25 26 Mycobacterium tuberculosis (Mtb) lineage identification and typing of clinical isolates in 27 general is performed only retrospectively. The results are rarely linked to drug susceptibility 28 testing (DST) or patient data. Consequently, the association between Mtb lineage, (multi)drug 29 resistance and treatment history is not fully explored at the local level. Here we evaluated a 30 new SNP based typing assay. We furthermore assessed the added value of genotyping of Mtb 31 isolates for epidemiological purposes and guidance of tuberculosis (TB) control. Mtb lineage, 32 DST profile and treatment history were determined for 399 samples at the National TB 33 Reference Laboratory (NRL) in Tbilisi, Georgia by local staff. Data was shared electronically 34 and analysis was performed remotely. Out of 399 isolates, 74 (74/399, 18.5%) were at least 35 multidrug resistant (MDR)-TB, of which 63 (63/74, 85.1%) were members of three different 36 Mtb Beijing lineages. Previous treatment was reported in 38/74 (51.4%) MDR(+) patients. The 37 availability of this data allows associations with lineages. Notably, multidrug resistant TB was 38 more strongly associated with the Beijing lineage than treatment history. Of all MDR-TB 39Beijing strains 56.7% (42/74) were members of a genetic cluster. This is most easily explained 40 by (ongoing) MDR-TB transmission rather than drug resistance amplification. This knowledge 41 is useful when designing intervention strategies for MDR-TB. Our study provides an example 42 that on-site integrated Mtb genotyping is realistic and could support TB control activities. 43 44 48 TB control activities (1, 2). Justifying investment in effective TB control strategies in a 49 country can be achieved in part by defining and monitoring the (MDR) TB epidemic to 50 identify appropriate interventions. 51 52 Molecular tools can positively impact on earlier detection of Mtb and identification of drug 53 resistance (3, 4). Genotyping of Mtb isolates has revealed associations between drug 54resistance and Mtb lineage (5-8), identified routes of transmission (9, 10) and described the 55 dynamics of epidemic clones (3,(11)(12)(13)(14). Further developments in multiplex assays as well as 56 the expanded use of next generation sequencing assays will increasingly allow Mtb strains to 57 be simultaneously screened for resistance associated mutations and the bacterial lineage they 58 represent.
60A robust link has been found between previous treatment for TB and multidrug resistance 61 (15), and is identified as a risk factor for MDR-TB by the WHO (16) but other factors are 62 also important, for example the bacterial lineage. This is especially true when transmission of 63 resistant strains is more common than the acquisition of resistance during treatment. 64 Members of the East Asia lineage (Mtb lineage 2) (17, 18) have repeatedly been associated 65 with multidrug resistance in high burden MDR-TB countries (11, 19) but less so in low 66 burden (MDR)-TB countries (20-22). The relative importance and interdepen...