2. Monitoring and evaluation

Coverage of contact investigation and TB preventive treatment among child contacts and People with HIV are among the top 10 core indicators for monitoring implementation of the End TB Strategy (8). National TB and HIV programmes report data yearly to WHO and UNAIDS on progress in LTBI care in target populations. PMTPT should include monitoring and evaluation systems that are aligned with national patient monitoring and surveillance systems (103),(104). Appropriate recording and reporting tools should be developed and electronic case-based monitoring will facilitate LTBI management and individual care¹⁰. Standardized indicators should be measured to regularly inform decision-making for programme implementation. Some may require changes to national regulations or health policies (e.g. making LTBI a notifiable condition or mandating a reporting framework), which should be addressed according to the local and national context. It is important to engage the private health sector and to ensure proper recording and reporting from both the private and public sectors.

Most individuals who receive TB preventive treatment are healthy and adverse reactions to treatment are likely to influence their likelihood of completing it. Drug-related toxicity should therefore be minimized. Medicines used for TB preventive treatment regimens are generally safe and well tolerated but adverse reactions have been associated with isoniazid (asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy and hepatotoxicity) and rifampicin and rifapentine (cutaneous reactions, hypersensitivity reactions, gastrointestinal intolerance and hepatotoxicity). While most of these reactions are minor and occur rarely, specific attention should be paid to preventing drug-induced hepatotoxicity.

Individuals on TB preventive treatment should be monitored routinely at monthly encounters with healthcare providers, who should explain the disease process and the rationale of the treatment and emphasize the importance of completing it. They should also be advised to contact their healthcare provider at any time if they become aware of symptoms such as anorexia, nausea, vomiting, abdominal discomfort, persistent fatigue or weakness, dark-coloured urine, pale stools, jaundice, confusion or drowsiness. If a healthcare provider cannot be consulted at the onset of such symptoms, the patient should stop treatment immediately. This is one of the critical areas for frontline healthcare workers and students to receive training on.

There is insufficient evidence to support testing of baseline liver function (105). It is, however, strongly encouraged, where feasible, for individuals with the following risk factors: history of liver disease, harmful use of alcohol, chronic liver disease, HIV infection, age > 35 years, pregnancy or in the immediate postpartum period (within 3 months of delivery). For individuals with abnormal baseline test results, sound clinical judgement is required to ensure that the benefit of TB preventive treatment outweighs the risks, and they should be tested routinely at subsequent visits. Appropriate laboratory testing should also be performed for patients who become symptomatic while on treatment (e.g. liver function tests for those with symptoms of hepatotoxicity). Trial criteria for when to stop a medicine – e.g. an increase in transaminases to 5 times the upper limit of normal or to 3 times plus symptoms in people on rifampicin – will need to be adapted to something more practical under field conditions.

There is no evidence of a significant association between anti-TB drug resistance and use of isoniazid or rifamycins for the treatment of LTBI (106),(107). Nonetheless, active TB disease must be excluded before TB preventive treatment is initiated (Section 1.2), and regular follow-up is required to ensure early identification of people who develop active TB while receiving TB preventive treatment. National surveillance systems for anti-TB drug resistance may need to be strengthened in countries scaling up PMTPT.

Monitoring the adherence to TB preventive treatment and ensuring its completion are conducive to clinical benefit. An electronic application for mobile phones has been created by WHO to guide national programmes on critical data to collect along the LTBI care pathway, as an accessory to monitoring and evaluation (103). It could also be helpful to collect information about the occurrence of active TB in people who have received TB preventive treatment. This can be done by asking patients registered for TB treatment about any history of starting or completing TB preventive treatment or the cross linkage of registers (e.g. LTBI registers compared with TB treatment or mortality registers). In people who develop TB after or well into a TB preventive treatment it would be important to test for emergence of resistance.

In people on MDR-TB preventive treatment the close monitoring for adverse events and adherence to treatment is essential. The types of adverse reactions depend on the medicines used (for more details see (101),(102),(108)). Adverse events should be monitored according to the WHO framework for monitoring and managing the safety of medicines against active TB (109). Evidence for the effectiveness and safety of MDR-TB preventive treatment is urgently needed (see also Section 3). The GDG reiterated that strict clinical observation and close monitoring for active TB disease based on sound clinical practice and national guidelines is required for at least 2 years after MDR-TB exposure, regardless of whether preventive treatment was given or not. Consideration should also be given to interactions with ART, immunosuppressants and other medicines when providing MDR-TB preventive treatment.

¹⁰ More detail will be provided in the practical operational guide that WHO is releasing with these guidelines.

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