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. 2019 Jan;24(4):1800005.
doi: 10.2807/1560-7917.ES.2019.24.4.1800005.

Whole genome sequencing-based analysis of tuberculosis (TB) in migrants: rapid tools for cross-border surveillance and to distinguish between recent transmission in the host country and new importations

Estefanía Abascal  1   2   3 , Laura Pérez-Lago  1   2   3 , Miguel Martínez-Lirola  4 , Álvaro Chiner-Oms  5 , Marta Herranz  1   2   6 , Imane Chaoui  7 , Iñaki Comas  8   9 , My Driss El Messaoudi  10 , José Antonio Garrido Cárdenas  11 , Sheila Santantón  1   2 , Emilio Bouza  1   12   2   6 , Darío García-de-Viedma  1   2   6
Affiliations

Whole genome sequencing-based analysis of tuberculosis (TB) in migrants: rapid tools for cross-border surveillance and to distinguish between recent transmission in the host country and new importations

Estefanía Abascal et al. Euro Surveill. 2019 Jan.

Abstract

BackgroundThe analysis of transmission of tuberculosis (TB) is challenging in areas with a large migrant population. Standard genotyping may fail to differentiate transmission within the host country from new importations, which is key from an epidemiological perspective.AimTo propose a new strategy to simplify and optimise cross-border surveillance of tuberculosis and to distinguish between recent transmission in the host country and new importationsMethodsWe selected 10 clusters, defined by 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR), from a population in Spain rich in migrants from eastern Europe, north Africa and west Africa and reanalysed 66 isolates by whole-genome sequencing (WGS). A multiplex-allele-specific PCR was designed to target strain-specific marker single nucleotide polymorphisms (SNPs), identified from WGS data, to optimise the surveillance of the most complex cluster.ResultsIn five of 10 clusters not all isolates showed the short genetic distances expected for recent transmission and revealed a higher number of SNPs, thus suggesting independent importations of prevalent strains in the country of origin. In the most complex cluster, rich in Moroccan cases, a multiplex allele-specific oligonucleotide-PCR (ASO-PCR) targeting the marker SNPs for the transmission subcluster enabled us to prospectively identify new secondary cases. The ASO-PCR-based strategy was transferred and applied in Morocco, demonstrating that the strain was prevalent in the country.ConclusionWe provide a new model for optimising the analysis of cross-border surveillance of TB transmission in the scenario of global migration.

Keywords: TB; WGS; cross-border surveillance; immigration; importation; migrants; molecular epidemiology; surveillance; transmission; tuberculosis; whole genome sequencing.

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Conflict of interest statement

Conflict of interest: None declared.

Figures

Figure 1
Figure 1
Chart summarising the general data of the clusters analysed, rich in cases from sub-Saharan Africa, eastern Europe and north Africa, 2003–2017 (n = 10 clusters)
Figure 2
Figure 2
Networks of relationships obtained from the whole genome sequencing analysis for clusters rich in cases from sub-Saharan Africa
Figure 3
Figure 3
Networks of relationships obtained from the whole genome sequencing analysis for clusters rich in cases from eastern Europe
Figure 4
Figure 4
Networks of relationships obtained from the whole genome sequencing analysis for clusters rich in cases from North Africa
Figure 5
Figure 5
Results for the multiplex ASO-PCR designed to precisely assign new incident cases infected by the strain 113 in Almería and labelling them as due to recent transmission or importation.
Figure 6
Figure 6
Extended network of relationships obtained from the whole genome sequencing analysis for cluster 113 including Almería, Madrid, Valencia and Morocco isolates
Figure 7
Figure 7
Results for the multiplex ASO-PCR designed to (A) retrospectively track strain 113 in Madrid and (B) retrospectively track strain 113 in Morocco
See this image and copyright information in PMC

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