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1. Evolutionary origin and population diversity of a cryptic hybrid pathogen

Author

Steenwyk, Jacob L., Knowles, Sonja, Bastos, Rafael W., Balamurugan, Charu, Rinker, David, Mead, Matthew E., Roberts, Christopher D., Raja, Huzefa A., Li, Yuanning, Colabardini, Ana Cristina, de Castro, Patrícia Alves, dos Reis, Thaila Fernanda, Gumilang, Adiyantara, Almagro-Molto, María, Alanio, Alexandre, Garcia-Hermoso, Dea, Delbaje, Endrews, Pontes, Laís, Pinzan, Camila Figueiredo, Schreiber, Angélica Zaninelli, Canóvas, David, Sanchez Luperini, Rafael, Lagrou, Katrien, Torrado, Egídio, Rodrigues, Fernando, Oberlies, Nicholas H., Zhou, Xiaofan, Goldman, Gustavo H., and Rokas, Antonis

Published
2024
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2. Evolutionary origin and population diversity of a cryptic hybrid pathogen

Author

Jacob L. Steenwyk, Sonja Knowles, Rafael W. Bastos, Charu Balamurugan, David Rinker, Matthew E. Mead, Christopher D. Roberts, Huzefa A. Raja, Yuanning Li, Ana Cristina Colabardini, Patrícia Alves de Castro, Thaila Fernanda dos Reis, Adiyantara Gumilang, María Almagro-Molto, Alexandre Alanio, Dea Garcia-Hermoso, Endrews Delbaje, Laís Pontes, Camila Figueiredo Pinzan, Angélica Zaninelli Schreiber, David Canóvas, Rafael Sanchez Luperini, Katrien Lagrou, Egídio Torrado, Fernando Rodrigues, Nicholas H. Oberlies, Xiaofan Zhou, Gustavo H. Goldman, and Antonis Rokas

Subjects
Science
Abstract

Abstract Cryptic fungal pathogens pose disease management challenges due to their morphological resemblance to known pathogens. Here, we investigated the genomes and phenotypes of 53 globally distributed isolates of Aspergillus section Nidulantes fungi and found 30 clinical isolates—including four isolated from COVID-19 patients—were A. latus, a cryptic pathogen that originated via allodiploid hybridization. Notably, all A. latus isolates were misidentified. A. latus hybrids likely originated via a single hybridization event during the Miocene and harbor substantial genetic diversity. Transcriptome profiling of a clinical isolate revealed that both parental subgenomes are actively expressed and respond to environmental stimuli. Characterizing infection-relevant traits—such as drug resistance and growth under oxidative stress—revealed distinct phenotypic profiles among A. latus hybrids compared to parental and closely related species. Moreover, we identified four features that could aid A. latus taxonomic identification. Together, these findings deepen our understanding of the origin of cryptic pathogens.

Published
2024
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3. Implementation and validation of a new qPCR assay to detect imported human Plasmodium species

Author

Camille Cordier, Samia Hamane, Théo Ghelfenstein-Ferreira, Sarah Dellière, Élodie Da Silva, Blandine Denis, Sandrine Houzé, Valentin Joste, and Alexandre Alanio

Subjects
malaria, qPCR, duplex, Plasmodium, diagnosis, Microbiology, QR1-502
Abstract

ABSTRACT Diagnosis of imported malaria is based on microscopic examination of blood smears (BS), detection of circulating plasmodial antigen by immunochromatography (ICT), or detection of Plasmodium spp. DNA by loop mediated isothermal amplification. We have developed duplex (Plasmodium spp. and Plasmodium falciparum) real-time PCR (qPCR) and species-specific qPCR assays for the identification and quantification of human Plasmodium species. Whole nucleic acids from 523 samples prospectively collected from 410 patients suspected of malaria between June 2016 and March 2021 were tested by qPCRs and compared to standard diagnostic procedures. All qPCRs were designed on 18S ribosomal ribonucleic acid. The limit of detection of duplex qPCR was 8 copies/reaction, and analytical specificity of species-specific qPCRs was 100%. Seventy-nine patients diagnosed for single species malaria involving P. falciparum, P. vivax, P. ovale, and P. malariae were positive with duplex and species-specific qPCRs. P. knowlesi qPCR detected DNA from a P. knowlesi culture. Of eight cases of mixed Plasmodium species infection, five were identified with our qPCR assays with better sensitivity as compared to BS and ICT. Eight out of 323 patients with negative BS were hospitalized for symptoms suggestive malaria after malaria-endemic area travel or known with history of malaria had a low positive duplex qPCR. Between day of diagnosis and post-treatment follow-up at D2-D4 of malaria, a 3.1-log P. falciparum load decrease was observed by qPCR. These new Plasmodium qPCRs allowing detection of human plasmodial species have excellent species specificity and allow rapid detection of P. falciparum cases, malaria with low parasitaemia, and mixed Plasmodium species infection.IMPORTANCEMalaria is a disease transmitted by a Plasmodium parasite genus. Most cases are caused by Plasmodium falciparum. Despite a significant drop of incidence and mortality since 2000, 249million cases and 608,000 deaths have been estimated in 2022, mainly in Africa. Due to the increasing number of travels to endemic areas, incidence of imported malaria is rising in Europe. Various techniques are used in European laboratories, such as microscopic examination of thin and thick smears and rapid diagnostic tests. However, these techniques require skilled operators to differentiate plasmodial species and have limited sensitivity. Actually, molecular diagnosis is carried out using point-of-care test for rapid results with excellent sensitivity but is unabled to determine involved species and assess parasitaemia. In this study, we developed a combined molecular tool based on both detection of all human plasmodial species (Plasmodium spp.) and P. falciparum. We have also developed specific qPCRs for each human plasmodial species.

Published
2025
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4. Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial

Author

Bagley, Stephen J., Binder, Zev A., Lamrani, Lamia, Marinari, Eliana, Desai, Arati S., Nasrallah, MacLean P., Maloney, Eileen, Brem, Steven, Lustig, Robert A., Kurtz, Goldie, Alonso-Basanta, Michelle, Bonté, Pierre-Emmanuel, Goudot, Christel, Richer, Wilfrid, Piaggio, Eliane, Kothari, Shawn, Guyonnet, Lea, Guerin, Coralie L., Waterfall, Joshua J., Mohan, Suyash, Hwang, Wei-Ting, Tang, Oliver Y., Logun, Meghan, Bhattacharyya, Meghna, Markowitz, Kelly, Delman, Devora, Marshall, Amy, Wherry, E. John, Amigorena, Sebastian, Beatty, Gregory L., Brogdon, Jennifer L., Hexner, Elizabeth, Migliorini, Denis, Alanio, Cecile, and O’Rourke, Donald M.

Published
2024
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5. Recursive Least Squares Identification with Extreme Learning Machine (RLS-ELM)

Author

Lima, Alanio F., dos Reis, Laurinda L. N., Souza, Darielson A., Batista, Josias G., Júnior, Antonio B. S., Silva, Francisco Heleno V., Cortêz, Vinícius R., Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Rocha, Alvaro, editor, Adeli, Hojjat, editor, Dzemyda, Gintautas, editor, Moreira, Fernando, editor, and Colla, Valentina, editor

Published
2024
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6. Epidemiology and prognostic factors of mucormycosis in France (2012–2022): a cross-sectional study nested in a prospective surveillance programmeResearch in context

Author

Laura Gouzien, Didier Che, Sophie Cassaing, Olivier Lortholary, Valérie Letscher-Bru, Olivier Paccoud, Thomas Obadia, Florent Morio, Maxime Moniot, Estelle Cateau, Marie Elisabeth Bougnoux, Taieb Chouaki, Lilia Hasseine, Guillaume Desoubeaux, Cecile Gautier, Caroline Mahinc-Martin, Antoine Huguenin, Julie Bonhomme, Karine Sitbon, Julien Durand, Alexandre Alanio, Laurence Millon, Dea Garcia-Hermoso, and Fanny Lanternier

Subjects
Epidemiology, Mucormycosis, Zygomycosis, Mucorales, Fungal infection, Mucormycosis serum PCR, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Mucormycosis is a deadly invasive fungal infection recently included in the WHO priority pathogen list. Here we sought to describe epidemiological trends of mucormycosis in France, and to evaluate factors associated with mortality. Methods: From 2012 to 2022, we implemented a nationwide prospective surveillance programme for mucormycosis in France, focusing on epidemiology, species, seasonal variations. Factors associated with 3-month mortality were studied by univariable and multivariable logistic regression. Findings: Among 550 cases of mucormycosis, the main underlying conditions were haematological malignancy (HM, 65.1%, 358/550), trauma (8%, 44/550), diabetes (7.5%, 41/550) and solid-organ transplants (6.5%, 36/550). Site of infection was pulmonary in 52.4% (288/550), rhinocerebral in 14.5% (80/550), and cutaneo-articular in 17.1% (94/550). Main species identified were Rhizopus arrhizus (21%, 67/316), Rhizopus microsporus (13.6%, 43/316), Lichtheimia corymbifera and Mucor circinelloides (13.3%, 42/316 each), Rhizomucor pusillus (12%, 38/316), and Lichtheimia ramosa (10.8%, 34/316). We found associations between underlying condition, site of infection, and infecting species, including a previously undescribed triad of trauma, cutaneo-articular localisations, and L. ramosa/M. circinelloides. Diagnostic contribution of Polymerase Chain Reaction (PCR) increased from 16% (4/25) in 2012 to 91% (61/67) in 2022, with more than 50% of diagnoses relying solely on PCR in 2022. We also found seasonal variations with relatively more cases in autumn. Ninety-day mortality was 55.8% (276/495). Independent prognostic factors were age, diagnosis in Intensive Care Unit (ICU), and HM while diagnosis after 2015 (i.e. large implementation of PCR) and surgery were associated with reduced mortality. Interpretation: This study reveals major mucormycosis epidemiological changes in France, with a large predominance of HM patients, and a parallel between PCR multicentre implementation and improved prognosis. We also evidence new associations between species, localisations and risk factors, as well as seasonal variations. Funding: Recurrent financial support from Santé Publique France and Institut Pasteur.

Published
2024
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8. Laboratory practices for the diagnosis and management of mucormycosis in France, 2024

Author

Millon, Laurence, Botterel, Françoise, Bonhomme, Julie, Valot, Stéphane, Poirier, Philippe, Durieux, Marie-Fleur, Bigot, Jeanne, Desoubeaux, Guillaume, Chesnais, Adélaïde, Morio, Florent, Pihet, Marc, Brunet, Kévin, Bellanger, Anne-Pauline, Imbert, Sébastien, Nevez, Gilles, Gal, Solène Le, Bourgeois, Nathalie, Debourgogne, Anne, Cornu, Marjorie, Persat, Florence, Hasseine, Lilia, Bougnoux, Marie-Elisabeth, Brun, Sophie, Cornet, Muriel, Favennec, Loïc, Gargala, Gilles, Bonnal, Christine, Gangneux, Jean-Pierre, Alanio, Alexandre, Iriart, Xavier, Mahinc, Caroline, Chouaki, Taieb, Paugam, André, Letscher-Bru, Valérie, and Dannaoui, Eric

Published
2024
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9. WHO global research priorities for antimicrobial resistance in human health

Author

Aanensen, David, Alanio, Alexandre, Alastruey-Izquierdo, Ana, Alemayehu, Tinsae, Al-Hasan, Majdi, Allegaert, Karel, Al-Maani, Amal Saif, Al-Salman, Jameela, Alshukairi, Abeer Nizar, Amir, Afreenish, Applegate, Tanya, Araj, George F, Villalobos, Marlen Arce, Årdal, Christine, Ashiru-Oredope, Diane, Ashley, Elizabeth A, Babin, François-Xavier, Bachmann, Laura H, Bachmann, Till, Baker, Kate Susan, Balasegaram, Manica, Bamford, Colleen, Baquero, Fernando, Barcelona, Laura Isabel, Bassat, Quique, Bassetti, Matteo, Basu, Sulagna, Beardsley, Justin, Vásquez, Grey Benoit, Berkley, James A, Bhatnagar, Anuj K, Bielicki, Julia, Bines, Julie, Bongomin, Felix, Bonomo, Robert A, Bradley, John S, Bradshaw, Catriona, Brett, Ana, Brink, Adrian, Brown, Colin, Brown, Jeremy, Buising, Kirsty, Carson, Carolee, Carvalho, Anna Cristina, Castagnola, Elio, Cavaleri, Marco, Cecchini, Michele, Chabala, Chishala, Chaisson, Richard E, Chakrabarti, Arunaloke, Chandler, Clare, Chandy, Sujith John, Charani, Esmita, Chen, Lisa, Chiara, Francesca, Chowdhary, Anuradha, Chua, Arlene, Chuki, Pem, Chun, Doo Ryeon, Churchyard, Gavin, Cirillo, Daniela, Clack, Lauren, Coffin, Susan E, Cohn, Jennifer, Cole, Michelle, Conly, John, Cooper, Ben, Corso, Alejandra, Cosgrove, Sara E, Cox, Helen, Daley, Charles L, Darboe, Saffiatou, Darton, Tom, Davies, Gerry, de Egea, Viviana, Dedeić-Ljubović, Amela, Deeves, Miranda, Denkinger, Claudia, Dillon, Jo-Anne R, Dramowski, Angela, Eley, Brian, Roberta Esposito, Susanna Maria, Essack, Sabiha Y, Farida, Helmia, Farooqi, Joveria, Feasey, Nicholas, Ferreyra, Cecilia, Fifer, Helen, Finlayson, Heather, Frick, Mike, Gales, Ana Cristina, Galli, Luisa, Gandra, Sumanth, Gerber, Jeffrey S, Giske, Christian, Gordon, Bruce, Govender, Nelesh, Guessennd, Nathalie, Guindo, Ibrehima, Gurbanova, Elmira, Gwee, Amanda, Hagen, Ferry, Harbarth, Stephan, Haze, John, Heim, Jutta, Hendriksen, Rene, Heyderman, Robert Simon, Holt, Kathryn Elizabeth, Hönigl, Martin, Hook, Edward W, Hope, William, Hopkins, Heidi, Hughes, Gwenda, Ismail, Ghada, Issack, Mohammad Iqbal, Jacobs, Jan, Jasovský, Dušan, Jehan, Fyeza, Pearson, Antonieta Jimenez, Jones, Makoto, Joshi, Mohan P, Kapil, Arti, Kariuki, Samuel, Karkey, Abhilasha, Kearns, Gregory L, Keddy, Karen Helena, Khanna, Nina, Kitamura, Akiko, Kolho, Kaija-Leena, Kontoyiannis, Dimitrios P, Kotwani, Anita, Kozlov, Roman S, Kranzer, Katharina, Kularatne, Ranmini, Lahra, Monica M, Langford, Bradley J, Laniado-Laborin, Rafael, Larsson, Joakim, Lass-Flörl, Cornelia, Le Doare, Kirsty, Lee, Hyukmin, Lessa, Fernanda, Levin, Anna S, Limmathurotsakul, Direk, Lincopan, Nilton, Lo Vecchio, Andrea, Lodha, Rakesh, Loeb, Mark, Longtin, Yves, Lye, David Chien, Mahmud, Asif Mujtaba, Manaia, Célia, Manderson, Lenore, Mareković, Ivana, Marimuthu, Kalisvar, Martin, Irene, Mashe, Tapfumanei, Mei, Zeng, Meis, Jacques F, Lyra Tavares De Melo, Flávio Augusto, Mendelson, Marc, Miranda, Angelica Espinosa, Moore, David, Morel, Chantal, Moremi, Nyambura, Moro, Maria Luisa, Moussy, Francis, Mshana, Stephen, Mueller, Arno, Ndow, Francis J, Nicol, Mark, Nunn, Andrew, Obaro, Stephen, Obiero, Christina W, Okeke, Iruka N, Okomo, Uduak, Okwor, Tochi J, Oladele, Rita, Omulo, Sylvia, Ondoa, Pascale, Ortellado de Canese, Juana Medarda, Ostrosky-Zeichner, Luis, Padoveze, Maria Clara, Pai, Madhukar, Park, Benjamin, Parkhill, Julian, Parry, Christopher M, Peeling, Rosanna, Sobreira Vieira Peixe, Luísa Maria, Perovic, Olga, Pettigrew, Melinda M, Principi, Nicola, Pulcini, Céline, Puspandari, Nelly, Rawson, Timothy, Reddy, Denasha Lavanya, Reddy, Kessendri, Redner, Paulo, Rodríguez Tudela, Juan Luis, Rodríguez-Baño, Jesús, Van Katwyk, Susan Rogers, Roilides, Emmanuel, Rollier, Christine, Rollock, Leslie, Ronat, Jean-Baptiste, Ruppe, Etienne, Sadarangani, Manish, Salisbury, David, Salou, Mounerou, Samison, Luc Hervé, Sanguinetti, Maurizio, Sartelli, Massimo, Schellack, Natalie, Schouten, Jeroen, Schwaber, Mitchell J, Seni, Jeremiah, Senok, Abiola, Shafer, William M, Shakoor, Sadia, Sheppard, Donald, Shin, Jong-Hee, Sia, Sonia, Sievert, Dawn, Singh, Ishwar, Singla, Rupak, Skov, Robert Leo, Soge, Olusegun O, Sprute, Rosanne, Srinivasan, Arjun, Srinivasan, Subasree, Sundsfjord, Arnfinn, Tacconelli, Evelina, Tahseen, Sabira, Tangcharoensathien, Viroj, Tängdén, Thomas, Thursky, Karin, Thwaites, Guy, Tigulini de Souza Peral, Renata, Tong, Deborah, Tootla, Hafsah Deepa, Tsioutis, Constantinos, Turner, Katy M, Turner, Paul, Omar, Shaheed Vally, van de Sande, Wendy WJ, van den Hof, Susan, van Doorn, Rogier, Veeraraghavan, Balaji, Verweij, Paul, Wahyuningsih, Retno, Wang, Hui, Warris, Adilia, Weinstock, Hillard, Wesangula, Evelyn, Whiley, David, White, Peter J, Williams, Phoebe, Xiao, Yonghong, Moscoso, Martin Yagui, Yang, Hsu Li, Yoshida, Sachiyo, Yu, Yunsong, Żabicka, Dorota, Zignol, Matteo, Rudan, Igor, Bertagnolio, Silvia, Dobreva, Zlatina, Centner, Chad M, Olaru, Ioana Diana, Donà, Daniele, Burzo, Stefano, Huttner, Benedikt D, Chaillon, Antoine, Gebreselassie, Nebiat, Wi, Teodora, Hasso-Agopsowicz, Mateusz, Allegranzi, Benedetta, Sati, Hatim, Ivanovska, Verica, Kothari, Kavita U, Balkhy, Hanan H, Cassini, Alessandro, Hamers, Raph L, and Weezenbeek, Kitty Van

Published
2024
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10. Reappraising Cladophialophora bantiana phaeohyphomycosis in France: retrospective nation-based study

Author

Lortholary, Olivier, Garcia-Hermoso, Dea, Sturny-Leclère, Aude, Sitbon, Karine, Nourrisson, Céline, Letscher-Bru, Valérie, Desbois-Nogard, Nicole, Bani-Sadr, Ferouze, Bastides, Frédéric, Bienvenu, Boris, Cordier, Camille, Coste, Anne, Danion, François, Dégot, Tristan, Delarbre, David, Fekkar, Arnaud, Garcie, Christophe, Garrouste, Cyril, Gits-Muselli, Maud, Guemas, Emilie, Huguenin, Antoine, Janvier, Frédéric, Kamar, Nassim, Kervinio, Cyril, Le Gal, Solène, Lesens, Olivier, Machouart, Marie, Persat, Florence, Picot, Sandrine, Rouze, Anahita, Ranque, Stéphane, Ruch, Yvon, Saada, Matthieu, Stabler, Sarah, Alanio, Alexandre, Lanternier, Fanny, and Desoubeaux, Guillaume

Published
2024
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11. Epidemiology and prognostic factors of mucormycosis in France (2012–2022): a cross-sectional study nested in a prospective surveillance programme

Author

Gouzien, Laura, Che, Didier, Cassaing, Sophie, Lortholary, Olivier, Letscher-Bru, Valérie, Paccoud, Olivier, Obadia, Thomas, Morio, Florent, Moniot, Maxime, Cateau, Estelle, Bougnoux, Marie Elisabeth, Chouaki, Taieb, Hasseine, Lilia, Desoubeaux, Guillaume, Gautier, Cecile, Mahinc-Martin, Caroline, Huguenin, Antoine, Bonhomme, Julie, Sitbon, Karine, Durand, Julien, Alanio, Alexandre, Millon, Laurence, Garcia-Hermoso, Dea, and Lanternier, Fanny

Published
2024
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12. Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8+ T cells

Author

Wang, Kevin, Coutifaris, Paulina, Brocks, David, Wang, Guanning, Azar, Tarek, Solis, Sabrina, Nandi, Ajeya, Anderson, Shaneaka, Han, Nicholas, Manne, Sasikanth, Kiner, Evgeny, Sachar, Chirag, Lucas, Minke, George, Sangeeth, Yan, Patrick K., Kier, Melanie W., Laughlin, Amy I., Kothari, Shawn, Giles, Josephine, Mathew, Divij, Ghinnagow, Reem, Alanio, Cecile, Flowers, Ahron, Xu, Wei, Tenney, Daniel J., Xu, Xiaowei, Amaravadi, Ravi K., Karakousis, Giorgos C., Schuchter, Lynn M., Buggert, Marcus, Oldridge, Derek, Minn, Andy J., Blank, Christian, Weber, Jeffrey S., Mitchell, Tara C., Farwell, Michael D., Herati, Ramin S., and Huang, Alexander C.

Published
2024
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15. Current knowledge and practice of Candida auris screening in France: A nationwide survey from the French Society of Medical Mycology (SFMM)

Author

Guitard, J., Bellanger, A.P., Dorin, J., Cassaing, S., Capitaine, A., Gabriel, F., Nicolas, M., Coron, N., Penn, P., Moniot, M., Quinio, D., Ranque, S., Sasso, M., Lepape, P., Dannaoui, E., Brun, S., Lacroix, C., Cornu, M., Debourgogne, A., Durieux, M.F., Laurent, G., Bru, V., Bourgeois, N., Brunet, K., Chouaki, T., Huguenin, A., Hasseine, L., Maubon, D., Gangneux, J.P., Desbois-Nogard, N., Houze, S., Dalle, F., Bougnoux, M.E., Alanio, A., Costa, D., Botterel, F., and Hennequin, C.

Published
2024
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16. Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM

Author

Chang, Christina C, Harrison, Thomas S, Bicanic, Tihana A, Chayakulkeeree, Methee, Sorrell, Tania C, Warris, Adilia, Hagen, Ferry, Spec, Andrej, Oladele, Rita, Govender, Nelesh P, Chen, Sharon C, Mody, Christopher H, Groll, Andreas H, Chen, Yee-Chun, Lionakis, Michail S, Alanio, Alexandre, Castañeda, Elizabeth, Lizarazo, Jairo, Vidal, José E, Takazono, Takahiro, Hoenigl, Martin, Alffenaar, Jan-Willem, Gangneux, Jean-Pierre, Soman, Rajeev, Zhu, Li-Ping, Bonifaz, Alexandro, Jarvis, Joseph N, Day, Jeremy N, Klimko, Nikolai, Salmanton-García, Jon, Jouvion, Grégory, Meya, David B, Lawrence, David, Rahn, Sebastian, Bongomin, Felix, McMullan, Brendan J, Sprute, Rosanne, Nyazika, Tinashe K, Beardsley, Justin, Carlesse, Fabianne, Heath, Christopher H, Ayanlowo, Olusola O, Mashedi, Olga M, Queiroz-Telles Filho, Flavio, Hosseinipour, Mina C, Patel, Atul K, Temfack, Elvis, Singh, Nina, Cornely, Oliver A, Boulware, David R, Lortholary, Olivier, Pappas, Peter G, and Perfect, John R

Published
2024
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19. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial

Author

Padrón, Lacey J, Maurer, Deena M, O’Hara, Mark H, O’Reilly, Eileen M, Wolff, Robert A, Wainberg, Zev A, Ko, Andrew H, Fisher, George, Rahma, Osama, Lyman, Jaclyn P, Cabanski, Christopher R, Yu, Jia Xin, Pfeiffer, Shannon M, Spasic, Marko, Xu, Jingying, Gherardini, Pier Federico, Karakunnel, Joyson, Mick, Rosemarie, Alanio, Cécile, Byrne, Katelyn T, Hollmann, Travis J, Moore, Jonni S, Jones, Derek D, Tognetti, Marco, Chen, Richard O, Yang, Xiaodong, Salvador, Lisa, Wherry, E John, Dugan, Ute, O’Donnell-Tormey, Jill, Butterfield, Lisa H, Hubbard-Lucey, Vanessa M, Ibrahim, Ramy, Fairchild, Justin, Bucktrout, Samantha, LaVallee, Theresa M, and Vonderheide, Robert H

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Pancreatic Cancer, Clinical Trials and Supportive Activities, Cancer, Orphan Drug, Clinical Research, Rare Diseases, Digestive Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Albumins, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Pancreatic Ductal, Humans, Nivolumab, Pancreatic Neoplasms, Tumor Microenvironment, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34) but was not met for sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials.

Published
2022

21. Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study

Author

Goodall, J, Mawoko, N, Milburn, J, Mmipi, R, Muthoga, C, Ponatshego, P, Rulaganyang, I, Seatla, K, Tlhako, N, Tsholo, K, April, S, Bekiswa, A, Boloko, L, Bookholane, H, Crede, T, Davids, L, Goliath, R, Hlungulu, S, Hoffman, R, Kyepa, H, Masina, N, Maughan, D, Mnguni, T, Moosa, S, Morar, T, Mpalali, M, Naude, J, Oliphant, I, Sayed, S, Sebesho, L, Shey, M, Swanepoel, L, Chasweka, M, Chimang’anga, W, Chimphambano, T, Dziwani, E, Gondwe, E, Kadzilimbile, A, Kateta, S, Kossam, E, Kukacha, C, Lipenga, B, Ndaferankhande, J, Ndalama, M, Shah, R, Singini, A, Stott, K, Zambasa, A, Banda, T, Chikaonda, T, Chitulo, G, Chiwoko, L, Chome, N, Gwin, M, Kachitosi, T, Kamanga, B, Kazembe, M, Kumwenda, E, Kumwenda, M, Maya, C, Mhango, W, Mphande, C, Msumba, L, Munthali, T, Ngoma, D, Nicholas, S, Simwinga, L, Stambuli, A, Tegha, G, Zambezi, J, Ahimbisibwe, C, Akampurira, A, Alice, A, Cresswell, F, Gakuru, J, Kiiza, D, Kisembo, J, Kwizera, R, Kugonza, F, Laker, E, Luggya, T, Lule, A, Musubire, A, Muyise, R, Namujju, O, Ndyetukira, J, Nsangi, L, Okirwoth, M, Sadiq, A, Tadeo, K, Tukundane, A, Williams, D, Atwine, L, Buzaare, P, Collins, M, Emily, N, Inyakuwa, C, Kariisa, S, Mwesigye, J, Niwamanya, S, Rodgers, A, Rukundo, J, Rwomushana, I, Ssemusu, M, Stead, G, Boyd, K, Gondo, S, Kufa, P, Makaha, E, Moyo, C, Mtisi, T, Mudzingwa, S, Mwarumba, T, Zinyandu, T, Dromer, F, Johnstone, P, Hafeez, S, Mbangiwa, Tshepiso, Sturny-Leclère, Aude, Lechiile, Kwana, Kajanga, Cheusisime, Boyer-Chammard, Timothée, Hoving, Jennifer C, Leeme, Tshepo, Moyo, Melanie, Youssouf, Nabila, Lawrence, David S, Mwandumba, Henry, Mosepele, Mosepele, Harrison, Thomas S, Jarvis, Joseph N, Lortholary, Olivier, and Alanio, Alexandre

Published
2024
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22. Dynamics of Histoplasma fungal load in people living with HIV with disseminated histoplasmosis under treatment with liposomal amphotericin B

Author

Sturny-Leclère, Aude, Da Silva, Elodie, Godoy, Cassia S.M., Soares, Renata B.A., Leitão, Terezinha do Menino Jesus Silva, Damasceno, Lisandra Serra, Bay, Monica B., Melo, Marineide, Lana, Daiane Dalla, Silva, Larissa R., Israelski, Dennis, Falci, Diego R., Pasqualotto, Alessandro C., and Alanio, Alexandre

Published
2024
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26. 579-C Reinvigoration of progenitor-exhausted CD8 T cells by anti-CTLA-4 contributes to the sustained activity of combination checkpoint blockade

Author

Xiaowei Xu, Wei Xu, Alexander Huang, Jeffrey Weber, Andy Minn, Kevin Wang, Tara Mitchell, Sasikanth Manne, Divij Mathew, E John Wherry, Daniel Tenney, Paulina Coutifaris, David Brocks, Sabrina Solis, Nicholas Han, Evgeny Kiner, Chirag Sachar, Sangeeth George, Patrick Yan, Melanie W Kiner, Amy I Laughlin, Shawn Kothari, Josephine R Giles, Rheem Ghinnagow, Cecile Alanio, Ahron Flowers, Ravi K Amaravadi, Giorgos C Karakousis, Lynn M Schuchter, Marcus Buggert, and Ramin S Herati

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
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27. Kicking sleepers out of bed: Macrophages promote reactivation of dormant Cryptococcus neoformans by extracellular vesicle release and non-lytic exocytosis.

Author

Raffael Júnio Araújo de Castro, Clara Luna Marina, Aude Sturny-Leclère, Christian Hoffmann, Pedro Henrique Bürgel, Sarah Sze Wah Wong, Vishukumar Aimanianda, Hugo Varet, Ruchi Agrawal, Anamélia Lorenzetti Bocca, and Alexandre Alanio

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Macrophages play a key role in disseminated cryptococcosis, a deadly fungal disease caused by Cryptococcus neoformans. This opportunistic infection can arise following the reactivation of a poorly characterized latent infection attributed to dormant C. neoformans. Here, we investigated the mechanisms underlying reactivation of dormant C. neoformans using an in vitro co-culture model of viable but non-culturable (VBNC; equivalent of dormant) yeast cells with bone marrow-derived murine macrophages (BMDMs). Comparative transcriptome analysis of BMDMs incubated with log, stationary phase or VBNC cells of C. neoformans showed that VBNC cells elicited a reduced transcriptional modification of the macrophage but retaining the ability to regulate genes important for immune response, such as NLRP3 inflammasome-related genes. We further confirmed the maintenance of the low immunostimulatory capacity of VBNC cells using multiplex cytokine profiling, and analysis of cell wall composition and dectin-1 ligands exposure. In addition, we evaluated the effects of classic (M1) or alternative (M2) macrophage polarization on VBNC cells. We observed that intracellular residence sustained dormancy, regardless of the polarization state of macrophages and despite indirect detection of pantothenic acid (or its derivatives), a known reactivator for VBNC cells, in the C. neoformans-containing phagolysosome. Notably, M0 and M2, but not M1 macrophages, induced extracellular reactivation of VBNC cells by the secretion of extracellular vesicles and non-lytic exocytosis. Our results indicate that VBNC cells retain the low immunostimulatory profile required for persistence of C. neoformans in the host. We also describe a pro-pathogen role of macrophage-derived extracellular vesicles in C. neoformans infection and reinforce the impact of non-lytic exocytosis and the macrophage profile on the pathophysiology of cryptococcosis.

Published
2023
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29. Coregulation of extracellular vesicle production and fluconazole susceptibility in Cryptococcus neoformans

Author

Juliana Rizzo, Adèle Trottier, Frédérique Moyrand, Jean-Yves Coppée, Corinne Maufrais, Ana Claudia G. Zimbres, Thi Tuong Vi Dang, Alexandre Alanio, Marie Desnos-Ollivier, Isabelle Mouyna, Gérard Péhau-Arnaude, Pierre-Henri Commere, Sophie Novault, Iuliana V. Ene, Leonardo Nimrichter, Marcio L. Rodrigues, and Guilhem Janbon

Subjects
Cryptococcus neoformans, extracellular vesicles, antimicrobial resistance, fluconazole, transcription factor, Microbiology, QR1-502
Abstract

ABSTRACT Resistance to fluconazole (FLC), the most widely used antifungal drug, is typically achieved by altering the azole drug target and/or drug efflux pumps. Recent reports have suggested a link between vesicular trafficking and antifungal resistance. Here, we identified novel Cryptococcus neoformans regulators of extracellular vesicle (EV) biogenesis that impact FLC resistance. In particular, the transcription factor Hap2 does not affect the expression of the drug target or efflux pumps, yet it impacts the cellular sterol profile. Subinhibitory FLC concentrations also downregulate EV production. Moreover, in vitro spontaneous FLC-resistant colonies showed altered EV production, and the acquisition of FLC resistance was associated with decreased EV production in clinical isolates. Finally, the reversion of FLC resistance was associated with increased EV production. These data suggest a model in which fungal cells can regulate EV production in place of regulating the drug target gene expression as a first line of defense against antifungal assault in this fungal pathogen. IMPORTANCE Extracellular vesicles (EVs) are membrane-enveloped particles that are released by cells into the extracellular space. Fungal EVs can mediate community interactions and biofilm formation, but their functions remain poorly understood. Here, we report the identification of the first regulators of EV production in the major fungal pathogen Cryptococcus neoformans. Surprisingly, we uncover a novel role of EVs in modulating antifungal drug resistance. Disruption of EV production was associated with altered lipid composition and changes in fluconazole susceptibility. Spontaneous azole-resistant mutants were deficient in EV production, while loss of resistance restored initial EV production levels. These findings were recapitulated in C. neoformans clinical isolates, indicating that azole resistance and EV production are coregulated in diverse strains. Our study reveals a new mechanism of drug resistance in which cells adapt to azole stress by modulating EV production.

Published
2023
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30. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium

Author

Cornely, Oliver A, Alastruey-Izquierdo, Ana, Arenz, Dorothee, Chen, Sharon CA, Dannaoui, Eric, Hochhegger, Bruno, Hoenigl, Martin, Jensen, Henrik E, Lagrou, Katrien, Lewis, Russell E, Mellinghoff, Sibylle C, Mer, Mervyn, Pana, Zoi D, Seidel, Danila, Sheppard, Donald C, Wahba, Roger, Akova, Murat, Alanio, Alexandre, Al-Hatmi, Abdullah MS, Arikan-Akdagli, Sevtap, Badali, Hamid, Ben-Ami, Ronen, Bonifaz, Alexandro, Bretagne, Stéphane, Castagnola, Elio, Chayakulkeeree, Methee, Colombo, Arnaldo L, Corzo-León, Dora E, Drgona, Lubos, Groll, Andreas H, Guinea, Jesus, Heussel, Claus-Peter, Ibrahim, Ashraf S, Kanj, Souha S, Klimko, Nikolay, Lackner, Michaela, Lamoth, Frederic, Lanternier, Fanny, Lass-Floerl, Cornelia, Lee, Dong-Gun, Lehrnbecher, Thomas, Lmimouni, Badre E, Mares, Mihai, Maschmeyer, Georg, Meis, Jacques F, Meletiadis, Joseph, Morrissey, C Orla, Nucci, Marcio, Oladele, Rita, Pagano, Livio, Pasqualotto, Alessandro, Patel, Atul, Racil, Zdenek, Richardson, Malcolm, Roilides, Emmanuel, Ruhnke, Markus, Seyedmousavi, Seyedmojtaba, Sidharthan, Neeraj, Singh, Nina, Sinko, János, Skiada, Anna, Slavin, Monica, Soman, Rajeev, Spellberg, Brad, Steinbach, William, Tan, Ban Hock, Ullmann, Andrew J, Vehreschild, Jörg J, Vehreschild, Maria JGT, Walsh, Thomas J, White, P Lewis, Wiederhold, Nathan P, Zaoutis, Theoklis, Chakrabarti, Arunaloke, and Group, Mucormycosis ECMM MSG Global Guideline Writing

Subjects
Clinical Research, Good Health and Well Being, Disease Management, Humans, Mucormycosis, Mucormycosis ECMM MSG Global Guideline Writing Group, Clinical Sciences, Medical Microbiology, Public Health and Health Services, Microbiology
Abstract

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.

Published
2019

31. Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial

Author

Goodall, Jack, Lechiile, Kwana, Mawoko, Norah, Mbangiwa, Tshepiso, Milburn, James, Mmipi, Refilwe, Ponatshego, Ponego, Rulaganyang, Ikanyang, Seatla, Kaelo, Siamisang, Keatlaretse, Tlhako, Nametso, Tsholo, Katlego, April, Samantha, Bekiswa, Abulele, Boloko, Linda, Bookholane, Hloni, Crede, Thomas, Davids, Lee-Ann, Goliath, Rene, Hlungulu, Siphokazi, Hoffman, Regina, Kyepa, Henriette, Masina, Noma, Maughan, Deborah, Mnguni, Trevor, Moosa, Sumaiyya, Morar, Tania, Mpalali, Mkanyiseli, Naude, Jonathan, Oliphant, Ida, Singh, Achita, Sayed, Sumaya, Sebesho, Leago, Shey, Muki, Swanepoel, Loraine, Chasweka, Madalitso, Chimang'anga, Wezi, Chimphambano, Tipatseni, Gondwe, Ebbie, Mzinganjira, Henry, Kadzilimbile, Aubrey, Kateta, Steven, Kossam, Evelyn, Kukacha, Christopher, Lipenga, Bright, Ndaferankhande, John, Ndalama, Maureen, Shah, Reya, Singini, Andreas, Stott, Katherine, Zambasa, Agness, Banda, Towera, Chikaonda, Tarsizio, Chitulo, Gladys, Chiwoko, Lorren, Chome, Nelecy, Gwin, Mary, Kachitosi, Timothy, Kamanga, Beauty, Kazembe, Mussah, Kumwenda, Emily, Kumwenda, Masida, Maya, Chimwemwe, Mhango, Wilberforce, Mphande, Chimwemwe, Msumba, Lusungu, Munthali, Tapiwa, Ngoma, Doris, Nicholas, Simon, Simwinga, Lusayo, Stambuli, Anthony, Tegha, Gerald, Zambezi, Janet, Ahimbisibwe, Cynthia, Akampurira, Andrew, Alice, Anamudde, Cresswell, Fiona, Gakuru, Jane, Kagimu, Enock, Kasibante, John, Kiiza, Daniel, Kisembo, John, Kwizera, Richard, Kugonza, Florence, Laker, Eva, Luggya, Tonny, Lule, Andrew, Musubire, Abdu, Muyise, Rhona, Namujju, Carol Olivie, Ndyetukira, Jane Francis, Nsangi, Laura, Okirworth, Michael, Rhein, Joshua, Rutakingirwa, Morris K, Sadiq, Alisat, Ssebambulidde, Kenneth, Tadeo, Kiiza, Tukundane, Asmus, Atwine, Leo, Buzaare, Peter, Collins, Muganzi, Emily, Ninsima, Inyakuwa, Christine, Kariisa, Samson, Mwesigye, James, Nuwamanya, Simpson, Rodgers, Ankunda, Rukundo, Joan, Rwomushana, Irene, Ssemusu, Mike, Stead, Gavin, Boyd, Kathyrn, Gondo, Secrecy, Kufa, Prosper, Makaha, Edward, Moyo, Colombus, Mtisi, Takudzwa, Mudzinga, Shepherd, Mutata, Constantine, Mwarumba, Taddy, Zinyandu, Tawanda, Alanio, Alexandre, Dromer, Francoise, Lortholary, Olivier, Sturny-Leclere, Aude, Griffin, Philippa, Hafeez, Sophia, Loyse, Angela, van Widenfelt, Erik, Lawrence, David S, Muthoga, Charles, Meya, David B, Tugume, Lillian, Williams, Darlisha, Rajasingham, Radha, Boulware, David R, Mwandumba, Henry C, Moyo, Melanie, Dziwani, Eltas N, Maheswaran, Hendramoorthy, Kanyama, Cecilia, Hosseinipour, Mina C, Chawinga, Chimwemwe, Meintjes, Graeme, Schutz, Charlotte, Comins, Kyla, Bango, Funeka, Muzoora, Conrad, Jjunju, Samuel, Nuwagira, Edwin, Mosepele, Mosepele, Leeme, Tshepo, Ndhlovu, Chiratidzo E, Hlupeni, Admire, Shamu, Shepherd, Boyer-Chammard, Timothée, Molloy, Síle F, Youssouf, Nabila, Chen, Tao, Shiri, Tinevimbo, Jaffar, Shabbar, Harrison, Thomas S, Jarvis, Joseph N, and Niessen, Louis W

Published
2022
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33. Invasive fungal diseases in patients with autoimmune diseases: a case series from the French RESSIF network

Author

Vincent Poindron, Benjamin Terrier, François Maillot, Jean-Pierre Gangneux, Nassim Kamar, Valéry Salle, Lilia Hasseine, François Danion, Lilia Merabet, Guillaume Desoubeaux, Éric Bailly, Milène Sasso, Antoine Néel, Simon Galmiche, Benjamin Thoreau, Stéphane Bretagne, Alexandre Alanio, André Paugam, Valérie Letscher-Bru, Sophie Cassaing, Hélène Guegan, Loïc Favennec, Alida Minoza, Florent Morio, Julie Bonhomme, Odile Eloy, Laurence Millon, Anne-Pauline Bellanger, Philippe Poirier, Maxime Moniot, Taieb Chouaki, Antoine Huguenin, Frédéric Dalle, Bernard Bouteille, Muriel Nicolas, Nicole Desbois-Nogard, Marie-Elisabeth Bougnoux, Karine Boukris-Sitbon, Fanny Lanternier, Caroline Mahinc, Marc Pihet, Magalie Demar, Céline Damiani, Marie-Fleur Durieux, Elena Charpentier, Cécile Nourrisson, and Benoit Suzon

Subjects
Medicine
Abstract

Objectives We aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality.Methods We analysed cases of IFD associated with AID from the surveillance network of invasive fungal diseases (Réseau de surveillance des infections fongiques invasives, RESSIF) registry of the French national reference centre for invasive mycoses. We studied association of AID-specific treatments with 30-day mortality. We analysed total lymphocyte and CD4-T cell counts in patients with Pneumocystis jirovecii pneumonia (PCP).Results From 2012 to 2018, 549 individuals with IFD and AID were included, mainly with PCP (n=227, 41.3%), fungemia (n=167, 30.4%) and invasive aspergillosis (n=84, 15.5%). Rheumatoid arthritis (RA) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) were the most frequent AID in PCP (n=55 and 25, respectively) and invasive aspergillosis (n=15 and 10, respectively), inflammatory bowel diseases (IBDs) were predominant in fungemia (n=36). At IFD diagnosis, 365 (66.5%) patients received glucocorticoids (GCs), 285 (51.9%) immunosuppressants, 42 (7.7%) tumor necrosis factor (TNF)-α blockers, 75 (13.7%) other biologics. Mortality at 30 days was 28.1% (143/508). Fungemia and high-dose GCs were independently associated with higher 30-day mortality. In PCP patients, lymphopenia

Published
2023
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36. The current state of clinical mycology in Africa: a European Confederation of Medical Mycology and International Society for Human and Animal Mycology survey

Author

Driemeyer, Cândida, Falci, Diego R, Oladele, Rita O, Bongomin, Felix, Ocansey, Bright K, Govender, Nelesh P, Hoenigl, Martin, Gangneux, Jean Pierre, Lass-Flörl, Cornelia, Cornely, Oliver A, Alanio, Alexandre, Guinea, Jesus, Morrissey, C Orla, Rautemaa-Richardson, Riina, Chakrabarti, Arunaloke, Meis, Jacques F, Bruns, Caroline, Stemler, Jannik, and Pasqualotto, Alessandro C

Published
2022
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39. Primary immune responses are negatively impacted by persistent herpesvirus infections in older people: results from an observational study on healthy subjects and a vaccination trial on subjects aged more than 70 years old

Author

Nicoli, Francesco, Clave, Emmanuel, Wanke, Kerstin, von Braun, Amrei, Bondet, Vincent, Alanio, Cécile, Douay, Corinne, Baque, Margaux, Lependu, Claire, Marconi, Peggy, Stiasny, Karin, Heinz, Franz X., Muetsch, Margot, Duffy, Darragh, Boddaert, Jacques, Sauce, Delphine, Toubert, Antoine, Karrer, Urs, and Appay, Victor

Published
2022
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40. Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study

Author

Gangneux, Jean-Pierre, Dannaoui, Eric, Fekkar, Arnaud, Luyt, Charles-Edouard, Botterel, Françoise, De Prost, Nicolas, Tadié, Jean-Marc, Reizine, Florian, Houzé, Sandrine, Timsit, Jean-François, Iriart, Xavier, Riu-Poulenc, Béatrice, Sendid, Boualem, Nseir, Saad, Persat, Florence, Wallet, Florent, Le Pape, Patrice, Canet, Emmanuel, Novara, Ana, Manai, Melek, Cateau, Estelle, Thille, Arnaud W, Brun, Sophie, Cohen, Yves, Alanio, Alexandre, Mégarbane, Bruno, Cornet, Muriel, Terzi, Nicolas, Lamhaut, Lionel, Sabourin, Estelle, Desoubeaux, Guillaume, Ehrmann, Stephan, Hennequin, Christophe, Voiriot, Guillaume, Nevez, Gilles, Aubron, Cécile, Letscher-Bru, Valérie, Meziani, Ferhat, Blaize, Marion, Mayaux, Julien, Monsel, Antoine, Boquel, Frédérique, Robert-Gangneux, Florence, Le Tulzo, Yves, Seguin, Philippe, Guegan, Hélène, Autier, Brice, Lesouhaitier, Matthieu, Pelletier, Romain, Belaz, Sorya, Bonnal, Christine, Berry, Antoine, Leroy, Jordan, François, Nadine, Richard, Jean-Christophe, Paulus, Sylvie, Argaud, Laurent, Dupont, Damien, Menotti, Jean, Morio, Florent, Soulié, Marie, Schwebel, Carole, Garnaud, Cécile, Guitard, Juliette, Le Gal, Solène, Quinio, Dorothée, Morcet, Jeff, Laviolle, Bruno, Zahar, Jean-Ralph, and Bougnoux, Marie-Elisabeth

Published
2022
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41. Decade-long leukaemia remissions with persistence of CD4+ CAR T cells

Author

Melenhorst, J. Joseph, Chen, Gregory M., Wang, Meng, Porter, David L., Chen, Changya, Collins, McKensie A., Gao, Peng, Bandyopadhyay, Shovik, Sun, Hongxing, Zhao, Ziran, Lundh, Stefan, Pruteanu-Malinici, Iulian, Nobles, Christopher L., Maji, Sayantan, Frey, Noelle V., Gill, Saar I., Loren, Alison W., Tian, Lifeng, Kulikovskaya, Irina, Gupta, Minnal, Ambrose, David E., Davis, Megan M., Fraietta, Joseph A., Brogdon, Jennifer L., Young, Regina M., Chew, Anne, Levine, Bruce L., Siegel, Donald L., Alanio, Cécile, Wherry, E. John, Bushman, Frederic D., Lacey, Simon F., Tan, Kai, and June, Carl H.

Published
2022
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42. Multicenter Evaluation of the FilmArray Blood Culture Identification 2 Panel for Pathogen Detection in Bloodstream Infections

Author

François Caméléna, Gauthier Péan de Ponfilly, Hélène Pailhoriès, Lucas Bonzon, Alexandre Alanio, Thibaut Poncin, Matthieu Lafaurie, François Dépret, Emmanuel Cambau, Sylvain Godreuil, Rachel Chenouard, Alban Le Monnier, Hervé Jacquier, and Béatrice Berçot

Subjects
BCID2, BSI, Biofire, bloodstream infection, FilmArray, molecular diagnosis, Microbiology, QR1-502
Abstract

ABSTRACT The FilmArray Blood Culture Identification 2 panel (BCID2; bioMérieux) is a fully automated PCR-based assay for identifying bacteria, fungi, and bacterial resistance markers in positive blood cultures (BC) in about 1 h. In this multicenter study, we evaluated the performance of the BCID2 panel for pathogen detection in positive BC. Conventional culture and BCID2 were performed in parallel at four tertiary-care hospitals. We included 152 positive BC—130 monomicrobial and 22 polymicrobial cultures—in this analysis. The BCID2 assay correctly identified 90% (88/98) of Gram-negative and 89% (70/79) of Gram-positive bacteria. Five bacterial isolates targeted by the BCID2 panel and recovered from five positive BC, including three polymicrobial cultures, were missed by the BCID2 assay. Fifteen isolates were off-panel organisms, accounting for 8% (15/182) of the isolates obtained from BC. The mean positive percent agreement between the BCID2 assay and standard culture was 97% (95% confidence interval, 95 to 99%), with agreement ranging from 67% for Candida albicans to 100% for 17 targets included in the BCID2 panel. BCID2 also identified the blaCTX-M gene in seven BC, including one for which no extended-spectrum β-lactamase (ESBL)-producing isolate was obtained in culture. However, it failed to detect ESBL-encoding genes in three BC. Two of the 18 mecA/C genes detected by the BCID2 were not confirmed. No carbapenemase, mecA/C, or MREJ targets were detected. The median turnaround time was significantly shorter for BCID2 than for culture. The BCID2 panel may facilitate faster pathogen identification in bloodstream infections. IMPORTANCE Rapid molecular diagnosis combining the identification of pathogens and the detection of antibiotic resistance genes from positive blood cultures (BC) can improve the outcome for patients with bloodstream infections. The FilmArray BCID2 panel, an updated version of the original BCID, can detect 11 Gram-positive bacteria, 15 Gram-negative bacteria, 7 fungal pathogens, and 10 antimicrobial resistance genes directly from a positive BC. Here, we evaluated the real-life microbiological performance of the BCID2 assay in comparison to the results of standard methods used in routine practice at four tertiary care hospitals.

Published
2023
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43. Outbreak of Invasive Wound Mucormycosis in a Burn Unit Due to Multiple Strains of Mucor circinelloides f. circinelloides Resolved by Whole-Genome Sequencing

Author

Garcia-Hermoso, Dea, Criscuolo, Alexis, Lee, Soo Chan, Legrand, Matthieu, Chaouat, Marc, Denis, Blandine, Lafaurie, Matthieu, Rouveau, Martine, Soler, Charles, Schaal, Jean-Vivien, Mimoun, Maurice, Mebazaa, Alexandre, Heitman, Joseph, Dromer, Françoise, Brisse, Sylvain, Bretagne, Stéphane, Alanio, Alexandre, Lockhart, Shawn, and Voigt, Kerstin

Subjects
Infectious Diseases, Emerging Infectious Diseases, Biotechnology, Aetiology, 2.2 Factors relating to the physical environment, Infection, Burn Units, Burns, Cluster Analysis, Cross Infection, Disease Outbreaks, France, Genetic Variation, Genotype, Humans, Molecular Epidemiology, Molecular Typing, Mucor, Mucormycosis, Phylogeny, Whole Genome Sequencing, Wound Infection, Wounds and Injuries, Mucor circinelloides, Mucorales, burn, clade, genome, genotype, mixed infection, mucormycosis, outbreak, strains, whole-genome sequencing, wound, Microbiology
Abstract

Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole-genome sequencing (WGS) analysis. We analyzed M. circinelloides isolates from patients in our burn unit (BU1, Hôpital Saint-Louis, Paris, France) together with nonoutbreak isolates from Burn Unit 2 (BU2, Paris area) and from France over a 2-year period (2013 to 2015). A total of 21 isolates, including 14 isolates from six BU1 patients, were analyzed by whole-genome sequencing (WGS). Phylogenetic classification based on de novo assembly and assembly free approaches showed that the clinical isolates clustered in four highly divergent clades. Clade 1 contained at least one of the strains from the six epidemiologically linked BU1 patients. The clinical isolates were specific to each patient. Two patients were infected with more than two strains from different clades, suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients from BU1 shared one strain, which could correspond to direct transmission or contamination with the same environmental source. In conclusion, WGS of several isolates per patients coupled with precise epidemiological data revealed a complex situation combining potential cross-transmission between patients and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.IMPORTANCE Invasive wound mucormycosis (IWM) is a severe infection due to environmental molds belonging to the order Mucorales. Severely burned patients are particularly at risk for IWM. Here, we used whole-genome sequencing (WGS) analysis to resolve an outbreak of IWM due to Mucor circinelloides that occurred in our hospital (BU1). We sequenced 21 clinical isolates, including 14 from BU1 and 7 unrelated isolates, and compared them to the reference genome (1006PhL). This analysis revealed that the outbreak was mainly due to multiple strains that seemed patient specific, suggesting that the patients were more likely infected from a pool of diverse strains from the environment rather than from direct transmission among them. This study revealed the complexity of a Mucorales outbreak in the settings of IWM in burn patients, which has been highlighted based on WGS combined with careful sampling.

Published
2018

44. Yeast Infections

Author

Alanio, Alexandre, Chen, Sharon C. -A., Dreyling, Martin, Series Editor, Cornely, Oliver A., editor, and Hoenigl, Martin, editor

Published
2021
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45. Emergence of Difficult-to-Treat Tinea Corporis Caused by Trichophyton mentagrophytes Complex Isolates, Paris, France

Author

Delliere, Sarah, Joannard, Brune, Benderdouche, Mazouz, Mingui, Anselme, Gits-Muselli, Maud, Hamane, Samia, Alanio, Alexandre, Petit, Antoine, Gabison, Germaine, Bagot, Martine, and Bretagne, Stephane

Subjects
Drug resistance in microorganisms -- Causes of -- Genetic aspects, Ringworm -- Drug therapy -- Causes of, Dermatophytes -- Identification and classification -- Genetic aspects, Health
Abstract

Dermatophytes are filamentous keratinophilic fungi responsible for superficial fungal diseases involving the skin, hair, or nails. On the basis of the site of the lesions, conditions are called tinea corporis, [...]

Published
2022
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46. Polymerase Chain Reaction on Respiratory Tract Specimens of Immunocompromised Patients to Diagnose Pneumocystis Pneumonia: A Systematic Review and Meta-analysis

Author

Brown, Lottie, primary, Rautemaa-Richardson, Riina, additional, Mengoli, Carlo, additional, Alanio, Alexandre, additional, Barnes, Rosemary A, additional, Bretagne, Stéphane, additional, Chen, Sharon C A, additional, Cordonnier, Catherine, additional, Donnelly, J Peter, additional, Heinz, Werner J, additional, Jones, Brian, additional, Klingspor, Lena, additional, Loeffler, Juergen, additional, Rogers, Thomas R, additional, Rowbotham, Eleanor, additional, White, P Lewis, additional, and Cruciani, Mario, additional

Published
2024
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48. Emergence of Difficult-to-Treat Tinea Corporis Caused by Trichophyton mentagrophytes Complex Isolates, Paris, France

Author

Sarah Dellière, Brune Joannard, Mazouz Benderdouche, Anselme Mingui, Maud Gits-Muselli, Samia Hamane, Alexandre Alanio, Antoine Petit, Germaine Gabison, Martine Bagot, and Stéphane Bretagne

Subjects
antimicrobial resistance, Trichophyton mentagrophytes complex, Trichophyton indotineae, squalene epoxidase, terbinafine, skin infections, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We describe 7 cases of extensive tinea corporis since 2018 in a hospital in Paris, France, after failure to cure with terbinafine. Molecular analysis indicated Trichophyton mentagrophytes internal transcribed spacer type VIII (T. indotineae). This strain, which has mutations in the squalene epoxidase gene, is spreading on the Indian subcontinent.

Published
2022
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49. Imported leishmaniasis in travelers: a 7-year retrospective from a Parisian hospital in France

Author

Nesrine Aissaoui, Samia Hamane, Maud Gits-Muselli, Antoine Petit, Mazouz Benderdouche, Blandine Denis, Alexandre Alanio, Sarah Dellière, Martine Bagot, and Stéphane Bretagne

Subjects
Cutaneous leishmaniasis, Visceral leishmaniasis, Quantitative PCR, Cytochrome b sequencing, Leishmania major, Leishmania tropica, Infectious and parasitic diseases, RC109-216
Abstract

Highlights Imported leishmaniases are regularly seen in non-endemic areas. Cutaneous forms are due to different species that need to be correctly identified for adapting treatment and epidemiologic purposes. The index of suspicion for the visceral form is often low because of the non-specificity of the clinical symptoms and the notion of travel in endemic areas often remote. The strategy, based on diagnostic quantitative PCR followed by sequencing for species identification, allows for rapid and safe diagnoses in a routine laboratory.

Published
2021
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50. Evaluation of a New Histoplasma spp. Quantitative RT-PCR Assay

Author

Woimant, Marine Gosset, blanchard, Geneviève, Silhadi, Souad, Vignier, Nicolas, Pitsch, Aurelia, Jidar, Kaoutar, Traversier, Nicolas, Poisson, Didier, Lecointre, Claire, Foulet, Françoise, Botterel, Françoise, Ammar, Nawel Ait, Amsellem, Gabriel, Frederic, Poirier, Philipe, Cornu, Marjorie, Loridant, Severine, Morio, Florent, Boutoille, David, Jeddi, Fakhri, Hasseine, Lilia, Ouissa, Rachida, Toubas, Dominique, Bailly, Eric, Désoubeaux, Guillaume, Ronez, Emily, Foulon, Guillaume, Lefrançois, Sebastien, Bonnal, Christine, Paugam, André, Dougados, Maxime, Desroches, Marine, Barazzutti, Hélène, Paleiron, Nicolas, rabodonirina, Meja, Catherinot, Emilie, Cardot-Martin, Emilie, Hiesse, Chrisian, Salvator, Hélène, Aguilar, Claire, Gigandon, Anne, de Montpreville, Thomas, Bougnoux, Marie-Elisabeth, Sitterlé, Emilie, Fekkar, Arnaud, Imbert, Sébastien, Bleibtreu, Alexandre, Senghor, Yaye, Denis, Blandine, Molina, Jean-Michel, Liegeon, Geoffroy, Munnier, Anne-Lise, Malphettes, Marion, Denis, Julie, Berlioz-Arthaud, Alain, Lange, Franciska, Chiaruzzi, Myriam, Epelboin, Loic, Alanio, Alexandre, Gits-Muselli, Maud, Lanternier, Fanny, Sturny-Leclère, Aude, Benazra, Marion, Hamane, Samia, Rodrigues, Anderson Messias, Garcia-Hermoso, Dea, Lortholary, Olivier, Dromer, Françoise, and Bretagne, Stéphane

Published
2021
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