Operational Handbooks

The only experience using these new regimens stems from two clinical trials; it is therefore suggested that the programmatic implementation be aligned with this experience. Safe management of adverse events may warrant dose reduction or discontinuation of the component drugs. However, the BPaLM/ BPaL regimen has been studied as a standardized course of treatment. Modification of the regimen through early discontinuation or replacement of any of the component drugs may result in poor treatment outcomes.

Linezolid is by far the most toxic drug in the BPaLM and BPaL regimens; it requires significant monitoring and at times a mitigation strategy to reduce adverse effects. Although it is preferred to continue linezolid at the full dose for the entire duration, the dose of linezolid can be reduced to 300 mg or discontinued (and restarted when possible) if there is significant toxicity. In general, action should be taken in the following manner for the common toxicities associated with linezolid:

Patients with susceptibility to fluoroquinolones can be started on the BPaLM regimen for 6 months (26 weeks). In the case of resistance to fluoroquinolones, identified after treatment initiation, moxifloxacin may be discontinued and the regimen can be continued as BPaL. When the regimen is BPaL from the start or is changed to BPaL, it can be extended to a total of 9 months (39 weeks) (continuing from the start of the therapy with BPaLM/BPaL).

The BPaL regimen can be prescribed for those who have proven fluoroquinolone resistance. In cases of possible fluoroquinolone resistance (e.g. a history of >4 weeks of fluoroquinolone use or close contact with a person infected with a fluoroquinolone-resistant strain), it is best to use the BPaLM regimen until DST for fluoroquinolones is available, to decide whether or not moxifloxacin should be continued. Where DST is pending, BPaLM can be commenced, subsequently dropping moxifloxacin from the regimen once fluoroquinolone resistance is confirmed.

BCG vaccine is used extensively worldwide, with about 100 million newborns vaccinated each year. Severe adverse events are reported only occasionally. For some adverse events (e.g. disseminated BCG disease), the diagnosis may depend on the culturing of M. bovis BCG to distinguish it from other forms of mycobacterial disease (33). It is important to recognize that M.

WHO policy guidance on TB diagnostics and laboratory strengthening

WHO consolidated guidelines on tuberculosis. Module 3: Diagnosis – rapid diagnostics for tuberculosis detection, third edition. Geneva: World Health Organization; In press.WHO End TB Strategy: global strategy and targets for tuberculosis prevention, care and control after 2015. Geneva: World Health Organization; 2015 (https://www.who.int/publications/i/item/WHO-HTM-TB-2015.19).

The DOI forms submitted by the experts reviewing this handbook and information retrieved from the internet, were examined by WHO staff members Nazir Ismail and Carl-Michael Nathanson to assess whether there were, or might be, actual or perceived conflicts of interest and, if so, whether a management plan was required. This evaluation process, and resultant management plans, were based on the Guidelines for declaration of interests (WHO experts) and the WHO handbook for guideline development (2nd edition).

The World Health Organization (WHO) recently published The use of next-generation sequencing for the surveillance of drug-resistant tuberculosis: an implementation manual (1) which provides practical guidance on planning and implementing next-generation sequencing (NGS) technology for characterization of Mycobacterium tuberculosis complex (MTBC) bacteria. In this manual, the focus is on the detection of mutations associated with drug resistance for the surveillance of drug resistance in tuberculosis (TB).