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There was no difference in outcomes between children with nonsevere tuberculosis (TB) treated for 4 or 6 months with standard first-line therapeutics, results from the SHINE trial showed.

In over 1,200 African and Indian children under the age of 16 with smear-negative, nonsevere TB, 3% of participants in both the 4- and 6-month groups had an unfavorable outcome (defined as TB recurrence or treatment failure, extension, or drug change), reported Anna Turkova, MD, of University College London, and colleagues.

This noninferiority was maintained in a per-protocol analysis and extended to key subgroups, according to findings in the .

"People think that a child with TB must be very sick -- that's not true. It is known that two-thirds of children who fall ill with TB every year have non-severe TB and therefore could be treated with shorter treatment," Turkova said in a press release.

Based on the results of this study, the World Health Organization (WHO) released a recommending the 4-month regimen over the 6-month regimen in children with non-severe, presumed drug-susceptible TB. Their full guidelines have yet to be published.

"This study elegantly shows the majority of children do not need a full 6 months of therapy and can be safely treated with 4 months of standard TB medications with good outcomes," said Nicole Salazar-Austin, MD, ScM, of Johns Hopkins University School of Medicine in Baltimore, who was not involved in the study.

"The drugs and formulations used are already in place and can be feasibly implemented in many high- and low-resource settings in the near future," she told 名媛直播.

The study also found that the 4-month treatment was more cost-effective, saving approximately $17 per child.

In 2020, 1.1 million children across the globe contracted TB, . In the U.S., TB is rare, with just over 7,000 reported cases in 2020 and only 317 cases in children 14 or younger, .

Children have historically been excluded from clinical trials for anti-TB treatments because of difficulties in obtaining respiratory specimens and low rates of bacteriologic confirmation of TB, and treatment guidelines for children are often extrapolated from adult trials, the study authors said.

"Such challenges were overcome with appropriate training, and samples were successfully obtained for tuberculosis testing in all 1,204 children who underwent randomization," the researchers said of their study.

The treatment course used in this trial consisted of 8 weeks of initial standard therapy for both groups with isoniazid, rifampin, pyrazinamide, and, depending on local guidelines, ethambutol. Afterwards, the 4-month group received an additional 8 weeks of standard therapy with isoniazid and rifampin, while the 6-month group continued standard therapy for 16 weeks. Treatments were given in a child friendly formula. Retention and adherence were both high, at 95% and 94%, respectively.

"Challenges remain in terms of the availability of child-friendly formulations of rifapentine and moxifloxacin, data on doses in children, and cost," Turkova and colleagues wrote. "However, our results show that a new regimen with new drugs is not necessary for the shortening of treatment in the majority of children with drug-susceptible tuberculosis, since such treatment shortening can be accomplished with the affordable, child-friendly, fixed-dose combinations that are already available."

There were 192 serious adverse events in 150 participants spread over both groups of the intervention. Twelve deaths occurred in the 4-month group and 19 occurred in the 6-month group. Of the 31 total deaths, 25 were in children younger than two, the researchers noted.

In addition, 66 participants were hospitalized for a respiratory bacterial infection. Of those, 26 participants in the 4-month group and 19 in the 6-month group were hospitalized after month 4 of treatment, Turkova and colleagues reported. Fifteen children experienced severe adverse drug reactions.

There were no significant differences between groups in time-to-event analyses of unfavorable status and death, the investigators said.

The open-label, clinical trial was conducted from 2016 to 2018 in the high TB burden countries of Uganda, Zambia, South Africa, and India -- 602 were randomly assigned to each group. The median age of the participants was 3.5 years, and 52% were male. Of note, 11% of children in this study were also diagnosed with HIV. Children with confirmed drug-resistance or known exposure to an adult with drug-resistant TB were excluded.

Two-thirds of the participants had respiratory TB alone, while only 3% had peripheral lymph node TB. Twenty nine percent had both.

In the study, nonsevere TB was determined in part by chest radiography. However, "there are some low-resource settings that will not be able to assess severity due to lack of chest radiography," Salazar-Austin pointed out.

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