Institute Pasteur Of La Guadeloupe

la Guadeloupe, Guadeloupe

Institute Pasteur Of La Guadeloupe

la Guadeloupe, Guadeloupe
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Cadelis G.,Service Route | Rossigneux E.,Service Route | Millet J.,Institute Pasteur Of La Guadeloupe | Rastogi N.,Institute Pasteur Of La Guadeloupe
Revue des Maladies Respiratoires | Year: 2012

Most of the migrants residing in Guadeloupe are from neighboring Caribbean islands, some of which are characterized by a high incidence of tuberculosis. The objective of this retrospective and observational study was to define the epidemiological characteristics of tuberculosis affecting migrant and native populations in Guadeloupe. Methods.-We describe all cases of tuberculosis in Guadeloupe identified in these two populations between 1 July 2006 and 30 June 2011. Results.-The incidence of TB among migrants in Guadeloupe was seven times higher than that in native subjects in 2010 (33.4 vs. 5.5 new cases/100,000 inhabitants). Tuberculosis affecting the migrant population was characterized by young age of the patients (42 vs. 55 years) and a significant proportion of co-infection by the human immunodeficiency virus (HIV) (47 vs. 14%, P > 0.001). Among the patient population studied, the HIV infection increased the risk of developing severe tuberculosis (adjusted odds ratio: 2.9; 95%CI: 1.2-6.8). Moreover, HIV infection was also a risk factor for death where the infection was not controlled (CD4 count > 200 units per microliter; adj risk ratio: 3.9; 1.2-12.4). Conclusion.-This study shows that the migrant population in Guadeloupe is at increased risk of tuberculosis and should be considered as a priority target for tuberculosis control program. © 2012 SPLF.

Marais B.J.,University of Sydney | Mlambo C.K.,University of Witwatersrand | Rastogi N.,Institute Pasteur Of La Guadeloupe | Zozio T.,Institute Pasteur Of La Guadeloupe | And 4 more authors.
Journal of Clinical Microbiology | Year: 2013

Numerous reports have documented isolated transmission events or clonal outbreaks of multidrug-resistant Mycobacterium tuberculosis strains, but knowledge of their epidemic spread remains limited. In this study, we evaluated drug resistance, strain diversity, and clustering rates in patients diagnosed with multidrug-resistant (MDR) tuberculosis (TB) at the National Health Laboratory Service (NHLS) Central TB Laboratory in Johannesburg, South Africa, between March 2004 and December 2007. Phenotypic drug susceptibility testing was done using the indirect proportion method, while each isolate was genotyped using a combination of spoligotyping and 12-MIRU typing (12-locus multiple interspersed repetitive unit typing). Isolates from 434 MDR-TB patients were evaluated, of which 238 (54.8%) were resistant to four first-line drugs (isoniazid, rifampin, ethambutol, and streptomycin). Spoligotyping identified 56 different strains and 28 clusters of variable size (2 to 71 cases per cluster) with a clustering rate of 87.1%. Ten clusters included 337 (77.6%) of all cases, with strains of the Beijing genotype being most prevalent (16.4%). Combined analysis of spoligotyping and 12-MIRU typing increased the discriminatory power (Hunter Gaston discriminatory index [HGDI] = 0.962) and reduced the clustering rate to 66.8%. Resolution of Beijing genotype strains was further enhanced with the 24-MIRU-VNTR (variable-number tandem repeat) typing method by identifying 15 subclusters and 19 unique strains from twelve 12-MIRU clusters. High levels of clustering among a variety of strains suggest a true epidemic spread of MDR-TB in the study setting, emphasizing the urgency of early diagnosis and effective treatment to reduce transmission within this community. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Couvin D.,Institute Pasteur Of La Guadeloupe | Zozio T.,Institute Pasteur Of La Guadeloupe | Rastogi N.,Institute Pasteur Of La Guadeloupe
Tuberculosis | Year: 2017

Spoligotyping is one of the most commonly used polymerase chain reaction (PCR)-based methods for identification and study of genetic diversity of Mycobacterium tuberculosis complex (MTBC). Despite its known limitations if used alone, the methodology is particularly useful when used in combination with other methods such as mycobacterial interspersed repetitive units – variable number of tandem DNA repeats (MIRU-VNTRs). At a worldwide scale, spoligotyping has allowed identification of information on 103,856 MTBC isolates (corresponding to 98049 clustered strains plus 5807 unique isolates from 169 countries of patient origin) contained within the SITVIT2 proprietary database of the Institut Pasteur de la Guadeloupe. The SpolSimilaritySearch web-tool described herein (available at: incorporates a similarity search algorithm allowing users to get a complete overview of similar spoligotype patterns (with information on presence or absence of 43 spacers) in the aforementioned worldwide database. This tool allows one to analyze spread and evolutionary patterns of MTBC by comparing similar spoligotype patterns, to distinguish between widespread, specific and/or confined patterns, as well as to pinpoint patterns with large deleted blocks, which play an intriguing role in the genetic epidemiology of M. tuberculosis. Finally, the SpolSimilaritySearch tool also provides with the country distribution patterns for each queried spoligotype. © 2017 Elsevier Ltd

Hill V.,Institute Pasteur Of La Guadeloupe | Zozio T.,Institute Pasteur Of La Guadeloupe | Sadikalay S.,Institute Pasteur Of La Guadeloupe | Viegas S.,National Institute of Health | And 3 more authors.
PLoS ONE | Year: 2012

Multiple-locus variable-number tandem repeat analysis (MLVA) is useful to establish transmission routes and sources of infections for various microorganisms including Mycobacterium tuberculosis complex (MTC). The recently released SITVITWEB database contains 12-loci Mycobacterial Interspersed Repetitive Units - Variable Number of Tandem DNA Repeats (MIRU-VNTR) profiles and spoligotype patterns for thousands of MTC strains; it uses MIRU International Types (MIT) and Spoligotype International Types (SIT) to designate clustered patterns worldwide. Considering existing doubts on the ability of spoligotyping alone to reveal exact phylogenetic relationships between MTC strains, we developed a MLVA based classification for MTC genotypic lineages. We studied 6 different subsets of MTC isolates encompassing 7793 strains worldwide. Minimum spanning trees (MST) were constructed to identify major lineages, and the most common representative located as a central node was taken as the prototype defining different phylogenetic groups. A total of 7 major lineages with their respective prototypes were identified: Indo-Oceanic/MIT57, East Asian and African Indian/MIT17, Euro American/MIT116, West African-I/MIT934, West African-II/MIT664, M. bovis/MIT49, M.canettii/MIT60. Further MST subdivision identified an additional 34 sublineage MIT prototypes. The phylogenetic relationships among the 37 newly defined MIRU-VNTR lineages were inferred using a classification algorithm based on a bayesian approach. This information was used to construct an updated phylogenetic and phylogeographic snapshot of worldwide MTC diversity studied both at the regional, sub-regional, and country level according to the United Nations specifications. We also looked for IS6110 insertional events that are known to modify the results of the spoligotyping in specific circumstances, and showed that a fair portion of convergence leading to the currently observed bias in phylogenetic classification of strains may be traced back to the presence of IS6110. These results shed new light on the evolutionary history of the pathogen in relation to the history of peopling and human migration. © 2012 Hill et al.

Molina-Torres C.A.,Hospital Universitario Jose nzalez | Moreno-Torres E.,Hospital Universitario Jose nzalez | Ocampo-Candiani J.,Hospital Universitario Jose nzalez | Rendon A.,Hospital Universitario Jose nzalez | And 5 more authors.
Journal of Clinical Microbiology | Year: 2010

Although tuberculosis is still a public health problem in Mexico, there is little information about the genetic characteristics of the isolates. In the present study, we analyzed by spoligotyping 180 Mycobacterium tuberculosis clinical isolates from the urban area of Monterrey, Mexico, including drug-susceptible and drug-resistant isolates. The spoligotype patterns were compared with those in the international SITVIT2 spoligotyping database. Four isolates presented spoligotype patterns not found in the database (orphan types); the rest were distributed among 44 spoligo international types (SITs). SIT53 (clade T1) and SIT119 (clade X1) were predominant and included 43 (23.8%) and 28 (15.5%) of the isolates, respectively. In order to determine if there was a dominant spoligotype in the group of multidrug-resistant isolates, 37 of them were analyzed by IS6110-based restriction fragment length polymorphism assays, and scarce clustering of strains with more than five bands was observed. Fourteen isolates of this multidrug-resistant group presented four bands or less and were distributed in four SITs: SIT53 (n = 8), SIT92 (n = 3), SIT70 (n = 2), and SIT3038 (n = 1). When the molecular detection of mutations in the katG and rpoB genes were analyzed in these isolates with low copy numbers of IS6110, only two isolates shared the same IS6110, spoligotyping, and mutations patterns. When the distribution of the spoligotypes was analyzed by age cohort, SIT119 was predominantly found in patients 0 to 20 years old, especially in males, accounting for up to 40% of the isolates. In contrast, SIT53 was more prevalent in older females. This analysis demonstrates the variability of M. tuberculosis isolates in Monterrey and the partial dominance of SIT53 and SIT119 in that area of Mexico. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Jagielski T.,University of Warsaw | Minias A.,Polish Academy of Sciences | van Ingen J.,Radboud University Nijmegen | Rastogi N.,Institute Pasteur Of La Guadeloupe | And 3 more authors.
Clinical Microbiology Reviews | Year: 2016

Molecular typing has revolutionized epidemiological studies of infectious diseases, including those of a mycobacterial etiology. With the advent of fingerprinting techniques, many traditional concepts regarding transmission, infectivity, or pathogenicity of mycobacterial bacilli have been revisited, and their conventional interpretations have been challenged. Since the mid-1990s, when the first typing methods were introduced, a plethora of other modalities have been proposed. So-called molecular epidemiology has become an essential subdiscipline of modern mycobacteriology. It serves as a resource for understanding the key issues in the epidemiology of tuberculosis and other mycobacterial diseases. Among these issues are disclosing sources of infection, quantifying recent transmission, identifying transmission links, discerning reinfection from relapse, tracking the geographic distribution and clonal expansion of specific strains, and exploring the genetic mechanisms underlying specific phenotypic traits, including virulence, organ tropism, transmissibility, or drug resistance. Since genotyping continues to unravel the biology of mycobacteria, it offers enormous promise in the fight against and prevention of the diseases caused by these pathogens. In this review, molecular typing methods for Mycobacterium tuberculosis and nontuberculous mycobacteria elaborated over the last 2 decades are summarized. The relevance of these methods to the epidemiological investigation, diagnosis, evolution, and control of mycobacterial diseases is discussed. © 2016, American Society for Microbiology. All Rights Reserved.

Reynaud Y.,Institute Pasteur Of La Guadeloupe | Millet J.,Institute Pasteur Of La Guadeloupe | Rastogi N.,Institute Pasteur Of La Guadeloupe
PLoS ONE | Year: 2015

Tuberculosis (TB) remains broadly present in the Americas despite intense global efforts for its control and elimination. Starting from a large dataset comprising spoligotyping (n = 21183 isolates) and 12-loci MIRU-VNTRs data (n = 4022 isolates) from a total of 31 countries of the Americas (data extracted from the SITVIT2 database), this study aimed to get an overview of lineages circulating in the Americas. A total of 17119 (80.8%) strains belonged to the Euro-American lineage 4, among which the most predominant genotypic family belonged to the Latin American and Mediterranean (LAM) lineage (n = 6386, 30.1% of strains). By combining classical phylogenetic analyses and Bayesian approaches, this study revealed for the first time a clear genetic structuration of LAM9 sublineage into two subpopulations named LAM9C1 and LAM9C2, with distinct genetic characteristics. LAM9C1 was predominant in Chile, Colombia and USA, while LAM9C2 was predominant in Brazil, Dominican Republic, Guadeloupe and French Guiana. Globally, LAM9C2 was characterized by higher allelic richness as compared to LAM9C1 isolates. Moreover, LAM9C2 sublineage appeared to expand close to twenty times more than LAM9C1 and showed older traces of expansion. Interestingly, a significant proportion of LAM9C2 isolates presented typical signature of ancestral LAM-RDRio MIRU-VNTR type (224226153321). Further studies based on Whole Genome Sequencing of LAM strains will provide the needed resolution to decipher the biogeographical structure and evolutionary history of this successful family. © 2015 Reynaud et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Streit E.,Institute Pasteur Of La Guadeloupe | Millet J.,Institute Pasteur Of La Guadeloupe | Rastogi N.,Institute Pasteur Of La Guadeloupe
International Journal of Mycobacteriology | Year: 2015

Introduction: The advent of molecular typing using MIRU-VNTR mini-satellites has largely facilitated tuberculosis (TB) molecular epidemiological studies. Apart from detecting the chains of transmission and risk factors, these markers have also allowed to study the phenomena of mixed strain infections versus microevolutionary events. Methods: An initial set of Mycobacterium tuberculosis strains (n. = 161) genotyped using spoligotyping and MIRU-VNTRs in Guyana and Suriname was evaluated for indications mixed strain infections (characterized by the detection of double alleles in 2 or more MIRU loci) versus "in-patient" microevolutionary events (characterized by the detection of double alleles in a single locus). Results: The present study hereby reports evidence of microevolution in 3.7% (n= 6/161) of the studied population, vs. 0.6% (n= 1/161) for mixed infection. The strains belonged to three different spoligotyping-based lineages, namely the T (SITs 44, 53, and 1081), Haarlem (SIT47), and EAI (SITs 72 and 349) lineages, while 1 isolate (SIT237) could not be assigned to any lineage. Discussion: By comparing these results on microevolutionary cases (n= 6) to 112,000 strains present in the SITVIT2 database, evidence is presented that in 2/6 cases (each case corresponding to 2 patterns due to MIRU double bands), one of the patterns corresponded to a shared type found exclusively in Suriname or Guyana. Phylogenetic analysis showed that no spoligotyping lineage in particular was more prone to microevolutionary events in this study's sample. Overall, the observations fortify the awareness regarding the existence of microevolution and polyclonal TB infections which has important implications for patient care. © 2015 Asian-African Society for Mycobacteriology.

Couvin D.,Institute Pasteur Of La Guadeloupe | Rastogi N.,Institute Pasteur Of La Guadeloupe
Tuberculosis | Year: 2015

We argue in favor of a concerted and coordinated response to stop tuberculosis (TB) by monitoring global TB spread, drug-resistance surveillance and populations at risk using available molecular and web tools to identify circulating clones of Mycobacterium tuberculosis complex (MTBC). We took specific example of the Beijing lineage associated with worldwide emergence of both multiple, and extensively drug resistant (MDR/XDR)-TB. The study dataset (n = 10,850 isolates, 92 countries of patient origin) was extracted from our multimarker SITVIT2 database on MTBC genotyping (n = 111,635 isolates, 169 countries of patient origin). Epidemiological and demographic information in conjunction with spoligotyping (n = 10,850), MIRU-VNTR minisatellites (n = 2896), and drug resistance (n = 2846) data was mapped at macro-geographical (United Nations subregions) and country level, followed by statistical, bioinformatical, and phylogenetical analysis. The global male/female sex ratio was 1.96, the highest being 4.93 in Russia vs. range of 0.8-1.13 observed in Central America, Caribbean, Eastern Africa and Northern Europe (p < 0.0001). The major patient age-group was 21-40 yrs worldwide except Japan (with majority of patients >60 yrs). Younger patients were more common in South America, South Asia, and Western Africa since 25-33% of TB cases due to Beijing genotype occurred in the age group 0-20 yrs. A continuous progression in the proportion of MDR and XDR strains is visible worldwide since 2003 and 2009 respectively. Pansusceptible TB mainly concerned older patients >60 yrs (44%) whereas Drug resistant, MDR and XDR-TB concerned patients preferentially aged 21-40 yrs (between 52 and 58%). Although the proportion of SIT1 pattern vs. other patterns was very high (93%); the proportion of MDR was highest for an emerging genotype SIT190 (p < 0.0001). Lastly, proportion of pansusceptible strains was highest in Japan, while MDR/XDR strains were most common in Russia and Northern Europe. We underline remarkable macro/micro-geographical cleavages in phylogenetic and epidemiologic diversity of Beijing genotype, with phylogeographical specificity of certain genotypes. © 2015 Elsevier Ltd. All rights reserved.

Reynaud Y.,Institute Pasteur Of La Guadeloupe | Rastogi N.,Institute Pasteur Of La Guadeloupe
Tuberculosis | Year: 2016

We recently showed that the Mycobacterium tuberculosis sublineage LAM9 could be subdivided as two distinct subpopulations – each reflecting its unique biogeographical structure and evolutionary history. We subsequently attempted to verify if this genetic structuration could be traced in an enlarged global sample. For this purpose, we analyzed global evolutionary relationships of LAM strains in a large dataset (n = 1923 isolates from 35 countries worldwide) with concomitant spoligotyping and MIRU-VNTR data, followed by a deeper analysis of LAM9 sublineage (n = 851 isolates). Based on a combination of phylogenetical analysis and Bayesian statistics, a total of three different clusters, tentatively named LAM9C1, C2 and C3 were described in this dataset. Closer inspection of the phylogenetic tree with concomitant data on origin of isolates with genetic clusterization revealed LAM9C3 being the most tightly knit group exclusively found in the Old World as opposed to LAM9C2 being a loosely-knit group without any phylogeographical specificity; while LAM9C1 appeared with a majority of strains being well-clustered despite some isolates that intermixed with unrelated LAM clusters. Subsequently, we hereby describe a new M. tuberculosis LAM sublineage named LAM9C3 with phylogeographical specificity for the Old World. These findings open new perspectives to study respective migration histories and adaptation to human hosts of specific M. tuberculosis clones during the exploration and conquest of the New World. We therefore plan to reevaluate the nomenclature and evolutionary history of various LAM sublineages using Whole Genome Sequencing (WGS). © 2016 Elsevier Ltd

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