Risk factors for TB among close IGRA-negative contacts of persons with infectious TB

Who

• Study population: Close contacts aged ≥2 years of laboratory-confirmed pulmonary TB patients in Singapore.

• Sample size: 60,377 unique contacts (62,724 observations) linked to 7,737 index TB cases.

• Key characteristics: Majority male, predominantly Chinese ethnicity, mostly Singapore residents; 75% of contacts were aged >25 years.

• Outcome group: 150 contacts (0.3%) who developed active TB disease despite being IGRA-negative.

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What

• Focus: Identification of risk factors for developing active TB disease among IGRA-negative close contacts.

• Key findings: Independent risk factors included:

  • Age >25 years

  • Malay ethnicity

  • Diabetes mellitus

  • End-stage renal failure

  • Exposure to smear-positive index cases

  • Family relationship with the index case

  • Exposure in dormitories or nursing homes

• Implications: IGRA-negative contacts with these risk factors have a substantially higher TB incidence than the general population, suggesting possible false-negative IGRA results and need for enhanced follow-up.

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When

• Study period: January 2014 to December 2022.

• Follow-up: Median time to TB disease development was 92 weeks after index case notification.

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Where

• Setting: Singapore.

• Program context: National Tuberculosis Programme (NTBP), using data from the national TB registry.

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Why

• To inform context-specific follow-up strategies for IGRA-negative close contacts, addressing uncertainty about residual TB risk after a negative IGRA result and supporting Singapore’s goal of reducing TB incidence to 10 per 100,000 by 2040.

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How

• Design: Retrospective cohort study.

• Inclusion criteria: Close contacts with a negative QuantiFERON-TB Gold Plus (QFT-Plus) result at 8 weeks post-exposure.

• Exclusions: Prior TB treatment or preventive therapy; screening with TB-SPOT only.

• Analysis:

  • Univariate analyses (chi-square, Fisher’s exact, Mann–Whitney U tests).

  • Multivariable logistic regression including variables with P <0.1 or strong prior evidence.

  • Model performance assessed using ROC curve (AUC = 0.79).

• Conclusion: Authors recommend reviewing IGRA retesting timing and extending follow-up to 24 months for high-risk IGRA-negative contacts.

Source: Tavitian-Exley, I., Kyaw, W.M., Kang-Yang, L.L., Foo, K., Boudville, I.C., Cutter, J.L. and Ng, D.H.L., 2024. Risk factors for tuberculosis among close IGRA-negative contacts of persons with infectious tuberculosis in Singapore. International Journal of Infectious Diseases, 147, p.107166.