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1. Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease

Author

Benadji, Amine, Danis, Kostas, Brieu, Nathalie, Gaillat, Jacques, Mourvillier, Bruno, Bollaert, Pierre-Edouard, Gaillot, Olivier, Taha, Muhamed-Kheir, Bonacorsi, Stephane, Lecuit, Marc, Frachet, Bruno, Debroucker, Thomas, Levy Bruhl, Daniel, Preau, Marie, Anguel, Nadia, Argaud, Laurent, Arista, Sophie, Armand-Lefevre, Laurence, Balavoine, Stéphanie, Baraduc, Régine, Barnaud, Guilène, Béraud, Guillaume, Bernars, Georges, Bertei, Dominique, Bessede, Emilie, Billard Pomares, Typhaine, Biron, Charlotte, Bland, Stéphane, Boileau, Julien, Boubeau, Patrice, Bourdon, Sandra, Bousquet, Aurore, Boyer, Sophie, Bozorg-Grayeli, Alexis, Bretonniere, Cédric, Bricaire, François, Brocas, Elsa, Brun, Michel, Buret, Jennifer, Burucoa, Christophe, Cabalion, Jean, Cabon, Mathieu, Cambau, Emmanuelle, Camuset, Guillaume, Canevet, Christophe, Caron, François, Carricajo, Anne, Castan, Bernard, Caumes, Eric, Cazanave, Charles, Chabrol, Amélie, Challan-Belval, Thibaut, Chanteperdrix-Marillier, Vanessa, Chaplain, Chantal, Charlier-Woerther, Caroline, Chaussade, Hélène, Chirouze, Catherine, Clair, Bernard, Colot, Julien, Conil, Jean-Marie, Cordel, Hugues, Cormier, Philippe, Cousson, Joël, Cronier, Pierrick, Cua, Eric, Dao-Dubremetz, Anne, Dargere, Sylvie, Degand, Nicolas, Dekeyser, Sophie, Delaune, Deborah, Denes, Eric, Dequin, Pierre-Francois, Descamps, Diane, Descloux, Elodie, Desmaretz, Jean-Luc, Diehl, Jean-Luc, Dimet, Jérôme, Dinh, Aurélien, Duval, Xavier, Escaut, Lelia, Fabe, Claude, Faibis, Frédéric, Flateau, Clara, Fonsale, Nathalie, Fortineau, Nicolas, Gagneux-Brunon, Amandine, Garandeau, Caroline, Garcia, Magali, Garot, Denis, Gaudry, Stéphane, Goehringer, François, Gravet, Alain, Gregoire-Faucher, Valérie, Grosset, Marine, Gueit, Isabelle, Guelon, Dominique, Guimard, Thomas, Hadou, Tahar, Helene, Jean-Pierre, Henard, Sandrine, Henry, Benoit, Hochart, Anne-Cécile, Hoen, Bruno, Illes, Gabriela, Jaffuel, Sylvain, Jarrin, Irène, Jaureguy, Françoise, Joseph, Cédric, Juvin, Marie-Emmanuelle, Kayal, Samer, Kerneis, Solen, Lamaury, Isabelle, Laurens, Etienne, Laurichesse, Henri, Le Brun, Cécile, Le Moing, Vincent, Le Turnier, Paul, Lecuyer, Hervé, Ledru, Sylvie, Legrix, Céline, Lemaignen, Adrien, Lemble, Chantal, Lemee, Ludovic, Lesens, Olivier, Lhommet, Claire, Males, Silvija, Malpote, Edith, Martin-Blondel, Guillaume, Marx, Matthieu, Masson, Raphael, Matray, Olivier, Mbadi, Aurore, Mechai, Frédéric, Mellon, Guillaume, Merens, Audrey, Meyohas, Marie Caroline, Michon, Adrien, Mootien Yoganaden, Joy, Morquin, David, Mouly, Stéphane, Mrozek, Natacha, Nguyen, Sophie, Oziol, Eric, Page, Bernard, Patrat-Delon, Solène, Patry, Isabelle, Picot, Sandrine, Pierrejean, Denys, Piroth, Lionel, Plassart, Claire, Plessis, Patrice, Ploy, Marie-Cécile, Portel, Laurent, Poubeau, Patrice, Poupard, Marie, Poyart, Claire, Prazuck, Thierry, Quaesaet, Luc, Raffi, François, Ramanantsoa, Adriatsiferana, Rapp, Christophe, Raskine, Laurent, Raymond, Josette, Revest, Matthieu, Riche, Agnès, Robaday-Voisin, Stéphanie, Robin, Frédéric, Romaszko, Jean-Pierre, Rousseau, Florence, Roux, Anne-Laure, Royer, Cécile, Saada, Matthieu, Salmon, Dominique, Saroufim, Carlo, Schmit, Jean Luc, Sebire, Manuela, Segonds, Christine, Sivadon-Tardy, Valérie, Soismier, Nathalie, Son, Olivia, Sunder, Simon, Suy, Florence, Tande, Didier, Tankovic, Jacques, Valin, Nadia, van Grunderbeeck, Nicolas, Vandenesch, François, Varon, Emmanuelle, Verdon, Renaud, Vergnaud, Michel, Vidal, Magali, Vittecoq, Daniel, Vuotto, Fanny, Gorenne, Isabelle, Laouenan, Cédric, Marcault, Estelle, Mentre, France, Pasquet, Blandine, Roy, Carine, Tubiana, Sarah, Arsac, Philippe, Benoit, Martha, Bernard, Louis, Bissuel, François, Bret, Laurent, Brieu, Natalie, Burret, Jennifer, Carvalhoschneider, Claudia, Champagne, Hélène, Chapalain, Joséphine, Chardon, Hubert, Chavanet, Pascal, Ducruet, Judith, Epaulard, Olivier, Fabre, Marc, Fasquelle, Dominique, Forestier, Emmanuel, Galempoix, Jean-Marc, Gautier, Guillaume, de Curraize, Claire Goulard, Gracet, Alain, Gubavu, Camélia, Guinard, Jérôme, Habet, Tarik, Haudour, Aurélie, Henry, Caroline, Hombrouckalet, Cécile, Janssen, Céline, Kisteman, Jean-Paul, Lanotte, Philippe, Lartigue, Marie-Frédérique, Launois, Claire, Lebrun, Cécile, Legout, Laurence, Levast, Marion, Madoux, Yannick, Maulin, Laurence, Mestrallet, Stéphanie, Mohareb, Abdo, Mootien, Joy, Nguyen, Yohan, Noel, Franck, Ogielska, Maja, Ogier Desserrey, Agathe, Paleau, Anne, Pavel, Simona, Pechinot, André, Pelloux, Isabelle, Petillon, Camille, Petitprez, Hélène, Podac, Bianca, Poirot, Jerome, Ponceau, Bénédicte, Prieur, Nathalie, Recule, Christine, Saraceni, Orlando, Sartre, Jacques, Sifaoui, Farid, Simonin, Catherine, Strady, Christophe, Tellini, Charlotte, Texier, Anthony, Thouvenin, Maxime, Tixier, Anne, Tremeaux, Pauline, Verger, Pascale, Vernet-Garnier, Véronique, Verquin, Jean-Pierre, Vitrat, Virginie, Vray, Isabelle, Zamfir, Oana, Zucchini, Laure, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-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), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-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 ), CHU Pontchaillou [Rennes], CHI Créteil, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), The COMBAT study was supported by the Assistance Publique Hopitaux de Paris, French Ministry of Health, Inserm, SPILF, and the Pfizer Pharmaceutical company, which also funded ORP. The study was endorsed by the following professional organizations: Association Pour l’enseignement de la Thérapeutique, Société de Pathologie Infectieuse de Langue Française, Société Française de Microbiologie, Société Nationale Française de Médecine Interne, Société de Réanimation de Langue Française, Société Française de Gérontologie, Société Française d’Anesthésie-Réanimation. The SIIP study was supported by (i) the Société de Pathologie Infectieuse de Langue Fran.aise (SPILF, the French Infectious Diseases Society), (ii) Santé Publique France (SpFrance, the French National Public Health Agency), (iii) the European Centre for Disease Prevention and Control (ECDC), and (iv) Pfizer. The Regional Observatories of Pneumococci (Observatoires Régionaux du Pneumocoque) were supported by Pfizer, BioMerieux, and Sanofi., and Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE)

Subjects
Adult, Microbiology (medical), Serotype, medicine.medical_specialty, Multivariate analysis, Adolescent, [SDV]Life Sciences [q-bio], 30-day mortality, Serogroup, medicine.disease_cause, Logistic regression, Pneumococcal Infections, Cohort Studies, Pneumococcal Vaccines, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Streptococcus pneumoniae, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Aged, 0303 health sciences, Meningitis, Pneumococcal, 030306 microbiology, business.industry, Mortality rate, Infant, Invasive pneumococcal disease, Pneumococcal vaccine, General Medicine, bacterial infections and mycoses, medicine.disease, 3. Good health, Infectious Diseases, business, Meningitis, Cohort study
Abstract

International audience; Purpose: Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015.Methods: This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression.Results: Among the 771 enrolled patients (median age 66 years, IQR [52.0-79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines.Conclusion: We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients.Clinical trial: ClinicalTrial. Gov identification number: NCT01730690.

Published
2021

2. Evolution of Bordetella pertussis over a 23-year period in France, 1996 to 2018

Author

Bouchez, Valérie, Guillot, Sophie, Landier, Annie, Armatys, Nathalie, Matczak, Soraya, Toubiana, Julie, Brisse, Sylvain, Brieu, Nathalie, Hamdad, Farida, Kempf, Marie, Pailhoriès, Hélène, Jensen, Cécile, Lehours, Philippe, Guiraud, Jennifer, Le Bars, Hervé, Isnard, Christophe, Wilhelm, Nathalie, Le Coustumier, Alain, Delmas, Julien, De Briel, Dominique, Souply, Laurent, Aberrane, Saïd, Coudé, Marie, Garnier, Fabien, Descours, Ghislaine, Jean-Pierre, Hélène, Alauzet, Corentine, Gibaud, Sophie-Anne, Bonacorsi, Stéphane, Brasme, Lucien, Lemée, Ludovic, Koebel, Christelle, Lanotte, Philippe, Bland, Stéphane, Petitprez, Hélène, Raffenot, Didier, Levast, Marion, Doucet-Populaire, Florence, Bourgeois-Nicolaos, Nadège, Burucoa, Christophe, Grattard, Florence, Marque-Juillet, Stéphanie, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Département de Pédiatrie et maladies infectieuses [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), Université de Paris (UP), This work was performed with the financial support of the Institut Pasteur and of Santé Publique France., French pertussis microbiology study group: Nathalie Brieu, Farida Hamdad, Marie Kempf, Hélène Pailhoriès, Cécile Jensen, Philippe Lehours, Jennifer Guiraud, Hervé Le Bars, Christophe Isnard, Nathalie Wilhelm, Alain Le Coustumier, Julien Delmas, Dominique De Briel, Laurent Souply, Saïd Aberrane, Marie Coudé, Fabien Garnier, Ghislaine Descours, Hélène Jean-Pierre, Corentine Alauzet, Sophie-Anne Gibaud, Stéphane Bonacorsi, Lucien Brasme, Ludovic Lemée, Christelle Koebel, Philippe Lanotte, Stéphane Bland, Hélène Petitprez, Didier Raffenot, Marion Levast, Florence Doucet-Populaire, Nadège Bourgeois-Nicolaos, Christophe Burucoa, Florence Grattard, Stéphanie Marque-Juillet, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Collège Doctoral, Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Institut Pasteur [Paris]

Subjects
Serotype, Bordetella pertussis, population evolution, Whooping Cough, Epidemiology, [SDV]Life Sciences [q-bio], Fimbria, MESH: Pertussis Toxin, MESH: Virulence Factors, Bordetella, Pertussis toxin, Microbiology, pertactin, MESH: Bordetella pertussis, 03 medical and health sciences, 0302 clinical medicine, Antigen, Virology, MESH: Child, medicine, Humans, Virulence Factors, Bordetella, 030212 general & internal medicine, Child, Whooping cough, 030304 developmental biology, Pertussis Vaccine, vaccine antigen deficiency, 0303 health sciences, Surveillance, MESH: Humans, biology, MESH: Bacterial Outer Membrane Proteins, Public Health, Environmental and Occupational Health, MESH: Whooping Cough, biology.organism_classification, medicine.disease, fimbriae serotype, 3. Good health, respiratory tract diseases, Vaccination, MESH: France, Pertussis Toxin, MESH: Pertussis Vaccine, France, Pertactin, Bacterial Outer Membrane Proteins
Abstract

Background Bordetella pertussis is the main agent of whooping cough. Vaccination with acellular pertussis vaccines has been largely implemented in high-income countries. These vaccines contain 1 to 5 antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and/or fimbrial proteins (FIM2 and FIM3). Monitoring the emergence of B. pertussis isolates that might partially escape vaccine-induced immunity is an essential component of public health strategies to control whooping cough. Aim We aimed to investigate temporal trends of fimbriae serotypes and vaccine antigen-expression in B. pertussis over a 23-year period in France (1996–2018). Methods Isolates (n = 2,280) were collected through hospital surveillance, capturing one third of hospitalised paediatric pertussis cases. We assayed PT, FHA and PRN production by Western blot (n = 1,428) and fimbriae production by serotyping (n = 1,058). Molecular events underlying antigen deficiency were investigated by genomic sequencing. Results The proportion of PRN-deficient B. pertussis isolates has increased steadily from 0% (0/38) in 2003 to 48.4% (31/64) in 2018 (chi-squared test for trend, p 481 insertion within the prn gene or a 22 kb genomic inversion involving the prn promoter sequence, indicative of convergent evolution. FIM2-expressing isolates have emerged since 2011 at the expense of FIM3. Conclusions B. pertussis is evolving through the rapid increase of PRN-deficient isolates and a recent shift from FIM3 to FIM2 expression. Excluding PRN, the loss of vaccine antigen expression by circulating B. pertussis isolates is epidemiologically insignificant.

Published
2021

3. Factors Associated With Severe Nonmeningitis Invasive Pneumococcal Disease in Adults in France

Author

Danis, Kostas, Varon, Emmanuelle, Lepoutre, Agnès, Janssen, Cécile, FORESTIER, Emmanuel, Epaulard, Olivier, N’Guyen, Yohan, Labrunie, Anaïs, Lanotte, Philippe, Lartigue, Marie-Frédérique, Gravet, Alain, Pelloux, Isabelle, CHAVANET, Pascal, Levy-Bruhl, Daniel, Ploy, Marie-Cecile, Gaillat, Jacques, Peloux, Isabelle, Haudour, Aurélie, Recule, Christine, Blachon, A, Petitprez, Hélène, Janssen, Céline, Vitrat, Virginie, Tremeaux, Pauline, Ducruet, J, Legout, Laurence, Sifaoui, Farid, Levast, Marion, Habet, Tarik, Telini, Charlotte, Fabre, Marc, Tixier, Anne, Vray, Isabelle, Guillaume, Mathilde, Henry, X, Verger, Pascale, Lebrun, Cécile, Carvalhoschneider, C, Bernard, Louis, Courtellemont, Laura, Guinard, Jerome, Gubavu, Camelia, Petillon, Camille, Brieu, Nathalie, Maulin, Laurence, Vernet-Garnier, Véronique, Launois, Claire, Nguyen, Yohan, Madoux, Yannick, Strady, Christophe, Noel, Franck, Pavel, Simona, Thouvenin, Maxime, Galempoix, Jean-Marc, Prieur, Natahlie, Mestrallet, Stéphanie, Zucchini, Laure, Tetu, Jennifer, Pechinnot, André, Texier, Anthony, Kisterman, Jean-Paul, Chapalain, Josephine, Simonin, Catherine, Paleau, A, Benoit, Martha, Podac, Bianca, Desserrey, Agathe Ogier, Poirot, Jerome, Gautier, Guillaume, Mootien, Joy, Saraceni, Orlando, Mohareb, Abdo, Centre Hospitalier Intercommunal de Créteil (CHIC), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Observatoires Régionaux du Pneumocoque, Partenaires INRAE, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-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), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), 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)-CHU Limoges, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Métropole Savoie [Chambéry], Centre Hospitalier Universitaire [Grenoble] (CHU), Plate forme de bioinformatique et biostatistique (CEBIMER), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), The study was supported by (i) the Societe de Pathologie Infectieuse de Langue Francaise (SPILF, the French Infectious Diseases Society), (ii) Sante Publique France (SpFrance, the French National Public Health Agency), (iii) the European Centre for Disease Prevention and Control (ECDC), and (iv) Pfizer. The Regional Observatories of Pneumococci (Observatoires Regionaux du Pneumocoque) were supported by Pfizer, BioMerieux, and Sanofi., and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, invasive pneumococcal disease, Pneumococcal conjugate vaccine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Acute care, Major Article, medicine, 030212 general & internal medicine, business.industry, medicine.disease, mortality, Pneumococcal polysaccharide vaccine, Intensive care unit, 3. Good health, pneumococcal conjugate vaccine, Vaccination, Streptococcus pneumoniae, Infectious Diseases, Oncology, Pneumococcal vaccine, Relative risk, surveillance, outcome, business, Meningitis, medicine.drug
Abstract

Background In France, pneumococcal vaccination in adults is recommended for risk groups (chronic conditions/immunosuppression). We conducted a study on invasive pneumococcal disease (IPD) in adults to identify factors associated with disease severity and death. Methods We included IPD cases, excluding meningitis, from 25 acute care hospitals in 6 regions. We defined severe cases as those with shock or severe sepsis or intensive care unit admission/mechanical ventilation. We included deaths occurring within 30 days of hospitalization. Infectious disease specialists collected clinical/microbiological data on cases. Results During 2014–2017, 908 nonmeningitis IPD cases were diagnosed; 48% were severe, 84% had comorbidities, 21% died. Ninety percent of cases with comorbidities who previously sought health care were not vaccinated against pneumococcus. Compared with previously healthy cases, the risk of severe IPD increased from 20% (adjusted risk ratio [aRR], 1.2; 95% confidence interval [CI], 1.0–1.4) in cases with 1–2 chronic diseases to 30% (aRR, 1.3; 95% CI, 1.0–7.0) in those with >2 chronic diseases. Among risk groups, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and 23-valent pneumococcal polysaccharide vaccine (PPSV23) nonPCV13 serotypes were more likely to induce severe IPD compared with nonvaccine serotypes (aRR, 1.5; 95% CI, 1.3–1.9; aRR, 1.3; 95% CI, 1.0–1.5, respectively). Conclusions We observed a cumulative effect of concurrent comorbidities on severe IPD. Vaccine serotypes were more likely to induce severe IPD among risk groups. The missed opportunities for vaccination underscore the need to enhance vaccination in risk groups.

Published
2019

4. Multicenter Outbreak of Infections by Saprochaete clavata , an Unrecognized Opportunistic Fungal Pathogen

Author

Vaux, Sophie, Criscuolo, Alexis, Desnos-Ollivier, Marie, Diancourt, Laure, Tarnaud, Chloé, Vandenbogaert, Matthias, Brisse, Sylvain, Coignard, Bruno, Dromer, Françoise, Garcia-Hermoso, Dea, Blanc, Catherine, Hoinard, Damien, Lortholary, Olivier, Bretagne, Stéphane, Thiolet, Jean-Michel, de Valk, Henriette, Courbil, Rémi, Chabanel, Anne, Simonet, Marion, Maire, Francoise, Jbilou, Saadia, Tiberghien, Pierre, Blanchard, Hervé, Venier, Anne-Gaëlle, Bernet, Claude, Simon, Loïc, Sénéchal, Hélène, Pouchol, Elodie, Angot, Christiane, Ribaud, Patricia, Socié, G., Flèche, M., Brieu, Nathalie, Lagier, Evelyne, Chartier, Vanessa, Allegre, Thierry, Maulin, Laurence, Lanic, Hélène, Tilly, Hervé, Bouchara, Jean-Philippe, Pihet, Marc, Schmidt, Aline, Kouatchet, Achille, Vandamme, Yves-Marie, Ifrah, Norbert, Mercat, Alain, Accoceberry, Isabelle, Albert, Olivier, Leguay, Thibaut, Rogues, Anne-Marie, Bonhomme, Julie, Reman, Oumédaly, Lesteven, Claire, Poirier, Philippe, Chabrot, Cécile Molucon, Calvet, Laure, Baud, Olivier, Cambon, Monique, Farkas, Jean Chistophe, Lafon, Bruno, Dalle, Frédéric, Caillot, Denis, Lazzarotti, Aline, Aho, Serge, Combret, Sandrine, Facon, Thierry, Sendid, Boualem, Loridant, Séverine, Louis, Terriou, Cazin, Bruno, Grandbastien, Bruno, Bourgeois, Nathalie, Lotthé, Anne, Cartron, Guillaume, Ravel, Christophe, Colson, Pascal, Gaudard, Philippe, Bonmati, Caroline, Simon, Loic, Rabaud, Christian, Machouart, Marie, Poisson, Didier, Carp, Diana, Meunier, Jérôme, Gaschet, Anne, Miquel, Chantal, Sanhes, Laurence, Ferreyra, Milagros, Leibinger, Franck, Geudet, Philippe, Toubas, Dominique, Himberlin, Chantal, Bureau-Chalot, Florence, Delmer, Alain, Favennec, Loïc, Gargala, Gilles, Michot, Jean-Baptiste, Girault, Christophe, David, Marion, Leprêtre, Stéphane, Jardin, Fabrice, Honderlick, Pierre, Caille, Vincent, Cerf, Charles, Cassaing, Sophie, Recher, Christian, Picard, Muriel, Protin, Caroline, Huguet, Françoise, Huynh, Anne, Ruiz, Jean, Riu-Poulenc, Béatrice, Letocart, Philippe, Marchou, Bruno, Verdeil, Xavier, Cavalié, Laurent, Chauvin, Pamela, Iriart, Xavier, Valentin, Alexis, Bouvet, Emmanuelle, Delmas-Marsalet, Béatrice, Jeblaoui, Asma, Kassis-Chikhani, Najiby, Mühlethaler, Konrad, Zimmerli, Stefan, Zalar, Polona, Sánchez-Reus, Ferran, Gurgui, Merce, Institut de Veille Sanitaire (INVS), Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8), Institut Pasteur [Paris], Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunologie des Infections fongiques - immunology of fungal infections, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Genotype, Molecular Sequence Data, Geotrichum-capitatum, Fungal contamination, Sequence Homology, High-throughput, Diseases, Fungus, Sequences, Microbiology, Saprochaete clavata, Disease Outbreaks, 03 medical and health sciences, Yeasts, Virology, Cluster Analysis, DNA, Fungal, Mycological Typing Techniques, Clade, Pathogen, Genotyping, Phylogeny, Alignment, Blastoschizomyces-capitatus, 030304 developmental biology, Cross Infection, Molecular Epidemiology, 0303 health sciences, Leukemia, biology, 030306 microbiology, Outbreak, Sequence Analysis, DNA, Agents, Fungal pathogen, biology.organism_classification, QR1-502, 3. Good health, Molecular Typing, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Mycoses, Saccharomycetales, [SDV.IMM]Life Sciences [q-bio]/Immunology, Health Facilities, France, Research Article
Abstract

Rapidly fatal cases of invasive fungal infections due to a fungus later identified as Saprochaete clavata were reported in France in May 2012. The objectives of this study were to determine the clonal relatedness of the isolates and to investigate possible sources of contamination. A nationwide alert was launched to collect cases. Molecular identification methods, whole-genome sequencing (WGS), and clone-specific genotyping were used to analyze recent and historical isolates, and a case-case study was performed. Isolates from thirty cases (26 fungemias, 22 associated deaths at day 30) were collected between September 2011 and October 2012. Eighteen cases occurred within 8 weeks (outbreak) in 10 health care facilities, suggesting a common source of contamination, with potential secondary cases. Phylogenetic analysis identified one clade (clade A), which accounted for 16/18 outbreak cases. Results of microbiological investigations of environmental, drug, or food sources were negative. Analysis of exposures pointed to a medical device used for storage and infusion of blood products, but no fungal contamination was detected in the unused devices. Molecular identification of isolates from previous studies demonstrated that S. clavata can be found in dairy products and has already been involved in monocentric outbreaks in hematology wards. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen. This report also underlines further the potential of WGS for investigation of outbreaks due to uncommon fungal pathogens., IMPORTANCE Several cases of rapidly fatal infections due to the fungus Saprochaete clavata were reported in France within a short period of time in three health care facilities, suggesting a common source of contamination. A nationwide alert collected 30 cases over 1 year, including an outbreak of 18 cases over 8 weeks. Whole-genome sequencing (WGS) was used to analyze recent and historical isolates and to design a clade-specific genotyping method that uncovered a clone associated with the outbreak, thus allowing a case-case study to analyze the risk factors associated with infection by the clone. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen.

Published
2014

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