Measuring recent in-country TB transmission using a classification model with whole genome sequencing data.

BACKGROUND: Molecular typing ofisolates provides insight into TB transmission by identifying clustering isolates. However, clustering alone does not necessarily indicate ongoing in-country transmission, as infections may have occurred abroad or long ago.

METHODS: We developed a classification model categorising clustering TB patients into three groups: i) likely, ii) possibly, and iii) unlikely to have been recently infected in the Netherlands. The model consists of two stages: i) individual labelling, followed by ii) cluster labelling for the remaining cases, and includes epidemiological, whole genome sequencing (WGS) data, and confirmed epidemiological links based on cluster investigation.

RESULTS: We found that 28% of TB patients with WGS results in 2018-2023 had a clustered isolate. However, when we classified cases by individual labelling (48% of cases) and cluster labelling (52% of cases), only 11% to a maximum of 15% were likely to have been infected within the last 2 years in the Netherlands.

CONCLUSION: Our WGS-based classification model provides a valuable tool for monitoring progress towards TB pre-elimination by enabling estimation of recent in-country transmission. Importantly, our findings indicate that a substantial proportion of clustered cases were likely the result of infections acquired abroad or from non-recent transmission events.