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A Tuberculosis Guide for Specialist Physicians

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A Tuberculosis Guide for Specialist Physicians A Tuberculosis Guide for Specialist Physicians 2004 José A. Caminero Luna International Union Against Tuberculosis and Lung Disease (IUATLD) 68 boulevard Saint Michel, 75006 Paris - France ii © International Union Against Tuberculosis and Lung Disease (IUATLD) 68 boulevard Saint Michel, 75006 Paris – France September 2004 Author: J.A. Caminero ISBN: 2-914365-13-6 iii i Dedication To my parents, for their unconditional support, humanity, honesty, hard work, and sacrifice. Their teachings and tolerance have been the best guides in my life. Acknowledgements First, I especially wish to express my most sincere gratitude to Drs. Paula Fujiwara (USA) and Dr. Victorino Farga (Chile), professors and friends, whose exhaustive review of this Guide has greatly improved it in terms of content and clarity. I also wish to thank: Dr. Nils E. Billo, Director of the International Union Against Tuberculosis and Lung Disease, for his unconditional support of my daily work and for his constant encouragement in the preparation of this book. Dr. Raúl Díaz, an excellent professional and friend, for his constant help and excellent editing activities in relation to the Guide. Dr. Rodolfo Rodríguez (Cuba), Regional Advisor for Tuberculosis (Pan American Health Organization/World Health Organization), who was largely responsible for the improvements in tuberculosis control throughout Latin America in the past six years. My thanks for his constant support of the Tuberculosis Updating Courses for Specialist Physicians, which have helped to ensure improved tuberculosis control in Latin America. The development of these courses has generated the material presented in the present Guide. My colleagues in the Pneumology Service of “Dr. Negrín” University Hospital in Gran Canaria, and particularly Dr. Pedro Cabrera-Navarro, for his understanding and constant support and stimulus in my assistential and operative activities. To the following colleagues, friends, and companions with whom long hours have been spent discussing tuberculosis, and whose teachings and publications have formed the basis of the information presented in this publication: Drs. José Alcaide (Barcelona), Nieves Altet (Barcelona), Vicente Ausina (Barcelona), María José Báguena (Valencia), César Bonilla (Peru), María Isolina Campos (Las Palmas de Gran Canaria), Manuel Casal (Córdoba), Joán Caylá (Barcelona), Donald Enarson (Canada), Antonio Lobo (Jerez-Cádiz), Pilar López-Facal (Las Palmas de Gran Canaria), José María Manterola (Barcelona), Juán Ruiz Manzano (Barcelona), Pere de March (Barcelona), Carlos Martín (Zaragoza), Juan Domingo Palmero (Argentina), María José Pena (Las Palmas de Gran Canaria), José Luís Pérez-Arellano (Las Palmas de Gran Canaria), José María Pina (Barcelona), Rafael Rey (Madrid), Miguel Angel Salázar (Mexico), Jesús Sauret (Barcelona), and Rafael Vidal (Barcelona). i Abbreviations ADA adenosine deaminase AIDS acquired immunodeficiency syndrome ARI annual rate of infection Ak amikacin AUC area under the curve BCG bacille Calmette-Guérin CDC Centers for Disease Control and Prevention Cfz clofazimine Cmax maximum concentration Cp capreomycin Cs cycloserine DNA deoxyribonucleic acid DOTS Directly Observed Therapy, Short Course E ethambutol ELISA enzyme-linked immunosorbent assay ETH ethionamide H isoniazid HAART highly active antiretroviral therapy HIV human immunodeficiency syndrome IUATLD International Union Against Tuberculosis and Lung Disease Kn kanamycin LCR ligase chain reaction LTBI latent tuberculous infection MDR multidrug resistance MIC minimum inhibitory concentration NTP National Tuberculosis Control Programme Ofl ofloxacin PAHO Pan American Health Organization PAS para-aminosalicylic acid PCR polymerase chain reaction PPD purified protein derivative PPV positive predictive value R rifampicin RNA ribonucleic acid ii S streptomycin SGOT serum glutamic oxaloacetic transaminase SGPT serum glutamic pyruvate transaminase T thiacetazone TB tuberculosis TLC thin-layer chromatography LTBI latent tuberculous infection Tmax time to maximum concentration TU tuberculin unit UN United Nations UNICEF United Nations Children’s Fund UV ultraviolet WHO World Health Organization Z pyrazinamide iii Contents Chapter 1. Guide rationale. The need for cooperation between tuberculosis control programmes and specialist physicians 1 Introduction Extent of the problem of tuberculosis in middle-income countries Reasons for the lack of integration of specialist physicians in tuberculosis control programmes The role of specialist physicians in an NTP Chapter 2. Importance of the role of specialist physicians and their integration in the strategies of a tuberculosis control programme 8 Rationale for the operational applicability of current knowledge on tuberculosis The need for specific training among specialist physicians Experience of the IUATLD in the specific training of specialist physicians Chapter 3. A brief history of tuberculosis 16 Speculations on the origin of Mycobacterium tuberculosis History of tuberculosis and the struggle to combat the disease History of tuberculosis control Chapter 4. Epidemiology of tuberculosis 23 The epidemiological chain Causal agent Source of infection Mechanism of transmission The susceptible host: risk factors Analytical parameters of tuberculosis The current situation of tuberculosis in the world Causes for the increase in tuberculosis in the world Poor or no application of tuberculosis control programmes Poverty and the widening gap between the rich and the poor The impact of HIV infection Massive immigration from tuberculosis endemic zones i The demographic explosion Measures for reducing tuberculosis in the community Improvement in socioeconomic conditions Adequate chemotherapy with high cure rates Chemoprophylaxis of infected individuals at high risk of developing tuberculosis BCG vaccination Chapter 5. Pathogenesis of tuberculosis: infection and disease 50 Primary infection Tuberculous reactivation Chapter 6. Diagnosis of tuberculosis infection: the tuberculin test 59 Pathogenic basis of the tuberculin test Factors affecting the result of the test Test standardisation Tuberculin Dosage Method of administration Reading of results Tuberculin storage False-negative and false-positive readings False-negative readings False-positive readings Interpretation of results Tuberculin test repetition. Tuberculin conversion. “Booster effect” Indications for tuberculin testing Positivity criteria and indications in low- and middle-income countries Chapter 7. Diagnosis of tuberculosis 76 Clinical assessment Clinical symptoms Physical examination General laboratory tests Tests indicated for patients with suspected tuberculosis Microbiological diagnosis Importance of sample collection and processing Evolution of the microbiological techniques used to diagnose tuberculosis Conventional microbiological techniques for diagnosing tuberculosis Smear microscopy Mycobacterial culture Identification of mycobacteria In vitro M. tuberculosis susceptibility testing Imaging techniques Tuberculin testing Histopathological diagnosis Non-conventional methods for diagnosing tuberculosis: new techniques Conclusions regarding the diagnosis of tuberculosis with conventional methods Chapter 8. Non-conventional methods and new techniques for diagnosing tuberculosis 131 Non-conventional smear microscopy techniques New mycobacterial culture methods Liquid culture media Radiometric methods (Bactec® system) Non-radiometric automated systems Non-radiometric biphasic culture media (MB-Septi-Check®) Systems for mycobacterial culture in blood New techniques for identifying mycobacteria NAP test in Bactec 12B Chromatography Genetic probes Other molecular techniques New techniques for drug susceptibility testing Drug susceptibility testing based on phenotypic techniques Drug susceptibility testing of M. tuberculosis in solid medium Drug susceptibility testing of M. tuberculosis in liquid medium In vitro susceptibility studies of M. tuberculosis using new technologies Drug susceptibility testing based on genetic techniques DNA probes Single-strand conformation polymorphism INNO-LipA solid-phase hybridisation i Diagnosis of tuberculosis using genetic amplification techniques Techniques that amplify mycobacterial DNA Polymerase chain reaction Ligase chain reaction Strand displacement amplification Techniques that amplify mycobacterial RNA Transcription-mediated amplification Q beta replicase Nucleic acid sequence–based amplification Serological diagnosis of tuberculosis Microbiological techniques as an aid in tuberculosis epidemiology Other non-microbiological techniques Interpretation of pleural fluid testing Adenosine deaminase Other determinations in serosal fluid with suspected tuberculosis Chapter 9. Treatment of tuberculosis 162 A brief history Microbiological bases for the treatment of tuberculosis Prevention of resistance: the need for drug combinations The need for prolonged treatments. Bacillary populations of M. tuberculosis Metabolically active and under conditions of continuous growth Bacilli in the acid-inhibition phase Bacilli in the sporadic multiplication phase Persistent or totally dormant populations Rationale for an ideal initial treatment regimen Why the need for a fourth drug in the initial phase? What is the ideal drug to add to isoniazid, rifampicin, and pyrazinamide in the initial phase? Can the drugs be administered only 2 to 3 times a week? Intermittent treatments Should regimens without rifampicin be used in the second phase? When are they advisable? Should preparations
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