TUBERCULOSIS - CURRENT ISSUES IN DIAGNOSIS AND MANAGEMENT Edited by Bassam H. Mahboub and Mayank G. Vats Tuberculosis - Current Issues in Diagnosis and Management http://dx.doi.org/10.5772/56396 Edited by Bassam H. Mahboub and Mayank G. Vats Contributors Raquel Lima De Figueiredo Teixeira, Marcia Lopes, Philip Suffys, Adalberto Santos, Luciene Scherer, Mochammad Hatta, Andi Rofian Sultan, Gunes Senol, Héctor Javier Sánchez-Pérez, Attapon Cheepsattayakorn, Zakaria Hmama, Beatrice Saviola, Isamu Sugawara, Qin Zhang, Wolfgang Frank, Said Hamed Abbadi, Claude Kirimuhuzya, Magana- Arachchi, Antonio De Miranda, Marcos Catanho, Handzel, Matthias Stehr, Armando Acosta, Hum Nath Jnawali, Sungweon Ryoo, Simona Alexandra Iacob, Diana-Gabriela Iacob, Raquel Teixeira, Rafael Pinto, Lizania Spinasse, Fernanda Mello, Jose Roberto Lapa E Silva, Wellman Ribón Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. 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Publishing Process Manager Iva Lipovic Technical Editor InTech DTP team Cover InTech Design team First published March, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Tuberculosis - Current Issues in Diagnosis and Management, Edited by Bassam H. Mahboub and Mayank G. Vats p. cm. ISBN 978-953-51-1049-1 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Section 1 Pathophysiology and Immunogenesis of Tuberculosis 1 Chapter 1 Mycobacterium tuberculosis Adaptation to Survival in a Human Host 3 Beatrice Saviola Chapter 2 The Immune Response to Mycobacterium tuberculosis Infection in Humans 19 Zeev Theodor Handzel Chapter 3 Lipid Inclusions in Mycobacterial Infections 31 Matthias Stehr, Ayssar A. Elamin and Mahavir Singh Chapter 4 The Role of Antibodies in the Defense Against Tuberculosis 57 Armando Acosta, Yamile Lopez, Norazmi Mohd Nor, Rogelio Hernández Pando, Nadine Alvarez, Maria Elena Sarmiento and Aharona Glatman-Freedman Chapter 5 Influence of the Interferon–Gamma (IFN–γ) and Tumor Necrosis Factor Alpha (TNF–α) Gene Polymorphisms in TB Occurrence and Clinical Spectrum 79 Márcia Quinhones Pires Lopes, Raquel Lima de Figueiredo Teixeira, Antonio Basilio de Miranda, Rafael Santos Pinto, Lizânia Borges Spinassé, Fernanda Carvalho Queiroz Mello, José Roberto Lapa e Silva, Philip Noel Suffys and Adalberto Rezende Santos Chapter 6 Tuberculosis Pharmacogenetics: State of The Art 105 Raquel Lima de Figueiredo Teixeira, Márcia Quinhones Pires Lopes, Philip Noel Suffys and Adalberto Rezende Santos Chapter 7 Pathophysiology of Tuberculosis 127 Ruiru Shi and Isamu Sugawara Section 2 Diagnosis and Management of Tuberculosis 141 Chapter 8 Laboratory Diagnosis of Tuberculosis - Latest Diagnostic Tools 143 Gunes Senol Chapter 9 Diagnostic Evaluation of Tuberculosis 153 Mochammad Hatta and A. R. Sultan Chapter 10 First– and Second–Line Drugs and Drug Resistance 163 Hum Nath Jnawali and Sungweon Ryoo Section 3 Multi-Drug Resistant Tuberculosis 181 Chapter 11 Epidemiology of Multidrug Resistant Tuberculosis (MDR-TB) 183 Dhammika Nayoma Magana-Arachchi Chapter 12 Drug Resistance in M. Tuberculosis 203 Said Hamed Abbadi Chapter 13 Management of Drug-Resistant TB 225 Zakaria Hmama Chapter 14 Drug-Resistant Tuberculosis – Diagnosis, Treatment, Management and Control: The Experience in Thailand 261 Attapon Cheepsattayakorn Section 4 Extra Pulmonary Tuberculosis 287 Chapter 15 Tuberculous Pleural Effusion 289 Wolfgang Frank Chapter 16 Neurotuberculosis and HIV Infection 315 Simona Alexandra Iacob and Diana Gabriela Iacob ContentsVI Section 5 Miscellaneous 351 Chapter 17 Research and Development of New Drugs Against Tuberculosis 353 Juan D. Guzman, Ximena Montes-Rincón and Wellman Ribón Chapter 18 Web Resources on TB: Information, Research, and Data Analysis 381 Marcos Catanho and Antonio Basílio de Miranda Chapter 19 Peadiatric Tuberculosis: Is the World Doing Enough? 393 Claude Kirimuhuzya Chapter 20 Economic Evaluation of Diagnosis Tuberculosis in Hospital Setting 451 Luciene C. Scherer Chapter 21 Pulmonary Tuberculosis in Latin America: Patchwork Studies Reveal Inequalities in Its Control – The Cases of Chiapas (Mexico), Chine (Ecuador) and Lima (Peru) 465 Héctor Javier Sánchez-Pérez, Olivia Horna–Campos, Natalia Romero-Sandoval, Ezequiel Consiglio and Miguel Martín Mateo Contents VII 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 PrefaceX [...]... availability of iron Proinflammatory cytokines stimulate hepcidin production, decrease iron uptake from the gut, and inhibits the iron efflux protein ferroportin (Johnson and Wessingling-Resnick, 2012) Inflammation thus inhibits iron uptake by the intestinal epithelium thus preventing iron from being loaded onto transferrin Interfering with uptake limits iron availability in the host, and M tuberculosis has... inflammation, produces siderocalins such as lipocalin-2 that can bind to and inactivate my‐ cobactin from M tuberculosis thus interfering with mycobacterial iron acquisition (Johnson and Wessingling-Resnick, 2012) In fact mice deleted for genes involved in production of siderocalin are much more susceptible to mortality due to M tuberculosis infection (Johnson and Wessingling-Resnick, 2012) Inside the mycobacterial... badly needed resources in the mycobacterium during times of stress RelA may be a target to prevent M tuberculosis from entering dormancy or a target to force M tuberculosis out of dormancy (Murphy and Brown, 2007) 5 6 Tuberculosis - Current Issues in Diagnosis and Management The ability of M tuberculosis to survive in a dormant state relies on maintaining cell integrity, viability, and a proton motive... IdeR This protein can act both as an activator and a repressor depending on where it binds within a mycobacterial promoter region (Manabe et al, 1999; Banerjee et al, 2011) Within 9 10 Tuberculosis - Current Issues in Diagnosis and Management promoters of genes involved in mycobactin synthesis it acts as a repressor, inhibiting expres‐ sion of these genes at high iron concentrations In promoters of... contain other molecules to detoxify oxidative damage including superoxide dismutase (SOD) and catalase (KatG) which can inactivate superoxide (Table 1.) (Shi et al, 2008) SOD and KatG are upregulated early in infection indicating an increase in oxidative damage due to superoxide Oxidative damage is capable of harming DNA, and histone like proteins (LSR2) can protect against damage by compacting DNA and. .. required M tuberculosis can persist for decades in a dormant state within hypoxic granulomas in the lung Studies have suggested that in a dormant state M tuberculosis is occupied mainly with maintaining cell wall integrity, membrane potential, and protecting its DNA structure The mycobacterium must also resist the host’s immune system A number of in vivo and in vitro models have been used to investigate... hours After this ini‐ tial 24 hour period other regulators play a role in hypoxic responses such as sigE and sigC (Table 1.) An enduring hypoxic response begins after the initial response, and this may be important for M tuberculosis to enter and stay in a dormant state (Rustad et al, 2008) 11 Toxin-antitoxin systems Interestingly there are many toxin-antitoxin systems within the M tuberculosis genome... rapidly, potentially in response to environmental stressors The toxin is not a protein secreted and targeted against the human host, but targeted against mycobacterial cellular components The toxin is a stable protein which may be complexed with an antitoxin forming a toxin-antitoxin pair The antitoxin is relatively unstable and environmental stressors can inactivate it causing release of a free toxin The... upregulated in M tuberculosis in vivo are heat shock proteins that have chaperonine activity While these proteins may benefit the organism by complexing with and refolding heat damaged proteins, they are also recognized by the immune system Both the 65Kd heat shock protein and the HSP70 protein can be found extracellularly to M tuberculo‐ sis, and are potent stimulators of an inflammatory response (Anand et... Pittius N, Champion P, Cox J, Luirink J, Vandenbroucke-Grauls C, Appelmelk B, and Bitter W 2007 Type VII secretion-mycobacteria show the way Nature Reviews in Microbiology 5: 883-891 13 14 Tuberculosis - Current Issues in Diagnosis and Management [2] Anand PK, Anand E, Bleck CKE, Anes E, Griffiths G Exosomal Hsp70 induces a proinflammatory response to foreign particles including mycobacteria Plos One 5(4):e10136 . TUBERCULOSIS - CURRENT ISSUES IN DIAGNOSIS AND MANAGEMENT Edited by Bassam H. Mahboub and Mayank G. Vats Tuberculosis - Current Issues in Diagnosis and Management http://dx.doi.org/10.5772/56396 Edited. protein ferroportin (Johnson and Wessingling-Resnick, 2012). Inflammation thus inhibits iron uptake by the intestinal epithelium thus preventing iron from being loaded onto transferrin. Interfering. stress in M. tuberculosis. Interestingly when M. tuberculosis is engulfed by the Tuberculosis - Current Issues in Diagnosis and Management6 phagosomes of macrophages many genes are upregulated, and