Table 2.
Regimens for treating pediatric TB infection and drug-susceptible TB (non-severe, severe, and meningitis and osteoarticular).
| Regimen | Drugs * | Interval of Administration |
Duration (Months) | Monitoring Considerations ** |
Preferred Regimen | Considerations for Use |
|---|---|---|---|---|---|---|
| TB Infection | ||||||
| 3HR ‡ | Isoniazid (H) Rifampicin (R) |
Daily | 3 | Evaluate monthly For CLHIV: TPT monitoring can be aligned with ART; Consider drug–drug interactions for CLHIV on ART and TPT *** |
If fixed-dose combination (FDC) available, preferred for HIV-negative children < 25 kg |
Children of all ages; child-friendly FDC (HR 50 mg/75 mg) is available; If FDC not available, for HIV-negative children <25 kg, WHO recommends 6H for those < 2 years, and 3HP or 6H for those ≥ 2 years of age. Pyridoxine for select patients. † |
| 3HP ‡ | Isoniazid (H) Rifapentine (P) |
Weekly (12 doses) | 3 | Preferred for PLHIV (>15 years), on TDF, EFV, DTG or RAL-based ART | Not for use in children < 2 years (Lack of data on appropriate rifapentine dosing); Pharmacokinetic and safety studies on 3HP and other rifapentine-based TPT in CLHIV on ART (lopinavir/ritonavir (LPV/r), DTG, NVP) are ongoing; WHO does not recommend 3HP for CLHIV. Take with food containing fat if possible. Pyridoxine for select patients. † |
|
| 4R | Rifampicin (R) | Daily | 4 | Children of all ages; No pediatric formulation available: rifampin tablet (300 mg) can be used in older children and adolescents; for younger children, pill crushing or compounding may be necessary. |
||
| 6H or 9H | Isoniazid (H) | Daily | 6 or 9 | Preferred for CLHIV on ART |
Children of all ages; Preferably use dispersible tablets in children; 3HR may be considered as an alternative regimen for children on EFV-based ART; Monitor for signs of H-induced hepatotoxicity. Pyridoxine for select patients. † |
|
| 1HP | Isoniazid (H) Rifapentine (P) |
Daily (28 doses) |
1 | 1HP is recommended by WHO as an alternative TPT regimen for HIV-negative children aged ≥13 years and > 25 kg and CLHIV ≥13 years if on TDF, EFV, DTG or RAL-based ART. Take with food containing fat if possible. Pyridoxine for select patients. † |
||
| Non-Severe Drug-Susceptible TB Disease | ||||||
| 2 months HRZ(E), 2 months HR |
Isoniazid (H) Rifampicin (R) Pyrazinamide (Z) ±Ethambutol (E) |
Daily | 4 | Evaluate bi-weekly during intensive phase and monthly thereafter | Children (3 months < 16 years) with non-severe pulmonary or peripheral lymph node disease |
Follow definitions for non-severe disease to determine eligibility. For young children, child-friendly, dispersible, and appropriate FDC available (R75/H50/Z150; R75/H50; E100) |
| Drug-Susceptible TB Disease | ||||||
| 2 months HRZ(E), 4 months HR |
Isoniazid(H) Rifampicin (R) Pyrazinamide (Z) ±Ethambutol (E) |
Daily | 6 | Evaluate bi-weekly during intensive phase; monthly thereafter | Children with severe disease and no presumptive drug resistance; children not responding to shorter regimen | Child-friendly formulations available (see above) |
| 2 months HPZM, 2 months (9 weeks) HPM |
Isoniazid (H) Rifapentine (P) Pyrazinamide (Z) Moxifloxacin (M) |
Daily | 4 | Evaluate bi-weekly during intensive phase and monthly thereafter | Children ≥ 12 years weighing ≥ 40 kg with drug-susceptible pulmonary TB | Child friendly formulations available for all medications (see above) including moxifloxacin (100 mg). No FDC for full regimen. Cost may be prohibitive in some settings [14]. |
| Drug-Susceptible TB Meningitis or Osteoarticular TB | ||||||
| 2 months HRZE 10 months HR |
Isoniazid (H) Rifampicin (R) Pyrazinamide (Z) Ethambutol (E) |
Daily | 12 | Evaluate bi-weekly or at clinician discretion | Children with TBM or osteoarticular TB | The optimal rifampicin dosages are still being evaluated but higher CSF penetration can be achieved with higher dosages (20–30 mg/kg) [14]. Child-friendly formulations available (see above) |
| 6 months HRZEto | Isoniazid (H) Rifampin (R) Pyrazinamide (Z) Ethionomide (Eto) |
Daily | 6 | Evaluate bi-weekly or at clinician discretion | Children with TBM | See above regarding optimal rifampicin dosages. Child-friendly formulations available for RHZE (see above), plus Eto 125 mg |
Table adapted from: Nolt D, et al. [38]; and Yuen CM, et al. [76], and informed by the WHO operational handbook [39]; * For more detailed dosing information, including dosing based on weight bands please see WHO operational handbook. ** Monitoring should focus on the following: (1) weight checks; (2) presence of TB symptoms; (3) presence of adverse events related to TBI and TB drug regimen; and (4) adherence to treatment. Routine laboratory monitoring is not necessary for healthy children and adolescents, but should be considered for those with immunocompromise, existing hepatic disease, or on other hepatotoxic medications. *** For more detailed information on TPT regimens to use with ART, please see WHO operational handbook on tuberculosis. † Select patients include exclusively breastfed infants, children and adolescents on meat or milk-deficient diets, symptomatic CLHIV, children with nutritional deficiencies, and pregnant females. ‡ WHO Guidelines are expected out in July 2024 that will directly impact age limitations for 3HR and 3HP.