Quantitative interferon gamma responses to Mycobacterium tuberculosis in a community-based survey of adolescents and adults in Blantyre, Malawi

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Abstract Background Binary interpretation of Mycobacterium tuberculosis (Mtb) interferon gamma release assay (IGRA) results discards information about recency of exposure and disease risk. We analysed quantitative IGRA responses to Mtb in a community-based survey to investigate associations with response magnitude and inform understanding of transmission dynamics. Methods We included QuantiFERON-TB Gold Plus (QFT-Plus) results from 2,895 participants (10-40 years old) in Blantyre, Malawi. Bayesian regression models assessed the probability of a positive response (≥0.35 IU/mL), response magnitude, and associated factors. We also investigated associations with a TB2-TB1 differential >0.6 IU/mL (proposed to reflect recent transmission), and how hypothetical alternative IGRA positivity thresholds affected inference about age- and sex-specific transmission. Results 17.4% (503/2,895) of participants had positive TB1 or TB2 responses at the QFT-Plus positivity threshold (0.35 IU/mL). The distributions of TB1 and TB2 responses, among participants with positive QFT-Plus, were similar across age and sex. A TB2-TB1 differential >0.6 IU/mL occurred in 3.8% (109/2,895) of participants and was not associated with age or sex. However, participants with HIV had reduced odds of TB2-TB1>0.6 IU/mL (adjusted odds ratio 0.37 [0.14-0.93]). At higher hypothetical positivity thresholds, the mean predicted Mtb immunoreactivity prevalence among males exceeded that in females at an earlier age: at 19 years, predicted immunoreactivity prevalence ratios were 0.90 (0.83-0.99) and 1.02 (0.89-1.15) at 0.1 IU/mL and 0.5 IU/mL thresholds, respectively. Conclusions Quantitative IGRA responses offer information about age- and sex-specific immunoreactivity and transmission risks that dichotomisation obscures. In high-burden settings, quantitative IGRA responses may clarify Mtb transmission patterns and guide targeted public health strategies. Main point We found high prevalence of Mycobacterium tuberculosis immunoreactivity (QuantiFERON-TB Gold Plus [QFT-Plus] positivity), in a community random sample of 10–40-year-olds in Blantyre, Malawi. Quantitative QFT-Plus responses showed an association between TB2-TB1>0.6 IU/mL (possible recent Mtb exposure) and HIV positivity.

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