A distinctive genetic 'signature' found in the blood of children with tuberculosis (TB) offers new hope for improved diagnosis of the disease.
TB is very difficult to diagnose in children and is often recognised late when the child is already critically ill and the disease has spread from the lungs to the brain or other organs. Now an international team of researchers has shown that the disease can be identified in over 80 percent of cases by looking at 51 specific genes in the blood of affected children.
The researchers hope the findings - published on 30 April in the New England Journal of Medicine - could be used to develop a cheap, quick and effective diagnostic test.
Lead researcher, Professor Michael Levin, Director of the Wellcome Centre for Clinical Tropical Medicine at Imperial College London, explained: "We urgently need better methods to diagnose TB in children, so treatment can be started earlier and to avoid unnecessary treatment of children who are wrongly diagnosed. The symptoms of TB in children are common to many other childhood diseases, and the standard tests used on adults are not effective in children. Although the disease is treatable, thousands of children still die each year due to late diagnosis and many more are left with damage to their brain, bones and lungs."
The study - funded through the EU and carried out at Wellcome Trust-supported units in Africa -looked at over 2,800 children admitted to hospitals in South Africa, Malawi and Kenya with symptoms of TB. The researchers identified those who had proven TB and those in whom TB was excluded as the cause of the child's illness.
Blood samples from the South African and Malawian children were examined to see which genes were activated or suppressed in those with the disease. The researchers found that TB could be distinguished from other diseases by looking at just 51 genes from over 30,000 in the human genome and seeing whether they were activated or suppressed. This information was used to give a single TB risk score for each child which, when tested in the Kenyan patients, accurately diagnosed over 80 percent of the children with TB.
Professor Levin said: "It has taken seven years and the combined efforts of clinicians and scientists in the UK, Africa and Singapore to identify this gene signature of childhood TB. What we now need is collaboration from biotechnology and industrial partners to turn these findings into a simple, rapid and affordable test for TB that can be used in hospitals worldwide."
According to World Health Organisation (WHO) statistics, TB is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent. A significant proportion of TB cases worldwide are children. An estimated 530,000 children became ill with TB in 2012 and 74,000 HIV-negative children died of TB.
Professor Brian Eley from the University of Cape Town, who led the clinical study in South Africa, said: "Childhood TB is a major problem in African hospitals. An accurate test for childhood TB would be an enormous breakthrough, enabling earlier diagnosis, reducing long hospital admissions for investigation of TB suspects, and limiting the number of children treated inappropriately."
Dr Suzanne Anderson from Brighton and Sussex Medical School, who led recruitment in Malawi, said: "This study has highlighted the benefit of research institutions in Europe collaborating with hospitals in Africa to apply sophisticated technology to major public health problems."
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Notes to editors:
1. Anderson et al. 'Diagnosis of childhood tuberculosis and host RNA expression in Africa. The New England Journal of Medicine, 1 May 2014. DOI: 10.1056/NEJMoa1303657. Download a copy of the paper (under embargo for 22.00 BST Wednesday 30 April 2014) using this link: https:/
2. WHO figures on TB from Fact Sheet 104, reviewed March 2014. http://www.
3. The research team involved:
- UK academic institutions (Imperial College London; London School of Hygiene and Tropical Medicine; Brighton and Sussex Medical School, University of Sussex; Liverpool School of Tropical Medicine, University of Liverpool)
- Wellcome Trust supported Institutions in Malawi, South Africa, Kenya and London (Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya; and Imperial College/Welcome Trust Centre for Clinical Tropical Medicine)
- The Genome Institute of Singapore.
4. About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.http://www.
5. About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.