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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

Multinomial space-time cluster of the M. tuberculosis Haarlem in Florida, 2009–2013.Maps show the location of significant multinomial space-time clusters of M. tuberculosis Haarlem in Florida, 2009–2013. Categories refer to case country/region of birth and timing of immigration among foreign-born cases. Relative Risk (RR) estimates indicate whether or not greater than expected numbers occurred in a given category. RR>1 represents a greater than expected number of individuals of certain category inside the spatial cluster compared to outside. 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.g003: Multinomial space-time cluster of the M. tuberculosis Haarlem in Florida, 2009–2013.Maps show the location of significant multinomial space-time clusters of M. tuberculosis Haarlem in Florida, 2009–2013. Categories refer to case country/region of birth and timing of immigration among foreign-born cases. Relative Risk (RR) estimates indicate whether or not greater than expected numbers occurred in a given category. RR>1 represents a greater than expected number of individuals of certain category inside the spatial cluster compared to outside. Base map layer reprinted from [28] under a CC BY license, with permission from University of Florida GeoPlan Center, original copyright 2012.

Mentions: The multinomial models showed three areas of high occurrence of the Haarlem sublineage; one which expanded over the Northern region of the state and the other two localized in the Southeast Region (Fig 3). The characteristics of the cases included inside each of these clusters are presented in Table 3. The Northern cluster included a total of 50 cases all born in the U.S./Canada (RR = 1.75). Fifty percent of the strains were of the H2 clade, 48.0% of the H1, and 2.0% were of the H3 clade. Four percent of the strains were resistant to at least one first-line anti-tuberculosis drugs (Isoniazid, Rifampin, and Ethambutol), a quarter of the cases were HIV positive and 56.0% were incarcerated at the time of TB diagnosis. Among persons with a history of incarceration, infection with the H2 sublineage was significantly higher (89.3%) compared to the other sublineages (p < .0001), while there was no significant difference in HIV and drug resistance prevalence between the three clades. The two Southern clusters (A and B) included a total of 66 cases. Over 90.0% of the 35 cases in Cluster A were born in Haiti (RR = 5.05); 60.0% had immigrated to the U.S. more than five years prior to diagnosis (RR = 2.51) and 29% had immigrated less than five years prior to diagnosis (RR = 3.48). Thirty percent of cases within cluster A were HIV positive and 5.7% were incarcerated at the time of diagnosis. Over 34% of the cases were infected with an H1 clade, 17.1% H2 and 48.6% H3. About 14.0% of the strains were resistant to at least one first-line TB drugs. Within Cluster B, there were greater than expected occurrence of foreign-born individuals from Latin America (RR = 6.53), South America (RR = 4.48) and Haiti (RR = 2.00) as compared to outside the cluster. In addition, the relative risk of cluster membership was 2.3 among recent immigrants and 3.16 among immigrants who had been in Florida at least five years prior to diagnosis. About 16% of the strains were of the H1 clade while 25.8% and 48.4% were of the H2 and H3 clades respectively. Resistance to at least one anti-tuberculosis drug was 9.7% and 19.4% of the cases were HIV positive. Prevalence of HIV, drug resistance or history of incarceration did not differ by infection with either one of the three Haarlem clades in either of the two Southern clusters. Based on the multinomial scan results, recent transmission was estimated at 46.40% (116/250) overall; 36.81% (60/163) among U.S-born cases, 62.07% (18/29) among recent immigrants and 65.52% (38/58) among immigrants who have lived in Florida at least five years.


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)

Multinomial space-time cluster of the M. tuberculosis Haarlem in Florida, 2009–2013.Maps show the location of significant multinomial space-time clusters of M. tuberculosis Haarlem in Florida, 2009–2013. Categories refer to case country/region of birth and timing of immigration among foreign-born cases. Relative Risk (RR) estimates indicate whether or not greater than expected numbers occurred in a given category. RR>1 represents a greater than expected number of individuals of certain category inside the spatial cluster compared to outside. 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.g003: Multinomial space-time cluster of the M. tuberculosis Haarlem in Florida, 2009–2013.Maps show the location of significant multinomial space-time clusters of M. tuberculosis Haarlem in Florida, 2009–2013. Categories refer to case country/region of birth and timing of immigration among foreign-born cases. Relative Risk (RR) estimates indicate whether or not greater than expected numbers occurred in a given category. RR>1 represents a greater than expected number of individuals of certain category inside the spatial cluster compared to outside. Base map layer reprinted from [28] under a CC BY license, with permission from University of Florida GeoPlan Center, original copyright 2012.
Mentions: The multinomial models showed three areas of high occurrence of the Haarlem sublineage; one which expanded over the Northern region of the state and the other two localized in the Southeast Region (Fig 3). The characteristics of the cases included inside each of these clusters are presented in Table 3. The Northern cluster included a total of 50 cases all born in the U.S./Canada (RR = 1.75). Fifty percent of the strains were of the H2 clade, 48.0% of the H1, and 2.0% were of the H3 clade. Four percent of the strains were resistant to at least one first-line anti-tuberculosis drugs (Isoniazid, Rifampin, and Ethambutol), a quarter of the cases were HIV positive and 56.0% were incarcerated at the time of TB diagnosis. Among persons with a history of incarceration, infection with the H2 sublineage was significantly higher (89.3%) compared to the other sublineages (p < .0001), while there was no significant difference in HIV and drug resistance prevalence between the three clades. The two Southern clusters (A and B) included a total of 66 cases. Over 90.0% of the 35 cases in Cluster A were born in Haiti (RR = 5.05); 60.0% had immigrated to the U.S. more than five years prior to diagnosis (RR = 2.51) and 29% had immigrated less than five years prior to diagnosis (RR = 3.48). Thirty percent of cases within cluster A were HIV positive and 5.7% were incarcerated at the time of diagnosis. Over 34% of the cases were infected with an H1 clade, 17.1% H2 and 48.6% H3. About 14.0% of the strains were resistant to at least one first-line TB drugs. Within Cluster B, there were greater than expected occurrence of foreign-born individuals from Latin America (RR = 6.53), South America (RR = 4.48) and Haiti (RR = 2.00) as compared to outside the cluster. In addition, the relative risk of cluster membership was 2.3 among recent immigrants and 3.16 among immigrants who had been in Florida at least five years prior to diagnosis. About 16% of the strains were of the H1 clade while 25.8% and 48.4% were of the H2 and H3 clades respectively. Resistance to at least one anti-tuberculosis drug was 9.7% and 19.4% of the cases were HIV positive. Prevalence of HIV, drug resistance or history of incarceration did not differ by infection with either one of the three Haarlem clades in either of the two Southern clusters. Based on the multinomial scan results, recent transmission was estimated at 46.40% (116/250) overall; 36.81% (60/163) among U.S-born cases, 62.07% (18/29) among recent immigrants and 65.52% (38/58) among immigrants who have lived in Florida at least five years.

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