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Interrogation of an Multi Drug Resistant Tuberculosis outbreak using Whole Genome Sequencing

J Sims-Handcock(1) P Tshavhungwe(1) J Loubser(1) A Dippenaar(2) N Kriel(1) R Warren(1) E Streicher(1)

1:Stellenbosch University; 2:University of Antwerp

The spread of drug-resistant strains which has been reported to be attributed to primary transmission threatens TB control and prevention programmes. Previous molecular epidemiological studies have reported that the dynamics of tuberculosis transmission varies geographically. After a reported increase in drug resistant TB cases in the West Coast region of the Western Cape Province, South Africa, the aim of this study was to identify transmission hotspots and possible outbreaks of drug-resistant tuberculosis within this region. Spoligotyping and Sanger sequencing of first line drug resistance conferring mutations of drug resistant strains in the region over 5 years (2008-2012) identified an MDR-TB outbreak of the X-family mainly located in the Northern parts of the region. Whole genome sequencing (WGS) were done on all available strains (n=177) to establish the phylogenetic relationships of this outbreak.  Through WGS and sanger sequencing we found identical mutations conferring resistance to the 4 first-line drugs used in tuberculosis treatment in this lineage 4.1.1 cluster, including a rare katG315 double mutation. This is indicative of transmission of MDR-TB. Isolates belonging to this outbreak, but with different additional mutations conferring to resistance to second-line drugs were also identified, indicating that Pre-XDR-TB are primarily acquired on an existing MDR strain genotype. XDR-TB has not yet been seen, as this outbreak peaked before the introduction of new generation anti TB drugs. Monitoring and interrogation of drug resistant TB outbreaks plays an important part in our understanding of the drug resistant TB epidemic to ultimately eradicate TB disease worldwide.

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