Issue date: 2 April 2003

130 hours: exposure time needed to contract tuberculosis

Groundbreaking new test for TB verified in students at centre of UK school outbreak

A new test which promises to revolutionise methods of TB diagnosis and control has been used in Britain's biggest outbreak of the disease since the second world war, which involved 324 people at a Leicestershire school.

In a remarkable stroke of luck, electronic school timetables allowed researchers to identify how many minutes each child spent sharing room air with the source case of infection. For the first time, researchers were able to determine the amount of exposure time needed to be sure of contracting TB infection, and the answer was 130 hours.

The study results published in this week's edition of the Lancet show the new rapid blood test, developed by Wellcome Trust researcher Dr Ajit Lalvani and his team at the University of Oxford, UK, is significantly more effective than the century-old tuberculosis skin-prick test for diagnosing TB infection. The researchers compared how the old and new tests correlated with the amount of exposure to the source case of TB in 535 school children.

The test enables doctors to screen people who have been in contact with an infectious TB sufferer and reliably identify those who are infected long before they actually develop the disease.

TB causes more deaths worldwide than any other infectious disease, with 8 million cases of active TB each year. In England and Wales alone, a total of 6669 tuberculosis cases were reported in 2001 a 6% increase over the previous year, according to the Public Health Laboratory Service.

Diagnosis and preventative treatment of people with early tuberculosis infection before they develop disease (active tuberculosis) is essential for TB control. The existing skin test for diagnosing early infection is inconvenient, takes 3 to 7 days before it can be read and gives 'false-positive' results in people vaccinated with BCG. In contrast, the new blood test is easy, rapid and not confounded by BCG vaccination - it uses TB proteins which genetic studies showed are present in the TB bacteria but not in the BCG vaccine.

Application of the blood test, known as ELISPOT, in the TB outbreak in the Leicestershire school indicates that it is set to supersede the skin test as the primary diagnostic test for tuberculosis infection. Working closely with Leicestershire Health Authority and the staff and students at the school, Lalvani and co-workers used their new test to investigate the outbreak and offer the best possible management to the children at risk of infection. Children who were more exposed to the student with full-blown tuberculosis (in terms of physical proximity and duration of exposure, such as children from the same class or school year) were significantly more likely to test positive with ELISPOT than with the skin test.

These results have important implications for future control of a disease whose incidence has increased markedly in recent years. Improvements in the early diagnosis of TB infection will enable more people to be treated while their infection is still dormant thus preventing them from developing full-blown tuberculosis which is highly infectious to others. Such precise and effective targeting of treatment will have substantial long-term benefits for public health, and could ultimately help health authorities and national TB control programmes to eliminate this disease.

The ELISPOT works in a unique way. Whereas conventional diagnostic tests rely on detecting antibodies induced by an infection, such antibodies are not generated by TB infection, which is why there has been no blood test until now. However, TB infection induces a strong response by immune cells in the blood called T-cells. It is these T-cells which are detected by the ELISPOT blood test. It appears that the oldest diagnostic test still in use is likely to be replaced by the first T-cell based test in medicine.

Dr Lalvani said: "Recent scientific advances have not yet resulted in any significant improvement in how we manage TB patients and their contacts, and diagnosis of early TB infection still relies on the 100-year old skin test. The ELISPOT is the first diagnostic test in medicine to work by detecting T-cells rather than antibodies, which is why it is so effective at detecting TB infection."

"We worked closely with the school and the local health authority in the midst of the outbreak to improve diagnosis for students at risk of TB infection. Our results have confirmed that ELISPOT is more accurate than the skin test. This means that our test is set to supersede the skin test and improve the control and prevention of this resurgent disease."

Further information

Dr Ajit Lalvani: 01865 221331
E-mail: ajit.lalvani@ndm.ox.ac.uk

Dr Shaun Griffin, Wellcome Trust Media Office: 020 7611 8612
E-mail: s.griffin@wellcome.ac.uk

Notes to Editors

The Wellcome Trust is an independent research-funding charity, established under the will of Sir Henry Wellcome in 1936. It is funded from a private endowment which is managed with long-term stability and growth in mind. The Trust's mission is to promote research with the aim of improving human and animal health. Website: www.wellcome.ac.uk