Full text loading...
Genomic surveillance of pathogens important to public health, such as Mycobacterium tuberculosis (Mtb), offers the opportunity to characterize the geographic movements of pathogens on a range of spatial and temporal scales and to explore the consequences of these inferred movements on the impacts of public health interventions. Pathogen movements can affect the impact of interventions that are geographically focused, with interventions in high-transmission areas, potentially leading to indirect benefits in other locations due to the prevention of transmission. We supplemented a large genomic surveillance dataset from Blantyre, Malawi (518 Lineage 4 sequences and 103 Lineage 1 sequences) with publicly available sequences collected across the world from 2015 to 2019 (910 Lineage 4 sequences and 445 Lineage 1 sequences) to reconstruct global and regional movements of Mtb in order to clarify the extent of importation into Blantyre. Standard phylogeographic methods are unsuitable for this task because they do not account for sampling heterogeneity across locations, so we build on a new method called sampling-aware ancestral state inference, incorporating wide disparities in the sampling fractions between different regions across the world, and also the fact that sampling only occurred from 2015 to 2019. Reconstructed phylogenetic trees contain strong signals of spatial localization of individual clades, with very limited numbers of introductions to, or exports from, Blantyre, and considerable movements within the city itself. Inferring which zone of the Blantyre nodes of the tree was in allows us to perform simple simulations of geographically focused interventions such as active case finding (ACF). We find that zone-focused ACF in Blantyre is likely to have modest impacts, with a focus on Zones 2 and 4 likely to have the most impact. As genomic surveillance becomes more commonplace, analyses such as this may be useful for public health practitioners developing interventions to reduce local TB transmission and incidence.