P72
Population structure and transmission dynamics of multidrug-resistant Mycobacterium tuberculosis strains in Sierra leone
H NA Blankson(1,2,3) C Utpatel(1,2) R Kamara(4) O S Conteh(4) I Barilar(1,2) S Andreas(6) T Dallenga(7) S Homolka(1,2) K Kranzer(5) F Maurer(2,6) L Foray(4) S Niemann(1,2)
1:Molecular and Experimental Mycobacteriology, Research Center Borstel Leibniz Lung Center, Borstel, 23845, Germany; 2:German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Reims, Borstel, Germany; 3:School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Korle-Bu, Accra, Ghana; 4:National Leprosy and Tuberculosis Control Programme Sierra Leone, Freetown, Sierra Leone; 5:Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom; 6:National and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel Leibniz Lung Center, Borstel, Germany; 7:Cellular Microbiology, Research Center Borstel Leibniz Lung Center, Borstel, 23845, Germany
Treatment of rifampicin/multidrug-resistant tuberculosis (RR/MDR-TB) cases are associated with poor treatment outcomes and toxic side effects. Country specific understanding of RR/MDR-TB genetic variability and drug resistance profile is important. Here, we characterize the genomic variability of MDR-TB strains from Sierra Leone. A total of 326 Mycobacterium tuberculosis isolates were cultured from the sputum of patients from Sierra Leone who were either failing on first-line TB regimens or were found to have RR-TB using the Xpert MTB/Rif were analysed by WGS. RR/MDR isolates were identified by genotypic drug resistance prediction (gDST). Data was then used for phylogenetic strain classification, mutation and cluster analysis. A total of 247 RR/MDR isolates fell into seven major lineages: 151(61%), 51(21%), 25(10%) belonged to lineage 4, 6 and 2 respectively. The overall clustering rate was 30%, grouped in 32 clusters, ranging in size from 2 to 16 strains. The largest clusters were formed by 2.2.1 Beijing Ancestral 3, 4.8 mainly T and 6.3.3 West Africa 2 sublineage strains. 200(81%) and 47(19%) of the strains were MDR and RR respectively. None of the strains was resistant to fluoroquinolones and 3 isolates were resistant to bedaquiline. Transmission of RR/MDR-TB in Sierra Leone is lineage depended. The largest number of MDR-TB strains in a cluster was found in the Beijing ancestral 3 sublineage where MDR-TB was mostly developed after transmission. Resistance to bedaquiline and fluoroquinolones was scarce, an indication that most of the MDR-TB cases in the country can be treated based on the WHO short treatment guidelines.