New NICE Guideline Updates Recommendations For Diagnosing Latent Tuberculosis

Main Category: Tuberculosis
Also Included In: Infectious Diseases / Bacteria / Viruses
Article Date: 23 Mar 2011 - 3:00 PDT


The National Institute for Health and Clinical Excellence (NICE) has today (23 March) published its clinical guideline on the diagnosis and management of tuberculosis, and measures for its prevention and control. A partial update of NICE clinical guideline 33 (published in March 2006), the new recommendations focus on the diagnosis of latent TB using interferon-gamma tests (IGT). All the other advice remains largely unchanged from the original guideline.

The guideline 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; in adults and children who are immunocompromised; healthcare workers and hard to reach populations.

TB is caused by a bacterium called Mycobacterium tuberculosis ('M. tuberculosis' or 'M.Tb'). It is spread by one person inhaling the bacterium in droplets coughed or sneezed out by someone with infectious tuberculosis. In over 80% of people the immune system kills the bacteria and they are removed from the body. However, in a small number of cases the TB bacteria are not killed and lie dormant (latent TB). 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.

New recommendations for diagnosing latent TB in the guideline include:

To diagnose latent TB in:

-- household contacts aged 5 years and older and non-household contacts of all people with active TB:

- A Mantoux test should be performed. Those with positive results (or in whom Mantoux testing may be less reliable - for example, people who have had the BCG vaccination) should then be considered for IGT.
- If Mantoux testing is inconclusive, refer the person to a TB specialist.

-- New entrants from high-incidence countries aged 5 - 15 years:

- Offer a Mantoux test followed by IGT if positive.

-- New entrants from high-incidence countries aged 16-34 years:

- Offer either IGT alone or a dual strategy. For people aged 35 years or older, consider the individual risks and benefits of likely subsequent treatment before offering testing.

-- New entrants from high-incidence countries aged under 5 years:

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

-- People who are immunocompromised:

- If latent TB is suspected in children and young people who are immunocompromised, refer to a TB specialist.

- 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 than 200 cells/mm3, perform an IGT and a concurrent Mantoux test. If either test is positive assess for active TB and consider treating for latent TB.

- For people with HIV and CD4 counts of 200-500 cells/mm3, perform an IGT alone or an IGT with concurrent Mantoux test. If either test is positive, assess for active TB and consider treating for latent TB.

Dr Fergus Macbeth, Director of the Centre for Clinical Practice at NICE, said: "Contrary to popular belief TB is not one of those diseases which, like smallpox, has been all but eradicated from our shores. In fact, latest figures show it is on the increase, particularly in our major cities. It is therefore important that the strategies that are used to detect the disease before it has the opportunity to develop into full-blown TB are as robust as possible and based on the best available evidence. When the original guideline was published NICE recommended further research to compare the latent TB diagnostic strategies of conventional skin test only, skin test then interferon gamma test if positive, and interferon gamma test only. Based on a detailed analysis of this further research, the independent Guideline Development Group has concluded that the relative benefit of IGT over the Mantoux test 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 after Mantoux testing."

NICE has produced a range of tools to help health professionals implement this guideline, including audit support, a costing tool and a slide set, all of which are available on the NICE website.

Notes

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 active 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. There are marked differences in the incidence of tuberculosis in different parts of England and Wales, with most new cases occurring in cities.

6. In 2009 in the UK, 9040 cases of tuberculosis were reported, an increase of 4.2% in the rate of the disease compared with 2008. The majority of cases continue to occur in the non-UK-born population (73%) and those aged 15-44 years (60%). From 2004 to 2009 the most common settings in which new cases of TB occurred were healthcare and education.

7. 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, nearly 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.

8. 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.

9. 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%.

10. 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.

11. 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.

About the guideline

12. The guideline, together with implementation tools to help health professionals put it into practice, is available on the NICE website.

13. The original NICE guidance published in 2006, 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.

14. 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?

Source:
NICE

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