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Standard genotyping overestimates transmission of Mycobacterium tuberculosis among immigrants in a low-incidence country

Stucki, David and Ballif, Marie and Egger, Matthias and Furrer, Hansjakob and Altpeter, Ekkehardt and Battegay, Manuel and Droz, Sara and Bruderer, Thomas and Coscolla, Mireia and Borrell, Sonia and Zürcher, Kathrin and Janssens, Jean-Paul and Calmy, Alexandra and Mazza Stalder, Jesica and Jaton, Katia and Rieder, Hans L. and Pfyffer, Gaby E. and Siegrist, Hans H. and Hoffmann, Matthias and Fehr, Jan and Dolina, Marisa and Frei, Reno and Schrenzel, Jacques and Böttger, Erik C. and Gagneux, Sebastien and Fenner, Lukas. (2016) Standard genotyping overestimates transmission of Mycobacterium tuberculosis among immigrants in a low-incidence country. Journal of clinical microbiology, 54 (7). pp. 1862-1870.

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Official URL: http://edoc.unibas.ch/43620/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Tuberculosis Research (Gagneux)
UniBasel Contributors:Stucki, David and Ballif, Marie and Coscollá, Mireja and Borrell, Sonia and Gagneux, Sebastien and Fenner, Lukas
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1098-660X
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:31 Aug 2016 13:13
Deposited On:31 Aug 2016 13:13

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