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The use of FDC child-friendly tablets is recommended instead of separate formulations in the treatment of children with drug-susceptible TB (100). FDC tablets have advantages over single medicines as they reduce the pill burden and the likelihood of prescription errors. By reducing selective non-adherence, FDC tablets can reduce the risk of development of drug resistance.
Table 5.3 shows the recommended dosages for first-line TB medicines for children. These dosages are applicable to all children, irrespective of the type of TB (except for TBM treated with the short intensive regimen) and HIV status. They also apply to the 12-month TBM regimen. Evidence on alternative compositions or dosages in the longer TBM regimen has not been assessed by WHO.
Following infection with M. tuberculosis, young children are at high risk of developing the most severe forms of disease, of which the most devastating is TBM. This mainly affects young children (4). Up to 15% of childhood TB presents as TBM (92). With a decreasing incidence of bacterial meningitis attributed to other causes, TB is the leading cause of bacterial meningitis in many settings (93). TBM is associated with significant mortality and morbidity.
Children aged between 3 months and 16 years with EPTB limited to peripheral lymph nodes (i.e. without involvement of other sites of disease) should be treated with the shorter regimen (2HRZ(E)/2HR). Children with forms of drug-susceptible EPTB other than TBM and osteoarticular TB should be treated with a 6-month treatment regimen of 2HRZE/4HR. Children with osteoarticular TB should be treated with 2HRZE/10HR.
Given the increased risk of treatment failure and drug resistance, children and adolescents who had been treated in the preceding 2 years were not eligible for inclusion in the SHINE trial. These children should be treated with the 6-month treatment regimen (2HRZ(E)/4HR).
Children and young adolescents with PTB who do not meet the eligibility criteria for the 4-month regimen should be treated with a standard 6-month regimen that includes a fourth drug – ethambutol – in the intensive phase (2HRZE/4HR).
Children presenting with severe acute pneumonia who are diagnosed with TB should be treated for 6 months (2HRZE/4HR) in view of the severity of their symptoms, which, according to the definition of severe acute pneumonia, include cough or difficulty in breathing with at least one of the following:
No separate subgroup analysis could be conducted for children with SAM (defined as weight-forheight Z-score below −3 or mid-upper arm circumference below 115 mm (91)) in the SHINE trial due to the low numbers (30 children with SAM in the 16-week arm and 33 in the 24-week arm). As SAM is defined as a danger sign, even if children with SAM have a non-severe form of TB they should preferably receive 6 months of TB treatment.
Children and young adolescents living with HIV were eligible for enrolment in the SHINE trial. A total of 65 children and adolescents living with HIV (11%) were enrolled in the 16-week arm and 62 (10%) in the 24-week arm. The 16-week regimen was non-inferior when compared with the 24-week regimen (risk difference −4.3, 95% CI −14.9 to 6.2) (86).
Although the numbers of children with peripheral lymph node TB in the SHINE trial were small (N = 19 in the 16-week arm, N = 21 in the 24-week arm), there was no difference in the proportion of unfavourable outcomes between the two arms (86). These results may provide reassurance for clinicians regarding a seemingly delayed clinical response to TB treatment, frequently seen in children with peripheral lymph node TB (where lymph nodes remain enlarged even after treatment), even if these children are treated for 4 months.