Serial T-SPOT.TB responses in Tanzanian adolescents: Transient, persistent and irregular conversions

Area of Science:

• Immunology
• Infectious Diseases
• Clinical Trials

Background:

• Long-term variability of serial interferon-gamma release assays (IGRA) in healthy individuals in tuberculosis-endemic regions remains understudied.
• This variability is critical for interpreting tuberculosis (TB) vaccine trial outcomes, particularly those focused on preventing infection.

Purpose of the Study:

• To evaluate the long-term variability of serial interferon-gamma release assays (IGRA) in healthy adolescents.
• To assess the implications of IGRA variability for the design and interpretation of tuberculosis vaccine trials.

Main Methods:

• Prospective analysis of T-SPOT.TB assay results from 928 healthy adolescents over 3 years in Tanzania.
• Manual and automated reader analyses were compared, with a focus on quantitative spot-forming cell (SFC) counts for serial assay interpretation.

Main Results:

• High concordance (97%) between manual and automated T-SPOT.TB assay readings.
• An annual IGRA conversion rate of 2.9% was observed among initially IGRA-negative participants.
• Among converters, 35% were classified as 'irregular converters' with multiple, inconsistent assay results over time.

Conclusions:

• The definition and frequency of testing significantly impact the interpretation of IGRA conversion, reversion, and persistence.
• Observed IGRA fluctuations may indicate multiple subclinical infections, variable host immune responses, or assay variability.
• Findings necessitate careful consideration in designing and interpreting TB vaccine trials, with potential value in household contact studies to clarify transient IGRA conversions.