Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in East Greenland.
In East Greenland, a dramatic increase of tuberculosis (TB) incidence has been observed in recent years. Classical genotyping suggests a genetically similar Mycobacterium tuberculosis (Mtb) strain population as cause, however, precise transmission patterns are unclear. We performed whole genome sequencing (WGS) of Mtb isolates from 98% of culture-positive TB cases through 21 years (n = 182) which revealed four genomic clusters of the Euro-American lineage (mainly sub-lineage 4.8 (n = 134)). The time to the most recent common ancestor of lineage 4.8 strains was found to be 100 years. This sub-lineage further diversified in the 1970s, and massively expanded in the 1990s, a period of lowered TB awareness in Greenland. Despite the low genetic strain diversity, WGS data revealed several recent short-term transmission events in line with the increasing incidence in the region. Thus, the isolated setting and the uniformity of circulating Mtb strains indicated that the majority of East Greenlandic TB cases originated from one or few strains introduced within the last century. Thereby, the study shows the consequences of even short interruptions in TB control efforts in previously TB high incidence areas and demonstrates the potential role of WGS in detecting ongoing micro epidemics, thus guiding public health efforts in the future.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.|International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.|Greenland's Center of Health Research, Nuuk, Greenland.|Institute of Clinical Medicine, University of Southern Denmark, Odense, Denmark.
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Bjorn-Mortensen
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
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Soborg
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
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Koch
Department of Internal Medicine, Queen Ingrid's Hospital, Nuuk, Greenland.
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Ladefoged
Molecular and Experimental Mycobacteriology, Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.|German Center for Infection Research (DZIF), partner site Borstel, Borstel, Germany.
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Merker
International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.
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Lillebaek
Institute of Clinical Medicine, University of Southern Denmark, Odense, Denmark.|Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
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Andersen
Molecular and Experimental Mycobacteriology, Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.|German Center for Infection Research (DZIF), partner site Borstel, Borstel, Germany.
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Niemann
Molecular and Experimental Mycobacteriology, Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany.
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Kohl
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005838:Genotype; D006116:Greenland / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D058889:Molecular Typing; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D012189:Retrospective Studies; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D000073336:Whole Genome Sequencing; D055815:Young Adult