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Spatiotemporal Clustering of Mycobacterium tuberculosis Complex Genotypes in Florida: Genetic Diversity Segregated by Country of Birth.

Séraphin MN, Lauzardo M, Doggett RT, Zabala J, Morris JG, Blackburn JK - PLoS ONE (2016)

Bottom Line: Both groups had HIV prevalence above twenty percent.Almost five percent of TB cases reported in Florida during 2009-2013 were potentially due to recent transmission.Due to the monomorphic nature of available markers, whole genome sequencing is needed to conclusively delineate recent transmission events between U.S. and foreign-born persons.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL, United States of America.

ABSTRACT

Background: Tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). Although the MTBC is highly clonal, between-strain genetic diversity has been observed. In low TB incidence settings, immigration may facilitate the importation of MTBC strains with a potential to complicate TB control efforts.

Methods: We investigated the genetic diversity and spatiotemporal clustering of 2,510 MTBC strains isolated in Florida, United States, between 2009 and 2013 and genotyped using spoligotyping and 24-locus MIRU-VNTR. We mapped the genetic diversity to the centroid of patient residential zip codes using a geographic information system (GIS). We assessed transmission dynamics and the influence of immigration on genotype clustering using space-time permutation models adjusted for foreign-born population density and county-level HIV risk and multinomial models stratified by country of birth and timing of immigration in SaTScan.

Principal findings: Among the 2,510 strains, 1,245 were reported among foreign-born persons; including 408 recent immigrants (<5 years). Strain allelic diversity (h) ranged from low to medium in most locations and was most diverse in urban centers where foreign-born population density was also high. Overall, 21.5% of cases among U.S.-born persons and 4.6% among foreign-born persons clustered genotypically and spatiotemporally and involved strains of the Haarlem family. One Haarlem space-time cluster identified in the mostly rural northern region of Florida included US/Canada-born individuals incarcerated at the time of diagnosis; two clusters in the mostly urban southern region of Florida were composed predominantly of foreign-born persons. Both groups had HIV prevalence above twenty percent.

Conclusions/significance: Almost five percent of TB cases reported in Florida during 2009-2013 were potentially due to recent transmission. Improvements to TB screening practices among the prison population and recent immigrants are likely to impact TB control. Due to the monomorphic nature of available markers, whole genome sequencing is needed to conclusively delineate recent transmission events between U.S. and foreign-born persons.

No MeSH data available.


Related in: MedlinePlus

Spatial Distribution of Mycobacterium tuberculosis complex Allelic Diversity in Florida.Maps show genotyping coverage as a percent of reported cases that were genotyped (Panel A) and the allelic diversity of the different sublineages (Panel B) isolated in different study locations from 2009 to 2013. Allelic diversity shown is an average for the 24-Locus MIRU-VNTR loci isolated at a local. The smaller the number the less diverse the M. tuberculosis complex population diversity is at that location. Base map layer reprinted from [28] under a CC BY license, with permission from University of Florida GeoPlan Center, original copyright 2012.
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pone.0153575.g001: Spatial Distribution of Mycobacterium tuberculosis complex Allelic Diversity in Florida.Maps show genotyping coverage as a percent of reported cases that were genotyped (Panel A) and the allelic diversity of the different sublineages (Panel B) isolated in different study locations from 2009 to 2013. Allelic diversity shown is an average for the 24-Locus MIRU-VNTR loci isolated at a local. The smaller the number the less diverse the M. tuberculosis complex population diversity is at that location. Base map layer reprinted from [28] under a CC BY license, with permission from University of Florida GeoPlan Center, original copyright 2012.

Mentions: The 2,531 isolates were categorized into 1,644 distinct 24-locus MIRU-VNTR patterns consisting of 291 genotype clusters of two or more isolates. The discriminatory index for the sample was very high (HGDI = 0.997). The final sample size for the genetic diversity analyses consisted of 2,510 observations; 21 genotyped observations were excluded as they could not be geocoded. Genotyping coverage over the five year study period was low in some locations where we observed a percentage of culture-confirmed cases genotyped ranging from 0.0% to 25.0% (Fig 1A). Overall, genotyping coverage reached above 80.0% for most parts of the study region. In addition, the spatial distribution of genotyping efforts, based on spatial descriptors, showed little difference from the distribution of reported TB cases in the study region over the five-year study period when comparing the reported culture-confirmed cases to the genotyped cases (S1 Fig). In Table 2 we show the allelic diversity (h) for each of 24 MIRU-VNTR loci. The diversity ranged from 0.09 for the MIRU 27 locus to 0.824 for the MIRU 4156 locus. Four loci (MIRU 02, MIRU 20, MIRU 24, MIRU 27) exhibited low level of diversity (h <0.30). We have provided a supplemental table showing the sublineage specific allelic diversity for isolates included in this study (S1 Table). Some of the sublineages were highly diverse at the loci, while most of the others were completely monomorphic (0.00 > h <0.30). In Fig 1B we show the spatial distribution of average allelic diversity (h) of the MTBC strain families isolated during the study period. Although a number of locations did not report cases during the study period, allelic diversity ranged from low to moderate (0.00 > h < 0.30) in most locations. Diversity was especially high (h > 0.40) in the Southeast, East Central and Northeast Regions, with the highest level of genetic diversity observed in known foreign-born population hubs in Central and South Florida.


Spatiotemporal Clustering of Mycobacterium tuberculosis Complex Genotypes in Florida: Genetic Diversity Segregated by Country of Birth.

Séraphin MN, Lauzardo M, Doggett RT, Zabala J, Morris JG, Blackburn JK - PLoS ONE (2016)

Spatial Distribution of Mycobacterium tuberculosis complex Allelic Diversity in Florida.Maps show genotyping coverage as a percent of reported cases that were genotyped (Panel A) and the allelic diversity of the different sublineages (Panel B) isolated in different study locations from 2009 to 2013. Allelic diversity shown is an average for the 24-Locus MIRU-VNTR loci isolated at a local. The smaller the number the less diverse the M. tuberculosis complex population diversity is at that location. Base map layer reprinted from [28] under a CC BY license, with permission from University of Florida GeoPlan Center, original copyright 2012.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836742&req=5

pone.0153575.g001: Spatial Distribution of Mycobacterium tuberculosis complex Allelic Diversity in Florida.Maps show genotyping coverage as a percent of reported cases that were genotyped (Panel A) and the allelic diversity of the different sublineages (Panel B) isolated in different study locations from 2009 to 2013. Allelic diversity shown is an average for the 24-Locus MIRU-VNTR loci isolated at a local. The smaller the number the less diverse the M. tuberculosis complex population diversity is at that location. Base map layer reprinted from [28] under a CC BY license, with permission from University of Florida GeoPlan Center, original copyright 2012.
Mentions: The 2,531 isolates were categorized into 1,644 distinct 24-locus MIRU-VNTR patterns consisting of 291 genotype clusters of two or more isolates. The discriminatory index for the sample was very high (HGDI = 0.997). The final sample size for the genetic diversity analyses consisted of 2,510 observations; 21 genotyped observations were excluded as they could not be geocoded. Genotyping coverage over the five year study period was low in some locations where we observed a percentage of culture-confirmed cases genotyped ranging from 0.0% to 25.0% (Fig 1A). Overall, genotyping coverage reached above 80.0% for most parts of the study region. In addition, the spatial distribution of genotyping efforts, based on spatial descriptors, showed little difference from the distribution of reported TB cases in the study region over the five-year study period when comparing the reported culture-confirmed cases to the genotyped cases (S1 Fig). In Table 2 we show the allelic diversity (h) for each of 24 MIRU-VNTR loci. The diversity ranged from 0.09 for the MIRU 27 locus to 0.824 for the MIRU 4156 locus. Four loci (MIRU 02, MIRU 20, MIRU 24, MIRU 27) exhibited low level of diversity (h <0.30). We have provided a supplemental table showing the sublineage specific allelic diversity for isolates included in this study (S1 Table). Some of the sublineages were highly diverse at the loci, while most of the others were completely monomorphic (0.00 > h <0.30). In Fig 1B we show the spatial distribution of average allelic diversity (h) of the MTBC strain families isolated during the study period. Although a number of locations did not report cases during the study period, allelic diversity ranged from low to moderate (0.00 > h < 0.30) in most locations. Diversity was especially high (h > 0.40) in the Southeast, East Central and Northeast Regions, with the highest level of genetic diversity observed in known foreign-born population hubs in Central and South Florida.

Bottom Line: Both groups had HIV prevalence above twenty percent.Almost five percent of TB cases reported in Florida during 2009-2013 were potentially due to recent transmission.Due to the monomorphic nature of available markers, whole genome sequencing is needed to conclusively delineate recent transmission events between U.S. and foreign-born persons.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL, United States of America.

ABSTRACT

Background: Tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). Although the MTBC is highly clonal, between-strain genetic diversity has been observed. In low TB incidence settings, immigration may facilitate the importation of MTBC strains with a potential to complicate TB control efforts.

Methods: We investigated the genetic diversity and spatiotemporal clustering of 2,510 MTBC strains isolated in Florida, United States, between 2009 and 2013 and genotyped using spoligotyping and 24-locus MIRU-VNTR. We mapped the genetic diversity to the centroid of patient residential zip codes using a geographic information system (GIS). We assessed transmission dynamics and the influence of immigration on genotype clustering using space-time permutation models adjusted for foreign-born population density and county-level HIV risk and multinomial models stratified by country of birth and timing of immigration in SaTScan.

Principal findings: Among the 2,510 strains, 1,245 were reported among foreign-born persons; including 408 recent immigrants (<5 years). Strain allelic diversity (h) ranged from low to medium in most locations and was most diverse in urban centers where foreign-born population density was also high. Overall, 21.5% of cases among U.S.-born persons and 4.6% among foreign-born persons clustered genotypically and spatiotemporally and involved strains of the Haarlem family. One Haarlem space-time cluster identified in the mostly rural northern region of Florida included US/Canada-born individuals incarcerated at the time of diagnosis; two clusters in the mostly urban southern region of Florida were composed predominantly of foreign-born persons. Both groups had HIV prevalence above twenty percent.

Conclusions/significance: Almost five percent of TB cases reported in Florida during 2009-2013 were potentially due to recent transmission. Improvements to TB screening practices among the prison population and recent immigrants are likely to impact TB control. Due to the monomorphic nature of available markers, whole genome sequencing is needed to conclusively delineate recent transmission events between U.S. and foreign-born persons.

No MeSH data available.


Related in: MedlinePlus