5. Research gaps

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• Consolidated Guidelines
  • Module 1: Prevention
    • Module 1: TB Preventive Treatment
      • Acknowledgements
      • Abbreviations and acronyms
      • Definitions
      • Executive summary
      • Introduction
        • 1. Background
        • 2. Rationale
        • 3. Scope of the current update
        • 4. Target readership
      • 1. Recommendations
        • 1.1. Identifying populations for TB preventive treatment
        • 1.2 TB screening and ruling out TB disease
        • 1.3 Testing for TBI
        • 1.4 TB preventive treatment options
      • 2. Monitoring and evaluation
      • 3. Research gaps
      • References
      • Annex 1. Recommendations in the WHO consolidated guidelines on tuberculosis: tuberculosis preventive treatment, second edition (2024) and in the previous edition (2020)
      • Annex 2. Methods and expert panels
      • Annex 3. GRADE summary of evidence tables
      • Annex 4. GRADE evidence-to-decision tables
      • Annex 5. Summary of unpublished studies (PICO 10)
        • A5.1 Summary of TB CHAMP and V-QUIN clinical trials
        • A5.2 Use of fluoroquinolones for TB preventive treatment in contacts of persons with MDR-/RR-TB: A systematic review
        • A5.3 Assessing fluoroquinolone (levofloxacin) acceptability among contacts of MDR-TB patients: a qualitative study¹⁰
        • A5.4 A survey to explore the programmatic feasibility of levofloxacin (Lfx) TPT for MDR-TB contacts¹¹
    • Module 1: TB infection prevention and control
      • Acknowledgements
      • Abbreviations
      • Definitions
      • How to use these guidelines
      • Executive summary
        • Guideline development methods
        • Summary of recommendations
      • 1. Introduction
        • Scope of the guidelines
        • Objective
        • Target audience
      • 2. Recommendations
        • 2.1. Administrative controls
        • 2.2 Environmental controls
        • 2.3 Respiratory protection
      • 3. Core components of IPC programmes
      • 4. Research priorities
      • References
      • Web annexes
      • Online annexes
        • Annex 4 – GRADE evidence summary tables
        • Annex 5 – GRADE evidence-to-decision tables
        • Annex 6 – Results of the systematic reviews on the development of these guidelines
  • Module 2: Screening
    • Module 2: Systematic screening for tuberculosis disease
      • Acknowledgements
      • Abbreviations and acronyms
      • Definitions
      • Executive summary
      • 1. Introduction
        • 1.1 Background
        • 1.2 Definition and objectives of systematic screening for TB disease
        • 1.3 Scope of the 2021 update
        • 1.4 Rationale for the guideline update
        • 1.5 Objectives of the guideline update
        • 1.6 Target audience
      • 2. Recommendations for systematic screening for TB disease in targeted populations
        • 2.1 Systematic screening for TB disease among the general population
          • 2.1.1 Summary of the evidence and rationale
          • 2.1.2 Implementation considerations
        • 2.2 Systematic screening for TB disease among people with structural risk factors for TB
          • 2.2.1 Summary of evidence and rationale
          • 2.2.2 Implementation considerations
        • 2.3 Systematic screening for TB disease among people living with HIV
          • 2.3.1 Summary of evidence and rationale
          • 2.3.2 Implementation considerations
        • 2.4 Systematic screening for TB disease among household and other close contacts of individuals with TB disease
          • 2.4.1 Summary of evidence and rationale
          • 2.4.2 Implementation considerations
          • 2.4.3 Subgroup considerations
        • 2.5 Systematic screening for TB disease in prisons and other penitentiary institutions
          • 2.5.1 Summary of evidence and rationale
          • 2.5.2 Implementation considerations
        • 2.6 Systematic screening for TB disease among miners and others exposed to silica dust
          • 2.6.1 Summary of evidence and rationale
          • 2.6.2 Implementation considerations
        • 2.7 Systematic screening for TB disease among people attending health care services who have clinical risk factors for TB
          • 2.7.1 Summary of evidence and rationale
          • 2.7.2 Implementation considerations
      • 3. Recommendations for tools for systematic screening for TB disease
        • 3.1 Tools for screening for TB disease among the general population and high-risk groups
          • 3.1.1 Summary of the evidence and rationale
          • 3.1.2 Implementation considerations for all tools
        • 3.2 Use of computer-aided detection software for automated reading of digital chest radiographs
          • 3.2.1 Summary of the evidence and rationale
          • 3.2.2 Implementation considerations
        • 3.3 Tools for screening for TB disease among people living with HIV
          • 3.3.1 Summary of the evidence and rationale
            • 3.3.1.1 WHO-recommended four-symptom screen
            • 3.3.1.2 C-reactive protein
            • 3.3.1.3 Chest radiography
            • 3.3.1.4 Molecular WHO-recommended rapid diagnostic tests for medical inpatients living with HIV in settings with a high TB burden
            • 3.3.1.5 Molecular WHO-recommended rapid diagnostic tests for all other people living with HIV
          • 3.3.2 Implementation considerations for all tools for screening people living with HIV
        • 3.4 Tools for systematic screening for TB disease among children and adolescents
          • 3.4.1 Summary of the evidence and rationale
            • 3.4.1.1 Close contacts younger than 15 years
            • 3.4.1.2 Children younger than 10 years who are living with HIV
          • 3.4.2 Considerations for screening children and adolescents
      • 4. Monitoring and evaluation
        • 4.1 Indicators
        • 4.2 Routines for recording and reporting
        • 4.3 Programmatic evaluations
        • 4.4 Initial calibration for computer-aided detection technologies
      • 5. Research gaps
        • 5.1 Screening for TB in targeted populations
          • 5.1.1 The general population and high-risk groups
          • 5.1.2 People living with HIV
          • 5.1.3 Children and adolescents
        • 5.2 Tools for screening for TB
          • 5.2.1 Computer-aided detection
          • 5.2.2 C-reactive protein
          • 5.2.3 Screening algorithms
        • 5.3 Operational research
      • 6. References
      • Supplementary Table
      • Web annexes
        • Web Annex A. Methods and Expert Panels
        • Web Annex B. GRADE Summary of Findings Tables
        • Web Annex C. GRADE Evidence to Decision Tables
  • Module 3: Diagnosis
    • Module 3: Diagnosis
      • Acknowledgements
      • Abbreviations and acronyms
      • Definitions
      • Executive summary
      • 1. Introduction
        • 1.1. Background
        • 1.2. WHO TB diagnostic class determination and product prequalification
        • 1.3. Testing classes and products
        • 1.4. Scope of the document
        • 1.5. Target audience
        • 1.6. Scope of the document
        • 1.7. Target audience
      • 2. Recommendations for diagnosis of TB disease
        • 2.1. Initial diagnostic tests for diagnosis of TB with drug-resistance detection
        • 2.2. Initial diagnostic tests for diagnosis of TB without drug-resistance detection
        • 2.3. Concurrent use of initial diagnostic tests for diagnosis of TB in People living with HIV and children
        • 2.4. Follow-on diagnostic tests for detection of additional drug-resistance after TB confirmation
        • 2.5. References
      • 3. Recommendations for diagnosis of TB infection
        • 3.1. Mycobacterium tuberculosis antigen-based skin tests for the diagnosis of TB infection
        • 3.2. TB skin tests and interferon gamma release assays for the diagnosis of TB infection
        • 3.3. TB skin tests and interferon gamma release assays for the diagnosis of TB disease
        • 3.4. References
      • Annex 1. Guideline development methods
      • Annex 2. Conflict of interest assessment for Guideline Development Group and External Review Group members
      • Annex 3. GDG members expertise, region, gender
  • Module 4: Treatment
    • Module 4: treatment and care
      • Acknowledgements
      • Abbreviations and acronyms
      • Definitions
      • Executive summary
      • Chapter 1. Drug-susceptible TB treatment
        • Introduction
          • Structure of the chapter
          • Summary of WHO recommendations on drug-susceptible TB treatment
        • Recommendations
          • 1. Treatment of drug-susceptible TB using a 6-month regimen
          • 2. Treatment of drug-susceptible TB using 4-month regimens
          • 3. Drug-susceptible TB treatment and ART in people living with HIV
          • 4. The use of adjuvant steroids in the treatment of TB meningitis and pericarditis
        • Research gaps
        • References (Chapter 1)
      • Chapter 2. Drug-resistant TB treatment
        • Introduction
          • Structure of the chapter
          • Background
          • Scope of the 2025 update and available evidence
          • Summary of WHO recommendations on drug-resistant TB treatment
          • Target audience
        • Recommendations
          • 1. Treatment of drug-resistant TB using 6-month regimens
          • 2. Treatment of drug-resistant TB using 9-month regimens
          • 3. Treatment of drug-resistant TB using longer regimens
          • 4. Treatment of rifampicin-susceptible and isoniazid-resistant TB (Hr-TB)
          • 5. Monitoring and management strategies for MDR/RR-TB treatment
          • 6. Starting antiretroviral therapy in patients on MDR/RR-TB regimens
          • 7. Surgery for patients on MDR/RR-TB treatment
          • 8. Hepatitis C virus (HCV) and MDR/RR-TB treatment co-administration
        • Research gaps
        • References (Chapter 2)
      • Chapter 3. Tuberculosis care and support
        • Introduction
          • Structure of the chapter
          • Summary of WHO recommendations on TB care and support
        • Recommendations
          • 1. Care and support interventions for all people with TB
          • 2. Models of care for people with drug-resistant TB
          • 3. Models of care for children and adolescents exposed to TB or with TB disease
        • Research gaps
        • References (Chapter 3)
      • Annex 1. Summary of recommendations
        • Annex 1.1. Summary of changes to the World Health Organization (WHO) treatment recommendations for drug-susceptible TB (DS-TB) between 2010 and the update and consolidation in 2025
        • Annex 1.2. Summary of changes to the World Health Organization (WHO) treatment recommendations for multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) between 2019 and the update and consolidation in 2025
        • Annex 1.3. Summary of changes to the World Health Organization (WHO) treatment recommendations for Tuberculosis care and support between 2011 and the update and consolidation in 2025
      • Annex 2. Methods and expert panels
        • 2.1 Methods
        • 2.2 Expert panels
      • Annex 3. Declarations of interest
        • 3.1 Drug-susceptible tuberculosis treatment
        • 3.2 Drug-resistant tuberculosis treatment
      • Annex 4. PICO questions
      • Annex 5. GRADE evidence profiles and evidence-to-decision tables
      • Annex 6. Statistical analysis plans
      • Annex 7. Reports of the systematic reviews for Tuberculosis care and support
  • Module 5: Children and adolescents
    • Module 5: Management of tuberculosis in children and adolescents
      • Acknowledgements
      • Abbreviations
      • Definitions
      • Executive summary
      • 1. Introduction
        • 1.1. Background
        • 1.2. Rationale for the development of the 2022 consolidated guidelines
        • 1.3. Objectives of the 2022 consolidated guidelines
        • 1.4. Target audience
        • 1.5. WHO recommendations relevant to the management of TB in children and adolescents
        • 1.6. Scope of the guideline update
          • 1.6.1. PICO questions
          • 1.6.2. Background questions
        • 1.7. Publication, dissemination, evaluation and expiry
        • 1.8. Document structure
      • 2. TB screening and contact investigation
      • 3. Prevention of TB
      • 4. Diagnostic approaches for TB in children and adolescents
        • 4.1. The use of the Xpert MTB/RIF Ultra assay in gastric aspirate and stool specimens for the diagnosis of pulmonary TB and rifampicin resistance
          • 4.1.1. Justification and evidence
          • 4.1.2. Subgroup considerations
          • 4.1.3. Implementation considerations
          • 4.1.4. Monitoring and evaluation
        • 4.2. Treatment decision algorithms for the diagnosis of pulmonary TB in children aged below 10 years of age
          • 4.2.1. Justification and evidence
          • 4.2.2. Subgroup considerations
          • 4.2.3. Implementation considerations
          • 4.2.4. Monitoring and evaluation
        • 4.3. Consolidated recommendations on TB diagnostics and diagnostic approaches relevant to children and adolescents
      • 5. Treatment of TB disease in children and adolescents
        • 5.1. Treatment shortening in children and adolescents with non-severe TB
          • 5.1.1. Justification and evidence
          • 5.1.2. Subgroup considerations
          • 5.1.3. Implementation considerations
          • 5.1.4. Monitoring and evaluation
        • 5.2. Treatment regimens for TB meningitis in children and adolescents
          • 5.2.1. Justification and evidence
          • 5.2.2. Subgroup considerations
          • 5.2.3. Implementation considerations
          • 5.2.4. Monitoring and evaluation
        • 5.3. Treatment of multi-drug and rifampicin resistant TB in children
          • 5.3.1. The use of bedaquiline in children with MDR/RR-TB aged below 6 years
          • 5.3.2. The use of delamanid in children with MDR/RR-TB aged below 3 years
        • 5.4. Consolidated recommendations on TB treatment for children and adolescents
      • 6. Models of TB care for case detection and provision of TPT in children and adolescents
        • 6.1. Decentralized and family-centred, integrated models of care to deliver child and adolescent TB services
          • 6.1.1. Justification and evidence
          • 6.1.2. Subgroup considerations
          • 6.1.3. Implementation considerations
          • 6.1.4. Monitoring and evaluation
        • 6.2. Consolidated recommendations on models of TB care relevant to children and adolescents
      • 7. Special situations
      • 8. Research priorities
      • 9. References
      • Annex 1. WHO recommendations incorporated in the guidelines on the management of TB in children and adolescents
      • Annex 2. Supplementary table
  • Module 6: Comorbidities
    • Module 6: Tuberculosis and comorbidities
      • Introduction
      • HIV
        • Acknowledgements
        • Abbreviations and acronyms
        • Definitions
        • Executive summary
        • 1. HIV: introduction
          • 1.1 Background
          • 1.2 Rationale
          • 1.3 Scope
          • 1.4 Objectives
          • 1.5 Target audience
          • 1.6 Process of consolidating the guidelines
          • 1.7 Publication, dissemination, implementation, evaluation and expiry
        • 2. Reduce the burden of TB among people living with HIV
          • 2.1 TB screening
          • 2.2 TB diagnosis
          • 2.3 High quality tuberculosis treatment for people living with HIV
          • 2.4 Prevention of TB
        • 3. Reduce the burden of HIV among people with presumptive or diagnosed TB
          • 3.1 HIV testing services for people with presumptive and diagnosed TB
          • 3.2 HIV treatment and care for people living with HIV diagnosed with TB
          • 3.3 HIV prevention
        • 4. Monitoring and evaluation
        • 5. Research gaps
        • References
        • Annex 1. Current methodology for WHO guideline development
        • Annex 2. Summary of changes to recommendations
      • Undernutrition
        • Acknowledgements
        • Abbreviations and acronyms
        • Definitions
        • Executive summary
        • 1. Undernutrition: introduction
          • 1.1 Background
          • 1.2 Rationale for the guideline update
          • 1.3 Scope
          • 1.4 Objectives
          • 1.5 Target audience
        • 2. Recommendations
          • 2.1 Nutritional assessment and counselling in people with TB and their household contacts
          • 2.2 Nutritional interventions and food assistance
          • 2.3 Micronutrient supplementation in people with TB
          • 2.4 TB screening for people with undernutrition and people with structural risk factors such as food insecurity
        • 3. Monitoring and evaluation
        • 4. Research gaps
        • Supplementary table: summary of changes to recommendations
        • References
        • Web Annexes
• Operational Handbooks
  • Module 1: Prevention
    • Module 1: TB preventive treatment
      • Acknowledgements
      • Abbreviations and acronyms
      • Definitions
      • 1. Introduction
      • 2. Identifying populations for TB preventive treatment
      • 3. Screening for TB and ruling out TB disease before TB preventive treatment
      • 4. Testing for TB infection
      • 5. TB preventive treatment
        • 5.1 Recommended TPT regimens
      • 6. Safety and management of adverse drug reactions in TB preventive treatment
        • 6.1 Drug safety and adverse drug reactions
      • 7. Supporting people in adhering to and completing TB preventive treatment
        • 7.1 Monitoring TPT
      • 8. Monitoring and evaluation
      • 9. Ethics and TB preventive treatment
      • References
      • Annexes
        • Annex 1. Investment case for TB screening and preventive treatment
        • Annex 2. Messages for different stakeholders
        • Annex 3. Coordination mechanisms to support PMTPT
        • Annex 4. Costing considerations for PMTPT
        • Annex 5. Checklist for PMTPT components in reviews of national programmes
        • Annex 6. Variables to be collected for TB contact evaluation
      • Web annexes
        • Web Annex A
        • Web Annex B
    • Module 1: TB laboratory biosafety
      • Executive summary
      • Participants in the guideline development process
      • Abbreviations
        • Definitions of terms
      • Introduction
      • 1. Risk assessment and the classification of tb laboratories
        • 1.1 Risk assessment for tb laboratories: what is it?
        • 1.2 Hazard identification
        • 1.3 Determining risks
        • 1.4 Monitoring risks and mitigation measures
        • 1.5 Employee occupational health programme
        • 1.6 Classification of tb laboratories
      • 2. Essential biosafety measures for tb laboratories
        • 2.1 Codes of practice
          • 2.1.1 Laboratory access
          • 2.1.2 Responsibilities of the laboratory manager
          • 2.1.3 Personal protective equipment
          • 2.1.4 Procedures
          • 2.1.5 Work areas
        • 2.2 Equipment
        • 2.3 Design and facilities
        • 2.4 Training
        • 2.5 Waste handling
          • 2.5.1 Incineration
          • 2.5.2 Autoclaving
          • 2.5.3 Disinfection
        • 2.6 Disposal procedures for contaminated materials
          • 2.6.1 Broken glass and glass slides
          • 2.6.2 Contaminated or potentially infectious materials for disposal
      • 3. Low-risk tb laboratories
        • 3.1 Factors that increase the risk of infection
        • 3.2 Specific features and essential minimum biosafety measures
      • 4. Moderate-risk tb laboratories
        • 4.1 Factors that increase the risk of infection
        • 4.2 Specific features and essential minimum biosafety measures
      • 5. High-risk tb laboratories (tb-containment laboratories)
        • 5.1 Factors that increase the risk of infection
        • 5.2 Specific features and required biosafety measures
      • 6. Safety equipment
        • 6.1 Biological safety cabinets
          • 6.1.1 Selecting a biological safety cabinet for a TB laboratory
          • 6.1.2 Class I biological safety cabinets
          • 6.1.3 Class II type A2 biological safety cabinets
          • 6.1.4 Thimble connections
          • 6.1.5 Using biological safety cabinets in the laboratory
        • 6.2 Centrifuges with safety buckets
        • 6.3 Autoclaves
      • 7. Personal protective equipment and clothing
        • 7.1 Laboratory gowns
        • 7.2 Respirators
          • 7.2.1 Fitting a respirator
          • 7.2.2 Removing a respirator
        • 7.3 Gloves
          • 7.3.1 Removing gloves
      • 8. Plans for emergency preparedness and response
        • 8.1 Emergency preparedness plan
        • 8.2 Emergency response procedures for tb laboratories
          • 8.2.1 Infectious spills (outside a biological safety cabinet)
          • 8.2.2 Infectious spills (contained within a biological safety cabinet)
          • 8.2.3 Breakage of tubes inside sealed buckets (safety cups)
        • 8.3 Spill clean-up kit
      • 9. References
      • 10. Annex
        • Annex 1: Meeting participants
        • Annex 2: Declarations of interest
        • Annex 3: Peer review panel
    • Module 1: Infection prevention and control
      • Acknowledgements
      • Abbreviations and acronyms
      • Definitions
      • 1. Introduction
      • 2. Administrative controls
      • 3. Environmental controls
      • 4. Respiratory protection
      • 5. TB IPC in special situations
      • 6. Monitoring and evaluation
      • References
      • Annexes
        • Annex 1. Data elements for monitoring implementation of tuberculosis infection prevention and control
        • Annex 2. Facility tuberculosis risk assessment tool
        • Annex 3. Example of an outline of facility tuberculosis infection prevention and control plan
        • Annex 4. Health care worker tuberculosis screening form
        • Annex 5. Health care worker TB screening register
        • Annex 6. Sample posters for health education
        • Annex 7. How to choose upper-room germicidal ultraviolet light fixtures
        • Annex 8. Choosing a radiometer for measurement of ultraviolet C irradiation
        • Annex 9. Checklist for the review of programmatic implementation of tuberculosis infection prevention and control
        • Annex 10. Country example: education messages for tuberculosis and for tuberculosis infection prevention and control
  • Module 2: Screening
    • Module 2: Systematic screening for tuberculosis disease
      • Acknowledgements
      • Abbreviations and acronyms
      • Definitions
      • Chapter 1. Introduction
        • 1.1 Rationale for systematic screening for TB disease
        • 1.2 Principles of TB screening
        • 1.3 Objectives of the operational handbook
        • 1.4 Target audience of the operational handbook
      • Chapter 2. The six steps in the planning and implementation cycle
        • 2.1 Introduction
          • 2.1.1 Enhancing the patient-initiated pathway to TB diagnosis
          • 2.1.2 The provider-initiated screening pathway to TB diagnosis
        • 2.2 Assessing the situation
          • 2.2.1 Existing screening and outreach activities
          • 2.2.2 Societal context
          • 2.2.3 Epidemiology of TB
          • 2.2.4 National TB programmes and the general health-care system
          • 2.2.5 Health-care coverage and access to health services
          • 2.2.6 Protection from stigmatization, discrimination and harm
        • 2.3 Setting goals and specific objectives
        • 2.4 Identifying and prioritizing risk groups
          • 2.4.1 Potential benefits for the individual
          • 2.4.2 Potential risks and harms for the individual
          • 2.4.3 Potential impact on prevalence and transmission
          • 2.4.4 Potential total yield of true TB cases
          • 2.4.5 Number needed to screen to detect a person with TB
          • 2.4.6 Cost–effectiveness and cost–benefit analyses
        • 2.5 Choosing algorithms for screening and diagnosis
        • 2.6 Planning, budgeting and implementing
          • 2.6.1 Requirements for planning, human resources, commodities and budgeting
          • 2.6.2 Choosing a screening programme model
          • 2.6.3 Ethical considerations
          • 2.6.4 Involving stakeholders and partner organizations and establishing roles
          • 2.6.5 Mobilizing resources
          • 2.6.6 Pilot-testing
        • 2.7 Monitoring, evaluating and modifying the programme
          • 2.7.1 Developing a plan for monitoring and evaluation
          • 2.7.2 Proposed indicators
          • 2.7.3 Routines for recording and reporting
          • 2.7.4 Programmatic evaluations
          • 2.7.5 Monitoring time trends for re-screening and re-prioritization
      • Chapter 3. Screening tools and algorithms
        • 3.1 Screening tools
          • 3.1.1 Symptom screening
          • 3.1.2 CXR screening
          • 3.1.3 CAD technologies for screening and triage
          • 3.1.4 Molecular WHO-recommended rapid diagnostics for screening
          • 3.1.5 Tests of TB infection
        • 3.2 Algorithms for screening
          • 3.2.1 Basic features of TB screening and diagnostic algorithms
          • 3.2.2 Screening and diagnostic algorithm options
          • 3.2.3 Choosing an algorithm for a screening programme
        • 3.3 ScreenTB tool
      • Chapter 4. Implementation of CAD technologies in a new setting
        • 4.1 Considerations in selecting and using CAD for screening in TB programmes
        • 4.2 Toolkit for CAD calibration to enable implementation
        • 4.3 Online tool for calibration of CAD in a new setting
      • Chapter 5. Screening for tuberculosis disease among adults and adolescents living with HIV
        • 5.1 Introduction
        • 5.2 Screening tools
          • 5.2.1 WHO-recommended four-symptom screen
          • 5.2.2 C-reactive protein (CRP)
          • 5.2.3 Chest X-ray
          • 5.2.4 WHO-recommended rapid molecular diagnostic tests
        • 5.3 Considerations for use of all screening tools
        • 5.4 Algorithms for screening
      • Chapter 6. Screening for tuberculosis disease in children
        • 6.1 Introduction
        • 6.2 Screening child contacts of patients with TB
          • 6.2.1 Symptom screening
          • 6.2.2 CXR
          • 6.2.3 WHO-recommended rapid molecular diagnostic tests
          • 6.2.4 Tests of TB infection
          • 6.2.5 Considerations for implementation
        • 6.3 Screening children living with HIV
          • 6.3.1 Screening for symptoms and contact
          • 6.3.2 Other screening tests
          • 6.3.3 Considerations for implementation
        • 6.4 Algorithms for screening
      • References
      • Annex 1 Screening algorithms for the general population and high-risk groups (not including people living with HIV)
        • A.1.1 – Screening with cough
        • A.1.2 – Parallel screening with cough and CXR
        • A.1.3 – Sequential positive serial screening with cough and CXR
        • A.1.4 – Sequential negative serial screening with cough and CXR
        • A.1.5 – Screening with any TB symptom
        • A.1.6 – Parallel screening with any TB symptom and CXR
        • A.1.7 – Sequential positive serial screening with any TB symptom and CXR
        • A.1.8 – Sequential negative serial screening with any TB symptom and CXR
        • A.1.9 – Screening with CXR
        • A.1.10 – Screening with mWRD
      • Annex 2 Comparative performance of algorithms for the general population and high-risk groups (not including people living with HIV)
      • Annex 3 Screening algorithms for adults and adolescents living with HIV
        • A.3.1 – W4SS single screening algorithm
        • A.3.2 – CRP single screening algorithm
        • A.3.3 – CXR single screening algorithm
        • A.3.4 – Parallel screening algorithm with W4SS and CRP
        • A.3.5 – Sequential positive screening algorithm with W4SS and CRP
        • A.3.6 – Sequential negative screening algorithm with W4SS and CRP
        • A.3.7 – Parallel screening algorithm with W4SS and CXR
        • A.3.8 – Sequential positive screening algorithm with W4SS and CXR
        • A.3.9 – Sequential negative screening algorithm with W4SS and CXR
        • A.3.10 – mWRD single screening algorithm for medical inpatients in settings with TB prevalence > 10%
        • A.3.11 – mWRD single screening algorithm for people living with HIV
      • Annex 4 Comparative performance of algorithms for adults and adolescents living with HIV
      • Annex 5 Screening algorithms for children
        • A.5.1 – Screening with symptoms
        • A.5.2 – Screening with CXR
        • A.5.3 – Parallel screening with symptoms and CXR
        • A.5.4 – Sequential positive serial screening with symptoms and CXR
        • A.5.5 – Sequential negative serial screening with symptoms and CXR
        • A.5.6 – Screening with symptoms (for children living with HIV < 10 years)
  • Module 3: Diagnosis
    • Module 3: Diagnosis
      • Acknowledgements
      • Abbreviations and acronyms
      • 1. Introduction
        • 1.1 Background
        • 1.2 Advances in TB diagnostic test development, assessment and WHO recommendations
        • 1.3 Scope of this operational handbook
        • 1.4 Target audience
        • 1.5 New in this version: a summary of changes
      • 2. TB tests with WHO recommendations
        • 2.1 Conventional tests for the diagnosis of TB
        • 2.2 Initial tests for diagnosis of TB with drug resistance detection
        • 2.3 Initial tests for diagnosis of TB without drug resistance detection
        • 2.4 Follow-on diagnostic tests for detection of additional drug resistance
        • 2.5 Phenotypic and genotypic drug resistance testing methods
        • 2.6 Tests for TB infection
        • 2.7 Tests WHO recommends against using or recommends limited usage
      • 3. Strategies and considerations for diagnostic testing
        • 3.1 Epidemiological considerations
        • 3.2 Pretest probability and test accuracy considerations
        • 3.3 Planning for and implementing quality-assured TB testing services
        • 3.4 Concurrent testing to improve case detection in children and in people (of all ages) living with HIV
        • 3.5 Testing for TB infection
        • 3.6 Multidisease testing considerations
      • 4. Placement of diagnostic tests in the tiered laboratory network
        • 4.1 Peripheral level
        • 4.2 Intermediate level
        • 4.3 Central level
        • 4.4 Structure of network and testing packages
      • 5. Steps and processes for implementing a new diagnostic test
        • 5.1 Area 1 – Policies, budgeting and planning
        • 5.2 Area 2 – Regulatory issues
        • 5.3 Area 3 – Equipment
        • 5.4 Area 4 – Supply chain
        • 5.5 Area 5 – Procedures
        • 5.6 Area 6 – Digital data
        • 5.7 Area 7 – Quality assurance, control and assessment
        • 5.8 Area 8 – Recording and reporting
        • 5.9 Area 9 – Human resource training and competency assessment
        • 5.10 Area 10 – Monitoring and evaluation
      • 6. Model algorithms
        • 6.1 Implementing a new diagnostic algorithm
        • 6.2 The cascade of the four model algorithms
        • 6.3 Algorithm 1 – WRDs as initial diagnostic tests for TB
        • 6.4 Algorithm 2 – DST for second-line drugs for people with MDR/RR-TB
        • 6.5 Algorithm 3 – Follow-on testing for individuals with RIF-susceptible TB at risk of resistance to other drugs
        • 6.6 Discordant results
        • 6.7 Algorithm 4 – Testing for TB infection
        • 6.8 Illustrative algorithm combinations
      • References⁷
      • Annex 1. Budgetary considerations for implementing a new diagnostic test
      • Annex 2. Drug susceptibility testing methods and critical concentrations
      • Annex 3. Implementation of next-generation sequencing technologies
      • Annex 4. Skin tests for tuberculosis infection – detailed description
      • Web Annexes
  • Module 4: Treatment
    • Module 4: treatment and care
      • Acknowledgements
      • Abbreviations and acronyms
      • Definitions
      • Executive summary
      • Chapter 1 Drug-susceptible TB treatment
        • 1. Introduction
        • 2. Key considerations in DS-TB treatment
        • 3. Treatment of DS-TB using the 6-month regimen
        • 4. Treatment of DS-TB using the 4-month 2HPMZ/2HPM regimen
        • 5. Treatment of DS-TB using the 4-month 2HRZ(E)/2HR regimen
        • 6. Treatment of DS-TB in people living with HIV
        • 7. Treatment of extrapulmonary TB
        • 8. Treatment of DS-TB in special situations
        • 9. Monitoring treatment response
        • 10. Outcome definitions
        • References (Chapter 1)
      • Chapter 2 Drug-resistant TB treatment
        • 1. Introduction
        • 2. WHO recommendations on DR-TB treatment
        • 3. Key considerations in DR-TB treatment
        • 4. Treatment of DR-TB using 6-month regimens
        • 5. Treatment of drug-resistant TB using 9-month regimens
        • 6. Treatment of drug-resistant TB using longer regimens
        • 7. Regimen for rifampicin-susceptible and isoniazid-resistant TB
        • 8. Adjuncts to DR-TB treatment and comorbidities
        • 9. Programmatic implementation of DR-TB regimens
        • References (Chapter 2)
      • Chapter 3 Tuberculosis care and support
        • 1. Introduction
        • 2. People-centred approach
        • 3. Care and support interventions to enable TB treatment adherence
        • 4. Health education and counselling for people affected with TB
        • 5. Models of care for TB services
        • 6. Palliative care
        • References (Chapter 3)
      • Annex 1. Tuberculosis medicine information sheets
      • Annex 2. Monitoring and management of adverse events in treatment of drug-resistant tuberculosis
      • Annex 3. Active TB drug-safety monitoring and management for treatment of drug-resistant tuberculosis
      • Annex 4. Dosing of medicines used in TB regimens, adults and children
  • Module 5: Children and adolescents
    • Module 5: Management of tuberculosis in children and adolescents
      • Acknowledgments
      • Abbreviations
      • Definitions
      • 1. Introduction
        • 1.1 Background
        • 1.2 Children and adolescents as a key vulnerable population
        • 1.3 Rationale and objectives of this operational handbook
        • 1.4. Preferences of end-users regarding content and structure of this operational handbook
        • 1.5. Structure of the operational handbook
        • 1.6 Target audience
      • 2. TB screening and contact investigation
        • 2.1 Introduction
        • 2.2 Contact investigation
          • 2.2.1 Prioritizing household contacts
          • 2.2.2 Planning and budgeting to implement or strengthen household contact investigation
          • 2.2.3 Key implementation steps in contact investigation
          • 2.2.4 Examples of facility- and community-based approaches for TB contact investigation
        • 2.3 TB screening approaches in children and adolescents
          • 2.3.1. Screening child contacts of people with bacteriologically confirmed TB
            • 2.3.1.1. Symptom screening
            • 2.3.1.2. Chest X-ray
            • 2.3.1.3. Molecular WHO-recommended rapid diagnostic tests
            • 2.3.1.4. Tests for TB infection
          • 2.3.2. Considerations for implementation of screening of child close contacts
        • 2.4 Screening children and adolescents living with HIV
          • 2.4.1. Screening for symptoms and contact
          • 2.4.2. Other screening tests
          • 2.4.3. Considerations for implementation
          • 2.4.4. Screening of adolescents living with HIV
        • Key messages
      • 3. Prevention of TB in children and adolescents
        • 3.1 Introduction
        • 3.2 BCG vaccination
          • 3.2.1. Recommendations from the WHO BCG position paper
            • 3.2.1.1. Children living with HIV and neonates
            • 3.2.1.2. Administering BCG
            • 3.2.1.3. Contraindications for BCG
            • 3.2.1.4. Adverse reactions
        • 3.3 TB preventive treatment
          • 3.3.1. Introduction
          • 3.3.2. Target groups for TB preventive treatment
            • 3.3.2.1. Children and adolescents living with HIV
            • 3.3.2.2. Child and adolescent household contacts
          • 3.3.3. Ruling out TB disease before starting TB preventive treatment
            • 3.3.3.1. HIV-negative household and close contacts of a person with pulmonary TB: infants and children aged under 5 years
            • 3.3.3.2. HIV-negative household and close contacts of a person with pulmonary TB: children and adolescents aged 5 years and over
            • 3.3.3.3. Children and adolescents living with HIV
          • 3.3.4. Testing for TB infection
            • 3.3.4.1. Tuberculin skin testing
            • 3.3.4.2. Interferon-gamma release assay
          • 3.3.5. Options for TB preventive treatment regimens: drug-susceptible TB
            • 3.3.5.1. Implementation considerations
            • 3.3.5.2. Dosages
          • 3.3.6. Options for TB preventive treatment regimens: drug-resistant TB
          • 3.3.7. Follow-up of children and adolescents on TB preventive treatment
          • 3.3.8. Adherence to TB preventive treatment
            • 3.3.8.1. Special considerations for adherence in children
          • 3.3.9. Other issues related to TB preventive treatment in children and adolescents
        • 3.4 TB infection prevention and control
        • Key messages
      • 4. TB diagnostic approaches for children and adolescents
        • 4.1 Introduction
        • 4.2 Diagnosing TB in children and adolescents
        • 4.3 Diagnostic approaches: pulmonary TB
          • 4.3.1. Typical symptoms of pulmonary TB
          • 4.3.2. History of TB contact
          • 4.3.3. Clinical examination
          • 4.3.4. Atypical clinical presentations of children with pulmonary TB
          • 4.3.5. Bacteriological confirmation
            • 4.3.5.1. Sample types
            • 4.3.5.2. WHO-recommended rapid diagnostic tests
            • 4.3.5.3. Molecular WHO-recommended rapid diagnostic tests for TB
            • 4.3.5.4. Antigen detection in a lateral flow format (biomarker-based detection)
            • 4.3.5.5. Repeat testing with molecular WHO-recommended rapid diagnostic tests
          • 4.3.6. Testing for TB infection
          • 4.3.7. Role of chest X-ray
          • 4.3.8. HIV testing
          • 4.3.9. Integrated treatment decision algorithms for pulmonary TB in children
            • 4.3.9.1. Algorithm A (for settings with chest X-ray) and Algorithm B (for settings without chest X-ray)
            • 4.3.9.2. Using the integrated treatment decision algorithms
        • 4.4 Diagnostic approaches: extrapulmonary TB
        • 4.5 Disease severity
        • 4.6 Diagnostic approaches: drug-resistant TB
        • Key messages
      • 5. Treatment of drug-susceptible and drug-resistant pulmonary and extrapulmonary TB in children and adolescents
        • 5.1 Introduction
        • 5.2 Treatment of drug-susceptible TB in children and adolescents
          • 5.2.1. Principles of TB management
          • 5.2.2. Treatment of pulmonary TB in children and adolescents
          • 5.2.3. Recommended regimens for treatment of drug susceptible pulmonary TB in children
          • 5.2.4. Implementation considerations
            • 5.2.4.1. Assessing eligibility for the 4-month regimen
            • 5.2.4.2. Inclusion of ethambutol in the intensive phase of treatment
            • 5.2.4.3. Implementation considerations for the isoniazid, rifapentine, moxifloxacin and pyrazinamide regimen
            • 5.2.4.4. Dosing frequency
          • 5.2.5. Subgroup considerations
            • 5.2.5.1. Children with peripheral lymph node TB
            • 5.2.5.2. Children and adolescents living with HIV
            • 5.2.5.3. Children with severe acute malnutrition
            • 5.2.5.4. Children with severe acute pneumonia
            • 5.2.5.5. Infants aged under 3 months or weighing less than 3 kg
            • 5.2.5.6. Children and adolescents treated for TB in past 2 years
            • 5.2.5.7. Children and young adolescents with severe pulmonary TB
          • 5.2.6. Treatment of drug-susceptible extrapulmonary TB in children and adolescents
            • 5.2.6.1. Treatment of TB meningitis and osteoarticular TB
            • 5.2.6.2. Implementation considerations: treatment of TB meningitis
          • 5.2.7. Recommended dosing of first-line medicines in children
            • 5.2.7.1. Recommended dosages for first-line TB medicines
            • 5.2.7.2. Dosage tables and formulations for treatment of drug-susceptible TB in children and adolescents
            • 5.2.7.3. Dosing table for the short intensive TB meningitis regimen
            • 5.2.7.4. Dosing of first-line medicines in older children and adolescents over 25 kg (excluding the short intensive TB meningitis regimen)
            • 5.2.7.5. Pyridoxine supplementation
          • 5.2.8. Additional management considerations
            • 5.2.8.1. Indications for referral and hospitalization
            • 5.2.8.2. Indications for adjuvant therapy
          • 5.2.9. Nutritional support
          • 5.2.10. Management of adverse events from medicines used to treat drug-susceptible TB
            • 5.2.10.1. Hepatotoxicity
            • 5.2.10.2. Peripheral neuropathy
            • 5.2.10.3. Optic neuritis
            • 5.2.10.4. Overview of common adverse events and their management
          • 5.2.11. Treatment adherence
          • 5.2.12. Follow-up and monitoring of children and adolescents on TB treatment
            • 5.2.12.1. Follow-up after treatment completion
            • 5.2.12.2. Treatment interruption
            • 5.2.12.3. Treatment failure
            • 5.2.12.4. Children and adolescents requiring retreatment for TB
            • 5.2.12.5. Registration of TB treatment in children and adolescents
        • Key messages: treatment of DS-TB
        • 5.3 Treatment of multidrug-resistant and rifampicin-resistant TB in children and adolescents
          • 5.3.1. Identifying children who should be treated for multidrug-resistant and rifampicin-resistant TB
          • 5.3.2. Multidrug-resistant and rifampicin-resistant TB treatment regimens for children and adolescents
            • 5.3.2.1. Overview and approach to selecting a treatment regimen
            • 5.3.2.2. Shorter all-oral bedaquiline-containing regimen for multidrug-resistant and rifampicin-resistant TB in children
            • 5.3.2.3. Longer individualized regimens for children with multidrug-resistant and rifampicin-resistant TB who are not eligible for the standardized all-oral bedaquiline-containing regimen
            • 5.3.2.4. Practical approach to designing individualized multidrug-resistant and rifampicin-resistant TB treatment regimens
            • 5.3.2.5. Special considerations: TB meningitis
            • 5.3.2.6. Special considerations: TB/HIV coinfection
          • 5.3.3. Dosing and formulations of second-line TB medicines in children and young adolescents
            • 5.3.3.1. Dosing
            • 5.3.3.2. Formulations
          • 5.3.4. Monitoring of children and adolescents on multidrugresistant and rifampicin-resistant TB treatment
            • 5.3.4.1. Monitoring response to treatment
            • 5.3.4.2. Monitoring for adverse effects
        • Key messages: treatment of DR-TB
        • 5.4 Practical guidance for assessment and management of post-TB health in children and adolescents
          • 5.4.1. Post-TB health
          • 5.4.2. Post-TB meningitis in children and adolescents
          • 5.4.3. Post-TB lung disease in children and adolescents
          • 5.4.4. Post-TB osteoarticular disease in children and adolescents
          • 5.4.5. Post-TB health-related quality of life
      • 6. Models of TB care for children and adolescents
        • 6.1 Introduction
        • 6.2 Decentralized, family-centred, integrated TB services
          • 6.2.1. Implementation considerations
            • 6.2.1.1. Stakeholder engagement
            • 6.2.1.2. Regulatory framework and policy guidance
            • 6.2.1.3. Health workforce
            • 6.2.1.4. Treatment support
            • 6.2.1.5. Recording and reporting
            • 6.2.1.6. Access to diagnostic supplies and child-friendly formulations of TB medicines
            • 6.2.1.7. Resource requirements
            • 6.2.1.8. Opportunities for integration of TB services into other services
            • 6.2.1.9. Socioeconomic impact of TB on children, adolescents and families
            • 6.2.1.10. Examples of country experiences in development of family-centred, decentralized and integrated TB services for children and adolescents
        • 6.3 Private-sector involvement in care for children and adolescents with TB
          • 6.3.1. Background
          • 6.3.2. Rationale
          • 6.3.3. Benefits of involving the private sector in TB care
          • 6.3.4. Implementation considerations
        • 6.4 Differentiated TB service delivery
          • 6.4.1. Background
          • 6.4.2. Rationale
          • 6.4.3. Implementation considerations
        • 6.5 TB and health emergencies
        • Key messages
      • 7. Special situations
        • 7.1 Management of TB in children and adolescents living with HIV
          • 7.1.1. Introduction
          • 7.1.2. TB screening in children and adolescents living with HIV
          • 7.1.3. Prevention of TB in children and adolescents living with HIV
          • 7.1.4. Diagnosis of TB in children and adolescents living with HIV
          • 7.1.5. Treatment of TB in children and adolescents living with HIV
          • 7.1.6. Co-trimoxazole preventive therapy
          • 7.1.7. Antiretroviral therapy
            • 7.1.7.1. Timing of antiretroviral therapy
            • 7.1.7.2. Choice of antiretroviral therapy regimen
            • 7.1.7.3. Adjustments to antiretroviral therapy regimens with TB treatment
            • 7.1.7.4. TPT in children and adolescents living with HIV on antiretroviral therapy
          • 7.1.8. Immune reconstitution inflammatory syndrome
        • 7.2 TB in pregnancy and management of newborns of mothers with TB disease
          • 7.2.1. Screening for TB in pregnant women living with HIV
          • 7.2.2. Congenital and neonatal TB
            • 7.2.2.1. Management of congenital and neonatal TB
          • 7.2.3. Management of asymptomatic neonates of mothers with TB
        • 7.3 Palliative care for children and adolescents with TB
          • 7.3.1. Introduction
          • 7.3.2. Palliative care for people with TB
          • 7.3.3. Palliative care for children and adolescents with TB
        • 7.4 Care for adolescents with or at risk of TB
          • 7.4.1. Physical and mental health
          • 7.4.2. Connectedness and positive contribution to society
          • 7.4.3. Safety and a supportive environment
          • 7.4.4. Learning, competence, education, skills and employability
          • 7.4.5. Agency and resilience
          • 7.4.6. Substance abuse and late presentation to care
          • 7.4.7. Poor adherence
          • 7.4.8. Making TB services more adolescent-friendly
        • 7.5 TB in children with severe acute pneumonia
        • 7.6 Management of children with TB and malnutrition
          • 7.6.1. Introduction
          • 7.6.2. Diagnosis and treatment of TB in children with malnutrition
          • 7.6.3. Nutritional care for children and adolescents with TB
        • Key messages
      • 8. References
      • Annex 1. Selected resources on child and adolescent TB
      • Annex 2. Tuberculin skin testing: administration, reading and interpretation
      • Annex 3. Sample collection methods
      • Annex 4. Standard operating procedures for sample collection methods
      • Annex 5. Treatment decision algorithms
      • Annex 6. Dosing of medicines used in second-line multidrug-resistant TB regimens by weight band (below 46 kg)
      • Annex 7. Overview of options for neurocognitive and functional testing at end of treatment for TB meningitis
  • Module 6: Comorbidities
    • Module 6: Tuberculosis and comorbidities
      • Introduction
      • Mental health conditions and substance use disorders
        • Acknowledgements
        • Abbreviations
        • Definitions
        • 1. Mental health conditions and substance use disorders: background and rationale
        • 2. People-centred care for mental health conditions and substance use disorders in people affected by TB
        • 3. Identifying and managing care for mental health conditions and substance use disorders in people affected by TB
          • 3.1 Depression
          • 3.2 Anxiety
          • 3.3 Psychoses
          • 3.4 Substance use disorders
          • 3.5 Suicidal behaviours
        • 4. Special considerations
          • 4.1 Stigma
          • 4.2 Palliative care
          • 4.3 Homelessness
          • 4.4 Multimorbidity and TB-associated disabilities
        • References
        • Annex. WHO resources for mental and substance use disorders
          • References for the annex
      • HIV
        • Acknowledgements
        • Abbreviations and acronyms
        • Definitions
        • 1. Background and rationale
          • 1.1 Background and burden of HIV-associated TB
          • 1.2 Development of the document
          • 1.3 Summary of recommendations
        • 2. Establish and strengthen collaboration across health programmes and across sectors for delivering people-centred services for HIV-associated TB
          • 2.1 Strengthen governance and accountability for TB/HIV collaborative activities
          • 2.2 Conduct an analysis of access to quality services for TB and HIV
          • 2.3 Coordinate planning and resource mobilization for collaborative action
          • 2.4 Implement and scale up people-centred services for HIV-associated TB
          • 2.5 Strengthen monitoring, evaluation and research
        • 3. Reduce the burden of TB among people living with HIV
          • 3.1 TB screening
          • 3.2 TB diagnosis
          • 3.3 Algorithms for informing the decision to treat TB infection or TB disease among people living with HIV
          • 3.4 TB treatment
          • 3.5 Prevention of TB
        • 4. Reduce the burden of HIV among people with TB
          • 4.1 HIV testing services for people with presumptive and diagnosed TB
          • 4.2 HIV treatment and care for people living with HIV diagnosed with TB
          • 4.3 HIV prevention
        • References
        • Annex 1. Monitoring and evaluation of collaborative TB/HIV activities
        • Annex 2. Methods for algorithms for diagnosis of TB in people living with HIV
        • Annex 3. Checklist for TB infection prevention and control
        • Annex 4. Package of care for advanced HIV disease
      • Diabetes
        • Acknowledgements
        • Abbreviations
        • Definitions
        • References
        • 1. Background and rationale
          • 1.1 Background and burden of TB and diabetes
          • 1.2 Development of the document
          • 1.3 Summary of recommendations
        • 2. Establish and strengthen collaboration across health programmes and across sectors for delivering people-centred services for TB and diabetes.
          • 2.1 Strengthen governance and accountability for collaborative TB/DM activities.
          • 2.2 Conduct an analysis of access to quality services for TB and diabetes.
          • 2.3 Coordinate planning and resource mobilization for collaborative action.
          • 2.4 Implement and scale up people-centred services for TB and diabetes.
          • 2.5 Strengthen monitoring, evaluation and research.
        • 3. Reduce the burden of TB among people living with diabetes.
          • 3.1 TB screening among people living with diabetes
          • 3.2 TB diagnosis among people living with diabetes
          • 3.3 TB treatment among people living with diabetes
          • 3.4 Glycaemic control to prevent TB among people living with diabetes
          • 3.5 TPT for people living with diabetes
          • 3.6 TB IPC in clinics that provide diabetes care
        • 4. Reduce the burden of diabetes among people with TB.
          • 4.1 Diabetes screening and diagnosis
          • 4.2 Management of diabetes
        • References
        • Annex 1. Summary of declaration of interests
        • Annex 2. Research gaps in the response to TB and diabetes
        • Annex 3. Criteria for referral to higher levels of care
        • Annex 4. Monitoring and evaluation of collaborative TB/DM activities
        • Annex 5. Examples of recording and reporting forms
        • Annex 6. A standardized checklist for periodic evaluation of TB infection prevention and control
• Training Catalogue
• TB Drug Dosage Finder