FeedbackUnless otherwise specified, the terms defined here apply as used in this operational handbook. They may have different meanings in other contexts.
Active (tuberculosis) case-finding: Provider-initiated screening and testing in communities by mobile teams, often using mobile X-ray and rapid molecular tests. The term is sometimes used synonymously with “systematic screening”.
Adherence: Extent to which a person’s behaviour (e.g. taking medicines, following a particular diet, changing lifestyle) corresponds with agreed recommendations from a health care provider.
Advanced HIV disease: For adolescents and children aged 5 years and over, this is defined as a CD4 cell count below 200 cells/mm3 or a WHO clinical stage 3 or 4 event at presentation for care. All children aged under 5 years living with HIV should be considered as having advanced disease at presentation.
Adverse event: Any untoward medical occurrence that may present in a person with TB during treatment with a pharmaceutical product but that does not necessarily have a causal relationship with the treatment.
Age groups: Unless stated otherwise in the text, the following definitions apply to the terms used in this handbook:
- Infant: aged under 1 year (12 months).
- Child: aged under 10 years.
- Young child: aged under 5 years.
- Adolescent: aged 10–19 years (inclusive).
- Young adolescent: aged 10–14 years.
- Older adolescent: aged 15–19 years.
- Adult: aged 20 years or over.
Background HIV and tuberculosis drug resistance prevalence: Settings with high HIV prevalence are defined as those in which the HIV prevalence is 1% or higher among adult pregnant women, or 5% or higher among people with TB. WHO does not intend to establish thresholds for low, moderate or high levels of prevalence of isoniazid resistance. National TB programmes will establish definitions for their own countries.
Bacteriologically confirmed tuberculosis: TB diagnosed in a biological specimen by a WHOapproved rapid test such as Xpert® MTB/RIF or LF-LAM, smear microscopy or culture.
Contact: Any person exposed to a person with TB.
Contact investigation: Systematic identification of people, including children and adolescents, with previously undiagnosed TB disease and TB infection among the contacts of an index TB patient in the household and in comparable settings in which transmission occurs. It consists of identification, clinical evaluation and/or testing and provision of appropriate TB treatment (for people with confirmed TB) or TB preventive treatment (for people without TB disease).
Decentralization: Depending on the standard in the research settings used for the comparator, this includes provision of, access to or capacity for child and adolescent TB services at a lower level of the health system than the lowest level where this is currently routinely provided. In most settings, decentralization applies to the district hospital (first referral level hospital) level and/or primary health care level and/or community level. Interventions for decentralization include capacity-building of
various cadres of health care workers, expanding access to diagnostic services, ensuring availability of TB medicines for children and adolescents, and follow-up of children and adolescents with TB or on TB preventive treatment.
Differentiated HIV service delivery model: Person-centred approach to simplify provision of HIV services across the cascade in ways that better serve the needs of people living with HIV and reduce unnecessary burdens on the health system.
Drug susceptibility testing (DST): In vitro testing using either molecular genotypic techniques to detect resistance-conferring mutations, or phenotypic methods to determine susceptibility to a medicine.1
Extensive (or advanced) pulmonary tuberculosis disease: Presence of bilateral cavitary disease or extensive parenchymal damage on chest radiography (CXR). In children aged under 15 years, advanced disease is usually defined by the presence of cavities or bilateral disease on CXR.
Extensively drug-resistant tuberculosis (XDR-TB):2
- Pre-XDR-TB: TB caused by Mycobacterium tuberculosis strains that fulfil the definition of multidrugresistant TB (MDR-TB) or rifampicin-resistant TB (RR-TB) and that are also resistant to any fluoroquinolone.3
- XDR-TB: TB caused by M. tuberculosis strains that fulfil the definition of MDR/RR-TB and that are also resistant to any fluoroquinolone and at least one additional Group A medicine.4
Extrapulmonary tuberculosis (EPTB) (classification): Any bacteriologically confirmed or clinically diagnosed case of TB involving organs other than the lungs (e.g. pleura, peripheral lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meninges).5
Family-centred, integrated care: Family-centred models of care refer to interventions selected on the basis of the needs, values and preferences of the child or adolescent and their family or caregiver. This can include health education, communication, material or psychological support. Integrated services refer to approaches to strengthen collaboration, coordination, integration and harmonization of child
and adolescent TB services with other child health-related programmes and services. This can include integration of models of care for TB screening, prevention, diagnosis and treatment with other existing service delivery platforms for maternal and child health (e.g. antenatal care, integrated community case management, integrated management of childhood illnesses) and other related services (e.g. HIV, nutrition, immunization). Other examples include evaluation of children and adolescents with
common comorbidities (e.g. meningitis, malnutrition, pneumonia, chronic lung disease, diabetes, HIV) for TB and community health strategies integrating child and adolescent TB awareness, education, screening, prevention and case-finding into training and service delivery activities.
Grading of Recommendations Assessment, Development and Evaluation (GRADE): System for rating quality of evidence and strength of recommendations. This approach is explicit, comprehensive, transparent and pragmatic.6
High tuberculosis transmission setting: Setting with a high frequency of people with undetected or undiagnosed TB disease, or where people with infectious TB are present and there is a high risk of TB transmission. People with TB are most infectious when they are untreated or inadequately treated. Spread is increased by aerosol-generating procedures and by the presence of highly susceptible people.
Household contact: Person who shared the same enclosed living space as the index case for one or more nights or for frequent or extended daytime periods during the 3 months before the start of current treatment.
Index case (index patient) of tuberculosis: Initially identified person of any age with new or recurrent TB in a specific household or other comparable setting in which others may have been exposed. An index case is the person on which a contact investigation is centred but is not necessarily the source case.
Inpatient health care setting: Health care facility where people are admitted and assigned a bed while undergoing diagnosis and receiving treatment and care, for at least one overnight stay.
Integrated treatment decision algorithm: Flowchart allocating evidence-based scores to microbiological, clinical and radiological features that allow clinicians to make decisions regarding starting TB treatment in children.
Interferon-gamma release assay (IGRA): Blood test used to test for Mycobacterium tuberculosis infection by measuring the body’s immune response to TB bacteria.
Multidrug-resistant tuberculosis (MDR-TB): TB caused by Mycobacterium tuberculosis strains that are resistant to at least both rifampicin and isoniazid.
New case: Newly registered episode of TB in a person who has never been treated for TB or has taken TB medicines for less than 1 month.
Non-severe pulmonary tuberculosis for the purpose of determining treatment duration for drug-susceptible tuberculosis: Intrathoracic lymph node TB without airway obstruction; uncomplicated TB pleural effusion or paucibacillary, non-cavitary disease confined to one lobe of the lungs and without a miliary pattern.
Number needed to screen: Number of people who need to undergo screening in order to diagnose one person with TB disease.
Operational research or implementation research: In the context of this handbook, applied research that aims to develop the critical evidence base that informs the effective, sustained and embedded adoption of interventions within a health system to improve health or patient outcomes. Such research deals with the knowledge gap between efficacy, effectiveness and current practice to produce the greatest gains in disease control.7 Operational research also provides decision-makers with information to enable them to improve the performance of their health programmes.8
Outpatient health care setting: Health care facility where people are undergoing diagnosis and receiving treatment and care but are not admitted for overnight stays (e.g. ambulatory clinic, dispensary).
Passive case-finding: Patient-initiated pathway to TB diagnosis involving a person with TB disease who experiences symptoms that they recognize as serious; the person having access to and seeking care, and presenting spontaneously at an appropriate health facility; a health worker correctly assessing that the person fulfils the criteria for presumptive TB; and successful use of a diagnostic algorithm with sufficient sensitivity and specificity to diagnose TB.
People who use drugs: People who engage in the harmful or hazardous use of psychoactive substances that could impact negatively on their health, social life, resources or legal situation.
Presumptive tuberculosis: Person who presents with symptoms or signs suggestive of TB.
Previously treated: People who have previously received 1 month or more of TB medicines. Previously treated people may have been treated with a first-line regimen for drug-susceptible TB or a second-lineregimen for drug-resistant forms.
Programmatic management of tuberculosis preventive treatment: All coordinated activities by public and private health caregivers and the community aimed at scaling up TB preventive treatment to people who need it.
Pulmonary tuberculosis (PTB) (classification): Any bacteriologically confirmed or clinically diagnosed case of TB involving the lung parenchyma or the tracheobronchial tree, including tuberculous intrathoracic lymphadenopathy (mediastinal and/or hilar), without radiographic abnormalities in the lungs.9 Miliary TB is classified as PTB because there are lesions in the lungs. A person with both PTB and extrapulmonary TB should be classified as having PTB.
Rifampicin-resistant tuberculosis (RR-TB): TB caused by Mycobacterium tuberculosis strains resistant to rifampicin. These strains may be susceptible or resistant to isoniazid (i.e. MDR-TB) or resistant to other first-line or second-line TB medicines. In these guidelines and elsewhere, MDR-TB and RR-TB cases are often grouped together as MDR/RR-TB and are eligible for treatment with an MDR-TB regimen.
Rifampicin-susceptible, isoniazid-resistant tuberculosis: TB caused by Mycobacterium tuberculosis strains resistant to isoniazid and susceptible to rifampicin.
Serious adverse event: Adverse event that can lead to death or a life-threatening experience, to hospitalization or prolongation of hospitalization, to persistent or significant disability, or to a congenital anomaly. Serious adverse events that do not immediately result in one of these outcomes but that require an intervention to prevent such an outcome from happening are included. Serious adverse events may require a drastic intervention, such as termination of the medicine suspected of
having caused the event.
Severe acute malnutrition: Presence of oedema of both feet or severe wasting (weight-for-height/length less than −3 standard deviations/Z-scores or mid-upper arm circumference less than 115 mm).10
Severe extrapulmonary tuberculosis: Presence of miliary (disseminated) TB or TB meningitis. In children and young adolescents aged under 15 years, extrapulmonary forms of disease other than lymphadenopathy (peripheral nodes or isolated mediastinal mass without compression) are considered to be severe.
Severe pneumonia: Cough or difficulty in breathing plus at least one of the following:
- central cyanosis or oxygen saturation <90% on pulse oximetry;
- severe respiratory distress (e.g. grunting, nasal flaring, very severe chest indrawing);
- signs of pneumonia with a general danger sign (inability to breastfeed or drink, persistent vomiting, lethargy or unconscious, convulsions, stridor in a calm child, severe malnutrition).8
Source case: Person with TB disease who infected others in a new setting. This could be the index patient or another person who was not identified.
Systematic screening for tuberculosis disease: Systematic identification of people at risk for TB disease in a predetermined target group by assessing symptoms and using tests, examinations or other procedures that can be applied rapidly. For those who screen positive, the diagnosis needs to be established by one or several diagnostic tests and additional clinical assessments. This term is sometimes used interchangeably with “active tuberculosis case-finding”. It should be distinguished from testing for TB infection (with a TB skin test or interferon-gamma release assay).
Treatment outcomes and relapse: Categories for treatment outcomes used in this operational handbook and the term “relapse” were applied according to the definitions agreed for use by TB programmes, unless otherwise specified.11,12
Tuberculin skin test (TST): Intradermal injection of a combination of mycobacterial antigens that elicit an immune response (delayed-type hypersensitivity), represented by induration, which can be measured in millimetres. TST is used to diagnose TB infection.
Tuberculosis (TB): Disease state due to Mycobacterium tuberculosis. In this handbook, it is commonly referred to as “TB disease” to distinguish it from “TB infection”.
Tuberculosis infection: State of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifest TB disease. This is referred to as “TB infection” as distinct from “TB disease”. There is no gold standard test for direct identification of M. tuberculosis infection in humans. Most infected people have no signs or symptoms of TB but are at risk for TB disease. The term “latent TB infection” has been replaced by the term “TB infection”.
Tuberculosis preventive treatment (TPT): Treatment offered to people considered at risk of TB disease to reduce that risk. Also referred to as “treatment of TB infection” or “TB preventive therapy”.
Underweight: Among adolescents, this usually refers to a body mass index below 18.5. Among children aged under 10 years, it usually refers to a weight-for-age Z-score below −2 standard deviations.
1 Implementing tuberculosis diagnostics: a policy framework. Geneva: World Health Organization; 2015 (https://apps.who.int/iris/handle/10665/162712, accessed 11 March 2022).
2 Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis, 27–29 October 2020. Geneva: World Health Organization; 2021 (https://www.who.int/publications/i/item/meeting-report-of-the-who-expert-consultationon-the-definition-of-extensively-drug-resistant-tuberculosis, accessed 11 March 2022).
3 The fluoroquinolones include levofloxacin and moxifloxacin as currently recommended by WHO for inclusion in shorter and longer regimens.
4 Group A medicines are currently levofloxacin or moxifloxacin, bedaquiline and linezolid; therefore, XDR-TB is MDR/RR-TB that is resistant to a fluoroquinolone and either bedaquiline or linezolid (or both). Group A medicines could change in the future. Therefore, the terminology “Group A” is appropriate here and will apply to any Group A medicines in the future.
5 Following a WHO expert consultation in September 2021, intrathoracic lymph node TB is now classified as pulmonary TB in children.
6 GRADE is a transparent framework for developing and presenting summaries of evidence. It provides a systematic approach for making clinical and public health practice recommendations. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924.
7 Guide to operational research in programs supported by the Global Fund. Geneva: Global Fund to Fight AIDS, Tuberculosis and Malaria; 2007 (https://www.who.int/hiv/pub/operational/or_guide_gf.pdf, accessed 11 March 2022).
8 Expanding capacity for operations research in reproductive health: summary report of a consultative meeting. Geneva: World Health Organization; 2003 (https://apps.who.int/iris/bitstream/handle/10665/67936/WHO_RHR_02.18.pdf?sequence=1&isAllowed=y, accessed 11 March 2022).
9 Following a WHO expert consultation in September 2021, intrathoracic lymph node TB is now classified as pulmonary TB in children.
10 Pocket book of hospital care for children: guidelines for the management of common childhood illnesses, 2nd edition. Geneva: World Health Organization; 2013 (https://apps.who.int/iris/bitstream/handle/10665/81170/9789241548373_eng.pdf, accessed 27 September 2021).
11 Definitions and reporting framework for tuberculosis – 2013 revision. Geneva: World Health Organization; 2013 (WHO/ HTM/TB/2013.2;
http://apps.who.int/iris/bitstream/10665/79199/1/9789241505345_eng.pdf, accessed 11 March 2022).
12 Meeting report of the WHO expert consultation on drug-resistant tuberculosis treatment outcome definitions, 17–19 November 2020. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/rest/bitstreams/1336957/retrieve, accessed 11 March 2022).