QuantiFERON-TB Gold Plus CD8+ T cell responses in contacts with TB disease and recent TB infection

Who

• Participants: Close contacts of pulmonary or laryngeal tuberculosis (TB) cases in Singapore

• Population size:

  • 22,355 contacts attended screening

  • 19,397 had valid QFT-Plus results

• Eligibility: Immunocompetent individuals ≥5 years old (QFT-Plus); immunocompromised contacts received T-SPOT.TB; children <5 years received TST

• Key subgroups:

  • Contacts with TB disease

  • “Stringent Converters” (recent TB infection)

  • All others with TB infection (likely remote infection)

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What

• Study focus: Evaluation of the CD8⁺ T-cell response measured by the QFT-Plus assay for its ability to:

  • Predict active TB disease

  • Identify recent TB infection (TBI)

• Key findings:

  • TB disease and recent TBI (stringent conversion) were significantly associated with stronger CD8⁺ responses (TB2–TB1 IFN-γ >0.6 IU/mL)

  • TB2 tube responses increased diagnostic sensitivity for TB disease (from 84.6% to 95.2%)

  • Higher IFN-γ levels in TB1 and TB2 tubes were observed in TB disease and recent TBI compared with other TBI cases

• Conclusion: CD8⁺ IFN-γ responses in QFT-Plus may help identify individuals at higher risk of TB disease or recent infection who could benefit from further investigation or TB preventive treatment (TPT)

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When

• Data collection period: January 2018 to October 2018

• Relevant program timeline:

  • TPT implemented since 1998

  • QFT-GIT introduced from 2006

  • QFT-Plus used from December 2017

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Where

• Setting: Nationwide TB contact screening in Singapore

• Clinical site: TB Contact Clinic (TBCC)

• Laboratory: Tan Tock Seng Hospital Microbiology Laboratory

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Why

• To improve identification of:

  • Individuals with active TB disease

  • Those with recent TB infection, who are at higher risk of progression

• To assess whether CD8⁺ responses in QFT-Plus add value beyond standard IGRA positivity in a setting with high background TB infection

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How

• Study design: Retrospective observational analysis

• Testing strategy:

  • Initial and post-window QFT-Plus testing (≥8 weeks after exposure)

  • Chest radiography for IGRA-positive or high-risk contacts

• Key definitions:

• Stringent Converters: IFN-γ increase from <0.35 to >0.7 IU/mL, excluding results in the uncertainty zone

• CD8⁺ response: TB2–TB1 IFN-γ difference >0.6 IU/mL

Source: Chee, C.B.E., Kyi-Win, K., Tan, S. and Wang, Y.T., 2025. QuantiFERON-TB Gold Plus CD8+ T cell responses in contacts with tuberculosis disease and recent tuberculosis infection. Microbiology Spectrum, 13(12), pp.e01353-25.