Decision point on how to exclude TB disease before offering TPT
How can TB disease be reliably ruled out among target populations identified for TPT?
Offering TPT to someone who has TB disease can delay the resolution of disease and favour the emergence of drug resistance. Thus, excluding TB disease before initiating TPT is one of the critical steps in the preventive TB care pathway. This chapter covers WHO recommendations as well as key policy and implementation considerations in the development of national algorithms to rule out TB disease, mindful of the barriers that additional steps could create towards successful implementation of TPT. The process has much in common with screening for TB disease: similar risk groups, same tests, and same monitoring principles. The decision points centre around determining HIV status, eliciting history of the household or other close contacts, other risk factors, eliciting suggestive signs and symptoms depending on the person’s age, results of TST or IGRA and abnormality on chest radiography. TB disease must be excluded using available tools within the context and policies of the country, before starting TPT. Once at-risk populations that are likely to benefit from TPT are identified, the ministry of health should choose appropriate screening and diagnostic approaches best suited for the respective target population. Systematic implementation of clinical symptom screening and testing among target populations requires assessments of health system capacity and availability of human and financial resources. The programme would need to mobilize funds from domestic and external sources to address these needs adequately.
Screening for TB disease using signs and symptoms
Using a standard set of signs and symptoms to screen for TB disease has multiple advantages. Firstly, in many settings it has a high sensitivity and a high negative predictive value, meaning that it can reliably rule out TB if none of the clinical manifestations are present (even if presence of only one of the features has a low specificity for TB disease and could be due to other conditions). Secondly, it is a straightforward intervention inherent to any clinical encounter and can be repeated as often as necessary without special equipment. Additional tests such as chest radiography can be combined with a symptom screen to improve its accuracy.
Evidence reviewed by WHO over the past decade, ahead of updates to its guidelines, showed that among:
• PLHIV aged 10 years and older, the absence of current cough, fever, weight loss or night sweats had a sensitivity of 79% and a negative predictive value of 97%.
• Infants and children living with HIV, the absence of poor weight gain, fever or current cough or a history of contact with a TB patient had a sensitivity of 90% and a negative predictive value of 99%.
• HIV-negative household contacts aged five years and older and other clinical risk groups, the absence of cough of any duration, haemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath or fatigue had a sensitivity of 73% and a negative predictive value of 99%.
Therefore WHO recommends that screening for the absence of symptoms could be used to rule out TB disease (18,40). It is suggested that for PLHIV aged 10 years or above the standard four-symptom screening be applied; in younger children a broader set of clinical manifestations may be used to decide on who to refer for diagnostic work-up before offering TPT.
11. Adults and adolescents living with HIV should be screened for TB according to a clinical algorithm. Those who do not report any of the symptoms of current cough, fever, weight loss or night sweats are unlikely to have active TB and should be offered preventive treatment, regardless of their ART status.
12. Adults and adolescents living with HIV who are screened for TB according to a clinical algorithm and who report any of the symptoms of current cough, fever, weight loss or night sweats may have active TB and should be evaluated for TB and other diseases that cause such symptoms.
13. Chest radiography may be offered to people living with HIV and on ART and preventive treatment given to those with no abnormal radiographic findings.
14. Infants and children living with HIV who have poor weight gain, fever or current cough or who have a history of contact with a person with TB should be evaluated for TB and other diseases that cause such symptoms. If TB disease is excluded after an appropriate clinical evaluation or according to national guidelines, these children should be offered TB preventive treatment, regardless of their age.
15. The absence of any symptoms of TB and the absence of abnormal chest radiographic findings may be used to rule out active TB disease among HIV-negative household contacts aged ≥ 5 years and other risk groups before preventive treatment.
WHO recommends that chest radiography may be offered to PLHIV who are receiving ART. If there are no abnormal radiographic findings, TPT should be considered. However, chest radiography should not be considered a mandatory requirement and become a barrier in starting TPT for PLHIV as there is only a marginal gain in accuracy as compared with symptom screening alone.
Role of chest radiography
One of the key policy decisions with financial implications is whether to consider systematic use of chest radiography along with TB symptom screening to rule out TB disease.
Chest radiography is known to have high sensitivity but low specificity for TB (41). Use of chest radiography in an asymptomatic child, five to nine years of age (as for < 5 years) has poor specificity and thus a very low yield of true positive TB, with a risk of over-diagnosis for conditions caused by other conditions (such as pneumonia or perihilar adenopathy) and unnecessary treatment for TB. Moreover, addition of chest radiography to symptom screening may present logistical difficulties and increase cost to programmes and individuals, leading to missed opportunities to give TPT to people who could benefit from it. Among PLHIV, symptom screening alone before TPT is not only less costly but also prevents more TB deaths and cases (42). However, use of chest radiography together with TB symptom screening is likely to increase the confidence of health providers given the very high sensitivity of the combination (less chance of missing TB disease). This may conceivably reduce provider concerns around the development of drug resistant-TB resulting from inadvertent treatment of TB disease with a TPT regimen. This is particularly important among HIV-negative household contacts who are adolescents and adults, other close contacts and clinically at-risk populations. Similarly, use of chest radiography may increase provider confidence among PLHIV who are receiving ART.
Chest radiography may therefore be considered in TB screening algorithms where it is available and not burdensome to the individual. If there are no abnormal radiographic findings, TPT should be considered. However, chest radiography should not be considered a mandatory requirement and become a barrier for starting TPT. When chest radiography is not available, the absence of symptoms alone suffices to exclude TB disease before starting TPT.
When any abnormal chest radiographic findings are noted (not just those suggestive of TB), detailed investigation for TB disease and other diseases should be undertaken in accordance with national guidelines and sound clinical practice.
With the increase in availability of digital radiography, the use of computer aided detection (CAD) to interpret films, and the engagement of private health facilities to purchase radiography services is expected to increase access to radiography in TB screening and diagnostic algorithms. In mid- 2020 WHO will review evidence to assess whether guidance can be issued on the use of CAD for chest radiograph reading as part of screening algorithms for TB and continue to monitor evidence emerging from this rapidly evolving technology.
Key point: Chest radiography can play a role in ruling-out TB before TPT and increase the confidence of the provider and person radiographed that TB disease is absent. Governments and donors should invest to scale up access to chest radiography, including from private sector providers. However, lack of access to chest radiography should not be a barrier to TPT introduction and scale-up.
Implementation considerations to rule out TB disease
Health ministries should coordinate implementation of activities articulated below to screen for and exclude TB disease ahead of TPT provision.
• Make ACF among at-risk populations for TB an integral part of the overall package of health care for these populations (such as a HIV care package for PLHIV). In principle, the overall responsibility for planning, resource allocation, service delivery (ACF and activities to rule out TB disease) and monitoring and evaluation, should be vested in the national authority responsible for services to the respective populations. The national TB programme, in collaboration with primary care and maternal and child health services, should assume responsibility for ACF among contacts of index TB patients; the national HIV programme should organize services for PLHIV in collaboration with the national TB control programme; the clinical services within the ministry of health should support ACF and linkages to treatment and care among other clinical at-risk populations, and likewise for state agencies responsible for prisons, occupational health and migrant care.
• Receive advice from a national coordinating body or technical expert group or similar body for respective national programmes in the development of a national scale-up plan for programmatic implementation of ACF and services to rule out TB disease across different target populations and geographies. The coordinating body or group may also advise on standard operating procedures (SOPs), plan for capacity building of various types of providers and coordinate procurement and supplies of commodities for interventions across different programmes.
• Develop a standard implementation guide including roles and responsibilities, operating procedures, implementation tools, job-aids and recording and reporting tools (integrated across HIV, TB and maternal and child health services) for ruling out TB disease among at-risk populations.
• Develop communication materials for display and use at all service delivery sites implementing intensified TB screening.
• Identify a cadre of health care workers at different levels of the health care system to perform clinical screening as well as referral for further testing for TB disease, infection and evaluation, as per national guidelines.
• Undertake training and on-the-job capacity building for health care workers, community health workers and other service providers in systematic TB symptom screening.
• Conduct regular supportive supervision at national, provincial and district levels for TB screening activities, especially those carried out by community health workers to ensure good quality screening and adherence to national algorithms.
• Develop job-aids highlighting steps in ruling out TB disease.
• Organize access to chest radiography through: public or private health facilities or mobile vans as required by the national policy; memoranda of understanding (MoU) with private hospitals and radiologists; as well as free vouchers for people to access private services.
• 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 key steps in the cascade and report indicators of programme performance to the national level (see also Chapter 8)
Table 3.1 provides an overview of the considerations for ruling out TB disease among various target populations before starting TPT. While effective TB symptom screening forms the backbone of TPT services, tests for TB infection, chest radiography and diagnostic testing may be used
Additional funding considerations to rule out TB disease
• Support regular convening of and consultation with the national technical working group or a similar existing mechanism to review strategies for ruling out TB disease before TPT among target populations.
• Develop and implement a plan for human resource development including hiring, training, mentoring, and ongoing sensitization in TB symptom screening, family counselling and evaluation of eligibility for TPT.
• If chest radiography is used for TB screening as per national guidelines, funding allocation will be required for
– equipment (such as for digital radiography),
– supply of logistics,
– maintenance of equipment,
– training of clinicians and health care workers in reading chest radiographs, and/or
– hiring of radiography services from the private sector (such as free vouchers for individuals receiving care either in public or private facilities).
• Expand access to rapid TB diagnostics, such as Xpert MTB/Rif, lateral flow urine lipoarabinomannan assay (LF-LAM).
• Establish or strengthen specimen collection and transportation based on needs of different target opulations (including children).
• Printing and dissemination of SOPs and job-aids for TB symptom screening.
Also refer to Annex 3
ᵃ Screening for children and pregnant or breastfeeding women may be integrated into various entry points for care (such as maternal and child health, immunization, well baby clinics, nutrition clinics).
ᵇ Among PLHIV, all the above steps should be incorporated if differentiated HIV service delivery models are implemented. ACF and TPT should be an integral part of the care package for PLHIV