Preface
Contents
Part I: Epidemiology and Pathogenesis
Chapter 1: Epidemiology: Who Develops Pulmonary TB? How Does an Understanding of Global TB Epidemiology Help Clinicians Manage their Patients with Pulmonary TB?
1 Introduction
1.1 The Role of Epidemiology in Clinical Diagnosis and Management
1.2 The Implication of Clinical Practice for Public Health
2 The Disease Process of TB
3 Exposure to MTB
3.1 Risk Factors for Exposure to MTB
3.1.1 MTB Side Factors
3.1.2 Prevalence of Infectious TB Cases in a Community
3.1.3 Population Density and Environmental Conditions
4 Infection with MTB
4.1 Definition, Measurement, and Mode of Infection
4.2 The Risk of Infection with MTB
4.2.1 Estimated Risk of Infection with MTB
4.2.2 MTB Side Factors
4.2.3 Host Side Factors
Factors Influencing the Risk of Infection Associated with the Infectious Source Case
Factors Affecting the Risk of Infection Associated with an Exposed Host
5 TB Disease
5.1 Definition of Active TB Disease
5.2 Progression to TB Disease
5.2.1 Natural History of Active TB Disease
5.2.2 The Components Contributing to TB Disease
5.2.3 Risk Factors for TB Disease after Infection
MTB Side Factors
Host Side Factors
6 TB Deaths
6.1 TB Deaths in the Pre-Chemotherapy Era
6.2 Factors Related to TB Deaths in the Chemotherapy Era
6.2.1 TB Treatment Delays
6.2.2 Comorbidities and Aging
6.2.3 Failure to Complete TB Treatment and Drug Resistance
7 The Molecular Epidemiology of TB
8 The Impact of Coronavirus Disease 2019 (COVID-19) on TB Epidemiology
9 The Global Burden of TB
9.1 Measurement of Disease Burden
9.2 The Historical View of TB Epidemiology
9.3 Current TB Epidemiology
9.3.1 HIV/TB
9.3.2 Multidrug-Resistant TB
9.3.3 Migrants
9.3.4 Elderly Population
9.3.5 Global TB Strategy by the WHO
The DOTS Strategy
9.3.6 The Stop TB Strategy
9.3.7 The End TB Strategy
10 Conclusion
References
Chapter 2: Immunology: How Does the Immune System Affect the Development of Pulmonary TB? How Does an Understanding of TB Immunology Help Clinicians Manage their Patients with Pulmonary TB?
1 Introduction
2 Innate Immunity against M. Tuberculosis
2.1 Recognition of M. Tuberculosis by Pattern Recognition Receptors
2.2 Phagosomal Defense in Macrophages
3 Initiation of Adaptive Immunity to M. Tuberculosis by DCs
4 The Role of Adaptive Immunity against M. Tuberculosis
4.1 The IFN-γ/IL-12 Axis and TB Immunity
4.2 The Role of CD8 T-Cells in M. Tuberculosis Infection
5 LTBI and its Reactivation
5.1 TNF-α Inhibitors and Mycobacterial Infections
5.2 Role of the PD-1 Pathway in TB
6 Conclusion
References
Chapter 3: Impact of Biologic and JAK Inhibitor Therapies on TB: How Do Biologic Therapies Affect the Presentation and Treatment Course of Pulmonary TB?
1 Introduction
1.1 The Dawn of the Era of Biologics
2 Pathophysiology of TB
3 TNF Inhibitors and TB
3.1 Why Do TNF Inhibitors Make TB More Prone to Activation?
3.2 Treatment of Latent TB Infections When RA Patients Are Administered with Biologics, Especially with Anti-TNF Inhibitors
3.3 Differences in Prognosis Between Miliary TB and Pulmonary TB That Developed During Biologics Administration
3.4 If Miliary TB Develops During Administration of a TNF Inhibitor, Discontinuation of the TNF Inhibitor Activates Immunity, Causes IRIS, and Worsens the Prognosis
3.5 Even if TB Develops during Administration of an Anti-TNF Inhibitor, It Is Possible to Readminister the Anti-TNF Inhibitor After TB Treatment
3.6 Is It Possible to Readminister Anti-TNF Inhibitor After TB Treatment in Patients Who Develop Active TB during Anti-TNF Inhibitor Administration and Discontinue Anti-TNF Inhibitor?
4 JAK Inhibitor
4.1 Endogenenous JAK inhibitors, SOCSs, and TB
4.2 JAK Inhibitors and TB
4.3 JAK Inhibitors and TB Therapy
5 Host-Directed TB Therapy
6 Conclusion
References
Chapter 4: Advances in Mycobacterial Laboratories: What Is the Latest Laboratory Approach to Diagnose and Manage Pulmonary TB?
1 Introduction
2 Clinical Specimen Collection
3 Pretreatment Methods
3.1 Sodium Hydroxide
3.2 Chlorhexidine
3.3 Concentration Methods
3.4 Culture Methods
4 Nucleic Acid Amplification
4.1 Xpert Series
4.1.1 Xpert MTB/RIF
4.1.2 Xpert MTB/RIF Ultra
4.1.3 Xpert MTB/XDR
4.2 TB-Loop-Mediated Isothermal Amplification (TB-LAMP)
4.3 TrueNAT
4.4 Line Probe Assay (LPA)
5 Species Identification
5.1 MPT64
5.2 Matrix-Assisted Laser Deionization–Time of Flight Mass Spectrometry (MALDI-TOF MS)
5.3 Multilocus Sequencing Typing (MLST)
6 Biomarkers
6.1 ESAT-6 and CFP-10
6.2 Lipoarabinomannan
6.3 Immunogenic Protein MPT64
7 Drug Susceptibility Testing
7.1 Phenotypic DST
7.2 Genetic DST
8 Conclusion
References
Part II: Pulmonary TB
Chapter 5: Advances in Diagnostics of Pulmonary TB: What Is the Latest Approach to Diagnose Pulmonary TB?
1 Introduction
2 Symptoms
3 Delays
4 TB Diagnostic Methods
4.1 Conventional Examinations
4.2 Advances from Microbiological Reference Standard
4.3 Chest Imaging
4.3.1 Chest X-Ray Diagnosis
4.3.2 Computed Tomography
4.3.3 Other Imaging
4.4 Bronchoscopy
5 New Technologies
5.1 Lipoarabinomannan (LAM)
5.2 Other Biomarkers
5.3 Computer-Aided Detection Software
5.4 PET
6 Special Status
6.1 Elderly
6.2 People Living with HIV(PLWHIV)
7 Case Findings
7.1 Low Prevalence Areas
7.1.1 Symptomatic Visit
7.1.2 Contact Investigations
7.1.3 Screening
7.2 TB Endemic Areas
7.2.1 Countries with High TB Burden but Abundant Resources
7.2.2 Countries with High TB Burden and Scarce Resources
8 Conclusion
References
Chapter 6: HRCT Diagnosis of Pulmonary TB: Microlesions
1 Introduction
2 HRCT of Pulmonary Lobules and Pulmonary TB
3 Achievements of Predecessors Who Influenced HRCT Diagnosis of Pulmonary TB
References
Chapter 7: Advances in Treatment of Drug-Resistant Pulmonary TB: What Is the Latest Approach to Treat Drug-Resistant Pulmonary TB?
1 Introduction
2 Definitions of MDR, Pre-XDR, and XDR-TB
3 Treatment of Drug-Resistant TB
3.1 Isoniazid-Resistant, Rifampin Susceptible TB
3.2 MDR/RR-TB
3.2.1 Grouping of Second-Line TB Drugs
Group A Drugs
Fluoroquinolones (Moxifloxacin and Levofloxacin)
Bedaquiline
Linezolid
Group B Drugs
Clofazimine
Cycloserine and Terizidone
Group C Drugs
Pyrazinamide
Ethambutol
Delamanid
Carbapenems with Clavulanic Acid
Aminoglycosides and Polypeptides
Thioamides (Ethionamide and Prothionamide)
Para-Aminosalicylic Acid (PAS)
Drugs Not Ranked but Used
High-Dose Isoniazid
Pretomanid
Use of Bedaquiline and Delamanid in Combination
3.3 Choosing Between a Longer or Shorter Regimen
3.4 Designing a Longer Duration Treatment Regimen
3.5 Shorter Course Regimens
3.5.1 Standardized Shorter Course Injectable-Containing Regimen
3.5.2 Standardized Shorter Course Oral Bedaquiline-Containing Regimen
3.5.3 BPaL and BPaLM Regimens
4 Surgery
5 Treatment Outcomes
6 Special Situations
6.1 Extrapulmonary Disease
6.2 Children
6.3 Pregnant Women
6.4 People Living with HIV
7 Monitoring for Treatment Response
8 Monitoring for Adverse Drug Reactions
9 Treatment of Contacts to MDR-TB
10 Conclusion
References
Chapter 8: The Role of Surgical Interventions for Pulmonary TB: What Is the Role of Surgical Intervention in Pulmonary TB?
1 Introduction
2 Indications for Surgical Treatment
3 Preoperative Management
4 Preoperative Assessments for Pulmonary Resection
5 Surgical Procedure
5.1 The Resectional Range of the Lungs
5.2 Pitfalls of the Surgical Procedure
5.3 Prevention of Complications
5.4 The Surgical Approach for Lung Resections
6 Postoperative Management and Chemotherapy
7 Surgical Treatment Outcomes
8 Conclusion
References
Part III: Latent TB Infection: TB Prevention
Chapter 9: Advances in Diagnosis of Latent TB Infection: What Is the Latest Approach to Diagnose Latent TB Infection to Prevent TB?
1 Introduction
2 The Science of LTBI Testing
2.1 TB Exposure and the Immune Response
2.2 Measuring the Immune Response to M. tuberculosis Exposure
3 Tuberculin Skin Test
3.1 TST History
3.2 Performing TST
3.3 Safety
3.4 TST Interpretation
3.5 Accuracy
3.6 Summary
4 Interferon-Gamma Release Assays
4.1 History of IGRAs, Discussion of QFT, T-SPOT
4.2 Procedure and Results
4.2.1 QFT-Plus Procedure
4.2.2 T-SPOT.TB Procedure
4.2.3 Indeterminate/Invalid Results
4.2.4 Sources of Variation/Error
4.3 Accuracy
5 Comparisons of TST, QFT, and T-SPOT.TB
5.1 Alternative Cut-Points
6 Test Application in Special Situations and Populations
6.1 Marker of Treatment Response
6.2 Pediatrics
6.3 Pregnancy
6.4 Serial Testing
6.5 People with HIV
6.6 Other Immunocompromise
6.7 Society Recommendations
7 Future Directions of LTBI Testing
7.1 Novel Skin-Based Tests
7.2 Novel Cytokine-Based Assays
7.2.1 Use of New Antigens
7.2.2 Use of Alternative Cytokines
7.3 Serology
7.4 Transcriptomics
7.5 Other Novel Diagnostic Strategies
8 Conclusion
References
Chapter 10: Advances in Treatment of Latent TB Infection: What Is the Latest Approach to Treat Latent TB Infection to Prevent Pulmonary TB?
1 Introduction
1.1 The Spectrum of TB Manifestations in Humans
1.2 Rationale For LTBI Treatment
1.3 Content and Focus of This Chapter
2 Targeting LTBI Testing and Therapy
3 Pretreatment Evaluation
3.1 Ruling Out TB Disease
3.2 Assessing Risk for Adverse Effects
3.3 Evaluating for Potential Drug Interactions
3.4 Other Important Pretreatment Considerations
4 Drug Regimens to Treat LTBI
4.1 LTBI Treatment History
4.2 Efficacy and Hepatotoxicity of Each LTBI Regimen
4.3 Adverse Effects
5 LTBI Therapy in Special Situations
5.1 HIV and LTBI
5.2 Pediatric LTBI
5.3 Window Prophylaxis
5.4 Individuals with Fibrotic Changes on Chest X-Ray
5.5 Contacts Who Have Previously Been Treated
5.6 Contacts to Drug-Resistant Infectious TB Cases
5.7 Pregnancy
5.8 Advanced Age
5.9 Low Suspicion for Active TB Disease
6 Future Directions
References
Part IV: Research Areas
Chapter 11: TB Vaccines: What Type of TB Vaccines Are Studied and Will Be Available in the Future?
1 Introduction
2 Prophylactic DNA Vaccines
2.1 The HVJ-Liposome/HSP65 DNA + IL-12 DNA Vaccine
2.2 The HVJ-E/HSP65 DNA + IL-12 DNA Vaccine
3 Prophylactic Vaccine (NHP Model)
4 Therapeutic DNA Vaccine
4.1 Therapeutic Vaccine (Mouse)
4.2 Therapeutic Vaccine (NHP)
4.3 Preclinical Trial (Toxicology·Safety Pharmacology)
4.4 Clinical Trial (Phase I)
5 Clinical Trial of Novel Vaccines
5.1 Protein or Adjuvant TB Vaccine
5.1.1 Final Analysis of a Trial of M72/AS01E Vaccine for TB Prevention
5.1.2 H4:IC31 Protein Vaccine
5.1.3 H56:IC31
6 Clinical Trial of Novel Vaccines
6.1 Viral-Vectored Vaccines
6.1.1 MVA85A
7 Clinical Trials of Novel Vaccines
7.1 Live rBCG Vaccines
7.1.1 VPM1002 [29]
8 Clinical Trial of Novel Vaccine
8.1 TB DNA Vaccines
8.1.1 BCG Revaccination
9 Therapeutic Vaccine and Preventive Vaccine
9.1 ID93 + GLA-SE Vaccine
9.2 H56 Vaccine
9.3 HVJ-E/HSP65 DNA + IL-12 DNA Vaccine
10 Conclusion (TB Vaccines Available in the Future)
References
Chapter 12: Clinical Trials of TB: Challenges and Opportunities
1 Introduction
1.1 History of Trials of TB Treatment
1.2 Overview of Recent TB Clinical Trial Results
1.2.1 Clinical Trials of Drug-Susceptible Pulmonary TB
1.2.2 Clinical Trials of Drug-Resistant Pulmonary TB
2 Challenges to Conducting Clinical Trials for Pulmonary TB
2.1 Design Challenges
2.2 Statistical Challenges
2.3 Challenges, Example 1 (Control Populations)
2.4 Challenges, Example 2 (Follow-Up Duration)
2.5 Challenges, Example 3 (Surrogate Markers)
2.6 Challenges, Example 4 (Pragmatic Trials)
2.7 Challenges, Example 5 (Non-inferiority Design)
2.8 Challenges, Example 6 (Transition from Phase 2 to Phase 3)
3 Current TB Clinical Trials
3.1 Overview
3.2 Example 1 (Adaptive Trial Design: endTB)
3.3 Example 2 (Duration Randomized Design: DRAMATIC)
3.4 Example 3 (Strategy Trials: BEAT Tuberculosis and endTB-Q)
4 Future Perspectives
References
Chapter 13: Contributions of Japanese Scholars to Advances in Clinical TB Management: In TB World, What Kind of Achievements Are Accomplished by Japanese Researchers?
1 Introduction
2 Bacille Calmette-Guérin (BCG) Tokyo 172: Substrain of Pasteur BCG: Since 1924
2.1 BCG Tokyo 172: Since 1924
2.2 The Development of Highly Heat-Resistant, Long-Life Dried Vaccines: Since 1943
2.3 Devising a Route for Administration: Percutaneous Vaccination with a Nine-Needle Stamp: 1961
3 The Theory of TB Onset Following Primary Infection: 1929
3.1 Caseous Foci in Adolescent Patients with TB: 1929
3.2 The Relationship Between Tuberculin Conversions and TB Onset: 1931
3.3 The Relationship Between Infections and TB Onset as Revealed by X-Rays: Since 1941
4 Delayed-Type Hypersensitivity: 1954
4.1 Cavitation Experiments: 1954 [25–27]
4.2 Cavity Prevention Experiments: 1968, 1974 [29, 30]
4.3 The Search for Cavity-Forming Antigens: 1977 [31]
5 Kanamycin (KM): 1957
5.1 The Discovery of KM and Bacteria That Produce it: 1957
5.2 KM Is Approved for Therapeutic Use the Year after Its Discovery: 1958
5.3 Research on the Mechanism Underlying KM Resistance and the Resultant Novel Antibiotics
6 Conclusion
References
Correction to: Immunology: How Does the Immune System Affect the Development of Pulmonary TB? How Does an Understanding of TB Immunology Help Clinicians Manage their Patients with Pulmonary TB?
Correction to: Chapter 2 in: T. Saito et al. (eds.), Pulmonary Tuberculosis and Its Prevention, Respiratory Disease Series: Diagnostic Tools and Disease Managements, https://doi.org/10.1007/978-981-19-3995-2_2