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Diagnosis and treatment of latent TB

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Consult expert advice.

The NICE guideline provides guidance based on whether a patient has latent TB (evidence of previous infection and TB is dormant) or have active TB (an ongoing TB related illness such as pulmonary TB)

Treatment of latent TB infection should be considered for people in the following groups, once active TB has been excluded by chest Xray and examination

  • people identified through screening who are:
    • 35 years or younger (because of increasing risk of hepatotoxicity with age)
    • any age with HIV
    • any age and a healthcare worker
    • and are either:
      • Mantoux positive (6 mm or greater), and without prior BCG vaccination,
      • or strongly Mantoux positive (15 mm or greater), interferon-gamma positive, and with prior BCG vaccination

  • children aged 1-15 years identified through opportunistic screening to be:
    • strongly Mantoux positive (15 mm or greater), and
    • interferon-gamma positive (if this test has been performed),
    • and without prior BCG vaccination

  • people with evidence of TB scars on chest X-ray,
    • and without a history of adequate treatment

  • people with HIV who are in close contact with people with sputum-smear-positive respiratory TB should have active disease excluded and then be given treatment for latent TB infection

  • for people, including those with HIV, aged younger than 65 years with evidence of latent TB who have been in close contact with people who have suspected infectious or confirmed active pulmonary or laryngeal drug-sensitive TB, offer either of the following drug treatments (4):
    • 3months of isoniazid (with pyridoxine) and rifampicin or
    • 6months of isoniazid (with pyridoxine)

  • base the choice of regimen on the person's clinical circumstances (4). Offer:
    • 3 months of isoniazid (with pyridoxine) and rifampicin to people younger than 35 years if hepatotoxicity is a concern after an assessment of both liver function (including transaminase levels) and risk factors
    • 6 months of isoniazid (with pyridoxine) if interactions with rifamycins are a concern, for example, in people with HIV or who have had a transplant
  • managing latent TB in adults
    • for adults between the ages of 35 and 65 years, offer drug treatments only if hepatotoxicity is not a concern
    • offer testing for HIV before starting treatment for latent TB
    • offer adults testing for hepatitis B and C before starting treatment for latent TB

  • people eligible for treatment of latent TB infection, but who decline to take this treatment, should be given 'Inform and advise' information about TB and have chest X-rays at 3 and 12 months later
    • for guidance concerning treatment of latent TB in children under the age of 16 years then consult the full guidance (1)

Notes (1)

  • certain groups of people with latent TB are at increased risk of going on to develop active TB, including people who:
    • Be aware that certain groups of people with latent TB are at increased risk of going on to develop active TB, including people who (4):
      • are HIV-positive
      • are younger than 5 years
      • have excessive alcohol intake
      • are injecting drug users
      • have had solid organ transplantation
      • have a haematological malignancy
      • are having chemotherapy
      • have had a jejunoileal bypass
      • have diabetes
      • have chronic kidney disease or receive haemodialysis
      • have had a gastrectomy
      • are having treatment with anti-tumour necrosis factor-alpha or other biologic agents
      • have silicosis

    • if a patient is in one of these groups then s/he should be advised of the risks and symptoms of TB, on the basis of an individual risk assessment, usually in a standard letter of the type referred to as 'Inform and advise' information

  • a meta-analysis revealed that commercial interferon-gamma release assays have high specificity but suboptimal sensitivity for detecting latent TB (3)

  • neonates who have been in close contact with people with sputum-smear-positive TB who have not received at least 2 weeks' anti-tuberculosis drug treatment should be treated as follows
    • the baby should be started on isoniazid (according to the current 'British national formulary for children' for 3 months and then a Mantoux test performed after 3 months' treatment
      • if the Mantoux test is positive (6 mm or greater) the baby should be assessed for active TB
        • f this assessment is negative, then isoniazid should be continued for a total of 6 months
      • if the Mantoux test is negative (less than 6 mm), it should be repeated together with an interferon-gamma test. If both are negative then isoniazid should be stopped and a BCG vaccination performed

  • BCG-vaccinated children older than 4 weeks but younger than 2 years, in close contact with people with sputum-smear-positive respiratory TB, should be treated as follows
    • the child should have a Mantoux test. If this is positive (15 mm or greater), the child should be assessed for active TB

       
      • if active TB is excluded, then treatment for latent TB infection should be given

      • if the result of the test is as expected for prior BCG (less than 15 mm), it should be repeated after 6 weeks together with an interferon-gamma test

      • if the repeat Mantoux test is also less than 15 mm, and the interferon-gamma test is also negative, no further action is needed

      • if the repeat Mantoux test becomes more strongly positive (15 mm or greater and an increase of 5 mm or more over the previous test), or the interferon-gamma test is positive the child should be assessed for active TB
        • if active TB is excluded, treatment for latent TB infection should be given

Reference:

  1. NICE (March 2011). Tuberculosis Clinical diagnosis and management of tuberculosis, and measures for its prevention and control
  2. MeReC bulletin (2003); 14(3):9-12.
  3. Menzies D et al. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med. 2007 Mar 6;146(5):340-54.
  4. NICE (May 2016). Tuberculosis

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