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Following M. tuberculosis infection, young children are at high risk of developing the most severe forms of the disease, of which the most devastating form is TBM. This predominantly affects young children with a peak age of onset of 2-4 years (2). Up to 15% of childhood TB may present as TBM (62); with a decreasing incidence of bacterial meningitis attributed to other causes, TB is the leading cause of bacterial meningitis in many settings (63).
Recommendation
In children and adolescents with bacteriologically confirmed or clinically diagnosed TB meningitis (without suspicion or evidence of MDR/RR-TB), a 6-month intensive regimen (6HRZEto) may be used as an alternative option to the 12-month regimen (2HRZE/10HR) (Conditional recommendation, very low certainty of the evidence).
Remarks
The clinical monitoring requirements for the shorter regimen remain the same as for the 6-month regimen and treatment outcomes are determined at the end of the 4-month regimen.
Should there be insufficient clinical improvement after completion of the 4-month regimen, the clinician may decide to extend treatment to 6 months while considering alternative diagnoses, including DR-TB.
Assessing severity of disease:The feasibility of assessing the severity of TB disease, particularly in settings without access to CXR or capacity for CXR interpretation and WHO-recommended diagnostic tests was identified as a major implementation consideration. Chest radiography was identified by the GDG as a critical tool to evaluate the severity of intrathoracic disease.
Children with peripheral lymph node TB: Although the number of children with peripheral lymph node TB in the SHINE trial were small (N=19 in the 16-week arm and N=21 in the 24-week arm), there was no difference in the proportion of unfavourable outcomes between the two arms. The SHINE trial also found that 16 weeks of treatment was non-inferior compared to 24 weeks of treatment among children with both peripheral lymph node disease and pulmonar y disease (N=182 in the 16-week arm and N=171 in the 24-week arm).
The majority of children with TB have less severe forms of the disease than adults. Treatment regimens that are shorter than those for adults may be effective in treating children with TB, however solid evidence to substantiate this has been lacking to date. Shorter treatment regimens can result in lower costs to families and health services, potentially less toxicity, lower risks of drug-drug interactions in children living with HIV, and fewer problems with adherence.
Recommendation:
In children and adolescents between 3 months and 16 years of age with non-severe TB (without suspicion or evidence of MDR/RR-TB), a 4-month treatment regimen (2HRZ(E)/2HR) should be used.
(Strong recommendation, moderate certainty of evidence)
Remarks
This chapter contains four new recommendations (published for the first time and described in full detail here) relevant to the treatment of TB disease in children and adolescents as well as other valid WHO recommendations that apply to the treatment of TB in children and adolescents (section 5.4).
The integrated treatment decision algorithms need to be monitored and evaluated for their impact on case notifications and treatment outcomes.
Clinical monitoring of people with TB started on treatment based on clinical criteria is equally important, such as the need to monitor response to treatment (to identify an alternative diagnosis for children who may be misdiagnosed as having TB), adverse events and deterioration in the clinical condition.
