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1. Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004-2020 1 .

Author

Garcia-Hermoso D, Hamane S, Fekkar A, Jabet A, Denis B, Siguier M, Galeazzi G, Haddad E, Brun S, Vidal V, Nevez G, Le Berre R, Gits-Muselli M, Lanternier F, and Bretagne S

Subjects
Africa South of the Sahara, Africa, Western epidemiology, Animals, France epidemiology, Humans, Microbial Sensitivity Tests, Onygenales, Antifungal Agents pharmacology, Antifungal Agents therapeutic use
Abstract

Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification.

Published
2020
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3. Active Surveillance Program to Increase Awareness on Invasive Fungal Diseases: the French RESSIF Network (2012 to 2018)

Author

Bretagne, Stéphane, Sitbon, Karine, Desnos-Ollivier, Marie, Garcia-Hermoso, Dea, Letscher-Bru, Valérie, Cassaing, Sophie, Millon, Laurence, Morio, Florent, Gangneux, Jean-Pierre, Hasseine, Lilia, Favennec, Loïc, Cateau, Estelle, Bailly, Eric, Moniot, Maxime, Bonhomme, Julie, Desbois-Nogard, Nicole, Chouaki, Taieb, Paugam, André, Bouteille, Bernard, Pihet, Marc, Dalle, Frédéric, Eloy, Odile, Sasso, Milène, Demar, Magalie, Mariani-Kurkdjian, Patricia, Robert, Vincent, Lortholary, Olivier, Dromer, Françoise, French Mycoses Study Group, The, Damiani, Céline, Dupont, Hervé, Maizel, Julien, Totet, Anne, Bouchara, Jean-Philippe, Bellanger, Anne Pauline, Berceanu, Ana, Navellou, Jean Christophe, Scherer, Emeline, Abboud, Philippe, Aznar, Christine, Blanchet, Denis, Djossou, Félix, Cayot, Sophie, Garrouste, Cyril, Lesens, Olivier, Moluçon, Cécile, Nourrisson, Céline, Poirier, Philippe, Bailly, Éloïse, Basmaciyan, Louise, Belaid, Bouhemad, Blot, Mathieu, Caillot, Denis, Charles, Pierre-Emmanuel, Quenot, Jean Pierre, Amazan, Emmanuelle, Baubion, Emilie, Cabie, André, Chabartier, Cyrille, Deligny, Christophe, Emal, Violaine, Flechelle, Olivier, Hatchuel, Yves, Le Govic, Yohann, Merle, Harold, Miossec, Charline, Turmel, Jean-Marie, Valentino, Ruddy, Durieux, Marie-Fleur, Turlure, Pascal, Mercier, Victor, Gari-Toussaint, Martine, Risso, Karine, Simon, Loïc, Bretonnière, Cedric, Boutoille, David, Gastinne, Thomas, Lakhal, Karim, Launay, Elise, Lepoivre, Thierry, Peterlin, Pierre, Rialland, Fanny, Le Pape, Patrice, Canoui, Etienne, Dahane, Naima, Kerneis, Solène, Angebault, Cécile, Bougnoux, Marie-Elisabethh, Guennouni, Nadia, Lanternier, Fanny, Neven, Bennedicte, Oualha, Mehdi, Scemla, Anne, Sitterlé, Emilie, Suarez, Felipe, Toubiana, Julie, Bonacorci, Stéphane, Alanio, Alexandre, Bergeron, Anne, Denis, Blandine, Gits-Muselli, Maud, Hamane, Samia, Touratier, Sophie, Chaumeil, Christine, Merabet, Lilia, Claudéon, Joelle, Curlier, Elodie, Galantine, Valérie, Gallois, Jean Claude, Markowicz, Samuel, Nicolas, Muriel, Musson, Pascal, Schepers, Kinda, Minoza, Alida, Kauffmann-Lacroix, Catherine, Guégan, Hélène, Costa, Damien, Dehais, Marion, Gargala, Gilles, Bajolet, Odile, Banisadr, Firouze, Cousson, Joel, Himberlin, Chantal, Huguenin, Antoine, Toubas, Dominique, Flori, Pierre, Mahinc, Caroline, Raberin, Hélène, Denis, Julie, Herbrecht, Raoul, Mertes, Paul-Michel, Meziani, Fehrat, Sabou, Marcela, Schneider, Francis, Bertozzi, Anne-Isabelle, Chauvin, Pamela, Charpentier, Elena, Cointault, Olivier, Cottrel, Claire, Delavigne, Karen, Faguer, Stanislas, Fillaux, Judith, Guemas, Emilie, Iriart, Xavier, Lelièvre, Lucie, Ruiz, Jean, Bastides, Frédéric, Chesnay, Adélaïde, Desoubeaux, Guillaume, Therby, Audrey, Chachaty, Elisabeth, Gachot, Bertrand, Westerdijk Fungal Biodiversity Institute, Westerdijk Fungal Biodiversity Institute - Software and Databasing, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Dynamique des interactions hôte pathogène (DIHP), Université de Strasbourg (UNISTRA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Chrono-environnement (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), Nantes Université (Nantes Univ), 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 ), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU de la Martinique [Fort de France], CHU Amiens-Picardie, Hôpital Cochin [AP-HP], CHU Limoges, SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), 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), Infections Respiratoires Fongiques (IRF), Université d'Angers (UA)-Université de Brest (UBO), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre Hospitalier de Versailles André Mignot (CHV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Hôpital Robert Debré Paris, Hôpital Robert Debré, Westerdijk Fungal Biodiversity Institute [Utrecht] (WI), Royal Netherlands Academy of Arts and Sciences (KNAW), Service des Maladies infectieuses et tropicales [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), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Laboratoire de Parasitologie-Mycologie [CHU Angers], Hôpital Bretonneau, 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), This work was supported by recurrent financial support from Santé Publique France and Institut Pasteur. The funders had no role in study design, data collection, analysis, interpretation of data, or the decision to submit the work for publication., We thank Didier Che (Direction des Maladies Infectieuses, Santé Publique France) for his continuous support and interest in invasive fungal infections and Etienne Sevin (EpiConcept, Paris, France) for his contribution in the development of the RESSIF website using the VOOZANOO platform. We are thankful for the technical help of Catherine Blanc, Anne Boullié, Cécile Gautier, Virginie Geolier, and Damien Hoinard (Institut Pasteur) for the characterization of the isolates received at the NRCMA., The French Mycoses Study Group includes collaborators who contributed to these data by their involvement in the management of patients, expertise in diagnostic tools, and/or characterization of fungal isolates. They are listed in alphabetical order of a city in France and for each center, in alphabetical order of the last names: in Amiens, Céline Damiani, Hervé Dupont, Julien Maizel, and Anne Totet, in Angers, Jean-Philippe Bouchara, in Besançon, Anne Pauline Bellanger, Ana Berceanu, Jean Christophe Navellou, and Emeline Scherer, in Cayenne, Philippe Abboud, Christine Aznar, Denis Blanchet, and Félix Djossou, in Clermont-Ferrand, Sophie Cayot, Cyril Garrouste, Olivier Lesens, Cécile Moluçon, Céline Nourrisson, and Philippe Poirier, in Dijon, Éloïse Bailly, Louise Basmaciyan, Bouhemad Belaid, Mathieu Blot, Denis Caillot, Pierre-Emmanuel Charles, and Jean Pierre Quenot, in Fort de France, Emmanuelle Amazan, Emilie Baubion, André Cabie, Cyrille Chabartier, Christophe Deligny, Violaine Emal, Olivier Flechelle, Yves Hatchuel, Yohann Le Govic, Harold Merle, Charline Miossec, Jean-Marie Turmel, and Ruddy Valentino, in Limoges, Marie-Fleur Durieux and Pascal Turlure, in Nîmes, Victor Mercier, in Nice, Martine Gari-Toussaint, Karine Risso, and Loïc Simon, in Nantes, Cedric Bretonnière, David Boutoille, Thomas Gastinne, Karim Lakhal, Elise Launay, Thierry Lepoivre, Pierre Peterlin, Fanny Rialland, and Patrice Le Pape, in Paris, in Hôpital Cochin, Etienne Canoui, Naima Dahane, and Solène Kerneis, in Hôpital Necker-Enfants Malades, Cécile Angebault, Marie-Elisabethh Bougnoux, Nadia Guennouni, Fanny Lanternier, Bennedicte Neven, Mehdi Oualha, Anne Scemla, Emilie Sitterlé, Felipe Suarez, and Julie Toubiana, in Hôpital Robert-Debré, Stéphane Bonacorci, in Hôpital Saint-Louis, Alexandre Alanio, Anne Bergeron, Blandine Denis, Maud Gits-Muselli, Samia Hamane, and Sophie Touratier, in hôpital des XV-XX, Christine Chaumeil and Lilia Merabet, in Pointe-à-Pitre, Joelle Claudéon, Elodie Curlier, Valérie Galantine, Jean Claude Gallois, Samuel Markowicz, Muriel Nicolas, Pascal Musson, and Kinda Schepers, in Poitiers, Alida Minoza and Catherine Kauffmann-Lacroix, in Rennes, Hélène Guégan, in Rouen, Damien Costa, Marion Dehais, and Gilles Gargala, in Reims, Odile Bajolet, Firouze Banisadr, Joel Cousson, Chantal Himberlin, Antoine Huguenin, and Dominique Toubas, in Saint Etienne, Pierre Flori, Caroline Mahinc, and Hélène Raberin, in Strabourg, Julie Denis, Raoul Herbrecht, Paul-Michel Mertes, Fehrat Meziani, Marcela Sabou, and Francis Schneider, in Toulouse, Anne-Isabelle Bertozzi, Pamela Chauvin, Elena Charpentier, Olivier Cointault, Claire Cottrel, Karen Delavigne, Stanislas Faguer, Judith Fillaux, Emilie Guemas, Xavier Iriart, Lucie Lelièvre, and Jean Ruiz, in Tours, Frédéric Bastides, Adélaïde Chesnay, and Guillaume Desoubeaux, in Versailles, Audrey Therby, and in Villejuif, Elisabeth Chachaty and Bertrand Gachot., and CLEMENT, Nathalie

Subjects
Antifungal Agents, pneumocytosis, invasive fungal infections, Pneumonia, Pneumocystis, [SDV]Life Sciences [q-bio], candidemia, Microbiology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, mucormycosis, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Virology, Humans, aspergillosis, epidemiology, Watchful Waiting, Fungemia, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged
Abstract

International audience; The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.16 to 2.36/10,000 hospitalization days, P = 0.0562) in relation with an increase of fungemia incidence (1.03 to 1.19/10,000, P = 0.0023), while that of other IFDs remained stable. The proportion of ≥65-year-old patients increased from 38.4% to 45.3% (P < 0.0001). Yeast fungemia (n = 5,444) was due mainly to Candida albicans (55.6%) with stable proportions of species over time. Echinocandins became the main drug prescribed (46.7% to 61.8%), but global mortality rate remained unchanged (36.3% at 1 month). Pneumocystis jirovecii pneumonia (n = 2,106) was diagnosed mostly in HIV-negative patients (80.7%) with a significantly higher mortality than in HIV-positive patients (21.9% versus 5.4% at 1 month, P < 0.0001). Invasive aspergillosis (n = 1,661) and mucormycosis (n = 314) were diagnosed mostly in hematology (>60% of the cases) with a global mortality rate of 42.5% and 59.3%, respectively, at 3 months and significant changes in diagnosis procedure over time. More concurrent infections were also diagnosed over time (from 5.4% to 9.4% for mold IFDs, P = 0.0115). In conclusion, we observed an aging of patients with IFD with a significant increase in incidence only for yeast fungemia, a trend toward more concurrent infections, which raises diagnostic and therapeutic issues. Overall, global survival associated with IFDs has not improved despite updated guidelines and new diagnostic tools.IMPORTANCE The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs. Globally, although the incidence of Pneumocystis pneumonia, invasive aspergillosis, and mucormycosis remained stable over the study period (2012 to 2018), that of yeast fungemia increased slightly. We also show here that IFDs seem to affect older people more frequently. The most worrisome observation is the lack of improvement in the global survival rate associated with IFDs despite the increasing use of more sensitive diagnostic tools, the availability of new antifungal drugs very active in clinical trials, and a still low/marginal rate of acquired in vitro resistance in France. Therefore, other tracks of improvement should be investigated actively.

Published
2022

4. Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004-20201.

Author

Garcia-Hermoso, Dea, Hamane, Samia, Fekkar, Arnaud, Jabet, Arnaud, Denis, Blandine, Siguier, Martin, Galeazzi, Guy, Haddad, Elie, Brun, Sophie, Vidal, Valérie, Nevez, Gilles, Le Berre, Rozenn, Gits-Muselli, Maud, Lanternier, Fanny, and Bretagne, Stéphane

Subjects
SEQUENCE analysis, CLINICAL drug trials, INFECTION, ETIOLOGY of diseases, REPTILES, ANTIFUNGAL agents, RESEARCH, ANIMAL experimentation, RESEARCH methodology, FUNGI, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, MICROBIAL sensitivity tests, PHARMACODYNAMICS
Abstract

Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
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5. Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004-20201.

Author

Garcia-Hermoso, Dea, Hamane, Samia, Fekkar, Arnaud, Jabet, Arnaud, Denis, Blandine, Siguier, Martin, Galeazzi, Guy, Haddad, Elie, Brun, Sophie, Vidal, Valérie, Nevez, Gilles, Le Berre, Rozenn, Gits-Muselli, Maud, Lanternier, Fanny, and Bretagne, Stéphane

Subjects
*SEQUENCE analysis, *CLINICAL drug trials, *INFECTION, *ETIOLOGY of diseases, *REPTILES, *ANTIFUNGAL agents, *RESEARCH, *ANIMAL experimentation, *RESEARCH methodology, *FUNGI, *MEDICAL cooperation, *EVALUATION research, *COMPARATIVE studies, *MICROBIAL sensitivity tests, *PHARMACODYNAMICS
Abstract

Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

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