Operational Handbooks

Non-severe TB is defined as peripheral lymph node TB, intrathoracic lymph node TB without airway obstruction, uncomplicated TB pleural effusion or paucibacillary, non-cavitary disease confined to one lobe of the lungs and without a miliary pattern.

It is both important and feasible for NTPs to ascertain cure at the end of treatment. The notion of relapse-free cure or sustained treatment success after the end of treatment is critical; however, it is beyond the means of routine programmatic monitoring and is feasible only under operational research conditions (e.g. in special cohorts, in patients undergoing rehabilitation and during follow-up for post-TB lung disease).

Given the increased use of newer and repurposed medicines in combination MDR-TB regimens, aDSM is particularly important. aDSM defines the active and systematic clinical and laboratory assessment of patients on MDR-TB treatment to detect, manage and report suspected or confirmed drug toxicities (18). It applies the principles of active pharmacovigilance to the specific needs and context of NTPs, and is embedded within the routine patient monitoring function (e.g. treatment outcome cohort monitoring) of NTPs.

The classification of medicines used in MDR/RR-TB treatment regimens was revised following the evidence-informed update of the WHO guidelines on DR-TB treatment in 2018. TB medicines to be used for treatment of MDR/RR-TB are categorized into Groups A, B and C (Table 6.1) (1). This classification is based on drug class and level of certainty in the evidence on effectiveness and safety (i.e. balance between benefits and risk of harm). The data analysed relate mainly to adult patients who received regimens in recent years.

Response to treatment is monitored by monthly sputum smear microscopy and culture. Older children who had microbiological confirmation of TB disease should also be encouraged to produce respiratory samples for monitoring whenever possible. Treatment response can also be monitored through regular clinical assessment of signs and symptoms of TB disease, and children should be monitored for changes in weight, height and BMI using age-appropriate growth charts.

The 9-month all-oral regimen is not adequate for the treatment of pre-XDR-TB or XDR-TB, and the efficacy of the regimen for treatment of MDR-TB where both inhA and katG mutations are present is largely unknown. Therefore, DST is recommended at or before the start of this regimen to exclude resistance to at least fluoroquinolones and to determine the mutations conferring resistance to isoniazid. Results of DST should not delay the start of an appropriate MDR/RR-TB treatment regimen, particularly if DST relies on phenotypic methods.

As with all TB programmes, active surveillance for adverse events is critical to ensure safety and minimize short-term and long-term morbidity of patients. A schedule for monitoring examinations should be established and applied to all patients receiving treatment with the BPaLM/BPaL regimen. Patients should undergo appropriate evaluation at the beginning of treatment (baseline), and during and after treatment.

Response to treatment should be monitored on the basis of monthly sputum smear microscopy and culture (ideally at the same frequency). Individuals prescribed the BPaLM/BPaL regimen should be monitored to assess regimen effectiveness and safety. Given that the BPaLM/BPaL regimen is a new and shorter regimen that includes novel medications, it is also important to follow up patients after the completion of treatment, to ensure that there is no treatment relapse or unexpected adverse events.

Pregnant and breastfeeding women were excluded from both the ZeNix and TB-PRACTECAL trials; therefore, no analysis specific to this subgroup of patients could be performed, and safety of the BPaLM/ BPaL regimen, especially of pretomanid, in pregnant and breastfeeding women has not been established. For pregnant and breastfeeding women, the longer 9-month oral regimen can be used (Chapter 5).