Children and Adolescents

TBM is the most debilitating form of TB in children. It has high rates of neurological sequalae despite cure and disproportionately affects children aged under 5 years (4, 134). The pooled risk for neurological sequelae in children with TBM was approximately 50% in a systematic review of treatment outcomes, with more advanced clinical stage of disease at diagnosis (stages 2a/b and 3) associated with worse outcomes at the end of treatment (94).

Awareness of the consequences of TB disease in children and adolescents that go beyond survival and completion of treatment has increased (131, 132). Each child or adolescent on TB treatment should be assigned a mutually exclusive treatment outcome at the end of treatment, but follow-up and care may need to go beyond the conclusion of TB treatment (71).

Monitoring the response to treatment in children and adolescents includes clinical, radiological and microbiological parameters. In children, microbiological monitoring of the response to treatment may be challenging for the same reasons as it being difficult to obtain a microbiological diagnosis. In children and adolescents with a bacteriologically confirmed diagnosis, however, it is important to monitor smear and culture conversion and confirm cure, as recommended by WHO.

Once on MDR/RR-TB treatment, children and adolescents must be monitored regularly to evaluate their response to treatment; identify treatment failure early; monitor for adverse events; and provide adherence, psychosocial and financial support to children and their caregivers.

Child-friendly dispersible formulations of many second-line TB medicines have been developed. These should be procured by NTPs and are strongly preferred for the treatment of young children with MDR/RR-TB over adult formulations, which must be manipulated (split, crushed, dissolved). Many of these are available through GDF, including bedaquiline 20 mg, delamanid 25 mg,²⁰ levofloxacin 100 mg, moxifloxacin 100 mg, pyrazinamide 150 mg, ethambutol 100 mg, isoniazid 100 mg, ethionamide 125 mg and cycloserine 125 mg minicapsules.

Recommendations on longer MDR/RR-TB treatment regimens for adults also apply to children and adolescents with severe forms of extrapulmonary MDR/RR-TB, as they are not eligible for the short all-oral bedaquiline-containing regimen. In addition to the principles described above, treatment of MDR/RR-TBM should be guided by the ability of the medicines to cross the blood–brain barrier and resulting CSF concentrations, where this is known (Table 5.13).

Table 5.12 summarizes possible individualized MDR/RR-TB treatment regimens for children of all ages and adolescents based on the above-described principles and taking into consideration fluoroquinolone and other resistance and eligibility for the shorter regimen.

Children who are not eligible for the standardized all-oral bedaquiline-containing regimen include those without bacteriological confirmation (e.g. with a clinical diagnosis); or without fluoroquinolone resistance ruled out (in their own specimens); or with drug-resistant EPTB other than peripheral lymphadenopathy; or with extensive pulmonary disease; or with prior exposure for more than 1 month to the medicines in the shorter regimen.

The standardized shorter all-oral bedaquiline-containing regimen may now be used in children of all ages under programmatic conditions.¹⁷ The eligibility criteria for this regimen for children with confirmed MDR/RR-TB are the same as for adolescents and adults: