Decision point on target populations for systematic testing and TPT
Which of the at-risk populations are priority targets for the programmatic scale-up of TPT, based on your country context?
The WHO guidelines on TPT recommends target populations fulfilling one or more of the following criteria for PMTPT (12):
- High prevalence of TB infections
- High risk of progression to TB disease
- High incidence of TB disease compared to the general population, indicating high TB transmission setting
- Benefits of TPT outweighing potential risk of acquiring TB or drug toxicity.
WHO recommends two broad groups of at-risk populations that fulfil the above criteria for systematic assessment of eligibility and provision of TPT.
1. People with elevated risk of progression from infection to TB disease
– People living with HIV
– Patients suffering from silicosis, patients starting or preparing for anti-tumour necrosis factor (TNF) treatment, patients receiving dialysis, and patients preparing for organ or haematologic transplantation.
2. People with increased likelihood of exposure to TB disease
– Household contacts of people with bacteriologically confirmed TB, usually subdivided into:
a. Children below five years of age
b. Children five years and above, adolescents and adults
– Persons who live or work in institutional or crowded settings, such as prisoners, health workers, recent immigrants from countries with a high TB burden, homeless people and people who use drugs.
Although, systematic testing and treatment of people with diabetes, people who engage in harmful use of alcohol, tobacco smokers and underweight people are not specifically recommended for systematic testing and TPT, these populations may still be considered for TPT on a case-by-case basis to reduce the risk of TB, especially if they have heightened likelihood of unfavourable outcome should disease develop or if the person has multiple risk factors for TB.
The following paragraphs detail the rationale and implementation considerations that national programmes may use to inform policies on the choice of target populations for PMTPT.
People living with HIV
People with HIV are around 20 times more likely to develop TB disease than those without HIV infection and should be prioritized for systematic evaluation and TPT in all settings (10). Despite major progress in access to and effectiveness of antiretroviral treatment (ART), TB is the most frequent cause of acquired immunodeficiency syndrome (AIDS)-related deaths worldwide (16). In 2018, TB caused over 250 000 deaths among People with HIV i.e. about one third of all HIV deaths (10). Existing evidence shows that TPT increases the survival of People with HIV even when they are on ART (17). TPT also provides additional protection when given immediately after the successful completion of treatment for TB disease in People with HIV (17–19) (the box below presents relevant recommendations from the 2020 WHO guideline on TPT (12)).
WHO recommendations:
1. Adults and adolescents living with HIV who are unlikely to have active TB should receive TB preventive treatment as part of a comprehensive package of HIV care. Treatment should also be given to those on antiretroviral treatment, to pregnant women and to those who have previously been treated for TB, irrespective of the degree of immunosuppression and even if LTBI testing is unavailable
2. Infants aged < 12 months living with HIV who are in contact with a person with TB and who are unlikely to have active TB on an appropriate clinical evaluation or according to national guidelines should receive TB preventive treatment.
3. Children aged ≥ 12 months living with HIV who are considered unlikely to have active TB on an appropriate clinical evaluation or according to national guidelines should be offered TB preventive treatment as part of a comprehensive package of HIV prevention and care if they live in a setting with high TB transmission, regardless of contact with TB.
4. All children living with HIV who have successfully completed treatment for TB disease may receive TB preventive treatment.
While TPT should be considered in infants aged < 12 months living with HIV who have a history of contact with a TB patient, children living with HIV (CLHIV) aged ≥ 12 months should be considered for TPT irrespective of contact with a TB patient. TPT is recommended for CLHIV, regardless of whether they are on ART or not. The evidence for additive benefit of TPT among CLHIV on ART is limited, but it is plausible given the efficacy observed among adults with HIV receiving ART plus TPT. Similarly, the effect of TPT in CLHIV after successful completion of TB treatment is largely extrapolated from benefits observed in adults exposed to reinfection and recurrence of TB.
Similar to infants aged < 12 months who are living with HIV, infants born to HIV-infected mothers are vulnerable to early TB infection due to the mother’s risk of contracting TB disease (20,21). Given the poor outcomes of TB disease in infancy, it is important to consider TPT for such infants who show no signs of TB disease. Prevention of mother-to-child transmission (PMTCT) of HIV offers an important platform to screen these infants for TB disease. A strong linkage should therefore be established between PMTCT services and national TB programmes (22)
WHO also recommends provision of TPT among CLHIV who successfully complete treatment for TB disease. People with HIV face higher risk of recurrence of TB disease compared to HIV-negative individuals. While a complete course of TB treatment with a four-drug regimen has a very high treatment success rate and very low incidence (2–3%) of recurrence, in HIV-infected patients, the risk is several times higher, possibly due to treatment failure, emergence of drug resistance during therapy or reinfection with a new strain of M. tuberculosis (23–26). In a study among HIV-infected patients whose initial episode of TB was deemed cured, 14% experienced a recurrence of TB, of which close to 90% were due to reinfection with a different strain of M. tuberculosis (27). Key interventions to minimize recurrence of TB include: ensuring completion of the initial course of TB treatment, effective infection control measures in clinical and community settings frequented by People with HIV, and secondary TB preventive treatment (28,29)
Household contacts (regardless of HIV status)
Child household contacts below five years of age who are household contacts of TB patients, have significantly higher risk of acquiring TB infection and progressing rapidly to TB disease. Children below two years of age are also at greater risk for severe and disseminated forms of TB with very high risk of morbidity and mortality. Therefore, TPT is strongly recommended once TB disease is ruled out. Similarly, other household contacts of TB patients have high risk of acquiring TB infection compared to the general population and should be considered for inclusion in PMTPT.
WHO recommendations:
5. Children aged < 5 years who are household contacts of people with bacteriologically confirmed pulmonary TB and who are found not to have active TB on an appropriate clinical evaluation or according to national guidelines should be given TB preventive treatment even if LTBI testing is unavailable.
6. Children aged ≥ 5 years, adolescents and adults who are household contacts of people with bacteriologically confirmed pulmonary TB who are found not to have active TB by an appropriate clinical evaluation or according to national guidelines may be given TB preventive treatment.
7. In selected high-risk household contacts of patients with multidrug-resistant tuberculosis, preventive treatment may be considered based on individualized risk assessment and a sound clinical justification.
WHO also recommends consideration of TPT for select household contacts of multidrug-resistant TB (MDR-TB) patients (such as children, people receiving immunosuppressive therapy and People with HIV), as the available evidence shows more benefits than harm (12). The decision to treat MDR-TB contacts should be taken on an individual basis both with respect to the selection of person to treat and the TPT regimen. There is limited evidence to support one single regimen for MDR-TB contacts: studies that informed this recommendation used levofloxacin with or without ethambutol/ethionamide daily for six months.
TPT should be considered only after TB disease is ruled out by an appropriate clinical evaluation or according to national guidelines and after a careful risk assessment, including intensity of exposure, certainty of the source of disease, reliable information on the drug resistance pattern of the source and potential adverse drug reactions. Confirmation of infection by tuberculin skin test (TST) or interferongamma release assay (IGRA) is desirable before the start of TPT to confirm TB infection. This maximizes the likelihood of TPT not being given unnecessarily. There is less evidence on the balance of benefit to harm of medicines used in the TPT of MDR-TB than for drug-susceptible TB, and therefore the decision to give TPT needs to consider any potential risk carefully. If levofloxacin is used for TPT of MDR-TB, it is important to ascertain careful exclusion of TB disease so as to limit the risk of emergence of resistance to levofloxacin (a key drug in second-line treatment regimens), should the person require treatment for MDR-TB disease in the future. Strict clinical observation for signs of TB disease for at least two years after exposure should be ensured, regardless whether TPT for MDR-TB is given or not.
Clinical and other at-risk population groups
WHO recommendations:
8. People who are initiating anti-TNF treatment, or receiving dialysis, or preparing for an organ or haematological transplant, or who have silicosis should be systematically tested and treated for LTBI.
9. Systematic LTBI testing and treatment may be considered for prisoners, health workers, immigrants from countries with a high TB burden, homeless people and people who use drugs.
10. Systematic LTBI testing and treatment is not recommended for people with diabetes, people who engage in the harmful use of alcohol, tobacco smokers and underweight people unless they also belong to other risk groups included in the above recommendations.
Benefits of TPT outweigh the potential harm among other HIV-negative clinical risk groups considering increased risk of exposure and/or progression to TB disease. However, despite evidence of increased prevalence of TB infection and TB disease among persons with diabetes, people who engage in the harmful use of alcohol, tobacco smokers and underweight people, there is a paucity of data from clinical trials on the relative benefits and harm of systematic testing and TPT. Testing and treatment among people with one or more of these risks may be considered on a case-by-case basis. Additional evidence on systematic TPT services among these populations is required to inform future WHO guidelines.
Integrating active TB case finding in PMTPT
Complementary to recommendations on target populations for systematic testing and TPT for TB infection above, WHO also recommends systematic screening for TB disease among various at-risk populations. National programmes may consider integration of TPT services with TB case finding among these populations (30,31). WHO is currently reviewing latest evidence to update the recommendations for at-risk populations for active TB case finding (ACF) and recommend optimal TB screening strategies. National programmes may integrate systematic evaluation for TPT eligibility among these populations, depending on individual risk in terms of recent exposure to a TB patient, immune status and other comorbidities, and provide access to TPT once TB disease is ruled out. National programmes may adapt the algorithm for other risk groups (Fig. 4.1) when integrating ACF and TPT in populations at risk.
Key point: National programmes implementing ACF among at-risk populations should consider integration of TPT services within the package of care to increase coverage with minimal additional investment, and vice versa programmes implementing TPT should link eligible individuals to services for TB disease diagnosis and treatment.
The scope of activities performed during contact investigations may also be expanded beyond TB services, based on country context. For example, when the index TB patient is HIV positive, household contacts should also be offered HIV counselling and testing systematically or when malnutrition is noted during contact investigation, nutrition screening and assessment should be done.
Implementation steps to identify TPT target populations
1. Establish a national technical working group or expand the mandate of an existing technical working group or equivalent mechanism to advise the ministry of health and national TB and HIV programmes. The technical working group may consist of national experts, stakeholders from national TB, HIV, maternal and child health and other relevant programmes, representatives from patient groups, civil society, frontline health providers/nurses, national research institutes, technical partners and WHO. The group may be mandated to lead the identification of target populations and strategies to reach these populations under PMTPT (Annex 2).
2. Review national policies and guidelines. The technical working group may review current national policies and guidelines for PMTPT and lead the process of updating them and aligning with the latest global guidelines.
3. Undertake a situational assessment. The technical working group and/or national programme may undertake the following reviews to guide decisions on identification of target populations for PMTPT:
– Burden of TB disease (and TB infection) among various at-risk populations
– Capacity of the existing health system (staff, skills and equipment) to assess intensity and risk of TB exposure and exclude TB disease
– Availability of financial resources and identifying gaps to support nationwide scale-up of TPT services
– Opportunities to mobilize additional resources
4. At a minimum, all countries should aim to achieve universal coverage of TPT among People with HIV and household contacts of TB patients under five years of age.
5. Identify other target populations. This may be guided by small scale demonstration or phased implementation of PMTPT among the various target populations to identify operational issues. Experience from demonstration projects may inform identification of populations and strategies to reach them with TPT services. Extensive research to review efficacy of TPT regimen is not required, given that the WHO guideline process involves in-depth review of latest clinical trial evidence. Moreover, such country-specific or population-specific studies risk delaying the scale-up of TPT services thereby denying benefits of TPT to vulnerable populations.
6. Prioritize individuals who are likely to have recently acquired TB infection (e.g. children, recent and young immigrants from countries with a high TB burden to low TB burden countries, recent contact with a TB patient, or documented conversion of TB infection test from negative to positive)
It is important to consider, particularly for populations in congregate settings, that surveillance and treatment of TB disease and infection control measures are effectively implemented (32). These are essential prerequisites in deciding about the implementation of TPT services in such populations. Without implementation of good measures for airborne infection control, sustained benefits from TPT may be jeopardized due to high risk for reinfection. Therefore, once target populations for TPT are identified, ministries of health, donors and stakeholders should support capacity building of programmes to strengthen infection control measures and establish access to rapid TB diagnosis and treatment.
Key point: ACF with linkages to TB treatment and TB infection prevention and control are essential elements of programmatic scale-up of TPT among at-risk populations, particularly in congregate settings.
Implementation considerations to reach TPT target populations
Reaching People with HIV and other target populations
• All HIV testing and treatment facilities including community-based HIV care and support, should systematically implement intensified TB case finding, TPT and TB infection control. This requires close collaboration between national TB and HIV programmes (33).
• All People with HIV should be screened for TB symptoms at every opportunity or when in contact with a health worker. Those with TB symptoms should be referred for diagnostic testing, and those without symptoms should be evaluated for eligibility and started on TPT, as appropriate.
• National TB and HIV programmes should provide resources and undertake site monitoring to ensure implementation and quality improvement measures when gaps are noted (such as lack of screening, cursory screening, lack of linking to TPT).
• For other target populations, the national programme should tailor TB screening and TPT services to the needs and capacities of existing health infrastructures. The approach should aim to optimize and synergize delivery of TPT services along with other health and social welfare services. Target populations and screening approaches should be monitored regularly to improve delivery of services.
Reaching household contacts
Household contacts of TB patients are well recognized at-risk groups for TB infection and TB disease, including prevalent TB detected at the time of initial contact investigation, as well as incident TB that occurs within the subsequent two to five years. TPT among household contacts may have important potential benefits since prevalence of TB infection exceeds 50% in many low and middle income countries (LMICs) (34,35). In systematic reviews, the prevalence of TB disease among household contacts in LMICs ranged from 3% to 5% (34,35). Results of the PHOENIx Feasibility study (crosssectional) from eight high TB burden countries, showed that of a total 1007 household contacts of 284 MDR-TB patients with no TB at diagnosis, systematic household contact investigation helped detect new TB disease in 12% contacts; TB infection prevalence (defined as either TST or IGRA positivity) in this group was 72% (36). Thus, screening of household contacts for TB disease is considered a high priority for virtually all TB control programmes because it is a very high yield and cost-effective ACF strategy (37). This further paves the way to effective treatment for TB disease and TPT and thus optimizes public health impact on transmission as well as improves TB-related outcomes for contacts. It is a key strategy for infection control as well in all settings.
Investigation and treatment of all household contacts have important advantages and can provide important health and financial benefits to the entire family. Occurrence of TB in the family has serious social and economic effects including catastrophic costs due to loss of income or cost of health care. By investigating, detecting and treating both TB disease and TB infection, transmission in the household can be stopped and the catastrophic costs and dire health outcomes due to TB prevented. This is a holistic ‘family health’ approach, offering more efficient TB care to all members. Offering TPT to all family members at the same time and during the period when the index TB patient is still receiving treatment and care, can help maximize the understanding and impact of TPT, as well as enhance costeffectiveness of interventions such as home visits. Further, a strong contact investigation programme will pave the way for achievement of commitments made by the Member States to provide TPT to 24 million household contacts by 2022.
Key point: Investments to strengthen national programme capacity to undertake contact investigation prevents future TB disease by improving access to TPT for children and adult contacts and identifying missed TB patients for treatment, thus reducing onward transmission.
Strengthening household contact investigation
Contact investigation is an important first step both for ACF and TPT. It is a systematic process to identify people with TB disease and contacts of index TB patients who need TPT. It consists of identification, clinical evaluation and/or testing and provision of access to appropriate anti-TB therapy (for people with confirmed TB) or TPT (for those without TB disease). It should be a standard component of all national TB control efforts. Moreover, contact investigation is a good public health practice and essential for tracking several infectious diseases (such as COVID-19) and therefore the ministries of health should invest in strengthening health system capacity. If the mechanisms to undertake contact investigation are in place, national programmes need to strengthen the same to ensure that contacts above five years of age are also covered. If such mechanisms are lacking, the ministry of health should dedicate necessary human and financial resources to establish effective mechanisms for contact investigation. Fig. 2.1 provides an indicative list of items to consider for determining appropriate unit costs for budgeting and planning to strengthen contact investigations.
In addition to extra funding, national TB programmes should consider and strengthen activities highlighted in Fig. 2.2 to ensure effective contact investigation.
Key implementation steps in contact investigation
1. Provide standard guidance and approaches to reach contacts and undertake investigations to ensure uniformity in implementation
2. Provide national guidance that:
– defines priority populations for contact investigation (household and beyond);
– defines model of care, i.e. facility- or community-based;
– defines the role and responsibilities of programme personnel, health care worker and community health worker, in reaching the contacts, symptom screening, referral for testing and clinical evaluation (e.g. cadre of health care workers responsible for contact investigation and its inclusion in respective job descriptions, health care workers responsible for supervision of personnel conducting contact investigation if community-based model is implemented);
– defines data elements to capture the index patient’s record and/or digital tools (see also Chapter 7);
– includes tools/referral slips to record TB screening and referral of identified contacts for further care if the community-based model is implemented;
– defines level of service delivery points for systematic recording and reporting as well as frequency; and
– provides locally tested messages for demand generation and patient education.
3. Leverage existing human resources and mechanisms across multiple disease programmes (such as public health response model promoted by U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) for People with HIV) to implement contact investigation and ensure sustainability and efficiency. TB and HIV screening could be integrated throughout the process.
4. Implement contact investigation
– The index patient should be interviewed as soon as possible after diagnosis, preferably within one week, to elicit details about household and other close contacts. Health providers should clearly and sensitively explain the urgency of initiating contact investigations to the index patient, considering the increased risks of progression to TB disease with recent exposure. A second interview may be required to elicit additional contacts as well as complete any missing information.
– Ideally, the interview should be conducted by a person who speaks the same language as the index patient and is familiar with his or her social and cultural context.
– Education of the index patient and household members regarding the benefits of taking TPT and risks of NOT taking it, should be central to the contact investigation process. The overall aim should be to enable informed decision by the individuals to receive a complete course of TPT regimen.
– Counselling to index TB patients should also help them to appreciate the importance of identifying all significant contacts. This will permit preventive action to reach more people at risk.
– Where the community-based model is implemented, it is desirable to seek approval from the index patient for a home visit. In addition to counselling of the index patient, arrangements should be made to counsel contacts before starting TPT.
– Preferably, the health provider conducting the contact investigation should visit the home or workplace of the index patient, conduct interviews and underscore the importance of identifying and evaluating contacts, perform symptom screening and document, gather more accurate information about the intensity and duration of exposure and ensure that all relevant contacts are referred for further evaluation and a treatment decision (Box 2.1) (38). Visits may need to be done outside of normal working hours since contacts may be at work or school during these hours.
– Home visits also provide the opportunity to identify the needs for social support, nutrition and education on infection control measures. After the visit, the health provider may link the index patient and contacts to relevant social and nutritional support programmes.
– During the home visit the health provider should make an assessment of the residence and provide counselling and education to family members on TB symptoms. If required, prompt medical attention and referrals should be made especially for child contacts and People with HIV, in whom TB could progress rapidly. HIV testing and counselling should be offered as part of this process, including to biological children of any adults living with HIV.
- If the home or workplace cannot be visited, the index patient may be interviewed at a health facility and contacts listed. Complete address and modality for future communication should be mutually agreed with the index patient (such as phone numbers, email, contact of an intermediary or treatment provider). Responsible persons or health care workers should then systematically follow up with the index patient or treatment provider and mobilize all relevant contacts to the health facility for symptom screening, testing for TB and TB infection when indicated and evaluation for eligibility of TPT.
– While the focus of the contact investigation should be household members, contacts at the workplace, residential care facilities, residential schools, long-term care facilities, prisons, correctional facilities and acute medical care facilities, should be considered as per national guideline for evaluation, especially when exposure is likely to have been prolonged and the index patient is likely to be highly infectious (due to prolonged cough, strongly acid-fast bacilli (AFB) smear-positive sputum and/or extensive cavitatory disease on chest radiograph).
– Maintaining confidentiality during contact investigation is a challenge because of the social connections between index patients and their contacts. All persons should be treated with respect, and confidentiality should be maintained. National programme guidelines on data protection, confidentiality and consent should be adhered to.
– When the index patient is reluctant to give information regarding both household and social contacts, counselling efforts should continue over time to gain the trust of the patient. The index patient should not be coerced, nor should her/his TB treatment or services provided be made conditional on cooperation with contact investigation.
Key point: Index TB patients should not be compelled to disclose contacts or help ensure completion of contact investigation. Due diligence is necessary in safeguarding the index patient’s privacy and rights and avoiding stigma. Ongoing patient education is preferred over use of force and coercion.
– Information from the interview should be recorded (31).
– Contact investigations should also be conducted for people who died of TB by gathering information from family members and service providers
5. Provide guidance on monitoring and evaluation (see also Chapter 8):
– Use standard tools and a protocol for data collection during contact investigation, data entry and analysis.
– Monitor yield of contact investigations and the proportion of TB disease and TB infection detected to inform programme adjustments.
Key point: The biggest component of UNHLM targets is to provide TPT to at least 24 million household contacts of TB patients between 2018 and 2022. Global progress towards achieving this target has been negligible. Scaling-up TPT among this target population is likely to generate significant community dividends and return on investment. Hence ministries of health and stakeholders should commit adequate funding and resources to build capacity of programmes to undertake effective contact investigations.
Additional funding considerations to find target populations
• Integrating contact investigations into the roles and responsibilities of existing health and community workforce.
• Dedicating human resources as required to implement and to monitor implementation of contact investigations.
• Training and capacity building of health care workers, community workers and other implementers.
• Travel support or incentives for health care workers, community workers or other implementers of contact investigations.
• Travel support for index TB patients and contacts to reach facilities for screening, testing and continuation of TPT.
• Strengthening recording and reporting of data (updating existing electronic data systems with variables for PMTPT or adoption of digital tools such as the WHO Prevent TB mobile application (39)).
• Awareness generation among patients, contacts and communities.
Also refer to Annex 3