NICE Guideline 2016-Latent TB

Latent tuberculosis infection (LTBI) is a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active TB. A direct measurement tool for M. tuberculosis infection in humans is currently unavailable. One-third of the world's population is estimated to have LTBI: they do not have active TB disease but may develop it in the near or remote future, a process called "TB reactivation". The lifetime risk of reactivation for a person with documented LTBI is estimated to be 5–10%, with the majority developing TB disease within the first five years after initial infection. However, the risk is considerably higher in the presence of predisposing factors.

The National Institute for Health and Care Excellence (NICE) along with Tuberculosis. London (UK): National Institute for Health and Care Excellence (NICE)published the Guideline on Tuberculosis in Jan 2016. Following are its recommendations on Latent TB:

Diagnosing Latent TB in Children and Young People

Only consider using interferon-gamma release assays alone in children and young people if Mantoux testing is not available or is impractical. This includes for example, situations in which large numbers need to be tested (see the section "Incident and Outbreak Response" below and the recommendation under "Diagnosing Latent TB in All Age Groups" below). [new 2016]

Refer children younger than 2 years and in close contact with people with smear-negative pulmonary or laryngeal TB to a specialist to determine what testing strategy for latent TB should be done. This should be a paediatrician with experience and training in TB, or a general paediatrician with advice from a specialised clinician. [new 2016]

If a neonate has been in close contact with people with smear-positive pulmonary or laryngeal TB who have not had at least 2 weeks of anti-TB treatment:

• Assess for active TB (see under "Active TB" below).


• Start isoniazid (with pyridoxine).


• Carry out a Mantoux test after 6 weeks of treatment.


• If the Mantoux test is inconclusive, refer the child to a TB specialist.


• If the Mantoux test is positive (5 mm or larger, regardless of BCG history), reassess for active TB; if this assessment is negative, continue isoniazid (with pyridoxine) for a total of 6 months.


• If the Mantoux test is negative, reassess for active TB and consider an interferon-gamma release assay:
  
  
  
  • If the interferon-gamma release assay is negative then stop isoniazid (and pyridoxine) and give a BCG vaccination (see "BCG Vaccination" above)
  
  
  • If the interferon-gamma release assay is positive, reassess for active TB; if this assessment for active TB is negative, continue isoniazid (with pyridoxine) for a total of 6 months. [new 2016]
  
  
  
  

If a child aged between 4 weeks and 2 years has been in close contact with people with smear-positive pulmonary or laryngeal TB who have not had at least 2 weeks of anti-TB treatment:

• Assess for active TB.


• Start treatment for latent TB (see "Managing Latent TB in All Age Groups" and "Managing Latent TB in Children and Young People" below) and carry out a Mantoux test.


• If the Mantoux test is inconclusive, refer the child to a TB specialist.


• If the Mantoux test is positive (5 mm or larger, regardless of BCG history), reassess for active TB; if this assessment is negative, complete treatment for latent TB.


• If the Mantoux test is negative, continue treatment for latent TB, reassess for active TB after 6 weeks and repeat the Mantoux test:
  
  
  
  • If the Mantoux test is negative, consider an interferon-gamma release assay.
  
  
  • If the interferon-gamma release assay is negative, treatment for latent TB may be stopped; give a BCG vaccination if the child has not already had one.
  
  
  • If either test is positive, reassess for active TB; if this assessment is negative, complete treatment for latent TB. [new 2016]
  
  
  
  

If a child or young person aged between 2 and 17 years has been in close contact with people with pulmonary or laryngeal TB:

• Offer Mantoux testing.


• If the Mantoux test is inconclusive, refer the child or young person to a TB specialist.


• If the Mantoux test is positive (5 mm or larger, regardless of BCG history), assess for active TB; if this assessment is negative, offer them treatment for latent TB infection.


• If the initial Mantoux test is negative, offer an interferon-gamma release assay after 6 weeks and repeat the Mantoux test.[new 2016]

Immuno compromised Children and Young People

If latent TB is suspected in children and young people who are anticipated to be or are currently immuno compromised (for example, if they are from a high incidence country or have been in close contact with people with suspected infectious or confirmed pulmonary or laryngeal TB), refer to a TB specialist. [2016]

Diagnosing Latent TB in All Age Groups

New Entrants from High-Incidence Countries

Offer Mantoux testing as the initial diagnostic test for latent TB infection in people who have recently arrived from a high-incidence country who present to healthcare services. If the Mantoux test is positive (5 mm or larger, regardless of BCG history):

• Assess for active TB (see recommendations under "Active TB" below) and


• If this assessment is negative, offer them treatment for latent TB infection (see recommendations under "Managing Latent TB in All Age Groups," "Managing Latent TB in Adults, and "Managing Latent TB in Children and Young People" below).

If Mantoux testing is unavailable, offer an interferon-gamma release assay. [new 2016]

Contacts – Incident Situation

In an incident situation when large numbers of people may need to be screened, consider a single interferon-gamma release assay for people aged 18 to 65 years. For children and young people, follow recommendations under "Diagnosing Latent TB in Children and Young People" above. [2011, amended 2016]

Under-served Groups

Offer people younger than 65 years from under-served groups a single interferon-gamma release assay. [2011, amended 2016]

Substance misuse services with access to an interferon-gamma release assay should provide testing for people younger than 65 years who misuse substances if they:

• Live in a high incidence area


• Are likely to be involved with substance misuse services or other support services on a regular basis (for example, for opioid substitution therapy), when support should be available for directly observed preventive therapy [2012, amended 2016]

In high incidence areas (and at prisons that receive prisoners from high incidence areas), prison health services should offer an interferon-gamma release assay for TB to inmates younger than 65 years who are in regular contact with substance misuse services or other support services. This is provided arrangements have been made for this support to continue after release.[2012, amended 2016]

Substance misuse services and prison health services should incorporate interferon-gamma release assay testing with screening for hepatitis B and C, and HIV testing. They should refer prisoners and people who misuse substances with positive interferon-gamma release assays to local multidisciplinary TB teams for further clinical investigations. For prisoners, these investigations should be done in the prison if practically possible. [2012, amended 2016]

If the interferon-gamma release assay is positive, assess for active TB (see sections under "Active TB" below); if this assessment is negative, offer them treatment for latent TB infection (see recommendations under "Managing Latent TB in All Age Groups," "Managing Latent TB in Adults, and "Managing Latent TB in Children and Young People" below). [new 2016]

Managing Latent TB in All Age Groups

Be aware that certain groups of people with latent TB are at increased risk of going on to develop active TB, including people who:

• 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 [new 2016]

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:

• 3 months of isoniazid (with pyridoxine) and rifampicin or


• 6 months of isoniazid (with pyridoxine) [new 2016]

Base the choice of regimen on the person's clinical circumstances. 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 [new 2016]

Clearly explain the risks and potential benefits of each treatment regimen. In discussion with the person, select a suitable regimen if they wish to proceed with preventive treatment. [new 2016]

If a person also has severe liver disease, for example, Child-Pugh level B or C, work with a specialist multidisciplinary team with experience of managing TB and liver disease. [new 2016]

Manage treatment with caution, ensuring careful monitoring of liver function, in:

• People with non-severe liver disease


• People with abnormal liver function (including abnormal transaminase levels) before starting treatment for latent TB infection


• People who misuse alcohol or drugs [new 2016]

Ensure people having treatment for latent TB who also have social risk factors, such as misusing alcohol or drugs or being homeless, are linked to support services. They should also have an assessment of social needs and stability, including potential barriers to adherence or treatment completion (see recommendations under "Adherence, Treatment Completion and Follow-up" below). [new 2016]

People in the groups listed in the first recommendation in this section who do not have treatment for latent TB, as specified in the recommendations above, for any reason 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 (see recommendations under "Providing information for the Public about TB" above). [new 2016]

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. [new 2016]

Offer testing for HIV before starting treatment for latent TB. See NICE guidelines on increasing the uptake of HIV testing among black Africans in England and increasing the uptake of HIV testing among men who have sex with men . [new 2016]

Offer adults testing for hepatitis B and C before starting treatment for latent TB. See the NICE guideline on hepatitis B and C: ways to promote and offer testing to people at increased risk of infection and the NGC summary of the NICE guideline Hepatitis B (chronic). Diagnosis and management of chronic hepatitis B in children, young people and adults. [new 2016]

Managing Latent TB in Children and Young People

Consider testing children and young people for hepatitis B and C before starting treatment for latent TB. See NICE guideline onhepatitis B and C: ways to promote and offer testing to people at increased risk of infection

and the NGC summary of the NICE guideline Hepatitis B (chronic). Diagnosis and management of chronic hepatitis B in children, young people and adults. [new 2016]

To read the full guideline click on the following link:

https://www.nice.org.uk/guidance/ng33/chapter/Recommendations#latent-tb