title: Armed conflict and population displacement as drivers of the evolution and dispersal of Mycobacterium tuberculosis.
abstract: The "Beijing" Mycobacterium tuberculosis (Mtb) lineage 2 (L2) is spreading globally and has been associated with accelerated disease progression and increased antibiotic resistance. Here we performed a phylodynamic reconstruction of one of the L2 sublineages, the central Asian clade (CAC), which has recently spread to western Europe. We find that recent historical events have contributed to the evolution and dispersal of the CAC. Our timing estimates indicate that the clade was likely introduced to Afghanistan during the 1979-1989 Soviet-Afghan war and spread further after population displacement in the wake of the American invasion in 2001. We also find that drug resistance mutations accumulated on a massive scale in Mtb isolates from former Soviet republics after the fall of the Soviet Union, a pattern that was not observed in CAC isolates from Afghanistan. Our results underscore the detrimental effects of political instability and population displacement on tuberculosis control and demonstrate the power of phylodynamic methods in exploring bacterial evolution in space and time.
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway; v.eldholm@gmail.com.
authors.forename: Vegard
authors.identifier: 0000-0001-6721-3375
authors.initials: V
authors.lastname: Eldholm
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: John H-O
authors.initials: JH
authors.lastname: Pettersson
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: Ola B
authors.initials: OB
authors.lastname: Brynildsrud
authors.affiliation: Department of Anthropology, University of Iowa, Iowa City, IA 52242.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kitchen
authors.affiliation: International Reference Laboratory of Mycobacteriology, Statens Serum Institute, DK-2300 Copenhagen, Denmark.
authors.forename: Erik Michael
authors.initials: EM
authors.lastname: Rasmussen
authors.affiliation: International Reference Laboratory of Mycobacteriology, Statens Serum Institute, DK-2300 Copenhagen, Denmark.
authors.forename: Troels
authors.initials: T
authors.lastname: Lillebaek
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: Janne O
authors.initials: JO
authors.lastname: Rønning
authors.affiliation: Microbiology and Morphology Laboratory, Phthisiopneumology Institute, MD 2025 Chisinau, Moldova.
authors.forename: Valeriu
authors.initials: V
authors.lastname: Crudu
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: Anne Torunn
authors.initials: AT
authors.lastname: Mengshoel
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: Nadia
authors.initials: N
authors.lastname: Debech
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Alfsnes
authors.affiliation: Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: Jon
authors.initials: J
authors.lastname: Bohlin
authors.affiliation: Division of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706.|Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706.
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: Pepperell
authors.affiliation: UCL Genetics Institute, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Francois
authors.initials: F
authors.lastname: Balloux
mesh_terms: D000346:Afghanistan / Q000453:epidemiology; D000068337:Armed Conflicts; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005060:Europe; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D010802:Phylogeny; D014376:Tuberculosis / Q000453:epidemiology / Q000235:genetics / Q000382:microbiology* / Q000517:prevention & control; D014586:USSR / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
keywords: Mycobacterium tuberculosis; antimicrobial resistance; evolution; phylodynamic analysis; tip-dating