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Impact of Mycobacterium tuberculosis complex strain diversity on tuberculosis transmissions in a cosmopolitan low-incidence setting

N Ullrich(1) R Diel(2,3) F P Maurer(4) K Meywald-Walter(5) C Schwarzbach(5) M Kuhns(4) I Friesen(4) S Niemann(1,6) V Dreyer(1,6)

1:Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, 23845, Germany.; 2:Institute for Epidemiology, University Medical Hospital Schleswig-Holstein, Kiel, 24105, Germany.; 3:LungClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Großhansdorf, 22927, Germany.; 4:National and Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, 23845, Germany.; 5:Public Health Department Hamburg-Mitte, Hamburg, 20355, Germany.; 6:German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, 23845, Germany

Understanding the factors driving tuberculosis (TB) transmission in a particular setting is essential to guide effective public health measures. Interestingly, only strains of some Mycobacterium tuberculosis complex (Mtbc) lineages occur globally (generalists), while others are only found in particular regions (specialists). This points towards differences in the Mtbc strain transmissibility, potentially influencing TB epidemiology in low-incidence settings by import of more transmissible strain types. To understand interactions between TB transmission, host and pathogen type in a low-incidence setting, we analysed notified TB cases in Hamburg, Germany, from 1997 – 2021 in relation to strain type and transmission data inferred from whole genome sequencing data of the 3062 Mtbc strains. Strains of Mtbc L1 to L6 and M. bovis were found in the strain collection, with a dominance of L4 strains (75%). Within L4, L4.1.2.1 (“Haarlem”) and L4.8 (“mainly T”) strains were most prevalent (32% and 20% of L4 strains, respectively) and also most frequently transmitted (30% and 18% of clustered L4 strains, respectively). Associations of ancestry and strain types, reflected in the transmission events were found at lineage and L4 sublineage level consistently over the entire 25-year period. For example, transmissions of L3 strains were mostly found between patients born in Eastern Africa, while L4.1.2.1 and L4.8 strains transmitted in patients with a wider range of origins. Our findings support the hypothesis that strains of generalist lineages can efficiently transmit in wider range of host genetics background. L4.8 strains appear to be an important widespread generalist lineage.

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