Imperial College London

Scientists step towards improved diagnostic test for TB

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TB bacteria, shown as orange in a sputum sample.

TB bacteria, shown as orange in a sputum sample.

Scientists have discovered a signature of tuberculosis that can be detected in patients' blood, paving the way for an improved diagnostic test.

Tuberculosis (TB) is curable and preventable, but according to the World Health Organization, 1.4 million people died from the disease in 2011, 95 per cent of them in low- and middle-income countries.

In sub-Saharan Africa, where rates of TB are the highest in the world, current methods for diagnosis are unreliable, resulting in many people going untreated and spreading infection in their communities. The symptoms, such as persistent coughing and weight loss, are common to other diseases, and people can be infected with TB bacteria without becoming ill from it, which is known as latent TB infection.

In the new study, researchers found that active TB can be distinguished from latent TB and other diseases by looking at which genes are switched on in people with suspected disease. When genes are switched on, the genetic code is copied onto molecules called RNA, which can be detected in blood.

The current study, published in PLOS Medicine, used sophisticated, expensive technologies to reveal the RNA signature, but the researchers hope to use new technologies to develop a simple, low-cost test.

The usual technique for diagnosis of TB in Africa is to make the patient cough and examine the sputum under the microscope.  If the patient also has HIV, this can result in low levels of TB bacteria in the lungs, resulting in the test being negative. Growing bacteria from the sputum is a more sensitive test, but this takes about six weeks and isn’t available at most hospitals in Africa. Instead, doctors rely on clinical features and chest X-rays, but these don’t enable them to rule out other common chest infections such as pneumonia.

Immunological tests, which look for the immune system’s responses to TB bacteria, are used in the developed world where TB infection is less common, but they don’t distinguish active from latent TB.

In the new study, an international team of scientists led by Professor Michael Levin at Imperial College London used modern molecular techniques to determine which genes are switched on in patients with TB and whether the pattern of gene activity could act as a reliable indicator of the disease.

They recruited 584 patients with suspected TB at two clinics in South Africa and Malawi over four years and used a series of tests to get an accurate diagnosis. By analysing the patients’ blood samples, they found that RNA signatures could reliably distinguish TB from other conditions.

The researchers hope to use the findings to develop a simple, affordable test that can be used in African hospitals.

“Many patients with TB go undiagnosed because their symptoms overlap with other diseases,” said Professor Levin. “As a consequence, they infect family members and other people they come into contact with. Global TB control would be greatly improved if there was a test that reliably identified those who have the disease”.

“This study has proved the concept that RNA signatures can be used to make a reliable diagnosis. The challenge will be to translate that into a simple, cheap test suitable for use in Africa and other resource poor regions.

“There are some very exciting technologies for detecting RNA and DNA that could be applicable. We’re working with colleagues at Imperial who have expertise in these technologies and we’re also hoping that biotechnology companies will work with us to take up this challenge.”

The study was funded by an EU Action for Diseases of Poverty program grant and involved researchers at Imperial College London, London School of Hygiene & Tropical Medicine, Brighton and Sussex Medical School of University of Sussex and Liverpool School of Tropical Medicine in the UK; Wellcome Trust supported institutions in Malawi and South Africa (Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi; Clinical Infectious Diseases Research Initiative, Red Cross War Memorial Children’s Hospital, University of Cape Town) as well as the Genome Institute of Singapore.

Reference

Kaforou M, Wright VJ, Oni T, French N, Anderson ST, et al. (2013) Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using WholeBlood RNA Expression Signatures: A Case-Control Study. PLoS Med 10(10): e1001538. doi:10.1371/journal.pmed.1001538

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Sam Wong

Sam Wong
School of Professional Development

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