Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children

About two-thirds of children with tuberculosis have a nonsevere disease, which may be managed with a shorter regimen than the current 6-month regimen.

The present study enrolled children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. It randomized children younger than 16 years of age to 4 months (16 weeks) or six months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as per the World Health Organization guidelines. 

The study looked for unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss of follow-up, or death) by 72 weeks and excluded the participants who did not complete four months of treatment (modified intention-to-treat population). It also assessed safety as an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.

The study observed-

• Randomization of 1204 children (602 in each group). 
• The median age of the participants was 3.5 years (range, two months to 15 years), with 52% being male, 11% containing human immunodeficiency virus infection, and 14% suffering bacteriologically confirmed tuberculosis.
• Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. 
• 3% of participants in the 4-month group had a primary-outcome event, similar to 3% in the 6-month group.
• Including only 80% of participants who were independently adjudicated to have tuberculosis at baseline, the intention-to-treat, per-protocol, and key secondary analyses all showed noninferiority for four months of treatment. 
• 8% of participants experienced an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, 9 of which occurred within the first eight weeks, when the treatments were the same in the two groups).

This study proves the noninferiority of four months of antituberculosis treatment to 6 months in children with drug-susceptible, nonsevere, smear-negative tuberculosis. 

Turkova A, Wills GH, Wobudeya E, Chabala C. Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children. N Engl J Med 2022; 386:911-922. DOI: 10.1056/NEJMoa2104535