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1. Rapid and Accurate Diagnosis of Dermatophyte Infections Using the DendrisCHIP® Technology

Author

Aurore Anton, Mathilde Plinet, Thomas Peyret, Thomas Cazaudarré, Stéphanie Pesant, Yannick Rouquet, Marie-Andrée Tricoteaux, Matthieu Bernier, Jérémy Bayette, Remi Fournier, Mélanie Marguerettaz, Pierre Rolland, Thibaud Bayol, Nadia Abbaoui, Antoine Berry, Xavier Iriart, Sophie Cassaing, Pamela Chauvin, Elodie Bernard, Richard Fabre, and Jean-Marie François

Subjects
dermatophytes, in vitro diagnostic, syndromic approach, multiplex PCR, biochips, microbial cultures, Medicine (General), R5-920
Abstract

Dermatophytosis is a superficial fungal infection with an ever-increasing number of patients. Culture-based mycology remains the most commonly used diagnosis, but it takes around four weeks to identify the causative agent. Therefore, routine clinical laboratories need rapid, high throughput, and accurate species-specific analytical methods for diagnosis and therapeutic management. Based on these requirements, we investigated the feasibility of DendrisCHIP® technology as an innovative molecular diagnostic method for the identification of a subset of 13 pathogens potentially responsible for dermatophytosis infections in clinical samples. This technology is based on DNA microarray, which potentially enables the detection and discrimination of several germs in a single sample. A major originality of DendrisCHIP® technology is the use of a decision algorithm for probability presence or absence of pathogens based on machine learning methods. In this study, the diagnosis of dermatophyte infection was carried out on more than 284 isolates by conventional microbial culture and DendrisCHIP®DP, which correspond to the DendrisCHIP® carrying oligoprobes of the targeted pathogens implicated in dermatophytosis. While convergence ranging from 75 to 86% depending on the sampling procedure was obtained with both methods, the DendrisCHIP®DP proved to identify more isolates with pathogens that escaped the culture method. These results were confirmed at 86% by a third method, which was either a specific RT-PCR or genome sequencing. In addition, diagnostic results with DendrisCHIP®DP can be obtained within a day. This faster and more accurate identification of fungal pathogens with DendrisCHIP®DP enables the clinician to quickly and successfully implement appropriate antifungal treatment to prevent the spread and elimination of dermatophyte infection. Taken together, these results demonstrate that this technology is a very promising method for routine diagnosis of dermatophytosis.

Published
2023
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2. Evaluation of the Performance of the Novodiag® Stool Parasites Assay for the Detection of Intestinal Protozoa and Microsporidia

Author

Pamela Chauvin, Florie Barba, Emilie Guemas, Eléna Charpentier, Claire Cottrel, Judith Fillaux, Alexis Valentin, Sarah Baklouti, Sophie Cassaing, Sandie Ménard, Antoine Berry, and Xavier Iriart

Subjects
stool, protozoa, microsporidia, diagnosis, microscopy, qPCR, Medicine
Abstract

Objectives: We aimed to assess the performance of the Novodiag® Stool Parasites (NSP) assay in the diagnosis of the most common intestinal protozoan and microsporidia infections. Methods: A panel of 167 selected stool samples was retrospectively analysed with the NSP assay and compared to routine microscopy and qPCR methods for the detection of pathogenic protozoa and microsporidia. Results: Whereas specificity was high for all protozoa and microsporidia, NSP sensitivity was strongly dependent on the comparative method used as reference. When compared to microscopic methods, NSP sensitivity was high (96.7 to 100%) for Blastocystis hominis, Entamoeba histolytica and Cyclospora cayetanensis but was lower for Giardia intestinalis (85.2%) and ≤50% for Cystoisospora belli and Dientamoeba fragilis. In comparison to conventional qPCR, the NSP assay demonstrated lower sensitivity characteristics dependent on parasite loads, reaching 60 to 70% for G. intestinalis, D. fragilis, Cryptosporidium spp. and E. histolytica. Sensitivity was 100% for Enterocytozoon bieneusi, but none of the five samples containing Encephalitozoon spp. were detected. Conclusions: The overall performance of the NSP assay in the diagnosis of gastrointestinal protozoa and microsporidia seems to be better than or equivalent to that observed with microscopic methods but inferior to that obtainable with classical targeted qPCR.

Published
2023
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3. Misdiagnosis of imported falciparum malaria from African areas due to an increased prevalence of pfhrp2/pfhrp3 gene deletion: the Djibouti case

Author

Xavier Iriart, Sandie Menard, Pamela Chauvin, Hasna S. Mohamed, Elena Charpentier, Mohamed A. Mohamed, Antoine Berry, and Mohamed H. Aboubaker

Subjects
Plasmodium falciparum, histidine-rich protein 2, deletion, Djibouti, rapid diagnostic test, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

ABSTRACTFollowing the diagnosis of a falciparum malaria case imported from Djibouti and not detected by a pfHRP2-based rapid diagnostic test (RDT), we investigated the prevalence of the pfhrp2/pfhrp3-deleted parasites in Djibouti using 378 blood samples collected between January and May 2019, from Djiboutian patients with suspected malaria. Malaria diagnosis by quantitative PCR confirmed the presence of Plasmodium falciparum for 20.9% (79/378) samples while RDTs did not detect HRP2 antigen in 83.5% (66/79) of these samples. Quantitative PCRs targeting the pfhrp2/pfhrp3 genes confirmed the absence of both genes for 86.5% of P. falciparum strains. The very large number (86.5%) of falciparum parasites lacking the pfhrp2/pfhrp3 genes observed in this study, now justifies the use of non-HRP2 alternative RDTs in Djibouti. In this area and in most countries where HRP2-based RDTs constitute the main arsenal for falciparum malaria diagnosis, it is important to implement a systematic surveillance and to inform biologists and clinicians about the risk of malaria misdiagnosis. Further investigations are needed to better understand the mechanism of selection and diffusion of the pfhrp2/pfhrp3-deleted parasites.

Published
2020
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4. A Clustered Case Series of Mucorales Detection in Respiratory Samples from COVID-19 Patients in Intensive Care, France, August to September 2021

Author

Emilie Guemas, Sophie Cassaing, Sandra Malavaud, Judith Fillaux, Pamela Chauvin, Lucie Lelièvre, Stéphanie Ruiz, Béatrice Riu, Antoine Berry, and Xavier Iriart

Subjects
fungal infection, COVID-19, mucormycosis, aspergillosis, Aspergillus, Mucorales, Biology (General), QH301-705.5
Abstract

While COVID-19-associated pulmonary aspergillosis is now well described in developed countries, COVID-19-associated mucormycosis (CAM) has seemed to remain quite rare in Europe. A retrospective study was performed between March 2020 to September 2021 among COVID-19 adult patients in the intensive care unit (ICU) at Toulouse Hospital (Southern France). PCR screening on respiratory samples, which target Aspergillus or Mucorales DNA, were performed, and the number of fungal detections was evaluated monthly during the study period. During the 19 months of the study, 44 (20.3%) COVID-19 ICU patients had a positive PCR for Aspergillus, an overall rate in keeping with the incidence of ICU COVID-19 patients. Ten patients (7.1%) had a positive Mucorales PCR over the same period. Surprisingly, 9/10 had a positive Mucor/Rhizopus PCR in August-September 2021, during the fourth Delta SARS-CoV-2 variant wave. Epidemic investigations have identified a probable environmental cause linked to construction works in the vicinity of the ICU (high levels of airborne spores due to the mistaken interruption of preventive humidification and summer temperature). Even if CAM are apparently rare in Europe, a cluster can also develop in industrialised countries when environmental conditions (especially during construction work) are associated with a high number of COVID-19 patients in the ICU.

Published
2022
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5. New Insights into Blood Circulating Lymphocytes in Human Pneumocystis Pneumonia

Author

Eléna Charpentier, Catherine Marques, Sandie Ménard, Pamela Chauvin, Emilie Guemas, Claire Cottrel, Sophie Cassaing, Judith Fillaux, Alexis Valentin, Nicolas Blanchard, Antoine Berry, and Xavier Iriart

Subjects
Pneumocystis jirovecii, pneumocystosis, immunophenotyping, lymphocyte, T helper, B lymphocytes, Biology (General), QH301-705.5
Abstract

The host lymphocyte response is decisive in Pneumocystis pneumonia (PCP) pathophysiology but little is known of the specific roles of lymphocyte subpopulations in this fungal infection. Peripheral NK, NKT, B, TCD4+ and TCD8+ subpopulations were compared by immunophenotyping between 20 patients diagnosed with PCP (PCP(+)] and 20 uninfected immunosuppressed patients (PCP(−)). Among PCP(+) subjects, the lymphocyte populations were also compared between surviving and deceased patients. Low B cell count (p = 0.03), while there was no difference for the TCD4 count. Among the PCP(+) group, the 7 deceased patients had lower Th1 (p = 0.02) and Tc1 (p = 0.03) populations, higher Th2 response (p = 0.03), higher effector TCD8 (p < 0.01), lower central memory TCD8 (p = 0.04) and reduced NK cells (p = 0.02) compared with the 13 survivors. Th1/Th2 ratio < 17, CD8 Tc1 < 44%, effector TCD8 < 25%, central memory TCD8 < 4%, NK cells < 50 cells/µL and total lymphocytes < 0.75 G/L were associated with a higher risk of mortality (p = 0.003, p = 0.007, p = 0.0007, p = 0.004, p = 0.02 and p = 0.019, respectively). The traditional analysis of TCD4 and TCD8 populations may be insufficient in the context of PCP. It could be completed by using B cells to predict the risk of PCP, and by using lymphocyte subpopulations or total lymphocyte count, which are easy to obtain in all health care facilities, to evaluate PCP prognosis.

Published
2021
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6. Real-time PCR for diagnosis of imported schistosomiasis.

Author

Hélène Guegan, Judith Fillaux, Eléna Charpentier, Florence Robert-Gangneux, Pamela Chauvin, Emilie Guemas, Jérôme Boissier, Alexis Valentin, Sophie Cassaing, Jean-Pierre Gangneux, Antoine Berry, and Xavier Iriart

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BackgroundThe diagnosis of schistosomiasis currently relies on microscopic detection of schistosome eggs in stool or urine samples and serological assays. The poor sensitivity of standard microscopic procedures performed in routine laboratories, makes molecular detection methods of increasing interest. The aim of the study was to evaluate two in-house real-time Schistosoma PCRs, targeting respectively S. mansoni [Sm] and S. haematobium [Sh] in excreta, biopsies and sera as potential tools to diagnose active infections and to monitor treatment efficacy.MethodsSchistosoma PCRs were performed on 412 samples (124 urine, 86 stools, 8 biopsies, 194 sera) from patients with suspected schistosomiasis, before anti-parasitic treatment. Results were compared to microscopic examination and serological assays (enzyme-linked immunosorbent assay (ELISA), indirect haemagglutination (HA) and Western Blot (WB) assay).ResultsCompared to microscopy, PCRs significantly increased the sensitivity of diagnosis, from 4% to 10.5% and from 33.7% to 48.8%, for Sh in urine and Sm in stools, respectively. The overall sensitivity of PCR on serum samples was 72.7% and reached 94.1% in patients with positive excreta (microscopy). The specificity of serum PCR was 98.9%. After treatment, serum PCR positivity rates slowly declined from 93.8% at day 30 to 8.3% at day 360, whereas antibody detection remained positive after 1 year.ConclusionSchistosoma PCRs clearly outperform standard microscopy on stools and urine and could be part of reference methods combined with WB-based serology, which remains a gold standard for initial diagnosis. When serological assays are positive and microscopy is negative, serum PCRs provide species information to guide further clinical exploration. Biomarkers such as DNA and antibodies are of limited relevance for early treatment monitoring but serum PCR could be useful when performed at least 1 year after treatment to help confirm a cured infection.

Published
2019
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7. Evaluation of the Performance of the Novodiag® Stool Parasites Assay for the Detection of Intestinal Protozoa and Microsporidia

Author

Iriart, Pamela Chauvin, Florie Barba, Emilie Guemas, Eléna Charpentier, Claire Cottrel, Judith Fillaux, Alexis Valentin, Sarah Baklouti, Sophie Cassaing, Sandie Ménard, Antoine Berry, and Xavier

Subjects
stool, protozoa, microsporidia, diagnosis, microscopy, qPCR, Novodiag Stool Parasites, performance
Abstract

Objectives: We aimed to assess the performance of the Novodiag® Stool Parasites (NSP) assay in the diagnosis of the most common intestinal protozoan and microsporidia infections. Methods: A panel of 167 selected stool samples was retrospectively analysed with the NSP assay and compared to routine microscopy and qPCR methods for the detection of pathogenic protozoa and microsporidia. Results: Whereas specificity was high for all protozoa and microsporidia, NSP sensitivity was strongly dependent on the comparative method used as reference. When compared to microscopic methods, NSP sensitivity was high (96.7 to 100%) for Blastocystis hominis, Entamoeba histolytica and Cyclospora cayetanensis but was lower for Giardia intestinalis (85.2%) and ≤50% for Cystoisospora belli and Dientamoeba fragilis. In comparison to conventional qPCR, the NSP assay demonstrated lower sensitivity characteristics dependent on parasite loads, reaching 60 to 70% for G. intestinalis, D. fragilis, Cryptosporidium spp. and E. histolytica. Sensitivity was 100% for Enterocytozoon bieneusi, but none of the five samples containing Encephalitozoon spp. were detected. Conclusions: The overall performance of the NSP assay in the diagnosis of gastrointestinal protozoa and microsporidia seems to be better than or equivalent to that observed with microscopic methods but inferior to that obtainable with classical targeted qPCR.

Published
2023
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8. Misdiagnosis of imported falciparum malaria from African areas due to an increased prevalence of pfhrp2/pfhrp3 gene deletion: the Djibouti case

Author

Mohamed Houmed Aboubaker, Xavier Iriart, Eléna Charpentier, Pamela Chauvin, Antoine Berry, Hasna S. Mohamed, Mohamed Ali Mohamed, and Sandie Menard

Subjects
0301 basic medicine, Letter, Epidemiology, 030106 microbiology, Immunology, Plasmodium falciparum, Protozoan Proteins, Antigens, Protozoan, rapid diagnostic test, Microbiology, Sensitivity and Specificity, 03 medical and health sciences, Virology, Drug Discovery, parasitic diseases, Prevalence, Medicine, Humans, deletion, Diagnostic Errors, Malaria, Falciparum, Rapid diagnostic test, biology, business.industry, Diagnostic Tests, Routine, General Medicine, Gene deletion, biology.organism_classification, medicine.disease, histidine-rich protein 2, 030104 developmental biology, Infectious Diseases, Population Surveillance, Djibouti, Parasitology, business, Malaria, Gene Deletion
Abstract

Following the diagnosis of a falciparum malaria case imported from Djibouti and not detected by a pfHRP2-based rapid diagnostic test (RDT), we investigated the prevalence of the pfhrp2/pfhrp3-deleted parasites in Djibouti using 378 blood samples collected between January and May 2019, from Djiboutian patients with suspected malaria. Malaria diagnosis by quantitative PCR confirmed the presence of Plasmodium falciparum for 20.9% (79/378) samples while RDTs did not detect HRP2 antigen in 83.5% (66/79) of these samples. Quantitative PCRs targeting the pfhrp2/pfhrp3 genes confirmed the absence of both genes for 86.5% of P. falciparum strains. The very large number (86.5%) of falciparum parasites lacking the pfhrp2/pfhrp3 genes observed in this study, now justifies the use of non-HRP2 alternative RDTs in Djibouti. In this area and in most countries where HRP2-based RDTs constitute the main arsenal for falciparum malaria diagnosis, it is important to implement a systematic surveillance and to inform biologists and clinicians about the risk of malaria misdiagnosis. Further investigations are needed to better understand the mechanism of selection and diffusion of the pfhrp2/pfhrp3-deleted parasites.

Published
2020

10. New Insights into Blood Circulating Lymphocytes in Human Pneumocystis Pneumonia

Author

Claire Cottrel, Nicolas Blanchard, Xavier Iriart, Emilie Guemas, Pamela Chauvin, Sophie Cassaing, Alexis Valentin, Judith Fillaux, Antoine Berry, Catherine Marques, Eléna Charpentier, Sandie Menard, Benson-Rumiz, Alicia, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Microbiology (medical), QH301-705.5, Lymphocyte, Context (language use), Plant Science, lymphocyte, Pneumocystis pneumonia, Article, Pneumocystis jirovecii, pneumocystosis, Immunophenotyping, immunophenotyping, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, T helper, medicine, Pneumocystosis, Biology (General), Ecology, Evolution, Behavior and Systematics, B cell, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, biology.organism_classification, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, business, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, B lymphocytes
Abstract

The host lymphocyte response is decisive in Pneumocystis pneumonia (PCP) pathophysiology but little is known of the specific roles of lymphocyte subpopulations in this fungal infection. Peripheral NK, NKT, B, TCD4+ and TCD8+ subpopulations were compared by immunophenotyping between 20 patients diagnosed with PCP (PCP(+)] and 20 uninfected immunosuppressed patients (PCP(−)). Among PCP(+) subjects, the lymphocyte populations were also compared between surviving and deceased patients. Low B cell count (&lt, 40 cells/µL) was more frequent in PCP(+) than in PCP(−) patients (p = 0.03), while there was no difference for the TCD4 count. Among the PCP(+) group, the 7 deceased patients had lower Th1 (p = 0.02) and Tc1 (p = 0.03) populations, higher Th2 response (p = 0.03), higher effector TCD8 (p &lt, 0.01), lower central memory TCD8 (p = 0.04) and reduced NK cells (p = 0.02) compared with the 13 survivors. Th1/Th2 ratio &lt, 17, CD8 Tc1 &lt, 44%, effector TCD8 &lt, 25%, central memory TCD8 &lt, 4%, NK cells &lt, 50 cells/µL and total lymphocytes &lt, 0.75 G/L were associated with a higher risk of mortality (p = 0.003, p = 0.007, p = 0.0007, p = 0.004, p = 0.02 and p = 0.019, respectively). The traditional analysis of TCD4 and TCD8 populations may be insufficient in the context of PCP. It could be completed by using B cells to predict the risk of PCP, and by using lymphocyte subpopulations or total lymphocyte count, which are easy to obtain in all health care facilities, to evaluate PCP prognosis.

Published
2021
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11. Demon Hunters : 1 - The Walher Brothers

Author

Paméla Chauvin and Paméla Chauvin

Abstract

Dans un monde peuplé de créature surnaturelles en tout genre, Fox, descendante d'une famille de Chasseurs cherche à venger le meurtre de ses parents commis sous ses yeux. Elle fait équipe avec deux frères, les réputés Chasseurs Carl et Will Walher, qui ne tarderont pas à l'embarquer dans leur équipe pour retrouver le démon qui l'a rendue orpheline. Enchaînant les Chasses aux monstres à travers les Etats-Unis, ils ne vont pas tarder à se lier d'amitié et créer des liens indéfectibles. Fox parviendra-t-elle à retrouver l'auteur de la mort de ses parents et à mener à bien sa vengeance? Embarquez à bord de la voiture des Chasseurs, pour les suivre dans leurs enquêtes parfois dangereuses, à vos risques et périls.Auteure de nombreux ouvrages, Paméla Chauvin est originaire de Haute-Garonne où elle vit dans une petite ville au milieu des champs, avec ses enfants et son fiancé. Depuis l'âge de douze ans elle imagine des histoires d'univers peuplés de créatures magiques, fantastiques et de romance. Elle a commencé à écrire sur la plateforme Wattpad il y a neuf ans, en se lançant dans des fanfictions, où elle a su se constituer un lectorat. Puis en 2017, elle publie son premier roman'Au bout de mes rêves!', avant d'en publier d'autres via la plateforme Amazon.

Published
2024

12. Performance evaluation of different strategies based on microscopy techniques, rapid diagnostic test and molecular loop-mediated isothermal amplification assay for the diagnosis of imported malaria

Author

Catherine Armengol, Sandie Menard, Antoine Berry, Xavier Iriart, Judith Fillaux, A.-S. Salabert, Arnaud Pagès, H. Guegan, Emilie Guemas, Pamela Chauvin, Eléna Charpentier, E. Benichou, Alexis Valentin, Sophie Cassaing, CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CCSD, Accord Elsevier, and Institut Fédératif de Biologie (IFB) - Hôpital Purpan

Subjects
0301 basic medicine, Plasmodium, Alethia, [SDV]Life Sciences [q-bio], Buffy coat, Rapid diagnostic test, MESH: Africa, MESH: Malaria / diagnosis, Gastroenterology, MESH: Communicable Diseases, Imported / diagnosis, MESH: Nucleic Acid Amplification Techniques / standards, 0302 clinical medicine, Communicable Diseases, Imported, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Diagnosis, MESH: Communicable Diseases, Imported / parasitology, Prospective Studies, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Imported malaria, MESH: Molecular Diagnostic Techniques / methods, Microscopy, Temperature, General Medicine, MESH: Temperature, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Real-time polymerase chain reaction, Molecular Diagnostic Techniques, MESH: Microscopy / methods, France, Nucleic Acid Amplification Techniques, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Loop-mediated isothermal amplification, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, QBC, 03 medical and health sciences, Thin smear, LAMP, Internal medicine, parasitic diseases, medicine, Humans, MESH: Molecular Diagnostic Techniques / standards, MESH: Malaria / parasitology, RDT, MESH: Microscopy / standards, Plasmodium species identification, MESH: Humans, business.industry, MESH: Plasmodium, Thick smear, medicine.disease, MESH: Nucleic Acid Amplification Techniques / methods, MESH: Prospective Studies, MESH: Sensitivity and Specificity, Malaria, MESH: France, MESH: Real-Time Polymerase Chain Reaction / standards, Blood smear, Africa, business
Abstract

Objectives Malaria is one of most common tropical diseases encountered in travellers and migrants. It requires an urgent and reliable diagnosis considering its potential severity. In this study, performance of five diagnostic assays were evaluated in a nonendemic region and compared prospectively to quantitative PCR (qPCR). Methods A prospective study was conducted at Toulouse Hospital from August 2017 to January 2018 and included all patients with initial Plasmodium screening. Thin and thick blood smears (TnS, TkS), quantitative buffy coat (QBC), rapid diagnostic tests (RDTs) and commercial loop-mediated isothermal amplification (LAMP) were independently performed on each blood sample and compared to our qPCR reference standard. Results The study encompassed 331 patients, mainly returning from Africa. qPCR detected 73 Plasmodium-positive samples (including 58 falciparum). Individually, LAMP had a 97.3% (71/73) sensitivity, far ahead of TnS (84.9%, 62/73), TkS (86.3%, 63/73), QBC (86.3%, 63/73) and RDT (86.3%, 63/73). RDT demonstrated a high sensitivity for falciparum (98.3%, 57/58) but missed all ovale, malariae and knowlesi infections. Specificity was excellent for all techniques (99.6–100%). The most sensitive diagnosis strategies were TnS + RDT (95.9%, 70/73), TnS + LAMP (97.3%, 71/73) and TnS + RDT + LAMP (100%, 73/73), about 10% higher than strategies using exclusively microscopy, TkS + TnS (87.7%, 64/73) or QBC + TnS (87.7%, 64/73). TnS remains necessary for Plasmodium species identification and quantification. Adding sequentially TnS only on LAMP-positive samples did not decrease TnS + LAMP strategy sensitivity. Conclusions In nonendemic countries, the currently recommended microscopy-based strategies seem unsatisfactory for malaria diagnosis considering RDT and LAMP performance, two rapid and sensitive assays that require limited training.

Published
2020
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13. Time before anti-Toxoplasma IgG seroconversion detection by 7 commercial assays in French pregnant women

Author

Xavier Iriart, Catherine Armengol, Judith Fillaux, Antoine Berry, Pamela Chauvin, Christine Roques-Malecaze, Sophie Cassaing, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)

Subjects
Adult, 0301 basic medicine, Microbiology (medical), Time Factors, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibodies, Protozoan, Toxoplasma gondii, Immunoblot, 03 medical and health sciences, Pregnancy, medicine, Humans, Pregnancy Complications, Infectious, Immunodiagnosis, Seroconversion, Automation, Laboratory, biology, Diagnostic Tests, Routine, business.industry, General Medicine, medicine.disease, biology.organism_classification, Virology, 3. Good health, Infectious Diseases, Immunoglobulin G, Immunology, Female, France, Reagent Kits, Diagnostic, Automated tests, business, Toxoplasma, Toxoplasmosis
Abstract

International audience; We assessed the ability to early detect a toxoplasmic seroconversion between 1 immunoblot (LDBIO II®) and 6 automated assays (TGS TA®, Architect®, Vidas II®, Liaison II®, Platelia®, and Elecsys®), comparing the time before anti-Toxoplasma gondii IgG detection during infection in pregnant women. From 2007 to 2015, 620 sera of 269 women were included. The median durations before positive IgG detection with Vidas II®, Liaison II®, Platelia®, and Elecsys® were significantly longer than Architect® with differential times from 11 to 28days (P

Published
2017
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14. Optimization of MALDI-ToF mass spectrometry for yeast identification: a multicenter study

Author

Frédéric Gabriel, Elisa Rubio, Marijke Hendrickx, Michiel L. Bexkens, Nathalie Bourgeois, Antoine Huguenin, Deborah De Geyter, Stephane Ranque, Carole Cassagne, Renaud Piarroux, Arnaud Riat, Anne-Cécile Normand, Pamela Chauvin, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Institut d’Histoire des Représentations et des Idées dans les Modernités (IHRIM), Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Clermont Auvergne (UCA)-Université Jean Monnet [Saint-Étienne] (UJM), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Protozooses Transmises par l'Alimentation (Cryptosporidiose, Giardose et Toxoplasmose) : Mode de Contamination et Pathogénie (PROTAL) - EA 3800 (PROTAL), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, CHU Bordeaux [Bordeaux], Geneva University Hospital (HUG), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Universitair Ziekenhus Brussel (UZ Brussel), Erasmus University Rotterdam, Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), Universitat de Barcelona (UB), Sciensano [Bruxelles], Réseau International des Instituts Pasteur (RIIP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Microbiology & Infectious Diseases, Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), Laboratoire Chrono-environnement - CNRS - UFC (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), Basic (bio-) Medical Sciences, Supporting clinical sciences, Experimental Pharmacology, Microbiology and Infection Control, Clinical Biology, and Biology

Subjects
Formic acid, Mycology, Mass spectrometry, Sensitivity and Specificity, 03 medical and health sciences, chemistry.chemical_compound, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Yeasts, MESH: Yeasts / classification, Humans, MESH: Mycology / methods, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, human, Prospective Studies, hospital, MESH: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Chromatography, MESH: Humans, 030306 microbiology, Chemistry, Extraction (chemistry), MALDI-TOF mass spectrometry, General Medicine, MALDI-TOF Mass Spectrometry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Yeast, MESH: Prospective Studies, MESH: Sensitivity and Specificity, Identification (information), Yeast identification, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Multicenter study, Microflex, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, MESH: Yeasts / isolation & purification, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Extraction methods
Abstract

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) is routinely used in mycology laboratories to rapidly identify pathogenic yeasts. Various methods have been proposed to perform routine MS-based identification of clinically relevant species. In this study, we focused on Bruker technology and assessed the identification performance of three protocols: two pretreatment methods (rapid formic acid extraction directly performed on targets and full extraction using formic acid/acetonitrile in tubes) and a direct deposit protocol that omits the extraction step. We also examined identification performance using three target types (ground-steel, polished-steel, and biotargets) and two databases (Bruker and online MSI [biological-mass-spectrometry-identification application]) in a multicenter manner. Ten European centers participated in the study, in which a total of 1511 yeast isolates were analyzed. The 10 centers prospectively performed the three protocols on approximately 150 yeast isolates each, and the corresponding spectra were then assessed against two reference spectra databases (MSI and Bruker), with appropriate thresholds. Three centers evaluated the impact of the targets. Scores were compared between the various combinations, and identification accuracy was assessed. The protocol omitting the extraction step was inappropriate for yeast identification, while the full extraction method yielded far better results. Rapid formic acid extraction yielded variable results depending on the target, database and threshold. Selecting the optimal extraction method in combination with the appropriate target, database and threshold may enable simple and accurate identification of clinically relevant yeast samples. Concerning the widely used polished-steel targets, the full extraction method still ensured better scores and better identification rates.

Published
2019
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15. Real-time PCR for diagnosis of imported schistosomiasis

Author

Sophie Cassaing, Jérôme Boissier, Hélène Guegan, Antoine Berry, Alexis Valentin, Judith Fillaux, Florence Robert-Gangneux, Eléna Charpentier, Jean-Pierre Gangneux, Emilie Guemas, Pamela Chauvin, Xavier Iriart, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Hôtes-Pathogènes-Environnements (IHPE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Perpignan Via Domitia (UPVD), ANR 18 CE35 0001 03, U.S. Department of Defense, 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 ), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Perpignan Via Domitia (UPVD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Perpignan Via Domitia (UPVD), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), ANR-18-CE35-0001,HySWARM,Hybrid Swarm: rôle de l'hybridation dans les capacités invasives, l'épidémiologie et le diagnostic de la schistosomiase(2018), and Modat, Anne

Subjects
0301 basic medicine, Schistosoma Mansoni, Physiology, Biopsy, RC955-962, Artificial Gene Amplification and Extension, Urine, Pathology and Laboratory Medicine, Gastroenterology, Polymerase Chain Reaction, Serology, MESH: DNA, Helminth / analysis, Feces, Schistosomiasis haematobia, MESH: Biopsy, 0302 clinical medicine, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Schistosomiasis, MESH: Animals, MESH: Schistosomiasis haematobia / blood, MESH: Travel, ComputingMilieux_MISCELLANEOUS, Schistosoma haematobium, Travel, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Eukaryota, DNA, Helminth, 6. Clean water, 3. Good health, Body Fluids, Infectious Diseases, Real-time polymerase chain reaction, Helminth Infections, Schistosoma, Schistosoma mansoni, Anatomy, Public aspects of medicine, RA1-1270, MESH: Schistosomiasis mansoni / urine, Research Article, Neglected Tropical Diseases, medicine.medical_specialty, 030231 tropical medicine, Surgical and Invasive Medical Procedures, MESH: Schistosomiasis mansoni / diagnosis, MESH: Schistosoma haematobium / isolation & purification, Real-Time Polymerase Chain Reaction, Research and Analysis Methods, Sensitivity and Specificity, 03 medical and health sciences, Internal medicine, Helminths, parasitic diseases, medicine, Parasitic Diseases, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Animals, Humans, Molecular Biology Techniques, MESH: Real-Time Polymerase Chain Reaction / methods, Molecular Biology, MESH: Humans, MESH: Schistosomiasis haematobia / urine, business.industry, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, Gold standard (test), biology.organism_classification, medicine.disease, Tropical Diseases, Invertebrates, Schistosoma Haematobium, MESH: Schistosomiasis haematobia / diagnosis, Schistosomiasis mansoni, MESH: Sensitivity and Specificity, 030104 developmental biology, MESH: Feces / parasitology, MESH: Schistosomiasis mansoni / blood, business
Abstract

Background The diagnosis of schistosomiasis currently relies on microscopic detection of schistosome eggs in stool or urine samples and serological assays. The poor sensitivity of standard microscopic procedures performed in routine laboratories, makes molecular detection methods of increasing interest. The aim of the study was to evaluate two in-house real-time Schistosoma PCRs, targeting respectively S. mansoni [Sm] and S. haematobium [Sh] in excreta, biopsies and sera as potential tools to diagnose active infections and to monitor treatment efficacy. Methods Schistosoma PCRs were performed on 412 samples (124 urine, 86 stools, 8 biopsies, 194 sera) from patients with suspected schistosomiasis, before anti-parasitic treatment. Results were compared to microscopic examination and serological assays (enzyme-linked immunosorbent assay (ELISA), indirect haemagglutination (HA) and Western Blot (WB) assay). Results Compared to microscopy, PCRs significantly increased the sensitivity of diagnosis, from 4% to 10.5% and from 33.7% to 48.8%, for Sh in urine and Sm in stools, respectively. The overall sensitivity of PCR on serum samples was 72.7% and reached 94.1% in patients with positive excreta (microscopy). The specificity of serum PCR was 98.9%. After treatment, serum PCR positivity rates slowly declined from 93.8% at day 30 to 8.3% at day 360, whereas antibody detection remained positive after 1 year. Conclusion Schistosoma PCRs clearly outperform standard microscopy on stools and urine and could be part of reference methods combined with WB-based serology, which remains a gold standard for initial diagnosis. When serological assays are positive and microscopy is negative, serum PCRs provide species information to guide further clinical exploration. Biomarkers such as DNA and antibodies are of limited relevance for early treatment monitoring but serum PCR could be useful when performed at least 1 year after treatment to help confirm a cured infection., Author summary Schistosomiasis is one of the most important human parasitic neglected tropical diseases. It is a major source of morbidity and mortality in Africa but also in South America, the Caribbean, the Middle East, and Asia. It is transmitted by skin penetration of schistosome cercariae via contact with freshwater. Schistosoma mansoni and S. haematobium are the most common species and are frequent causes of infection in travelers and migrants returning from endemic areas. Chronic infections with these two species can cause irreversible damage to the liver or genitourinary tract. Diagnosis mainly relies on serological screening and microscopic procedures from urine and stool specimens that can, however, fail to detect low parasite burden and depend on operator competence. So there is a need to improve the detection of this disease. With this retrospective study, we evaluate the accuracy of a specific Schistosoma PCR assay for the diagnosis of schistosomiasis on a large cohort of migrants and travelers returning from endemic areas. Our study showed that PCR, a technique allowing Schistosoma DNA amplification and detection, greatly improved the diagnosis of both parasite species in urine, feces and biopsies. We also demonstrate that the detection of circulating Schistosoma DNA in blood by PCR is useful to confirm schistosomiasis diagnosis, to provide a species identification when the microscopy research is negative and to monitor the treatment efficacy.

Published
2019
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16. Performance of seven commercial automated assays for the detection of low levels of anti-Toxoplasma IgG in French immunocompromised patients

Author

Tiphaine Douet, Catherine Armengol, Pamela Chauvin, Judith Fillaux, Antoine Berry, Xavier Iriart, Sophie Cassaing, Eléna Charpentier, Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Comminges Pyrénées (CHCP), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Parasitologie-Mycologie [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Bordeaux [Bordeaux], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées

Subjects
Adult, Male, Veterinary (miscellaneous), [SDV]Life Sciences [q-bio], Toxoplasma gondii, Antibodies, Protozoan, Biology, IgG low level, Sensitivity and Specificity, lcsh:Infectious and parasitic diseases, Serology, 03 medical and health sciences, Immunocompromised Host, Young Adult, medicine, Humans, Mass Screening, lcsh:RC109-216, In patient, Serologic Tests, Immunodiagnosis, Mass screening, 030304 developmental biology, Automation, Laboratory, 0303 health sciences, 030306 microbiology, Middle Aged, medicine.disease, biology.organism_classification, Toxoplasmosis, 3. Good health, Titer, Infectious Diseases, Insect Science, Immunoglobulin G, Immunology, biology.protein, Animal Science and Zoology, Parasitology, Female, Enzyme immunoassays, Automated tests, Reagent Kits, Diagnostic, Antibody, Toxoplasma, Research Article
Abstract

International audience; Background: Immunocompromised patients are at high risk for the development of severe toxoplasmosis from tissue cyst reactivation, the most frequently, or from recently acquired acute infections. Knowledge of serologic status is therefore crucial. Screening for toxoplasmosis is sometimes performed while patients are already immunocompromised and have a low or even undetectable IgG titer by routine automated enzyme immunoassays. The aim of this study was to assess the sensitivity and specificity of seven reagents for the detection of low levels of IgG. Sera from 354 patients were collected and analysed. Results: Elecsys® offered the best analytic performances, superior to those of Architect® and Platelia®, which were superior to those of Access II® and TGS TA®. Vidas II® and Liaison II® reagents exhibited poor analytical performances in this cohort. For Elecsys®, Platelia® and Architect®, new thresholds for the grey zone and positive zone have been defined to improve the sensitivity of these reagents while maintaining excellent specificity. Conclusions: Commercialized assays for toxoplasmosis screening are not suitable for IgG low-level detection in patients without adapting the supplier thresholds to avoid false negative results and risk generalized toxoplasmosis.; Contexte : Les patients immunodéprimés courent un risque élevé de développer une toxoplasmose grave résultant de la réactivation de kystes tissulaires, le plus souvent, ou d’infections aiguës récemment contractées. La connaissance du statut sérologique est donc cruciale. Le dépistage de la toxoplasmose est parfois effectué chez des patients déjà immunodéprimés et dont le titre en IgG est faible, voire indétectable, par les immunoessais enzymatiques automatisés de routine. Le but de cette étude était d’évaluer la sensibilité et la spécificité de sept réactifs pour la détection de faibles taux d’IgG. Les sérums de 354 patients ont été recueillis et analysés. Résultats : Elecsys® offre les meilleures performances analytiques, supérieures à celles d’Architect® et de Platelia®, supérieures à celles d’Access II® et de TGS TA®. Les réactifs Vidas II® et Liaison II® ont présenté des performances analytiques médiocres dans cette cohorte. Pour Elecsys®, Platelia® et Architect®, de nouveaux seuils pour la zone grise et la zone positive ont été définis pour améliorer la sensibilité de ces réactifs tout en maintenant une excellente spécificité. Conclusions : Les tests commercialisés pour le dépistage de la toxoplasmose ne conviennent pas à la détection de faibles taux d’IgG chez les patients sans adaptation des seuils des fournisseurs pour éviter les résultats faux négatifs et le risque de toxoplasmose généralisée.

Published
2019
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17. Prevalence ofPlasmodium falciparumparasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistantpfdhfr/pfdhpsalleles

Author

Antoine Berry, Sandrine E. Nsango, Sandie Menard, Pamela Chauvin, Luc Abate, Majoline T. Tchioffo, Xavier Iriart, Isabelle Morlais, Parfait Awono-Ambene, Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Douala, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire d’Entomologie Médicale, and Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale

Subjects
Adult, Microbiology (medical), Sulfadoxine, medicine.medical_treatment, Plasmodium falciparum, Drug Resistance, Gene mutation, Biology, Antimalarials, Young Adult, Gene Frequency, Pregnancy, parasitic diseases, Prevalence, medicine, Humans, Pharmacology (medical), Cameroon, Malaria, Falciparum, Pregnancy Complications, Infectious, Allele, ComputingMilieux_MISCELLANEOUS, Pharmacology, Dihydropteroate Synthase, Polymorphism, Genetic, Sequence Analysis, DNA, medicine.disease, biology.organism_classification, Virology, Sulfadoxine/pyrimethamine, 3. Good health, Drug Combinations, Tetrahydrofolate Dehydrogenase, Pyrimethamine, Infectious Diseases, Mutation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Dihydropteroate synthase, Malaria, medicine.drug
Abstract

OBJECTIVES To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles. METHODS pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaounde (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP- group (control) (n = 51)] or afterwards [SP+ group (n = 49)] were sequenced. RESULTS The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP- group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P = 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant. CONCLUSIONS Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.

Published
2015
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18. Risk Factors of Pneumocystis Pneumonia in Solid Organ Recipients in the Era of the Common Use of Posttransplantation Prophylaxis

Author

Laurence Lavayssière, O. Roques, Jean-François Magnaval, Sandie Menard, Lionel Rostaing, A. Del Bello, Sophie Cassaing, Olivier Cointault, Antoine Berry, Judith Fillaux, Rose-Anne Lavergne, Isabelle Cardeau-Desangles, Pamela Chauvin, Nassim Kamar, Xavier Iriart, L. Esposito, T. Challan Belval, CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Graft Rejection, Male, Antifungal Agents, [SDV]Life Sciences [q-bio], Cytomegalovirus, Pneumocystis carinii, Pneumocystis pneumonia, Clinical research, Postoperative Complications, Risk Factors, Immunology and Allergy, Pharmacology (medical), Univariate analysis, risk stratification, Pneumonia, Pneumocystis, Graft Survival, risk assessment, Middle Aged, complication: infectious, practice, Tissue Donors, 3. Good health, fungal, Cytomegalovirus Infections, Female, Risk assessment, infection and infectious agents, medicine.medical_specialty, infectious disease, lung, disease: infectious, Immunocompromised Host, Internal medicine, Trimethoprim, Sulfamethoxazole Drug Combination, medicine, Humans, Retrospective Studies, Transplantation, business.industry, Organ Transplantation, Odds ratio, Antibiotic Prophylaxis, medicine.disease, Transplant Recipients, Tacrolimus, Confidence interval, Surgery, Case-Control Studies, business, Follow-Up Studies
Abstract

International audience; Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni- and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim-sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma-globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

Published
2015
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19. Contribution of molecular diagnosis to the management of cutaneous leishmaniasis in travellers

Author

Sandie Menard, Jean-François Magnaval, Sophie Cassaing, Guillaume Martin-Blondel, Alexis Valentin, Judith Fillaux, Rose-Anne Lavergne, Pamela Chauvin, S. Arnaud, Christine Roques-Malecaze, Xavier Iriart, Antoine Berry, Bruno Marchou, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Laboratoire d'Anthropobiologie (LA), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Pagès, Nathalie, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Microbiology (medical), Adolescent, diagnosis, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Direct examination, Leishmaniasis, Cutaneous, Polymerase Chain Reaction, Sensitivity and Specificity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cutaneous leishmaniasis, medicine, Humans, Child, leishmaniasis, Aged, Aged, 80 and over, Leishmania, Travel, 0303 health sciences, biology, cutaneous, 030306 microbiology, business.industry, Leishmaniasis, Sequence Analysis, DNA, sequencing, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Optimal management, 3. Good health, [SDV] Life Sciences [q-bio], PCR, Infectious Diseases, Molecular Diagnostic Techniques, Child, Preschool, Immunology, Female, Identification (biology), business
Abstract

International audience; Cutaneous leishmaniasis is one of the most frequent skin diseases occurring after travelling in endemic areas. Optimal management requires identification of the species of Leishmania involved. In this study we aimed to evaluate the use of molecular diagnosis as routine, in comparison with direct examination and culture. Thirty positive diagnoses were carried out between 2007 and 2013. Classical PCR enabled 11 positive cases to be identified that were found to be negative by conventional methods. Sequencing led to the identification of eight different species. Routine use of PCR and sequencing appears very efficient in the management of cutaneous leishmaniasis.

Published
2014
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20. Concomitant cases of disseminatedGeotrichum clavatuminfections in patients with acute myeloid leukemia

Author

Jean Ruiz, Françoise Huguet, Béatrice Riu-Poulenc, Pamela Chauvin, Alexis Valentin, Laurent Cavalié, Philippe Letocart, Xavier Verdeil, Christian Recher, Caroline Protin, Muriel Picard, Xavier Iriart, Sophie Cassaing, Bruno Marchou, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Male, Acute / complications, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Geotrichosis / drug therapy, Intensive chemotherapy, Neutropenia, Gastroenterology, MESH: Opportunistic Infections / diagnosis, MESH: Leukemia, Myeloid, Acute / complications, 03 medical and health sciences, Fatal Outcome, hemic and lymphatic diseases, Internal medicine, Humans, Medicine, Opportunistic Infections / drug therapy, In patient, Opportunistic Infections / complications, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Acute leukemia, 030306 microbiology, business.industry, MESH: Geotrichosis / drug therapy, MESH: Opportunistic Infections / complications, Myeloid leukemia, Hematology, Middle Aged, medicine.disease, MESH: Geotrichosis / complications, Geotrichum, Opportunistic Infections / diagnosis, 3. Good health, MESH: Geotrichosis / diagnosis, Oncology, Geotrichosis / complications, Leukemia Myeloid, Concomitant, Female, MESH: Opportunistic Infections / drug therapy, Geotrichum clavatum, business, Geotrichosis / diagnosis
Abstract

Patients with acute leukemia receiving intensive chemotherapy encounter deep and prolonged neutropenia, exposing them to life-threatening invasive fungal infections (IFIs). IFIs are frequently caus...

Published
2013
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21. Recherche de seuils d’interprétation de la PCR Pneumocystis sur LBA chez les patients VIH(−), basée sur la mise en évidence de facteurs de risque discriminant la pneumocystose classique des formes pauci ou asymptomatiques

Author

A. Berry, Judith Fillaux, Alexis Valentin, M. Le Bouar, S. Menard, Sophie Cassaing, B. Dubouil, X. Iriart, and Pamela Chauvin

Subjects
0301 basic medicine, 03 medical and health sciences, Infectious Diseases, 030106 microbiology
Abstract

Pneumocystis jirovecii (Pj) est un champignon responsable de la pneumocystose pulmonaire (PCP), pneumopathie interstitielle touchant frequemment les patients immunodeprimes. La PCR specifique de Pj a permis une augmentation considerable de la sensibilite diagnostique en comparaison avec les techniques de microscopie mais a aussi fait emerger le concept de colonisation ou de formes pauci-symptomatiques. La distinction entre ces differentes formes d’infection a Pj est difficile, et influence de maniere importante la mise sous traitement. La PCR quantitative peut permettre d’orienter vers l’une de ces entites en se basant sur la charge fongique mais il est necessaire de valider precisement des seuils quantitatifs discriminants. Dans cette demarche, le principal ecueil est de constituer les 2 groupes de reference « PCP » et « pauci ou asymptomatique ». Si l’on se base sur la methode microscopique de reference (immunofluorescence) pour definir ces groupes, on se heurte au manque de sensibilite de cette technique par rapport a la PCR, qui entraine le classement inadequat des patients atteints de pneumocystose mais presentant une faible charge fongique. D’autre part, lorsque l’on se base sur les criteres cliniques classiquement presents au cours de la PCP pour constituer les groupes « PCP » et « pauci ou asymptomatique », on peut observer des biais de selection, la clinique et le contexte evocateurs etant eux-memes des motivations a la recherche de Pj. A la difference des deux approches precedentes, la methodologie developpee ici est basee sur une etude de facteurs de risque sans a priori, et permet donc de lever ces ecueils. 322 immunodeprimes VIH(−), avec un LBA positif en PCR Pj [1] ont ete inclus. Ils presentaient une distribution homogene des charges fongiques, quel que soit le type d’immunosuppression identifie, permettant une analyse commune de ces patients. Afin de constituer 2 groupes de comparaison dont le statut « PCP » ou « pauci ou asymptomatique » etait tres probable, les patients presentant des charges fongiques extremes (Ct 75eme percentile), ont ete selectionnes puis compares sans a priori sur 85 criteres differents. 9 facteurs de risque cliniques (dyspnee, LLC ou LNH, greffe cardiaque), therapeutiques (corticoides, ciclosporine, rituximab), biologiques (LDH, lymphocytes totaux) et radiologiques (syndrome interstitiel bilateral), ont ete identifies, permettant de differencier les patients pauci ou asymptomatiques des patients atteints de PCP. Un score prenant en compte le poids relatif de chacun de ces facteurs de risque a ete calcule, permettant de classer dans des groupes definitifs « pauci ou asymptomatique » ou « PCP », des patients dont le statut n’avait pu etre determine precedemment. A partir de ces groupes definitifs, un seuil de Ct de PCR a 27,5 a ete etabli (specificite : 98 % ; VPP : 97 %), permettant de classer les patients en « PCP probable » ou « PCP possible », uniquement grâce au resultat de la PCR diagnostique. En conclusion, il est possible d’etablir des seuils de PCR en limitant les biais lies a l’etablissement des groupes « PCP » et « pauci ou asymptomatique », grâce a une demarche basee sur la recherche de facteurs de risque sans a priori pour discriminer les 2 entites.

Published
2016
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22. Mucormycose pulmonaire chez un enfant diabétique

Author

Claire Fougère, Sylvain Blanchon, Sophie Cassaing, Marcel Dahan, Pamela Chauvin, Fabien Gayda, Fanny Lanternier, Isabelle Serres, J Berjaud, Antoine Berry, Olivier Lortholary, Maeva Da Costa, F. Brémont, Judith Fillaux, Audrey Martin-Blondel, Xavier Iriart, and Guillaume Martin-Blondel

Subjects
Infectious Diseases
Abstract

Plusieurs etudes ont mis en evidence que les mucormycoses connaissent une incidence croissante. Leur morbi-mortalite significative est connue chez les adultes mais il existe a ce jour peu de donnees en pediatrie. Ces infections, causees par les champignons filamenteux de l’ordre des mucorales, sont caracterisees par leur tendance a une invasion vasculaire rapide. Des atteintes localisees peuvent rapidement progresser vers les tissus mous, rhinocerebraux, orbitaires, gastro-intestinaux ou pulmonaires. Nous rapportons un cas de mucormycose invasive survenu chez une adolescente de 15 ans atteinte d’un diabete insulinodependant admise aux urgences pediatriques du CHU de Toulouse pour une decompensation acidocetosique accompagnee d’une pneumopathie bilaterale evoquant une infection virale surinfectee. Au 10 e jour, apres une phase d’amelioration et de sortie de reanimation, une infection fongique est evoquee devant une condensation lobaire inferieure gauche, une re-ascension de son syndrome inflammatoire et une aggravation de son etat general en depit d’une antibiotherapie probabiliste menee de facon optimale. L’expectoration induite, au 12 e jour d’hospitalisation, permet de mettre en evidence a l’examen direct des filaments de mucorales, confirmes a j14 sur le LBA et les biopsies bronchiques. Le traitement antifongique par Ambisome ® 7,5 mg/kg est immediatement debute. Les cultures fongiques sont restees steriles. Une PCR ciblant les mucorales (realisee sur les prelevements pulmonaires et le serum) et le sequencage nucleotidique ont permis de confirmer l’espece Rhizopus arrhizus . Compte tenu de la persistance de la positivite de la PCR serique et de l’aggravation endoscopique et tomodensitometrique, il est associe au 11eme jour de traitement du posaconazole et de la Caspofungine. Au 17 e jour une pneumonectomie gauche de sauvegarde est realisee dans des conditions difficiles. Depuis, l’etat de la patiente est en constante amelioration. Les PCRs fongiques se sont negativees tres rapidement apres l’intervention chirurgicale. En conclusion, les techniques moleculaires permettent une amelioration considerable du diagnostic biologique des mucormycoses. Devant la severite de ces infections, bien que rares, elles devraient etre recherchees de facon systematique chez d’adolescent diabetique se presentant pour une symptomatologie infectieuse pulmonaire lors d’une acidocetose afin d’instaurer un traitement optimal precocement.

Published
2017
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23. A complementary tool for management of disseminated Histoplasma capsulatum var. capsulatum infections in AIDS patients

Author

Denis Blanchet, Sophie Cassaing, Jean-François Magnaval, Pamela Chauvin, Rose-Anne Lavergne, Pierre Couppié, Antoine Berry, Sandie Menard, Magalie Demar, Judith Fillaux, Bernard Carme, Marie-Hélène Bessières, Antoine Adenis, Christine Aznar, Xavier Iriart, and Mathieu Nacher

Subjects
Microbiology (medical), Adult, Male, Opportunistic infection, AIDS-Related Opportunistic Infections, Histoplasma, Aspergillosis, Microbiology, Sensitivity and Specificity, Histoplasmosis, Cohort Studies, Mannans, 03 medical and health sciences, Galactomannan, chemistry.chemical_compound, 0302 clinical medicine, Blood serum, Antigen, parasitic diseases, medicine, Humans, 030212 general & internal medicine, Antibodies, Fungal, 0303 health sciences, Acquired Immunodeficiency Syndrome, biology, 030306 microbiology, business.industry, Galactose, General Medicine, Middle Aged, South America, bacterial infections and mycoses, medicine.disease, biology.organism_classification, Virology, 3. Good health, French Guiana, Infectious Diseases, chemistry, Immunology, Female, business
Abstract

In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66-0.92], Sp: 1.00 [95% CI: 0.86-1.00], LR+: >10, LR-: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available.

Published
2013

24. An extraction method of positive blood cultures for direct identification of Candida species by Vitek MS matrix-assisted laser desorption ionization time of flight mass spectrometry

Author

Sophie Cassaing, Christine Roques-Malecaze, Jean-Fran Ç Ois Magnaval, Rose-Anne Lavergne, Sylvie Arnaud, Antoine Berry, Sandie Menard, Pamela Chauvin, Xavier Iriart, Alexis Valentin, Judith Fillaux, CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)

Subjects
Microbiological Techniques, MALDI-TOF, Time Factors, [SDV]Life Sciences [q-bio], Matrix assisted laser desorption ionization time of flight, Mycology, Biology, Mass spectrometry, blood culture, Sensitivity and Specificity, Microbiology, Specimen Handling, 03 medical and health sciences, medicine, Humans, Blood culture, 030304 developmental biology, Candida, 0303 health sciences, medicine.diagnostic_test, 030306 microbiology, Candidemia, General Medicine, 3. Good health, Infectious Diseases, Blood, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Candida spp, extraction, identification, Extraction methods, Subculture (biology), Time-of-flight mass spectrometry, Mixed infection
Abstract

International audience; Candida spp. are an important cause of nosocomial bloodstream infections. Currently, complete identification of yeasts with conventional methods takes several days. We report here the first evaluation of an extraction method associated with the Vitek MS matrix-assisted laser desorption ionization time of flight mass spectrometry for direct identification of Candida species from positive blood cultures. We evaluated this protocol with blood cultures that were inoculated with reference and routine isolates (eight reference strains, 30 patients isolates and six mixed cultures containing two strains of different Candida species), or from patients with candidemia (28 isolates). This method performed extremely well (97% correct identification) with blood cultures of single Candida spp. and significantly reduced the time of diagnosis. Nevertheless, subculture remains indispensable to test fungal resistance and to detect mixed infections.

Published
2013
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25. 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
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