Clinical Pearls & Morning Reports

By Carla Rothaus

Published March 9, 2022


How did 4 months of antituberculosis treatment compare with 6 months in the trial by Turkova et al.?

Turkova et al. investigated whether 4 months of antituberculosis treatment would be as good as 6 months of treatment in children living in Uganda, Zambia, South Africa, and India who had presumably nonsevere, drug-susceptible tuberculosis. Read the NEJM Original Article here.

Clinical Pearls

Q: What are the treatment recommendations for children with tuberculosis based on?

A: More than 1 million children become ill with tuberculosis annually, and almost 20% of them die, but children have historically been excluded from clinical efficacy trials of antituberculosis treatment. This situation is due in part to low rates of bacteriologic confirmation of disease among children, given high rates of paucibacillary disease and difficulties in obtaining respiratory specimens. Treatment recommendations for children are therefore extrapolated from trials involving adults for which the criteria for treatment entry have often included smear-positive respiratory disease.

Q: Is tuberculosis typically a severe illness in children?

A: In contrast to adults, most children have nonsevere, smear-negative tuberculosis. Although spontaneous resolution has been described, it is generally agreed that treatment is appropriate in children with mild forms of tuberculosis because of the risk of disease progression and dissemination, particularly among the youngest children or those with concurrent human immunodeficiency virus infection. It is likely that nonsevere forms of tuberculosis could be treated with shorter durations of therapy, but data are limited regarding the shortening of treatment for drug-susceptible tuberculosis in children. Current international guidelines recommend 6 months of antituberculosis treatment in children, which is the same duration as in adults.

Morning Report Questions

Q: How did 4 months of antituberculosis treatment compare with 6 months in the trial by Turkova et al.?

A: The trial showed the noninferiority of 4 months as compared with the standard 6 months of treatment. The primary efficacy outcome was unfavorable status by 72 weeks. Unfavorable status was defined as a composite of tuberculosis events (treatment failure, including treatment extension beyond the replacement of missed doses, antituberculosis-treatment drug change or restart due to suspected treatment failure, and tuberculosis recurrence as adjudicated by the end-point review committee), loss to follow-up during treatment, or death from any cause. In the primary modified intention-to-treat analysis, an unfavorable status was observed in 16 participants (3%) in the 4-month group and in 18 participants (3%) in the 6-month group (unadjusted difference, −0.3 percentage points; 95% confidence interval [CI], −2.3 to 1.6; adjusted difference, −0.4 percentage points; 95% CI, −2.2 to 1.5). 

Q: How do Turkova et al. describe the strengths and limitations of their trial?

A: The authors note that the trial had several strengths. It was well-powered, and the authors observed 94% adherence (to the receipt of ≥80% of the doses) in the assigned groups and 95% retention of trial participants. The trial also has several limitations. One limitation is that this trial was open-label, which had the potential to result in more frequent treatment extensions in the 4-month group, contributing to more unfavorable outcomes in this group. Despite this possible disadvantage in the 4-month group, the results showed consistently that the 4-month regimen was as good as the 6-month regimen. Another limitation relates to the generalizability of the results to settings where chest radiographs are not available for characterizing nonsevere tuberculosis.

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