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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.

Ferdinand S, Millet J, Accipe A, Cassadou S, Chaud P, Levy M, Théodore M, Rastogi N - BMC Infect. Dis. (2013)

Bottom Line: 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.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.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.

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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.

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UPGMA dendrogram obtained through a combined numerical analysis of spoligotypes and VNTR profiles of the 129 M. tuberculosis clinical isolates from Guadeloupe. The letters in front of the tree correspond to the following information: A: SIT numbers of the spoligotype profiles with, in brackets, the strain numbers; B: binary spoligotypes; C: 5-loci VNTR profiles. The “x” symbol among a profile indicates a missing or uninterpretable result; D: clusters numbers; E: clades attribution of the spoligotype profiles.
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Figure 1: UPGMA dendrogram obtained through a combined numerical analysis of spoligotypes and VNTR profiles of the 129 M. tuberculosis clinical isolates from Guadeloupe. The letters in front of the tree correspond to the following information: A: SIT numbers of the spoligotype profiles with, in brackets, the strain numbers; B: binary spoligotypes; C: 5-loci VNTR profiles. The “x” symbol among a profile indicates a missing or uninterpretable result; D: clusters numbers; E: clades attribution of the spoligotype profiles.

Mentions: Spoligotyping of the 129 clinical isolates generated 57 different patterns presented in Figure 1 and Additional file 1: Table S1, among which 49 profiles were already present in our database with a SIT number, 3 profiles matched orphan patterns in the database creating new shared-types (SITs 1913, 2383, and 2689), and 5 were not reported earlier and labeled as orphan. A total of 90/129 (69.8%) isolates were grouped into 18 clusters (2 to 12 strains per cluster) while 39/129 (30.2%) were unique in this study. The overall lineage distribution was as follows: LAM (n = 38/129 or 29.5%), ill-defined T family (n = 39/129 or 30.2%), Haarlem (n = 30/129 or 23.3%), X clade (n = 8/129 or 6.2%), S family (n = 3/129 or 2.3%), EAI (n = 2/129 or 1.6%), and AFRI (n = 1/129 or 0.8%).


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.

Ferdinand S, Millet J, Accipe A, Cassadou S, Chaud P, Levy M, Théodore M, Rastogi N - BMC Infect. Dis. (2013)

UPGMA dendrogram obtained through a combined numerical analysis of spoligotypes and VNTR profiles of the 129 M. tuberculosis clinical isolates from Guadeloupe. The letters in front of the tree correspond to the following information: A: SIT numbers of the spoligotype profiles with, in brackets, the strain numbers; B: binary spoligotypes; C: 5-loci VNTR profiles. The “x” symbol among a profile indicates a missing or uninterpretable result; D: clusters numbers; E: clades attribution of the spoligotype profiles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750484&req=5

Figure 1: UPGMA dendrogram obtained through a combined numerical analysis of spoligotypes and VNTR profiles of the 129 M. tuberculosis clinical isolates from Guadeloupe. The letters in front of the tree correspond to the following information: A: SIT numbers of the spoligotype profiles with, in brackets, the strain numbers; B: binary spoligotypes; C: 5-loci VNTR profiles. The “x” symbol among a profile indicates a missing or uninterpretable result; D: clusters numbers; E: clades attribution of the spoligotype profiles.
Mentions: Spoligotyping of the 129 clinical isolates generated 57 different patterns presented in Figure 1 and Additional file 1: Table S1, among which 49 profiles were already present in our database with a SIT number, 3 profiles matched orphan patterns in the database creating new shared-types (SITs 1913, 2383, and 2689), and 5 were not reported earlier and labeled as orphan. A total of 90/129 (69.8%) isolates were grouped into 18 clusters (2 to 12 strains per cluster) while 39/129 (30.2%) were unique in this study. The overall lineage distribution was as follows: LAM (n = 38/129 or 29.5%), ill-defined T family (n = 39/129 or 30.2%), Haarlem (n = 30/129 or 23.3%), X clade (n = 8/129 or 6.2%), S family (n = 3/129 or 2.3%), EAI (n = 2/129 or 1.6%), and AFRI (n = 1/129 or 0.8%).

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

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.

Show MeSH
Related in: MedlinePlus