Adult

2. Latent TB Infection Screening (before biologic drug therapy)

There is no single test for latent TB infection (LTBI): risk is determined by consideration of personal and epidemiological risk and supplemented by laboratory assays of TB exposure.

Prior to starting RED or AMBER biologic therapy, patients should be screened by:

  1. Interferon gamma release assay (IGRA)
  2. Symptom screen for active TB
  3. Chest X-ray
  4. ± TB risk factor assessment (if immunosuppressed – see 'Immunosuppressed – risk of false negative IGRA' table below)

Comments

  • LTBI testing and treatment should not delay the urgent treatment of serious disease; it is acceptable to proceed if the patient is believed to be low risk and has a reassuring chest X-ray.
  • Advice should be given about symptoms of active TB infection, and treating teams should be vigilant for these developing during treatment, particularly in those with risk factors for TB infection.
  • If the patient is being initiated on a GREEN drug but there is a high possibility that they will be switched to an AMBER/RED drug in the future, it is reasonable to undertake the full TB screen at this time as it is likely to be more accurate.
  • If past history of TB treatment, only screen for active TB as IGRA test is unhelpful.

1. Interferon gamma release assays (IGRAs)

These are tests of TB exposure.

To request IGRA:

  • Order on EPR: “TB Interferon gamma release, blood test (IGRA)”.
  • Ensure heparin blood (adult 8mls) arrives in Immunology (Churchill site) within 6 hours of venepuncture and before 3pm Monday - Thursday only.

Interpretation of results:

  • Positive IGRA: A positive IGRA increases the likelihood of LTBI, provided no history of prior LTBI or active TB treatment.
  • Negative IGRA: This suggests LTBI is unlikely. False negative results are more common in the pre-transplant or immunosuppressed population (see table below). Greater weight should be placed on the individual / epidemiological / radiological risk assessment
  • Indeterminate IGRA: Reduced T cell responses in the positive control may make the results uninterpretable. The assay can be repeated in the first instance, but if still indeterminate or negative, individual / epidemiological / radiological risk should be assessed.

Immunosuppressed – risk of false negative IGRA

End-stage renal failure, end-stage liver failure, advanced HIV infection, haematopoietic stem cell transplant (HSCT)

Receiving/have received in past 3/12:

  • 1 week high-dose corticosteroid (more than 40 mg/day prednisolone)
  • More than 2 weeks lower-dose corticosteroid (more than 20 mg/day prednisolone)
  • Non-biological immune modulating drugs (leflunomide, tacrolimus, more than 25 mg/week methotrexate, more than 3 mg/kg/day azathioprine, more than 1.5 mg/kg/day 6-mercaptopurine)

Receiving/have received in past 6/12:

  • Immunosuppressive chemotherapy or radiotherapy
  • Immunosuppressive therapy for a solid organ transplant

Receiving/have received in past 12/12:

  • Immunosuppressive biological therapy

2. Symptom screen for active TB

Latent TB infection is asymptomatic. The symptom screen is required to help exclude active TB before starting treatment for latent disease.

“At present, do you have any of the following symptoms*:”

  • A persistent cough (lasting more than 3 weeks)
  • Coughing up blood
  • Drenching night sweats
  • High temperatures
  • Unexplained weight loss
  • Unexplained loss of appetite
  • Lymphadenopathy

If the symptom screen suggests active TB, discuss with the TB Team.

* Not adequately explained by another disease process

3. Chest X-ray

  • A normal chest X-ray suggests pulmonary TB is unlikely.
  • There are multiple possible chest X-ray findings in pulmonary/pleural TB, including cavitation, consolidation, nodular changes, hilar / paratracheal lymphadenopathy, miliary changes or pleural effusion.
  • If the chest X-ray suggests active TB, consider CT chest and discuss with the TB Team. If the chest X-ray suggests old TB and no history of treatment, LTBI treatment may be warranted.

4. TB risk factor assessment (selected patients)

False negative IGRAs are more common in some immunosuppressed patients. Those with a negative IGRA when immunosuppressed should have an additional screen for TB risk factors.

If there are no additional risk factors, no symptoms on TB screening and a normal chest X-ray, they do NOT need latent TB treatment.

TB risk factors

High-incidence country of birth - born in a country with a high incidence of TB (greater than or equal to 40 / 100,000)

High-incidence country of residence - lived in a country for  3/12 or longer with a high incidence of TB (greater than or equal to 40 / 100,000) within the past 5 years

Any previous TB disease, inadequately treated (Infection Services can advise). Those with prior active TB treated adequately do not need LTBI treatment or TB prophylaxis at time of transplant

Close contact of someone with infectious TB. Those with prolonged, frequent or intense contact with a person with infectious TB (pulmonary / laryngeal) should be considered for LTBI treatment. Includes 'household contacts' – those who share a bedroom, kitchen, bathroom or sitting room with the index case. Close contacts may also include boyfriends or girlfriends and frequent visitors to the home of the index case.

Individuals working in close contact with subjects at increased risk of active TB – e.g. medically underserved, low-income populations, drug or alcohol abusers

 

Treating LTBI

The TB Clinic will typically oversee latent TB treatment.

Positive IGRA results should be referred to the TB service through EPR. Details available here.

For clinical queries, or if concern for ACTIVE TB disease, please contact the relevant Infection Consult service through EPR (‘Communicate’ – ‘Pool’ – ‘Infection Advice Churchill / Horton /JR1 & 2 & Cardiac Centre / NOC / West Wing and Trauma’).

References

  • Alkadi A, Alduaji N, Alrehaily A. Risk of tuberculosis reactivation with rituximab therapy. Int J Health Sciences. 2017; 11(2): 41-44
  • Bogas M, Machado P, Maurano AF, Costa L, Santos MJ, Fonseca JE et al. Methotrexate treatment in rheumatoid arthritis: management in clinical remission, common infection and tuberculosis. Results from a systematic literature review. Clin Rheumatol. 2010; 29(6): 629-635
  • Bua A, Ruggeri M, Zanetti S, Molicotti P. Effect of teriflunomide on QuantiFERON-TB Gold results. Med Microbiol Immunol. 2017; 26: 73-75
  • Clinical guideline: screening for latent TB infection prior to commencing biological therapy. University Hospitals Bristol NHS Foundation Trust; updated October 2018
  • Clinical guideline: Tuberculosis (TB) screening prior to initiating targeted and biologic agents including anti-tumour necrosis factor (TNF) drugs; Frimley Health NHS Foundation Trust. January 2024
  • Clinical guideline: Guideline for tuberculosis screening for biologic and immunomodulatory drugs for inflammatory conditions. Gloucestershire Hospitals NHS Foundation Trust; January 2023
  • Clinical guideline: TB screening for targeted and biologic agents: Prescribing including Anti-Tumour Necrosis Factor Drugs; Imperial College Healthcare NHS Trust. September 2020
  • Electronic Medicines Compendium (eMC). In: eMC. https://www.medicines.org.uk/emc. Accessed 1 May 2019
  • Epstein DJ, Dunn J, Deresinski S. Infectious complications of multiple sclerosis therapies: implications for screening, prophylaxis and management. Open Forum Infect Dis. 2018; 5(8):ofy174
  • Fernandez-Ruiz M, Meije Y, Manuel O, Akan H, Carratala J, Aguado JM, Delaloye J. ESCMID study group for infections in compromised hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (Introduction). Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2018; 24(Suppl 2): S2-9
  • Moiola L, Barcella V, Benatti S, et al. The risk of infection in patients with multiple sclerosis treated with  disease-modifying therapies: A Delphi consensus statement. Mult Scler. 2021; 27:331–346.
  • Winkelmann A, Loebermann M, Reisinger EC, Hartung HP, Zettl UK. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol. 2016; 12(4): 217-33
  • Martin L, Russell G (2021). ‘Anti-tumour necrosis alpha factor treatment, immunosuppression and chemotherapy prophylaxis’ in Kon OM (ed.) Tuberculosis in clinical practice. Switzerland: Springer Nature Switzerland AG, pp.311-326

Editorial Information

Last reviewed: 01 Jan 2025