title: Use of genotyping based clustering to quantify recent tuberculosis transmission in Guadeloupe during a seven years period: analysis of risk factors and access to health care.
abstract: BACKGROUND
  The present study aimed to characterize Mycobacterium tuberculosis population structure and to identify transmission chains and risk factors by prospective molecular typing in conjunction with conventional epidemiological investigations in the French overseas department of Guadeloupe.
  
  
  METHODS
  The study included all the culture-positive TB cases (1 clinical isolate per patient; n = 129) diagnosed between a seven year period (April 4th, 1999 to December 31st, 2005). Prospective molecular typing was performed using spoligotyping and VNTRs, and a subset of 44 M. tuberculosis isolates found to be clustered was retrospectively typed using 12-loci MIRUs. Data were compared using the SITVIT2 database, followed by analysis of risk factors in function of clustering of the isolates and available demographic and socioeconomic data.
  
  
  RESULTS
  The study sample was characterized by a majority of new cases (87.4%); a moderate proportion of drug-resistance (7.8%); a high level of immigration (51.2% foreign-born) originating from high TB/HIV incidence neighboring islands such as Haiti or Dominican Republic; lower socioeconomic conditions (70.7% of jobless, average income 824 EUR/month); and a significantly higher proportion of TB/HIV co-infected cases (38.2% vs. 8.5%; p < 0.001), and extrapulmonary disease (18.2% vs. 4.8%; p < 0.02) among migrants as compared to French patients. The study revealed an important delay in access to healthcare with a median delay of 74.5 days between the 1st symptoms and clinical suspicion of TB. Prospective molecular typing based on spoligotyping and 5-loci VNTRs showed that evolutionary recent Euro-American lineages predominated in Guadeloupe (91.5% of isolates). In conjunction with epidemiological data, it allowed to estimate a recent transmission rate of 18.6%, which was close to the rate of 16.7% estimated using retrospective 12-loci MIRU typing. Although a higher proportion of cases in older age-group were apparently linked to reactivation; univariate analysis of risk factors did not allow pinpointing specific risk factors for a patient to belong to a TB transmission group.
  
  
  CONCLUSIONS
  Ongoing TB transmission in the insular, low TB-incidence setting of Guadeloupe can be defined as follows: (i) a significant proportion of imported cases of the disease from neighboring islands; (ii) significantly higher TB/HIV coinfection among foreign-born cases; and, (iii) a higher proportion of cases affecting older age-group among French patients due to reactivation. This study emphasizes the need for universal typing using spoligotyping and 15-loci MIRUs in prospective studies.
authors.forename: Séverine
authors.initials: S
authors.lastname: Ferdinand
authors.forename: Julie
authors.initials: J
authors.lastname: Millet
authors.forename: Annick
authors.initials: A
authors.lastname: Accipe
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cassadou
authors.forename: Pascal
authors.initials: P
authors.lastname: Chaud
authors.forename: Maryse
authors.initials: M
authors.lastname: Levy
authors.forename: Max
authors.initials: M
authors.lastname: Théodore
authors.forename: Nalin
authors.initials: N
authors.lastname: Rastogi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D024881:Drug Resistance, Bacterial; D005260:Female; D005838:Genotype; D019430:Guadeloupe / Q000453:epidemiology; D006297:Health Services Accessibility; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D058889:Molecular Typing; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology*; D055815:Young Adult
references.citation: FEMS Immunol Med Microbiol. 1998 Jul;21(3):203-12
references.pmid: 9718210
references.citation: Lancet Infect Dis. 2013 Feb;13(2):137-46
references.pmid: 23158499
references.citation: Infect Genet Evol. 2003 Jul;3(2):125-33
references.pmid: 12809807
references.citation: J Clin Microbiol. 2006 Dec;44(12):4498-510
references.pmid: 17005759
references.citation: J Clin Microbiol. 2001 Oct;39(10):3563-71
references.pmid: 11574573
references.citation: Microbiology (Reading). 1998 May;144 ( Pt 5):1189-1196
references.pmid: 9611793
references.citation: Infect Genet Evol. 2012 Jun;12(4):755-66
references.pmid: 22365971
references.citation: J Clin Microbiol. 2000 Jul;38(7):2520-4
references.pmid: 10878036
references.citation: Methods Enzymol. 1994;235:196-205
references.pmid: 8057895
references.citation: N Engl J Med. 1994 Jun 16;330(24):1710-6
references.pmid: 7993412
references.citation: J Clin Microbiol. 2008 Apr;46(4):1398-406
references.pmid: 18234864
references.citation: Int J Tuberc Lung Dis. 2006 Mar;10(3):240-1
references.pmid: 16562700
references.citation: Infect Genet Evol. 2009 Dec;9(6):1336-44
references.pmid: 19778638
references.citation: BMC Microbiol. 2006 Mar 06;6:23
references.pmid: 16519816
references.citation: Mol Microbiol. 2000 May;36(3):762-71
references.pmid: 10844663
references.citation: N Engl J Med. 1994 Jun 16;330(24):1703-9
references.pmid: 7910661
references.citation: Eur Respir J. 2007 Nov;30(5):937-44
references.pmid: 17567675
references.citation: J Clin Microbiol. 1997 Apr;35(4):907-14
references.pmid: 9157152
references.citation: J Clin Microbiol. 1998 Apr;36(4):1122-4
references.pmid: 9542951
references.citation: J Clin Microbiol. 2006 Jan;44(1):183-91
references.pmid: 16390968
references.citation: Clin Infect Dis. 1997 Oct;25(4):806-10
references.pmid: 9356792
references.citation: J Clin Microbiol. 2007 Nov;45(11):3606-15
references.pmid: 17898160
references.citation: Rev Mal Respir. 2012 Sep;29(7):858-70
references.pmid: 22980546
references.citation: J Clin Microbiol. 1997 Apr;35(4):843-6
references.pmid: 9157139