Study to compare two methods of treatment to prevent active tuberculosis (TB) in children

INTERVENTION: 1. The standard therapy will be daily self‐administered INH,10‐15 mg/kg/day for children (max=300mg/day) for 9 months (9INH) 2. As currently recommended vitamin B6 (pyridoxine) will be given with INH only to patients with risk factors for neuropathy ‐ malnutrition, alcoholism, diabetes, or renal insufficiency or HIV positive 3. The experimental arm will be daily self‐administered RIF, 10‐20 mg/kg/day for children (max=600mg/day) for 4 months (4RIF) 4. For children, dosing for both INH and RIF will be age and weight dependent, with highest doses for infants, and lowest for adolescents CONDITION: Tuberculosis ; Infections and Infestations ; Tuberculosis PRIMARY OUTCOME: To compare the rates of premature discontinuation of study therapy because of adverse events of all grades judged probably related to 4RIF or 9INH, by the majority of an independent panel of 3 reviewers, blinded to study drug SECONDARY OUTCOME: 1. To compare the rates of study drug completion of all children randomized to 4RIF or 9INH. Completion will be defined as taking at least 80% of total planned doses within 23 weeks for 4RIF, or within 52 weeks for 9INH; 2. To compare the rates of clinically diagnosed active TB as judged by an independent panel of paediatricians, up to 16 months post randomization in children who complete study therapy per protocol (efficacy); 3. To describe the occurrence of drug resistant microbiologically confirmed active TB among children randomized to the two arms, during 16 months post randomization INCLUSION CRITERIA: 1. Children (age <18) with documented positive tuberculin skin testing (TST) as defined below and prescribed 9INH for LTBI, for the indications below: Note: In the absence of a TST test, a positive QFT (or T‐Spot) (according to manufacturers recommendations) (see screening, recruitment and randomisation procedures) is equivalent to a TST of 10 mm. 1.1. HIV positive (TST >5 mm or QFT +) 1.2. Age 5 or less (TST >5 mm or QFT +) 1.3. Other reason for immuno‐compromised state ‐ such as therapy for malignancy or post‐transplant (TST >5 mm or QFT +) 1.4. Contact: with adult or adolescent with active contagious pulmonary TB TST >5 mm or QFT +) 1.5. Have both of the following factors if TST = 10‐14mm or QFT + or one factor if TST >15mm : 1.5.1. Arrival in Canada, Australia, or Saudi Arabia in the past 2 years from countries with estimated annual incidence of active TB greater than 100 per 100,000 1.5.2. Body mass index (BMI) less than 10th percentil