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Standard Genotyping Overestimates Transmission of Mycobacterium tuberculosis among Immigrants in a Low-Incidence Country.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Stucki David, Ballif Marie, Egger Matthias, Furrer Hansjakob, Altpeter Ekkehardt, Battegay Manuel, Droz Sara, Bruderer Thomas, Coscolla Mireia, Borrell Sonia, Zürcher Kathrin, Janssens Jean-Paul, Calmy Alexandra, Mazza Stalder Jesica, Jaton Katia, Rieder Hans L, Pfyffer Gaby E, Siegrist Hans H, Hoffmann Matthias, Fehr Jan, Dolina Marisa, Frei Reno, Schrenzel Jacques, Böttger Erik C, Gagneux Sebastien,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal Journal of clinical microbiology
Volume (Issue) 54(7)
Page(s) 1862 - 70
Title of proceedings Journal of clinical microbiology
DOI 10.1128/jcm.00126-16

Open Access

Type of Open Access Publisher (Gold Open Access)


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.