3. Screening for TB and ruling out TB disease before TB preventive treatment

The second step in the cascade of care for PMTPT is to rule out TB disease before offering TPT. The ministry of health should choose screening and diagnostic approaches appropriate for the target population.

Provision of TPT to someone with TB disease can delay resolution of disease and lead to emergence of drug resistance. Thus, exclusion of TB disease before initiating TPT is a critical step in the preventive care pathway. This section includes WHO recommendations and key policy and implementation considerations in development of national algorithms to rule out TB disease, keeping in mind the barriers that additional steps could create to successful implementation of TPT. The same tests are often used to screen for TB disease, the risk groups are often similar, and same monitoring principles are used. The activities at this step include determining HIV status, eliciting a history of household or other close contacts, determining the presence of other risk factors, eliciting suggestive signs and symptoms according to the person’s age, abnormality on CXR and the results of other screening tests. The introduction of systematic screening for TB disease in target populations requires assessment of health system capacity and the availability of human and financial resources. The programme must mobilize funds from domestic and external sources to address these needs adequately.

3.1 Screening for TB disease using signs and symptoms

Using a standard set of signs and symptoms to screen for TB disease has multiple advantages. First, in many settings, this is highly sensitive and has a high negative predictive value, such that it can reliably rule out TB if none of the clinical manifestations are present. Secondly, it is a straightforward intervention that can be conducted at any clinical encounter and can be repeated as often as necessary without special equipment or associated cost. Additional tests such as CXR can be combined with symptom screening to improve its accuracy.

Evidence reviewed by WHO during the past decade, before updates to the guidelines, showed the following.

For adults and adolescents with HIV, a symptom screening rule of a combination of current cough, fever, weight loss or night sweats has a negative predictive value of ≥ 99% when conducted in populations with a TB prevalence of 0.5–2% (13). It is therefore suggested that, for people with HIV aged ≥ 10 years, the WHO four-symptom screen (any one of cough, fever, night sweats or weight loss) be applied.
For infants and children with HIV, a symptom screen (any one of current cough, fever, poor weight gain or close contact with someone with TB) had a pooled sensitivity of 61% (95% CI 58% ; 64%) and a pooled specificity of 94% (95% CI 86% ; 98%) (17). In children < 10 years, a broader set of clinical manifestations may be used to exclude TB disease, including cough, fever, weight loss or lack of weight gain and reduced playfulness.
For children and adolescents < 15 years who are close contacts of someone with TB, symptom screening (any one of cough, fever or poor weight gain) has a pooled sensitivity of 89% (95% CI 52% ; 98%) and a pooled specificity of 69% (95% CI 51% ; 83%) (17).
Among individuals aged ≥ 15 years with negative or unknown HIV status, screening for cough has low sensitivity (51%) but higher specificity (88%), while screening for any TB symptom improves sensitivity (71%) but reduces specificity (64%). In this group, CXR has high sensitivity (94%) and specificity (89%) for any abnormality (13). A parallel screening algorithm consisting of any symptom of TB and any abnormal CXR findings is likely to be highly sensitive and may be the best tool for excluding pulmonary TB disease before initiating TPT among HIV-negative household contacts aged ≥ 5 years and other risk groups. Symptom screening without the addition of CXR should nevertheless be acceptable for individuals and programme managers.

3.2 Screening for TB with CXR and computer aided detection (CAD) software

A key policy decision with financial implications is whether to consider systematic use of CXR with TB symptom screening to rule out TB disease. CXR is a rapid imaging technique for identifying lung abnormalities. It is a good screening tool for pulmonary TB because of its high estimated accuracy for detecting TB disease, especially before the onset of symptoms. From the perspective of the person being screened, CXR is valuable because it can also detect medical conditions other than TB, such as other pulmonary and thoracic conditions (17).

In contacts aged ≥ 5 years, screening for TB with CXR is more sensitive than screening for symptoms (48). A combined screen comprising any abnormalities on CXR with any TB symptom had a negative predictive value of 1 (48) and was thus the most accurate means for excluding TB disease before TPT. Although CXR is the preferred screening tool from the viewpoint of test accuracy, it can be expensive and logistically challenging to use, especially when screening is done outside health services. It is important to keep in mind that people may have to travel from their usual facility for a CXR and pay for it out of pocket (17). The availability of mobile X-ray technology offers the opportunity for community CXR screening.

WHO recommends that CXR be offered to people with HIV. A combined strategy of the WHO recommended four symptom screen (cough, fever, weight loss or night sweats) and CXR is significantly more sensitive than symptom screening alone, particularly for outpatients enrolled in ART care, although with less specificity (33% compared with 70% for symptoms alone) and sensitivity (85% compared with 53% for symptoms alone (17). If there are no abnormal radiographic findings, TPT should be considered; however, CXR should not be considered a mandatory requirement, and lack of CXR should not be a barrier to starting TPT for people with HIV.

Use of CXR with TB symptom screening is likely to increase the confidence of health providers, given the very high sensitivity of the combination. This could reduce the concern of providers about development of drug-resistant TB resulting from inadvertent treatment of TB disease with a TPT regimen. This consideration is particularly important for HIV-negative household contacts who are adolescents and adults, other close contacts and clinically at-risk populations. Similarly, use of CXR may increase the confidence of care providers of people with HIV who are receiving ART.

In 2021, WHO first recommended use of CAD software in place of human readers for interpreting digital CXR for screening and triage for TB disease (17). This recommendation is currently limited to individuals aged ≥ 15 years in whom TB screening is recommended, while more evidence is being generated in the age group <15 years. Use of CAD requires thorough consideration of the infrastructure requirements, including digital radiography equipment, reliable electricity, computer availability, Internet access, fees for use and the cost of the license for CAD products. The resources required and cost–effectiveness will depend on the setting, including the current availability and salaries of human readers (49).

When any abnormal CXR findings are seen (not just those suggestive of TB), detailed investigation for TB disease, including confirmatory testing with a molecular WHO-recommended rapid diagnostic test (mWRD), and other diseases should be undertaken in accordance with national guidelines and sound clinical practice.

The increased availability of digital radiography, use of CAD to interpret films and engagement by private health facilities to purchase radiographic services is expected to increase access to radiography in TB screening and diagnostic algorithms.

3.3 Screening for TB disease with other tests

3.3.1 C-reactive protein

CRP may be used to screen for TB in people with HIV (17). CRP is an indicator of systemic inflammation that can be measured with a blood test. It is a point-of-care test that is performed on capillary blood collected from a finger-prick, making it simple, affordable and feasible in primary care. WHO recommends use of the cut-off value of > 5 mg/L, the lowest threshold that indicates abnormality in many clinical settings and because it is the most sensitive (49). This test may have a specific role in screening for TB among outpatients living with HIV who are not on ART, as it has clinically significantly greater sensitivity and specificity than screening for symptoms (CRP, sensitivity 89% and specificity 54%; symptom screen, sensitivity 84% and specificity 37%) in this group (49). CRP can also be used in combination with symptom screening.

3.3.2 Molecular WHO-recommended rapid diagnostics

mWRDs are not only diagnostic tests for TB but may also be used as screening tests in both people with and without HIV (17). It should be noted that the accuracy of a test for screening is different from that for diagnosis. The sensitivity of mWRDs for screening high-risk populations (non-HIV-infected) is estimated to be 69% and the specificity 99% (49). People who screen positive for TB with an mWRD should always be followed up with a thorough clinical evaluation, including symptom screening and further tests, such as CXR or repeat mWRDs on additional sputum samples, to establish a definitive diagnosis of TB. Use of mWRD for screening will require significant resources, including more capacity and expansion of diagnostic and sample transport networks. There has been limited experience in widescale use of mWRDs for screening under programmatic conditions. Priority should be given to ensuring universal access to mWRDs as diagnostic tests for TB and drug-resistant TB before extending their use to screening (49).

3.4 Screening algorithms

The screening tests described above can be used on their own or in combination with other screening tests. The WHO Operational Handbook on Tuberculosis. Module 2: Screening – systematic screening for TB disease (49) contains a number of algorithms in which screening tests are combined in different ways. A positive symptom screen or screening test (CXR, CRP or mWRD) should always be followed by a confirmatory diagnostic test. In most algorithms, the diagnostic confirmatory test is an mWRD. If an mWRD is used for screening, a thorough clinical evaluation should be conducted to confirm TB (see also section 3.3.2). WHO has developed the ScreenTB tool to help users choose the most suitable screening algorithms for different populations (50) (Box 4 ).

3.5 Considerations for ruling out TB disease

Health ministries should coordinate implementation of the activities outlined below to screen for and exclude TB disease before providing TPT.

Make screening of at-risk populations for TB an integral part of the overall package of health care for these populations (such as an HIV care package for people with HIV). In principle, the overall responsibility for planning, resource allocation, service delivery (TB screening and activities to rule out TB disease) and M&E should be vested in the national authority responsible for services to the respective populations. The NTP, in collaboration with primary care and maternal and child health services, should assume responsibility for TB screening among contacts of index people with TB; the national HIV programme should organize services for people with HIV in collaboration with the national TB control programme; the clinical services in the ministry of health should support TB screening and linkages to treatment and care for other clinical at-risk populations; and, likewise, state agencies should be responsible for prisons, occupational health and migrant care.
Solicit advice from a national coordinating body, technical expert group or similar body for each national programme in developing a national plan for scaling up programmatic implementation of TB screening and services to rule out TB disease in various target populations and locations. The coordinating body or group may also advise on standard operating procedures (SOPs) and a plan for building the capacity of various types of providers and coordinate procurement and supplies of commodities for interventions in various programmes.
Develop a standard implementation guide, including roles and responsibilities, operating procedures, implementation tools, job aids and recording and reporting tools (integrated for HIV, TB and maternal and child health services), for ruling out TB disease in at-risk populations.
Develop communication materials for display and use at all sites at which intensified TB screening is provided.
Identify a cadre of health-care workers at various levels of the health-care system to perform clinical screening and referral for further testing for TB disease, infection and evaluation, as per national guidelines.
Conduct training and on-the-job capacity-building for health-care workers, community health workers and other service providers in systematic screening for TB.
Conduct regular supportive supervision at national, provincial and district levels of TB screening activities, especially those conducted by community health workers, to ensure good-quality screening and adherence to national algorithms.
Develop job-aids highlighting the steps in ruling out TB disease.
Organize access to CXR in public or private health facilities or mobile vans, as required by national policy, memoranda of understanding with private hospitals and radiologists and vouchers to ensure free access to X-ray services in the private sector.
Develop standard tools for data capture or update existing tools (such as patient files and electronic records) with relevant data elements on ACF and activities to rule out TB disease. The national HMIS should summarize data at each step in the cascade and report indicators of programme performance to national level (see also section 8).

Table A2.1 in Annex 2 provides an overview of considerations for ruling out TB disease in various target populations before starting TPT. While effective TB symptom screening is the backbone of TPT services, CXR and other tests may be used to exclude TB disease

3.5.1 Models of care for TB in children

WHO guidelines on the management of TB in children and adolescents contain recommendation on models of care to improve detection of people with TB and provision of TPT that are applicable to TB screening and TPT (17):

In high TB burden settings, decentralized models of care may be used to deliver TB services to children and adolescents with signs and symptoms of TB and/or those exposed to TB (conditional recommendation, very low certainty of evidence).
Family-centred, integrated models of care to deliver TB services may be used in children and adolescents with signs and symptoms of TB and/or those exposed to TB, in addition to standard models of care (conditional recommendation, very low certainty of evidence).

Decentralization and provision of family-centred, integrated care allow for consistent, systematic action to fill gaps and remove bottlenecks along the pathway of care and can reduce transmission of TB, prevent TB infection and result in earlier TB diagnoses, with better outcomes. This continuum of care requires collaboration among service areas, disciplines and sectors, community engagement and decentralization and integration of service delivery at primary health-care level (51,52). The road map for ending TB among children and adolescents, third edition (53), proposes action to strengthen implementation of integrated people, family and community-centred strategies as part of primary health care. These activities are equally valid for adult populations: (i) integrated, family-centred, community-based models of care for contact investigation and TPT; (ii) differentiated HIV service delivery (DSD) models designed and used to improve access to and retention in TB care for children and adolescents; (iii) outreach programmes for special populations, such as children and adolescents who are abused or neglected; (iv) investing in education and sensitization of communities, with a focus on young generations, to create awareness, generate knowledge and understanding of TB and to destigmatize the disease; and (v) promoting decentralized models of TB care with diagnostic capacity available and accessible at primary health care level as part of comprehensive, integrated primary health care (53).