Quantitative TB blood tests reveal hidden transmission patterns in Malawi

Tuberculosis testing often reduces complex immune signals to a simple ‘positive’ or ‘negative’ result. That binary approach can throw away useful information about how recently someone was exposed to Mycobacterium tuberculosis (Mtb) and about their possible risk of onward transmission or disease. To explore what is lost by dichotomising test results, researchers led by Mphatso D. Phiri carried out a community-based survey in Blantyre, Malawi. They collected interferon gamma release assay (IGRA) data from 2,895 people aged 10–40 years using the QuantiFERON-TB Gold Plus (QFT-Plus) test. Rather than only reporting who crossed the standard positivity cut-off, the team analysed the actual quantitative interferon gamma responses measured in the TB1 and TB2 tubes. The goal was to see how the size of those responses related to age, sex, HIV status and patterns that might point to recent transmission. By keeping the numeric test values, the investigators aimed to gain a clearer view of Mtb immunoreactivity across the community and to test whether quantitative measures could reveal transmission dynamics that a yes/no result would obscure.

The study used QuantiFERON-TB Gold Plus (QFT-Plus) results from 2,895 participants aged 10–40 and applied Bayesian regression models to assess several things: the probability of a positive response at the standard threshold (≥0.35 IU/mL), the magnitude of responses, and factors associated with those responses. At the QFT-Plus positivity threshold of 0.35 IU/mL, 17.4% (503/2,895) of participants had positive TB1 or TB2 responses. Among those with positive QFT-Plus results, the distributions of TB1 and TB2 responses were similar across age and sex. The investigators also examined a TB2-TB1 differential greater than 0.6 IU/mL, a proposed marker of recent transmission: this occurred in 3.8% (109/2,895) of participants and was not linked to age or sex. However, participants with HIV had reduced odds of having TB2-TB1 >0.6 IU/mL (adjusted odds ratio 0.37 [0.14-0.93]). The team explored hypothetical alternative positivity thresholds and found that at higher thresholds the predicted male excess in immunoreactivity appeared at an earlier age; for example, at 19 years predicted prevalence ratios were 0.90 (0.83-0.99) at 0.1 IU/mL and 1.02 (0.89-1.15) at 0.5 IU/mL.

These findings show that keeping the numeric interferon gamma results from IGRA testing can add useful detail about who in a community shows immune responses to Mtb and how those patterns vary by age, sex and HIV status. The study’s main point is that quantitative QFT-Plus responses revealed a high prevalence of Mtb immunoreactivity in this random community sample of 10–40-year-olds in Blantyre, Malawi, and that the TB2-TB1 differential thought to mark recent exposure was less common in people with HIV. Importantly, the analysis demonstrates that the choice of positivity threshold changes apparent age- and sex-specific prevalence, so a single cut-off can mask or exaggerate differences between groups. The authors conclude that in high-burden settings, analysing quantitative IGRA responses rather than only a binary result may help clarify transmission patterns and support more targeted public health strategies. Such an approach could help programs better identify where recent transmission is occurring and whom to prioritise for prevention or further investigation.