P084

1:Stellenbosch Unversity; 2:National Health Laboratory Service, South Africa

Extensively drug-resistant tuberculosis (XDR-TB) is a global health threat, being expensive and difficult to treat, with high mortality rates. Drug resistance genotypes and transmission present substantial regional variability. Thus, a better understanding of genetic diversity and the factors related to transmission can aid in prioritizing resources to effectively target high-risk populations and regions that are disproportionately affected. We aimed to describe genetic diversity and drug resistance profiles of XDR-TB strains in the Western Cape Province over a 10 year period. 

We included 729 XDR-TB samples, identified through routine diagnosis from 2010-2019, from six healthcare districts (HCDs) in the province. Genomic DNA from cultured isolates was sequenced using the Illumina platform. Sequences were analysed for strain type, drug resistance mutations, and genomic clustering using TBProfiler and MTBseq pipelines. We conducted logistic regression to identify potential factors associated with genomic traits related to the spread of XDR-TB.

Of the 729 XDR-TB strains, sublineage 2.2.2 (Atypical Beijing: n=378, 58.79%) strains were predominant, followed by sublineage 2.2.1 (Typical Beijing: n=260, 40.43%). L2.2.2 were more likely to cluster than L2.2.1. Most of the clusters were small, with a few large and very large clusters, and the very large clusters (primarily L2.2.2.) were more likely to be found within 3 HCDs. Some L2.2.2 were found resistant to new and repurposed drugs recently introduced in the WHO treatment guidelines.

Near-untreatable Atypical Beijing strains are prevalent in the WCP. Hence, hotspot areas for clustering in 3 HCDs should be prioritized for targeted intervention to prevent ongoing XDR-TB transmission.