ReacciónCoverage of contact investigation and TPT among child contacts and people with HIV are two of 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 PMTPT in target populations (41,130). PMTPT should include monitoring and evaluation systems that are aligned with national TB patient monitoring and surveillance systems. They should include coverage of TPT with levofloxacin among contacts exposed to MDR/RR-TB. Appropriate recording and reporting tools should be available. Electronic case-based monitoring will facilitate PMTPT. Standardized indicators should be measured regularly to inform decision-makers for programme implementation. Some may require changes to national regulations or health policies (e.g. making TBI a notifiable condition or mandating a reporting framework), which should be addressed according to the context. The private health sector should be engaged to ensure proper recording and reporting from both the private and public sectors. More details on monitoring and evaluation are provided in the second edition of the WHO operational handbook on TB preventive treatment (12). Monitoring should adhere with ethical principles of surveillance (131).
Most individuals who receive TPT are healthy, and adverse reactions to treatment are likely to influence the likelihood of their completing it. Drug-related toxicity should therefore be minimized. Medicines used in TPT regimens are generally safe and well tolerated, but adverse reactions have been observed with isoniazid (particularly asymptomatic elevation of serum liver enzyme concentrations, peripheral neuropathy and hepatotoxicity), rifampicin and rifapentine (such as cutaneous reactions, hypersensitivity reactions, gastrointestinal intolerance and hepatotoxicity) and levofloxacin (such as arthritis, arthralgia, or tendinopathy) (124–126). While most of these reactions are minor and occur rarely, attention should be paid to preventing conditions such as drug-induced hepatotoxicity. Caregivers should be aware of the spectrum of adverse reactions associated with use of the drugs so that they can take action rapidly. Most reactions are minor and self-limiting, and severe or serious reactions occur less commonly.
Close monitoring for adverse events and of adherence to treatment is essential for people on TPT for MDR/RR-TB. The GDG reiterated that strict clinical observation and close monitoring for TB disease, based on sound clinical practice and national guidelines, is required for at least 1 year after exposure to MDR/RR-TB, regardless of whether TPT was given. Consideration should also be given to interactions with other medicines when providing TPT for MDR/RR-TB.
Individuals on TPT should be monitored routinely at monthly encounters with health-care providers, who should explain risk, how TB disease develops and the rationale for the treatment and emphasize the importance of completing it. They should also be advised to contact their health-care provider at any time if they become aware of symptoms such as anorexia, nausea, vomiting, abdominal discomfort, persistent fatigue or weakness, inflamed or torn tendons, muscle pain, difficulty in walking, paraesthesia, burning pain, dark-coloured urine, pale stools, jaundice, confusion or drowsiness, depression, problems with memory, sleeping, vision and hearing, and altered taste and smell. If a health-care provider cannot be consulted at the onset of such symptoms, treatment should be stopped immediately. This is a critical area in which front-line health-care workers and students should receive training.
There is insufficient evidence to support systematic testing of baseline liver function in people on regimens containing isoniazid and/or rifamycins (132). This is, however, strongly encouraged, where feasible and resources permit, 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 post-partum period (within 3 months of delivery). For individuals with abnormal baseline test results, sound clinical judgement is required to ensure that the benefit of TPT outweighs the risks, with routine testing 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 stopping a medicine, such as an increase in transaminases to five times the upper limit of normal or to three times plus symptoms in people on rifampicin, should be adapted to more practical terms for field conditions. (See further instructions in the WHO operational handbook on TPT (12)).
There is no evidence that use of isoniazid, rifamycins or levofloxacin for TPT contributes significantly to the emergence of additional drug resistance to TB medicines (133,134). Nonetheless, TB disease must be excluded before TPT is initiated (section 1.2), and regular follow-up is necessary to ensure early identification of people who develop TB disease while receiving TPT. National surveillance systems for anti-TB drug resistance might have to be strengthened in countries in which PMTPT is being scaled up.
Monitoring adherence to TPT and ensuring its completion are of clinical benefit. Electronic applications for mobile phones and other devices can be used to guide national programmes on the critical data to be collected during TB preventive care, in addition to monitoring and evaluation (135). Such applications could also be helpful for collecting information about the occurrence of TB disease in people who have received TPT, by asking patients registered for TB treatment about any history of starting or completing TPT or by cross-linking registers (e.g. registers of people given TPT with TB treatment or mortality registers). In people who develop TB after or well into TPT, emergence of resistance should be tested.