
VA Boston Healthcare System All India Institute of Medical Sciences All India Institute of Medical Sciences
West Roxbury, MA, USA New Delhi, India New Delhi, India
xii Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases
Divya Singh Srikanth Tripathy Andrew Vernon

Department of Radiodiagnosis Scientist G and Director-in-charge Chief
All India Institute of Medical Sciences National Institute for Research in Clinical Research Branch
New Delhi, India Tuberculosis Division of Tuberculosis Elimination
Chennai, Tamil Nadu, India National Center for HIV, Viral Hepatitis,
Rupak Singla STD and TB Prevention
Head Centers for Disease Control and
Department of Tuberculosis and AK Tyagi Prevention
Respiratory Diseases Vice-Chancellor Atlanta, Georgia, USA
National Institute of Tuberculosis and Guru Gobind Singh [GGS]
Respiratory Diseases Indraprastha University Late VK Vijayan
New Delhi, India Sector 16-C, Dwarka, New Delhi, India Former Advisor
Professor ICMR Bhopal Memorial Hospital and
Ramnath Subbaraman Department of Biochemistry Research Centre
Assistant Professor National Institute for Research in
University of Delhi [South Campus]
Department of Public Health and Environmental Health
New Delhi, India
Community Medicine Former Director
Tufts University School of Medicine Vallabhbhai Patel Chest Institute
Boston, MA, USA University of Delhi
Mukund Uplekar
Former Senior Medical Officer Delhi, India
Grant Theron Policy, Strategy and Innovations Unit
Lung Infection and Immunity Unit
Global TB Programme Kamini Walia
Division of Pulmonology and University
World Health Organization Scientist F
of Cape Town Lung Institute
Geneva, Switzerland Indian Council of Medical Research
Hon. Professor New Delhi, India
University of Cape Town
Cape Town, South Africa Interdisciplinary School of
Health Sciences Diana Weil
Deanna Tollefson Pune University Coordinator
Epidemiologist Pune, Maharashtra, India TB Policy, Strategy and Innovations [PSI]
International Research and Programs Global TB Programme [GTB]
Branch World Health Organization [WHO]
Division of Tuberculosis Elimination Pradeep Venkatesh Geneva, Switzerland
National Center for HIV, Viral Hepatitis, Professor
STD and TB Prevention Dr Rajendra Prasad Centre for Ting-Heng Yu
Centers for Disease Control and Ophthalmic Sciences McGill University Health Center
Prevention All India Institute of Medical Sciences McGill University
Atlanta, Georgia, USA New Delhi, India Montreal, Quebec, Canada
Foreword
“Rarely has any epidemic tormented the humankind with the tenacity and destructive impact of tuberculosis [TB]…TB
still constitutes a social, economic and political threat set to impede development of entire populations…”. This is what
I said in my foreword to the previous edition of this book in 2009. It is hardly surprising that the statements remain true
nine years later. On the occasion of the publication of the new edition that will explore in-depth from all angles this ancient
disease, I feel honoured to have been asked by Professor Surendra K Sharma, for a second time in a row, to write a foreword
of his Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases—3rd edition, a book that is a true state-of-the-art
manual on the disease. In the Global TB Report of the World Health Organization [WHO], published in October 2017 when
I was still director of the Global TB Programme, we highlighted several important facts. First, thanks to recent intensive
efforts to improve the collection and reporting of data through special surveys and surveillance, WHO now estimates that
there may be over a million more cases of TB than previously believed. This translated into 10.4 million people developing
TB in 2016 and 1.7 million dying of it. Second, the report stresses that, despite the rise in absolute numbers, the mortality
rate from TB continues falling at about 3% per year. As a result of control efforts, an estimated 53 million lives have been
saved since 2000. This is encouraging; however, the TB incidence rate is declining very slowly at an average of 1.5% a year.
With such an enormous toll in terms of number of deaths, TB, remains the biggest killer from a single infectious agent.
Thirdly, over 4 million people who develop TB are still being ‘missed’ by health systems each year: a large number of
them are not diagnosed due to poor access to services or lack of capacity; and an even larger number is probably diagnosed
and treated somehow outside the public sector but not notified. Fourth, the global multidrug-resistant TB [MDR-TB] crisis
continues, with an estimated 600,000 new MDR-TB and rifampicin-resistant cases in 2016. A trend analysis revealed that
the estimated percentage of new TB cases with MDR-TB globally remains roughly unchanged at 4%. However, severe
epidemics still ravage some regions, particularly Eastern Europe and Central Asia. Extensively drug-resistant TB
[XDR-TB], which is more expensive and difficult to treat than MDR-TB, has now been reported in most countries that are
capable of detecting it. Unfortunately, the progress in the MDR-TB response has been far too slow: while there has been
an increase of cases being diagnosed thanks to more laboratories rolling out rapid tests, only less than a quarter of the
estimated cases are being detected and treated. In 2019, at the time of publication of the 3rd edition of this book, therefore,
several major challenges remain to be faced. The first one is to ensure that all the cases are diagnosed, managed successfully
and notified; the second is to respond effectively to the MDR-TB crisis; the third is to consolidate achievements in the
response to HIV-associated TB; the fourth is to ensure research efforts are urgently intensified so that innovations emerge
within years instead of decades; and the fifth is to ensure all financial gaps in both control and research efforts are filled.
In May 2014, the World Health Assembly of WHO approved—through an historical resolution—a set of new and ambitious
targets for 2030 and 2035 to be reached through a new global TB strategy. This new End TB Strategy, based on three pillars
and four fundamental principles, incorporates all possible elements that are essential for a recipe towards TB elimination.
The TB-specific interventions are included in the first pillar of the new strategy: it consists of a modern version of DOTS
[1994-2005] and the Stop TB Strategy [2006-2015], which incorporates all technological innovations from early diagnosis
of TB and universal drug susceptibility testing using rapid molecular tests to treatment of all types of TB and management
of latent infection among people with a higher risk of getting TB. The second pillar consists of those broad health system
policies that are essential to render any disease control effort successful: these include regulatory approaches such as
mandatory case notifications and rational drug use, as well as essential far-reaching measures like universal health coverage
and social protection to ensure that the poorest among the poor can access care. The third pillar emphasises the role of
research and rapid intake and adaptation of all innovations in all countries world-wide. It is in this context that the
publication of the 3rd edition of this book by Professor Surendra K Sharma is particularly important. Indeed, this edition
represents a major advance over the previous ones as it is based on the feedback received from different categories of
students and health professionals and adapted to the needs of such different audiences. As a result of a “client survey”,
the editor decided to develop a set of two different textbooks: an elaborate version for postgraduates and more advanced
readers and a compact one providing the essentials for undergraduate students. The larger version, similar to the
2nd edition, although slimmer and more user-friendly, is a comprehensive and well-referenced textbook. It will contain
chapters focused on clinical aspects—a true reference for clinicians managing patients with any variety of TB. It will also
present the very basics of TB, from epidemiology to bacteriology, from genetics to immunology, and from diagnosis to
treatment. In some cases, the old chapters have been merged to make them more easily accessible. For some new areas,
xiv Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases
such as the place of TB in the post Millennium Development Goal [MDG] agenda or the engagement of communities in
TB care, new chapters have been added. Continuing its laudable trend, the inclusion of many chapters devoted to public
health and control aspects in this edition makes this textbook an international reference in a broader sense. Above all,
there are chapters that examine the delicate interface between public services and the private and non-state sector, an issue
that must be faced with an innovative spirit given its challenging nature, and the fundamental infection control measures
often neglected in many countries. Importantly, for every clinical and public health practitioner, the book contains a
description of the WHO’s new global strategy—the End TB Strategy 2016-2035—and the International Standards of TB
Care including their adaptation in the Indian context. These chapters provide the most modern and innovative thinking
about the way the TB epidemic must be addressed at the bedside, in the clinics, and in the health centres supervised by
TB control programmes. The second compact version of the book is a practical “handbook” for young undergraduates to
carry in the pockets of a coat. This will contain the essential information with additional sections made available “on-line”.
It is intended as a rapid reference to help quick learning and action. Naturally, to cover all needs and provide the best
possible information to readers, a remarkable panel of authors has been put together by Professor Sharma; it includes both
experts from India and international authorities. In conclusion, the two versions of this prestigious textbook, devoted
to a major disease that has affected humanity since its beginning, have all the characteristics to consolidate the
previous edition’s reputation of an authoritative and international reference for all readers. The fact that it is conceived
and produced in India, the country which not only has the highest TB burden in the world, but has also contributed to
many of the major advances in TB care and control over the past decades, is symbolic. And the fact that it is published in
the historical year during which TB will be the subject of a high-level meeting of leaders at the United Nations General
Assembly adds value to a book that expresses the latest scientific knowledges about the crucial topic of TB. It is my hope
that this modern and up-to-date textbook becomes a fundamental companion for all junior and senior practitioners tackling
TB prevention, care and control in India, elsewhere in Asia, and world-wide so that our global fight against this ancient
disease can be better informed and more effective.
Mario C Raviglione FRCP [UK] FERS Hon RSP [RF]

Professor
Department of Biomedical Sciences for Health
University of Milan
Milan, Italy
Former Director
Global TB Programme
World Health Organization
Geneva, Switzerland
Preface to the Third Edition
The first edition of Tuberculosis book in 2001 was widely acclaimed not only in India and South-East Asia, but also in several
other parts of the world. Subsequently, the second edition of Tuberculosis was published in 2009 which was well received
and established itself as a standard textbook on tuberculosis [TB]. The last decade has witnessed phenomenal changes in
our understanding of TB and there have been overwhelming requests for updating this textbook. Further, major advances
have also occurred in nontuberculous mycobacterial [NTM] diseases in the recent years. This prompted us to bring out the
third edition of the book which is now titled Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases with an aim
to provide a well referenced standard textbook on TB and NTM diseases that will chronicle the rich and vast experience
of clinicians and researchers from across the globe.
This edition has several new contributors, all of them are leading authorities, from various parts of the world. All the
chapters have been thoroughly re-written and updated, many of them are by new but renowned contributors. Several
new high quality clinical, radiographic images, gross pathology specimen photographs, and photomicrographs have been
included in this edition for the readers’ convenience. This edition documents the rapid advances that have occurred at a
blistering pace in TB diagnosis, universal drug-susceptibility testing [DST] and treatment of dug-susceptible and drug-
resistant TB, including multidrug-resistant and extensively drug-resistant TB [M/XDR-TB], programmatic management of
drug-resistant TB, public-private mix, the ENGAGE-TB approach, and END TB strategy, among others. The present edition
includes recent classification of drugs and drug combinations including recent generation quinolones, bedaquiline and
linezolid used in treating M/XDR-TB and a chapter detailing the latest developments in the field of laboratory diagnosis
and management of NTM diseases.
We sincerely believe that the third edition will help undergraduate and postgraduate medical students and medical
college faculty members in updating their knowledge. We hope that it will continue to be a valuable source of reference
to researchers and enhance the understanding of practising physicians and contribute to patient management. The third
edition is also envisaged to be a practical guide for health care workers, nurses, and other paramedical staff.
This effort would not have been possible but for the kind co-operation and magnanimity of our contributors who spared
their valuable time and patiently went through endless series of revisions and constant updating. We would like to thank
Shri Jitendar P Vij [Group Chairman], Mr Ankit Vij [Managing Director], Ms Chetna Malhotra Vohra [Associate Director–
Content Strategy] of M/s Jaypee Brothers Medical Publishers [P] Ltd, New Delhi, India, for their encouragement and
support, and excellent technical assistance. Our families have stood by us through these turbulent times and without their
unstinting support and constant encouragement, this third edition would not have materialised.
Surendra K Sharma
Alladi Mohan
Preface to the First Edition
Tuberculosis is an ancient disease which continues to haunt us even as we step into the next millennium. Tuberculosis is
the most common cause of death world over due to a single infectious agent in adults and accounts for over a quarter of all
avoidable deaths globally. One-third of India’s population is infected with Mycobacterium tuberculosis, there are 12 million
active tuberculosis cases in India. One person dies of tuberculosis every minute in India. The deadly synergy between
Mycobacterium tuberculosis and the human immunodeficiency virus [HIV] has resulted in a resurgence of tuberculosis
world over. The impact of this “cursed duet” on human suffering has been enormous. With HIV making rapid inroads in
India, the spectre of dual infection with HIV and tuberculosis is going to be a daunting prospect. In spite of this gloomy
scenario, the treatment of tuberculosis is one of the most cost-effective methods of cure. Research work carried out in India
has had a tremendous impact on tuberculosis control. The observations from the well-known, randomized controlled trial
“The Madras Study” carried out at the Tuberculosis Research Centre [TRC], Chennai, Tamil Nadu, India, established
the efficacy of the domiciliary treatment and has paved the way for the National Tuberculosis Programme in India and
several other countries. Pioneering contributions from eminent clinicians, bacteriologists and epidemiologists from the
TRC, Chennai; National Tuberculosis Institute, Bangalore; Sanatoria at Madanapalle, Kasauli, Dharampur, Bhowali,
have greatly enhanced our understanding of tuberculosis.
The changing clinical presentation of tuberculosis, advances in laboratory and imaging diagnostic modalities and
therapeutic measures such as directly observed treatment, short-course [DOTS] all suggest a pressing need to have a
recent textbook of tuberculosis. Furthermore, while every doctor working in India encounters the disease in one or other
form, very little has been documented regarding the Indian perspective of tuberculosis. Often, the medical students,
postgraduates and researchers returning empty handed from libraries expressed their desire for a book which documents
the Indian experience. Paucity of a well referenced, standard textbook of tuberculosis, which chronicles the rich and vast
clinical experience of clinicians from India prompted us to undertake this venture. We have attempted to present a picture
of tuberculosis as it is seen in India with contributions from experts who have vast experience in managing tuberculosis
in the Indian setting. Our book contains chapters on History, Pathology, Epidemiology, Clinical Presentation, Diagnosis,
Treatment, Prevention and Control of tuberculosis highlighting the Indian perspective of tuberculosis. We have also
provided guidelines published by the authorities concerned with tuberculosis control, and other statements as useful
appendices. Though we have made an effort to maintain a uniform style and format, we have been careful to preserve
the views expressed by the contributors in their original form. As we step into the new millennium, it is obvious that the
crusade against this ancient foe of mankind is still going on. Contrary to the wishful thinking in the 1980s, tuberculosis still
remain to be a research priority of paramount importance and is an important component of curricula of medical schools.
Keeping in mind the need of the hour, we have attempted to highlight the rationale behind DOTS and its importance in
tuberculosis control. We believe that our book will help undergraduate and postgraduate medical students to update their
knowledge. It will also be a source of reference to researchers and better the understanding of practising physicians and
help in patient management. We also hope that the book can serve as a practical guide on the management of tuberculosis
to health care workers, nurses and other paramedical staff.
A book of this magnitude would not have been possible but for the magnanimity and kindness of our contributors
who took time off their busy schedule to prepare their manuscripts. We would like to thank Mr Jitendar P Vij,
Chairman and Managing Director and Mr RK Yadav, Publishing Director, M/s Jaypee Brothers Medical Publishers Pvt
Ltd., for their support, co-operation and technical excellence. Without the unstinting support, constant encouragement and
help from our families this endeavour would not have been possible.
S.K. Sharma
A. Mohan
Acknowledgements
We would like to especially thank the M/s Jaypee Brothers Medical Publishers [P] Ltd, New Delhi, India, who have granted
permissions to reproduce various items from their published work and these have duly acknowledged in the respective
chapters. An invaluable help of the World Health Organization [WHO], Geneva, Switzerland for liberally granting
permission to reproduce figures and tables from several publications is gratefully acknowledged.
We express our sincere gratitude to the following Drs Mario Raviglione, Dennis Falzon, Mukund Uplekar, Knut Lonnroth,
Deanna Tollefson, N Sarita Shah, Andrew Vernon, Haileyesus Getahun, Mr Thomas Joseph, Drs Sreenivas A Nair,
Md Khurshid Alam Hyder, Vineet Bhatia, Diana Weil, Divya Reddy, Jussi Saukkonen, Keertan Dheda, Erwin Schurr,
Madhukar Pai and John Porter, for their excellent contributions. Special thanks are also due to Dr PC Hopewell, University
of California, San Francisco, USA for his suggestions on the International Standards for Tuberculosis Care [ISTC].
We especially thank Dr Jai P Narain, Former Director, Department of Communicable Diseases, WHO Regional Office for
South-East Asia, New Delhi, Dr Jagdish Prasad, Former Director General of Health Services [DGHS], Ministry of Health and
Family Welfare, Government of India [MoH & FW, GoI], Dr LS Chauhan, Former Deputy Director General [Tuberculosis],
Central TB Division, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India,
for their valuable contributions, critical comments, stimulating discussions, constant support and encouragement. We
would like to thank Dr VM Katoch, Former Secretary, Department of Health Research [DHR], MoH & FW, GoI, and
Former Director General, Indian Council of Medical Research [ICMR], New Delhi, and Dr CN Paramasivan, Foundation
for Innovative New Diagnostics [FIND], India, for their constant encouragement.
We thank Dr KS Sachdeva, Deputy Director General [Tuberculosis], Central TB Division, Directorate General of Health
Services, MoH & FW, GoI, for his constant support and encouragement. We also wish to thank Directors of National Institute
of Tuberculosis and Respiratory Diseases [NITRD], New Delhi; ICMR-National Institute for Research in Tuberculosis [NIRT],
Chennai and National Tuberculosis Institute [NTI], Bengaluru, Karnataka, the administration of Arogyavaram Medical
Centre, Madanapalle, Andhra Pradesh, and TB Sanatorium at Bhowali, Uttarakhand for permitting us to reproduce the
images of these well known institutions.
We are grateful to the Departments of Pathology, All India Institute of Medical Sciences [AIIMS], New Delhi;
Sri Venkateswara Institute of Medical Sciences [SVIMS], Tirupati, Andhra Pradesh; and Postgraduate Institute of Medical
Education and Research [PGIMER], Chandigarh for providing gross pathology specimen figures and histopatho
logy photomicrographs. We wish to thank the Departments of Radiod iagnosis, AIIMS, New Delhi and SVIMS,
Tirupati for providing classic radiographic imaging figures. We sincerely thank Dr Ajay Garg, Department of Neuroradio
logy, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi for providing radiographic images,
Dr C Narasimhan, CARE Hospitals, Hyderabad, Telangana, India, Dr Tara Roshini Paul, Professor, Department of Pathology,
Nizam’s Institute of Medical Sciences, Hyderabad, for providing echocardiographic images, photomicrographs respectively.
We also wish to thank faculty members of AIIMS, New Delhi; SVIMS, Tirupati; and other medical colleges across
India and several other parts of the world, several generations of undergraduate and postgraduate students, for their
constructive criticism and useful suggestions during our discussions. These inputs were indeed useful for the Third Edition
of the book.
Invaluable help rendered by Dr Krishna Srihasam, Boston, USA; and Dr Srinivas Bollineni, Dallas, USA, in getting full
text references is also thankfully acknowledged. We also wish to thank Mr Alladi V Srikumar’s timely help with broadband
connectivity.
Contents
1. History............................................................................................................................ 1
Alladi Mohan, Surendra K Sharma
2. Epidemiology of Tuberculosis: Global Perspective.......................................................................13

Dennis Falzon, Knut Lönnroth, Mario C Raviglione
3. Pathology of Tuberculosis....................................................................................................25
Siddhartha Datta Gupta, Prasenjit Das, Gaurav PS Gahlot, Ruma Ray
4. The Mycobacteria..............................................................................................................52
Aparna Singh Shah, Rajesh Bhatia
5. Immunology of Tuberculosis.................................................................................................59
DK Mitra, AK Rai, Amar Singh
6. Genetic Susceptibility Parameters in Tuberculosis......................................................................73

NK Mehra, Gaurav Sharma, Deepali K Bhat
7. Genetics of Susceptibility to Tuberculosis.................................................................................92

Ting-Heng Yu, Tania Di Pietrantonio, Erwin Schurr
8. Laboratory Diagnosis of Tuberculosis: Best Practices and Current Policies....................................... 106

Madhukar Pai, Marzieh Ghiasi, Kavitha Saravu
9. Roentgenographic Manifestations of Pulmonary and Extra-pulmonary Tuberculosis............................. 113

Chandan J Das, Ankur Goyal, Divya Singh
10. Pulmonary Tuberculosis.................................................................................................... 146

VK Vijayan, Sajal De
11. Lower Lung Field Tuberculosis............................................................................................ 155

Gautam Ahluwalia, Surendra K Sharma
12. Endobronchial Tuberculosis................................................................................................ 160

Samjot S Dhillon, Nicola A Hanania
13. Tuberculosis Pleural Effusion.............................................................................................. 175

AN Aggarwal
14. Silicotuberculosis............................................................................................................ 200

Prasanta Raghab Mohapatra
xxii Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases
15. Abdominal Tuberculosis.................................................................................................... 208

Govind K Makharia
16. Granulomatous Hepatitis................................................................................................... 222

Vineet Ahuja, SK Acharya
17. Neurological Tuberculosis.................................................................................................. 230

Pournamy Sarathchandran, Kurupath Radhakrishnan
18. Tuberculosis and Heart..................................................................................................... 253

SS Kothari, A Roy
19. Skeletal Tuberculosis....................................................................................................... 267

S Bhan, HL Nag
20. Musculoskeletal Manifestations of Tuberculosis....................................................................... 294

Aman Sharma, Kusum Sharma
21. Cutaneous Tuberculosis.................................................................................................... 302

M Ramam
22. Lymph Node Tuberculosis.................................................................................................. 313

Saurav Khatiwada, Arvind Kumar
23. Tuberculosis in Head and Neck............................................................................................ 326

Arvind Kumar Kairo, SC Sharma
24. Ocular Tuberculosis......................................................................................................... 335

Pradeep Venkatesh, Rohan Chawla, SP Garg
25. Tuberculosis in Pregnancy ................................................................................................. 346

Sunesh Kumar, Vatsla Dadhwal, K Aparna Sharma
26. Female Genital Tuberculosis .............................................................................................. 354

Sunesh Kumar, JB Sharma
27. Genitourinary Tuberculosis ................................................................................................ 368

Rajeev Kumar, AK Hemal
28. Tuberculosis in Chronic Kidney Disease................................................................................. 379

SK Agarwal
29. Disseminated/Miliary Tuberculosis....................................................................................... 391

Surendra K Sharma, Alladi Mohan
30. Tuberculosis at Uncommon Body Sites................................................................................... 411

Y Mutheeswaraiah, J Harikrishna
Contents xxiii
31. Complications of Pulmonary Tuberculosis............................................................................... 419

D Behera
32. Tuberculosis and Acute Respiratory Distress Syndrome.............................................................. 432

DR Karnad, KK Guntupalli
33. Haematological Manifestations of Tuberculosis ....................................................................... 442

Shaji Kumar
34. Endocrine Implications of Tuberculosis.................................................................................. 453

CV Harinarayan, Shalini Joshi, SP Munigoti
35. Tuberculosis and Human Immunodeficiency Virus Infection.......................................................... 466

BB Rewari, Amitabh Kumar, Srikanth Tripathy, Jai P Narain
36. Tuberculosis in Children ................................................................................................... 483

SK Kabra, Rakesh Lodha
37. Surgical Aspects of Childhood Tuberculosis............................................................................. 495

Minu Bajpai, Alisha Gupta, Manisha Jana, Arun K Gupta
38. Tuberculosis in the Elderly................................................................................................. 506

Surendran Deepanjali, Tamilarasu Kadhiravan
39. Tuberculosis in Health Care Workers..................................................................................... 520

SK Jindal
40. Nutrition and Tuberculosis................................................................................................. 529

Ramnath Subbaraman, Jason Andrews
41. Nontuberculous Mycobacterial Infections................................................................................ 540

VM Katoch, T Mohan Kumar, Babban Jee
42. Drug-resistant Tuberculosis................................................................................................ 579

Keertan Dheda, Grant Theron, Gregory Calligaro, Jason Limberis, Malika Davids, Alisgar Esmail, Rodney Dawson
43. Antituberculosis Drug Resistance Surveillance......................................................................... 609

CN Paramasivan, VH Balasangameshwara
44. Treatment of Tuberculosis.................................................................................................. 621

Rupak Singla, Sanjay Gupta, Amit Sharma
45. Hepatotoxicity Associated with Anti-tuberculosis Treatment......................................................... 637

Divya Reddy, Jussi Saukkonen
46. Surgery for Pleuropulmonary Tuberculosis.............................................................................. 644

Abha Chandra
xxiv Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases
47. Stopping TB: The Role of DOTS in Global Tuberculosis Control...................................................... 654
Deanna Tollefson, N Sarita Shah, Andrew Vernon
48. The Role of Medical Colleges in Tuberculosis Control................................................................. 668

D Behera, MPS Kohli, Jai P Narain
49. Public-Private Mix for TB Care............................................................................................. 676

Mukund Uplekar, Sreenivas Achutan Nair
50. Building Partnerships for Tuberculosis Control......................................................................... 684

Vineet Bhatia, Md Khurshid Alam Hyder
51. Integrating Community-based Tuberculosis Activities into the Work of Non-governmental and
other Civil Society Organisations [The ENGAGE-TB Approach]....................................................... 697
Haileyesus Getahun, Thomas Joseph
52. WHO’s New End TB Strategy............................................................................................... 704

Mukund Uplekar, Diana Weil
53. The Revised National Tuberculosis Control Programme.............................................................. 712

Jagdish Prasad, Sunil D Khaparde, KS Sachdeva
54. Tuberculosis Vaccine Development: A Current Perspective........................................................... 727

AK Tyagi, B Dey, R Jain
55. Ethical and Legal Issues in Tuberculosis Control....................................................................... 746

John Porter
56. Airborne Tuberculosis Transmission and Infection Control Strategies.............................................. 759

Kamini Walia, Jai P Narain
57. Standards for TB Care in India............................................................................................. 768
58. International Standards for Tuberculosis Care.......................................................................... 797
59. Index-TB Guidelines [Guidelines on Extra-pulmonary Tuberculosis for India]..................................... 886
Index......................................................................................................................................................................961
1
History
Alladi Mohan, Surendra K Sharma
INTRODUCTION TUBERCULOSIS IN ANCIENT TIMES

As a destroyer of mankind, tuberculosis has no equal... It is thought that TB probably existed in cattle before its
VA Moore (1) advent in man.
Tuberculosis [TB] has been a major cause of suffering muncami tva havisa jivanayakam
and death since times immemorial. Thought to be one of agnatayaksmad uta rajayakshma...
the oldest human diseases, the history of TB is at least as [I deliver you by means of oblation so that you may live from
old as the mankind. Over the years, not only the medical the unknown disease and from the “rajayakshma”]
implications but also the social and economic impact of TB [RV, X,161,1]
has been enormous.
There have been references to this ancient scourge in the In the Krishna Yajurveda Samhita, there is reference
Vedas [vide infra] and it was called “rajayakshma” [meaning to how, Soma [Moon] had been affected by “yakshma”.
“wasting disease”]. Hippocrates [460-377 B.C.] called the Since “Soma”, who was the “King and Ruler” was affected
disease “pthisis”, a Greek word which meant “to consume”, by “yakshma”, it came to be known as “rajayakshma”
“to spit” and “to waste away“ (2,3). The word “consumption” [Figure 1.1].
[derived from the Latin word “consumere”] has also been In Sanskrit, the disease has been called “rajayakshma”,
used to describe TB in English literature. The Hebrew word “ksayah”, and “sosa”.
“schachepheth” [meaning “waste away”] has been used in
Rajayakshma ksayah soso rogarad iti cha smritah
the Bible. J.L. Schonlein, Professor of Medicine at Zurich,
naksatranam, dvijanam cha rajno bhud yad aym pura
is credited to have named the disease “tuberculosis” (1).
yach cha raja cha yakshma cha rajayakshma tato matah
The word “tuberculosis” is a derivative of the Latin word
[Vagabhatta, Ast-s and Ast-hrd, Nidana V, 1-2]
“tubercula” which means “a small lump” (2,4,5). Several
names have been used to refer to TB in the years gone by. Krodho yakshma jvaro roga eko ‘rtho dukhasamjnitah
Acute progressive TB has been referred to as “galloping yasmat sa rajnah prag asid rajayakshma tatomatah
consumption”. Pulmonary TB has been referred to as “tabes [Charaka Samhita, Chikitsasthanam VIII, 11]
pulmonali”. Tuberculosis cervical lymphadenitis has been
called as “scrofula”, “King’s Evil”, “stroma”. Abdominal Changes resembling those caused by TB have been
TB has been called as “tabes mesenterica”. Cutaneous TB described in the skeletal remains of neolithic man (7).
has been called “lupus vulgaris”. Vertebral TB has been Terms such as “lung cough” and “lung fever” have been
called as “Pott’s disease”. Oliver Wendell Holmes referred used in ancient Chinese literature to describe a disease
to the disease as “white plague” (6). While scores of other which might have been TB (8). There have been references
diseases like smallpox and plague killed millions of people, to what could have been TB in the Code of Hammurabi
their reign has been relatively short-lived. Tuberculosis has of the Babylonian era (6). Evidences of TB lesions of bone
been ever present and is resurging with a vengeance. have also been found in Egyptian mummies dating back
2 Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases
Figure 1.1: Krishna Yajurveda Samhita, II kanda, III prasna, V anuvaka, 25th stanza, where the legend of “Soma” being afflicted with “rajayakshma”
is described
to 3400 B.C. (7). Mycobacterium tuberculosis has been Cappodocian [50 B.C.], in his book The causes and symptoms
demonstrated microscopically in the mummy of a child of of chronic diseases gave a very accurate description of TB and
five years (8). mentioned that fever, sweating, fatigue and lassitude were
There are several references to conditions resembling symptoms of the TB. He suggested testing the sputum with
TB in Greek literature by Homer [800 B.C.], Hippocrates, fire or water was of diagnostic value (7). Galen described
Aristotle [384-322 B.C.] and Plato [430-347 B.C.], that patients with “consumption” manifest cough, sputum,
Galen [129-199], Vegetius [420] were also familiar with wasting, chest pain and fever and considered haemoptysis
consumption. Arabic physicians Al Razi [850-953], Ibn Sina to be pathognomonic of the disease (6).
[980-1037] correlated lung cavities with skin ulceration. Following the pioneering efforts by Andreas Vesalius
During the middle ages, there are records of healing [1514-1564] post-mortem examination was performed
touch of monarchs was being used to treat “scrofula” frequently. This method of study facilitated understanding
[King’s Evil]. King Charles II bestowed the royal touch on of pathological findings, such as, lung cavities, empyema
an astounding 92,102 patients with “scrofula” (9). By around among others. Franciscus de Boe [1614-1672] [also known
1629, death certificates in London specified the disease as as Sylvius] for the first time associated small hard nodules
“consumption” which was a leading cause of death. By discovered in various tissues at autopsy with symptoms of
this time the contagious nature of TB was strongly believed “consumption” which the patients suffered during their life-
though there were people who contested this opinion. time though his explanation for the same was not correct (7).
The Republic of Lucca is credited to have passed the first John Jacob Manget in 1700 gave the description of classical
legislative action aimed at controlling TB in the world (4,9). miliary TB (10). The clinical presentation of consumption was
This was followed by similar measures in several Italian described in detail by Thomas Willis [1621-1675]. Richard
cities and Spain. Morton [1637-1698] had described several pathological
appearances of “pthisis” in his treatise Pthisiologica (4-6,7).
DIAGNOSIS Meaningful clinical examination became possible with
the description of the technique of percussion by Leopold
Why, when one comes near consumptives... does one Auenbrugger [1722-1809]. However, Auenbrugger’s
contract their disease, while one does not contract work was virtually ignored until the time of Jean Nicolas
dropsy, apoplexy, fever, or many other ills?.... Covisart [1775-1821], who rediscovered and propagated the
Aristotle technique. Gaspard Bayle [1774-1816] accurately described
In the early days, diagnosis of TB was based on symptoms many of the pathological changes of TB, but unfortunately
and signs. In Charaka Samhita [Nidanasthana, VI, 14], succumbed to the disease which he probably contracted
heaviness in the head, coughing, dyspnoea, hoarseness of while performing autopsy studies (11). The technique of
voice, vomiting of phlegm, spitting of blood, pain in the sides physical examination of the lung was further refined by
of the chest, grinding pain in the shoulder, fever, diarrhoea the invention of stethoscope by Rene Theophile Hyacinthe
and anorexia have been described as the eleven symptoms Laënnec [1781-1826], who was a student of Corvisart and a
of TB. Furthermore, a physician who is well versed in the friend of Bayle. Sadly, Laennec, his younger brother, mother
aetiology, clinical presentation and premonitory symptoms and two uncles all succumbed to TB (6).
of “consumption” was considered to be a “Royal Physician” Fracastorius [1443-1553] is credited to have originated the
[Charaka Samhita, Nidanasthana, VI, 17]. “germ theory” and believed that TB was contagious. He also
The earliest classical descriptions of TB in Greek literature mentioned about antiseptics in his chapter on the treatment
date back to the writings by Hippocrates. Aretaeus the of TB. In 1720, the English physician Benjamin Marten
History 3
conjectured, in his publication A new theory of consumption,

that TB could be caused by “certain species of animalcula
or wonderfully minute living creatures”, which, once they
had gained a foothold in the body, could generate the lesions
and symptoms of the disease. He also stated that
“it may be therefore very likely that by an habitual lying in
the same bed with a consumptive patient, constantly eating
and drinking with him, or by very frequently conversing so
nearly as to draw in part of the breath he emits from the lungs,
consumption may be caught by a sound person...I imagine that
slightly conversing with consumptive patients is seldom or
never sufficient to catch the disease” (12)
For unknown reason the work of Marten went into
oblivion for a long time. The likely reason could be that he
was thinking very much ahead of his time. Jean Antoine
Villemin [1827-1892] in a series of experiments provided
conclusive evidence that TB was indeed a contagious disease
though some workers of that era did not accept these results.
He presented his results to the Academie de Medcine on
December 5, 1865 and stated that TB was a specific infection
caused by an inoculable agent (3,6).
“During my wandering through medicine, I encountered sites
where gold was lying around. It needs a lot of serendipity
to distinguish gold from ignobility; this, however, is not a
Figure 1.2: Robert Koch: the discoverer of Mycobacterium tuberculosis
particular achievement.” Reproduced with permission from “Rubin SA. Tuberculosis. The
Robert Koch (13) captain of all these men of death. Radiol Clin North Am 1995;33:619-
Robert Heinrich Herman Koch [Figure 1.2], son of 39 (reference 6)”
a mining engineer, was born on December 11, 1843 in
Clausthal village in the Harz mountains (3,6,14,15). Koch Table 1.1: World TB Day themes
pursued medical studies at the Gottingen University in
Year World TB Day theme
1862 and qualified maxima cum laude in 1866 with his M.D.
thesis on succinic acid. On March 24, 1882 Koch announced 1997 Use DOTS more widely
1998 DOTS success stories
the discovery of the tubercle bacillus during the monthly
1999 Stop TB, use DOTS
evening meeting of the Berlin Physiological Society. In 1884, 2000 Forging new partnerships to stop TB
he published a more comprehensive paper Die aetiologic der 2001 DOTS: TB cure for all
tuberculose in the second volume of the Reports of the Imperial 2002 Stop TB, fight poverty
Health Office. In 1905, he was awarded the Nobel Prize for 2003 DOTS cured me–It will cure you too!
his contributions in the field of TB research (3,5,6). In 1982, 2004 Every breath counts–stop TB now
2005 Frontline TB care providers: Heroes in the fight against TB
a century after Dr Koch’s announcement, the World Health 2006 Actions for life–Towards a world free of TB
Organization [WHO] and the International Union Against 2007 TB anywhere is TB everywhere
Tuberculosis and Lung Disease [IUATLD], now called The 2008 I am stopping TB
Union proposed the 24th March as the “World TB Day” as a 2009 I am stopping TB
part of a year-long centennial effort under the theme “Defeat 2010 On the move against TB: Innovate towards action
TB: Now and Forever.” Thereafter, since 1996, 24th March is 2011 On the move against TB: Transforming the fight towards
elimination
celebrated as “World TB Day” every year (16,17). The event 2012 Call for a world free of TB
was intended to educate the public about the devastating 2013 Stop TB in my lifetime
health and economic consequences of TB, and its continued 2014 Reach the three million–A TB test, treatment and cure for all
tragic impact on the global health. Each “World TB Day” 2015 Gear up to end TB
addresses a different theme [Table 1.1]. Robert Koch died 2016 United to end TB
2017 Let’s unite to end TB
on May 27, 1910, aged 66 years.
2018 Wanted: Leaders for a TB-free world
It was Robert Koch who finally demystified the secret of
TB = tuberculosis; DOTS = directly observed treatment, short-course
the cause of TB and after thousands of years, the organism
finally revealed itself to humans. Though, Robert Koch was
wrong in his belief that tuberculin would cure TB, tuberculin With the advent of Wilhelm Conrad Roentgen [1845-1923],
became an invaluable tool for the diagnosis of latent TB the technique of radiological imaging became available.
infection (18). Francis Williams in Boston, L. Bouchard and A. Beclere
in France, John MacIntyre and David Lawson in Britain ‘Tis called the evil:
were pioneers in the use of radiography in the study A most miraculous work in this good king;
of TB (3,6). By this time, the deep mystery that was TB Which often since my here-remain in England
became demystified to some extent in that basic concepts of I have seen him do. How he solicits heaven,
the agent, the pathology as a result of it and its detection Himself best knows; but strangely visited people,
became established ushering in the era of definitive diagnosis All swollen and ulcerous, pitiful to the eye,
of TB. The mere despair of surgery, he cures,
Hanging a golden stamp about their necks,
TREATMENT Put on with holy prayers; and ’tis spoken,
To the succeeding royalty he leaves
In the Yajurveda, there are references to Soma performing The healing benediction
a “yagna” [sacred offering] seeking cure from TB. Since William Shakespeare
ancient times amulets, invocations, charms, Royal touch Macbeth, IV, iii, 146
and prayers have been used to treat TB. Chemicals such
as arsenic, sulphur, calcium, several vegetable, plant and There have been references to TB in several works of fiction.
animal products including excreta of humans and animals, There are references to TB in William Shakespeare’s plays
blood letting have been used over the centuries in the fond such as the “consumptive lover” of Much Ado About Nothing
hope of curing TB. Robert Koch, soon after his discovery of and “scrofula” in Macbeth. Charles Dickens describes the
the tubercle bacillus, ambitiously introduced the treatment sufferings of Little Blossom in David Copperfield. Thomas
using “Koch’s lymph” with disastrous results. It was later Mann’s The Magic Mountain contains one of the most
known that the substance was a glycerin extract of the well-known descriptions of TB sanatorium. Little Eva of
tubercle bacillus and was named as “tuberculin” (3,6). Harriet Beecher Stowe’s Uncle Tom’s Cabin, Milly Theale
During the 19th century, bed rest and change in in Henry James’ The Wings of the Dove, Marguerite Gautier
environment emerged as important forms of treatment of in Alexander Dumas’ La Dame aux Cameilas also suffered
TB. Hermann Brehmer, Peter Dettweiler, George Bodington, from TB.
Edward Livingston Trudeau, were all pioneers of the TB does not respect anybody. Several important
sanatorium movement. Hermann Brehmer, a Botany student personalities, statesmen, writers, poets, performing artists
suffering from TB, was instructed by his physician to seek have been consumed by TB [Table 1.2]. John Keats and
out a healthier climate. He travelled to the Himalayan Percy Bysshe Shelley symbolised the era of the “romantic
mountains where he could pursue his botanical studies consumptive youths of the 19th century” (3). The image of
while trying to rid himself of the disease. He returned home John Keats conveyed by the writings of contemporaries of
cured and began to study medicine. In 1854, he presented his era is that of a fragile poet who fell victim to TB because
his doctoral dissertation bearing the title, “Tuberculosis is his sensitive nature had been unable to withstand contact
a curable disease”. In the same year, he built an institution with a crude world (3). In a well-known anecdote, when his
in GÖrbersdorf where, in the midst of fir trees, and with friend John Brown discovers a drop of blood on the sheet
good nutrition, patients were exposed on their balconies while examining him, Keats says:
to continuous fresh air. This set up became the blueprint “I know the colour of that blood. It’s ‘arterial blood’...
for the subsequent development of sanatoria (12). During That blood is my death warrant, I must die ... (3)
this period, surgery was extensively used for the treatment Shelley, a fellow poet also suffered from TB pleurisy but
of TB. The reader is referred to the chapter “Surgery for did not succumb to the disease. On hearing the passing of
pleuropulmonary tuberculosis” [Chapter 46] for the details. Keats, Shelley wrote:
Efforts by Albert Calmette and his assistant Camille
From the contagion of the world’s slow stain
Guérin resulted in the introduction of bacille Calmette-
He is secure, and now can never mourn
Guérin [BCG] vaccine (19). Pioneering work of Selman
A heart grown cold, a head grown gray in vain;
Waksman led to the introduction of streptomycin as an
Nor, when spirit’s self has ceased to burn,
effective anti-TB drug. Jorgen Lehman was instrumental
With sparkless ashes load an unlamented urn...
in the discovery of para-amino salicylic acid [PAS]. With
the availability of these drugs and isoniazid, the era of The Bronte family included six children all of whom
modern predictably effective treatment ushered in. With the succumbed to TB. Maria and Elizabeth died at a very young
introduction of rifampicin, the treatment duration could be age. The son died of consumption, alcohol and opium. Emily
further shortened to the present-day six-month short-course [Wuthering Heights] and Charlotte [Jane Eyre] died aged 29
chemotherapy. and 39 respectively. It was thought that, their father Rev.
Patrick Bronte was the source of infection. The families of
TUBERCULOSIS IN ARTS AND LITERATURE Ralph Waldo Emerson and Henry David Thoreau were also
wiped out by consumption (3,6).
Youth grows pale, and spectre thin, and dies Several famous Indians had also succumbed to TB. The
John Keats list includes the famous mathematician Srinivasa Ramanujan,
Ode to a Nightingale writer Munshi Prem Chand, Kamala Nehru, among others.
History 5
Table 1.2: Well-known victims of tuberculosis DRUG-RESISTANT TUBERCULOSIS

Mathematician With the introduction of anti-TB drugs in the mid-1940s, the
Srinivasa Ramanujan era of cure for TB became a reality. Within a short period
Doctors of about a half-century, the menace of drug-resistant TB
Rene Theophile Hyacinthe Laënnec
Edward Livingston Trudeau
[DR-TB] became a serious threat to TB control. The 1990s
Writers and Poets witnessed mutlidrug-resistant TB [MDR-TB], then the early
Alexander Pope years of the new millennium have witnessed the menace
Samuel Johnson of extensively drug-resistant TB [XDR-TB]. The impact of
Jean-Jacques Rousseau X/MDR-TB on TB control is covered in “Drug-resistant
Johann Wolfgang von Goethe
tuberculosis” [Chapter 42].
Sir Walter Scott
Percy Bysshe Shelley
John Keats INDIA AND TUBERCULOSIS CONTROL
Leigh Hunt
Elizabeth Barrett Browning Research carried out in India has had a tremendous impact
Charlotte Brontë on TB and this experience has been of immense value in the
Emily Brontë control of TB worldwide. The first sanatorium in India was
Anne Brontë started in 1906 in Tilonia, Rajasthan. Subsequently, other
Fyodor Dostoevsky sanatoria were set-up in Almora in 1908 and Pendra Road,
Robert Louis Stevenson
Anton Chekhov
Central Provinces in Madhya Pradesh, at about the same
Franz Kafka time. The first sanatorium outside the patronage of Christian
Katherine Mansfield missionary organisations, called Hardinge Sanatorium was
George Orwell established at Dharampur, near Shimla in 1909 with the
Munshi Prem Chand help of donations from some Mumbai-based philanthropists,
Statesmen/Stateswomen
mainly Parsis, under the banner of the Consumptives’
Kamala Nehru
Eleanor Roosevelt Homes Society. The first Government-run sanatorium [King
Mohammed Ali Jinnah Edward Sanatorium] was started at Bhowali in Uttarakhand
Nelson Mandela [Figure 1.3]. The Union Mission Tuberculosis Sanatorium
Musicians [UMTS] was established in Arogyavaram, Madanapalle,
Frederic Francois Chopin Chittoor district, Andhra Pradesh in 1915 [Figure 1.4A].
Niccolo Paganini
With the advent of the National Tuberculosis Programme
Carl Maria von Weber
Performing Artists [NTP] in 1962, the UMTS was converted to a general hospital
Vivien Leigh called the Arogyavaram Medical Centre [Figure 1.4B] which
Elisa Rachel Felix is continuing to function even today. Till the mid-1950s,
Amitabh Bachchan important TB research activity in India was pioneered by
researchers [Figure 1.4C] at the UMTS sanatorium (26,27).
India became a member of the International Union
RISK FACTORS Against Tuberculosis in 1929. From the funds generated in
response to the appeal made on behalf of the government
Historically, several genetic, social, environmental and
by the then Vicereine Lady Linithgow, and the King George
biological determinants of health have been identified as
V Thanksgiving [Anti-Tuberculosis] Fund, the Tuberculosis
risk factors for TB. Role of genetic factors in the causation
Association of India [TAI] was formed in February, 1939.
of TB has been covered in the chapters “Genetic susceptibility
In 1940, the TAI and Government of India jointly set-up
parameters in tuberculosis” [Chapter 6] and “Genetics of
the New Delhi Tuberculosis Centre as a model clinic. In
susceptibility to tuberculosis” [Chapter 7]. No account of the
1951, the clinic was upgraded as first TB Training and
history of TB would be complete without a reference to
Demonstration Centre in the country. In 1941, the Lady
this modern foe. The impact of the twin disaster of human
Linlithgow sanatorium was setup at Kasauli (26-29). The
immunodeficiency virus [HIV] infection and TB on human
subsequent years saw the establishment of the Tuberculosis
suffering has been covered in the chapter “Tuberculosis
Chemotherapy Centre [TCC] at Chennai [then called
and human immunodeficiency virus infection” [Chapter 35].
Madras] and the National Tuberculosis Institute [NTI] at
The deadly interaction between diabetes mellitus [DM]
Bengaluru [then called Bangalore].
and TB is being increasingly recognised world over and
has lead to the institution of bi-directional screening for TB
National Institute for Research in Tuberculosis,
and DM (20-22). Evidence has become available suggesting
that use of immunomodulator drugs [biologicals] has been
Chennai
associated with the development of fatal TB in rheumatoid In October 1955, on the request of the Government of India,
arthritis (22,23). Data are also emerging suggesting that the WHO sponsored the visit to India of three representatives
tobacco smokers have about three-fold higher risk of TB than of the British Medical Research Council [BMRC] to advise
non-smokers; even after adjustment for other factors (24,25). on studies designed to provide information on the mass
A B
C D E F
Figure 1.3: King Edward Sanatorium at Bhowali, Nainital, Uttarakhand state [A,B]. Late Dr Tarachand, originally a physician, who became a
famous thoracic surgeon and his wife Dr Shanti Tarachand [expert in anaesthesiology] are well-known names at this Sanatorium. The museum in
the sanatorium houses many of the surgically resected gross pathology specimens [C to F]
Figure 1.4B: The Union Mission Tuberculosis Sanatorium, at Arogya

varam, Madanapalle, Chittoor district, Andhra Pradesh, that later
became the Arogyavaram Medical Centre
Figure 1.4A: Lord Pentland, Governor of the then Madras State of beds available for their admission at that time. It was
opened the Union Mission Tuberculosis Sanatorium at Madanapalle feared that outpatient treatment might prove inadequate for
on July 19, 1915, seen along with Dr Christian Frimodt-Moller, the first the treatment of the disease, and that a high proportion of
Medical Superintendent and members of the Governing Body patients so treated might become chronic excretors of drug-
[Kind courtesy: Dr B Wesley, Director, Arogyavaram Medical Centre, resistant organisms and might pose a serious public health
Madanapalle]
risk if use of domiciliary chemotherapy was widespread.
With the knowledge then available, it was agreed that it
domiciliary application of chemotherapy in the treatment would be premature to begin mass domiciliary application of
of pulmonary TB (30). This was particularly relevant as the chemotherapy, even in a limited area. It was finally decided
number of patients with TB far outnumbered the number to undertake a controlled comparative study of the treatment
History 7
of patients at home and in a sanatorium initially, and to auspices of the Indian Council of Medical Research [ICMR],
follow up the family contacts. Patients were to be admitted the Government of Tamil Nadu, the WHO and the BMRC.
to study from among those routinely diagnosed by the chest This Centre started its activities with eight international staff
clinic service of a large city. In order to implement these members belonging to the WHO and a team of national staff
decisions, the TCC was established at Madras [Chennai] members drawn from the ICMR and the Government of
in 1956 [Figure 1.5A] as a five-year project, under the joint Tamil Nadu under the dynamic leadership of Dr Wallace Fox
of the BMRC. The Centre was housed in two main blocks,
in a one-and-a-quarter hectare campus on Spur Tank Road,
Chetput, in the heart of Chennai city. The Centre, which
had an initial lease of life of only five years and had faced
the threat of closure in 1961, has evolved further. In keeping
with the wide sphere of activities of the Centre, the ICMR
in 1978 renamed the TCC as the “Tuberculosis Research
Centre” [TRC] (30) [Figure 1.5B]. The TRC was renamed
on August 1, 2011 as National Institute for Research in
Tuberculosis [NIRT] [Figure 1.5C]. Presently, a permanent
institute under the ICMR, the NIRT is an internationally
Figure 1.4C: Pioneers of research at Union Mission Tuberculosis recognized institution for TB research. It is a Supranational
Sanatorium, Arogyavaram, Madanapalle: Dr PV Benjamin [left panel],
Reference Laboratory and a WHO Collaborating Centre
Dr Johannes Frimodt-Moller [middle panel], and Dr KT Jesudian [right
panel] for TB Research and Training [Figure 1.5D]. Recently, an
[Kind courtesy: Dr B Wesley, Director, Arogyavaram Medical Centre, International Centre for Excellence in Research [ICER], in
Madanapalle] collaboration with NIH, was established at the Centre.
A B
C D
Figure 1.5: Tuberculosis Chemotherapy Centre, Madras [Chennai] [A]; Tuberculosis Research Centre, Madras [Chennai] [B]; renaming of
Tuberculosis Research Centre as National Institute for Research in Tuberculosis [C,D]
[Kind courtesy: National Institute for Research in Tuberculosis]
for medical and paramedical personnel, in policies and

procedures consistent with the WHO recommended DOTS
strategy. Other functions of the NTI include monitoring
and supervising TB control programme in the country, to
plan, co-ordinate and execute research in TB epidemiology
in India.
Figure 1.6: Pioneers of research at Tuberculosis Chemotherapy
Centre, Madras [Chennai]: Dr Wallace Fox [left panel]; Professor D.A. National Institute of Tuberculosis and
Mitchison [middle panel]; and Dr Hugh Stott [right panel]
[Kind courtesy: National Institute for Research in Tuberculosis, Chennai] Respiratory Diseases
The Lala Ram Sarup [LRS] TB hospital was established
The Madras Experiment by TAI in 1952. It was upgraded into an autonomous
institute, the LRS Institute of Tuberculosis and Respiratory
Pioneering researchers who worked at TCC, TRC, NIRT are Diseases under the Ministry of Health and Family Welfare
shown in Figure 1.6. The findings of the “Home-Sanatorium in 1991 by the Government of India. The institute has
study” conducted by the TRC, Madras [Chennai], have recently been renamed in 2012 as National Institute of
found their way into several journals and textbooks on Tuberculosis and Respiratory Diseases [NITRD] (32). The
TB. The finding that TB patients can be effectively treated LRS TB hospital functions in the NITRD. The WHO and the
as outpatients and continue to live in their homes without Global Laboratory Initiative [GLI] have recently recognised
added risk to their family contacts has revolutionised Microbiology Laboratory at NITRD as a National Centre
the whole concept of the management of TB (30). These of Excellence in 2014 for the WHO/GLI TB Supranational
pioneering studies also form the conceptual basis for the
Reference Laboratory Network. The NITRD [Figure 1.8]
modern-day “DOTS”.
has been designated by the WHO as a WHO Collaborating
Centre [WHO CC] in TB Training [WHOCC No. IND-128]
National Tuberculosis Institute on November 6, 2014. The NITRD-WHO CC was opened
In order to formulate an effective strategy to control TB in on World TB Day 2015. The NITRD is a key player in TB
India, the NTI was established under Directorate General control in India.
of Health Services, Ministry of Health and Family Welfare,
Government of India, at Bengaluru [then, called Bangalore] National JALMA Institute for Leprosy and Other
in 1959, and was formally inaugurated on September 16, Mycobacterial Diseases
1960 by Pandit Jawaharlal Nehru, the first Prime Minister
of India (31). The NTI is located in the northern part of The India Centre of Japanese Leprosy Mission for Asia
the Bengaluru near Rajamahal Guttahally on a sprawling [JALMA] was established in Agra by the Japanese in 1963
field of 23 acres of land [Figure 1.7A]. The main central and was managed by a Tokyo based voluntary organisation
old building of oriental architecture called “Avalon”, was JALMA (33). On April 1, 1976 the India Centre of JALMA
a palace belonging the erstwhile Maharaja of Mysore was officially handed over to the Government of India
[Figure 1.7B]. The NTI has grown rapidly and has been and subsequently to the ICMR. This was named as Central
designated as the WHO Collaborating Centre for TB JALMA Institute for Leprosy in 1976 and has been renamed
research and training since June 1985. The NTI plays an as “National JALMA Institute for Leprosy and other
important role in organising training activities in TB control Mycobacterial Diseases [NJILOMD]” in 2005 [Figure 1.9].
A B
Figure 1.7: National Tuberculosis Institute, Bengaluru: Entrance [A]; Avalon building [B]
History 9
Figure 1.8: National Institute of Tuberculosis and Respiratory Diseases Figure 1.9: National JALMA Institute for Leprosy and other
[NITRD], Lala Ram Sarup [LRS] TB hospital, New Delhi Mycobacterial Diseases, Agra. Inset: Main gate
The NJILOMD is equipped with the state-of-the art facilities National Antituberculosis Drug-resistance Survey
such as well-equipped laboratories, modern hospital and
The RNTCP, in collaboration with the NTI, Bengaluru; U.S.
well-set Field Programmes at Model Rural Health Research
Centers for Disease Control and Prevention and the WHO;
Unit [MRHRU] at Ghatampur and a satellite centre at Banda,
has initiated the first national anti-TB drug-resistance survey
serves as a National Reference Laboratory [NRL] for TB for
(36,37). In this survey covering 120 TB units in 24 states,
4 states [Assam, Himachal Pradesh, Uttarakhand and Eastern
13 drugs including all first-line and most of second-line
Uttar Pradesh] and repository centre for mycobacterial
anti-TB drugs were tested. The survey was conducted in
strains. The institute has a major thrust on research in TB
a representative sample of both newly diagnosed sputum
and other mycobacterial diseases (33).
smear-positive pulmonary TB cases [Category I] and
The history of TB and time line of various TB diagnostic
previously treated sputum smear-positive pulmonary TB
tests are shown in Figures 1.10 and 1.11 respectively.
cases [Category II] (36,37).
Revised National Tuberculosis Control
Other New Innovations
Programme
Since the beginning, the RNTCP had provided thrice-
Considered to be one of the most spectacular cost-
weekly intermittent treatment (38-41). With more recent
effective health interventions ever conceived, the Revised
evidence accumulating, the programme has introduced
National Tuberculosis Control Programme [RNTCP] of the
daily treatment from 2016 and the entire country is being
Government of India, which began in 1997, now covers the
covered in a phased manner. The RNTCP is also scaling up
whole country. The RNTCP has been the fastest expanding
the newer diagnostic modalities, namely, cartridge-based
programme, and the largest in the world in terms of
nucleic acid amplification tests [CBNAAT], such as, Xpert
patients initiated on treatment. The reader is referred to the
MTB/RIF and line probe assay [LPA] for early diagnosis
chapter “The revised national tuberculosis control programme”
of TB and molecular detection of drug susceptibility. The
[Chapter 53] for details on this topic.
evidence-based Indian Extrapulmonary TB [INDEX TB]
guidelines have been published in 2017 (42). Active case
Involvement of Medical Colleges in finding in vulnerable populations under the RNTCP is also
Tuberculosis Control being studied (43,44). Introduction of newer anti-TB drugs,
The RNTCP has the unique distinction of involving medical such as bedaquiline and delamanid under conditional access
colleges in TB control (34). This topic is covered in detail in program, under RNTCP is underway (45).
the chapter “The role of medical colleges in tuberculosis control”
[Chapter 48]. CHANGING GLOBAL FACE OF TUBERCULOSIS
CONTROL
Tuberculosis Notification
The recent paradigm shift in efforts directed at TB control
In order to have complete information of all TB cases, globally is highlighted in the chapters “Building partnerships
the Government of India declared TB to be a notifiable for tuberculosis control” [Chapter 50], Integrating Community-
disease on May 7, 2012 (35). Accordingly, all health care based Tuberculosis Activities into the Work of Non-governmental
providers including government, private, non-governmental and Other Civil Society Organisations [The ENGAGE-TB
organisations, individual practitioners are expected to notify Approach]” [Chapter 51] and “WHO’s new end TB strategy”
TB cases. [Chapter 52].
Figure 1.10: A brief history of TB

TB = tuberculosis; BCG = bacille Calmette-Guérin; HIV = human immunodeficiency virus; AIDS = acquired immunodeficiency syndrome;
MDR-TB = multidrug-resistant tuberculosis; XDR-TB = extensively drug-resistant tuberculosis; CBNAAT = cartridge-based nucleic acid
amplification tests; RNTCP = Revised National Tuberculosis Control Programme; FL-LPA = first-line line probe assay; DST = drug-susceptibility
testing; DR-TB = drug-resistant tuberculosis; SL-LPA = second-line line probe assay
EPILOGUE twin disaster of HIV and TB and X/MDR-TB seem to be

on the verge of threatening to ruin the mankind. While it
A look at the history of TB [Figure 1.10] and time line of is heatedly debated that TB is “resurging”, this may hold
various TB diagnostic tests [Figure 1.11] reveals that it true for the industrialised countries. But in the third-world
took several thousands of years for humans to identify the countries like India, TB never seems to have “disappeared”
causative organism, another 60 years to arrive at effective to “resurge” later. TB has always been with us, only
treatment. Towards the end of the twentieth century, the revealing itself every now and then and making us wiser.
History 11
Figure 1.11: Time-line of various TB diagnostic tests

TB = tuberculosis; LED = light emitting diode; DST = drug-susceptibility testing; PCR = polymerase chain reaction; FL-LPA = first-line line probe
assay; SL-LPA = second-line line probe assay; DRT = drug-resistance testing
ACKNOWLEDGEMENTS 11. Duffin JM. Sick doctors: Bayle and Laennec on their own pthisis.
J Hist Med Allied Sci 1988;43:165-82.
The authors wish to acknowledge the help rendered by Vedic 12. History of tuberculosis. Available from URL: http://globaltb.
scholars K Gopala Ghanapatigal, Vedaparayandar, Tirumala njms.rutgers.edu/abouttb/historyoftb.html. Accessed on July 15,
Tirupati Devasthanams, Tirupati, and V Swaminatha Iyer, 2018.
Retired Principal, Kendriya Vidyapeetha, Guruvayoor, 13. Kaufmann SHE. Robert Koch the Nobel Prize, and the ongoing
Kerala, India, for their invaluable help in tracing the threat of tuberculosis. N Engl J Med 2005;353:2423-6.
references to TB in the Vedas. 14. Sakula A. Robert Koch: centenary of the discovery of the tubercle
bacillus, 1882. Thorax 1982;37:246-51.
15. Akkermans R. Robert Heinrich Herman Koch. Lancet Respir
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2
Epidemiology of Tuberculosis:
Global Perspective
Dennis Falzon, Knut Lönnroth, Mario C Raviglione
INTRODUCTION and surveillance data reported by the national authorities

responsible for TB control in their respective countries.
No country in the world today, rich or poor, can claim to be
The burden of disease is expressed as the TB incidence
free of tuberculosis [TB]. In some high income countries, the
and prevalence; the burden of death as TB mortality.
rates of TB have been brought down to very low levels, but
The background data are collected online in aggregated
the demographic realities of aging and migration, shifts in
format by the Global TB Programme of WHO on an annual
host vulnerability, as well as the evolution of the organism
basis and are also supplemented periodically with data
itself, constantly threaten a comeback. The burden of TB
from special surveys [e.g., drug-resistance and disease
morbidity and mortality in the world as a whole impinges
prevalence]. Following collection, data undergo checks
most heavily on the people of developing countries, and
for internal consistency and are then consolidated into a
disproportionately on the poor and other disadvantaged
central database. Modelled estimates are used when data
subpopulations of better resourced countries. In 2014,
are missing; the methodology employed to derive these
9.6 million new TB cases were estimated by the World
estimates has been described elsewhere (1,4). The updated
Health Organization [WHO] to have occurred globally,
information is published each year in the annual Global
with 4 million in the South-East Asian Region [SEAR] of
Tuberculosis Reports that WHO has issued uninterruptedly
WHO and 2.2 million in India alone (1). Apart from posing
since 1997 (5,6). The information is updated each year and
a formidable burden of disease worldwide, TB ranks as the
the raw data can be downloaded free-of-charge or via
10th leading cause of global deaths and 13th in terms of years
interactive query tools [e.g., country profiles]. Mortality data
of healthy life lost worldwide (2). It competes with human
are also collected by WHO through a separate mechanism
immunodeficiency virus [HIV] as the leading cause of death
from the one described above and estimates are also used to
from an infectious disease. These staggering statistics jar with
replace missing data in the countries where vital registration
the fact that the large majority of TB patients could be cured
is not functional (7). The definitions and indicators in use
and many TB deaths avoided with 6 months of treatment,
in this Chapter have been revised and standardised over
which is generally well-tolerated, accessible and affordable
a number of years, and their latest update was released in
in most settings. This chapter traces the historical imprint of
2013 (8). The countries included in the regional groupings
TB upon humankind and looks at the major determinants
in this Chapter are as defined by WHO (1).
of TB in the world today and the evolution of the epidemic
in recent decades in different geographical regions.
HISTORICAL PERSPECTIVE
In conclusion, we outline the actions that need to be taken
in future to consign TB to history, as the perspective for Deoxyribonucleic acid [DNA] studies of archaeological
global health and development policy shifts beyond the material show that TB has afflicted mankind since the
2015 horizon of the United Nations Millennium Development Neolithic period (9). However, it is also likely that this host-
Goals [MDG] (3). pathogen relationship dates back much further than nine
This Chapter uses findings from several published millennia (10). Hippocrates [c.460-c.377 BCE], the Father of
sources. In addition to those referenced throughout the text Western Medicine, described the public health importance of
we use estimates derived by WHO based on notification what was referred to as phthisis at his time. Over the years,
the disease acquired evocative names such as “galloping countries to very low levels. Even if this decline was
consumption”, “the white plague” and “captain of all these temporarily halted or even reversed in a number of
men of death”, all attesting to its tragic legacy (11,12). At the industrialised countries from the late 1980s (20,21), rates
height of the epidemic in western Europe around the end of have since continued to fall bringing the TB incidence lower
the 18th and start of the 19th centuries, TB was likely to be than 10/100,000 in many of them today [Figure 2.1]. In
killing an astounding 1% of the population each year (13). western countries, the TB burden has now become largely
Around this time, TB was the cause of one-fourth of deaths concentrated in two broad age-bands in the population:
in London and of between one-third and one-sixth elsewhere [i] the elderly native patient with reactivation of TB infection
in England and Wales (14). TB mortality declined during the contracted at a time when TB was rife and [ii] younger adults
19th century in western Europe, albeit it remained a major who have a higher risk of recent infection [e.g., homeless
killer even at the end of the century (15). This decrease is persons, migrants from high prevalence settings] or of
commonly ascribed to improvements in socioeconomic progression [e.g., people living with HIV].
conditions (16), although it has been argued that the However, the TB caseload in the world today concentrates
isolation of cases in sanatoria and possibly the evolution of to a large extent in poorer countries where the disease
natural immunity may have contributed to this trend (17). remains an important public health threat. There is much
The decline in TB was disturbed during the period of the two less documentation about trends of TB in the developing
World Wars in the 20th century but resumed immediately world. In many low and lower-middle income countries the
after their end. In countries like France, Great Britain, impact of control efforts on annual risk of TB infection has
the Netherlands, and Norway, the annual risk of TB been less dramatic than in the richer ones (22).
infection fell at the fastest rates ever documented in the
decades after 1950 (18,19). Continued improvements in NATURAL HISTORY, RISK AND DETERMINANTS
the economic situation, nutrition, and living conditions, OF TUBERCULOSIS
effective preventive measures, and expanded curative
services equipped with the newly introduced anti-TB In humans, the natural course of TB from infection to disease
medicines brought the burden of disease in European shares some characteristics with other infectious conditions
Figure 2.1: Estimated TB incidence rates by country, 2014

Reproduced with permission from “World Health Organization. Global tuberculosis report 2015. WHO/HTM/TB/2015.22. Geneva: World Health
Organization; 2015 (1)”
The World Health Organization updates these data annually. The reader can access the updated information from the WHO report of the current
year available at the URL: http://www.who.int/topics/tuberculosis/en/
Epidemiology of Tuberculosis: Global Perspective 15
caused by directly transmissible organisms. Exposure to infected with HIV are on average less infectious, albeit the
the viable organisms, usually through respiratory droplets overall transmission of TB is increased within a community
expelled during coughing, but also possible through where HIV prevalence is elevated.
infected milk can lead to implantation in the lung or other In contrast to infection, the risk of progression to disease
tissues. This normally results in asymptomatic [latent is largely determined by predisposing factors in the host.
or persistent] infection. Progression to disease with the Many conditions which modulate the immune response can
clinical manifestations may then ensue rapidly in the first thus increase the likelihood of disease in a person infected
12-18 months post-exposure or after many decades. In up to with Mtb. HIV stands out as the most potent risk factor,
half of cases, pulmonary forms of the disease develop which increasing the relative risk for TB by more than 20, but others
are infectious to their contacts; other individuals contract such as under-nutrition, silicosis, tobacco smoking, diabetes,
less infectious pulmonary or non-infectious extrapulmonary harmful alcohol use, and immunomodulatory drugs such
forms. The disease, if left untreated, results in death in as anti-tumour necrosis factor agents also play a role. Age
over two-thirds of pulmonary sputum-smear positive cases is also an important factor and risk appears higher in late
within 10 years [without HIV infection], as was documented adolescence and young adulthood. Finally, besides these
in the pre-antibiotic era (23). Alternatively, it may resolve risks, the likelihood that a person is cured or dies of TB is
spontaneously in a minority of cases or evolve towards a influenced also by an array of other factors, including the
chronic form of disease that may last for years. Successful form of disease, for e.g., higher mortality in miliary TB and
resolution of the disease does not confer a lasting immunity TB meningitis (29-31) and whether effective chemotherapy
and the disease may later reactivate. Patients with chronic for TB is provided (32,33). If treated with combined,
disease may survive for several years and be infectious until first-line anti-TB chemotherapy, the chances of cure may
death or, rarely, spontaneous resolution. The propensity of exceed 90% among patients with drug-susceptible bacilli.
TB to chronicity and to recurrence makes it different from Patients treated for multidrug-resistant TB [MDR-TB],
many other infectious conditions. defined as isolates of Mtb resistant to rifampicin and
Spontaneous mutations create strains of Mycobacterium isoniazid, with or without resistance to other anti-TB drugs,
tuberculosis [Mtb] which are resistant to different drugs however, are less likely to have a successful outcome
used in their treatment (24). These events are rare, and than those without, and success is less likely if additional
have been estimated to occur at average rates of 2.56 × 108 resistance is present (34,35). The provision of anti-retroviral
and 2.25 × 1010 per bacterium per generation for isoniazid treatment [ART] to TB/HIV patients has been shown
and rifampicin respectively (25). However, exposure to to significantly decrease the chances of unsuccessful
individual anti-TB medicines favours the selection and outcomes (36-38).
replication of drug-resistant strains within an affected The impact that different risks factors for TB infection,
individual. TB patients who acquire drug-resistance from disease progression and unfavourable outcome have on TB
treatment may transmit these strains to their contacts epidemiology varies substantially across the world. The
[primary drug-resistant infection]. sum effect of the interplay of these risks on a population is
A number of factors influence the natural history of TB a function of the potency of these factors at the individual
at its different stages in an individual. Exposure to infection patient level and their prevalence in the population.
is more likely when the number of infectious cases is high For instance, the overall population level effect of HIV is
in a particular setting, when the period of transmissibility is very pronounced in southern African countries, where
long, and when opportunities for effective contact between infection is highly prevalent in contrast to countries of the
infectious and susceptible persons are high. In situations Indian subcontinent, where less potent risk factors which
where population density is high such as during rapid occur more frequently are more important. The use of
urbanization and the expansion of slum settlements, the population attributable fractions [PAF] is useful to analyse
risk of exposure may also increase, as crowded and poorly this interaction in individual countries (39,40). There are
ventilated settings are conducive to an intense exposure sharp differences among the 22 highest TB burden countries
to the infectious agent. Once exposed, not all individuals which concentrate about 80% of TB incidence in the world
have the same risk of infection and other factors come in the relative contribution of each of these determinants
into play: these determinants are largely external to the to their TB incidence. For instance, in all countries except
host and include those related to the infecting inoculum Thailand and those in Africa, the PAF for adult TB associated
[critical size of droplets, concentration of bacilli in sputum], with smoking was higher than for HIV while in 14 of the
environmental conditions which promote the persistence 22 countries the total PAF related to under-nutrition was the
of infectious nuclei in the air, and virulence of the strain. highest. Problems of alcohol use and diabetes are important
Certain genotypes of the Beijing lineage of Mtb have been in certain countries but if their prevalence increases in
associated with rapid worldwide spread and an association the world, they may become more prominent in future.
with disease clustering, suggesting increased virulence These risk factors for TB are eminently modifiable and,
even when drug-resistance is acquired by these strains, an therefore, amenable to public health interventions; in
added concern (26-28). It has been estimated in the past that, contrast, other risk factors like age and genetic predisposition
if left untreated, each person with active TB may infect on could serve to profile individuals and risk groups where
average between 10 and 15 people every year. TB patients action could be more meaningfully targeted.
THE GLOBAL BURDEN OF TUBERCULOSIS declining [Figure 2.3] achieving this MDG target far ahead
of the 2015 deadline. The MDG target has also been met in
Incidence all six WHO regions and in 16 of the 22 HBCs (1).
In 2014, there were an estimated 9.6 million [range 9.1-10
million] incident cases of TB in the world, equivalent overall
Table 2.1: TB incidence and case detection, South-
to 133 cases per 100,000 population but with very extreme
East Asia Region of WHO, by country, 2014
geographical variations [Figure 2.1] (1). One million incident
cases were children and 3.2 million [range, 3.0-3.4 million] Incidence
[in thousands;
occurred among women. Fifty-eight percent of incident TB Country including HIV] Case detection (%)
cases occurred in Asia and 28% in the African Region. India
Bangladesh 360 [320-410] 53 [47-60]
[23%], Indonesia and China [10% each] accounted for two-
fifths of global cases in 2014. Over one third of the world’s Bhutan 1.3 [1.1-1.4] 85 [77-94])
caseload was concentrated in the 11 countries of the South- DPR Korea 110 [100-120]) 93 [87-100]
East Asia Region, where the rate, at 211/100,000 population, India 2200 [2000-2300] 74 [70-80]
was much higher than the global value [Table 2.1] (1). Indonesia 1000 [700-1400] 32 [23-46]
In South Africa and Swaziland, about 1% of the
Maldives 0.15 [0.130-0.170] 89 [78-100]
population is estimated to develop TB each year, while
many countries in western Europe, the US, Australia and Myanmar 200 [180-220] 70 [64-78]
New Zealand have rates about a 100 times lower than this. Nepal 44 [39-50] 79 [71-90]
In 2014, 1.2 million [13%] of the 9.6 million new TB cases Sri Lanka 13 [12-15] 69 [62-79]
were HIV-seropositive globally, and 74% of TB cases among Thailand 120 [61-190] 59 [36-110]
people living with HIV worldwide were in the African Timor-Leste 5.8 [4.8-6.9] 63 [53-77]
Region [Figure 2.2] (1). In parts of southern Africa, more
All S-E Asia Region 4000 [3700-4400] 62 [56-68]
than 50% of TB cases were co-infected with HIV. Globally,
the estimated TB incidence rate was relatively stable from TB = tuberculosis; WHO = World Health Organization; HIV = human
immunodeficiency virus; S-E = South-East
1990 until around 2000, since when it has been slowly
Figure 2.2: Estimated HIV prevalence in new and relapse TB cases, 2014
Organization; 2015 (reference 1)”
Figure 2.3: Global trends in estimated rates of TB incidence [1990-2014], and prevalence and mortality rates [1990-2015]. Left: estimated
incidence rate including HIV-positive TB [green] and estimated incidence rate of HIV-positive TB [red]. Centre and right: The horizontal dashed
lines represent the Stop TB Partnership targets of a 50% reduction in prevalence and mortality rates by 2015 compared with 1990. Shaded areas
represent uncertainty bands. Mortality excludes TB deaths among HIV-positive people.
HIV = human immunodeficiency virus
Prevalence drug-susceptible disease (34,41,42). Representative data from

surveys performed at least once or on routine surveillance
There were an estimated 13 million prevalent cases
of diagnostic drug susceptibility testing of TB patients is
[range, 11-14 million] of TB in 2014, equivalent to a rate of
now available from 144 countries worldwide.
174 cases per 100,000 population. TB prevalence rates are
Based on these data, it is estimated that in 2014 there
declining in all six WHO regions and by the end of 2015
were 480,000 [360,000-600,000] newly emerging MDR-TB
and are estimated to have fallen by 42% globally since 1990
cases in the world, and 190,000 [120,000-260,000] MDR-TB
missing the international target of halving TB prevalence
deaths. Globally, 3.3% {95% confidence intervals [CI] 2.2%
by 2015, compared with the baseline in 1990. However, the
to 4.4%} of new [previously untreated] TB cases and 20%
target has already been met by the Region of the Americas
[95% CI 14% to 27%] of previously treated cases are
and the Western Pacific Region and SEAR (1).
estimated to have MDR-TB. These proportions, however,
differ markedly between countries, showing low levels
Deaths in the SEAR 2.2% [95% CI 1.9% to 2.6%] in new and 16%
There were an estimated 1.5 million total TB deaths in [14% to 18%] in previously treated patients and very high
2014 or about 16 deaths per 100,000 population in the levels in eastern Europe and central Asia compared with the
world. About 390,000 of these deaths were among people rest of the world [Figure 2.5]. Among new cases in Belarus
living with HIV. Approximately 90% of total TB deaths MDR-TB is present in 34%, and in 23%-26% in Kazakhstan,
occurred in the African Region and SEAR, with India and Kyrgyzstan, the Republic of Moldova, and Uzbekistan;
Nigeria accounting for about one-third of the global TB between 55% and 62% of previously treated patients in these
deaths in 2014. TB mortality rate [excluding deaths among countries had MDR-TB. Levels vary across the vast expanse
HIV-positive people] has fallen by 47% between 1990 of the Russian Federation but some regions have the highest
and 2015 narrowly missing the target of a 50% reduction proportions ever reported worldwide. The time trends in drug
[Figure 2.4]. Mortality rates are declining in all six WHO resistance levels vary substantially between countries (43),
regions but at a different pace (1). although comparable data from serial measurements over
time are not available for many countries. Extensively
drug-resistant TB [XDR-TB] or MDR-TB with additional
Drug-resistant TB
resistance to both the fluoroquinolones and the second-line
The prospect of an increase in the number of drug-resistant injectable drugs, the two most important classes of medicines
cases among the TB burden remains a matter of concern, in the treatment of MDR-TB, has now been reported by
even if the overall number of TB patients is on the decline. 105 countries globally, including all countries of the WHO
Cases with drug-resistant TB need more resources and SEAR except Sri Lanka and Timor-Leste. In countries with
support to treat appropriately with regimens that are representative data, globally 9.7% [95% CI 7.4% to 12%] of
longer, more toxic and costly than those in general use for MDR-TB cases have XDR-TB.
Figure 2.4: Estimated TB mortality rates [excluding TB deaths among HIV-positive people], 2014
Figure 2.5: Percentage of MDR among new [previously untreated] TB cases. Figures are based on the most recent year for which data have been
reported, which vary among countries. Data reported before the year 2000 are not shown.
A GLOBAL RESPONSE These differences may reflect geographical variations

in TB epidemiology as well as diagnostic and reporting
In the early 1990s, after more than a decade of neglect, WHO
practices. The 5.7 million new and relapse cases notified in
published new estimates showing that millions of people
2013 represent about 64% [range: 61-66%] of the estimated
were affected with TB and died from it (44). As a result, in
incidence that year. Case detection ratio [CDR] was highest
1993, WHO declared TB to be a global health emergency (45).
in 2014 in the Region of the Americas [77%; range 75%-81%],
It was realised back then that many countries were ill- the Western Pacific Region [85%; range 81%-90%] and the
prepared to counter the challenge that TB posed for the European Region [79%; range 75-83%]. All regions have
future. Political commitment was lacking, surveillance was improved their estimated CDRs since 1995, when the global
neglected, and treatment regimens and diagnostic services estimate was 39% [range 38%-41%] and when DOTS started
varied greatly in effectiveness. In 1994, WHO proposed a to be expanded in the world. However, in 2014, there still
basic package of interventions to address the emergency, remained a gap of approximately 3.6 million people with TB
which eventually acquired the term DOTS [originally an who were “missed” [Table 2.1]. The gap between estimated
acronym for “directly-observed treatment, short course”] (46). TB incidence and notified cases is a result of either under-
In 2006, DOTS evolved into a more comprehensive reporting of TB cases to the national surveillance systems
framework—the Stop TB Strategy—with activities covering of under-detection or both. Under-reporting of diagnosed
a larger set of dimensions important for TB care and TB cases may occur when the private sector providers fail
prevention (47,48). to notify cases to the national TB programme or else when
In 2000, an ambitious Global Plan to Stop TB was reporting from diagnostic facilities and laboratories within
launched by WHO and the Stop TB Partnership with the national TB programmes is dysfunctional. Under-
the long-term vision of eliminating TB as a public health diagnosis of patients with TB may occur because of lack of
problem (49). The planning became more elaborate over awareness of TB among communities, poor access to the
the following years and in its latest update, in 2010, it was health care services to appropriate diagnostics for people
estimated that US$ 47 billion would be required to be spent who do present to health facilities seeking care or a low
between 2011 and 2015 in order to achieve the targets set index of suspicion of TB among health professionals.
for 2015 (50). The detection and treatment of patients with rifampicin-
More than two decades after the WHO emergency resistant disease and MDR-TB, conditions requiring longer,
announcement, TB remains one of the principal public health more toxic and expensive treatment regimens, has also
concerns due to an infectious condition in all countries in the increased; in 2014, the number of new enrollments on
world. But despite the plight of the millions of patients who MDR-TB treatment reached about one third of estimated
have fallen ill with TB and died since 1993, much important cases that could potentially be detected among the
progress has been registered. National programmes have pulmonary TB cases notified by the countries.
been strengthened and learnt to adapt to the changes in The World Health Assembly [WHA] in a resolution in
the epidemic such as the challenges of HIV-associated TB 2009 urged countries to work towards providing universal
and of drug-resistant strains as well as the environment access to care for drug-resistant TB patients (51). Drug-
around them, including the impact of migration, health resistant strains have been detected in an increasing number
sector reforms, financial crises and perennial pressure to of countries over the last two decades, and the widespread
integrate TB services in primary health care. As a result, introduction and use of new, rapid molecular assays are
about 43 million lives have been saved between 2000 and destined to snowball this trend. The response of countries
2014 through effective diagnosis and treatment (1). The has varied but some of the countries with the highest burden
efforts of treatment programmes have thus had a profound are on track to achieve universal access to treatment for their
impact on sustaining the substantial decline in TB incidence population if they sustain the efforts put in place in the last
and mortality over the last decade in all regions of the world. few years (52).
TB/HIV interventions have progressed and by 2014, 51% of As a result of the worldwide expansion of effective care,
TB patients worldwide knew their HIV status [79% in the treatment success in new TB cases has reached 86% among
African Region where the TB/HIV burden is the highest]. patients placed on treatment in 2013 globally, a substantial
Among known TB/HIV patients coverage of therapy with increase from 2000 when it was 69%. The target of 85%
anti-retroviral drugs reached 77% in 2014, up from 49% in success has thus been reached and sustained. Success rates
2011. However, only 23% of countries globally reported are lower among retreatment patients [65%] and among
provision of isoniazid preventive therapy [IPT] to people MDR-TB patients [48%] attesting to the worse prognosis
living with HIV in 2014. when the effectiveness of first line drugs is diminished
In 2014, countries notified a total of 6.3 million TB [Figure 2.6]. Treatment of XDR-TB and forms of TB with
cases, just over 6 million newly diagnosed and 261,000 on additional resistance is fraught with difficulties and
treatment [Table 2.2]. About 15% of newly emerging cases outcomes are generally poorer than in MDR-TB (35,53,54);
reported globally were extrapulmonary; the proportion of patients with infectious forms of TB bearing such advanced
these cases varied substantially from 7% in the Western patterns of resistance present a challenge to infection
Pacific Region to 23% in the Eastern Mediterranean Region. control.
Table 2.2: TB case notifications in the 22 high TB burden countries, WHO Regions and globally, 2014
New or previous treatment history
Percentage
unknown Relapse
of pulmonary
Retreat- Pulmonary Pulmonary cases
ment bacterio- Pulmonary bacterio- Pulmonary Extra- bacteriol-
Total New and excluding logically clinically Extra- logically clinically pulmo- ogically
notified relapse relapse confirmed diagnosed pulmonary confirmed diagnosed nary confirmed
Afghanistan 32,712 31,746 966 14,737 8,573 7,227 1,209 65
Bangladesh 196,797 191,166 5,631 106,767 42,832 37,406 2,989 863 309 72
Brazil 81,512 73,970 7,542 41,120 17,801 9,479 3,602 1,488 480 70
Cambodia 43,738 43,059 679 12,168 11,286 18,310 445 709 141 51
China 826,155 819,283 6.872 235,704 526,106 32,348 25,125 33
DR Congo 116,894 115,795 1,099 75,631 13,494 19,566 4,298 1,892 914 84
Ethiopia 119,592 119,592 40,087 41,575 37,930 49

India 1,683,915 1,609,547 74,368 754,268 343,032 275,502 124,679 112,066 66
Indonesia 324,539 322,806 1,733 193,321 101,991 19,653 6,449 1,391 1 66
Kenya 89,294 88,025 1,269 34,997 30,872 14,640 3,569 2,947 1,000 53
Mozambique 58,270 57,773 497 24,430 23,455 6,276 1,542 2,070 50
Myanmar 141,957 138,352 3,605 42,608 70,305 16,108 5,276 3,650 405 39
Nigeria 91,354 86,464 4,890 49,825 29,460 4,764 2,415 0 64
Pakistan 316,577 308,417 8,160 122,537 120,350 57,463 7,420 426 221 52
Philippines 267,436 243,379 24,057 92,991 139,950 4,161 6,277 41
Russian 136,168 102,340 33,828 37,296 40,894 8,763 7,982 6,753 652 49
Federation
South Africa 318,193 306,166 12,027 155,473 106,482 33,522 7,430 2,693 566 60
Thailand 71,618 67,722 3,896 34,394 21,115 10,244 1,969 0 0 63
Uganda 46,171 44,187 1,984 26,079 11,854 4,180 1,499 468 107 69
UR Tanzania 63,151 61,571 1,580 23,583 23,380 13,600 1,008 51
Viet Nam 102,087 100,349 1,738 49,938 25,179 18 118 7,114 69
Zimbabwe 32,016 29,653 2,363 11,224 13,151 3,909 1,369 49
High-burden 5,160,146 4,961,362 198,784 2,179,178 1,763,137 653,169 223,666 137,416 4,796 56
countries
AFR 1,342,400 1,300,852 41,548 635,560 399,155 212,057 39,782 11,217 3,081 62
AMR 228,476 215,243 13,233 127,864 40,746 32,501 10,193 2,918 1,021 76
EMR 465,677 453,393 12,284 183,630 151,696 103,959 12,368 866 874 56
EUR 321,421 266,058 55,363 112,416 76,759 39,175 23,935 11,483 2,290 61
SEAR 2,580,605 2,482,074 98,531 1,188,654 632,418 389,819 152,498 117,970 715 64
WPR 1,375,572 1,335,816 39,756 449,845 734,179 103,085 44,354 3,037 1,316 40
Global 6,314,151 6,053,436 260,715 2,697,969 2,034,953 880,596 283,130 147,491 9,297 58
TB = tuberculosis; WHO = World Health Organization; AFR = African; AMR = American region; EMR = Eastern Mediterranean region; EUR = European
region; SEAR = South-East Asia region; WPR = Western Pacific region
THE FUTURE OF TB: A LONG-TERM of TB in the world. However, these gains have not benefited
PERSPECTIVE the whole of humanity in an equitable manner and huge
disparities have emerged within the globalised economies
The last 150 years have seen significant improvement in the of today’s world. TB remains a barometer of poverty,
social conditions of large swathes of the world’s population. insecurity, malnutrition and low basic health coverage,
They have also been characterised by significant scientific risk factors that abound in poor and rich countries alike.
discoveries and the broad scale application of interventions The HIV-epidemic has influenced the TB dynamic in
based on this knowledge. These two phenomena have many countries in Africa and elsewhere over the last three
contributed hugely to the gradual decline in global burden decades.
Figure 2.6: Treatment outcomes for patients diagnosed with MDR-TB by WHO Region, 2007-2012 cohorts. The total number of cases with
outcome data is shown beside each bar
MDR-TB = multidrug-resistant tuberculosis; WHO = World Health Organization
For a disease that is largely curable, the fact that reduction in the importance of TB as a public health priority
millions of people still develop it each year and that about worldwide, bringing down its burden to levels which have
4,000 TB patients die each day is a sordid reminder of only been achieved by industrialized countries to date.
the sad inequities of today’s world and the ability of the Three key targets are aimed for by 2035, namely: [i] a 95%
TB bacillus to elude modern medicine and public health reduction of TB mortality [in comparison with 2015 levels];
measures. Nonetheless, recent advances in diagnostics, [ii] a 90% reduction of TB incidence [down to <10 cases per
vaccine science and therapeutics bring fresh optimism 100,000 population]; and [iii] the elimination of catastrophic
to the future perspective of the TB pandemic. For the costs due to TB for all families affected by the disease. The
first time in four decades, new TB drugs are starting to reader is referred to the chapter “WHO’S New end TB strategy
become available with an express indication for TB (55,56). [Chapter 52]” for further details.
In addition, new compounds are being tested in clinical The activities encompassed by the new strategy will
trials and other medicines are being repurposed for use in build upon the successes achieved up until now but will also
TB. About 10 vaccine candidates have now entered clinical embark upon new ones within territories that lie beyond the
trials (57), albeit the prospect of having an effective vaccine traditional confines of TB care programs. The activities are
for the prevention of TB in adults in the near future remains grouped under three pillars: [i] integrated, patient-centred
uncertain. care and prevention; [ii] bold policies and supportive
For new technologies to make a difference to TB care and systems; and [iii] intensified research and innovation.
control they need to be effectively implemented in the target Components within all of the three pillars concern the
settings using, where possible, innovative methods. One practice of surveillance and epidemiology in one way or
illustrative example was the broad scale adoption of Xpert® another. For instance, the drive to rapidly find and treat the
MTB/RIF, a rapid, reliable molecular diagnostic method 3.6 million TB patients who escape detection or reporting
that the WHO endorsed in December 2010 (58,59). By will involve a number of articulated actions to improve the
September 2014, more than 3,500 machines and 8.8 million coverage of reliable diagnostics, implement early diagnostic
test cartridges had been procured by 110 low- or middle- strategies, increase the awareness about TB of the public and
income countries [http://www.who.int/tb/areas-of-work/ health care workers, mandate the obligatory notification of
laboratory/mtbrifrollout/en/]. This rapid, unprecedented TB, and ensure that this is matched by means to facilitate the
transfer of technology and expanded adoption of a new test reporting of cases and the capture of data from laboratories
was made possible in these countries through a lowering of and diagnostic centers [e.g., wider use of information and
the price for the equipment and the consumables following communication technology], provide universal health
negotiations with the manufacturers by its co-developer, coverage and build links with the private health care sector.
Foundation for Innovative and New Diagnostics [FIND] Broad-scale interventions aimed at active and earlier case
[www.finddiagnostics.org], and the financial support of the finding, increasing contact tracing and treatment of latently-
US Government, the Bill and Melinda Gates Foundation infected persons (61), will require close measurement of
[www.gatesfoundation.org] and UNITAID [www.unitaid.eu]. the response. Health workers who are monitoring patients
A new vision beyond 2015 has now been endorsed by on treatment would likewise need to exploit better the
the WHA (60). This strategy [End TB Strategy] envisages a communication technologies which are available even in
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Title: Journal et fragments

Publiés avec l'assentiment de sa famille par G. S.
Trébutien
Author: Eugénie de Guérin
Editor: G. S. Trébutien
Release date: October 14, 2023 [eBook #71878]
Language: French
Original publication: Paris: Didier et Cie, 1865
Credits: Laurent Vogel and the Online Distributed Proofreading

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*** START OF THE PROJECT GUTENBERG EBOOK JOURNAL ET

FRAGMENTS ***
EUGÉNIE
DE GUÉRIN
JOURNAL ET FRAGMENTS
PUBLIÉS AVEC L’ASSENTIMENT DE SA FAMILLE
PAR
G. S. TREBUTIEN
Conservateur-adjoint de la Bibliothèque de Caen
OUVRAGE COURONNÉ PAR L’ACADÉMIE FRANÇAISE
TREIZIÈME ÉDITION
PARIS
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35, QUAI DES AUGUSTINS, 35
M DCCC LXV
Tous droits réservés.
A LA MÊME LIBRAIRIE
LETTRES INÉDITES
D’EUGÉNIE DE GUÉRIN
PUBLIÉES PAR M. TREBUTIEN
DEUXIÈME ÉDITION
1 vol. in-12. — 3 fr. 50
MAURICE DE GUÉRIN
JOURNAL, LETTRES ET FRAGMENTS, POÈMES
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1 vol. in-12. — 3 fr. 50
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1 vol. in-12. — 3 fr. 50
PARIS. — IMPRIMERIE DE J. CLAYE, RUE SAINT-BENOIT, 7

AVERTISSEMENT DE L’ÉDITEUR.
Nous avons offert au public, il y a deux ans bientôt, les œuvres

de Maurice de Guérin [1] ; œuvres posthumes, annoncées le
lendemain de sa mort par un écrivain illustre [2] , et qui cependant
avaient tardé vingt ans à paraître.
[1] Maurice de Guérin, Reliquiæ, 2 vol. in-16 ; Paris,
Didier, 1861.
[2] George Sand, Revue des Deux Mondes, 15 mai
1840.
Le succès rapide de cette première édition nous a permis d’en

donner récemment une seconde [3] , revue avec soin et enrichie de
plusieurs morceaux qui avaient d’abord échappé à nos recherches.
[3] Maurice de Guérin, Journal, Lettres et fragments,
Poèmes, in-8o ; Paris, Didier, 1862.
Aujourd’hui nous sommes heureux de joindre aux œuvres du

frère celles de la sœur, connue déjà par la grande place qu’elle tient
dans la correspondance et les poésies de Maurice, mais qui méritait
assurément d’être connue un jour pour elle-même.
Mlle Eugénie de Guérin était née cinq ans avant son frère. Elle a
eu la douleur de lui survivre près de neuf ans, jusqu’au jour où elle
s’éteignit dans sa solitude du Cayla, le 31 mai 1848.
Nous ne raconterons pas sa vie. Ce qui en fait l’intérêt, ce sont
ses pensées et la façon dont elle les exprime. Du reste, cette vie est
si simple qu’un voyage à Alby ou à Toulouse, deux courts séjours
dans le Nivernais et à Paris, y ont fait époque. Un départ ou un
retour, les maladies de ceux qui lui sont chers, le mariage et la mort
de son plus jeune frère en ont été les véritables événements. Sur
tout ce qui la touche et les émotions qu’elle a ressenties, son Journal
et ses lettres ne nous ont rien laissé à dire qui vaille la peine d’être
dit.
Il est vrai que le seul projet de livrer à tout le monde ces lettres,
ce Journal surtout, a dû éveiller chez une sœur, pieuse dépositaire
de ce mystique héritage, des scrupules auxquels nous avons eu
nous-même quelque peine à nous soustraire. Combien de fois notre
attention ne s’est-elle pas fixée avec une sorte d’anxiété sur ces
paroles adressées par Mlle de Guérin à son cahier qu’elle dérobait
avec tant de soin à tous les regards : « Ceci n’est pas pour le public ;
c’est de l’intime, de l’âme, C’EST POUR UN [4] . »
[4] Page 91.
Il ne faudrait pas croire cependant que Mlle de Guérin ait ignoré

complétement, ni même qu’elle fût irrévocablement résolue à
ensevelir dans une obscurité volontaire les dons de l’esprit que Dieu
lui avait prodigués. Plus d’une fois, cédant aux exhortations
pressantes de son frère, au vœu d’un père qui avait deviné son
génie, et sans doute aussi à une vocation irrésistible, elle a songé à
écrire pour être lue ; et, sous la condition expresse de taire son nom,
elle eût consenti à livrer ses pensées, si, en retour de ce sacrifice,
elle avait espéré faire un peu de bien à quelques âmes : si, par
l’exemple de sa foi ou par l’expression de sa tendresse fraternelle,
elle avait pu inspirer à d’autres son espoir en Dieu, son admiration
pour Maurice : double amour qui se partageait et qui remplissait son
âme.
Or, de tous les ouvrages qu’elle eût entrepris de dessein
prémédité, aucun n’aurait mieux rempli l’un et l’autre de ces objets,
que le Journal où elle a noté, pendant huit ans, tous les élans
spontanés de son esprit, tous les battements involontaires de son
cœur.
Nous nous trompons fort, ou peu de livres publiés de notre temps
auront exercé sur les âmes une influence plus douce et plus pure.
En parlant ainsi nous pensons aux plus délicates, à celles qui
souffrent, à celles qui songent, à celles qui s’agitent et se consument
dans une lutte pénible et stérile entre leurs rêves et les vulgaires
réalités d’une existence commune.
Les femmes surtout qu’une imagination trop mobile désenchante
facilement de leur destinée trouveront dans le livre de Mlle de Guérin
plus qu’une froide leçon : elles y trouveront une consolation et un
exemple.
On verra, pour ainsi dire, d’heure en heure, combien cette
existence était obscure, modeste, isolée et, pourrait-on croire, en
désaccord par sa monotone simplicité avec l’activité d’une
intelligence prompte et ardente. Mlle de Guérin n’en a pas souffert ; à
peine surprendrait-on, dans la longue suite de ses épanchements
intimes, un mot amer. Chaque fois qu’elle a entrevu le monde, elle
l’a observé d’un œil curieux, elle s’est prêtée à lui sans trop d’efforts,
mais elle rentrait avec joie dans sa retraite, heureuse de reprendre
ses doux entretiens de tous les instants avec sa propre pensée et
avec les voix mystérieuses de la nature. La mort, qui lui était
apparue de bonne heure, était presque toujours présente à ses
yeux ; elle ne craignait point de telles images. Ce n’est pas sans
quelque joie qu’elle voyait s’entr’ouvrir la tombe, et, au delà de ses
ténèbres, le ciel avec les divines lumières et la pure félicité du jour
sans fin ; mais elle demeurait attachée à la vie par des affections,
par des devoirs. Dans les jours les plus pénibles de défaillance
physique, de souffrance morale, il lui restait auprès d’elle quelqu’un
à aimer, quelqu’un à servir ; et lorsque son père lui baisait le front :
« Hélas ! disait-elle, comment quitter ces tendres pères ? » C’est
ainsi qu’elle appréhendait de quitter son Cayla ou pour la ville, ou
pour le cloître, et même pour le ciel. L’horizon de ce petit monde ne
lui semblait pas trop étroit. Elle ne s’y sentait pas abandonnée. Son
secret, c’était de trouver la poésie en elle-même et Dieu en toutes
choses. Tel est l’enseignement de cette vie, et l’ineffable charme du
livre qu’on va lire.
Le lien qui attache le Cayla au monde, c’est Maurice, toujours

absent depuis sa onzième année. Il est au petit séminaire de
Toulouse, au collége Stanislas, à la Chênaie, à Paris encore, faisant
ses études, essayant sa vocation, cherchant à se faire sa place au
soleil : grand sujet de préoccupation pour son père et pour ses
sœurs, pour Mlle Eugénie surtout. Ainsi le voulaient l’affinité secrète
de leur nature et le souvenir de leur mère. Mlle Eugénie n’avait que
treize ans lorsqu’ils eurent le malheur de perdre cette mère, hélas !
bien jeune encore ; mais elle était l’aînée des sœurs ; c’est elle qui,
près du lit de mort, dut promettre de veiller sur Maurice, le dernier né
de la maison, aimable enfant de sept ans à peine, dont la santé
frêle, la beauté maladive et la précoce intelligence justifiaient tout à
la fois la complaisance et les alarmes dont il fut l’objet depuis le
berceau.
Il y eut ainsi quelque chose de maternel dans la tendresse de
Mlle de Guérin pour son frère. Avec quelle fidélité elle a tenu pendant
vingt ans sa promesse ! Par la pensée, elle suit Maurice partout, elle
veille sur les progrès de son esprit, sur tous les dangers de
l’absence pour sa santé, pour ses croyances ; elle l’interroge, elle
l’avertit doucement, elle le console et l’encourage. Lorsqu’il cesse
d’être un écolier pour devenir un homme, ses espérances et ses
inquiétudes redoublent ; elle se rapproche de Maurice, s’attache à
lui, le rattache à elle plus étroitement : comme si elle sentait que,
faible et entouré de périls nouveaux, il a plus que jamais besoin de
ne pas égarer sa confiance et ses affections. Alors les lettres qu’ils
échangent ne lui suffisent plus. Lui arrivât-il de passer les nuits à
écrire, elle n’en a pas dit assez ; ce jour encore et tous les jours son
cœur déborde ; tout ce qu’elle sent, tout ce qu’elle pense, tout ce qui
se passe autour d’elle, elle le dit au cahier qui suivra les lettres dès
qu’il sera rempli, et placera sous les yeux de l’exilé, pour le défendre
contre la tristesse et l’oubli, ces deux dangers de l’exil, l’image plus
naïve et plus complète de cette vie de famille qui lui manque et à
laquelle il fait défaut.
Ce Journal devient peu à peu sa grande affaire, le secret et la
joie de ses journées ; il adoucit l’amertume de la séparation ; en y
mettant son âme tout entière, elle a réussi à ne plus vivre sans son
frère, à ne plus vivre que pour lui ; il n’y a point pour elle d’autre
avenir que le sien ; le terme de ses vœux, c’est de le sentir heureux,
c’est de se faire elle-même sa part dans le bonheur de Maurice et
dans sa renommée, car il n’est rien qu’elle n’attende pour lui, et dont
il ne soit digne aux yeux de sa sœur.
Au moment où elle se croyait exaucée, la mort vint détruire
toutes ses illusions. Elle l’a perdu, mais dans son souvenir il vit, il
l’écoute et il lui répond. Aussi le Journal n’est-il point suspendu. Elle
écrit encore pour lui, pour Maurice au ciel. Un de ses cahiers est
adressé au dernier ami de son frère, à ce seul titre un frère
d’adoption pour elle ; mais c’est toujours de Maurice qu’elle parle,
toujours à lui. Elle s’entretient avec son âme.
Le jour vint pourtant où la plume devait lui tomber des mains. Elle
ne la reprend plus que par intervalles, pour marquer un anniversaire,
pour écrire des lettres où perce incessamment son unique et dernier
désir : celui que des amis fidèles sauvent de l’oubli les écrits de son
frère, ces écrits destinés à perpétuer le nom du poëte mort avant
l’âge, et à rajeunir l’antique blason du Cayla. Elle espéra longtemps,
lutta de loin contre les obstacles de toute sorte qui s’opposaient à
l’accomplissement de son vœu ; puis, lorsque cette dernière illusion
lui échappa, elle sentit que ses forces l’abandonnaient aussi ; elle
cessa d’écrire, elle allait cesser de vivre.
Peut-être a-t-elle quitté le monde avec le regret de n’avoir pas
rempli sa tâche ; tous ceux qui liront ce livre diront avec nous qu’elle
l’avait remplie. Ses dernières lettres, son Journal interrompu
suffisent pour honorer à jamais le frère qu’elle a tant aimé. Après
l’éclatant témoignage de George Sand, de M. Sainte-Beuve [5] , il ne
manquait plus à Maurice de Guérin que l’expression si touchante de
la tendresse et des regrets d’une telle sœur pour attacher à son nom
et à sa personne des sympathies plus profondes et plus durables
encore que l’admiration excitée par quelques pages de ses écrits ; et
s’il arrivait un jour que l’auteur du Centaure retombât dans l’oubli,
nous oserions promettre au frère d’Eugénie l’immortalité.
[5] Dans la belle Notice imprimée en tête des deux
éditions, et reproduite dans le tome XV des Causeries du
lundi.
Lui assurer cette gloire était son vœu. Jamais Mlle de Guérin
n’avait prétendu la partager. Il en sera pourtant ainsi. Et Maurice
aurait été le premier à trouver que cela était juste. En vain sa sœur
essaye-t-elle de lutter contre l’inspiration qui la sollicite et de
s’effacer devant lui : il envie à ce poëte qui veut se taire, à ce poëte
malgré lui la fécondité de sa pensée, l’originalité de son langage :
« Oh ! lui dit-il, si j’étais toi ! » En effet, c’est elle qui avait le plus reçu
de la nature. A peine a-t-elle connu les langueurs de l’épuisement
qui arrachent à Maurice des plaintes si pénétrantes ; dans ce qu’elle
écrit, jamais d’effort. « Je ne sais, avoue-t-elle quelque part, pourquoi
il est en moi d’écrire comme à la fontaine de couler. » Facilité qui
semble excessive lorsqu’on lit ses vers ; dans cette langue, il lui a
manqué, comme à son frère, et plus encore, de savoir se borner et
revenir sur les négligences de l’improvisation. Mais ce libre jet donne
à sa prose, précise et nerveuse, un relief et une ingénuité dont on
est saisi. Elle a l’énergie et la grâce, le don de dire simplement
toutes choses, et de s’élever des plus petites, par un mouvement
naturel, aux plus hautes ; elle est tour à tour et tout à la fois familière,
enjouée, naïve, profonde et sublime. L’étude et l’art n’ont guère
passé par là ; on le sent même à quelques termes singuliers, à
quelques expressions étranges, qui seraient ailleurs autant de
taches, qui sont ici comme un reste d’accent, le goût du terroir, le
parfum de la solitude. Aussi n’avons-nous point songé à les effacer.
Le Journal de Mlle de Guérin n’est malheureusement pas
complet. Trois cahiers ne nous sont point parvenus : ils ont été
égarés sans doute avec toutes les lettres adressées par la sœur à
son frère. Nous publions les douze autres cahiers tels qu’ils ont été
remis en nos mains par M. Auguste Raynaud au nom de Mlle Marie
de Guérin, qui nous permettra de lui témoigner ici notre éternelle
reconnaissance pour la haute confiance dont elle nous a honoré.
Nous en avons seulement réservé, pour nous conformer au juste
désir de la famille, un petit nombre de passages d’ailleurs très courts
et d’un médiocre intérêt littéraire, où des personnes qui vivent
encore étaient désignées trop directement, et qu’il sera facile de
rétablir dans les éditions postérieures, dès qu’on le pourra sans
blesser les convenances.
Le Journal est suivi de quelques lettres également remplies du

souvenir de Maurice. C’est pourquoi nous les avons choisies parmi
toutes celles qui nous ont été communiquées. Il en existe un nombre
considérable. Autour de Mlle de Guérin, parents, amis, et quelquefois
même des étrangers, tout le monde voulait avoir de ses lettres. On y
trouvait une joie pour l’esprit, un trésor pour l’âme. Elle ne savait pas
se défendre de telles demandes, et ce n’était pas trop de la facilité
merveilleuse dont elle était douée pour suffire à l’activité d’une telle
correspondance. Une grande partie de ces lettres existe encore ;
nous en avons vu beaucoup, on nous en a fait espérer d’autres, et si
ce volume trouve dans le monde l’accueil qu’il mérite et sur lequel
nous avons toujours compté, peut-être nous sera-t-il permis d’en
donner plus tard un recueil complet.
Alors nous croirons avoir rempli notre tâche et élevé, nous aussi,
à deux mémoires qui nous sont chères et sacrées, et à l’honneur
des lettres françaises, un monument.
Août 1862.
Le double espoir exprimé à la fin de cette préface a été rempli.

Huit éditions épuisées en seize mois ; les éloges spontanés et
unanimes de la critique, non-seulement à Paris, mais dans toutes les
provinces et à l’étranger ; enfin le suffrage de l’Académie française,
ont consacré le succès du Journal de Mlle Eugénie de Guérin.
En même temps, le zèle pieux de M. Trebutien ne s’est pas
ralenti. Les lettres qu’il attendait lui sont venues, assez intéressantes
et assez nombreuses pour que le choix qu’il en prépare forme
bientôt tout un volume destiné à faire suite au Journal et à recueillir
les mêmes sympathies.
Dès à présent, nous réservons les dix-neuf lettres qui terminaient
ce volume dans les éditions précédentes, pour les mettre à leur
place dans le recueil nouveau que les nombreux admirateurs de
Maurice et d’Eugénie de Guérin attendaient avec impatience, et que
nous sommes heureux de pouvoir leur promettre pour le courant de
cette année.
D. et Cie.
Janvier 1864.
JOURNAL
DE
EUGÉNIE DE GUÉRIN
(Novembre 1834-Octobre 1841)
I
A MON BIEN-AIMÉ FRÈRE MAURICE
Je me dépose dans votre âme.
(Hildegarde à saint Bernard.)
Le 15 novembre 1834. — Puisque tu le veux, mon cher Maurice,

je vais donc continuer ce petit Journal que tu aimes tant [6] . Mais
comme le papier me manque, je me sers d’un cahier cousu, destiné
à la poésie, dont je n’ôte rien que le titre [7] ; fil et feuilles, tout y
demeure, et tu l’auras, tout gros qu’il est, à la première occasion.
[6] On voit par le début du cahier suivant que celui-ci
était le second. Le premier ne s’est point retrouvé.
[7] Le mot Poésies se lit encore, à demi effacé, en
haut de la page.
C’est du 15 novembre que je prends date, huit jours juste depuis

ta dernière lettre. A l’heure qu’il est, je l’emportais dans mon sac, de
Cahuzac ici, avec une annonce de mort, celle de M. d’Huteau, dont
sa famille nous a fait part. Que de fois l’allégresse et le deuil nous
arrivent ensemble ! Ta lettre me faisait bien plaisir, mais cette mort
nous attristait, nous faisait regretter un homme bon et aimable qui
s’était en tout temps montré notre ami. Tout Gaillac l’a pleuré, grands
et petits. De pauvres femmes disaient en allant à son agonie :
« Celui-là n’aurait jamais dû mourir », et elles priaient en pleurant
pour sa bonne mort. Voilà qui donne à espérer pour son âme : des
vertus qui nous font aimer des hommes doivent nous faire aimer de
Dieu. M. le curé le voyait tous les jours, et sans doute il aura fait plus
que le voir. C’est l’Illustre [8] qui nous donne ces nouvelles avec
d’autres qui vont courant dans le monde de Gaillac, et moi, pour
passe-temps, je les lis et je pense à elle.
[8] On appelait quelquefois ainsi dans la famille l’autre
sœur, Mimi, Mimin ou Marie.
Le 17. — Trois lettres depuis hier, trois plaisirs bien grands, car
j’aime tant les lettres et celles qui m’écrivent : c’est Louise, Mimi et
Félicité. Cette chère Mimi me dit de charmantes et douces choses
sur notre séparation, sur son retour, sur son ennui, car elle s’ennuie
loin de moi comme je m’ennuie sans elle. A tout moment, je vois, je
sens qu’elle me manque, surtout la nuit où j’ai l’habitude de
l’entendre respirer à mon oreille. Ce petit bruit me porte sommeil. Ne
pas l’entendre me fait penser tristement. Je pense à la mort, qui fait
aussi tout taire autour de nous, qui sera aussi une absence. Ces
idées de la nuit me viennent un peu de celles du jour. On ne parle
que maladies, que morts ; la cloche d’Andillac n’a sonné que des
glas ces jours-ci. C’est la fièvre maligne qui fait ses ravages comme
tous les ans. Nous pleurons tous une jeune femme de ton âge, la
plus belle, la plus vertueuse de la paroisse, enlevée en quelques
jours. Elle laisse un tout petit enfant qui tétait. Pauvre petit ! C’était
Marianne de Gaillard. Dimanche dernier j’allai encore serrer la main
à une agonisante de dix-huit ans. Elle me reconnut, la pauvre jeune
fille, me dit un mot et se remit à prier Dieu. Je voulais lui parler, je ne
sus que lui dire ; les mourants parlent mieux que nous. On l’enterrait
lundi. Que de réflexions à faire sur ces tombes fraîches ! O mon
Dieu, que l’on s’en va vite de ce monde ! Le soir, quand je suis
seule, toutes ces figures de morts me reviennent. Je n’ai pas peur,
mais mes pensées prennent toutes le deuil, et le monde me paraît
aussi triste qu’un tombeau. Je t’ai dit cependant que ces lettres
m’avaient fait plaisir. Oh ! c’est bien vrai ; mon cœur n’est pas muet
au milieu de ces agonies, et ne sent que plus vivement tout ce qui lui
porte vie. Ta lettre donc m’a donné une lueur de joie, je me trompe,
un véritable bonheur, par les bonnes choses dont elle est remplie.
Enfin ton avenir commence à poindre ; je te vois un état, une
position sociale, un point d’appui à la vie matérielle. Dieu soit loué !
c’est ce que je désirais le plus en ce monde et pour toi et pour moi,
car mon avenir s’attache au tien, ils sont frères. J’ai fait de beaux
rêves à ce sujet, je te les dirai peut-être. Pour le moment, adieu ; il
faut que j’écrive à Mimi.
Le 18. — Je suis furieuse contre la chatte grise. Cette méchante

bête vient de m’enlever un petit pigeon que je réchauffais au coin du
feu. Il commençait à revivre, le pauvre animal ; je voulais le priver, il
m’aurait aimée, et voilà tout cela croqué par un chat ! Que de
mécomptes dans la vie ! Cet événement et tous ceux du jour se sont
passés à la cuisine ; c’est là que je fais demeure toute la matinée et
une partie du soir depuis que je suis sans Mimi. Il faut surveiller la
cuisinière, papa quelquefois descend et je lui lis près du fourneau ou
au coin du feu quelques morceaux des Antiquités de l’Église anglo-
saxonne. Ce gros livre étonnait Pierril. Qué de mouts aqui dédins [9] !
Cet enfant est tout à fait drôle. Un soir il me demanda si l’âme était
immortelle ; puis après, ce que c’était qu’un philosophe. Nous étions
aux grandes questions, comme tu vois. Sur ma réponse que c’était
quelqu’un de sage et de savant : « Donc, mademoiselle, vous êtes
philosophe. » Ce fut dit avec un air de naïveté et de franchise qui
aurait pu flatter Socrate, mais qui me fit tant rire que mon sérieux de
catéchiste s’en alla pour la soirée. Cet enfant nous a quittés un de
ces jours, à son grand regret ; il était à terme le jour de la Saint-
Brice. Le voilà avec son petit cochon cherchant des truffes. S’il vient
par ici, j’irai le joindre pour lui demander s’il me trouve toujours l’air
philosophe.
[9] En patois du pays : Que de mots là-dedans !
Avec qui croirais-tu que j’étais ce matin au coin du feu de la
cuisine ? Avec Platon : je n’osais pas le dire, mais il m’est tombé
sous les yeux, et j’ai voulu faire sa connaissance. Je n’en suis
qu’aux premières pages. Il me semble admirable, ce Platon ; mais je
lui trouve une singulière idée, c’est de placer la santé avant la
beauté dans la nomenclature des biens que Dieu nous fait. S’il eût
consulté une femme, Platon n’aurait pas écrit cela : tu le penses
bien ? Je le pense aussi, et cependant, me souvenant que je suis
philosophe, je suis un peu de son avis. Quand on est au lit bien
malade, on ferait volontiers le sacrifice de son teint ou de ses beaux
yeux pour rattraper la santé et jouir du soleil. Il suffit d’ailleurs d’un
peu de piété dans le cœur, d’un peu d’amour de Dieu pour renoncer
bien vite à ces idolâtries, car une jolie femme s’adore. Quand j’étais
enfant, j’aurais voulu être belle ; je ne rêvais que beauté, parce que,
me disais-je, maman m’aurait aimée davantage. Grâce à Dieu, cet
enfantillage a passé, et je n’envie d’autre beauté que celle de l’âme.
Peut-être même en cela suis-je enfant comme autrefois : je voudrais
ressembler aux anges. Cela peut déplaire à Dieu ; c’est aussi pour
en être aimée davantage. Que de choses me viennent, s’il ne fallait
pas te quitter ! Mais mon chapelet, il faut que je le dise, la nuit est là :
j’aime de finir le jour en prières.
Le 20. — J’aime la neige, cette blanche vue a quelque chose de

céleste. La boue, la terre nue me déplaisent, m’attristent ;
aujourd’hui je n’aperçois que la trace des chemins et les pieds des
petits oiseaux. Tout légèrement qu’ils se posent, ils laissent leurs
petites traces qui font mille figures sur la neige. C’est joli à voir ces
petites pattes rouges comme des crayons de corail qui les
dessinent. L’hiver a donc aussi ses jolies choses, ses agréments. On
en trouve partout quand on y sait voir. Dieu répandit partout la grâce
et la beauté. Il faut que j’aille voir ce qu’il y a d’aimable au coin du
feu de la cuisine, des bluettes si je veux. Ceci n’est qu’un petit
bonjour que je dis à la neige et à toi, au saut du lit.
Il m’a fallu mettre un plat de plus pour Sauveur Roquier qui nous
est venu voir. C’est du jambon au sucre, dont le pauvre garçon s’est
léché les doigts. Les bonnes choses ne lui viennent pas souvent à la
bouche, voilà pourquoi je l’ai voulu bien traiter. C’est pour les
délaissés, ce me semble, qu’il faut avoir des attentions ; l’humanité,
la charité nous le disent. Les heureux s’en peuvent passer, et il n’y
en a pourtant que pour eux dans le monde : c’est que nous sommes
faits à l’envers.
Pas de lecture aujourd’hui ; j’ai fait une coiffe pour la petite qui
m’a pris tous mes moments. Mais pourvu qu’on travaille, soit de tête
ou de doigts, c’est bien égal aux yeux de Dieu, qui tient compte de
toute œuvre faite en son nom. J’espère donc que ma coiffe me
tiendra lieu d’une charité. J’ai fait don de mon temps, d’un peu de
peau que m’a emportée l’aiguille, et de mille lignes intéressantes
que j’aurais pu lire. Papa m’apporta avant-hier, de Clairac, Ivanhoë
et le Siècle de Louis XIV. Voilà des provisions pour quelques-unes
de ces longues soirées d’hiver. C’est moi qui suis lectrice, mais à
bâtons rompus ; c’est tantôt une clef qu’on demande, mille choses,
souvent ma personne, et le livre se ferme pour un moment. O Mimin,
quand reviendras-tu aider la pauvre ménagère à qui tu manques à
tout moment ? T’ai-je dit qu’hier j’eus de ses nouvelles à la foire de
C… où je suis allée ? Que de bâillements j’ai laissés sur ce pauvre
balcon ! Enfin la lettre de Mimi m’arriva tout exprès comme un
contre-ennui, et c’est tout ce que j’ai vu d’aimable à C…
Je n’ai rien mis ici hier ; mieux vaut du blanc que des nullités, et
c’est tout ce que j’aurais pu te dire. J’étais fatiguée, j’avais sommeil.
Aujourd’hui c’est beaucoup mieux ; j’ai vu venir et s’en aller la neige.
Du temps que je faisais mon dîner, un beau soleil s’est levé ; plus de
neige ; à présent, le noir, le laid reparaissent. Que verrai-je demain
matin ? Qui sait ? La face du monde change si promptement !
Je viens toute contente de la cuisine, où j’ai demeuré ce soir plus
longtemps, pour décider Paul, un de nos domestiques, à aller se
confesser à Noël. Il me l’a promis ; c’est un bon garçon, il le fera.
Dieu soit loué ! ma soirée n’est pas perdue. Quel bonheur si je
pouvais ainsi tous les jours gagner une âme à Dieu ! Le bon Scott a

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Textbook of Tuberculosis and

Tuberculosis of the Gastrointestinal system Feb 23 2022

Problems and Solutions in Organic Chemistry for JEE

Principles of Pharmacology 3rd Edition Hl Sharma Kk

Textbook of Pediatric Infectious Diseases 2nd Edition

Textbook of Pharmacoepidemiology 3rd Edition

Problems and Solutions in Organic Chemistry for JEE 3rd

A Textbook on Modern Quantum Mechanics 1st Edition

Nuclear and Particle Physics 1st Edition K K Sharma B S

JAYPEE BROTHERS MEDICAL PUBLISHERS

SK Acharya VH Balasangameshwara Abha Chandra

Sajal De Gaurav PS Gahlot Sanjay Gupta

Manisha Jana DR Karnad Amitabh Kumar

Knut Lönnroth SP Munigoti John Porter

Ruma Ray Erwin Schurr K Aparna Sharma

Divya Singh Srikanth Tripathy Andrew Vernon

Mario C Raviglione FRCP [UK] FERS Hon RSP [RF]

2. Epidemiology of Tuberculosis: Global Perspective.......................................................................13

6. Genetic Susceptibility Parameters in Tuberculosis......................................................................73

7. Genetics of Susceptibility to Tuberculosis.................................................................................92

8. Laboratory Diagnosis of Tuberculosis: Best Practices and Current Policies....................................... 106

9. Roentgenographic Manifestations of Pulmonary and Extra-pulmonary Tuberculosis............................. 113

10. Pulmonary Tuberculosis.................................................................................................... 146

11. Lower Lung Field Tuberculosis............................................................................................ 155

12. Endobronchial Tuberculosis................................................................................................ 160

13. Tuberculosis Pleural Effusion.............................................................................................. 175

14. Silicotuberculosis............................................................................................................ 200

15. Abdominal Tuberculosis.................................................................................................... 208

16. Granulomatous Hepatitis................................................................................................... 222

17. Neurological Tuberculosis.................................................................................................. 230

18. Tuberculosis and Heart..................................................................................................... 253

19. Skeletal Tuberculosis....................................................................................................... 267

20. Musculoskeletal Manifestations of Tuberculosis....................................................................... 294

21. Cutaneous Tuberculosis.................................................................................................... 302

22. Lymph Node Tuberculosis.................................................................................................. 313

23. Tuberculosis in Head and Neck............................................................................................ 326

24. Ocular Tuberculosis......................................................................................................... 335

25. Tuberculosis in Pregnancy ................................................................................................. 346

26. Female Genital Tuberculosis .............................................................................................. 354

27. Genitourinary Tuberculosis ................................................................................................ 368

28. Tuberculosis in Chronic Kidney Disease................................................................................. 379

29. Disseminated/Miliary Tuberculosis....................................................................................... 391

30. Tuberculosis at Uncommon Body Sites................................................................................... 411

31. Complications of Pulmonary Tuberculosis............................................................................... 419

32. Tuberculosis and Acute Respiratory Distress Syndrome.............................................................. 432

33. Haematological Manifestations of Tuberculosis ....................................................................... 442

34. Endocrine Implications of Tuberculosis.................................................................................. 453

35. Tuberculosis and Human Immunodeficiency Virus Infection.......................................................... 466

36. Tuberculosis in Children ................................................................................................... 483

37. Surgical Aspects of Childhood Tuberculosis............................................................................. 495

38. Tuberculosis in the Elderly................................................................................................. 506

39. Tuberculosis in Health Care Workers..................................................................................... 520

40. Nutrition and Tuberculosis................................................................................................. 529

41. Nontuberculous Mycobacterial Infections................................................................................ 540

42. Drug-resistant Tuberculosis................................................................................................ 579

43. Antituberculosis Drug Resistance Surveillance......................................................................... 609

44. Treatment of Tuberculosis.................................................................................................. 621

45. Hepatotoxicity Associated with Anti-tuberculosis Treatment......................................................... 637

46. Surgery for Pleuropulmonary Tuberculosis.............................................................................. 644

Figure 1.4B: The Union Mission Tuberculosis Sanatorium, at Arogya

23. Scrivo R, Armignacco O. Tuberculosis risk and anti-tumour 2362168570 Guidance%20tool%20for%20TB%20notification%20