World TB Day 2016: Treating TB faster
Researchers at the MRC Clinical Trials Unit at UCL are working on projects to tackle different forms of tuberculosis (TB) with shorter treatment programmes. The STREAM project is looking at multidrug-resistant TB, the TRUNCATE project is looking at drug sensitive TB, and the SHINE project is investigating new, shorter treatments for children with TB.
Tuberculosis kills three people every minute. Treatment invariably involves a long course of drugs and the burden of disease falls hardest on low-income countries with stretched health systems. Three projects are running at the MRC Clinical Trials Unit to investigate the efficacy of shorter courses of drugs in some of the countries worst affected by TB.
Each year sees around 500,000 new cases of multidrug-resistant TB (MDR-TB). Current treatments are lengthy, taking up to two years to complete, and ineffective: no more than half those treated have a good outcome. Many patients fail to adhere to the full WHO-recommended course of treatment because of its length and adverse effects. The STREAM trial, led by Professor Andrew Nunn and Professor Sarah Meredith, is assessing three much shorter regimens, two taking nine months and one taking six months to complete. Two of these regimens include the new drug bedaquiline which is the first TB drug in over 40 years to use a novel mechanism to treat the infection.
Professor Nunn comments that “the trial is helping to address a seriously neglected area of research: the need for acceptable and effective treatments for the growing number of patients with MDR-TB. If STREAM leads to positive results it could revolutionise treatment for a high proportion of people diagnosed. A 9-month fully oral regimen would not only help more patients to complete treatment but could also help to reduce the spread of drug resistant infection.”
The trial is currently being conducted in Ethiopia, Mongolia, South Africa and Vietnam. During 2016 additional sites are expected to be opened in Africa, Asia, South America and Eastern Europe.
Even where the infection is sensitive to a known drug, treatment courses usually last six months. Reducing treatment length could mean fewer cases of MDR-TB as it would create fewer opportunities for any resistance to develop. The TRUNCATE trial is hoping to cut the length of treatment by two thirds, Dr Patrick Phillips explains why:
“A two-month regimen would help patients return to work and normal routines sooner, but it’s also an attractive prospect for national TB programmes: many of the resources currently used for six months of treatment supervision for each patient could be diverted to improve case finding and widen access to treatment. We will be studying several combinations of the most promising new and established drugs to develop a new treatment strategy that’s at least as good as the current standard of care.”
The team will follow patients for two years and re-treat any who may relapse. Trials will begin this year in collaboration with the National University of Singapore in approximately 12 large TB treatment centres within an Asian TB trials network.
The SHINE trial will look at whether the standard six month regimen can be safely reduced to 4 months in children with minimal TB. Approximately one million children fall ill with TB each year, resulting in 140,000 deaths, but few trials have been conducted to test paediatric treatments. Instead, regimens for TB treatment in children have been adjusted from those used in adults.
Professor Diana Gibb explains more: “For most children with TB, the disease is caused by a small number of bacteria (minimal TB) which is different from adults who most frequently have more severe forms of TB caused by a larger number of bacteria. This makes it more likely that minimal TB in children could be successfully treated with a shorter treatment than required in adults. The SHINE trial is the first paediatric randomised trial to address this question. The shorter treatment would have major advantages for the child, their family and carers, and for over-burdened health systems, by reducing the number of clinic visits children need to make to take their drugs.”
A total of 1200 HIV-infected and uninfected children aged 12 years and younger will be enrolled from clinical centres in South Africa, Zambia, Uganda and India. These countries have been chosen because they have high burden of TB and to ensure that the trial results are applicable to different populations.
World Tuberculosis Day 2016
Improvements in treatment and detection mean that an estimated 43 million lives were saved between 2000 and 2014. However, the annual decline in cases of infection is slow and the deadline for the 2030 WHO Sustainable Development Goal for elimination looks unlikely to be met.
The MRC Clinical Trials Unit is hosting a TB symposium today with UCL and the London School of Health and Tropical Medicine. A number of researchers involved in the symposium have contributed papers to a special TB series in the Open Access journal BioMed Central Medicine.