title: Standard Genotyping Overestimates Transmission of Mycobacterium tuberculosis among Immigrants in a Low-Incidence Country.
abstract: Immigrants from regions with a high incidence of tuberculosis (TB) are a risk group for TB in low-incidence countries such as Switzerland. In a previous analysis of a nationwide collection of 520 Mycobacterium tuberculosis isolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat [MIRU-VNTR] typing and spoligotyping). Here, we used whole-genome sequencing (WGS) to revisit these transmission clusters. Genome-based transmission clusters were defined as isolate pairs separated by ≤12 single nucleotide polymorphisms (SNPs). WGS confirmed 17/35 (49%) MIRU-VNTR typing clusters; the other 18 clusters contained pairs separated by >12 SNPs. Most transmission clusters (3/4) of Swiss-born patients were confirmed by WGS, as opposed to 25% (4/16) of the clusters involving only foreign-born patients. The overall clustering proportion was 17% (90 patients; 95% confidence interval [CI], 14 to 21%) by standard genotyping but only 8% (43 patients; 95% CI, 6 to 11%) by WGS. The clustering proportion was 17% (67/401; 95% CI, 13 to 21%) by standard genotyping and 7% (26/401; 95% CI, 4 to 9%) by WGS among foreign-born patients and 19% (23/119; 95% CI, 13 to 28%) and 14% (17/119; 95% CI, 9 to 22%), respectively, among Swiss-born patients. Using weighted logistic regression, we found weak evidence of an association between birth origin and transmission (adjusted odds ratio of 2.2 and 95% CI of 0.9 to 5.5 comparing Swiss-born patients to others). In conclusion, standard genotyping overestimated recent TB transmission in Switzerland compared to WGS, particularly among immigrants from regions with a high TB incidence, where genetically closely related strains often predominate. We recommend the use of WGS to identify transmission clusters in settings with a low incidence of TB.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.|Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Stucki
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.|Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Ballif
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.affiliation: Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.affiliation: Division of Communicable Diseases, Federal Office of Public Health, Bern, Switzerland.
authors.forename: Ekkehardt
authors.initials: E
authors.lastname: Altpeter
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.affiliation: Mycobacteriology Unit, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Droz
authors.affiliation: Center for Laboratory Medicine, St. Gallen, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruderer
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Mireia
authors.initials: M
authors.lastname: Coscolla
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Sonia
authors.initials: S
authors.lastname: Borrell
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Zürcher
authors.affiliation: Division of Pneumology, University Hospital Geneva, Geneva, Switzerland.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Janssens
authors.affiliation: Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.affiliation: Division of Pneumology, University Hospital Lausanne, Lausanne, Switzerland.
authors.forename: Jesica
authors.initials: J
authors.lastname: Mazza Stalder
authors.affiliation: Institute of Microbiology, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Katia
authors.initials: K
authors.lastname: Jaton
authors.affiliation: Epidemiology, Biostatistics, and Prevention Institute, University of Zürich, Zürich, Switzerland.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Rieder
authors.affiliation: Department of Medical Microbiology, Luzerner Kantonsspital, Lucerne, Switzerland.
authors.forename: Gaby E
authors.initials: GE
authors.lastname: Pfyffer
authors.affiliation: ADMed Microbiology, La Chaux-de-Fonds, Switzerland.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Siegrist
authors.affiliation: Division of Infectious Diseases, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Fehr
authors.affiliation: Servizio di Microbiologia EOLAB, Bellinzona, Switzerland.
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolina
authors.affiliation: Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Reno
authors.initials: R
authors.lastname: Frei
authors.affiliation: Laboratory of Bacteriology, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.affiliation: Institute of Medical Microbiology, National Center for Mycobacteria, University of Zürich, Zürich, Switzerland.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Böttger
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland lukas.fenner@ispm.unibe.ch.|University of Basel, Basel, Switzerland.|Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Fenner
mesh_terms: D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D018562:Disease Transmission, Infectious; D054242:Emigrants and Immigrants; D005260:Female; D005500:Follow-Up Studies; D016680:Genome, Bacterial; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D058889:Molecular Typing; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013557:Switzerland / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D055815:Young Adult