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


RESULTS
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
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.
Department of Medicine, Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL, United States of America.|Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States of America.|Department of Epidemiology, College of Public Health and Health Professions, College of Medicine, University of Florida, Gainesville, FL, United States of America.
Marie Nancy
MN
Séraphin
Department of Medicine, Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL, United States of America.|Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States of America.
Michael
M
Lauzardo
Bureau of Communicable Diseases, Tuberculosis Control Section, Florida Department of Health, Tallahassee, FL, United States of America.
Richard T
RT
Doggett
Bureau of Communicable Diseases, Tuberculosis Control Section, Florida Department of Health, Tallahassee, FL, United States of America.
Jose
J
Zabala
Department of Medicine, Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL, United States of America.|Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States of America.
J Glenn
JG
Morris
Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States of America.|Department of Geography, Spatial Epidemiology & Ecology Research Laboratory, University of Florida, Gainesville, FL, United States of America.
Jason K
JK
Blackburn
D000328:Adult; D000368:Aged; D015373:Bacterial Typing Techniques / Q000379:methods; D016000:Cluster Analysis; D054242:Emigrants and Immigrants; D004641:Emigration and Immigration; D005260:Female; D005431:Florida; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D015995:Prevalence; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology; D055815:Young Adult