A UCL-led international trial investigating the efficacy of tuberculosis (TB) treatment in children has resulted in a change in the World Health Organization’s global tuberculosis (TB) management guidelines.
The study, published in The New England Journal of Medicine, discovered that the majority of children with drug-sensitive tuberculosis can have their treatment duration reduced from six to four months, reducing the burden on families and healthcare systems around the world.
“It is estimated that nearly one-quarter of children with tuberculosis die, but the vast majority (90 percent) die because they are not diagnosed and started on treatment,” said Principal Investigator Professor Diana Gibb (MRC Clinical Trials Unit at UCL). Shorter treatment for children with non-severe tuberculosis saves on average $17 (£12) per child, which can be used to improve screening coverage and find missing children with tuberculosis.”
The SHINE study, conducted by researchers from UCL’s MRC Clinical Trials Unit in collaboration with partners in South Africa, Uganda, Zambia, and India, was the first randomized control trial to determine whether children with “minimal” tuberculosis could be effectively treated with a shorter course of treatment.
Minimal tuberculosis is non-severe lung or lymph gland tuberculosis in which the TB bacteria cannot be easily detected in the sputum using smear microscopy (smear negative). In 2020, an estimated 1.1 million children became ill with tuberculosis worldwide, and unlike adult patients, the majority of them (roughly two-thirds) had a non-severe form of the disease.
Despite the fact that children are more likely to have mild TB, their treatment duration has been based on the results of adult trials, which required six months of a combination of daily medicines. Children on TB treatment frequently miss school, which adds to the burden on caregivers.
For children with mild tuberculosis, the SHINE team discovered that four months of treatment with the same standard medicines was just as effective as a six-month treatment course.
The findings clearly demonstrated that children who received the shorter course performed just as well as those who received the standard six-month treatment, regardless of age, country, or HIV status, with few and similar side effects in both groups.
The evidence from SHINE was reviewed by the World Health Organization Guidelines Development Group, which recommended in August 2021 that a four-month regimen, rather than the standard six-month regimen, be used in children and adolescents with non-severe, presumed drug susceptible TB. Important considerations for determining eligibility for the shorter treatment regimen will be described in the WHO’s full consolidated guidelines, which will be released in March 2022, as well as in the operational handbook.
Dr. Chishala Chabala (University Teaching Hospital, Lusaka, Zambia), the lead investigator at the Zambian trial site, stated, “Children frequently present with mild disease.” They can now be treated with a shorter course if they are diagnosed on time. The SHINE findings provide an opportunity to improve the treatment of children with tuberculosis.”
The SHINE trial was supported by the Department of Health and Social Care, the Foreign, Commonwealth and Development Office, the Medical Research Council, and Wellcome. This UK-funded award is part of the European Union-supported EDCTP2 Programme.
“It’s fantastic to see that the trial results from this study have already been taken up in WHO TB guidelines,” said Jill Jones, Head of Global Health Strategy at the Medical Research Council.
“Because tuberculosis remains a major health burden for children, reducing treatment time by two months will have a significant impact on the health and well-being of TB-affected children.”