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EDITORIAL
March 10, 2022
N Engl J Med 2022; 386:988-989
DOI: 10.1056/NEJMe2200966
Madhukar Pai, M.D., Ph.D., and Heather J. Zar, M.B., B.Ch., Ph.D.
Well before the Covid-19 pandemic disrupted tuberculosis care,1 long treatment duration has been a weak link in the continuum of care. But the past decade has been a turning point in the pioneering of shorter treatment and differentiated care, as opposed to the traditional, one-size-fits-all approach. Shortening of treatment is being achieved by exploiting longer-acting drugs, adding new drugs, or, for persons with nonsevere disease, targeting shorter regimens.2
For latent Mycobacterium tuberculosis infection, several shorter alternatives to the traditional 6 to 9 months of isoniazid therapy now exist, including a 3-month regimen of weekly rifapentine plus isoniazid or a 4-month regimen of daily rifampin.3 For drug-resistant tuberculosis, 6 months of oral-only regimens such as bedaquiline, pretomanid, and linezolid4 or these drugs plus moxifloxacin5 could replace the 24-month standard regimen. For drug-sensitive tuberculosis in adults, a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in a recent trial.6
Where does this leave children, a vulnerable group that is often excluded from randomized trials of new treatments? According to the World Health Organization, 1.1 million children worldwide became ill with tuberculosis in 2020, predominantly in low- and middle-income countries.7 Increasingly, childhood tuberculosis is also identified in the context of acute lower respiratory tract infection or pneumonia.8However, difficulties in confirming a diagnosis of tuberculosis (particularly a lack of microbiologic confirmation), a long duration of treatment, lack of easy access to fixed-dose palatable pediatric formulations, pill burden, and medication side effects are big challenges in treating children. It is therefore timely and commendable that Turkova et al. present in this issue of the Journal9 the results of the SHINE trial — a trial that included only children and showed that 4 months of treatment provided similar efficacy to a standard 6-month regimen for nonsevere tuberculosis.
This multicenter, open-label trial involved 1204 children with symptomatic, nonsevere (as assessed radiologically), smear-negative tuberculosis. The median age of the participants was 3.5 years, and 11% of them had human immunodeficiency virus (HIV) infection. In children with microbiologic confirmation of tuberculosis (14% of the trial population), only those with drug-susceptible cases were included. Participants were randomly assigned in a 1:1 ratio to receive either 4 months (16 weeks) or 6 months (24 weeks) of antituberculosis therapy. All the participants received 8 weeks of standard treatment with isoniazid, rifampin, and pyrazinamide as a fixed-dose formulation, with or without ethambutol; this treatment was followed by either 8 weeks or 16 weeks of isoniazid and rifampin in a fixed-dose combination. The primary outcome was unfavorable status (defined as treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks. ...
March 10, 2022
N Engl J Med 2022; 386:988-989
DOI: 10.1056/NEJMe2200966
Madhukar Pai, M.D., Ph.D., and Heather J. Zar, M.B., B.Ch., Ph.D.
Well before the Covid-19 pandemic disrupted tuberculosis care,1 long treatment duration has been a weak link in the continuum of care. But the past decade has been a turning point in the pioneering of shorter treatment and differentiated care, as opposed to the traditional, one-size-fits-all approach. Shortening of treatment is being achieved by exploiting longer-acting drugs, adding new drugs, or, for persons with nonsevere disease, targeting shorter regimens.2
For latent Mycobacterium tuberculosis infection, several shorter alternatives to the traditional 6 to 9 months of isoniazid therapy now exist, including a 3-month regimen of weekly rifapentine plus isoniazid or a 4-month regimen of daily rifampin.3 For drug-resistant tuberculosis, 6 months of oral-only regimens such as bedaquiline, pretomanid, and linezolid4 or these drugs plus moxifloxacin5 could replace the 24-month standard regimen. For drug-sensitive tuberculosis in adults, a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in a recent trial.6
Where does this leave children, a vulnerable group that is often excluded from randomized trials of new treatments? According to the World Health Organization, 1.1 million children worldwide became ill with tuberculosis in 2020, predominantly in low- and middle-income countries.7 Increasingly, childhood tuberculosis is also identified in the context of acute lower respiratory tract infection or pneumonia.8However, difficulties in confirming a diagnosis of tuberculosis (particularly a lack of microbiologic confirmation), a long duration of treatment, lack of easy access to fixed-dose palatable pediatric formulations, pill burden, and medication side effects are big challenges in treating children. It is therefore timely and commendable that Turkova et al. present in this issue of the Journal9 the results of the SHINE trial — a trial that included only children and showed that 4 months of treatment provided similar efficacy to a standard 6-month regimen for nonsevere tuberculosis.
This multicenter, open-label trial involved 1204 children with symptomatic, nonsevere (as assessed radiologically), smear-negative tuberculosis. The median age of the participants was 3.5 years, and 11% of them had human immunodeficiency virus (HIV) infection. In children with microbiologic confirmation of tuberculosis (14% of the trial population), only those with drug-susceptible cases were included. Participants were randomly assigned in a 1:1 ratio to receive either 4 months (16 weeks) or 6 months (24 weeks) of antituberculosis therapy. All the participants received 8 weeks of standard treatment with isoniazid, rifampin, and pyrazinamide as a fixed-dose formulation, with or without ethambutol; this treatment was followed by either 8 weeks or 16 weeks of isoniazid and rifampin in a fixed-dose combination. The primary outcome was unfavorable status (defined as treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks. ...
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