This community-based survey evaluated quantitative interferon gamma responses to Mycobacterium tuberculosis using the QuantiFERON-TB Gold Plus (QFT-Plus) assay in 2895 adolescents and adults aged 10-40 years in Blantyre, Malawi. The study examined the probability of positive responses, response magnitude, and associated factors, including the effect of hypothetical alternative positivity thresholds on inferences regarding age- and sex-specific transmission patterns.
At the standard QFT-Plus positivity threshold of 0.35 IU/mL, 17.4% of participants (503 of 2895) demonstrated a positive TB1 or TB2 response. Additionally, 3.8% of participants (109 of 2895) exhibited a TB2-TB1 differential greater than 0.6 IU/mL. Analysis indicated that a TB2-TB1 differential exceeding 0.6 IU/mL was associated with reduced odds of HIV, with an adjusted odds ratio of 0.37 (95% CI 0.14-0.93).
Predicted Mtb immunoreactivity prevalence ratios were calculated for males versus females at age 19 years. At a hypothetical 0.1 IU/mL threshold, the prevalence ratio was 0.90 (95% CI 0.83-0.99), indicating lower predicted immunoreactivity in males. At a 0.5 IU/mL threshold, the prevalence ratio was 1.02 (95% CI 0.89-1.15). No adverse events, serious adverse events, discontinuations, or tolerability data were reported for this diagnostic assay.
Key limitations include the observational study design and lack of reported follow-up, which preclude causal inferences regarding clinical outcomes. In high-burden settings, these quantitative IGRA responses may help clarify Mtb transmission patterns and guide targeted public health strategies, though results must be interpreted within the context of survey data.
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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.