A UCL-led international trial exploring the effectiveness of
tuberculosis (TB) treatment in children has led to a change in
the World Health Organisation’s global guidelines for
managing the disease.
The research, published in
The New England Journal of Medicine, found that the treatment duration for the majority of children
with drug sensitive tuberculosis can be shortened from six to
four months, thereby reducing the burden on families and
healthcare systems around the world.
Principal Investigator, Professor Diana Gibb (MRC Clinical
Trials Unit at UCL) said: “It is estimated that nearly one
quarter of children with TB die, but the vast majority (90%) die
because they are not diagnosed and started on treatment. A
shorter treatment for children with non-severe TB allows savings
of on average $17 (£12) per child, which can be used to
improve the screening coverage and find the missing children
with TB.”
Researchers from the MRC Clinical Trials Unit at UCL worked with
partners in South Africa, Uganda, Zambia and India on the SHINE
study, the first randomised control trial to assess whether
children with ‘minimal’ TB could be effectively
treated with a shorter course of treatment.
Minimal tuberculosis is non-severe lung or lymph gland
TB, where the TB bacteria cannot easily be found in the
sputum through smear microscopy (smear negative). In 2020
an estimated 1.1 million children fell ill with TB
globally, and unlike adult patients, most of them
(approximately two thirds) had a non-severe form of the
disease.
Yet despite children being more likely to have minimal
TB, until now their treatment length has been based on the
results of trials in adults, requiring six months of a
combination of daily medicines. As children on TB
treatment often stay home from school, this also increases
the burden on caregivers.
The SHINE team found that treatment for four months using
the same standard medicines was as beneficial as a
six-month treatment course for children with minimal TB.
Spending less time on treatment will mean fewer clinic
visits, as well as making it easier to complete the full
course of medicine. Savings to TB programmes can instead
be spent on improving access to screening and diagnostic
tests for the disease, which can be poor at lower-level
health facilities, as well as on training health care
workers.
First author, Dr Anna Turkova (MRC Clinical Trials Unit
at UCL) said: “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.”
The trial involved 1,204 children aged from two months up
to 16 years with non-severe TB, who were divided randomly
into two groups to take either four or six months of
treatment with anti-TB medicines. Of the enrolled
children, 11% were living with HIV. All children were
followed for 18 months after enrolment to see whether
their treatment had been successful.
The results clearly showed that children who received the
shorter course did as well as those on the standard
six-month treatment, regardless of the age group, country
or HIV status, with few and similar side effects in both
groups.
The evidence from SHINE was reviewed by the World Health
Organisation Guidelines Development Group, who recommended
in August 2021 that in children and adolescents with
non-severe, presumed drug susceptible TB, a four-month
regimen should be used rather than the standard six-month
regimen. Important considerations about how to determine
eligibility for the shorter treatment regimen will be
described in WHO’s full consolidated guidelines
coming out in March 2022 and in the operational
handbook.
Lead investigator at the Zambian trial site, Dr
Chishala Chabala (University Teaching Hospital, Lusaka,
Zambia), said: “Children are often presenting with
mild disease. If they are diagnosed on time, they can
now be treated with a shorter course. The SHINE results
are an opportunity to improve treatment of children with
TB.”
Trial paediatrician Dr Priyanka Anand Kulkarni (B.J.
Medical College, Pune, India) added: “For parents
it’s very challenging to manage the pill burden
and to motivate kids to complete the full duration of
treatment. The short treatment course can make it more
manageable.”
Children living with HIV who also have TB face problems
of having to take treatment for both diseases, which
complicates HIV treatment options. The shorter TB
treatment will help to reduce these issues.
While undertaking the trial, training and community
education helped to diagnose children with mild TB. The
SHINE team is now working with its South African
partners to improve ways of identifying children with
the disease. They hope to explore use of artificial
intelligence to read chest radiographs and help
clinicians distinguish between severe and non-severe
cases.
The SHINE trial was funded by the Joint Global Health
Trials scheme, including the Department for Health and
Social Care, the Foreign, Commonwealth and Development
Office, the Medical Research Council and the Wellcome
Trust. This UK-funded award is part of the EDCTP2
Programme supported by the European Union.
Jill Jones, Head of Global Health Strategy at the Medical
Research Council said: “It’s fantastic to see
that the trial results from this study have already been
taken up in WHO TB guidelines.
“TB remains a major health burden for children and
so reducing treatment time by two months will have a major
impact on the health and wellbeing of children affected by
TB.”
Additional partners included Stellenbosch University,
South Africa; University of Cape Town, South Africa;
National Institute for Research in Tuberculosis, India;
Radboud University Medical Center, the Netherlands;
International Union Against Tuberculosis and Lung Disease,
France; University of Melbourne, Australia; University of
York; Imperial College London and University Hospitals
Birmingham.
