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1. Characterization of antibody response in neuroinvasive infection caused by Toscana virus

Author

Giada Rossini, Rémi N. Charrel, Vittorio Sambri, Silvia Morini, P. Cenni, Caterina Vocale, Nazli Ayhan, M. P. Landini, Anna Pierro, Paolo Gaibani, Stefania Varani, Michele Bartoletti, Antonio Mastroianni, F. Prati, Luigi Raumer, S. Schivazappa, Russell E. Lewis, S. Ficarelli, CRREM Laboratory [Bologna, Italy] (Unit of Microbiology), University hospital - Policlinico S.Orsola-Malpighi [Bologna, Italy], Unit of Microbiology [Pievesestina, Italy] (The Romagna Hub Laboratory), The Romagna Hub Laboratory [Pievesestina, Italy], Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical and Surgical Science [Bologna, Italy] (Infectious Disease Unit), University of Bologna/Università di Bologna, Infectious Disease Unit [Forlì, Italy], G.B. Morgagni-Pierantoni Hospital [Forlì, Italy], Infectious Disease Division [Reggio Emilia, Italy], Reggio Emilia Hospital [Italy], Emergency Department [Imola, Italy], Imola Hospital S. Maria della Scaletta [Imola, Italy], Department of Experimental, Diagnostic and Specialty Medicine [Bologna, Italy] (DIMES), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), This work was supported by the University of Bologna (RFO2013e2015 to SV, MPL) and by the Emilia-Romagna Region (Lab P3 funds). This work was also supported in part by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 653316 (to RNC), the EDENext FP7- n261504 EU project (to RNC) and this paper is catalogued by the EDENext Steering Committee (http://www.edenext.eu) as EDENext467. The work of RNC was done under the frame of EurNegVec COST Action TD1303., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), University of Bologna, BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, Biology and control of vector-borne infections in Europe - EDENEXT - - EC:FP7:HEALTH2011-01-01 - 2015-06-30 - 261504 - VALID, Pierro, A., Ficarelli, S., Ayhan, N., Morini, S., Raumer, L., Bartoletti, M., Mastroianni, A., Prati, F., Schivazappa, S., Cenni, P., Vocale, C., Rossini, G., Gaibani, P., Sambri, V., Landini, M.P., Lewis, R.E., Charrel, R.N., and Varani, S.

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), Patients' follow-up, IgG avidity test, 030231 tropical medicine, 030106 microbiology, Antibodies, Viral, Bunyaviridae Infections, Antibody production, Neutralizing antibodies, Immunoglobulin G, Neutralization, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Neutralizing antibodie, medicine, Humans, Avidity, Toscana virus infection, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, Toscana virus, Meningoencephalitis, Sandfly fever Naples virus, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Antibodies, Neutralizing, Meningitis, Viral, Virology, 3. Good health, Infectious Diseases, Immunoglobulin M, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Female, Antibody, Meningitis
Abstract

Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV-meningitis or meningoencephalitis in North-eastern Italy. Objectives: Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV meningitis or meningoencephalitis in northeastern Italy. Methods: Acute and follow-up serum samples were collected up to 20 months after diagnosis of TOSV infection and tested for the presence of specific antibody using immunoenzymatic and indirect immunofluorescence assays. In addition, maturation of anti-TOSV IgG over time was evaluated as well as production of neutralizing antibodies. Results: Specific IgM and IgG response was present at diagnosis in 100% of patients; TOSV-specific IgM and IgG were detected in patients' sera up to 6 and 20 months after diagnosis, respectively. The avidity index (AI) increased over the first month after infection in 100% of patients and most cases exceeded 60% by Day 30 post infection. The AI subsequently plateaued then declined at 20 months after diagnosis. Finally, neutralization assay to TOSV was performed in 217 sera collected from 41 patients; 69.6% of tested samples resulted in reactive and moderate levels of neutralizing antibodies observed during all phases of infection despite high titres of total anti-TOSV IgG. Conclusions: Specific antibody response develops rapidly and is long-lasting for neuroinvasive TOSV infection. Serodiagnosis of neuroinvasive TOSV requires simultaneous detection of specific IgM and IgG. Moderate levels of neutralizing antibodies were maintained over the study period, while the protective role of antibodies lacking neutralizing activity is unclear and requires further evaluation.

Published
2017

2. 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