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1. Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study

Author

Gilles Nevez, Brice Autier, Jean-Pierre Gangneux, Yves Cohen, Nadine François, Cécile Aubron, Emmanuel Canet, Sophie Brun, Alexandre Alanio, Philippe Seguin, Nicolas Terzi, Bruno Mégarbane, Jean-François Timsit, Romain Pelletier, Marie Soulié, Dorothée Quinio, Estelle Sabourin, Nicolas de Prost, Juliette Guitard, Frederique Boquel, Valérie Letscher-Bru, Jeff Morcet, Stephan Ehrmann, Guillaume Voiriot, Solène Le Gal, Florent Morio, Bruno Laviolle, Jean-Christophe Richard, Laurent Argaud, Estelle Cateau, Marion Blaize, Matthieu Lesouhaitier, Patrice Le Pape, Carole Schwebel, Florent Wallet, Jordan Leroy, Jean-Ralph Zahar, Ana Novara, Hélène Guegan, Béatrice Riu-Poulenc, Florence Robert-Gangneux, Jean Menotti, Eric Dannaoui, Sorya Belaz, Yves Le Tulzo, Muriel Cornet, Saad Nseir, Ferhat Meziani, Damien Dupont, Boualem Sendid, Antoine Monsel, Florian Reizine, Xavier Iriart, Francoise Botterel, Arnaud Fekkar, Charles-Edouard Luyt, Cécile Garnaud, Melek Manai, Lionel Lamhaut, Jean-Marc Tadié, Julien Mayaux, Sylvie Paulus, Florence Persat, Marie-Elisabeth Bougnoux, Christophe Hennequin, Christine Bonnal, Arnaud W. Thille, Antoine Berry, Sandrine Houze, Guillaume Desoubeaux, Centre Hospitalier Universitaire [Rennes], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Lille, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Avicenne [AP-HP], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Necker - Enfants Malades [AP-HP], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Strasbourg, and CarMeN, laboratoire

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Intensive care, Internal medicine, medicine, Humans, education, Mechanical ventilation, education.field_of_study, Coinfection, SARS-CoV-2, business.industry, Mucormycosis, COVID-19, Articles, Odds ratio, medicine.disease, [SDV] Life Sciences [q-bio], Mycoses, business, Cohort study
Abstract

International audience; BACKGROUND: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care. METHODS: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221. FINDINGS: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (\textgreater14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (\textless1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p\textless0·0001). INTERPRETATION: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19. FUNDING: Pfizer.

Published
2022
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2. Selection of Pneumocystis jirovecii Inosine 5′-Monophosphate Dehydrogenase Mutants in Solid Organ Transplant Recipients: Implication of Mycophenolic Acid

Author

Nicolas Papon, Gilles Nevez, Dorothée Quinio, Marie-Christine Moal, Claire V Hoffmann, Jean-Philippe Bouchara, Yannick Le Meur, Nathan Le Nan, Solène Le Gal, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)

Subjects
Microbiology (medical), QH301-705.5, [SDV]Life Sciences [q-bio], Population, selection, Plant Science, Pneumocystis pneumonia, Mycophenolic acid, Article, Pneumocystis jirovecii, Microbiology, IMPDH, 03 medical and health sciences, parasitic diseases, medicine, Inosine-5′-monophosphate dehydrogenase, Biology (General), education, Inosine, Gene, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, education.field_of_study, biology, 030306 microbiology, medicine.disease, biology.organism_classification, 3. Good health, Transplantation, biology.protein, mycophenolic acid, medicine.drug, transplantation
Abstract

Mycophenolic acid (MPA) targets the inosine 5′-monophosphate dehydrogenase (IMPDH) of human lymphocytes. It is widely used as an immunosuppressant to prevent rejection in solid organ transplant (SOT) recipients who, incidentally, are at risk for Pneumocystis pneumonia (PCP). We hypothesized that MPA exerts selective pressure on P. jirovecii microorganisms considering its in vitro antifungal activity on other fungi. Thus, we analysed impdh gene in P. jirovecii isolates from SOT recipients. P. jirovecii specimens from 26 patients diagnosed with PCP from 2010 to 2020 were retrospectively examined: 10 SOT recipients treated with MPA and 16 non-SOT patients without prior exposure to MPA. The P. jirovecii impdh gene was amplified and sequenced. Nucleotide sequences were aligned with the reference sequences retrieved from available P. jirovecii whole genomes. The deduced IMPDH protein sequences were aligned with available IMPDH proteins from Pneumocystis spp. and other fungal species known to be in vitro sensitive or resistant to MPA. A total of nine SNPs was identified. One SNP (G1020A) that results in an Ala261Thr substitution was identified in all SOT recipients and in none of the non-SOT patients. Considering that IMPDHs of other fungi, resistant to MPA, harbour Thr (or Ser) at the analogous position, the Ala261Thr mutation observed in MPA-treated patients was considered to represent the signature of P. jirovecii exposure to MPA. These results suggest that MPA may be involved in the selection of specific P. jirovecii strains that circulate in the SOT recipient population.

Published
2021
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3. Evaluation of posaconazole antifungal prophylaxis in reducing the incidence of invasive aspergillosis in patients with acute myeloid leukemia

Author

Christian Berthou, Marie-Anne Couturier, Jean-Christophe Ianotto, Gaelle Guillerm, Hervé Le Bars, Christopher Payan, Marie Uguen, Philippe Saliou, Valérie Narbonne, Lenaïg Le Clech, G. Nevez, Raoul Baron, Dorothée Quinio, Département d'Hématologie Clinique (BREST - Hémato Clinique), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Departement Médecine Générale [Brest] (Faculté de Médecine), Université de Brest (UBO), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), CHRU Brest, Laboratoire d'Hématologie, 29200 Brest, INSERM U1078, Department of Microbiology Brest, Department of Microbiology, Brest, Lab-STICC_UBO_CACS_MOCS, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and CCSD, Accord Elsevier

Subjects
Male, 0301 basic medicine, Posaconazole, Antifungal Agents, [SDV]Life Sciences [q-bio], Air Microbiology, Statistical difference, Kaplan-Meier Estimate, Aspergillosis, Construction works, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, education.field_of_study, Incidence, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Myeloid leukemia, General Medicine, Middle Aged, Spores, Fungal, Combined Modality Therapy, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, Aspergillus, Air Filters, Air Pollution, Indoor, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, Antifungal prophylaxis, medicine.drug, Adult, Antifungal, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, Population, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, medicine, Humans, Hospital Design and Construction, In patient, Hospitals, Teaching, education, Febrile Neutropenia, Retrospective Studies, Aerosols, Acute myeloid leukemia, business.industry, Environmental Exposure, Triazoles, medicine.disease, 030104 developmental biology, Invasive aspergillosis, business, Filtration, Invasive Fungal Infections
Abstract

International audience; Purpose of the study: Invasive aspergillosis (IA) is the most prevalent invasive fungal disease (IFD) in neutropenic patients. Environment is the main source of Aspergillus spores aerosolization especially during building construction. International guidelines recommend mechanical protection during hospital building works; otherwise the use of antifungal prophylaxis is not clearly indicated. Our objective was to determine the efficacy of antifungal prophylaxis by posaconazole on IA incidence in acute myeloid leukemia population and to analyse the benefit of this prophylaxis and HEPA-filters during hospital buildings works.Patients and methods: We included patients treated for acute myeloid leukemia at Brest teaching hospital from January 2009 to December 2015. We compared incidence of IA in the group treated by posaconazole from 2012 to 2015 to the incidence of IA in the first group who did not receive antifungal prophylaxis (from 2009 to 2011). The one-year overall survival was also analyzed using the Kaplan-Meier method.Results: 245 patients were enrolled including 151 treated with posaconazole. 23 IA were diagnosed between 2009 and 2011 (without antifungal prophylaxis), then 31 between 2012 and 2015 (with posaconazole) without statistical difference between the incidence densities (0.34 per 100 hospitalization-days vs. 0.30 per 100 hospitalization-days, p = 0.71). Incidence density of IA increased during building works (2.40 per 100 hospitalization-days vs. 0.28 per 100 hospitalization-days, p < 0.0001). The incidence density of IA significantly decreased during construction periods when posaconazole prophylaxis was used (1.59 per 100 hospitalization-days vs. 4.87 per 100 hospitalization-days p < 0.0001).Conclusion: Our study suggests, for the first time, the interest of antifungal prophylaxis in addition to HEPA filtration in prevention of IA during hospital building works.

Published
2020
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4. Epidemiological investigation for grouped cases of Trichosporon asahii using whole genome and IGS1 sequencing

Author

N. Brieu, B. Sendid, E. Sitterle, Frédéric Gabriel, I. Poilane, D. Moissenet, Christine Aznar, V. Blanc, N. Traversier, M. Sasso, N. Godineau, O. Eloy, Corinne Maufrais, Danièle Maubon, H. Rabérin, C. Lawrence, P. Mariani, P. Cahen, C. Bonnal, B. Bouteille, M. Cornet, F. Moriot, B. Heym, Elisabeth Chachaty, Dominique Toubas, M. Nicolas, Sophie Cassaing, A. Paugam, S. Picot, E. Moalic, Adela Angoulvant, Loïc Favennec, Françoise Dromer, M. Gari‐toussaint, Marc Pihet, Taieb Chouaki, Magalie Pierre Demar, Frédéric Grenouillet, N. Fauchet, L. Collet, Frédéric Dalle, Marie-Elisabeth Bougnoux, Céline Nourrisson, Marie Desnos-Ollivier, O. Faure, Françoise Botterel, C. Nabet, N. Bourgeois, E. Bailly, Dorothée Quinio, Alexandre Alanio, O. Mouquet, S. Brun, S. Bland, Julie Bonhomme, Jean-Pierre Gangneux, Stéphane Ranque, Philippe Poirier, N. Desbois, Florence Persat, Anne-Pauline Bellanger, H. Piarroux, E. Forget, L. Lachaux, V. Bru, Laurence Millon, A. Minoza, C. Kauffman, L. Hasseine, Martine Wallon, A.L. Roux, D. Poisson, S. Bonacorsi, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre d'Informatique pour la Biologie, Institut Pasteur [Paris], Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), 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), Observatoires Régionaux du Pneumocoque, Partenaires INRAE, Université de Picardie Jules Verne (UPJV), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), 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 Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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 Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Laboratoire de parasitologie [Pointe-à-Pitre], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Sud Saint Pierre [Ile de la Réunion], Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Huriez, CHU Limoges, Hospices Civils de Lyon (HCL), Institut de parasitologie et mycologie médicale, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Service de Maladies Infectieuses et Tropicales [Fort-de-France, Martinique], CHU Fort de France-CHU de la Martinique [Fort de France]-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France], Hydrosciences Montpellier (HSM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hôpital universitaire Bichat, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Curie [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Laboratoire Chrono-environnement (UMR 6249) (LCE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
0301 basic medicine, Adult, Male, Antifungal Agents, Adolescent, Genotype, Genotyping Techniques, [SDV]Life Sciences [q-bio], 030106 microbiology, Single-nucleotide polymorphism, Dermatology, Trichosporon asahii, Biology, Genome, DNA, Ribosomal, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Trichosporonosis, medicine, Humans, Child, DNA, Fungal, Mycological Typing Techniques, Genotyping, Phylogeny, ComputingMilieux_MISCELLANEOUS, Aged, Genetics, Voriconazole, Whole genome sequencing, Whole Genome Sequencing, Basidiomycota, Haplotype, Infant, General Medicine, Sequence Analysis, DNA, Middle Aged, medicine.disease, 3. Good health, Infectious Diseases, Child, Preschool, Female, France, Genome, Fungal, medicine.drug
Abstract

BACKGROUND Trichosporonosis is a rare invasive infection in humans mainly due to Trichosporon asahii, and especially recovered from patients having haematological malignancy. Since 2012, IGS1 region sequencing is used as a genotyping method to distinguish isolates, with high frequency of one haplotype worldwide and a geographic specificity for some haplotypes. OBJECTIVES We compared the IGS1 genotyping method and whole genome sequencing (WGS) to study the relationship between clinical isolates involved in two grouped cases in France. METHODS IGS1 sequencing and antifungal susceptibility testing were performed for 54 clinical isolates. Clinical data for 28 isolates included in surveillance programs were analysed. Whole genome was sequenced for 32 clinical isolates and the type strain. RESULTS All isolates were intrinsically resistant to flucytosine, while voriconazole had the most potent in vitro activity. The majority of the isolates was recovered from patients with haematological malignancies (42.86%), with a high proportion of children (

Published
2020
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5. Ultrasound features of fetal toxoplasmosis: A contemporary multicenter survey in 88 fetuses

Author

Nicole Ferret, Catherine Noel, Alexandra Benachi, Anne-Hélène Saliou, Olivier Picone, Léo Pomar, Estelle Cateau, Camille Codaccioni, Fabrice Cuillier, Laurent Mandelbrot, Dorothée Quinio, Norbert Winer, Denis Filisetti, Isabelle Villena, Martine Wallon, A. S. Weingertner, Valérie Vequeau-Goua, Christelle Pomares, Paul Maurice, Guillaume Benoist, Yves Ville, Rose-Anne Lavergne, Laurent Guibaud, Marc Dommergues, Véronique Lambert, Service de gynécologie et obstétrique [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Louis Mourrier, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre Hospitalier de l'Ouest Guyanais Franck Joly [Saint-Laurent-du-Maroni, Guyane Française], Service de Médecine Fœtale [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de parasitologie et de mycologie médicale [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Radiologie [HCL, Lyon], Hospices civils de Lyon (HCL), Service de Gynécologie-Obstétrique (BREST - Gynéco-Obs), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Service de gynécologie-obstétrique, médecine de la reproduction [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gynécologie-Obstétrique [CH Renée Dubos, Pontoise], Centre Hospitalier Renée Dubos [Pontoise], Université Paris Descartes - Paris 5 (UPD5), Service de Gynécologie Obstétrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Laboratoire de Parasitologie-Mycologie, Nice, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de parasitologie et mycologie médicale [CHU Strasbourg], CHU Strasbourg, Département de Gynécologie-Obstétrique [CHU Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de gynécologie et obstétrique [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire de Parasitologie-Mycologie (CHU de Poitiers), Université de Lausanne (UNIL), Hospices Civils de Lyon (HCL), Service de Gynécologie-Obstétrique, Maternité, Chirurgie Gynécologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), Dupuis, Christine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Lausanne = University of Lausanne (UNIL), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)

Subjects
0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030105 genetics & heredity, Toxoplasmosis, Congenital, Ultrasonography, Prenatal, Serology, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Ascites, medicine, Humans, Seroconversion, Pregnancy Complications, Infectious, Genetics (clinical), Retrospective Studies, Fetus, 030219 obstetrics & reproductive medicine, business.industry, Ultrasound, Obstetrics and Gynecology, medicine.disease, Toxoplasmosis, 3. Good health, [SDV] Life Sciences [q-bio], Fetal Diseases, Multicenter survey, Small for gestational age, Female, Radiology, medicine.symptom, business
Abstract

Objective: To describe the lesions detected by prenatal ultrasound examination in congenital toxoplasmosis (CT). Methods: We retrospectively analyzed all cases of fetal infection with T. gondii with ultrasound anomalies described by fetal medicine experts in 2009-2019 in 30 French centers. Results: Eighty-eight cases of CT were included. Forty-five (51.1%) had one or more cerebral signs only, 35 (39.8%) had cerebral plus extra-cerebral signs and 8 (9.1%) had extra-cerebral signs only. The main cerebral signs were intracranial hyperechogenic nodular foci (n=60) of which 20 were isolated, ventriculomegalies (n=44) which generally increased during follow-up, and periventricular abscesses (n=12). The main extra-cerebral signs were hepatomegaly and/or splenomegaly (n=14), small for gestational age (n=14), ascites (n=14, including 2 with hydrops), and hyperechogenic bowel (n=11). Maternal infection occurred mostly in the first or second trimester (81 cases), periconceptionally in 1 and in the third trimester in 6 cases. The first ultrasound signs were detected after a median of 7 weeks [range: 1.4; 24.0] following maternal toxoplasmosis seroconversion. Conclusion: While no sign was specific of CT, there were typical associations of cerebral signs with or without extracerebral signs. Detailed ultrasound examination could improve prognostic evaluation, as well as diagnosis of CT in settings lacking serological screening. This article is protected by copyright. All rights reserved.

Published
2020
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6. Pneumocystis jiroveciiin Patients With Cystic Fibrosis: A Review

Author

Pierre Bonnet, Solène Le Gal, Enrique Calderon, Laurence Delhaes, Dorothée Quinio, Florence Robert-Gangneux, Sophie Ramel, Gilles Nevez, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Hospital Universitario Virgen del Rocío [Sevilla], Aquitaine’s Care and Research organisation for inflammatory and Immune-Mediated diseases [CHU Bordeaux] (FHU ACRONIM), CHU Bordeaux [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Fondation ILDYS (ILDYS), Chard-Hutchinson, Xavier, Université d'Angers (UA)-Université de Rennes 1 (UR1), and 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 )

Subjects
0301 basic medicine, Cystic Fibrosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:QR1-502, Disease, Pneumocystis carinii, Pneumocystis pneumonia, Cystic fibrosis, lcsh:Microbiology, Organ transplantation, genomic diversity, cystic fibrosis, Cellular and Infection Microbiology, Child, Lung, Pneumocystis jirovecii, biology, Pneumonia, Pneumocystis, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, medicine.symptom, Brazil, Adult, Microbiology (medical), medicine.medical_specialty, Pneumocystis primary infection, Mini Review, 030106 microbiology, Immunology, Microbiology, Asymptomatic, 03 medical and health sciences, medicine, Pneumocystispneumonia, microbiota, lung transplantation, Humans, Lung transplantation, Risk factor, business.industry, Pneumocystisprimary infection, Infant, medicine.disease, biology.organism_classification, 030104 developmental biology, pulmonary colonization, business
Abstract

Réseau Muco Ouest., Pneumocystis pneumonia (PCP) remains the most frequent AIDS-defining illness in developed countries. This infection also occurs in non-AIDS immunosuppressed patients, e.g., those who have undergone an organ transplantation. Moreover, mild Pneumocystis jirovecii infections related to low pulmonary fungal burden, frequently designated as pulmonary colonization, occurs in patients with chronic pulmonary diseases, e.g., cystic fibrosis (CF). Indeed, this autosomal recessive disorder alters mucociliary clearance leading to bacterial and fungal colonization of the airways. This mini-review compiles and discusses available information on P. jirovecii and CF. It highlights significant differences in the prevalence of P. jirovecii pulmonary colonization in European and Brazilian CF patients. It also describes the microbiota associated with P. jirovecii in CF patients colonized by P. jirovecii. Furthermore, we have described P. jirovecii genomic diversity in colonized CF patients. In addition of pulmonary colonization, it appears that PCP can occur in CF patients specifically after lung transplantation, thus requiring preventive strategies. In other respects, Pneumocystis primary infection is a worldwide phenomenon occurring in non-immunosuppressed infants within their first months. The primary infection is mostly asymptomatic but it can also present as a benign self-limiting infection. It probably occurs in the same manner in CF infants. Nonetheless, two cases of severe Pneumocystis primary infection mimicking PCP in CF infants have been reported, the genetic disease appearing in these circumstances as a risk factor of PCP while the host-pathogen interaction in older children and adults with pulmonary colonization remains to be clarified.

Published
2020
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7. Pneumocystis primary infection in infancy: Additional French data and review of the literature

Author

Sergio L. Vargas, Nicolas Papon, Dorothée Quinio, Pierrick Cros, Gilles Nevez, Carolina A. Ponce, Thibaud Guillaud-Saumur, Solène Le Gal, S. Vallet, Theresa J. Ochoa, Loïc de Parscau, Jacques Sizun, Adissa Minoui-Tran, Léa Pilorgé, Beatriz Bustamante, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université de Brest (UBO), Service de pédiatrie, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), and Département de Pédiatrie

Subjects
Male, Multivariate analysis, Denmark, [SDV]Life Sciences [q-bio], Pneumocystis carinii, Pneumocystis pneumonia, Interquartile range, Nasopharynx, Peru, Genotype, Chile, DNA, Fungal, Mycological Typing Techniques, Pneumocystis jirovecii, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, Univariate analysis, biology, infants, Pneumonia, Pneumocystis, General Medicine, Middle Aged, 3. Good health, Infectious Diseases, Child, Preschool, primary infection, purl.org/pe-repo/ocde/ford#4.03.00 [https], Female, Original Article, France, MLST, Adult, medicine.medical_specialty, purl.org/pe-repo/ocde/ford#3.03.08 [https], 03 medical and health sciences, genotypes, Internal medicine, Lower respiratory tract infection, medicine, Humans, Aged, Retrospective Studies, 030304 developmental biology, 030306 microbiology, business.industry, Infant, Newborn, Infant, medicine.disease, biology.organism_classification, Multilocus sequence typing, business, Multilocus Sequence Typing
Abstract

Data on features of Pneumocystis primary infection in infancy are still fragmented. To study Pneumocystis primary infection, 192 infants who were monitored for acute pulmonary disease or fever over a 40-month period were retrospectively investigated. P. jirovecii detection on archival nasopharyngeal aspirates was performed using a qPCR assay. Factors associated with P. jirovecii were assessed using univariate and multivariate analyses. P. jirovecii genotypes in infants and a control group of adults contemporaneously diagnosed with Pneumocystis pneumonia were identified using unilocus, bilocus, and multilocus sequence typing (MLST). P. jirovecii was detected in 35 infants (18.2%). The univariate analysis pointed out four factors: viral infection (P = .035, OR [IC 95], 2.2 [1.1–4.7]), lower respiratory tract infection (P = .032, OR [IC 95], 2.5 [1.1–5.9]), absence of hospital discharge after birth (P = .003, OR (IC 95), 0.1 (0.02–0.5]), and the 63–189-day group (P < .001, OR [IC 95], 42.2 [5.4–332]). The multivariate analysis confirmed these two latter factors (P = .02, OR [IC 95], 0.1 [0.02–0.72]; P = .005, OR [IC 95], 11.5 [2.1–63.5]). Thus, P. jirovecii acquisition mostly takes place in the community. A comparison of these data with those of previously published studies showed that median and interquartile range of positive-infant ages were close to those observed in Chile, Denmark, and Peru, highlighting similar characteristics. Common unilocus or bilocus genotypes were identified in infants and adults, whereas no MLST genotypes were shared. Therefore, a common reservoir made up of infected infants and adults is still hypothetical. Finally, primary infection is a worldwide phenomenon occurring at the same time in childhood regardless of geographical location, rather than an incidental event.

Published
2019
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8. Encephalitozoon hellem in a patient with CD4+ T-cell prolymphocytic leukemia: case report and genomic identification

Author

Christian Berthou, Dorothée Quinio, Claudine Sarfati, Samia Hamane, Gilles Nevez, Jean-Christophe Ianotto, Jean Menotti, Solène Le Gal, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Institut de cancérologie et d'hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Parasitologie et Mycologie (Parasito-Myco - ST LOUIS PARIS), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
CD4-Positive T-Lymphocytes, Microbiology (medical), Leukemic patient, Encephalitozoon hellem, [SDV]Life Sciences [q-bio], Chronic lymphocytic leukemia, Molecular Sequence Data, Biology, Microsporidiosis, DNA, Ribosomal, hemic and lymphatic diseases, RNA, Ribosomal, 18S, medicine, Humans, DNA, Fungal, Prolymphocytic leukemia, Aged, Cd4 t cell, fungi, Encephalitozoon, Genes, rRNA, RNA, Fungal, Sequence Analysis, DNA, General Medicine, medicine.disease, Virology, 3. Good health, Encephalitozoonosis, Infectious Diseases, Leukemia, Prolymphocytic, T-Cell, Female, Identification (biology), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Five cases of microsporidioses among leukemic patients, 4 in myeloid-leukemic patients and 1 in a chronic lymphocytic leukemia, have been described until now. We report a case of microsporidiosis and the genomic identification of Encephalitozoon hellem in a patient with CD4(+) T-cell prolymphocytic leukemia.

Published
2015
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9. A Cluster of Pneumocystis Infections Among Renal Transplant Recipients: Molecular Evidence of Colonized Patients as Potential Infectious Sources of Pneumocystis jirovecii

Author

Elodie Moalic, Céline Damiani, Yann Le Meur, Dorothée Quinio, Marie-Christine Moal, Anne Totet, Amélie Rouillé, Christian Berthou, Gilles Nevez, Solène Le Gal, A. Grall, Philippe Saliou, Michèle Virmaux, and Laetitia Tréguer

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, Genotype, Context (language use), Pneumocystis carinii, Pneumocystis pneumonia, Disease Outbreaks, Internal medicine, DNA, Ribosomal Spacer, parasitic diseases, Epidemiology, medicine, Pneumocystosis, Humans, Pneumocystis jirovecii, DNA, Fungal, Mycological Typing Techniques, Aged, Molecular Epidemiology, Transplantation, biology, business.industry, Outbreak, Middle Aged, medicine.disease, biology.organism_classification, Kidney Transplantation, Molecular Typing, Pneumocystis Infections, Infectious Diseases, Female, France, business
Abstract

BACKGROUND Eighteen renal transplant recipients (RTRs) developed Pneumocystis jirovecii infections at the renal transplantation unit of Brest University Hospital (Brest, Brittany, France) from May 2008 through April 2010, whereas no cases of P. jirovecii infection had been diagnosed in this unit since 2002. This outbreak was investigated by identifying P. jirovecii types and analyzing patient encounters. METHODS The identification of P. jirovecii internal transcribed spacer (ITS) types was performed on P. jirovecii isolates from the 18 RTRs (12 patients with Pneumocystis pneumonia [PCP], 6 colonized patients), 22 unlinked control patients (18 patients with PCP, 4 colonized patients), and 69 patients (34 patients with PCP, 35 colonized patients) with contemporaneously diagnosed P. jirovecii infections in the Brest geographic area. A transmission map was drawn up. Its analysis was combined with the results of P. jirovecii typing. RESULTS P. jirovecii ITS type identification was successful in 14 of 18 RTRs, 15 of 22 control patients, and 48 of the 69 patients. Type Eg was the most frequent type in the 3 patient groups. However, its frequency was significantly higher in the first patient group than in the 2 other groups (P < .05 and P < .01, respectively). Fourteen encounters between RTRs who harbored an identical type were observed. Ten patients were considered as possible index patients, of whom 3 were colonized by the fungus, and 7 presented PCP. CONCLUSIONS The results provide to our knowledge the first data on the role of colonized patients as potential sources of P. jirovecii in a context of nosocomial acquisition of the fungus.

Published
2012
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10. Zygomycosis caused byCunninghamella bertholletiaein a kidney transplant recipient

Author

O. Masure, Marie-Christine Moal, A. Karam, A. M. Le Flohic, B. Bourbigot, Dorothée Quinio, B. Sassolas, and J.-P. Leroy

Subjects
Male, Mucorales, medicine.medical_specialty, Itraconazole, Opportunistic Infections, Lesion, Immunocompromised Host, Diabetes mellitus, medicine, Humans, Mucormycosis, Cunninghamella, Kidney transplantation, biology, business.industry, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Kidney Transplantation, Dermatology, Cunninghamella bertholletiae, Tacrolimus, Surgery, Infectious Diseases, medicine.symptom, Zygomycosis, business, medicine.drug
Abstract

Infections caused by Cunninghamella bertholletiae are rare but severe. Only 32 cases have been reported as yet, but in 26 of these this species was a contributing cause of the death of the patient. This opportunistic mould in the order Mucorales infects immunocompromized patients suffering from haematological malignancies or diabetes mellitus, as well as solid organ transplant patients. The lung is the organ most often involved. Two cases of primary cutaneous infection have been previously reported subsequent to soft-tissue injuries. We report a case of primary cutaneous C. bertholletiae zygomycosis in a 54-year-old, insulin-dependent diabetic man who was treated with tacrolimus and steroids after kidney transplantation. No extracutaneous involvement was found. In this patient, the infection may have been related to insulin injections. The patient recovered after an early surgical excision of the lesion and daily administration of itraconazole for 2 months. This case emphasizes the importance of an early diagnosis of cutaneous zygomycosis, which often presents as necrotic-looking lesions. Prompt institution of antifungal therapy and rapid surgical intervention are necessary to improve the prospects of patients who have contracted these potentially severe infections.

Published
2004
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11. Low rate of Candida parapsilosis -relatedcolonization and infection in hospitalized preterm infants: a one-year prospective study

Author

Dorothée Quinio, Jacques Sizun, L. de Parscau, E. Vernotte, A. M. Le Flohic, R. Baron, and Arnaud Gagneur

Subjects
Microbiology (medical), medicine.medical_specialty, Neonatal intensive care unit, Infant, Premature, Diseases, Sabouraud agar, Candida parapsilosis, Gastroenterology, chemistry.chemical_compound, Risk Factors, Intensive Care Units, Neonatal, Internal medicine, medicine, Humans, Colonization, Prospective Studies, Prospective cohort study, Mycosis, Candida, Cross Infection, Infection Control, Mouth, biology, business.industry, Candidiasis, Infant, Newborn, Rectum, Gestational age, General Medicine, medicine.disease, biology.organism_classification, Corpus albicans, Surgery, Infectious Diseases, chemistry, business, Infant, Premature
Abstract

We determined the rate of Candida parapsilosis colonization in preterm neonates (NN) and the relationship between colonization and systemic infection through a prospective study in the Neonatal Intensive Care Unit of a university hospital. All NN born at a gestational age of 32 weeks or less were included. Specimens from rectum, mouth and retro-auricular skin were obtained at admission and weekly thereafter. All samples were inoculated on to Sabouraud agar, CHROMagar® and Dixon media. Candida species were identified using API Candida® and API 20C®. DNA analysis was performed using pulse field gel electrophoresis. Fifty-four patients were included (mean age: 30 ± 1.5 weeks; mean birthweight: 1347 ± 301 g; male: 40%). Fungal colonization was detected in 43 (79.6%). Causative agents were C. parapsilosis ( N = 7); Malassezia furfur ( N = 30); C. albicans ( N = 21), C. guillermondii ( N = 1). No sample was positive for two different yeasts at the same time. C. parapsilosis colonization included anal ( N = 6), buccal ( N = 1), and skin ( N = 2). The average age at time of colonization was 17.8±9.8 days. Neither fungal septicaemia nor death were observed in colonized infants. Two central venous catheters were found to be colonized, one with C. parapsilosis and one with M. furfur . Logistic regression showed a link between colonization and gestational age alone. Three different DNA profiles were observed. This study suggests that in our units, the occurrence of C. parapsilosis colonization is low and bears no relation to systemic infection. The systematic identification of C. parapsilosis carriers for the purposes of isolation and preventive treatment does not appear to be warranted.

Published
2001
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12. Toxoplasma Seroconversion with Negative or Transient Immunoglobulin M in Pregnant Women: Myth or Reality? A French Multicenter Retrospective Study

Author

Dorothée Quinio, Isabelle Villena, Laurence Delhaes, Odile Villard, N. Godineau, Hélène Fricker-Hidalgo, Hervé Pelloux, Coralie L'Ollivier, B. Cimon, Ermanno Candolfi, Luc Paris, Cathy Chemla, Marie-Laure Dardé, Florence Robert-Gangneux, Sandrine Houzé, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Hôpital Bichat - Claude Bernard, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Parasitologie-Mycologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]

Subjects
Microbiology (medical), medicine.medical_specialty, Amniotic fluid, 030231 tropical medicine, Antiprotozoal Agents, Antibodies, Protozoan, Immunoglobulin G, Serology, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Spiramycin, Medicine, Humans, Seroconversion, Pregnancy Complications, Infectious, Retrospective Studies, 0303 health sciences, biology, 030306 microbiology, business.industry, Obstetrics, Infant, Newborn, medicine.disease, Toxoplasmosis, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Immunoglobulin M, Immunology, biology.protein, Parasitology, Female, France, Pregnant Women, business, Toxoplasma, medicine.drug
Abstract

Classically, Toxoplasma infection is associated with high levels of specific IgM antibody and a rise in specific IgG levels 1 to 3 weeks later. Atypical IgG seroconversion, without IgM detection or with transient IgM levels, has been described during serologic follow-up of seronegative pregnant women and raises difficulties in interpreting the results. To evaluate the frequency and the characteristics of these atypical cases of seroconversion, an investigation was conducted within the French National Reference Center for Toxoplasmosis, from which 26 cases collected from 12 laboratories belonging to the network were identified. The aim of this work was to retrospectively analyze the results of serologic testing, the treatments administered, and the results of prenatal and postnatal follow-up for these women. In each case, IgG antibodies were detected using both screening and confirmatory tests. IgM antibodies were not detected in 15 cases, and the levels were equivocal or low-positive in 11 cases. The IgG avidity results were low in 16 cases and high in one case. Most of the pregnant women (22/26) were treated with spiramycin from the time that IgG antibodies appeared until delivery. Amniotic fluid was analyzed for Toxoplasma gondii DNA by PCR in 11/26 cases, and the results were negative in all cases. Congenital toxoplasmosis was ruled out in 12/26 newborns. There was no abnormality observed at birth for 10 newborns and no information available for 4 newborns. In conclusion, when the interpretation of serological results is so difficult, it seems cautious to initiate treatment by spiramycin and to follow the pregnant women and their newborns.

Published
2013
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13. Clinical relevance of placenta examination for the diagnosis of congenital toxoplasmosis

Author

Jean-Pierre Gangneux, Florence Robert-Gangneux, Claude Guiguen, Dorothée Quinio, Patrice Poulain, Peggy Dupretz, Chantal Yvenou, CHU Pontchaillou [Rennes], Service de Pédiatrie, Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes]

Subjects
postnatal diagnosis, Pathology, Polymerase Chain Reaction, Toxoplasmosis, Congenital, Mice, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH: Animals, 030212 general & internal medicine, 0303 health sciences, biology, Obstetrics, MESH: Toxoplasma, MESH: Infant, Newborn, MESH: Placenta, 3. Good health, Infectious Diseases, medicine.anatomical_structure, PCR, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, congenital toxoplasmosis, Gestation, Female, medicine.symptom, Toxoplasma, Animal Experimentation, Microbiology (medical), medicine.medical_specialty, placenta, Toxoplasma gondii, MESH: DNA, Protozoan, Prenatal diagnosis, mouse assay, Sensitivity and Specificity, Asymptomatic, 03 medical and health sciences, Placenta, medicine, Animals, Humans, Clinical significance, MESH: Mice, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, 030306 microbiology, business.industry, Infant, Newborn, MESH: Polymerase Chain Reaction, DNA, Protozoan, medicine.disease, biology.organism_classification, MESH: Toxoplasmosis, Congenital, Toxoplasmosis, MESH: Sensitivity and Specificity, Pediatrics, Perinatology and Child Health, MESH: Animal Experimentation, business, MESH: Female
Abstract

International audience; BACKGROUND: Neonates with congenital toxoplasmosis, even asymptomatic at birth, should be treated early to reduce long-term sequelae. Postnatal diagnosis of congenital toxoplasmosis is essential because prenatal diagnosis fails to detect approximately 15% of cases or cannot be performed when maternal infection is acquired in late pregnancy. Detection of parasites in the placenta is one diagnostic approach to the early neonatal diagnosis of congenital toxoplasmosis. METHODS: The parasitic analyses of 102 placentas from cases of toxoplasmosis acquired during gestation were reviewed, with complete biologic follow-up of neonates. The value of quantitative PCR and mouse inoculation was assessed, and results are discussed in light of prenatal treatment and postnatal outcome. RESULTS: Congenital toxoplasmosis was diagnosed in 28 of the 102 cases. A prenatal diagnosis was obtained in only 16 cases. Specific IgM was detected in 57% of the babies at birth. A positive placental examination by PCR and mouse inoculation was the only evidence of infection in 3 neonates (11%) who were asymptomatic at birth. The sensitivities of PCR and mouse inoculation were 71% and 67%, respectively, and the specificities were 97% and 100%. Parasites were detected more often when maternal infection was acquired during the third trimester of pregnancy (P < 0.01), regardless the type of treatment. The sensitivity of IgM detection appeared to be related to maternal treatment since IgM was positive in 43% and 75% when mothers were treated or not, respectively (P < 0.01). Though 5/7 symptomatic infants had a positive placenta examination, there was no correlation between a positive placenta and the presence of clinical signs during the first year of life. The positive and negative predictive values of placental examination were 91% and 90%, respectively. CONCLUSION: Placental examination is an efficient tool for the early diagnosis of congenital toxoplasmosis.

Published
2010
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14. Genotype of 88 Toxoplasma gondii isolates associated with toxoplasmosis in immunocompromised patients and correlation with clinical findings

Author

Thanh Hai Duong, C. Kauffmann-Lacroix, Sophie Pujol, Meja Rabodonirina, Luc Paris, Françoise Gay-Andrieu, Daniel Ajzenberg, Pierre Flori, B. Cuisenier, Francine Pratlong, Bernard Carme, Marie-Hélène Bessières, Hélène Yera, Jean Menotti, Dominique Aubert, Marie-Laure Dardé, Pierre Marty, N. Desbois, Marie-Elisabeth Bougnoux, Philippe Thulliez, Anne Totet, Denis Filisetti, Isabelle Villena, Dorothée Quinio, Laurence Delhaes, Hervé Pelloux, Florence Robert-Gangneux, Gilles Nevez, Jacqueline Franck, Chantal Duhamel, Frédéric Dalle, Henri Bonnabau, Université de Limoges (UNILIM), Neuroépidémiologie Tropicale et Comparée (NETEC), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges (UNILIM), Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) (CNR Toxoplasmose-Toxoplasma BRC), CHU Limoges, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), and Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME)

Subjects
medicine.medical_specialty, Genotype, Lung Diseases, Parasitic, 030231 tropical medicine, Population, Acquired Toxoplasmosis, HIV Infections, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Immunopathology, Epidemiology, parasitic diseases, medicine, Immunology and Allergy, Animals, Humans, education, Genotyping, 030304 developmental biology, 0303 health sciences, education.field_of_study, biology, Toxoplasma gondii, biology.organism_classification, medicine.disease, Virology, Toxoplasmosis, 3. Good health, Infectious Diseases, Immunology, Encephalitis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Toxoplasma
Abstract

International audience; We report the genotyping analysis of Toxoplasma gondii isolates in samples collected from 88 immunocompromised patients, along with clinical and epidemiological data. Most of these samples were collected in France during the current decade by the Toxoplasma Biological Resource Center. Lack of specific anti-Toxoplasma treatment, pulmonary toxoplasmosis, and involvement of multiple organs were the 3 main risk factors associated with death for this patient group. Genotyping results with 6 microsatellite markers showed that type II isolates were predominant among patients who acquired toxoplasmic infection in Europe. Non-type II isolates included 13 different genotypes and were mainly collected from patients who acquired toxoplasmosis outside Europe. Type III was the second most common genotype recovered from patients, whereas type I was rare in our population. Three nonarchetypal genotypes were repeatedly recovered from different patients who acquired the infection in sub-Saharan Africa (genotypes Africa 1 and Africa 2) and in the French West Indies (genotype Caribbean 1). The distribution of genotypes (type II vs. non-type II) was not significantly different when patients were stratified by underlying cause of immunosuppression, site of infection, or outcome. We conclude that in immunocompromised patients, host factors are much more involved than parasite factors in patients' resistance or susceptibility to toxoplasmosis.

Published
2009
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