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J Clin Microbiol. 2016 Jul;54(7):1862-1870. doi: 10.1128/JCM.00126-16. Epub 2016 May 18.

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

Author information

1
Swiss Tropical and Public Health Institute, Basel, Switzerland.
2
University of Basel, Basel, Switzerland.
3
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
4
Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
5
Division of Communicable Diseases, Federal Office of Public Health, Bern, Switzerland.
6
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
7
Mycobacteriology Unit, Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
8
Center for Laboratory Medicine, St. Gallen, Switzerland.
9
Division of Pneumology, University Hospital Geneva, Geneva, Switzerland.
10
Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
11
Division of Pneumology, University Hospital Lausanne, Lausanne, Switzerland.
12
Institute of Microbiology, University Hospital of Lausanne, Lausanne, Switzerland.
13
Epidemiology, Biostatistics, and Prevention Institute, University of Zürich, Zürich, Switzerland.
14
Department of Medical Microbiology, Luzerner Kantonsspital, Lucerne, Switzerland.
15
ADMed Microbiology, La Chaux-de-Fonds, Switzerland.
16
Division of Infectious Diseases, Kantonsspital St. Gallen, St. Gallen, Switzerland.
17
University Hospital Zürich and University of Zürich, Zürich, Switzerland.
18
Servizio di Microbiologia EOLAB, Bellinzona, Switzerland.
19
Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland.
20
Laboratory of Bacteriology, University Hospitals of Geneva, Geneva, Switzerland.
21
Institute of Medical Microbiology, National Center for Mycobacteria, University of Zürich, Zürich, Switzerland.
22
Swiss Tropical and Public Health Institute, Basel, Switzerland lukas.fenner@ispm.unibe.ch.

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.

PMID:
27194683
PMCID:
PMC4922098
DOI:
10.1128/JCM.00126-16
[Indexed for MEDLINE]
Free PMC Article

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