Preface

One famous saying by Robert Louis Stevenson "It is not a hard thing to know what to write; the hard thing is to know what to leave out" holds very true for us while writing the preface of this book.

Tuberculosis (TB) is as old as mankind and continues to haunt the mankind despite several spectacular advances in the diagnosis and management of TB. TB is the commonest single infectious cause of death and accountable for over 25% of avoidable deaths worldwide but can still be labeled as "Captain of all these men of death".

In the initial sections of the book chapters covering the basic pathophysiology and the im‐ portant factors contributing to the same viz. epidemiology of TB, iron metabolism, unusual properties of M. Tuberculosis, lipid inclusion, role of small regulatory RNA and adaptation to survival in human host, which makes it "tough bug" to treat, has been included in details. Our understanding of the host pathogen interaction at the molecular level, especially immu‐ nopathogenesis of TB has improved enormously and has been extensively covered in the book. Chapters have been included to cover several new drug and potential vaccines for TB. New development such as the interferon-gamma release assays [IGRAs] for latent TB infec‐ tion, use of liquid culture and molecular method of diagnosis are ushering in a new era in TB diagnostics. Comprehensive knowledge of latest modes of diagnosis has been also incor‐ porated in the book. Furthermore, issues concerning quality assurance in antituberculosis drug susceptibility testing are getting established.

Data are rapidly accumulating from all over the world regarding the efficacy of standar‐ dized treatment regimens for drug-sensitive, drug-resistant TB and latent TB infection. While we are facing the menace of multi drug-resistant TB [MDR-TB], extensively drug-re‐ sistant tuberculosis [XDR¬ TB] has emerged threatening to undermine global efforts at TB control. Hence we have included chapters to cover all aspects of the diagnosis and manage‐ ment of MDR TB. This book will cover all these developments in great detail.

With the widespread availability of internet globally various standard web resources availa‐ ble on TB have also been included so that the readers may get the comprehensive and up‐ dated guidelines from these resources. The changing clinical presentation of TB, advances in laboratory, imaging diagnostic modalities, therapeutic measures and emergence of MDR TB all suggest a pressing need to have a updated book on TB. Furthermore, while all physicians encounter the TB disease in their clinical practice, there have been a lot of controversies and misconceptions over various issues for the diagnosis and management of TB.

Paucity of a well referenced, updated, standard book of TB has prompted us to undertake this venture sharing the clinical experience of global experts of TB.

Our book contains chapters on epidemiology, immune-pathology, diagnosis, treatment and latest advances for TB, highlighting the global perspective of tuberculosis. World-wide re‐ surgence of MDR TB indicates that the battle against this foe of mankind will continue in the coming years. TB still remains to be a research priority of paramount importance from medical, social and financial aspects and we have attempted to highlight all the aspects for the treatment of TB.

We believe that this book will serve as a practical guide for the diagnosis and management of TB for practicing physicians (especially pulmonologists and internists) and all those who are involved in the management of TB.

This book has several contributors, all of them leading authorities from various parts of the world. All the chapters have been thoroughly re-written and updated with preservation of the views of the contributors in a uniform format. This effort would not have been possible without the kind cooperation of our contributors who patiently went through revisions and updating of their chapters. We convey our heartfelt thanks to all contributors and to InTech Publisher, Croatia for their encouragement and excellent technical assistance as and when required.

Lastly we would like to thank the almighty god, our parents, wives and children, without their untiring support and encouragement this book would not have seen the light of the day.

> Editor: **Dr. Bassam H. Mahboub** Director, Department of Pulmonary Medicine and Allergy, Rashid Hospital & Dubai Hospital, Dubai; Assistant Professor, Dept of Medicine & Respiratory Disease & Allergy, University of Sharjah, UAE

> > Co-editor: **Dr. Mayank G. Vats** Senior Specialist, Pulmonologist, Intensivist & Sleep Physician, Rashid Hospital, Dubai Health Authority, Dubai, UAE

**Section 1**

**Pathophysiology and Immunogenesis of**

**Tuberculosis**

**Pathophysiology and Immunogenesis of Tuberculosis**

Our book contains chapters on epidemiology, immune-pathology, diagnosis, treatment and latest advances for TB, highlighting the global perspective of tuberculosis. World-wide re‐ surgence of MDR TB indicates that the battle against this foe of mankind will continue in the coming years. TB still remains to be a research priority of paramount importance from medical, social and financial aspects and we have attempted to highlight all the aspects for

We believe that this book will serve as a practical guide for the diagnosis and management of TB for practicing physicians (especially pulmonologists and internists) and all those who

This book has several contributors, all of them leading authorities from various parts of the world. All the chapters have been thoroughly re-written and updated with preservation of the views of the contributors in a uniform format. This effort would not have been possible without the kind cooperation of our contributors who patiently went through revisions and updating of their chapters. We convey our heartfelt thanks to all contributors and to InTech Publisher, Croatia for their encouragement and excellent technical assistance as and when required.

Lastly we would like to thank the almighty god, our parents, wives and children, without their untiring support and encouragement this book would not have seen the light of the day.

Editor:

Co-editor:

Dubai, UAE

**Dr. Bassam H. Mahboub**

University of Sharjah, UAE

Senior Specialist, Pulmonologist, Intensivist & Sleep Physician,

**Dr. Mayank G. Vats**

Director, Department of Pulmonary Medicine and Allergy,

Assistant Professor, Dept of Medicine & Respiratory Disease & Allergy,

Rashid Hospital & Dubai Hospital, Dubai;

Rashid Hospital, Dubai Health Authority,

the treatment of TB.

X Preface

are involved in the management of TB.

**Chapter 1**

*Mycobacterium tuberculosis*

Additional information is available at the end of the chapter

Beatrice Saviola

**1. Introduction**

http://dx.doi.org/10.5772/54956

**Adaptation to Survival in a Human Host**

*Mycobacterium tuberculosis* exists exclusively as a pathogen of humans and in some cases of animals. It is not thought to exist in the environment other than for brief periods during transfer from an infected host to an uninfected contact. Thus *M. tuberculosis* must adapt to an *in vivo* environment by modifying gene expression. Differential expression can occur in immune cells such as macrophages, larger immune structures such as granulomas, and within liquefied lesions of the lung. Within the human body tubercle bacilli experience reactive oxygen intermediates as well as acidity within the phagosomes of macrophages. In addition within the centers of caseating granulomas bacilli experience low oxygen tension as well as toxic lipases and proteases released by dead immune cells. High temperature is present within the body of a person with active tuberculosis in the form of a fever. There may be other unrecog‐ nized signals and stresses that modulate gene expression within invading *M. tuberculosis* bacilli as well. Examination of gene expression during *in vivo* growth, within macrophages, or during application of specific stresses can illuminate which critical pathways in the mycobacterium are upregulated that lead to an *M. tuberculosis* bacillus exquisitely adapted to *in vivo* survival.

**2. Adaptation to growth in the phagosomal compartment of macrophages**

Macrophages are the preferred intracellular location for *M. tuberculosis in vivo.* Infected individuals cough and expel droplet nuclei which contain *M. tuberculosis* bacilli and remain suspended in the air. After inhalation and within the body, the bacilli are transported to the small alveoli in the lungs where they encounter alveolar macrophages which are relatively nonactivated (Dannenberg, 1993; Dannenberg, 1997). These nonactivated macrophages are not

> © 2013 Saviola; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.
