P77
The burden of multi-drug resistant tuberculosis transmission in high incidence countries – Results from a multi country population-based study
C Utpatel(1) I Barilar(1) T A Kohl(1) A M Cabibbe(3) A S Dean(4) M Merker(1) V Dreyer(1) S MM Kamal(5) A Skrahina(6) S Tahseen(7) A Barbova(8) S V Omar(9) D M Cirillo(3) M Zignol(4) S Niemann(1,2)
1:Research Center Borstel, Leibniz Lung Center, Borstel, Germany; 2:German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany; 3:Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; 4:Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland; 5:Department of Pathology and Microbiology, National Institute of Diseases of the Chest and Hospital, Dhaka, Bangladesh; 6:Republican Scientific and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus; 7:National Reference Laboratory, National Tuberculosis Control Programme, Islamabad, Pakistan; 8:The State Organization "NATIONAL INSTITUTE OF PHTHISITRY AND PULMONOLOGY named after F.G. Yanovsky of the National Academy of Medical Sciences of Ukraine"; 9:Centre for TB, National Institute for Communicable Diseases/National Health Laboratory Service, Johannesburg, South Africa
Antibiotic resistance is an alarming problem for tuberculosis (TB) control worldwide and a threat to the WHO End TB strategy. Whole genome sequencing (WGS) is now frequently used for drug resistance surveillance studies. However, large-scale WGS studies addressing the transmissibility of multi drug resistant (MDR) Mycobacterium tuberculosis complex (Mtbc) strains in comparison to susceptible strains are scarce.
To investigate the transmission potential of Mtbc strains from different phylogenetic lineages in relation to antibiotic resistance and compensatory mutations, we performed a large-scale comparative genome analysis of 4518 Mtbc strains obtained from drug resistance surveillance studies performed in six countries (Azerbaijan, Bangladesh, Belarus, Pakistan, South Africa and Ukraine).
3068 (68%) strains were susceptible to all anti-TB drugs., 671(15%) were resistant to at least one drug, excluding rifampicin (RMP), while 779 (17%) were resistant at least to RMP. Highest rates of MDR TB were found in strains of lineage 2 (30% vs 9% in all other lineages). Cluster based analysis (12 SNP threshold) showed a clear association between transmission and lineage 2 strains, however, this was independent from drug resistant status (OR = 4.68, 0.96). Four compensatory mutations in a narrow region of the rpoC gene have a high prevalence and high homoplasy index and restore transmissibility of MDR L2 strains to that of susceptible L2 strains. Strains of several MDR clusters were found in different Eastern European countries.
In conclusion, our data indicate a high transmissibility of L2 strains and cross border transmission of MDR Mtbc outbreak strains between East European countries.