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1. CSF1R Inhibition Reduces Microglia Proliferation, Promotes Tissue Preservation and Improves Motor Recovery After Spinal Cord Injury

Author

Yannick Nicolas Gerber, Guillaume Patrick Saint-Martin, Claire Mathilde Bringuier, Sylvain Bartolami, Christophe Goze-Bac, Harun Najib Noristani, and Florence Evelyne Perrin

Subjects
spinal cord injury, reduced microglia proliferation, colony stimulating factor 1 receptor, GW2580, motor recovery, reduced gliosis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by activation and proliferation of resident microglia as well as infiltrating peripheral monocyte-derived macrophages. Depending on the time post-lesion, positive and detrimental influences of microglia/macrophages on axonal regeneration had been reported after SCI, raising the issue whether their modulation may represent an attractive therapeutic strategy. Colony-stimulating factor 1 (CSF1) regulates microglia/macrophages proliferation, differentiation and survival thus, pharmacological treatments using CSF1 receptor (CSF1R) inhibitors had been used to ablate microglia. We analyzed the effect of chronic (10 weeks) food diet containing GW2580 (a CSF1R inhibitor) in mice that underwent lateral spinal cord hemisection (HS) at vertebral thoracic level 9. Treatment started 4 weeks prior to SCI and continued until 6 weeks post-lesion. We first demonstrate that GW2580 treatment did not modify microglial response in non-injured spinal cords. Conversely, a strong decrease in proliferating microglia was observed following SCI. Second, we showed that GW2580 treatment improved some parameters of motor recovery in injured animals through better paw placement. Using in and ex vivo magnetic resonance imaging (MRI), we then established that GW2580 treatment had no effect on lesion extension and volume. However, histological analyses revealed that GW2580-treated animals had reduced gliosis and microcavity formation following SCI. In conclusion, CSF1R blockade using GW2580 specifically inhibits SCI-induced microglia/macrophages proliferation, reduces gliosis and microcavity formations and improves fine motor recovery after incomplete SCI. Preventing microglial proliferation may offer therapeutic approach to limit neuroinflammation, promote tissue preservation and motor recovery following SCI.

Published
2018
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2. Outbreak of Chikungunya in the French Caribbean Islands of Martinique and Guadeloupe: Findings from a Hospital-Based Surveillance System (2013–2015)

Author

Marie-José Romagne, Frédérique Dorléans, Elise Daudens-Vaysse, Annabel Preira, Laurence Fagour, Stéphanie Guyomard, Frédérique de Saint-Alary, Jacques Rosine, Isabelle Lamaury, Ghislain Leduc, Alexandra Septfons, Magguy Davidas, Marie-Claire Paty, A. Blateau, Sylvie Cassadou, K. Schepers, Fatiha Najioullah, Séverine Rochais, Cécile Herrmann-Storck, Luisiane Carvalho, Martine Ledrans, Amandine Vaidie, André Cabié, Patrick Saint-Martin, Mathilde Melin, Ruth Troudard, Bruno Hoen, Raymond Césaire, Sylvie Boa, Yvette Adélaïde, and Sylvie Abel

Subjects
medicine.medical_specialty, Pediatrics, 030231 tropical medicine, Population, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Virology, Medicine, 030212 general & internal medicine, Chikungunya, education, education.field_of_study, business.industry, Transmission (medicine), Public health, Medical record, Outbreak, virus diseases, Articles, 3. Good health, Infectious Diseases, Public hospital, Parasitology, business, Martinique
Abstract

Chikungunya virus (CHIKV) emerged in the Caribbean island of Saint-Martin in December 2013. We implemented a hospital-based surveillance system to detect and describe CHIKV cases including severe forms of the infection and deaths in the islands of Martinique and Guadeloupe. A case was defined as a patient with a CHIKV laboratory confirmation cared for in a public hospital for chikungunya for at least 24 hours, and a severe CHIKV case was defined as a CHIKV case presenting one or more organ failures. Sociodemographic, clinical, and laboratory data were collected and cases classified into severe or nonsevere based on medical records. From December 2013 to January 2015, a total of 1,836 hospitalized cases were identified. Rate of hospital admissions for CHIKV infection was 60 per 10,000 suspected clinical CHIKV cases and severity accounted for 12 per 10,000. A total of 74 deaths related to CHIKV infection occurred. Infants and elderly people were more frequently hospitalized compared with others and severity was more frequently reported in elderly subjects and subjects with underlying health condition. Fifteen neonatal infections consecutive to mother-to-child transmission were diagnosed, seven of which were severe. The most vulnerable groups of the population, such as the elderly, infants, individuals with comorbidities, and pregnant women, should remain the main targets of public health priorities.

Published
2018

3. Zika emergence in the French Territories of America and description of first confirmed cases of Zika virus infection on Martinique, November 2015 to February 2016

Author

Elise, Daudens-Vaysse, Martine, Ledrans, Noellie, Gay, Vanessa, Ardillon, Sylvie, Cassadou, Fatiha, Najioullah, Isabelle, Leparc-Goffart, Dominique, Rousset, Cécile, Herrmann, Raymond, Cesaire, Marianne, Maquart, Olivier, Flusin, Séverine, Matheus, Patricia, Huc-Anaïs, Josiane, Jaubert, Anne, Criquet-Hayot, Bruno, Hoen, Felix, Djossou, Corinne, Locatelli-Jouans, Alain, Blateau, Anne-Marie, McKenzie, Mathilde, Melin, Patrick, Saint-Martin, Frédérique, Dorléans, Claudine, Suivant, Luisiane, Carvalho, Marion, Petit-Sinturel, Audrey, Andrieu, Harold, Noël, Alexandra, Septfons, Anne, Gallay, Marie-Claire, Paty, Laurent, Filleul, André, Cabié, Agence régionale de santé (ARS) de Martinique (ARS Martinique), Cellule Inter Régionale d'Epidémiologie des Antilles - Guyane, Institut de Veille Sanitaire (INVS), Laboratoire de Virologie-Immunologie, Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], French National Reference Centre for Arboviruses, Institut de Recherche Biomédicale des Armées (IRBA), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Laboratoire d'Analyses Médicales, Clinique Saint Paul, URML Martinique, Dermatologie et Maladies infectieuses [Pointe-à-Pitre], CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre de Gestion du Risque Infectieux Nosocomial [Pointe-à-Pitre] (CGRIN), 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], Agence Régionale de Santé Guyane (ARS Guyane), Agence Régionale de la Santé (ARS), Agence régionale de santé Guadeloupe (ARS), Cellule Inter Régionale d'Epidémiologie Océan Indien, the Zika Surveillance Working Group, ADENIS, ANTOINE, IRBA Armed Forces Biomedical Research Institute, Agence Régionale de Santé de Guyane, Institut National de Veille Sanitaire, Institut national de veille sanitaire, Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Cellule interrégionale d'épidémiologie Antilles-Guyane [CIRE], CIRE Antilles-Guyane - Gourbeyre, CHU de la Martinique [Fort de France], Unité de Virologie, Institut de Médecine Tropicale du Service de Santé des Armées, Institut pluridisciplinaire de recherche appliquée dans le domaine du génie pétrolier (IPRADDGP), Université de Pau et des Pays de l'Adour (UPPA)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Fort-de-France, Martinique], CHU de la Martinique [Fort de France]-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France]-Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Centre de Recherche et de Veille sur les Maladies Émergentes dans l'Océan Indien (CRVOI), Université de La Réunion (UR), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Université Henri Poincaré - Nancy 1 (UHP), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Cellule Interrégionale d'Epidémiologie Antilles-Guyane, Service de santé publique et d'épidémiologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Cellule Interrégionale d'Epidémiologie, and 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)

Subjects
0301 basic medicine, Pediatrics, Pathology, Epidemiology, vector-borne infections, location.country, medicine.disease_cause, Communicable Diseases, Emerging, Disease Outbreaks, Zika virus, Dengue fever, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Maculopapular rash, Medicine, 030212 general & internal medicine, Chikungunya, Guadeloupe, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Reverse Transcriptase Polymerase Chain Reaction, Zika Virus Infection, Rash, French Guiana, 3. Good health, Population Surveillance, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, medicine.symptom, Martinique, medicine.medical_specialty, 030106 microbiology, 03 medical and health sciences, location, Zika, Virology, Humans, business.industry, Public Health, Environmental and Occupational Health, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Sequence Analysis, DNA, Zika Virus, biology.organism_classification, medicine.disease, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Martinique island, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

International audience; Following of the emergence of Zika virus in Brazil in 2015, an epidemiological surveillance system was quickly implemented in the French overseas Territories of America (FTA) according to previous experience with dengue and chikungunya and has detected first cases of Zika. General practitioners and medical microbiologists were invited to report all clinically suspectedcases of Zika, laboratory investigations were systematically conducted (RT-PCR). On 18 December, the first autochthonous case of Zika virus infection was confirmed by RT-PCR on French Guiana and Martinique, indicating introduction of Zika virus inFTA. The viral circulation of Zika virus was then also confirmed on Guadeloupe and Saint-Martin. We report here early findings on 203 confirmed cases of Zika virus infection identified by RT-PCR or seroneutralisation on Martinique Island between 24 November 2015 and 20 January 2016. All cases were investigated. Common clinical signs were observed (maculopapularrash, arthralgia, fever, myalgia and conjunctival hyperaemia) among these patients, but the rash, the foundation of our case definition, may be absent in a significant proportion of patients (16%). These results are important for the implementation of a suspected case definition, the main tool for epidemiological surveillance, in territories that may be affected by ZIKV emergence, including Europe.

Published
2016

4. Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas

Author

Yoann Madec, Cécile Herrmann-Storck, Arnaud Fontanet, Bruno Hoen, Caroline Callier, Raymond Césaire, Dominique Rousset, Alice Monthieux, Cédric Laouénan, Manon Boullard, Anna L. Funk, Maylis Douine, S. Stegmann-Planchard, Benoit Tressières, Bruno Schaub, Fatiha Najioullah, Jean-Luc Voluménie, Eustase Janky, André Cabié, Gabriel Carles, Kinda Schepers, Samson Yassinguezo, Sylvie Cassadou, Vanessa Ardillon, Philippe Kadhel, Mathieu Nacher, Catherine Ryan, CHU Pointe-à-Pitre/Abymes [Guadeloupe], 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], Université des Antilles et de la Guyane (UAG), Maison de la Femme de la Mère et de l'Enfant [CHU de la Martinique] (MFME [Fort de France]), CHU de la Martinique [Fort de France], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre Hospitalier de l'Ouest Guyanais Franck Joly [Saint-Laurent-du-Maroni, Guyane Française], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université des Antilles et de la Guyane - UFR des sciences médicales (UAG UFR SM), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Maladies infectieuses et tropicales dans la Caraïbe (MAITC EA 4537), CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Université des Antilles (UA), Centre Hospitalier Louis Constant Fleming, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Center for Global Health Research and Education - Centre pour la Recherche et la Formation en Santé Mondiale (CGH), Institut Pasteur [Paris] (IP)-Réseau International des Instituts Pasteur (RIIP), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Supported by the French Ministry of Health (Soutien Exceptionnel à la Recherche et à l’Innovation), by a grant (ANR-10-LABX-62-IBEID) from Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases project, by the ZIKAlliance consortium (the European Union’s Horizon 2020 Research and Innovation Program), and by INSERM. This study is part of the ZIKAlliance consortium project., We thank the women who participated in this study, all the physicians, midwives, clinical research assistants, health officers, and epidemiologists who helped conduct this study in each of the French territories in the Americas: Myriam Atine, Lyderic Aubert, Marie Barrau, Kebe Beavogui, Christelle Celeste, Joelle Colat-Peyron, Elvire Couchy, Véronique Davidas, Lucetta Delver, Jacqueline Dubois, Stanie Gaete, Dorothée Harrois, Marie-Laure Lalanne-Mistrih, Mathilde Melin, Marie-France Mirane, Francelise Nadessein, Marie-Josée Pelczar, Véronique Plantier, Céline Rocquet, Magdalena Saint-Marc, Patrick Saint-Martin, Valérie Soter, Ingrid Soubdhan, Jennifer Taillefond, Lambo Velonasy, and Véronique Walter (Guadeloupe), Nicole Ambroisine, Gilda Belrose, Alain Blateau, Patricia Blondel, Isabelle Calmont, Valérie Decatrelle, Michèle Gueneret, Eugénie Jolivet, Isabelle Komla-Soukha, Corinne Plavonil, Marie-andrée Pyram, and Jean-Luc Voluménie (Martinique), Antoine Adenis, Audrey Andrieu, Luisiane Carvalho, Sandy Dabrowski, Céline Delorme, Maryvonne Dueymes, Aniza Fahrasmane, Arthur Felix, Hélène Hilderal, Anne Jolivet, Justine Krajewsky, Véronique Lambert, Thomas Lemaitre, Myriam Livain, Jérémie Pasquier, Marion Petit-Sinturel, Céline Pomar, Léo Pomar, and Stéphanie Rogier (French Guiana), and David Baud (University of Lausanne, Switzerland) and Rebecca Grant (Institut Pasteur de Paris, France) for their critical review of an earlier version of the manuscript., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Jonchère, Laurent, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, 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 [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-CHU de la Martinique [Fort de France], and Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur [Paris]

Subjects
0301 basic medicine, Microcephaly, [SDV]Life Sciences [q-bio], Chromosome Disorders, MESH: Amniotic Fluid, Zika virus, Cohort Studies, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH: Martinique, ZikV Infection, Medicine, 030212 general & internal medicine, Pregnancy Complications, Infectious, Prospective cohort study, Guadeloupe, MESH: Cohort Studies, MESH: Chromosome Disorders, MESH: Middle Aged, biology, Zika Virus Infection, Obstetrics, MESH: Infant, Newborn, Pregnancy Outcome, Gestational age, MESH: Congenital Abnormalities, General Medicine, Middle Aged, French Guiana, 3. Good health, [SDV] Life Sciences [q-bio], Fetal Diseases, MESH: Fetal Diseases, MESH: Young Adult, Cohort, Female, Pregnancy Trimesters, Adult, medicine.medical_specialty, Adolescent, MESH: Zika Virus, Article, MESH: Microcephaly, Congenital Abnormalities, Young Adult, 03 medical and health sciences, MESH: Zika Virus Infection, MESH: French Guiana, Humans, MESH: Guadeloupe, Martinique, MESH: Pregnancy Complications, Infectious, Pregnancy outcomes, MESH: Adolescent, Fetus, MESH: Humans, business.industry, Infant, Newborn, MESH: Adult, Zika Virus, Amniotic Fluid, medicine.disease, biology.organism_classification, MESH: Pregnancy Outcome, Confidence interval, 030104 developmental biology, business, MESH: Female, MESH: Pregnancy Trimesters
Abstract

International audience; BACKGROUND:The risk of congenital neurologic defects related to Zika virus (ZIKV) infection has ranged from 6 to 42% in various reports. The aim of this study was to estimate this risk among pregnant women with symptomatic ZIKV infection in French territories in the Americas.METHODS:From March 2016 through November 2016, we enrolled in this prospective cohort study pregnant women with symptomatic ZIKV infection that was confirmed by polymerase-chain-reaction (PCR) assay. The analysis included all data collected up to April 27, 2017, the date of the last delivery in the cohort.RESULTS:Among the 555 fetuses and infants in the 546 pregnancies included in the analysis, 28 (5.0%) were not carried to term or were stillborn, and 527 were born alive. Neurologic and ocular defects possibly associated with ZIKV infection were seen in 39 fetuses and infants (7.0%; 95% confidence interval, 5.0 to 9.5); of these, 10 were not carried to term because of termination of pregnancy for medical reasons, 1 was stillborn, and 28 were live-born. Microcephaly (defined as head circumference more than 2 SD below the mean for sex and gestational age) was detected in 32 fetuses and infants (5.8%), of whom 9 (1.6%) had severe microcephaly (more than 3 SD below the mean). Neurologic and ocular defects were more common when ZIKV infection occurred during the first trimester (24 of 189 fetuses and infants [12.7%]) than when it occurred during the second trimester (9 of 252 [3.6%]) or third trimester (6 of 114 [5.3%]) (P=0.001).CONCLUSIONS:Among pregnant women with symptomatic, PCR-confirmed ZIKV infection, birth defects possibly associated with ZIKV infection were present in 7% of fetuses and infants. Defects occurred more frequently in fetuses and infants whose mothers had been infected early in pregnancy. Longer-term follow-up of infants is required to assess any manifestations not detected at birth. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT02916732 .).

Published
2018

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