Pulmonary and extrapulmonary TB disease in adults can be treated with the same regimens, the 6-month 2HRZE/4HR being the core regimen. Outside WHO recommendations, some experts suggest 9–12 months of treatment for tuberculous meningitis (given the serious risk of disability and mortality) (40), and 9 months of treatment for osteoarticular TB (given the difficulties in assessing treatment response) (40, 43-45).
Treatment of extrapulmonary TB is similar to that of pulmonary TB, being centred around the 6-month 2HRZE/4HR regimen; however, the regimen can be prolonged up to 12 months for tuberculous meningitis, osteoarticular TB or other types of extrapulmonary TB, as decided by clinicians. The 4-month 2HPMZ/2HPM regimen was not studied in extrapulmonary TB and thus cannot be recommended at this time. Furthermore, extrapulmonary TB is usually more difficult to diagnose, and evaluation of its outcomes can be more challenging because of the absence of bacteriological evidence in most patients and the need for cross-sectional imaging; hence, there is little quality evidence on this type of TB.
Following infection with M. tuberculosis, young children are at high risk of developing the most severe forms of disease, the most devastating being tuberculous meningitis, which predominantly affects young children (peak age of onset, 2–4 years). WHO currently recommends a 12-month regimen to treat tuberculous meningitis in children, comprising isoniazid, rifampicin, pyrazinamide and ethambutol given daily for the first 2 months, followed by isoniazid and rifampicin given daily for an additional 10 months (2HRZE/10HR) (20). Recommended doses to be used in this regimen are the same as those for the treatment of pulmonary TB. This regimen can be used in all children and adolescents, including those who are HIV-positive.
An alternative option of a shorter regimen is also conditionally recommended. This shorter regimen is recommended for children and adolescents with bacteriologically confirmed or clinically diagnosed tuberculous meningitis (without suspicion or evidence of MDR/RR-TB); it is a 6-month intensive regimen that comprises isoniazid, rifampicin, pyrazinamide and ethionamide (6HRZEto) (20). It is preferable to use child-friendly, dispersible and FDC medicines in children when possible.
In cases of non-severe TB, the 4-month 2HRZ(E)/2HR regimen (see Section 5 for details) can be used for children and adolescents with peripheral lymph node TB, intrathoracic lymph node TB without airway obstruction and uncomplicated TB pleural effusion (1).
Children with peripheral lymph node TB were included in the SHINE trial, and the results showed that the 4-month regimen (2HRZ(E)/2HR) can be used in children and adolescents aged between 3 months and 16 years with extrathoracic lymph node TB, which falls under the definition of nonsevere TB (1). These results should provide reassurance for clinicians regarding a seemingly delayed clinical response to TB treatment, which is often seen in children with peripheral lymph node TB (where lymph nodes remain enlarged even after treatment).