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1. Core genome sequencing and genotyping of Leptospira interrogans in clinical samples by target capture sequencing

Author: Linda Grillova, Thomas Cokelaer, Jean-François Mariet, Juliana Pipoli da Fonseca, Mathieu Picardeau, Biologie des Spirochètes / Biology of Spirochetes, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biomics (plateforme technologique), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, This work was supported by the Institut Pasteur through grant PTR 30-2017 and Santé Publique France to MP. TC and JP (Biomics Platform, C2RT, Institut Pasteur, Paris, France), supported by France Génomique (ANR-10-INBS-09) and IBISA., and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: Leptospira, MESH: Genotype, Genotyping, MESH: Leptospira interrogans, Infectious Diseases, MESH: Humans, [SDV]Life Sciences [q-bio], Leptospirosis, MESH: Animals, Genomics, MESH: Leptospirosis, MESH: Zoonoses, MESH: Leptospira
Abstract: Background The life-threatening pathogen Leptospira interrogans is the most common agent of leptospirosis, an emerging zoonotic disease. However, little is known about the strains that are currently circulating worldwide due to the fastidious nature of the bacteria and the difficulty to isolate cultures. In addition, the paucity of bacteria in blood and other clinical samples has proven to be a considerable challenge for directly genotyping the agent of leptospirosis directly from patient material. Our understanding of the genetic diversity of strains during human infection is therefore limited. Methods Here, we carried out hybridization capture followed by Illumina sequencing of the core genome directly from 20 clinical samples that were PCR positive for pathogenic Leptospira to elucidate the genetic diversity of currently circulating Leptospira strains in mainland France. Results Capture with RNA probes covering the L. interrogans core genome resulted in a 72 to 13,000-fold increase in pathogen reads relative to standard sequencing without capture. Variant analysis of the genomes sequenced from the biological samples using 273 Leptospira reference genomes was then carried out to determine the genotype of the infecting strain. For samples with sufficient coverage (19/20 samples with coverage > 8×), we could unambiguously identify L. interrogans serovars Icterohaemorrhagiae and Copenhageni (14 samples), L. kirschneri serovar Grippotyphosa (4 samples), and L. interrogans serovar Pyrogenes (1 sample) as the infecting strains. Conclusions We obtained high-quality genomic data with suitable coverage for confident core genome genotyping of the agent of leptospirosis for most of our clinical samples. The recovery of the genome of the serovars Icterohaemorrhagiae and Copenhageni directly from multiple clinical samples revealed low adaptive diversification of the core genes during human infection. The ability to generate culture-free genomic data opens new opportunities for better understanding of the epidemiology of this fastidious pathogen and pathogenesis of this neglected disease.
Published: 2023
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2. Investigating the role of the carbon storage regulator A (CsrA) in Leptospira spp

Author: Theerapat Phoka, Lenka Fule, Juliana Pipoli Da Fonseca, Thomas Cokelaer, Mathieu Picardeau, Kanitha Patarakul, Chulalongkorn University [Bangkok], Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Biomics (plateforme technologique), This work is part of the PhD thesis of T.P., who received financial support from 'the 100th Anniversary Chulalongkorn University for Doctoral Scholarship and the 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund)'. K.P. is partly supported by Chulalongkorn University GB-CU-61-12-30-02 and Ratchadaphiseksomphot Endowment Fund (Matching fund), Faculty of Medicine, Chulalongkorn University. This research was also supported by ANR LEPTOMOVE (18-CE15-0027-01) to M.P. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., We thank the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA., ANR-18-CE15-0027,LEPTOMOVE,Mécanismes moléculaires de la motilité chez les spirochètes: le modèle de l'endoflagelle des leptospires(2018), Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Subjects: Pathogen Motility, Virulence Factors, [SDV]Life Sciences [q-bio], Science, Gene Expression, Electrophoretic Mobility Shift Assay, Restriction Fragment Mapping, Pathology and Laboratory Medicine, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Bacterial Proteins, Gene Types, Medicine and Health Sciences, Genetics, Gene Expression and Vector Techniques, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Alleles, 030304 developmental biology, Leptospira, 2. Zero hunger, Molecular Biology Assays and Analysis Techniques, 0303 health sciences, Multidisciplinary, Bacteria, 030306 microbiology, Gene Mapping, Organisms, RNA-Binding Proteins, Biology and Life Sciences, Carbon, Bacterial Pathogens, Leptospira Interrogans, Phenotype, Genes, Bacterial, Medical Microbiology, Regulator Genes, Hyperexpression Techniques, Medicine, Pathogens, Gene Deletion, Research Article
Abstract: Carbon Storage Regulator A (CsrA) is a well-characterized post-transcriptional global regulator that plays a critical role in response to environmental changes in many bacteria. CsrA has been reported to regulate several metabolic pathways, motility, biofilm formation, and virulence-associated genes. The role of csrA in Leptospira spp., which are able to survive in different environmental niches and infect a wide variety of reservoir hosts, has not been characterized. To investigate the role of csrA as a gene regulator in Leptospira, we generated a L. biflexa csrA deletion mutant (ΔcsrA) and csrA overexpressing Leptospira strains. The ΔcsrA L. biflexa displayed poor growth under starvation conditions. RNA sequencing revealed that in rich medium only a few genes, including the gene encoding the flagellar filament protein FlaB3, were differentially expressed in the ΔcsrA mutant. In contrast, 575 transcripts were differentially expressed when csrA was overexpressed in L. biflexa. Electrophoretic mobility shift assay (EMSA) confirmed the RNA-seq data in the ΔcsrA mutant, showing direct binding of recombinant CsrA to flaB3 mRNA. In the pathogen L. interrogans, we were not able to generate a csrA mutant. We therefore decided to overexpress csrA in L. interrogans. In contrast to the overexpressing strain of L. biflexa, the overexpressing L. interrogans strain had poor motility on soft agar. The overexpressing strain of L. interrogans also showed significant upregulation of the flagellin flaB1, flaB2, and flaB4. The interaction of L. interrogans rCsrA and flaB4 was confirmed by EMSA. Our results demonstrated that CsrA may function as a global regulator in Leptospira spp. under certain conditions that cause csrA overexpression. Interestingly, the mechanisms of action and gene targets of CsrA may be different between non-pathogenic and pathogenic Leptospira strains.
Published: 2021
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3. First Report of Human Leptospira Santarosai Infection in French Guiana

Author: Didier Hommel, Séverine Matheus, Stéphanie Houcke, Valérie Caro, Hatem Kallel, Mathieu Picardeau, Claire Mayence, Pascale Bourhy, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris], Biologie des Spirochètes / Biology of Spirochetes, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), This study was supported in part by public funds allocated for the National Reference Center for Leptospirosis by the French Ministry of Health and also by the EMERGUY research program supported by European funds (FEDER) and assistance from the Region Guyane and Direction Régionale pour la Recherche et la Technologie., and Institut Pasteur [Paris] (IP)
Subjects: Male, 0301 basic medicine, Serotype, medicine.medical_specialty, Overseas department, [SDV]Life Sciences [q-bio], 030106 microbiology, Serogroup, Leptospira santarosai, lcsh:Infectious and parasitic diseases, Serology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Leptospira, law, Epidemiology, Animals, Humans, Medicine, lcsh:RC109-216, Leptospirosis, 030212 general & internal medicine, Retrospective Studies, biology, business.industry, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, General Medicine, Middle Aged, biology.organism_classification, medicine.disease, Intensive care unit, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, French Guiana, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Emergency medicine, business, Human
Abstract: International audience; Leptospirosis is a zoonotic disease with worldwide distribution. In French Guiana, a French overseas department of South America, this bacterial infection is endemic with the increase of human cases since the last 5 years. Nevertheless, the epidemiological data on the circulating infecting strain remains scarce due to the lack of specific symptoms and the used diagnostic approaches. We report a severe case of leptospirosis in a 52-years-old male, working as a street cleaner, hospitalized at the Intensive Care Unit of city capital hospital of French Guiana because of hemodynamic, neurological, renal, and respiratory failure. At ICU admission, the patient was comatose, his temperature was 37.3°C, heart rate 104 beats per minute, blood pressure 84/45mmHg, and oxygen saturation 95% while under mechanical ventilation. Retrospective exploration using molecular and serological approaches from the samples allowed reporting an infection by Leptospira santarosai serogroup Sejroe serovar Hardjo. To our knowledge, this is the first human case infected with this species in French Guiana. Through these analyses, this report provides new epidemiological information about the Leptospira strains circulating in French Guiana. In particular, this emphasizes the importance of accurate diagnosis to characterize with more precision the circulating Leptospira strains in this department.
Published: 2020
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4. The zoonotic pathogen Leptospira interrogans mitigates environmental stress through cyclic-di-GMP-controlled biofilm production

Author: Julien Fernandes, Emilie Bierque, Dominique Girault, Malia Kainiu, Mathieu Picardeau, Joëlle Vinh, Nicolas Eskenazi, Anthony Douyère, Heike Bähre, Marie-Estelle Soupé-Gilbert, Roman Thibeaux, Cyrille Goarant, Unité de Recherche et d'Expertise Leptospirose - Leptospirosis Research and Expertise Unit [Nouméa, Nouvelle-Calédonie] (UREL), Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Institut Pasteur [Paris] (IP), Hannover Medical School [Hannover] (MHH), Institut de sciences exactes et appliquées (ISEA), Université de la Nouvelle-Calédonie (UNC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), Spectrométrie de Masse Biologique et Protéomique (USR3149 / FRE2032) (SMBP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, This work was funded by a postdoctoral fellowship awarded by the AXA Research Fund (reference: 15-AXA-PDOC-037). Lastly, we thank the UTechS Photonic BioImaging facility (Imagopole, C2RT, Institut Pasteur) funded by the French National Research Agency (France BioImaging, ANR-10–INSB–04, Investments for the Future programme)., The authors thank Johann Peltier, Nadia Benaroudj, Robert Antony Gaultney, Linda Guentas, Arnaud Tarantola and Catherine Inizan for technical assistance and critical discussions. The authors are indebted to Professor Jean-Marc Ghigo for critical discussions and support at the start of this project. We thank Julien Colot and the Laboratoire de Biologie Médicale at Centre Hospitalier Territorial Gaston Bourret for granting access to their MALDI-TOF facilities. We also thank the CRESICA consortium for granting access to the electron microscopy facilities., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), and Institut Pasteur [Paris]
Subjects: Cyclic di-GMP, Bacterial Zoonoses, Virulence, Applied Microbiology and Biotechnology, Microbiology, lcsh:Microbial ecology, Article, 03 medical and health sciences, chemistry.chemical_compound, Spatio-Temporal Analysis, Bacterial Proteins, Stress, Physiological, Guanosine monophosphate, Animals, Humans, Cyclic GMP, 030304 developmental biology, 0303 health sciences, biology, Environmental microbiology, 030306 microbiology, Phosphoric Diester Hydrolases, Escherichia coli Proteins, Biofilm, Biofilm matrix, Gene Expression Regulation, Bacterial, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, chemistry, Biofilms, Mutation, biology.protein, lcsh:QR100-130, Diguanylate cyclase, Leptospira interrogans, Phosphorus-Oxygen Lyases, Bacteria, Biotechnology
Abstract: The zoonotic bacterium Leptospira interrogans is the aetiological agent of leptospirosis, a re-emerging infectious disease that is a growing public health concern. Most human cases of leptospirosis result from environmental infection. Biofilm formation and its contribution to the persistence of virulent leptospires in the environment or in the host have scarcely been addressed. Here, we examined spatial and time-domain changes in biofilm production by L. interrogans. Our observations showed that biofilm formation in L. interrogans is a highly dynamic process and leads to a polarized architecture. We notably found that the biofilm matrix is composed of extracellular DNA, which enhances the biofilm’s cohesiveness. By studying L. interrogans mutants with defective diguanylate cyclase and phosphodiesterase genes, we show that biofilm production is regulated by intracellular levels of bis-(3′–5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) and underpins the bacterium’s ability to withstand a wide variety of simulated environmental stresses. Our present results show how the c-di-GMP pathway regulates biofilm formation by L. interrogans, provide insights into the environmental persistence of L. interrogans and, more generally, highlight leptospirosis as an environment-borne threat to human health.
Published: 2020
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5. Usefulness of C-Reactive Protein in Differentiating Acute Leptospirosis and Dengue Fever in French Guiana

Author: Mathieu Nacher, Loïc Epelboin, Timothée Bonifay, Pascale Bourhy, Magalie Demar, Félix Djossou, Anne Jolivet, Emilie Mosnier, Paul Le Turnier, Roxane Schaub, Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université des Antilles (UA), Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Département des Centres Délocalisés de Prévention et de Soins, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Centre Hospitalier de l'Ouest Guyanais, Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris], The authors acknowledge Rachida Boukhari (Hopital Franck Joly, Saint-Laurent du Maroni, French Guiana), Anne Terraz (Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana), Denis Blanchet (Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana), and Mathieu Picardeau (Institut Pasteur, Centre National de Référence de la Leptospirose, Paris, France) for their help in the data collection., Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut Pasteur [Paris] (IP), and Matillon, Mirlène
Subjects: 0301 basic medicine, myalgia, medicine.medical_specialty, Anemia, diagnosis, [SDV]Life Sciences [q-bio], 030106 microbiology, 030231 tropical medicine, Neutropenia, Dengue fever, Major Articles, C-reactive protein, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, dengue fever, leptospirosis, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Creatinine, biology, business.industry, medicine.disease, Leptospirosis, 3. Good health, French Guiana, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Oncology, chemistry, biology.protein, Biomarker (medicine), medicine.symptom, business
Abstract: Objective Leptospirosis and dengue fever (DF) are hard-to-differentiate diseases in cocirculating areas, especially during DF epidemics. Misdiagnosis and ensuing lack of antibiotic therapy can be detrimental in leptospirosis. The objective of this study was to identify factors that help differentiate acute leptospirosis from dengue fever on admission. Method Patients with leptospirosis (positive serology or polymerase chain reaction) were compared with patients with DF (positive nonstructural 1 [NS1] antigen) in a case-control study with age matching. Data on admission were compared using bivariate analysis and multivariate analysis. Results Seventy-two patients with leptospirosis were compared to 216 patients with DF. In bivariate analysis, the factors associated with leptospirosis were male gender, cough, anemia, and elevated blood levels of C-reactive protein (CRP), leukocytes, creatinine, bilirubin, and creatine phosphokinase. Exanthema, purpura, myalgia, headache, and neutropenia were associated with DF. In multivariate analysis, elevated blood levels of leukocytes, bilirubin, and CRP were associated with leptospirosis. The CRP threshold of 50 mg/L taken alone had elevated sensitivity and specificity. Conclusions The CRP level, an easy-to-obtain biomarker, was a powerful tool to differentiate on admission leptospirosis and DF. Facing a dengue-like syndrome in cocirculating areas and awaiting new specific rapid diagnostic tests, CRP dosing could help the clinician to promptly consider the diagnosis of leptospirosis and initiate antibiotic therapy early., Leptospirosis and dengue fever are hard-to-differentiate diseases in the tropics. In this case-control study, their presentation on admission was compared. A C-reactive protein (CRP) level >50 mg/L was associated with leptospirosis. Facing a dengue-like syndrome in cocirculating areas and awaiting new specific rapid diagnostic tests, CRP dosing could help the clinician to promptly consider the diagnosis of leptospirosis and initiate antibiotic therapy early.
Published: 2019
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6. An outbreak of leptospirosis among kayakers in Brittany, North-West France, 2016

Author: Florence Ayral, Céline Richomme, Benoît Combes, Yvonnick Guillois, Pascale Bourhy, Mathilde Pivette, Célia Malhère, Marine Le Guyader, José Héctor Aranda Grau, Lisa Antoinette King, Benoît Champenois, Alexandra Septfons, Anouk Decors, SANTE PUBLIQUE FRANCE - RENNES, Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris], Rongeurs Sauvages, Risques Sanitaires et Gestion des Populations - UR 1233 (RS2GP), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA), Office Nationale de la Chasse et de la Faune Sauvage, Agence régionale de santé (ARS) de Bretagne (ARS Bretagne), Direction Générale de l'Alimentation (DGAL), Ministère de l'agriculture, de l'agroalimentaire et de la forêt, Entente de lutte interdépartementale contre les zoonoses (ELIZ), Etablissement Public Interdépartemental, Laboratoire de la rage et de la faune sauvage de Nancy (LRFSN), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Funding :- The Agence régionale de santé de Bretagne, Santé publique France and the National Reference Centre for Leptospirosis are supported by public funds allocated by the French Ministry of Health.- The Nancy laboratory for rabies and wildlife of the French Agency for Food, Environmental and Occupational Health & Safety (Anses) is supported by public funds mainly from the French Ministry of Agriculture and Food.- VetAgro Sup is supported by public funds allocated by the French Ministry of Agriculture and Food.The Entente de Lutte Interdépartementale contre les Zoonoses is an association of 40 administrative Local Collectivities mainly funded by French departmental Councils and partly by the French Ministry of Agriculture.- The Office National de la Chasse et de la Faune sauvage is supported by public funds from French Ministries of Agriculture and Environment., The authors wish to thank the team at the Agence régionale de santé Bretagne who validated the outbreak alert, Météo- France that provided weather data and all patients and private and clinical laboratories who cooperated with the investigations., Institut Pasteur [Paris] (IP), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), and Entente de Lutte Interdépartementale contre les Zoonoses (ELIZ)
Subjects: 0301 basic medicine, DNA, Bacterial, Male, Skin wound, descriptive study, Epidemiology, [SDV]Life Sciences [q-bio], 030106 microbiology, Animals, Wild, Disease cluster, Polymerase Chain Reaction, Serology, Disease Outbreaks, 03 medical and health sciences, Virology, Environmental health, medicine, Animals, Humans, leptospirosis, kayak, Water Sports, Leptospira, biology, outbreak, animal reservoir, Individual prevention, Public Health, Environmental and Occupational Health, Outbreaks, Outbreak, biology.organism_classification, medicine.disease, Leptospirosis, Antibodies, Bacterial, 3. Good health, Leptospira kirschneri, Geography, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, North west, Female, France, Sports
Abstract: In September 2016, a cluster of seven kayakers with clinical symptoms of leptospirosis with onset since July 2016 was reported to French health authorities. Human and animal investigations were undertaken to describe the outbreak, identify the likely place and source of infection and implement necessary control measures. We identified 103 patients with clinical symptoms of leptospirosis between 1 June and 31 October 2016 who lived in the Ille-et-Vilaine district in Brittany. Of these, 14 (including the original seven) reported contacts with the river Vilaine during the incubation period and were defined as outbreak cases: eight were confirmed by serology tests or PCR and six were probable without a laboratory confirmation for leptospirosis. All 14 cases were kayakers. Three distinct contamination sites were identified on a 30 km stretch of the river Vilaine. Nine cases reported having skin wounds while kayaking. None were vaccinated against leptospirosis. The outbreak was attributed to Leptospira kirschneri serogroup Grippotyphosa. Animal investigations did not allow identifying the possible reservoir. Leptospirosis outbreaks associated with freshwater sports are rare in temperate climates. The prevention of such outbreaks requires control of potential animal reservoirs in zones such as the Vilaine valley and that kayakers adopt the recommended individual prevention measures.
Published: 2018
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7. Deciphering the unexplored Leptospira diversity from soils uncovers genomic evolution to virulence

Author: Emilie Bierque, Dominique Girault, Ignacio Ferrés, Mathieu Picardeau, Gregorio Iraola, Roman Thibeaux, Cyrille Goarant, Marie-Estelle Soupé-Gilbert, Unité de Recherche et d'Expertise Leptospirose - Leptospirosis Research and Expertise Unit [Nouméa, Nouvelle-Calédonie] (UREL), Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Bioinformatics / Bioinformática [Montevideo], Institut Pasteur de Montevideo, Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, 030106 microbiology, Biodiversity, Virulence, Genomics, Microbial Evolution and Epidemiology: Zoonosis/Anthroponosis, Biology, Genome, Statistics, Nonparametric, Evolution, Molecular, 03 medical and health sciences, New Caledonia, Leptospira, Genus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Phylogenomics, Gene Duplication, evolution, genomics, Prevalence, Humans, Leptospirosis, Phylogeny, Soil Microbiology, Repetitive Sequences, Nucleic Acid, Phylogenetic tree, Whole Genome Sequencing, General Medicine, biology.organism_classification, 030104 developmental biology, Evolutionary biology, ecology, Genome, Bacterial, Research Article
Abstract: Despite recent advances in our understanding of the genomics of members of the genus Leptospira, little is known on how virulence has emerged in this heterogeneous bacterial genus as well as on the lifestyle of pathogenic members of the genus Leptospira outside animal hosts. Here, we isolated 12 novel species of the genus Leptospira from tropical soils, significantly increasing the number of known species to 35 and finding evidence of highly unexplored biodiversity in the genus. Extended comparative phylogenomics and pan-genome analyses at the genus level by incorporating 26 novel genomes, revealed that, the traditional leptospiral ‘pathogens’ cluster, as defined by their phylogenetic position, can be split in two groups with distinct virulence potential and accessory gene patterns. These genomic distinctions are strongly linked to the ability to cause or not severe infections in animal models and humans. Our results not only provide new insights into virulence evolution in the members of the genus Leptospira, but also lay the foundations for refining the classification of the pathogenic species.
Published: 2018
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8. Leptospirosis in French Guiana and the Guiana shield: Current knowledge in 2016

Author: Alain Berlioz-Arthaud, P. Le Turnier, F. Djossou, M. Demar, Pascale Bourhy, Mathieu Picardeau, Yann Reynaud, Emilie Mosnier, Loïc Epelboin, Cécile Richard-Hansen, Mathieu Nacher, Gabriel Carles, Roxane Schaub, B. de Thoisy, Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Université de Guyane (UG), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris], Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Unité de la Tuberculose et des Mycobactéries - WHO Supranational TB Reference Laboratory, Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Service de gynécologie-obstétrique, Centre Hospitalier de l'Ouest Guyanais, Office National de la Chasse et de la Faune Sauvage, Unité des Maladies Infectieuses et Tropicale, Centre Hospitalier de Cayenne, Institut Pasteur [Paris] (IP), and Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]
Subjects: 0301 basic medicine, medicine.medical_specialty, Latin Americans, [SDV]Life Sciences [q-bio], 030231 tropical medicine, 030106 microbiology, Q fever, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Leptospira, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, medicine, biology, Amazon rainforest, Public health, Zoonosis, medicine.disease, biology.organism_classification, Leptospirosis, 3. Good health, Geography, Ethnology, Malaria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Leptospirosis is a cosmopolitan zoonosis caused by bacteria of the genus Leptospira. Whether the distribution is worldwide, the hot and humid climate of the tropics is particularly conducive to its expansion. In most French overseas departments and territories, leptospirosis is considered as a public health problem. In French Guiana, a French department located in the northeastern part of the Amazon rainforest, it is supposed to be rare. The objective of this review was to make an inventory of the knowledge on human and animal leptospirosis in French Guiana and neighboring countries. A comprehensive search was conducted through the indexed and informal medical literature in English, French, Spanish and Portuguese. Thus, respectively ten and four publications were identified on human and animal leptospirosis in French Guiana, published between 1940 and 1995 in the form of case reports or case series. The publications concerning this disease in the other countries of the Guiana Shield, eastern Venezuela, Guyana, Suriname, and Brazilian state of Amapá, also scarce or nonexistent. However recent data from the French National Centre of leptospirosis showed a recent and sudden increase in the number of cases in the department, probably partly due to the development of diagnostic tools such as Elisa IgM serology. It is likely that leptospirosis is a neglected disease in the region, due to the lack of diagnostic tools readily available, the lack of knowledge of the local clinicians on this disease and the existence of many other pathogens with similar clinical presentation such as malaria, arboviruses and Q fever and Amazonian toxoplasmosis. The establishment of more large-scale studies on animal and human leptospirosis is necessary and urgent to know the true burden of this disease in our region.
Published: 2017
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9. Underestimation of leptospirosis incidence in the French West Indies

Author: Cassadou, Sylvie, Rosine, Jacques, Flamand, Claude, Escher, Martina, Ledrans, Martine, Bourhy, Pascale, Storck-Herrmann, Cécile, Guyomard-Rabenirina, Stéphanie, Olive, Claude, Theodose, Rafäelle, Hochedez, Patrick, Cabié, André, Lamaury, Isabelle, Adrien, Jean-Baptiste, Picardeau, Mathieu, Quénel, Philippe, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Unité d'Epidémiologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP), CHU de la Martinique [Fort de France], Centre Hospitalier de Basse-Terre, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Quénel, Philippe, Institut Pasteur [Paris], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: Disease surveillance, Incidence, Leptospirose, Mortalité, Morbidité, Hospitals, Public and occupational health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, French West Indies, Létalité, Martinique, Leptospirosis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Enzyme-linked immunoassays, Mortality, Morbidity, Antilles françaises, Guadeloupe, Case fatality
Abstract: Leptospirosis is a neglected disease which affects all tropical regions, particularly South America and the Caribbean. Its incidence and case-fatality rates are poorly known, and probably highly underestimated. In order to estimate the real incidence of leptospirosis in the French West Indies, an incidence study was performed in 2011 using the three prevailing available biological tests for diagnosis: Microscopic Agglutination Test (MAT), IgM ELISA and PCR. The study investigated inpatients as well as outpatients, and used active case ascertainment from data provided by a general practitioners’ sentinel network.The incidence of leptospirosis was estimated respectively at 69 and 61 annual cases per 100,000 inhabitants respectively in Guadeloupe and Martinique, representing an incidence 100 times higher than in Mainland France for the study period. The results also show that using PCR-real time for diagnosis has allowed identifying cases many more cases than that would not have been detected without having recourse to this test. It also contributes to early detection of the disease, reducing the risk of complications due to leptospirosis through the prescription of an antibiotic therapy.It has also been possible to describe the epidemiology of the disease in terms of severity, demographic characteristics and seasonal patterns. Besides, these results support the relevance of developing an integrated management strategy for surveillance, prevention and control of the disease in the French West Indies., La leptospirose est l'une des maladies dites négligées des pays du Sud, en particulier en Amérique latine et dans la Caraïbe. Son incidence réelle et sa létalité sont incertaines, cette dernière étant probablement élevée. Afin d'estimer l'impact sanitaire réel de la maladie aux Antilles françaises, une étude d'incidence a été conduite en 2011, en mettant en oeuvre l'ensemble des outils diagnostiques aujourd'hui disponibles : le test de micro-agglutination (MAT), la sérologie Elisa IgM et la PCR. Cette étude a pris en compte non seulement les patients hospitalisés mais également, grâce aux réseaux de médecins généralistes sentinelles, les patients ambulatoires pris en charge par leur médecin traitant. L'incidence de la leptospirose a été estimée à 69 et 61 cas annuels pour 100 000 habitants, respectivement en Guadeloupe continentale et en Martinique, soit une incidence plus de 100 fois supérieure à celle de la métropole à la période de l'étude. Les résultats montrent également que l'accès au diagnostic par PCR conduit à un nombre de cas aux Antilles très largement supérieur à celui dénombré antérieurement ; il permet en outre de diagnostiquer la maladie en phase précoce, limitant le risque de complications de la leptospirose par la prescription d'un traitement antibiotique. L'épidémiologie de la maladie a pu être également décrite en termes de sévérité, de caractéristiques démographiques et de saisonnalité. Les résultats confirment la pertinence de la mise en place d'un système de surveillance épidémiologique à visée d'alerte, étroitement articulé avec une stratégie de prévention et de contrôle de la maladie.
Published: 2017

10. Sous-estimation de l’incidence de la leptospirose aux Antilles françaises

Author: Sylvie Cassadou, Jacques Rosine, Claude Flamand, Martina Escher, Martine Ledrans, Pascale Bourhy, Cécile Storck-Herrmann, Stéphanie Guyomard-Rabenirina, Claude Olive, Rafäelle Theodose, Patrick Hochedez, André Cabié, Isabelle Lamaury, Jean-Baptiste Adrien, Mathieu Picardeau, PHILIPPE QUENEL, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Unité d'Epidémiologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP), CHU de la Martinique [Fort de France], Centre Hospitalier de Basse-Terre, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: Disease surveillance, Incidence, Leptospirose, Morbidité, Mortalité, Hospitals, Public and occupational health, French West Indies, Létalité, Martinique, Leptospirosis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Enzyme-linked immunoassays, Morbidity, Mortality, Antilles françaises, Guadeloupe, Case fatality
Abstract: National audience; Leptospirosis is a neglected disease which affects all tropical regions, particularly South America and the Caribbean. Its incidence and case-fatality rates are poorly known, and probably highly underestimated. In order to estimate the real incidence of leptospirosis in the French West Indies, an incidence study was performed in 2011 using the three prevailing available biological tests for diagnosis: Microscopic Agglutination Test (MAT), IgM ELISA and PCR. The study investigated inpatients as well as outpatients, and used active case ascertainment from data provided by a general practitioners’ sentinel network.The incidence of leptospirosis was estimated respectively at 69 and 61 annual cases per 100,000 inhabitants respectively in Guadeloupe and Martinique, representing an incidence 100 times higher than in Mainland France for the study period. The results also show that using PCR-real time for diagnosis has allowed identifying cases many more cases than that would not have been detected without having recourse to this test. It also contributes to early detection of the disease, reducing the risk of complications due to leptospirosis through the prescription of an antibiotic therapy.It has also been possible to describe the epidemiology of the disease in terms of severity, demographic characteristics and seasonal patterns. Besides, these results support the relevance of developing an integrated management strategy for surveillance, prevention and control of the disease in the French West Indies.; La leptospirose est l'une des maladies dites négligées des pays du Sud, en particulier en Amérique latine et dans la Caraïbe. Son incidence réelle et sa létalité sont incertaines, cette dernière étant probablement élevée. Afin d'estimer l'impact sanitaire réel de la maladie aux Antilles françaises, une étude d'incidence a été conduite en 2011, en mettant en oeuvre l'ensemble des outils diagnostiques aujourd'hui disponibles : le test de micro-agglutination (MAT), la sérologie Elisa IgM et la PCR. Cette étude a pris en compte non seulement les patients hospitalisés mais également, grâce aux réseaux de médecins généralistes sentinelles, les patients ambulatoires pris en charge par leur médecin traitant. L'incidence de la leptospirose a été estimée à 69 et 61 cas annuels pour 100 000 habitants, respectivement en Guadeloupe continentale et en Martinique, soit une incidence plus de 100 fois supérieure à celle de la métropole à la période de l'étude. Les résultats montrent également que l'accès au diagnostic par PCR conduit à un nombre de cas aux Antilles très largement supérieur à celui dénombré antérieurement ; il permet en outre de diagnostiquer la maladie en phase précoce, limitant le risque de complications de la leptospirose par la prescription d'un traitement antibiotique. L'épidémiologie de la maladie a pu être également décrite en termes de sévérité, de caractéristiques démographiques et de saisonnalité. Les résultats confirment la pertinence de la mise en place d'un système de surveillance épidémiologique à visée d'alerte, étroitement articulé avec une stratégie de prévention et de contrôle de la maladie.
Published: 2017

11. Human leptospirosis in French Guiana: current knowledge and perspectives

Author: Epelboin, Loïc, Le Turnier, Paul, Picardeau, Mathieu, Schaub, Roxane, Petit-Sinturel, Marion, Villemant, Nicolas, Trombert-Paolantoni, Sabine, Berlioz-Arthaud, Alain, Bisser, Sylvie, Mosnier, Emilie, Ardillon, Vanessa, Jolivet, Anne, Demar, Magalie, Nacher, Mathieu, Bourhy, Pascale, Djossou , Felix, Université de Guyane (UG), Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris] (IP), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Cellule Inter Régionale d'Epidémiologie des Antilles - Guyane, Institut de Veille Sanitaire (INVS), Université Paris 1 Panthéon-Sorbonne - UFR Géographie (UP1 UFR08), Université Paris 1 Panthéon-Sorbonne (UP1), Laboratoire CERBA [Saint Ouen l'Aumône], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Département des Centres Délocalisés de Prévention et de Soins, Centre Hospitalier de l'Ouest Guyanais, Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH Guyane), Centre d'Investigation Clinique Antilles Guyane, Inserm CIC1424, Institut Pasteur [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]
Subjects: Leptospira, Epidemiology, [SDV]Life Sciences [q-bio], Neglected tropical disease, Leptospirose, Maladie tropicale négligée, French Guiana, Épidémiologie, Zoonosis, Guyane française // Keywords: Leptospirosis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Guyane française, Zoonose, Leptospirosis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Leptospirosis is a cosmopolitan zoonosis caused by the bacteria of the genus Leptospira. The warm and wet climate of the intertropical zone is particularly favorable with its expansion. In French Guiana, a French territory located at the North-East of the South American continent in Amazonian area, it seems to be rare. The objective of this article is to make the inventory of current knowledge on the epidemiology of human leptospirosis in French Guiana, and to discuss the prospects concerning this disease and improve its surveillance. Publications on leptospirosis in French Guiana are rare and old, and date from 1940 to 1995. The annual reports of the National Reference Centre of Leptospirosis (NRC, Pasteur Institute) show a quite stable annual number of cases, varying from 6 to 18 between 1996 and 2012, depending on the year, with a significant increase from 2013 to 2015, respectively 36, 92 and 67 cases a year. A retrospective study conducted recently on the cases which occurred between 2007 and 2014 with very strict inclusion criteria, identified 72 cases on the territory, among whom 12 (16.7%) severe cases and 3 (4.2%) deaths. The disease affects mainly men (86.1%) aged between 20 and 49 years (63.9%). It is probable that leptospirosis is a neglected disease in the region, due to the absence of quickly available diagnostic tools, the lack of awareness of clinicians on this pathology, and the existence of many other infectious agents with similar clinical presentations during acute episodes (such as malarias, arboviruses, Q fever and Amazonian toxoplasmosis). The implementation of larger studies is necessary to know the true burden of this disease in French Guiana., La leptospirose est une zoonose cosmopolite causée par les bactéries du genre Leptospira. Le climat chaud et humide de la zone intertropicale est particulièrement propice à son expansion. En Guyane, département français situé au nord-est du continent sud-américain, en région amazonienne, elle semble rare. L’objectif de cet article est de récapituler l’état des connaissances actuelles sur l’épidémiologie de leptospirose humaine en Guyane et de discuter les perspectives pour en améliorer la surveillance.Les publications sur la leptospirose en Guyane sont rares et anciennes, datant des années 1940-1995. Les rapports annuels du Centre national de référence de la leptospirose (CNR, Institut Pasteur de Paris) montrent un nombre annuel de cas assez stable entre 1996 et 2012, variant de 6 à 18 selon les années, avec une augmentation importante de 2013 à 2015 : respectivement 36, 92 et 67 cas par an. Une étude rétrospective menée récemment sur les cas survenus entre 2007 et 2014, identifiés avec des critères diagnostiques très stricts, a comptabilisé 72 cas sur le département, parmi lesquels 12 (16,7%) cas graves et 3 (4,2%) décès. La maladie touchait principalement des hommes (86,1%) âgés de 20 à 49 ans (63,9%).Il est probable que la leptospirose soit une maladie négligée dans la région, du fait de l’absence d’outils diagnostiques rapidement disponibles, de la méconnaissance des cliniciens de cette pathologie et de la présence de nombreuses autres pathologies à symptômes cliniques similaires en phase aiguë (paludismes, arboviroses, fièvre Q, toxoplasmose amazonienne). La mise en place d’études de plus grande ampleur est nécessaire pour connaître le véritable impact de cette maladie en Guyane.
Published: 2017

12. Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population

Author: Desvars-Larrive, Amélie, Pascal, Michel, Gasqui, Patrick, Cosson, Jean-Francois, Benoit, Etienne, Lattard, Virginie, Crespin, Laurent, Lorvelec, Olivier, Pisanu, Benoît, Teynie, Alexandre, Vayssier-Taussat, Muriel, Bonnet, Sarah, Marianneau, Philippe, Lacôte, Sandra, Bourhy, Pascale, Berny, Philippe, Pavio, Nicole, Le Poder, Sophie, Gilot-Fromont, Emmanuelle, Jourdain, Elsa, Hammed, Abdessalem, Fourel, Isabelle, Chikh, Farid, Vourc'h, Gwenaël, Research Institute of Wildlife Ecology, University of Veterinary Medicine [Vienna] (Vetmeduni), Écologie et santé des écosystèmes (ESE), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Rongeurs Sauvages, Risques Sanitaires et Gestion des Populations - UR 1233 (RS2GP), Patrimoine naturel (PatriNat), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Agence Française pour la Biodiversité (AFB), Unité Virologie, Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, Interactions Cellules Environnement - UR (ICE), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Virologie UMR1161 (VIRO), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Biodémographie évolutive, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Conseil Départemental Hauts-de-Seine, Conseil Départmental des Hauts-de-Seine, Institut National de la Recherche Agronomique (INRA Grant), ANR-09-CESA-0008,RODENT,Impacts des rodenticides anticoagulants sur les écosystèmes - adaptation des populations de rongeurs cibles et effets sur leurs prédateurs(2009), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Lyon, Unité Virologie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut Pasteur [Paris], Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA), University of Veterinary Medicine [Vienna] ( Vetmeduni ), Écologie et santé des écosystèmes ( ESE ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Épidémiologie des maladies animales et zoonotiques ( UMR EPIA ), Institut National de la Recherche Agronomique ( INRA ), Biologie moléculaire et immunologie parasitaires et fongiques ( BIPAR ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort-AFSSA-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Rongeurs Sauvages – Risques Sanitaires et Gestion des Populations, INRA, VetAgro Sup ( USC1233/RS2GP ), Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), UMS 2006 Patrimoine Naturel, Muséum National d'Histoire Naturelle ( MNHN ) -Centre National de la Recherche Scientifique ( CNRS ) -Agence française pour la biodiversité, Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail ( ANSES Maisons-Alfort ), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, Virologie UMR1161 ( VIRO ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort-ANSES, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), ANR-09-CESA-0008,RODENT,Impacts des rodenticides anticoagulants sur les écosystèmes - adaptation des populations de rongeurs cibles et effets sur leurs prédateurs ( 2009 ), Épidémiologie des Maladies Animales et Zoonotiques - UMR 346 (EPIA), Agence Française pour la Biodiversité (AFB)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé
Subjects: analyse de données, 0301 basic medicine, Veterinary medicine, milieu urbain, Brown rat, Population genetics, Drug Resistance, lcsh:Medicine, Artificial Gene Amplification and Extension, Pathology and Laboratory Medicine, Polymerase Chain Reaction, détection moléculaire, Gene flow, Medicine and Health Sciences, caractérisation morphologique, Rodenticide, Immunogenetic Phenomena, lcsh:Science, Mammals, Leptospira, education.field_of_study, Multidisciplinary, biology, Geography, Biodiversity, Animal Models, Bacterial Pathogens, [ SDV.GEN.GPO ] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Experimental Organism Systems, Medical Microbiology, parasite, Vertebrates, France, résistance génétique, Pathogens, Bartonella, Autre (Sciences du Vivant), Research Article, Microsatellite loci, Trypanosoma, Genotype, Genetic loci, Population, rattus norvegicus, Research and Analysis Methods, Rodents, Microbiology, 03 medical and health sciences, Model Organisms, Gene Types, Vitamin K Epoxide Reductases, Helminths, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Genetics, Animals, Parasites, education, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Genetic diversity, Evolutionary Biology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Population Biology, Bacteria, anticoagulant, lcsh:R, Urban Health, Organisms, Genetic Variation, Rodenticides, Biology and Life Sciences, [ SDV.GEN.GA ] Life Sciences [q-bio]/Genetics/Animal genetics, biology.organism_classification, Invertebrates, Blood Cell Count, Rats, Medical risk factors, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, Genetics, Population, Amniotes, [ SDV.BA.ZV ] Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, paramètre hématologique, lcsh:Q, Species richness, Biomarkers, Microsatellite Repeats
Abstract: International audience; Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.
Published: 2017
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13. Molecular characterization of Leptospira sp by multilocus variable number tandem repeat analysis (MLVA) from clinical samples: a case report

Author: Sylvie Robert, Hélène Pailhoriès, Rodolphe Buzelé, Laurent Mereghetti, Philippe Lanotte, Mathieu Picardeau, Emmanuelle Mercier, Laboratoire de Bactériologie, Institut de Biologie en Santé, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Bactériologie-Virologie, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, Service de Réanimation Médicale, Clinical Research in Intensive Care and Sepsis Group (CRICS), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Institut Pasteur [Paris] (IP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Tours, and Lanotte, Philippe
Subjects: zoonose, Fastidious organism, Male, Microbiology (medical), Genotype, VNTR, 030231 tropical medicine, Médecine humaine et pathologie, Minisatellite Repeats, Multiple Loci VNTR Analysis, lcsh:Infectious and parasitic diseases, Leptospirosis, MLVA, 03 medical and health sciences, séquence repetee en tandem, 0302 clinical medicine, Fatal Outcome, Leptospira, medicine, Humans, lcsh:RC109-216, Genetics, Electrophoresis, Agar Gel, 0303 health sciences, biology, Zoonotic Infection, 030306 microbiology, General Medicine, Middle Aged, biology.organism_classification, medicine.disease, bacterial infections and mycoses, Virology, 3. Good health, Variable number tandem repeat, Infectious Diseases, Human health and pathology, Leptospira interrogans, humain, leptosirose, analyse génétique, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Multilocus Sequence Typing
Abstract: SummaryLeptospirosis is a zoonotic infection for which diagnosis is difficult. It has appeared as a global emerging infectious disease over recent years. Genotype determination often requires a Leptospira strain obtained by culture, which is a long and fastidious technique. A method based on multilocus variable number tandem repeat analysis (MLVA) to determine the genotype of Leptospira interrogans, performed directly on blood or urine samples, is proposed. This method was applied to a fatal case of leptospirosis for which the geographical origin of infection was unknown. This technique will allow a genotype to be obtained for L. interrogans, even when cultures remain negative.
Published: 2015
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14. Estimating the Burden of Leptospirosis among Febrile Subjects Aged below 20 Years in Kampong Cham Communities, Cambodia, 2007-2009

Author: Seiha Heng, Arnaud Tarantola, Rekol Huy, Touch Sok, Sopheak Hem, Florian Vogt, Sowath Ly, Mathieu Picardeau, Sovann Ly, Nima Asgari, Irene Votsi, Philippe Buchy, Simon Cauchemez, Bertrand Guillard, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Modélisation mathématique des maladies infectieuses, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), London School of Hygiene and Tropical Medicine (LSHTM), World Health Organization [Phnom Penh] (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Ministry of Health [Phnom Penh], National Center of Parasitology (CNM), National Malaria Center [Phnom Penh], This study was supported by the World Health Organization and the European Union and Pediatric Vaccine Dengue Initiative project (PDVI) from the International Vaccine Institute (IVI). Aside from coauthor NA who helped discuss the study results and edit the article, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), London School of Hygiene and Tropical Medicine ( LSHTM ), World Health Organization [Phnom Penh] ( WHO ), World Health Organization, Centre National de Référence des Leptospires-Biologie des Spirochètes ( CNR-CC FAO/OMS ), Communicable Disease Department [Phnom Penh] ( CDC MOH ), Ministry of Health, National Center for Malaria Control, Parasitology and Entomology, Ministry of Health of Cambodgia, and This study was supported by the World Health Organization and the European Union and Pediatric Vaccine Dengue Initiative project (PDVI) from the International Vaccine Institute (IVI).
Subjects: MESH : Cambodia/epidemiology, Male, Rural Population, Pathology and Laboratory Medicine, Biochemistry, 0302 clinical medicine, MESH : Immunoglobulin M/blood, MESH : Child, MESH: Rural Population, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Chikungunya, Enzyme-Linked Immunoassays, lcsh:Science, Child, MESH : Dengue/epidemiology, Leptospira, education.field_of_study, MESH : Antibodies, Bacterial/blood, MESH : Infant, MESH: Leptospirosis, Leptospirosis, MESH: Infant, MESH: Immunoglobulin M, 3. Good health, Bacterial Pathogens, Veterinary Diseases, Medical Microbiology, Child, Preschool, medicine.medical_specialty, 030106 microbiology, Immunology, MESH: Social Planning, Microbiology, 03 medical and health sciences, Signs and Symptoms, MESH : Adolescent, MESH : Leptospirosis/blood, Humans, education, Immunoassays, Microbial Pathogens, MESH: Adolescent, MESH: Humans, Bacteria, Public health, MESH : Humans, lcsh:R, MESH: Child, Preschool, Organisms, Infant, Biology and Life Sciences, Proteins, MESH: Adult, Japanese encephalitis, medicine.disease, Tropical Diseases, lcsh:Q, Veterinary Science, MESH: Female, Demography, 0301 basic medicine, Bacterial Diseases, Physiology, lcsh:Medicine, Fevers, MESH: Dengue, MESH : Child, Preschool, medicine.disease_cause, Serology, Dengue fever, Dengue, Geographical Locations, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Zoonoses, Immune Physiology, MESH: Antibodies, Bacterial, Medicine and Health Sciences, MESH : Female, Multidisciplinary, Immune System Proteins, biology, MESH: Infant, Newborn, MESH : Adult, Antibodies, Bacterial, Infectious Diseases, Female, Social Planning, Pathogens, Cambodia, Research Article, Neglected Tropical Diseases, Adult, MESH : Dengue/blood, Asia, Adolescent, MESH : Male, 030231 tropical medicine, Population, MESH : Infant, Newborn, Research and Analysis Methods, Antibodies, MESH : Social Planning, Diagnostic Medicine, medicine, MESH : Leptospirosis/epidemiology, business.industry, MESH: Cambodia, Infant, Newborn, biology.organism_classification, MESH: Male, MESH : Rural Population, Immunoglobulin M, People and Places, Immunologic Techniques, business
Abstract: International audience; BACKGROUND:Leptospirosis is an emerging but neglected public health challenge in the Asia/Pacific Region with an annual incidence estimated at 10-100 per 100,000 population. No accurate data, however, are available for at-risk rural Cambodian communities.METHOD:We conducted anonymous, unlinked testing for IgM antibodies to Leptospira spp. on paired sera of Cambodian patients
Published: 2016
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15. Underestimation of Leptospirosis Incidence in the French West Indies

Author: Sylvie Cassadou, Martine Ledrans, Pascale Bourhy, Philippe Quénel, Martina Escher, Claude Flamand, Jacques Rosine, Mathieu Picardeau, Institut de Veille Sanitaire (INVS), Cellule de l'Institut de Veille Sanitaire en régions Antilles Guyane, Cellule Interrégionale d'Epidémiologie Antilles-Guyane, Cellule interrégionale d'épidémiologie Antilles-Guyane [CIRE], Unité d'Epidémiologie, Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, Institut Pasteur [Paris], Institut de recherche, santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CIRE Antilles-Guyane - Gourbeyre, Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, CIRE Antilles-Guyane - Fort de France, The authors received specific funding only from the Institut de Veille Sanitaire, their institution. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conceived and designed the experiments: SC JR CF ME ML PB MP PQ. Performed the experi- ments: SC JR ME PB. Analyzed the data: SC JR CF. Contributed reagents/materials/analysis tools: PB MP. Wrote the paper: SC JR CF ME ML PB MP PQ. Organized and strenghtened the partners network: PQ ML., Jean-Baptiste Adrien, Hélène Bazus, Sylvie Boa, Fabrice Boulard, André Cabié, Arnaud Duthilly, Emilie Gaubert-Maréchal, Stéphanie Guyomard, Cécile Herrmann, Patrick Hoche- dez, Isabelle Lamaury, Claude Olive, Marion Petit-Sinturel, Raphaelle Théodose, the public health nurses of the CVAGS, all the General Practitionners of the two sentinel networks in Guadeloupe and Martinique, the ambulatory labs, the hospital labs, the hospital medical staffs, the Pasteur Institute of Guadeloupe, the Pasteur Institute of Paris and Jude Sweeney for the revision of the English text., Institut Pasteur [Paris] (IP), and École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Antibodies, Protozoan, Disease, Polymerase Chain Reaction, Dengue fever, 0302 clinical medicine, Environmental protection, Epidemiology, Enzyme-linked immunoassays, Child, Guadeloupe, Aged, 80 and over, Disease surveillance, Incidence (epidemiology), Incidence, lcsh:Public aspects of medicine, Middle Aged, Leptospirosis, Hospitals, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Child, Preschool, Female, France, Martinique, Adult, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, 030231 tropical medicine, 030106 microbiology, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, 03 medical and health sciences, Young Adult, Environmental health, Agglutination Tests, medicine, Humans, Aged, Demography, business.industry, Public Health, Environmental and Occupational Health, Infant, Newborn, Outbreak, Infant, Correction, lcsh:RA1-1270, DNA, Protozoan, medicine.disease, Public and occupational health, Immunoglobulin M, business
Abstract: BACKGROUND:Leptospirosis is a neglected zoonosis affecting mainly tropical and subtropical regions worldwide, particularly South America and the Caribbean. As in many other countries, under-reporting of cases was suspected in the French West Indies because of inadequate access to diagnostic tests for the general population. METHODOLOGY/PRINCIPAL FINDINGS:In order to estimate the real incidence of leptospirosis in Guadeloupe and Martinique, a study was performed in 2011 using the three prevailing available biological tests for diagnosis: Microscopic Agglutination Test (MAT), IgM ELISA and PCR. The study investigated inpatients and outpatients and used active case ascertainment from data provided by a general practitioners' sentinel network. The epidemiology of the disease was also described in terms of severity and demographic characteristics. Leptospirosis incidence was estimated at 69.4 (95%CI 47.6-91.1) and 60.6 (95%CI 36.3-85.0) annual cases per 100,000 inhabitants in Guadeloupe and Martinique, respectively, which was 3 and 4 times higher than previous estimations. CONCLUSION/SIGNIFICANCE:Inclusion of PCR and IgM ELISA tests for diagnosis of leptospirosis resulted in improved sensitivity in comparison with MAT alone. Our results highlighted the substantial health burden of the disease in these two territories and the importance of access to appropriate laboratory tests. Based on our results, PCR and IgM ELISA tests have now been included in the list of tests reimbursed by the national system of social security insurance in France. Our results also underline the relevance of implementing an integrated strategy for the surveillance, prevention and control of leptospirosis in the French West Indies.
Published: 2016
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16. La leptospirose en Guyane française : 1ère étude transversale multicentrique 2007-2014

Author: Le Turnier, P., Epelboin, Loïc, Mosnier, Emilie, Schaub, Roxane, Boukhari, R., Berlioz-Arthaud, Alain, Bourhy, Pascale, Djossou, Félix, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Unité des Maladies Infectieuses et Tropicales (UMIT), Université de Guyane (UG), Centre Hospitalier de l'Ouest Guyanais (CHOG), CHOG-Centre Hospitalier de l'Ouest Guyanais, Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, Unité de Maladie Infectieuses et Tropicales, Centre hospitalier Andrée Rosemon, Cayenne, and Institut Pasteur [Paris] (IP)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

17. Human leptospirosis in French Guiana: first multicentric transversal study (2007-2014)

Author: Le Turnier, P., Epelboin, Loïc, Mosnier, Emilie, Schaub, Roxane, Jolivet, A, Berlioz-Arthaud, Alain, Bourhy, Pascale, Picardeau, Mathieu, Demar, Magalie Pierre, Djossou, M, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Université de Guyane (UG), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre Hospitalier de l'Ouest Guyanais Franck Joly [Saint-Laurent-du-Maroni, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), and Institut Pasteur [Paris]
Subjects: french guiana, [SDV]Life Sciences [q-bio], leptospirosis, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

18. Human Leptospira Isolates Circulating in Mayotte (Indian Ocean) Have Unique Serological and Molecular Features

Author: Laure Diancourt, Louis Collet, Pascale Bourhy, Farida Zinini, Mathieu Picardeau, Sylvain Brisse, Jean-Michel Thiberge, Hans van der Linden, François Pettinelli, R.A. Hartskeerl, Tinne Lernout, Claude Giry, Medical Microbiology and Infection Prevention, Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, Laboratory of the Hospital Centre of Mayotte (CHM), Laboratory of the Hospital Centre of Mayotte, Regional office (Cire) of the French Institute for Public Health Surveillance (Institut de veille sanitaire), Institut de Veille Sanitaire (INVS), National Collaborating Centre for Reference and Research on Leptospirosis [Pays-bas], The Royal Tropical Institute (KIT), Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8), This work was funded by the Institut Pasteur and the French Ministry of Health (InVS), and Institut Pasteur [Paris] (IP)
Subjects: Adult, Male, Microbiology (medical), Serotype, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Comoros, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Leptospira, Genotype, medicine, Humans, Leptospirosis, Typing, Serotyping, Aged, 0303 health sciences, biology, Phylogenetic tree, 030306 microbiology, Middle Aged, medicine.disease, biology.organism_classification, Virology, Bacterial Typing Techniques, 3. Good health, Multilocus sequence typing, Female, Leptospira interrogans, Multilocus Sequence Typing
Abstract: Leptospirosis is one of the most widespread zoonoses in the world. However, there is a lack of information on circulating Leptospira strains in remote parts of the world. We describe the serological and molecular features of leptospires isolated from 94 leptospirosis patients in Mayotte, a French department located in the Comoros archipelago, between 2007 and 2010. Multilocus sequence typing identified these isolates as Leptospira interrogans , L. kirschneri , L. borgpetersenii , and members of a previously undefined phylogenetic group. This group, consisting of 15 strains, could represent a novel species. Serological typing revealed that 70% of the isolates belonged to the serogroup complex Mini/Sejroe/Hebdomadis, followed by the serogroups Pyrogenes, Grippotyphosa, and Pomona. However, unambiguous typing at the serovar level was not possible for most of the strains because the isolate could belong to more than one serovar or because serovar and species did not match the original classification. Our results indicate that the serovar and genotype distribution in Mayotte differs from what is observed in other regions, thus suggesting a high degree of diversity of circulating isolates worldwide. These results are essential for the improvement of current diagnostic tools and provide a starting point for a better understanding of the epidemiology of leptospirosis in this area of endemicity.
Published: 2012
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19. Factors Associated with Severe Leptospirosis, Martinique, 2010–2013

Author: Mathieu Picardeau, Isabelle Lamaury, Guillaume Hurtrel, Jean-Marie Delord, Ruddy Valentino, Roland Martinez, Pascale Bourhy, Patrick Hochedez, Hossein Mehdaoui, Claude Olive, Rafaelle Théodose, Nicolas Vignier, Cécile Herrmann, Raymond Césaire, André Cabié, Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Université des Antilles et de la Guyane (UAG), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier de Trinité MARTINIQUE, Centre hospitalier du Lamentin MARTINIQUE, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Institut National de la Santé et de la Recherche Médicale (INSERM), We also thank the French Ministry of Health with the participation of the Groupement Interrégional de Recherche Clinique et d’Innovation Sud-Ouest Outre-Mer for funding and the Direction de la Recherche Clinique et de Innovation of the University Hospital of Fort-de-France, Martinique, France, for methodologic support., We thank Olivier Verlaeten and Ludovic Jeanneau, who introduced the qPCR technique in the University Hospital of Fort de France, Dorothée Haug and the technical staff at the Service de Bactériologie of the University Hospital of Fort-de-France, Janick Jean-Marie and the staff at the Centre d’Investigation Clinique et d’Epidémiologie Clinique Antilles-Guyane (Institut National de la Santé et de la Re- cherche Médicale CIE 802), Christopher Pappas for editorial assistance, and Eric Caumes for critical review of the manu- script., MURGUET, SYLVIE, and Institut Pasteur [Paris]
Subjects: Male, Serotype, Epidemiology, [SDV]Life Sciences [q-bio], lcsh:Medicine, Disease Outbreaks, MESH: Dogs, 0302 clinical medicine, MESH: Martinique, Zoonoses, MESH: Animals, Dog Diseases, MESH: Disease Outbreaks, bacteria, 0303 health sciences, MESH: Middle Aged, medicine.diagnostic_test, biology, Dispatch, Factors Associated with Severe Leptospirosis, Martinique, 2010–2013, MESH: Leptospirosis, Middle Aged, Leptospirosis, 3. Good health, [SDV] Life Sciences [q-bio], qPCR, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, severe leptospirosis, Female, medicine.symptom, MESH: Zoonoses, Martinique, Leptospira interrogans, Adult, Microbiology (medical), MESH: Dog Diseases, 030231 tropical medicine, leptospiremia, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Dogs, Disease severity, medicine, Animals, Humans, lcsh:RC109-216, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Prothrombin time, MESH: Humans, 030306 microbiology, business.industry, lcsh:R, MESH: Adult, Auscultation, medicine.disease, biology.organism_classification, serogroup Icterohaemorrhagiae, MESH: Male, Immunology, quantitative PCR, Anuria, business, MESH: Female
Abstract: International audience; To identify factors associated with disease severity, we examined 102 patients with quantitative PCR-confirmed leptospirosis in Martinique during 2010-2013. Associated factors were hypotension, chest auscultation abnormalities , icterus, oligo/anuria, thrombocytopenia, prothrombin time
Published: 2015
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20. La leptospirose en Guyane : une maladie tropicale négligée ? Etude transversale multicentrique 2007-2014

Author: Le Turnier, Paul, Epelboin, Loïc, Schaub, Roxane, Mosnier, E., Boukhari, R., Jolivet, A., Terraz, A., Kallel, H., Berlioz-Arthaud, Alain, Trombert-Paolantoni, S., Bourhy, P., Picardeau, Mathieu, Demar, M., Djossou , Felix, Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Unité des Maladies Infectieuses et Tropicales [Cayenne, Guyane Française], Université de Guyane (UG), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, Unité de Maladie Infectieuses et Tropicales, Centre hospitalier Andrée Rosemon, Cayenne, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], and Institut Pasteur [Paris] (IP)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2015

21. Investigation of a leptospirosis outbreak in triathlon participants, Réunion Island, 2013

Author: Koussay Dellagi, Sophie Larrieu, Vanina Guernier, Erwan Lagadec, Marie-Christine Jaffar-Bandjee, Laurent Filleul, G. Le Minter, Alain Michault, Pablo Tortosa, B. Kurtkowiak, Yann Gomard, P. Lenabat, Mathieu Picardeau, Joana Simões, Frédéric Pagès, Cellule Interrégionale d'Epidémiologie (CIRE), Cellule Interregionale d'Epidemiologie (CIRE), Agence Régionale de Santé Océan Indien, Agence Régionale de la Santé (ARS), Centre de Recherche et de Veille sur les Maladies Émergentes dans l'Océan Indien (CRVOI), Université de La Réunion (UR), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: Male, Veterinary medicine, Epidemiology, Attack rate, Serology, Disease Outbreaks, Running, Rodent Diseases, Sports Equipment, 0302 clinical medicine, Protective Clothing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030212 general & internal medicine, triathlon, Child, Skin, Leptospira, biology, Middle Aged, 16. Peace & justice, Leptospirosis, Antibodies, Bacterial, Infectious Diseases, Reunion Island, Child, Preschool, Female, Réunion Island, Martinique, Sports, Adult, DNA, Bacterial, medicine.medical_specialty, Adolescent, 030231 tropical medicine, Animals, Wild, 03 medical and health sciences, Young Adult, Indian Ocean Islands, Internal medicine, medicine, Animals, Humans, Swimming, outbreak, business.industry, Outbreak, medicine.disease, biology.organism_classification, Health Surveys, Bicycling, Rats, Relative risk, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business
Abstract: SUMMARYWe report herein the investigation of a leptospirosis outbreak occurring in triathlon competitors on Réunion Island, Indian Ocean. All participants were contacted by phone or email and answered a questionnaire. Detection and molecular characterization of pathogenicLeptospirawas conducted in inpatients and in rodents trapped at the vicinity of the event. Of the 160 athletes competing, 101 (63·1%) agreed to participate in the study. Leptospirosis was biologically confirmed for 9/10 suspected cases either by real-time PCR or serological tests (MAT or ELISA). The total attack rate, children's attack rate, swimmers’ attack rate, and the attack rate in adult swimmers were respectively estimated at 8·1% [95% confidence interval (CI) 4·3–14·7], 0%, 12·7% (95% CI 6·8–22·4) and 23·1% (95% CI 12·6–33·8). Leptospirosis cases reported significantly more wounds [risk ratio (RR) 4·5, 95% CI 1·6–13], wore complete neoprene suits less often (RR 4·3, 95% CI 1·3–14·5) and were most frequently unlicensed (RR 6·6, 95% CI 2·9–14·8). The epidemiological investigation supported that some measures such as the use of neoprene suits proved efficient in protecting swimmers against infection. PCR detection in rats revealed highLeptospirainfection rates. Partial sequencing of the 16S gene and serology on both human and animal samples strongly suggests that rats were the main contaminators and were likely at the origin of the infection in humans.
Published: 2015
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22. Use of a New High Resolution Melting Method for Genotyping Pathogenic Leptospira spp

Author: Amélie Desvars, Alain Michault, Florence Naze, Pascale Bourhy, Mathieu Picardeau, Laboratoire de Bactériologie-Parasitologie-Virologie-Hygiène, Groupe Hospitalier Sud Réunion (GHSR), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, The authors have no support or funding to report., Conceived and designed the experiments: AM MP PB. Performed the experiments: FN AD. Analyzed the data: AD MP AM PB. Contributed reagents/materials/analysis tools: FN PB. Wrote the paper: FN AD MP PB AM., and Institut Pasteur [Paris]
Subjects: Serotype, DNA, Bacterial, Genotype, Genotyping Techniques, [SDV]Life Sciences [q-bio], lcsh:Medicine, Minisatellite Repeats, Nucleic Acid Denaturation, Real-Time Polymerase Chain Reaction, Melting curve analysis, High Resolution Melt, Species Specificity, Leptospira, medicine, Cluster Analysis, Humans, lcsh:Science, Genotyping, Genetics, Multidisciplinary, biology, lcsh:R, biology.organism_classification, medicine.disease, Leptospirosis, Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, lcsh:Q, Leptospira interrogans, Software, Research Article
Abstract: Background Leptospirosis is a worldwide zoonosis that is endemic in tropical areas, such as Reunion Island. The species Leptospira interrogans is the primary agent in human infections, but other pathogenic species, such as L. kirschner and L. borgpetersenii, are also associated with human leptospirosis. Methods and Findings In this study, a melting curve analysis of the products that were amplified with the primer pairs lfb1 F/R and G1/G2 facilitated an accurate species classification of Leptospira reference strains. Next, we combined an unsupervised high resolution melting (HRM) method with a new statistical approach using primers to amplify a two variable-number tandem-repeat (VNTR) for typing at the subspecies level. The HRM analysis, which was performed with ScreenClust Software, enabled the identification of genotypes at the serovar level with high resolution power (Hunter-Gaston index 0.984). This method was also applied to Leptospira DNA from blood samples that were obtained from Reunion Island after 1998. We were able to identify a unique genotype that is identical to that of the L. interrogans serovars Copenhageni and Icterohaemorrhagiae, suggesting that this genotype is the major cause of leptospirosis on Reunion Island. Conclusions Our simple, rapid, and robust genotyping method enables the identification of Leptospira strains at the species and subspecies levels and supports the direct genotyping of Leptospira in biological samples without requiring cultures.
Published: 2015
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23. Urban market gardening and rodent-borne pathogenic Leptospira in arid zones: a case study in Niamey, Niger

Author: Jean-Pierre Rossi, Anne Loiseau, Gauthier Dobigny, Madougou Garba, Mathieu Picardeau, Eric Bertherat, Maxime Galan, Ibrahima Kadaoure, Caroline Tatard, Dobigny, Gauthier, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Direction Générale de la Protection des Végétaux, Ministère de l'Agriculture du Niger, USAid/Fews-Net, Centre Régional Agrhymet, Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Lab and field work were funded by the 'Institut de Recherche pour le Developpement' (France). Funding support was partly provided to MG by a ‘BEST’ bursary from the 'Service de Renforcement des Capacites' (Institut de Recherche pour le Developpement), France, Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, Institut Pasteur [Paris], and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Disease reservoir, [SDV]Life Sciences [q-bio], risk-factors, infection, environment, epidemiology, africa, humans, impact, region, brazil, Infectious Diseases, Parasitology, Tropical Medicine, Minisatellite Repeats, 0302 clinical medicine, RNA, Ribosomal, 16S, Zoonoses, 11. Sustainability, Niger, Leptospira, 2. Zero hunger, 0303 health sciences, biology, Ecology, lcsh:Public aspects of medicine, Gardening, Leptospirosis, 3. Good health, Leptospira interrogans, Research Article, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Rodentia, Context (language use), 03 medical and health sciences, Urbanization, medicine, Animals, Urban agriculture, Disease Reservoirs, 030306 microbiology, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, medicine.disease, biology.organism_classification, Arid
Abstract: Leptospirosis essentially affects human following contact with rodent urine-contaminated water. As such, it was mainly found associated with rice culture, recreational activities and flooding. This is also the reason why it has mainly been investigated in temperate as well as warm and humid regions, while arid zones have been only very occasionally monitored for this disease. In particular, data for West African countries are extremely scarce. Here, we took advantage of an extensive survey of urban rodents in Niamey, Niger, in order to look for rodent-borne pathogenic Leptospira species presence and distribution across the city. To do so, we used high throughput bacterial 16S-based metabarcoding, lipL32 gene-targeting RT-PCR, rrs gene sequencing and VNTR typing as well as GIS-based multivariate spatial analysis. Our results show that leptospires seem absent from the core city where usual Leptospira reservoir rodent species (namely R. rattus and M. natalensis) are yet abundant. On the contrary, L. kirschneri was detected in Arvicanthis niloticus and Cricetomys gambianus, two rodent species that are restricted to irrigated cultures within the city. Moreover, the VNTR profiles showed that rodent-borne leptospires in Niamey belong to previously undescribed serovars. Altogether, our study points towards the importance of market gardening in maintain and circulation of leptospirosis within Sahelian cities. In Africa, irrigated urban agriculture constitutes a pivotal source of food supply, especially in the context of the ongoing extensive urbanization of the continent. With this in mind, we speculate that leptospirosis may represent a zoonotic disease of concern also in arid regions that would deserve to be more rigorously surveyed, especially in urban agricultural settings., Author Summary We surveyed rodent-borne Leptospira in rodents from Niamey, the capital town of Niger, using bacterial metabarcoding, RT-PCR, sequencing, VNTR typing and GIS-based geostatistics. Two new serovars of Leptospira kirschneri were identified in Arvicanthis niloticus and Cricetomys gambianus, two species that inhabit exclusively urban irrigated gardens. Since no rodent-borne leptospires could be found in the core city, our results point towards the importance of urban agriculture in the maintaining and the circulation of these bacteria in cities from semi-arid regions where they are usually poorly documented and even hardly looked for. Accordingly, this is one of the very rare mentions of these zoonotic agents in Sahel, and the first one in Niger. Keeping in mind the critical role of urban gardening for food security in extensively growing West African cities, we believe that leptospirosis should be more closely scrutinized in Sahelian countries where numerous cases of human fevers are of unknown origin.
Published: 2015
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24. Evaluation of different serological assays for early diagnosis of leptospirosis in Martinique (French West Indies)

Author: Patrick Hochedez, Dorothee Alexer, Yohann Le Govic, Claude Olive, Pascale Bourhy, Christophe Courdurie, Raymond Césaire, Jacques Rosine, Rafaelle Theodose, Karine Pailla, Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, Laboratoire de Virologie-Immunologie [Fort de France, Martinique] (EA 4537), Regional Office of the French Institute for Public Health Surveillance, Institut de Veille Sanitaire (INVS), CHU de la Martinique [Fort de France], and Institut Pasteur [Paris] (IP)
Subjects: Bacterial Diseases, 0301 basic medicine, Time Factors, Artificial Gene Amplification and Extension, Pathology and Laboratory Medicine, Polymerase Chain Reaction, Serology, 0302 clinical medicine, Antibiotics, Zoonoses, Direct agglutination test, Medicine and Health Sciences, Enzyme-Linked Immunoassays, Leptospira, Serodiagnosis, biology, Antimicrobials, lcsh:Public aspects of medicine, Zoonosis, Drugs, Leptospirosis, Bacterial Pathogens, 3. Good health, Infectious Diseases, Medical Microbiology, Physical Sciences, Pathogens, Martinique, Leptospira interrogans, Research Article, Neglected Tropical Diseases, Optimization, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Immunoblotting, 030231 tropical medicine, 030106 microbiology, Enzyme-Linked Immunosorbent Assay, Research and Analysis Methods, Sensitivity and Specificity, Microbiology, 03 medical and health sciences, Diagnostic Medicine, Microbial Control, Internal medicine, medicine, Humans, Serologic Tests, Immunoassays, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Pharmacology, Bacteria, business.industry, Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, lcsh:RA1-1270, Gold standard (test), Tropical Diseases, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, Early Diagnosis, Immunologic Techniques, business, Mathematics
Abstract: Background Leptospirosis is a potentially life-threatening but curable zoonosis whose prognosis depends on accurate and timely diagnosis. Because of its non-specific clinical presentation, laboratory testing is essential to confirm the diagnosis. Here, we aimed to assess the performance of two enzyme-linked immunosorbent assays (ELISAs) (ELISA Serion and ELISA-Hb Pasteur) and one immunodot (GenBio) using quantitative PCR (qPCR) as gold standard, instead of the traditional microscopic agglutination test, for the diagnosis of acute leptospirosis in an endemic area. Methodology/Principal findings Between January 2011 and December 2012, a total of 122 patients were diagnosed with leptospirosis, as confirmed by qPCR at the University Hospital of Martinique. Among them, 103 had at least one serum sample available for analysis. Performance of each serological assay was evaluated according to days' post onset of symptoms (DPO) and local species diversity (which included L. santarosai, L. interrogans, L. kirschneri, L. borgpetersenii, L. noguchii, and L. kmetyi). Several thresholds were tested to optimize accuracy. When considering the manufacturer's threshold, the sensitivity of ELISA Serion, ELISA-Hb Pasteur and GenBio immunodot was 75%, 67% and 64%, while specificity was 92%, 98% and 100%, respectively. Moreover, the threshold optimization allowed a significant improvement in specificity for the ELISA Serion from 92% to 99% (p, Author summary Leptospirosis is a ubiquitous zoonosis caused by spirochetes. This infection is responsible for a wide range of symptoms mimicking many other diseases. Laboratory tests are thus essential to confirm the diagnosis. Furthermore, earlier diagnosis helps to prevent severe outcomes by a prompt initiation of antibiotic therapy. In early phase, quantitative Polymerase Chain Reaction (qPCR) was proved to be more efficient than the traditional microagglutination test (MAT), which remains the ‘gold standard’ for diagnosis of leptospirosis. However, both tests are seldom available in resource-limited settings, where leptospirosis burden is highest. To find a suitable alternative to qPCR and MAT in the early phase (i.e., within the first 2 weeks) of the disease, we compared 3 serological assays (2 ELISAs plus one immunodot) using sera collected from patients with a qPCR-confirmed diagnosis of leptospirosis. This work reveals high performances for all serological assays after (but not before) 6 days’ post onset of symptoms, regardless of the species studied. Excellent specificity, as found after threshold optimization, suggests that these tests could useful in high prevalence areas.
Published: 2017
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25. Epidemiology of leptospira transmitted by rodents in southeast Asia

Author: Jean-François Cosson, Serge Morand, Philippe Buchy, Mathilde Mielcarek, Yupin Suputtamongkol, Mathieu Picardeau, Yannick Chaval, Caroline Tatard, Vincent Herbreteau, Sathaporn Jittapalapong, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, Institut Pasteur [Paris], Faculty of Medecine, Siriraj Hospital, Mahidol University [Bangkok], Unité de Virologie, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Kasetsart University, Department of Parasitology, Faculty of Veterinary Medicine (KU), Kasetsart University, UMR 228 Espace-Dev, Espace pour le développement, Université des Antilles (UA)-Université de Guyane (UG)-Université de Montpellier (UM)-Université de La Réunion (UR)-Avignon Université (AU)-Université de Perpignan Via Domitia (UPVD)-Institut de Recherche pour le Développement (IRD), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), NR BioDivHealth SEA (Local impacts and perceptions of global changes: health, biodiversity and zoonoses in Southeast Asia) [ANR-11-CEPL-002-01], Institut Pasteur, French Institute for Public Health Surveillance (InVS), French National Institute for Agricultural Research (INRA), ANR: ANR-11-CEPL-002-01, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, Unité de Virologie / Virology Unit [Phnom Penh], Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Department of Helminthology, Faculty of Tropical Medicine, ANR-11-CEPL-0002,BiodivHealthSEA,Impacts et perceptions locales des changements globaux : santé, biodiversité et zoonoses en Asie du Sud-Est(2011), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Institut Pasteur [Paris] (IP), Kasetsart University (KU), Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE)
Subjects: Male, Veterinary medicine, Rodent, Epidemiology, MESH: Rodentia, Minisatellite Repeats, Santé publique, MESH: Leptospira, law.invention, MESH: Genotype, MESH: Animals, Animal biology, Leptospira, MESH: Leptospirosis, Leptospirosis, 3. Good health, Épidémiologie, Veterinary Diseases, Habitat, Laos, Forêt, Leptospira interrogans, L72 - Organismes nuisibles des animaux, medicine.medical_specialty, Genotype, Rizière, lcsh:RC955-962, Molecular Sequence Data, Médecine humaine et pathologie, Rodentia, Locus (genetics), Leptospirose, Biodiversity and Ecology, biology.animal, Biologie animale, Humans, espèce réservoir, MESH: Molecular Epidemiology, maladie humaine, MESH: Prevalence, MESH: Disease Reservoirs, MESH: Molecular Sequence Data, MESH: Humans, Public Health, Environmental and Occupational Health, Biology and Life Sciences, lcsh:RA1-1270, 15. Life on land, Tropical Diseases, medicine.disease, MESH: DNA, Bacterial, Molecular Typing, MESH: Minisatellite Repeats, Veterinary Science, Human health and pathology, Rongeur, MESH: Female, Sciences agricoles, Bacterial Diseases, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Identification, MESH: Sequence Analysis, DNA, Biodiversité et Ecologie, L73 - Maladies des animaux, Rodent Diseases, Espèce, law, Zoonoses, Prevalence, Medicine and Health Sciences, Polymerase chain reaction, 2. Zero hunger, Molecular Epidemiology, biology, MESH: Molecular Typing, [SDV.BA]Life Sciences [q-bio]/Animal biology, lcsh:Public aspects of medicine, Thailand, Agricultural sciences, Infectious Diseases, asie du sud-est, S50 - Santé humaine, Female, Cambodia, MESH: Zoonoses, Research Article, Neglected Tropical Diseases, DNA, Bacterial, zoonose, lcsh:Arctic medicine. Tropical medicine, Environmental Epidemiology, Maladie de l'homme, medicine, Animals, MESH: Thailand, Transmission des maladies, Disease Reservoirs, Population Biology, MESH: Cambodia, Sequence Analysis, DNA, Morbidité, biology.organism_classification, MESH: Male, MESH: Laos, MESH: Rodent Diseases, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Leptospirosis is the most common bacterial zoonoses and has been identified as an important emerging global public health problem in Southeast Asia. Rodents are important reservoirs for human leptospirosis, but epidemiological data is lacking. Methodology/Principal Findings We sampled rodents living in different habitats from seven localities distributed across Southeast Asia (Thailand, Lao PDR and Cambodia), between 2009 to 2010. Human isolates were also obtained from localities close to where rodents were sampled. The prevalence of Leptospira infection was assessed by real-time PCR using DNA extracted from rodent kidneys, targeting the lipL32 gene. Sequencing rrs and secY genes, and Multi Locus Variable-number Tandem Repeat (VNTR) analyses were performed on DNA extracted from rat kidneys for Leptospira isolates molecular typing. Four species were detected in rodents, L. borgpetersenii (56% of positive samples), L. interrogans (36%), L. kirschneri (3%) and L. weilli (2%), which were identical to human isolates. Mean prevalence in rodents was approximately 7%, and largely varied across localities and habitats, but not between rodent species. The two most abundant Leptospira species displayed different habitat requirements: L. interrogans was linked to humid habitats (rice fields and forests) while L. borgpetersenii was abundant in both humid and dry habitats (non-floodable lands). Conclusion/Significance L. interrogans and L. borgpetersenii species are widely distributed amongst rodent populations, and strain typing confirmed rodents as reservoirs for human leptospirosis. Differences in habitat requirements for L. interrogans and L. borgpetersenii supported differential transmission modes. In Southeast Asia, human infection risk is not only restricted to activities taking place in wetlands and rice fields as is commonly accepted, but should also include tasks such as forestry work, as well as the hunting and preparation of rodents for consumption, which deserve more attention in future epidemiological studies., Author Summary Leptospirosis is the most prevalent bacterial zoonosis worldwide. Rodents are believed to be the main reservoirs of Leptospira, yet little epidemiological research has been conducted on rodents from Southeast Asia. Previous studies suggest that activities which place humans in microenvironments shared by rodents increase the probability of contracting leptospirosis. We therefore investigated the circulation of leptospiral species and strains in rodent communities and human populations in seven localities scattered throughout Southeast Asia; in Thailand, Lao PDR and Cambodia. Molecular typing assays were used to characterize leptospiral species and strains in both rodents and humans, which demonstrated common strains between humans and rodents. Additionally, we observed that the two most abundant leptospiral species; L. borgpetersenii and L. interrogans, have different habitat requirements, which supposes different modes of transmission. Lastly, in Southeast Asia, the risk of leptospiral transmission to humans is not solely limited to wetlands and rice paddy fields, but is also linked to forested areas, and activities such as the hunting and/or preparation of rodents for consumption.
Published: 2014
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26. Leptospirosis in the western Indian Ocean islands: what is known so far?

Author: Alain Michault, Amélie Desvars, Pascale Bourhy, Laboratoire de Bactériologie-Parasitologie-Virologie-Hygiène, Groupe Hospitalier Sud Réunion (GHSR), Contrôle des maladies animales exotiques et émergentes (UMR CMAEE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, and Institut Pasteur [Paris] (IP)
Subjects: Wet season, Fauna, 030231 tropical medicine, Review, 03 medical and health sciences, 0302 clinical medicine, Indian Ocean Islands, Leptospira, medicine, Animals, Humans, Leptospirosis, 14. Life underwater, 030212 general & internal medicine, Mammals, Molecular Epidemiology, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, Molecular epidemiology, biology, business.industry, Transmission (medicine), Ecology, Zoonosis, medicine.disease, biology.organism_classification, veterinary(all), 3. Good health, Livestock, business
Abstract: In the past decade, leptospirosis has emerged as a major zoonosis with a worldwide distribution. The disease is caused by bacteria of the genus Leptospira. The western Indian Ocean includes more than one hundred tropical or subequatorial islands where leptospirosis constitutes a major public health problem. The clinical signs of the human disease are generally similar to an influenza-like syndrome, but acute forms of the disease are reported and mortality remains significant in this region. In animals, clinical forms are mainly asymptomatic but leptospirosis reduces the fertility of livestock, resulting in economic losses. The data available about human and animal leptospirosis in the western Indian Ocean islands are diverse: human leptospirosis has been extensively studied in Reunion Island, Mayotte, and the Seychelles, whereas the human clinical disease has never been described in Madagascar, Comoros, Mauritius, or Rodrigues, mainly because of the deficiency in appropriate medical and diagnostic structures. The rat is recognized as the major reservoir host for the bacteria on all islands, but recent data from Reunion Island indicates that almost all mammals can be a source of contamination. The incidence of leptospirosis in humans is highly seasonal, and linked to the rainy season, which is favorable for the environmental maintenance and transmission of the bacteria. The epidemiology of leptospirosis is fully island-dependent, related to the number of mammalian species, the origins of the introduced mammalian species, the relationships between humans and fauna, and environmental as well as cultural and socio-economic factors.
Published: 2013
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27. Outbreak of leptospirosis among canyoning participants, Martinique, 2011

Author: Jacques Rosine, R. Théodose, André Cabié, Martine Ledrans, Pascale Bourhy, L. Pasgrimaud, Patrick Hochedez, H. Decoussy, Mathieu Picardeau, R Martinez, Claude Olive, M. Escher, Infectious and Tropical Diseases Unit, Fort-de-France University Hospital, Regional Office of the French Institute for Public Health Surveillance, Institut de Veille Sanitaire (INVS), European Programme for Intervention Epidemiology Training, EPIET, French Armed Forces in the French West Indies, Department of Medicine, Trinité Hospital, Laboratory for Microbiology, Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris], Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Institut Pasteur and the French Institute for Public Health Surveillance (InVS), Institut Pasteur [Paris] (IP), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], and ADENIS, ANTOINE
Subjects: MESH: Mountaineering, Male, Veterinary medicine, Time Factors, Epidemiology, MESH: Leptospira, Disease Outbreaks, 0302 clinical medicine, MESH: Risk Factors, MESH: Martinique, Risk Factors, Surveys and Questionnaires, Medicine, Young adult, MESH: Disease Outbreaks, Medical attention, Leptospira, 0303 health sciences, MESH: Middle Aged, biology, MESH: Real-Time Polymerase Chain Reaction, MESH: Patient Acceptance of Health Care, MESH: Leptospirosis, Middle Aged, Leptospirosis, 3. Good health, MESH: Young Adult, Female, Martinique, Adult, medicine.medical_specialty, 030231 tropical medicine, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, 03 medical and health sciences, Young Adult, Virology, Internal medicine, Humans, MESH: Humans, 030306 microbiology, business.industry, Public health, MESH: Questionnaires, MESH: Time Factors, Public Health, Environmental and Occupational Health, Outbreak, MESH: Adult, Patient Acceptance of Health Care, biology.organism_classification, medicine.disease, MESH: Sensitivity and Specificity, MESH: Male, Mountaineering, Leptospira species, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; Two gendarmes who participated in canyoning activities on 27 June 2011 on the Caribbean island of Martinique were diagnosed with leptospirosis using quantitative real-time polymerase chain reaction (qPCR), 9 and 12 days after the event. Among the 45 participants who were contacted, 41 returned a completed questionnaire, of whom eight met the outbreak case definition. The eight cases sought medical attention and were given antibiotics within the first week after fever onset. No severe manifestations of leptospirosis were reported. In seven of the eight cases, the infection was confirmed by qPCR. Three pathogenic Leptospira species, including L. kmetyi, were identified in four of the cases. None of the evaluated risk factors were statistically associated with having developed leptospirosis. Rapid diagnostic assays, such as qPCR, are particularly appropriate in this setting - sporting events with prolonged fresh-water exposure - for early diagnosis and to help formulate public health recommendations. Participants in such events should be made specifically aware of the risk of leptospirosis, particularly during periods of heavy rainfall and flooding.
Published: 2013
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28. Sensitivity and Specificity of a New Vertical Flow Rapid Diagnostic Test for the Serodiagnosis of Human Leptospirosis

Author: Pascale Bourhy, Lilian Bruyère-Ostells, Sylvie Dartevelle, Faridabano Nato, Eric D'Ortenzio, Marie-Estelle Soupé-Gilbert, Mathieu Picardeau, Suzanne Chanteau, Cyrille Goarant, Ann-Claire Gourinat, Carine Mauron, Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, Production de Protéines Recombinantes et d'Anticorps (Plate-Forme), This study has been supported by the Pasteur International Network, the French Ministries for Research, the Institut de Veille Sanitaire (InVS), and for Overseas Territories, the Government of New-Caledonia, and Institut Pasteur [Paris]
Subjects: medicine.medical_specialty, Veterinary medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, serology, rapid diagnostic test, Serology, 03 medical and health sciences, 0302 clinical medicine, Leptospira, Diagnostic Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Direct agglutination test, parasitic diseases, medicine, leptospirosis, Seroconversion, Intensive care medicine, 0303 health sciences, Rapid diagnostic test, biology, 030306 microbiology, business.industry, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Gold standard (test), biology.organism_classification, medicine.disease, Leptospirosis, 3. Good health, Infectious Diseases, Diagnostic odds ratio, Medicine, business, Research Article, Test Evaluation, Neglected Tropical Diseases
Abstract: Background: Leptospirosis is a growing public health concern in many tropical and subtropical countries. However, its diagnosis is difficult because of non-specific symptoms and concurrent other endemic febrile diseases. In many regions, the laboratory diagnosis is not available due to a lack of preparedness and simple diagnostic assay or difficult access to reference laboratories. Yet, an early antibiotic treatment is decisive to the outcome. The need for Rapid Diagnostic Tests (RDTs) for bedside diagnosis of leptospirosis has been recognized. We developed a vertical flow immunochromatography strip RDT detecting anti-Leptospira human IgM and evaluated it in patients from New Caledonia, France, and French West Indies. Methodology/Principal Findings: Whole killed Leptospira fainei cells were used as antigen for the test line and purified human IgM as the control line. The mobile phase was made of gold particles conjugated with goat anti-human IgM. Standards for Reporting of Diagnostic Accuracy criteria were used to assess the performance of this RDT. The Microscopic Agglutination Test (MAT) was used as the gold standard with a cut-off titer of ≥400. The sensitivity was 89.8% and the specificity 93.7%. Positive and negative Likelihood Ratios of 14.18 and 0.108 respectively, and a Diagnostic Odds Ratio of 130.737 confirmed its usefulness. This RDT had satisfactory reproducibility, repeatability, thermal tolerance and shelf-life. The comparison with MAT evidenced the earliness of the RDT to detect seroconversion. When compared with other RDT, the Vertical Flow RDT developed displayed good diagnostic performances. Conclusions/Significance This RDT might be used as a point of care diagnostic tool in limited resources countries. An evaluation in field conditions and in other epidemiological contexts should be considered to assess its validity over a wider range of serogroups or when facing different endemic pathogens. It might prove useful in endemic contexts or outbreak situations., Author Summary The major burden of leptospirosis happens in low-income populations from tropical or subtropical regions. Because of nonspecific symptoms in human leptospirosis, the biological confirmation is needed to ascertain the disease. However, this biological diagnosis relies on sophisticated and time-consuming techniques that are most often hardly (if ever) available to clinicians in peripheral health centers. Yet, the outcome of leptospirosis in humans largely depends on an early antibiotic treatment. Taken together, these factors highlight the need of rapid simple diagnostic tests for leptospirosis that could be used directly on the bedside even in remote health centers. In this study, we developed and evaluated a prototype point of care strip test for the serological diagnosis of human leptospirosis in New Caledonia, mainland France, and the French West Indies. The sensitivity was 89.8% [95% CI, 84.7–93.4] and the specificity 93.7% [95% CI, 89.65–96.2]. This easy, early and portable diagnostic test will be evaluated in other epidemiological conditions and under field conditions.
Published: 2013
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29. Seasonality of Human Leptospirosis in Reunion Island (Indian Ocean) and Its Association with Meteorological Data

Author: Amélie Desvars, Sylvaine Jégo, Eric Cardinale, Frédéric Chiroleu, Alain Michault, Pascale Bourhy, Laboratoire de Bactériologie-Parasitologie-Virologie-Hygiène, Groupe Hospitalier Sud Réunion (GHSR), Centre de Recherche et de Veille sur les Maladies Émergentes dans l'Océan Indien (CRVOI), Université de La Réunion (UR), Contrôle des maladies animales exotiques et émergentes (UMR CMAEE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université de La Réunion (UR), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris], Biologie des Spirochètes / Biology of Spirochetes, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut de Recherche pour le Développement (IRD)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de La Réunion (UR)-Institut National de la Recherche Agronomique (INRA), Centre National de Référence de la Leptospirose-Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose-Biologie des Spirochètes, and Institut Pasteur [Paris] (IP)
Subjects: Bacterial Diseases, medicine.medical_specialty, Seasonal distribution, Meteorological Concepts, Epidemiology, P40 - Météorologie et climatologie, Science, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Leptospirose, Infectious Disease Epidemiology, 03 medical and health sciences, Global solar radiation, 0302 clinical medicine, Meteorological Concept, Leptospira, medicine, Humans, Leptospirosis, 030212 general & internal medicine, Indian Ocean, Retrospective Studies, Multidisciplinary, biology, Seasonality, biology.organism_classification, medicine.disease, 3. Good health, Indian ocean, Variation saisonnière, Infectious Diseases, 13. Climate action, S50 - Santé humaine, Medicine, Seasons, Infectious Disease Modeling, Demography, Research Article, Genre humain
Abstract: International audience; Background: Leptospirosis is a disease which occurs worldwide but particularly affects tropical areas. Transmission of the disease is dependent on its excretion by reservoir animals and the presence of moist environment which allows the survival of the bacteria. Methods and Findings: A retrospective study was undertaken to describe seasonal patterns of human leptospirosis cases reported by the Centre National de References des Leptospiroses (CNRL, Pasteur Institute, Paris) between 1998 and 2008, to determine if there was an association between the occurrence of diagnosed cases and rainfall, temperature and global solar radiation (GSR). Meteorological data were recorded in the town of Saint-Benoit (Meteo France "Beaufonds-Miria'' station), located on the windward (East) coast. Time-series analysis was used to identify the variables that best described and predicted the occurrence of cases of leptospirosis on the island. Six hundred and thirteen cases were reported during the 11-year study period, and 359 cases (58.56%) were diagnosed between February and May. A significant correlation was identified between the number of cases in a given month and the associated cumulated rainfall as well as the mean monthly temperature recorded 2 months prior to diagnosis (r = 0.28 and r = 0.23 respectively). The predictive model includes the number of cases of leptospirosis recorded 1 month prior to diagnosis (b = 0.193), the cumulated monthly rainfall recorded 2 months prior to diagnosis (b = 0.145), the average monthly temperature recorded 0 month prior to diagnosis (b = 3.836), and the average monthly GSR recorded 0 month prior to diagnosis (b = -1.293). Conclusions: Leptospirosis has a seasonal distribution in Reunion Island. Meteorological data can be used to predict the occurrence of the disease and our statistical model can help to implement seasonal prevention measures.
Published: 2011
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30. Comparison of Real-Time PCR Assays for Detection of Pathogenic Leptospira spp. in Blood and Identification of Variations in Target Sequences

Author: Pascale Bourhy, Claude Giry, Sylvie Brémont, Farida Zinini, Mathieu Picardeau, Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Centre Hospitalier de Mayotte, and Institut Pasteur [Paris]
Subjects: Microbiology (medical), [SDV]Life Sciences [q-bio], 030231 tropical medicine, Biology, Polymerase Chain Reaction, Sensitivity and Specificity, Microbiology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Leptospira, Leptospiraceae, medicine, TaqMan, Humans, Leptospirosis, Polymerase chain reaction, Whole blood, Bacteriological Techniques, 0303 health sciences, Polymorphism, Genetic, 030306 microbiology, Bacteriology, biology.organism_classification, medicine.disease, 3. Good health, Blood, Real-time polymerase chain reaction, Primer (molecular biology)
Abstract: Leptospirosis is considered an underdiagnosed disease. Although several PCR-based methods are currently in use, there is little information on their comparability. In this study, four quantitative real-time PCR (qPCR) assays (SYBR green and TaqMan chemistries) targeting the secY , lfb1 , and lipL32 genes were evaluated as diagnostic assays. In our hands, these assays can detect between 10 2 and 10 3 bacteria/ml of pure culture, whole-blood, plasma, and serum samples. In three independent experiments, we found a slightly higher sensitivity of the PCR assays in plasma than in whole blood and serum. We also evaluated the specificity of the PCR assays on reference Leptospira strains, including newly described Leptospira species, and clinical isolates. No amplification was detected for DNA obtained from saprophytic or intermediate Leptospira species. However, among the pathogens, we identified sequence polymorphisms in target genes that result in primer and probe mismatches and affect qPCR assay performance. In conclusion, most of these assays are sensitive and specific tools for routine diagnosis of leptospirosis. However, it is important to continually evaluate and, if necessary, modify the primers and/or probes used to ensure effective detection of the circulating Leptospira isolates.
Published: 2011
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30 results on '"Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR)"'

1. Core genome sequencing and genotyping of Leptospira interrogans in clinical samples by target capture sequencing

2. Investigating the role of the carbon storage regulator A (CsrA) in Leptospira spp

3. First Report of Human Leptospira Santarosai Infection in French Guiana

4. The zoonotic pathogen Leptospira interrogans mitigates environmental stress through cyclic-di-GMP-controlled biofilm production

5. Usefulness of C-Reactive Protein in Differentiating Acute Leptospirosis and Dengue Fever in French Guiana

6. An outbreak of leptospirosis among kayakers in Brittany, North-West France, 2016

7. Deciphering the unexplored Leptospira diversity from soils uncovers genomic evolution to virulence

8. Leptospirosis in French Guiana and the Guiana shield: Current knowledge in 2016

9. Underestimation of leptospirosis incidence in the French West Indies

10. Sous-estimation de l’incidence de la leptospirose aux Antilles françaises

11. Human leptospirosis in French Guiana: current knowledge and perspectives

12. Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population

13. Molecular characterization of Leptospira sp by multilocus variable number tandem repeat analysis (MLVA) from clinical samples: a case report

14. Estimating the Burden of Leptospirosis among Febrile Subjects Aged below 20 Years in Kampong Cham Communities, Cambodia, 2007-2009

15. Underestimation of Leptospirosis Incidence in the French West Indies

16. La leptospirose en Guyane française : 1ère étude transversale multicentrique 2007-2014

17. Human leptospirosis in French Guiana: first multicentric transversal study (2007-2014)

18. Human Leptospira Isolates Circulating in Mayotte (Indian Ocean) Have Unique Serological and Molecular Features

19. Factors Associated with Severe Leptospirosis, Martinique, 2010–2013

20. La leptospirose en Guyane : une maladie tropicale négligée ? Etude transversale multicentrique 2007-2014

21. Investigation of a leptospirosis outbreak in triathlon participants, Réunion Island, 2013

22. Use of a New High Resolution Melting Method for Genotyping Pathogenic Leptospira spp

23. Urban market gardening and rodent-borne pathogenic Leptospira in arid zones: a case study in Niamey, Niger

24. Evaluation of different serological assays for early diagnosis of leptospirosis in Martinique (French West Indies)

25. Epidemiology of leptospira transmitted by rodents in southeast Asia

26. Leptospirosis in the western Indian Ocean islands: what is known so far?

27. Outbreak of leptospirosis among canyoning participants, Martinique, 2011

28. Sensitivity and Specificity of a New Vertical Flow Rapid Diagnostic Test for the Serodiagnosis of Human Leptospirosis

29. Seasonality of Human Leptospirosis in Reunion Island (Indian Ocean) and Its Association with Meteorological Data

30. Comparison of Real-Time PCR Assays for Detection of Pathogenic Leptospira spp. in Blood and Identification of Variations in Target Sequences

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