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The National Institute for Health and Clinical Excellence (NICE) has today (8 July) published its draft clinical guideline on diagnosing latent TB in children and adults. A partial update of its 2006 guideline, the draft focuses on the diagnosis of latent TB using tuberculin skin tests (TST, also known as Mantoux and Heaf tests) and the newer interferon-gamma tests (IGT). The draft addresses which diagnostic strategy is most accurate in diagnosing latent TB in adults and children who are recent arrivals from countries where TB is highly prevalent; in adults and children who have been in close contact with patients with active TB, and in adults and children who are immunocompromised.

The original NICE guidance recognised that there was a lack of good quality evidence to show whether interferon-gamma tests are acceptable to patients and are more effective than tuberculin skin tests for predicting subsequent development of active TB, or diagnosing or ruling out current active TB. NICE therefore recommended further research to compare the strategies of skin test only, skin test then interferon gamma test if positive, and interferon gamma test only. Concern was also raised about the appropriateness of IGT use in current clinical practice during the planned review process for the original NICE guideline on the diagnosis and management of TB.

Based on a detailed analysis of this further research, the independent Guideline Development Group (GDG) has concluded that the relative benefit of IGT over TST in determining the need for treatment of latent TB infection is not certain - and in the case of younger children it feels that IGT may even perform less well. However, the GDG has made recommendations in populations where they considered IGT to be of clear benefit, especially in cases where IGT would reduce the uncertain diagnosis of TST. Recommendations in the draft guideline therefore include the following:

To diagnose latent TB in:

• Household contacts 5 years and older, non household contacts and adult contacts:

- A Mantoux test should be performed. Those with positive results (or in whom Mantoux testing may be less reliable) should then be considered for IGT.

• Recent arrivals from highly prevalent countries aged 5 - 34 years:

- Offer a Mantoux test followed by IGT if positive.

• Recent arrivals from highly prevalent countries aged 16 years and above:

- An IGT test alone can be used.

• Recent arrivals from highly prevalent countries aged under 5 years:

- Use Mantoux as the initial test. If positive, taking into account BCG history, undertake clinical assessment to exclude active disease and consider treatment of latent TB.

• People who are immunocompromised:

- For people with HIV and CD4 counts (also called T-cells, these are types of cells that help protect the body from infection) of less that 200, perform both an IGT test and a TST. If either test is positive assess for active TB. Consider treatment of latent TB if active disease is excluded.

- For people with HIV and CD4 counts of 200-500, perform an IGT test alone or and IGT test with concurrent TST. If either test is positive, assess for active TB. Consider treatment of latent TB.if active disease is excluded.

Dr Fergus Macbeth, Director of the Centre for Clinical Practice at NICE said: "If TB is left untreated it can be very serious or fatal but antibiotic treatments are highly effective. Up to 15% of adults with latent TB will go on to develop active TB at some point in their lives and the risk in children may be much higher. In people who are immunocompromised - for example, if they are HIV positive - the chance of developing active TB within five years of infection is up to 50%. Detection of latent TB is therefore important in controlling the disease.

He continued: "The newer interferon gamma tests for latent TB may offer some advantages over the current internationally recognised standard test - the Mantoux test. However, despite the studies that have been carried out since the original NICE TB guidance was published, important questions remain unanswered about the potential role of these new tests in clinical practice in the UK. The draft guideline therefore adopts a cautious, pragmatic approach by recommending that for many cases the most effective way to diagnose latent TB infection is a Mantoux test followed, depending on the result, by an IGT test."

Stakeholders wishing to submit their comments on the draft guideline are invited to do so via the NICE website by 5 August 2010. NICE plans to publish its final guideline in December 2010.

Notes to Editors

About tuberculosis

1. Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, also known as 'the tubercle bacillus'. TB commonly affects the lungs, but can also affect other parts of the body. The symptoms of TB are varied and depend on the site of infection. General symptoms may include fever, loss of appetite, weight loss, night sweats and tiredness.

2. TB is usually spread by coughs, but prolonged close contact with a person with TB is usually necessary for infection to be passed on. It can take many years for a person infected with M. Tuberculosis to develop active TB.

3. Latent TB is where the person has been exposed to the tubercle bacillus, which remains in the body, but where there are no symptoms of TB.

4. In the UK, although the introduction of the universal programme of BCG vaccination significantly reduced rates from around 50,000 cases in the 1950s, TB is still an important public health issue, with some 8500 cases each year.

5. Although rates of the disease are now very low in some parts of the country, in other areas, mainly cities, rates of the disease are higher and, in some cases, increasing. For example, two in every five cases of TB occur in London. Specific groups are disproportionately affected by TB, including the homeless and those in poor housing, new entrants, particularly those who come from areas that have a high prevalence of TB and those living in inner city areas.

6. Almost all cases of clinical TB in the UK contract the disease by breathing in infected respiratory droplets from a person with infectious respiratory active TB disease. The initial infection may either be eliminated, remain latent, or progress to active TB over the following weeks or months.

7. In people with latent TB, 10-15% of adults will go on to develop active TB at some point in their lives and the risk in children may be much higher. However, in people who are immunocompromised (for example, if they are HIV positive), the chance of developing active TB within 5 years of infection is up to 50%.

About the draft guideline

1. There is no gold-standard test for latent tuberculosis. Diagnosis has in the past relied on the TST but this has poor specificity if there has been BCG vaccination or exposure to environmental (non-tuberculous) mycobacteria, which can lead to false positive results. The test results have to be interpreted within a certain timescale, and patients who do not return, or delay returning, will have either no result or a possibly inaccurate one.

2. recently, selective immunological (interferon-gamma, or IGT) tests have been developed using two tuberculosis antigens, ‘early secretion antigen target 6’ (ESAT-6 ) and ‘culture filtrate protein 10’ (CFP-10), which are not present in BCG, and are found in only a few species of environmental mycobacteria. These tests can be done on either cells or cell products derived from whole blood. These tests aim to be more specific by removing false positive results, and to be better correlated with latent infection or dormant organisms.

3. NICE was asked by the Dept of Health to produce a short clinical guideline on interferon-gamma immunological testing for diagnosing latent TB (partial review of CG33) and make recommendations on:

• Which diagnostic strategy is most accurate in diagnosing latent tuberculosis in adults and children who are recent arrivals from highly prevalent countries?
• Which diagnostic strategy is most accurate in diagnosing latent tuberculosis in children?
• Which diagnostic strategy is most accurate in diagnosing latent tuberculosis in adults and children (children considered as a separate population) who have been in close contact with patients with active tuberculosis?
• Which diagnostic strategy is most accurate in diagnosing latent tuberculosis in immunocompromised patients?

4. The draft clinical guideline is available on the NICE website from 8 July 2010.

About NICE

1. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.

2. NICE produces guidance in three areas of health:

• public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
• health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS
• clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.