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1. Automatic patient-level recognition of four Plasmodium species on thin blood smear by a real-time detection transformer (RT-DETR) object detection algorithm: a proof-of-concept and evaluation

Author

Emilie Guemas, Baptiste Routier, Théo Ghelfenstein-Ferreira, Camille Cordier, Sophie Hartuis, Bénédicte Marion, Sébastien Bertout, Emmanuelle Varlet-Marie, Damien Costa, and Grégoire Pasquier

Subjects
Plasmodium, artificial intelligence, deep learning, machine learning, object detection, YOLO, Microbiology, QR1-502
Abstract

ABSTRACTMalaria remains a global health problem, with 247 million cases and 619,000 deaths in 2021. Diagnosis of Plasmodium species is important for administering the appropriate treatment. The gold-standard diagnosis for accurate species identification remains the thin blood smear. Nevertheless, this method is time-consuming and requires highly skilled and trained microscopists. To overcome these issues, new diagnostic tools based on deep learning are emerging. This study aimed to evaluate the performances of a real-time detection transformer (RT-DETR) object detection algorithm to discriminate Plasmodium species on thin blood smear images. The algorithm was trained and validated on a data set consisting in 24,720 images from 475 thin blood smears corresponding to 2,002,597 labels. Performances were calculated with a test data set of 4,508 images from 170 smears corresponding to 358,825 labels coming from six French university hospitals. At the patient level, the RT-DETR algorithm exhibited an overall accuracy of 79.4% (135/170) with a recall of 74% (40/54) and 81.9% (95/116) for negative and positive smears, respectively. Among Plasmodium-positive smears, the global accuracy was 82.7% (91/110) with a recall of 90% (38/42), 81.8% (18/22), and 76.1% (35/46) for P. falciparum, P. malariae, and P. ovale/vivax, respectively. The RT-DETR model achieved a World Health Organization (WHO) competence level 2 for species identification. Besides, the RT-DETR algorithm may be run in real-time on low-cost devices such as a smartphone and could be suitable for deployment in low-resource setting areas lacking microscopy experts.IMPORTANCEMalaria remains a global health problem, with 247 million cases and 619,000 deaths in 2021. Diagnosis of Plasmodium species is important for administering the appropriate treatment. The gold-standard diagnosis for accurate species identification remains the thin blood smear. Nevertheless, this method is time-consuming and requires highly skilled and trained microscopists. To overcome these issues, new diagnostic tools based on deep learning are emerging. This study aimed to evaluate the performances of a real-time detection transformer (RT-DETR) object detection algorithm to discriminate Plasmodium species on thin blood smear images. Performances were calculated with a test data set of 4,508 images from 170 smears coming from six French university hospitals. The RT-DETR model achieved a World Health Organization (WHO) competence level 2 for species identification. Besides, the RT-DETR algorithm may be run in real-time on low-cost devices and could be suitable for deployment in low-resource setting areas.

Published
2024
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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. 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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4. 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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5. 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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6. Effect of sulfadoxine-pyrimethamine chemoprophylaxis in pregnant women on selection of the newP. falciparum dhpsquintuple mutant carrying the I431V mutation

Author

Olivia Cohen, Emilie Guemas, Sandie Menard, Martial Tsague Kenfack, Carine Talom Ngassa, Xavier Iriart, Marlise Bidzogo Lebobo, Celestin Ondobo Ekae, Carole Eboumbou, Calvin Tiyou Kenmeni, and Antoine Berry

Subjects
Pharmacology, Microbiology (medical), Infectious Diseases, Pharmacology (medical)
Abstract

BackgroundA new mutation in the Plasmodium falciparum dihydropteroate synthetase gene (pfdhps), I431V, has been identified in several countries of Central and West Africa. This mutation is mostly found in association with four other SNPs on pfdhps (S436A, A437G, A581G and A613S), forming a quintuple mutant (vagKgs) and almost always associated with the Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) CirnI (C50R, N51I, S108N) triple mutant. To date, nothing is known about the impact of this new pfdhps genotype on sulfadoxine-pyrimethamine (SP) resistance.ObjectivesWe sought to assess the prevalence of this pfdhps vagKgs quintuple mutant in two groups of pregnant women with malaria, one that took intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and one that did not.MethodsThe pfdhfr and pfdhps genes from Plasmodium falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria under IPTp-SP or not, were sequenced.ResultsOf 159 patients evaluated, 70 had already taken SP during pregnancy and 89 had never taken SP. Only the vagKgs allele was significantly overrepresented in the SP+ group (21.4% versus 3.4%; P ConclusionsWe found a strong overrepresentation of the CirnI/vagKgs haplotype in the IPTp-SP pregnant group, suggesting a high level of resistance of this mutant to SP. This could compromise not only the effectiveness of IPTp-SP but also the seasonal malaria chemoprevention of young children, now widely implemented.

Published
2023
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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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9. Diagnosis of Congenital Toxoplasmosis: Performance of Four IgG and IgM Automated Assays at Birth in a Tricentric Evaluation

Author

Marine Avignon, Maude F. Lévêque, Emilie Guemas, Milène Sasso, Sahar Albaba, Laurence Lachaud, and Judith Fillaux

Subjects
Microbiology (medical), Immunoglobulin M, Pregnancy, Immunoglobulin G, Pregnancy Complications, Parasitic, Infant, Newborn, Antibodies, Protozoan, Humans, Female, Immunoassays, Toxoplasma, Toxoplasmosis, Toxoplasmosis, Congenital
Abstract

For postnatal diagnosis of congenital toxoplasmosis (CT), the gold standard for the detection of anti-Toxoplasma IgM in newborns relies on the immunosorbent agglutination assay (ISAGA), which is manufactured from whole Toxoplasma parasites that become difficult to maintain. For IgG, only the Platelia assay provides a validated assay for cord blood according to the manufacturer, allowing its use in this context. We compared the analytical performance of four commercialized automated assays, Platelia, Abbott, Vidas, and Liaison, for the detection of IgG and IgM in the cord blood or peripheral blood of newborns from women infected during pregnancy. The assays were performed on samples from 509 newborns, collected from the university hospitals of Montpellier, Nîmes, and Toulouse. For IgM, the four assays appeared to be sufficiently informative to be used for congenital toxoplasmosis diagnosis (area under the curve [AUC] > 0.8, receiver operating characteristic [ROC] analysis), with Platelia showing the best performance, similar to ISAGA with regard to accuracy (83%). For the Vidas (76%), Abbott (75%), and Liaison (74%) assays, the accuracy was significantly lower. Maternal treatment significantly decreased the sensitivity of all the assays. For IgG, the four evaluated assays showed a sensitivity of over 90%, with Abbott (95%) and Liaison (94%), exhibiting a significantly higher sensitivity than Platelia (90%). Furthermore, Abbott showed its superiority in the cases of maternal infection during the third trimester. In the context of the newborns of mothers infected by Toxoplasma gondii during pregnancy, to ensure efficient care, Platelia and Abbott seemed to be the most suitable reference tests for the detection of IgM for the former and IgG for the latter.

Published
2022
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11. 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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12. [Abstracts of the 4th CoBioMe Congress]

Author

Soraya Sakhi, Magalie Lodin, Marie-Liesse Étienne, Khadija Ouaziz, Mathilde Filser, Amandine François, Amandine Caillault, Lamia Rouabah, Zoé Guilbert, Margaux Cadenet, Morgane Ducastel, Mathilda Bastide, Emilie Guemas, Julie Brousseau, Mathilde Puel, Pierre Jatteau, Bérénice Schell, and Mathilde Roche

Subjects
World Wide Web, Engineering, Text mining, business.industry, General Medicine, business
Published
2021

13. Histoplasma capsulatum and Histoplasmosis: Current Concept for the Diagnosis

Author

Magalie Demar, Loïc Sobanska, and Emilie Guemas

Subjects
biology, business.industry, InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL, Data_FILES, medicine, Current (fluid), medicine.disease, biology.organism_classification, business, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Histoplasma capsulatum, Virology, Histoplasmosis
Published
2020
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14. 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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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. Serotonin syndrome, rhabdomyolysis and convulsion associated with drug interaction between venlafaxine and amoxicillin/clavulanic acid

Author

Anxo, Fernández-Ferreiro, Antonio, Pose-Reino, Francisco, Martinez-Bahamonde, Marion, Paris, Emilie, Guemas, Miguel, González-Barcia, and M J, Lamas

Subjects
Serotonin Syndrome, Seizures, Venlafaxine Hydrochloride, Humans, Drug Interactions, Female, Serotonin and Noradrenaline Reuptake Inhibitors, Amoxicillin-Potassium Clavulanate Combination, beta-Lactamase Inhibitors, Rhabdomyolysis, Aged
Published
2016

17. PS-004 Analysis of the use of psychotropic drugs and pharmacological interactions in spanish chronic psychiatric patients

Author

A Fernández-Ferreiro, Emilie Guemas, F Martinez-Bahamonde, N Pazos-Simon, E Echarri-Arrieta, Marion Paris, Miguel González-Barcia, María Jesús Lamas, A Lopez-Lopez, and P Suarez-Artime

Subjects
Fluphenazine, Olanzapine, medicine.medical_specialty, Risperidone, business.industry, medicine.drug_class, medicine.medical_treatment, Typical antipsychotic, Medicine, Psychiatric hospital, Quetiapine, Paliperidone, General Pharmacology, Toxicology and Pharmaceutics, business, Antipsychotic, Psychiatry, medicine.drug
Abstract

Background Side effects produced by drugs are an emergent problem in developed countries, with major consequences for health assistance and economy. Polymedication produces important interactions which sometimes have relevant clinical repercussions. Purpose The aim of this present study was to describe the current use of antipsychotic drugs in chronic patients in a psychiatric hospital and the potential risk of producing drug interactions (DI). Material and methods This was a descriptive cross sectional study analysing psychopharmacological therapeutics in patients admitted to a psychiatric hospital of 300 beds. For each patient, we obtained the following data: psychiatric disease, gender and age. Concerning pharmacotherapy, we obtained the following information: total number of drugs and type of oral or depot injection of antipsychotic medicines. Afterwards the major DI were listed using Micromedex Solutions. Results Among 300 hospitalised patients who were studied, the majority were men (62%) with a median age of 49 ± 13 years; median age of women was 56 ± 16 years. The psychiatric diseases most frequently encountered were paranoid schizophrenia (34%) and undifferentiated schizophrenia (10%). 72% of patients were receiving more than 5 different medicines and the most prescribed being psychoactive drugs (62%). 94% of patients took antipsychotics, and among them, 27% as monotherapy. The average number of prescriptions of antipsychotic drugs per patient was 2.15, the most used being the atypical (70%) with olanzapine (20%), quetiapine (17%) and clozapine (13%). For typical antipsychotic drugs, we can highlight the use of levomepronazine (13%) and haloperidol (12%). 32% of patients (n = 95) were treated by depot injection of antipsychotic and the most frequently used were fluphenazine (34%), paliperidone (29%) and risperidone (28%). 68% of patients presented at least one major DI which increased the risk of developing side effects, with an average of 2 interactions per patient. The possible consequences of those DI were mostly increasing risk of a prolonged QT interval (59.4%) and an increasing risk of cardiac-respiratory arrest (8.3%). Conclusion Psychiatric patients receive a high number of medicines which interact, increasing the risk of occurrence of serious side effects. Detection of DI and therapy optimisation would reduce the risks associated with medication. No conflict of interest.

Published
2016
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18. 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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