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1. Cutaneous leishmaniasis in sub-Saharan Africa: a systematic review of Leishmania species, vectors and reservoirs

Author: Romain Blaizot, Gregoire Pasquier, Abdoulaye Kassoum Kone, Alexandre Duvignaud, and Magalie Demar
Subjects: Cutaneous leishmaniasis, Sub-Saharan Africa, Review, One Health, Vectors, Reservoirs, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Cutaneous leishmaniasis (CL) is understudied in sub-Saharan Africa. The epidemiology of CL is determined by the species involved in its transmission. Our objectives were to systematically review available data on the species of Leishmania, along with vectors and reservoirs involved in the occurrence of human cases of CL in sub-Saharan Africa, and to discuss implications for case management and future research. Methods We systematically searched PubMed, Scopus, Cochrane and African Index Medicus. There was no restriction on language or date of publication. The review was conducted according to PRISMA guidelines and was registered on PROSPERO (CRD42022384157). Results In total, 188 published studies and 37 reports from the grey literature were included. An upward trend was observed, with 45.7% of studies published after 2010. East Africa (55.1%) represented a much greater number of publications than West Africa (33.3%). In East Africa, the identification of reservoirs for Leishmania tropica remains unclear. This species also represents a therapeutic challenge, as it is often resistant to meglumine antimoniate. In Sudan, the presence of hybrids between Leishmania donovani and strictly cutaneous species could lead to important epidemiological changes. In Ghana, the emergence of CL in the recent past could involve rare species belonging to the Leishmania subgenus Mundinia. The area of transmission of Leishmania major could expand beyond the Sahelian zone, with scattered reports in forested areas. While the L. major–Phlebotomus duboscqi–rodent complex may not be the only cycle in the dry areas of West Africa, the role of dogs as a potential reservoir for Leishmania species with cutaneous tropism in this subregion should be clarified. Meglumine antimoniate was the most frequently reported treatment, but physical methods and systemic agents such as ketoconazole and metronidazole were also used empirically to treat L. major infections. Conclusions Though the number of studies on the topic has increased recently, there is an important need for intersectional research to further decipher the Leishmania species involved in human cases of CL as well as the corresponding vectors and reservoirs, and environmental factors that impact transmission dynamics. The development of molecular biology in sub-Saharan Africa could help in leveraging diagnostic and research capacities and improving the management of human cases through personalized treatment strategies. Graphical Abstract
Published: 2024
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2. Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease

Author: Geoffrey Garcia, Sylvie Labrouche-Colomer, Alexandre Duvignaud, Etienne Clequin, Charles Dussiau, David-Alexandre Trégouët, Denis Malvy, Renaud Prevel, Atika Zouine, Isabelle Pellegrin, Julien Goret, Maria Mamani-Matsuda, Antoine Dewitte, and Chloe James
Subjects: Medicine
Abstract: Abstract Background Thrombo-inflammation and neutrophil extracellular traps (NETs) are exacerbated in severe cases of COVID-19, potentially contributing to disease exacerbation. However, the mechanisms underpinning this dysregulation remain elusive. We hypothesised that lower DNase activity may be associated with higher NETosis and clinical worsening in patients with COVID-19. Methods Biological samples were obtained from hospitalized patients (15 severe, 37 critical at sampling) and 93 non-severe ambulatory cases. Our aims were to compare NET biomarkers, functional DNase levels, and explore mechanisms driving any imbalance concerning disease severity. Results Functional DNase levels were diminished in the most severe patients, paralleling an imbalance between NET markers and DNase activity. DNase1 antigen levels were higher in ambulatory cases but lower in severe patients. DNase1L3 antigen levels remained consistent across subgroups, not rising alongside NET markers. DNASE1 polymorphisms correlated with reduced DNase1 antigen levels. Moreover, a quantitative deficiency in plasmacytoid dendritic cells (pDCs), which primarily express DNase1L3, was observed in critical patients. Analysis of public single-cell RNAseq data revealed reduced DNase1L3 expression in pDCs from severe COVID-19 patient. Conclusion Severe and critical COVID-19 cases exhibited an imbalance between NET and DNase functional activity and quantity. Early identification of NETosis imbalance could guide targeted therapies against thrombo-inflammation in COVID-19-related sepsis, such as DNase administration, to avert clinical deterioration. Trial registration: COVERAGE trial (NCT04356495) and COLCOV19-BX study (NCT04332016). Graphical Abstract
Published: 2024
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3. Implementing an outpatient clinical trial on COVID-19 treatment in an emergency epidemic context: a mixed methods study among operational and research stakeholders within the Coverage trial, Bordeaux (France)

Author: Carine Grenier, Macha Loniewski, Mélanie Plazy, Racha Onaisi, Marie-Hélène Doucet, Jean-Philippe Joseph, Alexandre Duvignaud, Denis Malvy, Xavier Anglaret, Joanna Orne-Gliemann, and the Coverage study group
Subjects: Covid, Treatment, Ambulatory, Perceptions, Implementation, Public aspects of medicine, RA1-1270
Abstract: Abstract Background The emergency set-up and implementation of outpatient clinical trials on epidemic emerging infectious diseases such as COVID-19 raise many issues in terms of research structuration, regulations, and health systems organization. We aimed to describe the experience and points of view of different stakeholders involved in a French home-based outpatient trial on COVID-19 and to identify the early barriers and facilitators to the trial implementation. Methods We conducted a mixed-methods study in July 2020. A self-administered questionnaire was emailed to 213 clinical, operational and research stakeholders involved in the Coverage trial; individual semi-directed interviews were conducted among 14 stakeholders. Questionnaire data and written interview notes are presented together by key theme. Results One hundred fifty six stakeholders responded to the questionnaire. 53.4% did not have prior experience in clinical research. The motivation of most stakeholders to participate in the Coverage trial was to feel useful during the pandemic. 87.9% agreed that the trial had an unusual set-up timeframe, and many regretted a certain lack of regulatory flexibility. Mobile medical teams and specific professional skills were perceived as instrumental for outpatient research. Conclusions The implementation of a home-based outpatient clinical trial on COVID-19 was perceived as relevant and innovative although requiring important adaptations of usual professional responsibilities and standard research procedures. Lessons learned from the Coverage trial underline the need for improved networks between hospital and community medicine, and call for a dedicated and reactive outpatient research platform on emerging or threatening infectious diseases.
Published: 2022
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4. Self-application of aminoglycoside-based creams to treat cutaneous leishmaniasis in travelers.

Author: Oussama Mouri, Cléa Melenotte, Romain Guéry, Camille Cotteret, Arnaud Schweitzer-Chaput, Alice Perignon, Marc Thellier, Emmanuelle Bourrat, Florentia Kaguelidou, Jean Yves Siriez, Denis Malvy, Jean-Pierre Gangneux, Alexandre Duvignaud, Christophe Ravel, Salvatore Cisternino, Janet Ransom, Eric Caumes, Olivier Lortholary, Max Grogl, and Pierre Buffet
Subjects: Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract: BackgroundIn endemic foci, the use of an aquaphilic cream containing paromomycin with/without gentamicin to treat cutaneous leishmaniasis (CL) is safe, painless and cures 78-82% of patients with New and Old World CL. Self-application in travelers requires evaluation.MethodsTravelers with 1-10 lesions of confirmed CL were prospectively treated with the paromomycin-gentamicin formulation (WR279396, 2012-2017, Group 1) and carefully follow up, or treated with a locally produced paromomycin-only cream (2018-2022, Group 2). The cream was applied once under supervision, then self-applied daily for 20-30 days. A cured lesion was defined as 100% re-epithelialization at day 42 without relapse at three months.ResultsMedical features were similar in Group 1 (17 patients), and Group 2 (23 patients). Patients were infected with either Leishmania major, L. infantum, L. killicki, L. guyanensis, L. braziliensis, or L. naiffi. Intention-to-treat and per-protocol cure rates were 82% (95% confidence interval (CI) [64.23;100.00]) and 87% (95% CI [71,29;100.00]) in Group 1, and 69% (95% CI [50.76; 88.37]) and 76% (95% CI [57.97; 94.41]) in Group 2. In the pooled Group 1&2, 75% (95% CI [61.58;88.42]) (30/40) and 81% (95% CI [68,46;93.6]) (30/37) of patients were cured in intention-to-treat and per-protocol, respectively. There were no significant differences observed in the success rates between Old World and New World CL (83.3% vs. 60%, p = 0.14). Prospective observations in Group 1 showed that adverse events were mainly pruritus (24%) and pain (18%) on lesions (all mild or moderate). No mucosal involvement was observed in either group.DiscussionIn this representative population of travelers who acquired CL either in the Old or New World, the 81% per-protocol cure rate of a self-applied aminoglycoside cream was similar to that observed in clinical trials.
Published: 2023
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5. Can haematological changes constitute a surrogate diagnostic parameter to detect schistosomiasis in migrants and travellers? - A retrospective analysis

Author: Jenny L. Schnyder, Federico Gobbi, Mirjam Schunk, Andreas Lindner, Fernando Salvador, Alexandre Duvignaud, Marta Arsuaga Vicente, Jean Claude Dejon Agobé, Paolo Cattaneo, Giulia Bertoli, Camilla Rothe, Mia Wintel, Diana Pou, Denis Malvy, Ayola Akim Adegnika, Hanna K. De Jong, and Martin P. Grobusch
Subjects: Schistosomiasis, Haematology, Full blood count, Returned travellers, Travel, Migrants, Infectious and parasitic diseases, RC109-216
Abstract: Background: Earlier studies found characteristic haematological changes in African patients with active schistosomiasis. If consistently present, full blood counts (FBC) may be helpful to diagnose schistosomiasis also in migrants and returning travellers. Methods: A retrospective patient record review was conducted on data from seven European travel clinics, comparing FBC of Schistosoma egg-positive travellers and migrants to reference values. Sub-analyses were performed for children, returned travellers, migrants and different Schistosoma species. Results: Data analysis included 382 subjects (median age 21.0 years [range 2–73]). In returned travellers, decreases in means of haemoglobin particularly in females (β = −0.82 g/dL, p = 0.005), MCV (β = −1.6 fL, p = 0.009), basophils, neutrophils, lymphocytes and monocytes (β = −0.07, p
Published: 2023
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6. Pulmonary tuberculosis and management of contact patients in a Department of Nephrology and Kidney Transplantation

Author: Laure Burguet, Alexandre Duvignaud, Duc Nguyen, Marie-Catherine Receveur, Hannah Kaminski, Isabelle Pellegrin, Anne-Marie Rogues, Olivia Peuchant, Karine Moreau, Pierre Merville, and Lionel Couzi
Subjects: Contacts, Tuberculosis, Interferon gamma release assay, Therapy, Prophylaxis, Infectious and parasitic diseases, RC109-216
Abstract: Objectives: To describe the investigation, follow-up, management, and outcomes in a cohort of chronic kidney disease (CKD) and kidney transplant recipients (KTR) exposed to a case of pulmonary tuberculosis (TB). Methods: Contacts were investigated following a concentric circles approach and followed-up according to their level of priority. In those with evidence of latent TB infection, treatment decision was based on the level of exposure, individual vulnerability, as well as the results of an interferon-gamma release assay. Results: A total of 130 patients with CKD and 180 KTR were identified as contacts and followed-up over a 2-year period. Few vulnerable high-priority contacts received anti-TB treatment, including the two (100%) highly exposed patients in circle 1, 11/78 (14.1%) CKD patients and 4/142 (2.8%) KTR in circle 2, and 10/52 (19.2%) CKD patients and 2/36 (5.6%) KTR in circle 3; all had a positive interferon-gamma release assay result. No incident cases of TB disease occurred. Conclusions: These findings suggest that latent TB treatment, as recommended in European guidelines, might be reasonably avoided in vulnerable high-priority contacts of circle 2, with a negative interferon-gamma release assay and in countries with low prevalence of TB.
Published: 2022
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7. Renin‐Angiotensin System Inhibitors in Patients With COVID‐19: A Meta‐Analysis of Randomized Controlled Trials Led by the International Society of Hypertension

Author: Sonali R. Gnanenthiran, Claudio Borghi, Dylan Burger, Bruno Caramelli, Fadi Charchar, Julio A. Chirinos, Jordana B. Cohen, Antoine Cremer, Gian Luca Di Tanna, Alexandre Duvignaud, Daniel Freilich, D. H. Frank Gommans, Abraham E. Gracia‐Ramos, Thomas A. Murray, Facundo Pelorosso, Neil R. Poulter, Michael A. Puskarich, Konstantinos D. Rizas, Rodolfo Rothlin, Markus P. Schlaich, Michael Schreinlecher, Ulrike Muscha Steckelings, Abhinav Sharma, George S. Stergiou, Christopher J. Tignanelli, Maciej Tomaszewski, Thomas Unger, Roland R. J. van Kimmenade, Richard D. Wainford, Bryan Williams, Anthony Rodgers, and Aletta E. Schutte
Subjects: acute kidney injury, angiotensin II receptor blockers, angiotensin‐converting enzyme inhibitors, COVID‐19, hypertension, renin‐angiotensin system inhibitors, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin‐angiotensin system inhibitors (RASi) in adults with COVID‐19. We therefore performed a meta‐analysis to assess the safety and efficacy of RASi in adults with COVID‐19. Methods and Results MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID‐19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all‐cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow‐up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all‐cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID‐19 severity or trial type. Network meta‐analysis identified no difference between angiotensin‐converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05–3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. Conclusions This meta‐analysis of randomized controlled trials evaluating angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID‐19 found no difference in all‐cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID‐19.
Published: 2022
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8. Ribavirin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing.

Author: Alex P Salam, Alexandre Duvignaud, Marie Jaspard, Denis Malvy, Miles Carroll, Joel Tarning, Piero L Olliaro, and Peter W Horby
Subjects: Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract: Ribavirin is currently the standard of care for treating Lassa fever. However, the human clinical trial data supporting its use suffer from several serious flaws that render the results and conclusions unreliable. We performed a systematic review of available pre-clinical data and human pharmacokinetic data on ribavirin in Lassa. In in-vitro studies, the EC50 of ribavirin ranged from 0.6 μg/ml to 21.72 μg/ml and the EC90 ranged from 1.5 μg/ml to 29 μg/ml. The mean EC50 was 7 μg/ml and the mean EC90 was 15 μg/ml. Human PK data in patients with Lassa fever was sparse and did not allow for estimation of concentration profiles or pharmacokinetic parameters. Pharmacokinetic modelling based on healthy human data suggests that the concentration profiles of current ribavirin regimes only exceed the mean EC50 for less than 20% of the time and the mean EC90 for less than 10% of the time, raising the possibility that the current ribavirin regimens in clinical use are unlikely to reliably achieve serum concentrations required to inhibit Lassa virus replication. The results of this review highlight serious issues with the evidence, which, by today standards, would be unlikely to support the transition of ribavirin from pre-clinical studies to human clinical trials. Additional pre-clinical studies are needed before embarking on expensive and challenging clinical trials of ribavirin in Lassa fever.
Published: 2022
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9. Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection (COVID-19): A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatients aged 65 years or older (COVERAGE trial)

Author: Alexandre Duvignaud, Edouard Lhomme, Thierry Pistone, Racha Onaisi, Rémi Sitta, Valérie Journot, Duc Nguyen, Nathan Peiffer-Smadja, Antoine Crémer, Stéphane Bouchet, Thomas Darnaud, Delphine Poitrenaud, Lionel Piroth, Christine Binquet, Jean-François Michel, Benjamin Lefèvre, David Lebeaux, Josselin Lebel, Julie Dupouy, Caroline Roussillon, Anne Gimbert, Linda Wittkop, Rodolphe Thiébaut, Joanna Orne-Gliemann, Jean-Philippe Joseph, Laura Richert, Xavier Anglaret, Denis Malvy, and the COVERAGE study group
Subjects: Medicine (General), R5-920
Abstract: Abstract Objectives To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. Trial design Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. Participants Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate 5.5 mmol/L or
Published: 2020
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10. Research on COVID-19 therapy: Putting the cart alongside the horse

Author: Alexandre Duvignaud, MD, PhD and Xavier Anglaret, MD, PhD
Subjects: Medicine, Medicine (General), R5-920
Published: 2021
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11. Early complicated schistosomiasis in a returning traveller: Key contribution of new molecular diagnostic methods

Author: Simon Bonnefond, Lieselotte Cnops, Alexandre Duvignaud, Emmanuel Bottieau, Thierry Pistone, Jan Clerinx, and Denis Malvy
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Early schistosomiasis poses a serious diagnostic challenge, because current standard diagnostic techniques based on serology and egg microscopy lack sensitivity at the initial presentation. We report spinal cord neuroschistosomiasis in a traveller developing 6 weeks after exposure. The diagnosis was confirmed by Schistosoma mansoni-targeted real-time PCR in blood and cerebrospinal fluid, before the results of conventional methods became positive. Molecular assays represent a paradigm shift for the difficult diagnosis of early schistosomiasis and related complications. Keywords: Early schistosomiasis, Neuroschistosomiasis, PCR, Traveller
Published: 2019
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12. Impact of the Ebola outbreak on Trypanosoma brucei gambiense infection medical activities in coastal Guinea, 2014-2015: A retrospective analysis from the Guinean national Human African Trypanosomiasis control program.

Author: Mariame Camara, Eric Ouattara, Alexandre Duvignaud, René Migliani, Oumou Camara, Mamadou Leno, Philippe Solano, Bruno Bucheton, Mamadou Camara, and Denis Malvy
Subjects: Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract: BackgroundThe 2014-2015 Ebola outbreak massively hit Guinea. The coastal districts of Boffa, Dubreka and Forecariah, three major foci of Human African Trypanosomiasis (HAT), were particularly affected. We aimed to assess the impact of this epidemic on sleeping sickness screening and caring activities.Methodology/principal findingsWe used preexisting data from the Guinean sleeping sickness control program, collected between 2012 and 2015. We described monthly: the number of persons (i) screened actively; (ii) or passively; (iii) treated for HAT; (iv) attending post-treatment follow-up visits. We compared clinical data, treatment characteristics and Disability Adjusted Life-Years (DALYs) before (February 2012 to December 2013) and during (January 2014 to October 2015) the Ebola outbreak period according to available data. Whereas 32,221 persons were actively screened from February 2012 to December 2013, before the official declaration of the first Ebola case in Guinea, no active screening campaigns could be performed during the Ebola outbreak. Following the reinforcement and extension of HAT passive surveillance system early in 2014, the number of persons tested passively by month increased from 7 to 286 between April and September 2014 and then abruptly decreased to 180 until January 2015 and to none after March 2015. 213 patients initiated HAT treatment, 154 (72%) before Ebola and 59 (28%) during the Ebola outbreak. Those initiating HAT therapy during Ebola outbreak were recruited through passive screening and diagnosed at a later stage 2 of the disease (96% vs. 55% before Ebola, pConclusions/significanceThe 2014-2015 Ebola outbreak deeply impacted HAT screening activities in Guinea. Active screening campaigns were stopped. Passive screening dramatically decreased during the Ebola period, but trends could not be compared with pre-Ebola period (data not available). Few patients were diagnosed with more advanced HAT during the Ebola period and retention rates in follow-up were lowered. The drop in newly diagnosed HAT cases during Ebola epidemic is unlikely due to a fall in HAT incidence. Even if we were unable to demonstrate it directly, it is much more probably the consequence of hampered screening activities and of the fear of the population on subsequent confirmation and linkage to care. Reinforced program monitoring, alternative control strategies and sustainable financial and human resources allocation are mandatory during post Ebola period to reduce HAT burden in Guinea.
Published: 2017
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13. Cervical spondylitis and spinal abscess due to Actinomyces meyeri

Author: Alexandre Duvignaud, Emmanuel Ribeiro, Daniel Moynet, Maïté Longy-Boursier, and Denis Malvy
Subjects: Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract: Human actinomycosis with involvement of the spine is a rare condition although it has been first described a long time ago. It is probably underrecognized since its clinical presentation is often misleading and accurate bacteriological diagnosis is challenging. We herein report a rare case of cervical actinomycosis with paravertebral abscess and spondylitis imputed to an infection by Actinomyces meyeri in a 52-year-old immunocompetent Caucasian man. A. meyeri should be considered as a potential cause for subacute or chronic spondylitis, even in immunocompetent subjects. Modern diagnostic tools such as Matrix-Assisted Laser Desorption–Ionization Time of Flight mass spectrometry and 16S rRNA sequencing are efficient for accurate microbiological identification. Keywords: Actinomyces, Spondylitis, MALDI–TOF mass spectrometry, 16S rRNA
Published: 2014
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14. Strongyloidiasis in a young French woman raises concern about possible ongoing autochthonous transmission in Spain

Author: Alexandre Duvignaud, Thierry Pistone, and Denis Malvy
Subjects: Strongyloidiasis, Spain, Eosinophilia, Infectious and parasitic diseases, RC109-216
Abstract: Strongyloidiasis is one of the most common geohelminth infections in tropical and subtropical areas. Accurate diagnosis remains challenging, leading to an overall underestimation of strongyloidiasis prevalence. The possibility of ongoing autochthonous transmission in some temperate areas and especially in southern Europe is still debated, and data supporting this hypothesis are scarce. The case of a young French woman, who had travelled frequently to Spain and had acquired Strongyloides stercoralis infection as revealed by gastrointestinal symptoms and hypereosinophilia, is reported here. Physicians should keep in mind the risk of being infected in some areas of southern Europe, even if low, in order to avoid the life-threatening manifestations of strongyloidiasis favoured by pathological or therapeutic immunosuppression.
Published: 2016
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15. Sotrovimab therapy elicits antiviral activities against Omicron BQ.1.1 and XBB.1.5 in sera of immunocompromised patients

Author: Bruel, Timothée, primary, Vrignaud, Lou-Léna, additional, Porrot, Françoise, additional, Staropoli, Isabelle, additional, Planas, Delphine, additional, Guivel-Benhassine, Florence, additional, Puech, Julien, additional, Prot, Matthieu, additional, Munier, Sandie, additional, Bolland, William Henry, additional, Soulié, Cathia, additional, Zafilaza, Karen, additional, Lusivika-Nzinga, Clovis, additional, Meledge, Marie-Laure, additional, Dorival, Céline, additional, Molino, Diana, additional, Péré, Hélène, additional, Yordanov, Youri, additional, Simon-Lorière, Etienne, additional, Veyer, David, additional, Carrat, Fabrice, additional, Schwartz, Olivier, additional, Marcelin, Anne-Geneviève, additional, Martin-Blondel, Guillaume, additional, Garcia, Magalie, additional, Giraud, Valentin, additional, Metais, Agathe, additional, Cazenave-Roblot, Fance, additional, Martellosio Anne-Marie Ronchetti, Jean-Philippe, additional, Gabas, Thomas, additional, Hadjadj, Naima, additional, Salanoubat, Célia, additional, Chabrol, Amélie, additional, Housset, Pierre, additional, Pardon, Agathe, additional, Faucon, Anne-Laure, additional, Caudwell, Valérie, additional, Roland Liblau, Latifa Hanafi, additional, Alric, Laurent, additional, Pugnet, Grégory, additional, Mourguet, Morgane, additional, Bories, Eva, additional, Bonnet, Delphine, additional, Charpentier, Sandrine, additional, Delobel, Pierre, additional, Debard, Alexa, additional, Beck, Colleen, additional, Boumaza, Xavier, additional, Fanny Lanternier, Stella Rousset, additional, Delage, Claire, additional, Pires, Elisabete Gomes, additional, Cheminant, Morgane, additional, Anthony Chauvin, Nathalie Chavarot, additional, Véronique Delcey Simon Bessis, Xavier Eyer, additional, Cresta, Mélanie, additional, Pélagie Thibaut, Romain Gueneau, additional, Nadal, Marine, additional, Siguier, Martin, additional, Bachir, Marwa, additional, Valérie Pourcher, Christia Palacios, additional, Melenotte, Cléa, additional, Faycal, Antoine, additional, Berot, Vincent, additional, Brin, Cécile, additional, Djebara, Siham, additional, Marot, Stéphane, additional, Sayon, Sophie, additional, Leducq, Vincent, additional, Malet, Isabelle, additional, Teyssou, Elisa, additional, Karine Lacombe, Adélie Gothland, additional, Aad, Yasmine Abi, additional, Chiarabini, Thibault, additional, Feliho, Raynald, additional, Valin, Nadia, additional, Brigant, Fabien, additional, Boize, Julien, additional, Thiébaud, Pierre-Clément, additional, Moreau, Marie, additional, Nathalie De Castro, Charlotte Billard, additional, Liégeon, Geoffroy, additional, Denis, Blandine, additional, Molina, Jean-Michel, additional, André Cabié, Lucia Etheve, additional, Abel, Sylvie, additional, Cabras, Ornella, additional, Guitteaud, Karine, additional, François Vincent Dubee, Sandrine Pierre-, additional, Ndiaye, Diama, additional, Pehlivan, Jonathan, additional, Phelippeau, Michael, additional, Alexandre Duvignaud, Rafael Mahieu, additional, Pistone, Thierry, additional, Desclaux, Arnaud, additional, Neau, Didier, additional, Jean-François Faucher, Charles Cazanave, additional, Festou, Benjamin, additional, Dupuy-Grasset, Magali, additional, Loustaud-Ratti, Véronique, additional, Nathan Peiffer- Smadja, Delphine Chainier, additional, Choquet, Christophe, additional, Da Conceicao, Olivia, additional, Thy, Michael, additional, Collas, Lio, additional, Godard, Cindy, additional, Bouzid, Donia, additional, Ing, Vittiaroat, additional, Pereira, Laurent, additional, Pavlowsky, Thomas, additional, RavautAntoine Asquier-Khati, Camille, additional, Boutoille, David, additional, Chauveau, Marie, additional, Deschanvres, Colin, additional, Audrey Le Bot, François Raffi, additional, Cailleaux, Marine, additional, Benezit, François, additional, Maillard, Anne, additional, Hue, Benoit, additional, François Coustilleres, Pierre Tattevin, additional, Carvalho-Schneider, Claudia, additional, Jamard, Simon, additional, Petit, Laeticia, additional, Natacha Mrozek, Karl Stefic, additional, Theis, Clément, additional, Vidal, Magali, additional, Sauvat, Léo, additional, Benjamin Lefèvre, Delphine Martineau, additional, Baronnet, Guillaume, additional, Florence Ader, Agnès Didier, additional, Perpoint, Thomas, additional, Conrad, Anne, additional, Chabert, Paul, additional, Aurélie Martin, Pierre Chauvelot, additional, Loubet, Paul, additional, Mazet, Julien, additional, Larcher, Romaric, additional, Mathilde Devaux Jérôme Frey, Didier Laureillard, additional, Woerlen, Amos, additional, Remillon, Aline, additional, Absensur-Vuillaume, Laure, additional, Albert Trinh-Duc, Pauline Bouquet, additional, Philippe Petua, Patrick Rispal, additional, Aurore Perrot, Julien Carillo, additional, Delavigne, Karen, additional, Cougoul, Pierre, additional, Dion, Jérémie, additional, Mathieu Blot, Odile Rauzy, additional, Sixt, Thibault, additional, Moretto, Florian, additional, Charles, Carole, additional, Sophie Circosta, Lionel Piroth, additional, Leger, Lydia, additional, Arulananthan, Arulvani, additional, Lascoux, Carine, additional, Valérie, Pascaline, additional, Yazdan Yazdanpanah, Leia Becam, additional, Petrov-Sanchez, Ventzislava, additional, Diallo, Alpha, additional, Le Mestre, Soizic, additional, Le Meut Isabelle Goderel, Guillaume, additional, Chau, Frédéric, additional, Soltana, Brahim, additional, Chane Tang, Jessica, additional, Guedj, Jérémie, additional, and Caille, Yvanie, additional
Published: 2023
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16. Dengue outbreak amongst travellers returning from Cuba-GeoSentinel surveillance network, January-September 2022

Author: Marta Díaz-Menéndez, Kristina M Angelo, Rosa de Miguel Buckley, Emmanuel Bottieau, Ralph Huits, Martin P Grobusch, Federico Giovanni Gobbi, Hilmir Asgeirsson, Alexandre Duvignaud, Francesca F Norman, Emilie Javelle, Loïc Epelboin, Camilla Rothe, Francois Chappuis, Gabriela Equihua Martinez, Corneliu Popescu, Daniel Camprubí-Ferrer, Israel Molina, Silvia Odolini, Sapha Barkati, Susan Kuhn, Stephen Vaughan, Anne McCarthy, Mar Lago, Michael D Libman, Davidson H Hamer, Infectious diseases, AII - Infectious diseases, and APH - Global Health
Subjects: General Medicine
Abstract: Increasing numbers of travellers returning from Cuba with dengue virus infection were reported to the GeoSentinel Network from June to September 2022, reflecting an ongoing local outbreak. This report demonstrates the importance of travellers as sentinels of arboviral outbreaks and highlights the need for early identification of travel-related dengue.
Published: 2023

17. Sotrovimab therapy elicits antiviral activities against Omicron BQ.1.1 and XBB.1.5 in sera of immunocompromised patients

Author: Garcia, Magalie, Giraud, Valentin, Metais, Agathe, Cazenave-Roblot, Fance, Martellosio Anne-Marie Ronchetti, Jean-Philippe, Gabas, Thomas, Hadjadj, Naima, Salanoubat, Célia, Chabrol, Amélie, Housset, Pierre, Pardon, Agathe, Faucon, Anne-Laure, Caudwell, Valérie, Roland Liblau, Latifa Hanafi, Alric, Laurent, Pugnet, Grégory, Mourguet, Morgane, Bories, Eva, Bonnet, Delphine, Charpentier, Sandrine, Delobel, Pierre, Debard, Alexa, Beck, Colleen, Boumaza, Xavier, Fanny Lanternier, Stella Rousset, Delage, Claire, Pires, Elisabete Gomes, Cheminant, Morgane, Anthony Chauvin, Nathalie Chavarot, Véronique Delcey Simon Bessis, Xavier Eyer, Cresta, Mélanie, Pélagie Thibaut, Romain Gueneau, Nadal, Marine, Siguier, Martin, Bachir, Marwa, Valérie Pourcher, Christia Palacios, Melenotte, Cléa, Faycal, Antoine, Berot, Vincent, Brin, Cécile, Djebara, Siham, Zafilaza, Karen, Marot, Stéphane, Sayon, Sophie, Leducq, Vincent, Malet, Isabelle, Teyssou, Elisa, Karine Lacombe, Adélie Gothland, Aad, Yasmine Abi, Chiarabini, Thibault, Feliho, Raynald, Valin, Nadia, Brigant, Fabien, Boize, Julien, Thiébaud, Pierre-Clément, Moreau, Marie, Nathalie De Castro, Charlotte Billard, Liégeon, Geoffroy, Denis, Blandine, Molina, Jean-Michel, André Cabié, Lucia Etheve, Abel, Sylvie, Cabras, Ornella, Guitteaud, Karine, François Vincent Dubee, Sandrine Pierre, Ndiaye, Diama, Pehlivan, Jonathan, Phelippeau, Michael, Alexandre Duvignaud, Rafael Mahieu, Pistone, Thierry, Desclaux, Arnaud, Neau, Didier, Jean-François Faucher, Charles Cazanave, Festou, Benjamin, Dupuy-Grasset, Magali, Loustaud-Ratti, Véronique, Nathan Peiffer- Smadja, Delphine Chainier, Choquet, Christophe, Da Conceicao, Olivia, Thy, Michael, Collas, Lio, Godard, Cindy, Bouzid, Donia, Ing, Vittiaroat, Pereira, Laurent, Pavlowsky, Thomas, RavautAntoine Asquier-Khati, Camille, Boutoille, David, Chauveau, Marie, Deschanvres, Colin, Audrey Le Bot, François Raffi, Cailleaux, Marine, Benezit, François, Maillard, Anne, Hue, Benoit, François Coustilleres, Pierre Tattevin, Carvalho-Schneider, Claudia, Jamard, Simon, Petit, Laeticia, Natacha Mrozek, Karl Stefic, Theis, Clément, Vidal, Magali, Sauvat, Léo, Benjamin Lefèvre, Delphine Martineau, Baronnet, Guillaume, Florence Ader, Agnès Didier, Perpoint, Thomas, Conrad, Anne, Chabert, Paul, Aurélie Martin, Pierre Chauvelot, Loubet, Paul, Mazet, Julien, Larcher, Romaric, Mathilde Devaux Jérôme Frey, Didier Laureillard, Woerlen, Amos, Remillon, Aline, Absensur-Vuillaume, Laure, Albert Trinh-Duc, Pauline Bouquet, Philippe Petua, Patrick Rispal, Aurore Perrot, Julien Carillo, Delavigne, Karen, Cougoul, Pierre, Dion, Jérémie, Mathieu Blot, Odile Rauzy, Sixt, Thibault, Moretto, Florian, Charles, Carole, Sophie Circosta, Lionel Piroth, Leger, Lydia, Arulananthan, Arulvani, Lascoux, Carine, Valérie, Pascaline, Yazdan Yazdanpanah, Leia Becam, Petrov-Sanchez, Ventzislava, Diallo, Alpha, Le Mestre, Soizic, Le Meut Isabelle Goderel, Guillaume, Chau, Frédéric, Soltana, Brahim, Chane Tang, Jessica, Guedj, Jérémie, Caille, Yvanie, Bruel, Timothée, Vrignaud, Lou-Léna, Porrot, Françoise, Staropoli, Isabelle, Planas, Delphine, Guivel-Benhassine, Florence, Puech, Julien, Prot, Matthieu, Munier, Sandie, Bolland, William Henry, Soulié, Cathia, Lusivika-Nzinga, Clovis, Meledge, Marie-Laure, Dorival, Céline, Molino, Diana, Péré, Hélène, Yordanov, Youri, Simon-Lorière, Etienne, Veyer, David, Carrat, Fabrice, Schwartz, Olivier, Marcelin, Anne-Geneviève, and Martin-Blondel, Guillaume
Published: 2023
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18. Epidemiological and clinical characteristics of patients with monkeypox in the GeoSentinel Network

Author: Kristina M Angelo, Teresa Smith, Daniel Camprubí-Ferrer, Leire Balerdi-Sarasola, Marta Díaz Menéndez, Guillermo Servera-Negre, Sapha Barkati, Alexandre Duvignaud, Kristina L B Huber, Arpita Chakravarti, Emmanuel Bottieau, Christina Greenaway, Martin P Grobusch, Diogo Mendes Pedro, Hilmir Asgeirsson, Corneliu Petru Popescu, Charlotte Martin, Carmelo Licitra, Albie de Frey, Eli Schwartz, Michael Beadsworth, Susana Lloveras, Carsten S Larsen, Sarah Anne J Guagliardo, Florence Whitehill, Ralph Huits, Davidson H Hamer, Phyllis Kozarsky, Michael Libman, Lucille Blumberg, Hélène Chaussade, Arnaud Desclaux, Eric Florence, Simin Aysel Florescu, Hedvig Glans, Marielle Glynn, Abraham Goorhuis, Marina Klein, Denis Malvy, Andrea McCollum, José Muñoz, Duc Nguyen, Laura Quilter, Camilla Rothe, Patrick Soentjens, Camille Tumiotto, Jef Vanhamel, Repositório da Universidade de Lisboa, Infectious diseases, AII - Infectious diseases, and APH - Global Health
Subjects: Infectious Diseases
Abstract: © 2022 Elsevier Ltd. All rights reserved., Background: The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. We aimed to describe the epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection. Methods: We descriptively analysed data for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. We did descriptive analyses of epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm3 or 500 cells per mm3 and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination. Findings: 226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18-68; IQR 32-43). Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm3 (range 36-1659; IQR 500-885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1-8). Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control. No deaths were reported. Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0·002), perianal rash or lesions (p=0·03), and a higher rash burden (median rash burden score 9 [IQR 6-21] for patients with HIV vs median rash burden score 6 [IQR 3-14] for patients without HIV; p, US Centers for Disease Control and Prevention, International Society of Travel Medicine
Published: 2022
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19. Lassa fever outcomes and prognostic factors in Nigeria (LASCOPE): a prospective cohort study

Author: Claire Levy-Marchal, Jackson Katembo Vihundira, Sampson Omagbemi Owhin, Marion Bérerd-Camara, Justine Schaeffer, Sophie Duraffour, Johnson Etafo, Alex P. Salam, Chukwuyem Abejegah, Adewale Oladayo Akinpelu, Alexandre Duvignaud, Delphine Gabillard, Camille le Gal, Josephine Funmilola Alabi, Peter Horby, Kader Issaley, Abiodun Tolani Abidoye, Eric Ouattara, Moronke Uzuajemeh Ireneh, Denis Malvy, Liasu Adeagbo Ahmed, Ijeoma Chukwudumebi Etafo, Mahamadou Doutchi, Olufunke Gbenga-Ayeni, Benjamin Séri, Irmine Ahyi, Moses Adeniyi Adedokun, Ephraim Ogbaini-Emovon, Kehinde Gbemisola Fadiminiyi, Oyebimpe Ope Oyegunle, Akinola Nelson Adedosu, Ayoleyi Omowunmi Dede, Jean-Paul de Bruyne Mushenvula, Patience Iziegbe Ehigbor, Elvis Amani, Nicolas Danet, Titilola Deborah Sule, Marie Jaspard, Mamoudou Diabaté, B. Serra, Bertine Siloué, Stephan Günther, Augustin Augier, Larissa N'guessan-Koffi, Sophie Karcher, Oladele Oluwafemi Ayodeji, Xavier Anglaret, Macdonald Nonso Onyechi, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale, Wellcome Trust, Ministère des Affaires Etrangères, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Institut de Recherche pour le Développement, and Group, LASCOPE Study
Subjects: Male, Pediatrics, Time Factors, Palliative care, Kaplan-Meier Estimate, Severity of Illness Index, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, Child, 10. No inequality, Lassa fever, Prospective cohort study, Reverse Transcriptase Polymerase Chain Reaction, Mortality rate, Palliative Care, Age Factors, Articles, General Medicine, Middle Aged, Prognosis, 3. Good health, Hospitalization, Treatment Outcome, Child, Preschool, Cohort, Administration, Intravenous, Female, Adult, medicine.medical_specialty, Adolescent, 030231 tropical medicine, Nigeria, Young Adult, 03 medical and health sciences, Lassa Fever, Ribavirin, Severity of illness, Humans, Lassa virus, business.industry, Infant, Newborn, Infant, Odds ratio, medicine.disease, chemistry, DNA, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract: Summary Background Lassa fever is a viral haemorrhagic fever endemic in parts of west Africa. New treatments are needed to decrease mortality, but pretrial reference data on the disease characteristics are scarce. We aimed to document baseline characteristics and outcomes for patients hospitalised with Lassa fever in Nigeria. Methods We did a prospective cohort study (LASCOPE) at the Federal Medical Centre in Owo, Nigeria. All patients admitted with confirmed Lassa fever were invited to participate and asked to give informed consent. Patients of all ages, including newborn infants, were eligible for inclusion, as were pregnant women. All participants received standard supportive care and intravenous ribavirin according to Nigeria Centre for Disease Control guidelines and underwent systematic biological monitoring for 30 days. Patients' characteristics, care received, mortality, and associated factors were recorded using standard WHO forms. We used univariable and multivariable logistic regression models to investigate an association between baseline characteristics and mortality at day 30. Findings Between April 5, 2018, and March 15, 2020, 534 patients with confirmed Lassa fever were admitted to hospital, of whom 510 (96%) gave consent and were included in the analysis. The cohort included 258 (51%) male patients, 252 (49%) female patients, 426 (84%) adults, and 84 (16%) children (younger than 18 years). The median time between first symptoms and hospital admission was 8 days (IQR 7–13). At baseline, 176 (38%) of 466 patients had a Lassa fever RT-PCR cycle threshold (Ct) lower than 30. From admission to end of follow-up, 120 (25%) of 484 reached a National Early Warning Score (second version; NEWS2) of 7 or higher, 67 (14%) of 495 reached a Kidney Disease–Improving Global Outcome (KDIGO) stage of 2 or higher, and 41 (8%) of 510 underwent dialysis. All patients received ribavirin for a median of 10 days (IQR 9–13). 62 (12%) patients died (57 [13%] adults and five [6%] children). The median time to death was 3 days (1–6). The baseline factors independently associated with mortality were the following: age 45 years or older (adjusted odds ratio 16·30, 95% CI 5·31–50·30), NEWS2 of 7 or higher (4·79, 1·75–13·10), KDIGO grade 2 or higher (7·52, 2·66–21·20), plasma alanine aminotransferase 3 or more times the upper limit of normal (4·96, 1·69–14·60), and Lassa fever RT-PCR Ct value lower than 30 (4·65, 1·50–14·50). Interpretation Our findings comprehensively document clinical and biological characteristics of patients with Lassa fever and their relationship with mortality, providing prospective estimates that could be useful for designing future therapeutic trials. Such trials comparing new Lassa fever treatments to a standard of care should take no more than 15% as the reference mortality rate and consider adopting a combination of mortality and need for dialysis as the primary endpoint. Funding Institut National de la Sante et de la Recherche Medicale, University of Oxford, EU, UK Department for International Development, Wellcome Trust, French Ministry of Foreign Affairs, Agence Nationale de Recherches sur le SIDA et les hepatites virales, French National Research Institute for Sustainable Development.
Published: 2021
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20. Final results of the DisCoVeRy trial of remdesivir for patients admitted to hospital with COVID-19

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, France Mentré, Charles Burdet, Jérôme Aboab, Hafid Ait-Oufella, Antoine Altdorfer, Claire Andrejak, Pascal Andreu, Laurent Argaud, Firouzé Bani-Sadr, Drifa Belhadi, Leila Belkhir, François Benezit, Marc Berna, Mathieu Blot, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, David Bougon, Kevin Bouiller, Fanny Bounes-Vardon, David Boutoille, Alexandre Boyer, Sandra Braz, Cédric Bruel, André Cabié, Emmanuel Canet, Charles Cazanave, Cyrille Chabartier, Catherine Chirouze, Raphaël Clere-Jehl, Dominique Costagliola, Sandrine Couffin-Cadièrgues, Johan Courjon, Flora Crockett, François Danion, Aline Dechanet, Agathe Delbove, Jean Dellamonica, Christelle Delmas, Alpha Diallo, Félix Djossou, Clément Dubost, Alexandre Duvignaud, Alexander Egle, Olivier Epaulard, Loïc Epelboin, Hélène Esperou, Murielle Fartoukh, Karine Faure, Emmanuel Faure, Joao-Miguel Ferreira Ribeiro, Tristan Ferry, Cécile Ficko, Samy Figueiredo, Claire Fougerou, Vincent Fraipont, Benjamin Gaborit, Rostane Gaci, Amandine Gagneux-Brunon, Sébastien Gallien, Denis Garot, Alexandre Gaymard, Guillaume Geri, Sébastien Gibot, François Goehringer, Marie Gousseff, Richard Greil, Didier Gruson, Jérémie Guedj, Yves Hansmann, Olivier Hinschberger, Stéphane Jaureguiberry, Vanessa Jeanmichel, Michael Joannidis, Solen Kerneis, Antoine Kimmoun, Kada Klouche, Marie Lachâtre, Karine Lacombe, Fabrice Laine, Bernd Lamprecht, Jean-Philippe Lanoix, Odile Launay, Bruno Laviolle, Minh-Patrick Lê, Vincent Le Moing, Jérôme Le Pavec, Yves Le Tulzo, Paul Le Turnier, David Lebeaux, Benjamin Lefevre, Sylvie Leroy, François-Xavier Lescure, Henry Lessire, Benjamin Leveau, Bruno Lina, Paul Loubet, Alain Makinson, Denis Malvy, Charles-Hugo Marquette, Guillaume Martin-Blondel, Martin Martinot, Julien Mayaux, Armand Mekontso-Dessap, Noémie Mercier, Ferhat Meziani, Jean-Paul Mira, Jean-Michel Molina, Xavier Monnet, Joy Mootien, Bruno Mourvillier, Bruno Mourvilliers, Marlène Murris-Espin, Jean-Christophe Navellou, Marion Noret, Saad Nseir, Walid Oulehri, José-Artur Paiva, Thomas Perpoint, Gilles Peytavin, Gilles Pialoux, Benoît Pilmis, Vincent Piriou, Lionel Piroth, Julien Poissy, Valérie Pourcher, Jean-Pierre Quenot, François Raffi, Jean Reignier, Jean Reuter, Matthieu Revest, Jean-Christophe Richard, Béatrice Riu-Poulenc, Céline Robert, Pierre-Alexandre Roger, Claire Roger, Roberto Roncon-Albuquerque, Elisabeth Rouveix-Nordon, Yvon Ruch, Nadia Saidani, Juliette Saillard, Naomi Sayre, Eric Senneville, Albert Sotto, Thérèse Staub, Francois Stefan, Charles Tacquard, Nicolas Terzi, Julien Textoris, Guillaume Thiery, Jean-François Timsit, Violaine Tolsma, Sarah Tubiana, Jean-Marie Turmel, Florent Valour, Fanny Vardon-Bounes, Priyanka Velou, Gil Verschelden, Florent Wallet, Guilhem Wattecamps, Yazdan Yazdanpanah, Yoann Zerbib, UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, and UCL - (SLuc) Service de médecine interne générale
Subjects: Hospitalization, Clinical Trials as Topic, Alanine, Infectious Diseases, COVID-19, Humans, Adenosine Monophosphate, COVID-19 Drug Treatment
Published: 2022
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21. Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE)

Author: Alexandre Duvignaud, Edouard Lhomme, Racha Onaisi, Rémi Sitta, Ambre Gelley, Julie Chastang, Lionel Piroth, Christine Binquet, Julie Dupouy, Alain Makinson, Benjamin Lefèvre, Jean-Marc Naccache, Caroline Roussillon, Roland Landman, Cédrick Wallet, Sophie Karcher, Valérie Journot, Duc Nguyen, Thierry Pistone, Stéphane Bouchet, Marie-Edith Lafon, Mathieu Molimard, Rodolphe Thiébaut, Xavier de Lamballerie, Jean-Philippe Joseph, Laura Richert, Olivier Saint-Lary, Sarah Djabarouti, Linda Wittkop, Xavier Anglaret, Denis Malvy, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université - Département de médecine générale, Sorbonne Université (SU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), 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), Université Fédérale Toulouse Midi-Pyrénées, CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe Hospitalier Paris Saint-Joseph (hpsj), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-20-COVI-0040,COVERAGE,Traitement à domicile des personnes infectées par le SRAS-CoV-2 sans signe de gravité mais à risque de complications: un essai randomisé à plusieurs bras et en plusieurs étapes (MAMS) pour évaluer l'efficacité de plusieurs antiviraux(2020), Richert, Laura, Traitement à domicile des personnes infectées par le SRAS-CoV-2 sans signe de gravité mais à risque de complications: un essai randomisé à plusieurs bras et en plusieurs étapes (MAMS) pour évaluer l'efficacité de plusieurs antiviraux - - COVERAGE2020 - ANR-20-COVI-0040 - COVID-19 - VALID, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Toulouse (UT)
Subjects: Microbiology (medical), Male, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Ciclesonide, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Pregnenediones, Outpatients, Adults, Humans, Aged, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Inhaled corticosteroids, SARS-CoV-2, COVID-19, General Medicine, Middle Aged, COVID-19 Drug Treatment, Treatment, Oxygen, Infectious Diseases, Treatment Outcome, Randomized controlled trial, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female
Abstract: International audience; Objectives: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness.Methods: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here.Results: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms.Discussion: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.
Published: 2021
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22. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, Drifa Belhadi, Alpha Diallo, Minh-Patrick Lê, Gilles Peytavin, Thérèse Staub, Richard Greil, Jérémie Guedj, Jose-Artur Paiva, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentré, Alexander Egle, Michael Joannidis, Bernd Lamprecht, Antoine Altdorfer, Leila Belkhir, Vincent Fraipont, Gil Verschelden, Jérôme Aboab, Hafid Ait-Oufella, Claire Andrejak, Pascal Andreu, Laurent Argaud, Firouzé Bani-Sadr, François Benezit, Mathieu Blot, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, David Bougon, Kevin Bouiller, Fanny Bounes-Vardon, David Boutoille, Alexandre Boyer, Cédric Bruel, André Cabié, Emmanuel Canet, Charles Cazanave, Cyrille Chabartier, Catherine Chirouze, Raphaël Clere-Jehl, Johan Courjon, Flora Crockett, François Danion, Agathe Delbove, Jean Dellamonica, Félix Djossou, Clément Dubost, Alexandre Duvignaud, Olivier Epaulard, Loïc Epelboin, Murielle Fartoukh, Karine Faure, Emmanuel Faure, Tristan Ferry, Cécile Ficko, Samy Figueiredo, Benjamin Gaborit, Rostane Gaci, Amandine Gagneux-Brunon, Sébastien Gallien, Denis Garot, Guillaume Geri, Sébastien Gibot, François Goehringer, Marie Gousseff, Didier Gruson, Yves Hansmann, Olivier Hinschberger, Stéphane Jaureguiberry, Vanessa Jeanmichel, Solen Kerneis, Antoine Kimmoun, Kada Klouche, Marie Lachâtre, Karine Lacombe, Fabrice Laine, Jean-Philippe Lanoix, Odile Launay, Bruno Laviolle, Vincent Le Moing, Jérôme Le Pavec, Yves Le Tulzo, Paul Le Turnier, David Lebeaux, Benjamin Lefevre, Sylvie Leroy, François-Xavier Lescure, Henry Lessire, Benjamin Leveau, Paul Loubet, Alain Makinson, Denis Malvy, Charles-Hugo Marquette, Guillaume Martin-Blondel, Martin Martinot, Julien Mayaux, Armand Mekontso-Dessap, Ferhat Meziani, Jean-Paul Mira, Jean-Michel Molina, Xavier Monnet, Joy Mootien, Bruno Mourvillier, Marlène Murris-Espin, Jean-Christophe Navellou, Saad Nseir, Walid Oulehri, Thomas Perpoint, Gilles Pialoux, Benoît Pilmis, Vincent Piriou, Lionel Piroth, Valérie Pourcher, Jean-Pierre Quenot, François Raffi, Jean Reignier, Matthieu Revest, Jean-Christophe Richard, Béatrice Riu-Poulenc, Céline Robert, Pierre-Alexandre Roger, Claire Roger, Elisabeth Rouveix-Nordon, Yvon Ruch, Nadia Saidani, Naomi Sayre, Eric Senneville, Albert Sotto, Francois Stefan, Charles Tacquard, Nicolas Terzi, Julien Textoris, Guillaume Thiery, Jean-François Timsit, Violaine Tolsma, Jean-Marie Turmel, Florent Valour, Florent Wallet, Guilhem Wattecamps, Yoann Zerbib, Marc Berna, Jean Reuter, Sandra Braz, Joao-Miguel Ferreira Ribeiro, José-Artur Paiva, Roberto Roncon-Albuquerque, Alexandre Gaymard, Bruno Lina, Sarah Tubiana, Sandrine Couffin-Cadièrgues, Hélène Esperou, Aline Dechanet, Christelle Delmas, Claire Fougerou, Noémie Mercier, Marion Noret, Juliette Saillard, Priyanka Velou, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Internal Medicine, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Imperial College London, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Universidade do Porto = University of Porto, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, and UCL - (SLuc) Service de médecine interne générale
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, Antiviral Agents, law.invention, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Internal medicine, Humans, Medicine, media_common.cataloged_instance, 030212 general & internal medicine, European union, education, Contraindication, ComputingMilieux_MISCELLANEOUS, Aged, media_common, Mechanical ventilation, education.field_of_study, Alanine, business.industry, COVID-19, Standard of Care, Odds ratio, Articles, Middle Aged, Respiration, Artificial, Adenosine Monophosphate, COVID-19 Drug Treatment, 3. Good health, Europe, Hospitalization, Oxygen, Clinical trial, Infectious Diseases, Clinical research, Female, business
Abstract: Summary Background The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77–1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. Funding European Union Commission, French Ministry of Health, Domaine d'interet majeur One Health Ile-de-France, REACTing, Fonds Erasme-COVID-Universite Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Translation For the French translation of the abstract see Supplementary Materials section.
Published: 2021
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23. Multidrug-resistant tuberculosis imported into low-incidence countries-a GeoSentinel analysis, 2008-2020

Author: Eric Caumes, Martin P. Grobusch, Effrossyni Gkrania-Klotsas, Alexandre Duvignaud, Hilmir Asgeirsson, Lin H. Chen, Johannes Eimer, Elizabeth D. Barnett, Elena Trigo-Esteban, Davidson H. Hamer, Kristina M. Angelo, Mogens Jensenius, Christina Greenaway, Natasha S. Hochberg, Calvin Patimeteeporn, Maximilian Gertler, Infectious diseases, AII - Infectious diseases, APH - Global Health, APH - Aging & Later Life, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, medical migration, Tuberculosis, 030231 tropical medicine, Antitubercular Agents, MDR-TB, Article, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Epidemiology, Tuberculosis, Multidrug-Resistant, medicine, Humans, extensively drug-resistant tuberculosis, 030212 general & internal medicine, Travel, business.industry, Public health, Incidence (epidemiology), Incidence, Extensively drug-resistant tuberculosis, General Medicine, Mycobacterium tuberculosis, medicine.disease, 3. Good health, migrant, Tropical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, epidemiology, business, Rifampicin, medicine.drug, immigration
Abstract: Background Early detection of imported multidrug-resistant tuberculosis (MDR-TB) is crucial, but knowledge gaps remain about migration- and travel-associated MDR-TB epidemiology. The aim was to describe epidemiologic characteristics among international travellers and migrants with MDR-TB. Methods Clinician-determined and microbiologically confirmed MDR-TB diagnoses deemed to be related to travel or migration were extracted from GeoSentinel, a global surveillance network of travel and tropical medicine clinics, from January 2008 through December 2020. MDR-TB was defined as resistance to both isoniazid and rifampicin. Additional resistance to either a fluoroquinolone or a second-line injectable drug was categorized as pre-extensively drug-resistant (pre-XDR) TB, and as extensively drug-resistant (XDR) TB when resistance was detected for both. Sub-analyses were performed based on degree of resistance and country of origin. Results Of 201 patients, 136 had MDR-TB (67.7%), 25 had XDR-TB (12.4%), 23 had pre-XDR TB (11.4%) and 17 had unspecified MDR- or XDR-TB (8.5%); 196 (97.5%) were immigrants, of which 92 (45.8%) originated from the former Soviet Union. The median interval from arrival to presentation was 154 days (interquartile range [IQR]: 10–751 days); 34.3% of patients presented within 1 month after immigration, 30.9% between 1 and 12 months and 34.9% after ≥1 year. Pre-XDR- and XDR-TB patients from the former Soviet Union other than Georgia presented earlier than those with MDR-TB (26 days [IQR: 8–522] vs. 369 days [IQR: 84–827]), while patients from Georgia presented very early, irrespective of the level of resistance (8 days [IQR: 2–18] vs. 2 days [IQR: 1–17]). Conclusions MDR-TB is uncommon in traditional travellers. Purposeful medical migration may partly explain differences in time to presentation among different groups. Public health resources are needed to better understand factors contributing to cross-border MDR-TB spread and to develop strategies to optimize care of TB-infected patients in their home countries before migration.
Published: 2021
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24. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Author: François-Xavier Lescure, Hitoshi Honda, Robert A Fowler, Jennifer Sloane Lazar, Genming Shi, Peter Wung, Naimish Patel, Owen Hagino, Ignacio J. Bazzalo, Marcelo M. Casas, Sebastián A. Nuñez, Yael Pere, Carlos M. Ibarrola, Marco A. Solis Aramayo, Maria C. Cuesta, Andrea E. Duarte, Pablo M. Gutierrez Fernandez, Maria A. Iannantuono, Erica A. Miyazaki, Javier P. Silvio, Dario G. Scublinsky, Alessandra Bales, Daniela Catarino, Elie Fiss, Sara Mohrbacher, Victor Sato, Antonio Baylao, Adilson Cavalcante, Francini Correa, Celso A. de Andrade, Juvencio Furtado, Nelson Ribeiro Filho, Valéria Telles, Leopoldo T. Trevelin, Ricardo Vipich, Rodrigo Boldo, Paula Borges, Suzana Lobo, Graziela Luckemeyer, Luana Machado, Maysa B. Alves, Ana C. Iglessias, Marianna M. Lago, Daniel W. Santos, Hugo Chapdelaine, Emilia L. Falcone, Rahima Jamal, Me-Linh Luong, Madeleine Durand, Stephane Doucet, François-Martin Carrier, Bryan A. Coburn, Lorenzo Del Sorbo, Sharon L. Walmsley, Sara Belga, Luke Y. Chen, Allison D. Mah, Theodore Steiner, Alissa J. Wright, J. Hajek, Neill Adhikari, Robert A. Fowler, Nick Daneman, Kosar A. Khwaja, Jason Shahin, Carolina Gonzalez, Rafael Silva, Marcelo Lindh, Gabriel Maluenda, Patricia Fernandez, Maite Oyonarte, Martin Lasso, Alexandre Boyer, Didier Bronnimann, Hoang-Nam Bui, Charles Cazanave, Helene Chaussade, Arnaud Desclaux, Mailys Ducours, Alexandre Duvignaud, Denis Malvy, Lisa Martin, Didier Neau, Duc Nguyen, Thierry Pistone, Gaetane Soubrane-Wirth, Julie Leitao, Clotilde Allavena, Charlotte Biron, Sabelline Bouchez, Benjamin Gaborit, Antoine Gregoire, Paul Le Turnier, Anne-Sophie Lecompte, Raphael Lecomte, Maeva Lefebvre, Francois Raffi, David Boutoille, Pascale H. Morineau, Romain Guéry, Emmanuel Chatelus, Nathalie Dumoussaud, Renaud Felten, Florina Luca, Bernard Goichot, Francis Schneider, Marie-Caroline Taquet, Matthieu Groh, Mathilde Roumier, Mathilde Neuville, Antoine Bachelard, Valentina Isernia, F-Xavier Lescure, Bao-Chau Phung, Anne Rachline, Aurelie Sautereau, Dorothee Vallois, Yves Bleher, Delphine Boucher, Clémentine Coudon, Jean Esnault, Thomas Guimard, Sophie Leautez-Nainville, Dominique Merrien, Marine Morrier, Pauline Motte-Vincent, Romain Gabeff, Hélène Leclerc, Céline Cozic, Romain Decours, Ronan Février, Gwenhael Colin, Sophie Abgrall, Dorothee Vignes, Raluca Sterpu, Mira Kuellmar, Melanie Meersch-Dini, Raphael Weiss, Alexander Zarbock, Christiane Antony, Marc Berger, Thorsten Brenner, Christian Taube, Frank Herbstreit, Sebastian Dolff, Margarethe Konik, Karsten Schmidt, Markus Zettler, Oliver Witzke, Boris Boell, Jorge Garcia Borrega, Philipp Koehler, Thomas Zander, Fabian Dusse, Othman Al-Sawaf, Philipp Köhler, Dennis Eichenauer, Matthias Kochanek, Alexander Shimabukuro-Vornhagen, Sibylle Mellinghoff, Annika Claßen, Jan-Michel Heger, Charlotte Meyer-Schwickerath, Paul Liedgens, Katrin Heindel, Ana Belkin, Asaf Biber, Mayan Gilboa, Itzchak Levy, Vladislav Litachevsky, Galia Rahav, Anat Finesod Wiedner, Tal Zilberman-Daniels, Yonatan Oster, Jacob Strahilevitz, Sigal Sviri, Elena M. Baldissera, Corrado Campochiaro, Giulio Cavalli, Lorenzo Dagna, Giacomo De Luca, Emanuel Della Torre, Alessandro Tomelleri, Davide Bernasconi De Luca, Amedeo F. Capetti, Massimo Coen, Maria V. Cossu, Massimo Galli, Andrea Giacomelli, Guido A. Gubertini, Stefano Rusconi, Giulia J. Burastero, Margherita Digaetano, Giovanni Guaraldi, Marianna Meschiari, Cristina Mussini, Cinzia Puzzolante, Sara Volpi, Marina Aiello, Alarico Ariani, Alfredo A. Chetta, Annalisa Frizzelli, Andrea Ticinesi, Domenico Tuttolomondo, Stefano Aliberti, Francesco B. Blasi, Marta F. Di Pasquale, Sofia Misuraca, Tommaso Pilocane, Edoardo Simonetta, Alessio M. Aghelmo, Claudio Angelini, Enrico Brunetta, Giorgio W. Canonica, Michele Ciccarelli, Sara Dal Farra, Maria De Santis, Sebastian Ferri, Marco Folci, Giacomo M. Guidelli, Enrico M. Heffler, Ferdinando Loiacono, Giacomo Malipiero, Giovanni Paoletti, Rosa Pedale, Francesca A. Puggioni, Francesca Racca, Aurora Zumbo, Morihiko Satou, Tatyana Lisun, Denis Protsenko, Nikolay Rubtsov, Irina Beloglazova, Daria Fomina, Mariana Lysenko, Sofia Serdotetskova, Vitali Firstov, Ivan Gordeev, Ilia Kokorin, Ksenia Komissarova, Nina Lapochkina, Elena Luchinkina, Valentin Malimon, Sevinch Mamedguseyinova, Ksenia Polubatonova, Natalia Suvorova, Jose Arribas, Alberto M. Borobia Perez, Fernando de la Calle Prieto, Juan Carlos Figueira, Rocio Motejano Sanchez, Marta Mora-Rillo, Concepcion Prados Sanchez, Javier Queiruga Parada, Francisco Fernandez Arnalich, Maria Guerro Barrientos, Alejandro Bendala Estrada, Aranzazu Caballero Marcos, Maria E. Garcia Leoni, Rita García-Martínez, Ana María Collado, Patricia Munoz Garcia, Ana Torres do Rego, María V. Villalba García, Almudena Burrillo, Maricela Valerio Minero, Paloma Gijon Vidaurreta, Sonsoles Infante Herrero, Elena Velilla, Marina Machado, Maria Olmedo, Blanca Pinilla, Benito Almirante Gragera, Maria de la Esperanza Cañas Ruano, Sofia Contreras Medina, Alejandro Cortés Herrera, Vicenç Falcó Ferrer, Ricard Ferrer Roca, Xavier Nuvials Casals, Esteve Ribera Pascuet, Paula Suanzes Diez, Pedro Rebollo Castro, Felipe Garcia Alcaide, Alejandro Soriano, Aina Oliver Caldes, Ana González Cordón, Celia Cardozo, Lorena De la Mora Cañizo, Romina Pena López, Sandra Chamorro, Clara Crespillo-Andujar, Rosa Escudero Sanchez, Jesús Fortún-Abete, Begoña Monge-Maillo, Ana Moreno Zamora, Francesca Norman, Matilde Sanchez Conde, Sergio Serrano Villar, Pilar Vizcarra, Lescure, F. -X., Honda, H., Fowler, R. A., Lazar, J. S., Shi, G., Wung, P., Patel, N., Hagino, O., Bazzalo, I. J., Casas, M. M., Nunez, S. A., Pere, Y., Ibarrola, C. M., Solis Aramayo, M. A., Cuesta, M. C., Duarte, A. E., Gutierrez Fernandez, P. M., Iannantuono, M. A., Miyazaki, E. A., Silvio, J. P., Scublinsky, D. G., Bales, A., Catarino, D., Fiss, E., Mohrbacher, S., Sato, V., Baylao, A., Cavalcante, A., Correa, F., de Andrade, C. A., Furtado, J., Ribeiro Filho, N., Telles, V., Trevelin, L. T., Vipich, R., Boldo, R., Borges, P., Lobo, S., Luckemeyer, G., Machado, L., Alves, M. B., Iglessias, A. C., Lago, M. M., Santos, D. W., Chapdelaine, H., Falcone, E. L., Jamal, R., Luong, M. -L., Durand, M., Doucet, S., Carrier, F. -M., Coburn, B. A., Del Sorbo, L., Walmsley, S. L., Belga, S., Chen, L. Y., Mah, A. D., Steiner, T., Wright, A. J., Hajek, J., Adhikari, N., Daneman, N., Khwaja, K. A., Shahin, J., Gonzalez, C., Silva, R., Lindh, M., Maluenda, G., Fernandez, P., Oyonarte, M., Lasso, M., Boyer, A., Bronnimann, D., Bui, H. -N., Cazanave, C., Chaussade, H., Desclaux, A., Ducours, M., Duvignaud, A., Malvy, D., Martin, L., Neau, D., Nguyen, D., Pistone, T., Soubrane-Wirth, G., Leitao, J., Allavena, C., Biron, C., Bouchez, S., Gaborit, B., Gregoire, A., Le Turnier, P., Lecompte, A. -S., Lecomte, R., Lefebvre, M., Raffi, F., Boutoille, D., Morineau, P. H., Guery, R., Chatelus, E., Dumoussaud, N., Felten, R., Luca, F., Goichot, B., Schneider, F., Taquet, M. -C., Groh, M., Roumier, M., Neuville, M., Bachelard, A., Isernia, V., Phung, B. -C., Rachline, A., Sautereau, A., Vallois, D., Bleher, Y., Boucher, D., Coudon, C., Esnault, J., Guimard, T., Leautez-Nainville, S., Merrien, D., Morrier, M., Motte-Vincent, P., Gabeff, R., Leclerc, H., Cozic, C., Decours, R., Fevrier, R., Colin, G., Abgrall, S., Vignes, D., Sterpu, R., Kuellmar, M., Meersch-Dini, M., Weiss, R., Zarbock, A., Antony, C., Berger, M., Brenner, T., Taube, C., Herbstreit, F., Dolff, S., Konik, M., Schmidt, K., Zettler, M., Witzke, O., Boell, B., Garcia Borrega, J., Koehler, P., Zander, T., Dusse, F., Al-Sawaf, O., Kohler, P., Eichenauer, D., Kochanek, M., Shimabukuro-Vornhagen, A., Mellinghoff, S., Classen, A., Heger, J. -M., Meyer-Schwickerath, C., Liedgens, P., Heindel, K., Belkin, A., Biber, A., Gilboa, M., Levy, I., Litachevsky, V., Rahav, G., Finesod Wiedner, A., Zilberman-Daniels, T., Oster, Y., Strahilevitz, J., Sviri, S., Baldissera, E. M., Campochiaro, C., Cavalli, G., Dagna, L., De Luca, Giacomo., Della Torre, E., Tomelleri, A., Bernasconi De Luca, D., Capetti, A. F., Coen, M., Cossu, M. V., Galli, M., Giacomelli, A., Gubertini, G. A., Rusconi, S., Burastero, G. J., Digaetano, M., Guaraldi, G., Meschiari, M., Mussini, C., Puzzolante, C., Volpi, S., Aiello, M., Ariani, A., Chetta, A. A., Frizzelli, A., Ticinesi, A., Tuttolomondo, D., Aliberti, S., Blasi, F. B., Di Pasquale, M. F., Misuraca, S., Pilocane, T., Simonetta, E., Aghelmo, A. M., Angelini, C., Brunetta, E., Canonica, G. W., Ciccarelli, M., Dal Farra, S., De Santis, M., Ferri, S., Folci, M., Guidelli, G. M., Heffler, E. M., Loiacono, F., Malipiero, G., Paoletti, G., Pedale, R., Puggioni, F. A., Racca, F., Zumbo, A., Satou, M., Lisun, T., Protsenko, D., Rubtsov, N., Beloglazova, I., Fomina, D., Lysenko, M., Serdotetskova, S., Firstov, V., Gordeev, I., Kokorin, I., Komissarova, K., Lapochkina, N., Luchinkina, E., Malimon, V., Mamedguseyinova, S., Polubatonova, K., Suvorova, N., Arribas, J., Borobia Perez, A. M., de la Calle Prieto, F., Figueira, J. C., Motejano Sanchez, R., Mora-Rillo, M., Prados Sanchez, C., Queiruga Parada, J., Fernandez Arnalich, F., Guerro Barrientos, M., Bendala Estrada, A., Caballero Marcos, A., Garcia Leoni, M. E., Garcia-Martinez, R., Collado, A. M., Munoz Garcia, P., Torres do Rego, A., Villalba Garcia, M. V., Burrillo, A., Valerio Minero, M., Gijon Vidaurreta, P., Infante Herrero, S., Velilla, E., Machado, M., Olmedo, M., Pinilla, B., Almirante Gragera, B., Canas Ruano, M. D. L. E., Contreras Medina, S., Cortes Herrera, A., Falco Ferrer, V., Ferrer Roca, R., Nuvials Casals, X., Ribera Pascuet, E., Suanzes Diez, P., Rebollo Castro, P., Garcia Alcaide, F., Soriano, A., Oliver Caldes, A., Gonzalez Cordon, A., Cardozo, C., De la Mora Canizo, L., Pena Lopez, R., Chamorro, S., Crespillo-Andujar, C., Escudero Sanchez, R., Fortun-Abete, J., Monge-Maillo, B., Moreno Zamora, A., Norman, F., Sanchez Conde, M., Serrano Villar, S., and Vizcarra, P.
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, International Cooperation, Population, Antibodies, Monoclonal, Humanized, Placebo, Severity of Illness Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Intensive care, Severity of illness, medicine, Clinical endpoint, Humans, Immunologic Factors, 030212 general & internal medicine, Mortality, education, Respiratory Distress Syndrome, education.field_of_study, Dose-Response Relationship, Drug, SARS-CoV-2, business.industry, Hazard ratio, COVID-19, Articles, Middle Aged, Receptors, Interleukin-6, Sarilumab, Treatment Outcome, 030228 respiratory system, Female, Drug Monitoring, Cytokine Release Syndrome, business
Abstract: Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.
Published: 2021

25. Lassa fever clinical course and setting a standard of care for future randomized trials: A protocol for a cohort study of Lassa-infected patients in Nigeria (LASCOPE)

Author: Peter Horby, Marie Jaspard, Liasu Adeagbo Ahmed, Mahamadou Doutchi, Ephraim Ogbaini-Emovon, Bertine Siloué, Irmine Ahyi, Claire Levy-Marchal, Justine Schaeffer, Josephine Funmilola Alabi, Ijeoma Chukwudumebi Etafo, Alex P. Salam, Denis Malvy, Stephan Günther, Olufunke Gbenga-Ayeni, Adewale Oladayo Akinpelu, Larissa N'guessan-Koffi, Eric Ouattara, Delphine Gabillard, Johnson Etafo, Oyebimpe Ope Oyegunle, Chukwuyem Abejegah, Alexandre Duvignaud, Augustin Augier, Moronke Uzuajemeh Ireneh, Mamoudou Diabaté, Moses Adeniyi Adedokun, Kehinde Gbemisola Fadiminiyi, Sophie Karcher, B. Serra, Akinola Nelson Adedosu, Ayoleyi Omowunmi Dede, Patience Iziegbe Ehigbor, Oladele Oluwafemi Ayodeji, Macdonald Nonso Onyechi, Xavier Anglaret, Elvis Amani, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Programme PAC-CI, ANRS France Recherche Nord & sud Sida-hiv hépatites, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), The Alliance for International Medical Action [Dakar, Sénégal] (ONG ALIMA), Université de Zinder - University of Zinder [Zinder, Niger], University of Oxford [Oxford], and Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Nigeria, Viral hemorrhagic fever, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Informed consent, Pregnancy, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Intensive care medicine, Lassa fever, Prospective cohort study, Lassa virus, Randomized Controlled Trials as Topic, business.industry, Public Health, Environmental and Occupational Health, Standard of Care, medicine.disease, 3. Good health, Acute kidney injury, Clinical trial, Africa, Western, Infectious Diseases, Clinical research, Cohort, Female, business, Cohort study
Abstract: Background Lassa Fever (LF), is a severe viral disease prevalent in Western Africa. It is classified as a priority disease by the World Health Organization (WHO). Ribavirin is the recommended therapy despite weak evidence of its efficacy. Promising therapeutic agents are becoming available for evaluation in human. Before launching therapeutic trials, we need data on the evolution of the disease under the best possible conditions of care. Methods We have initiated a prospective study in Nigeria to better understand the clinical course and prognostic factors of LF while implementing high quality standardized care. Inclusion criteria are: suspected or confirmed LF and informed consent. Participants are followed 60 days from admission and receive free of charge standardized supportive care and biological monitoring, as well as intravenous ribavirin for those with confirmed LF. Data are collected using standardized case report forms (CRF). Primary and secondary outcomes are fatality and severe morbidity, with special focus on acute kidney dysfunction and pregnancy complications. Factors associated with outcomes will be investigated. Results The cohort is planned for 3 years. Inclusions started in April 2018 at the Federal Medical Center Owo in Ondo State. A second site will open in Nigeria in 2020 and discussions are underway to open a site in Benin. 150 to 200 new participants are expected per year. Conclusions This cohort will: provide evidence to standardize LF case management; provide key inputs to design future clinical trials of novel therapeutics; and establish clinical research teams capable of conducting such trials in LF-endemic areas. Study registration The LASCOPE study was registered on ClinicalTrial.gov (NCT03655561).
Published: 2020
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26. Travel-associated chikungunya acquired in Myanmar in 2019

Author: Guido Calleri, Marta Díaz-Menéndez, Alfred Lennart Bissinger, Spinello Antinori, Camilla Rothe, Jonathan D. Alpern, Emanuele Nicastri, Patricia Schlagenhauf, Mugen Ujiie, Elena Trigo Esteban, Denis Malvy, Davidson H. Hamer, Federico Gobbi, Alexandre Duvignaud, Emilie Javelle, Marc Grandadam, Takato Nakamoto, University of Zurich, Díaz-Menéndez, Marta, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Unit, Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), Université Paris Descartes - Paris 5 (UPD5), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), and Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)
Subjects: Male, 0301 basic medicine, Epidemiology, Myanmar, medicine.disease_cause, Chikungunya virus disease, Disease Outbreaks, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Travel medicine, Chikungunya, ComputingMilieux_MISCELLANEOUS, Travel, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Middle Aged, Arthralgia, 3. Good health, Geography, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Virus Infection, surveillance, Female, Chikungunya virus, Rapid Communication, Adult, medicine.medical_specialty, Fever, 030106 microbiology, 030231 tropical medicine, 610 Medicine & health, Mosquito Vectors, Virus, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Virology, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Aged, Public Health, Environmental and Occupational Health, Outbreak, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 2739 Public Health, Environmental and Occupational Health, Exanthema, travel medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 2406 Virology, Chikungunya Fever, Sentinel Surveillance, 2713 Epidemiology
Abstract: Eighteen cases of chikungunya virus infection in travellers returning from Myanmar were reported to the GeoSentinel Surveillance Network, its subnetwork EuroTravNet and TropNet in 2019, reflecting an ongoing local outbreak. This report reinforces the importance of travellers as sentinels of emerging arboviral outbreaks and highlights the importance of vigilance for imported cases, due to the potential for dissemination of the virus into areas with competent local vectors and conducive environmental conditions.
Published: 2020
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27. Early complicated schistosomiasis in a returning traveller: Key contribution of new molecular diagnostic methods

Author: Jan Clerinx, Lieselotte Cnops, Simon Bonnefond, Emmanuel Bottieau, Alexandre Duvignaud, Thierry Pistone, Denis Malvy, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Molecular Diagnostic Method, Schistosomiasis, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, White People, lcsh:Infectious and parasitic diseases, Serology, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Medicine, Neuroschistosomiasis, lcsh:RC109-216, 030212 general & internal medicine, Intensive care medicine, Schistosoma, Travel, biology, business.industry, Schistosoma mansoni, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, 3. Good health, Cote d'Ivoire, Infectious Diseases, Molecular Diagnostic Techniques, Spinal Cord, IDLIC, Early schistosomiasis, Neuroschistosomiasis, PCR, Traveller, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Early schistosomiasis poses a serious diagnostic challenge, because current standard diagnostic techniques based on serology and egg microscopy lack sensitivity at the initial presentation. We report spinal cord neuroschistosomiasis in a traveller developing 6 weeks after exposure. The diagnosis was confirmed by Schistosoma mansoni-targeted real-time PCR in blood and cerebrospinal fluid, before the results of conventional methods became positive. Molecular assays represent a paradigm shift for the difficult diagnosis of early schistosomiasis and related complications. Keywords: Early schistosomiasis, Neuroschistosomiasis, PCR, Traveller
Published: 2019
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28. The Antigen-Presenting Potential of Vγ9Vδ2 T Cells During Plasmodium falciparum Blood-Stage Infection

Author: Matthias Eberl, Matthieu Mechain, Odile Mercereau-Puijalon, Jennifer Howard, Julie Déchanet-Merville, Dorothée Duluc, Denis Malvy, Maria Mamani-Matsuda, Bernhard Moser, Jean-François Moreau, Marita Troye-Blomberg, Alexandre Duvignaud, Séverine Loizon, Christopher J. Tyler, and Charlotte Behr
Subjects: 0301 basic medicine, T-Lymphocytes, Plasmodium falciparum, Antigen presentation, Antigen-Presenting Cells, Lymphocyte Activation, 03 medical and health sciences, Immune system, Antigen, parasitic diseases, Humans, Immunology and Allergy, Malaria, Falciparum, Antigen Presentation, CD40, biology, Dendritic cell, Acquired immune system, biology.organism_classification, R1, Virology, Phenotype, 030104 developmental biology, Infectious Diseases, Immunology, biology.protein, CD80
Abstract: During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function; compromising development of effective anti-malarial adaptive immunity. Human Vγ9Vδ2 T-cells can act in vitro as APCs and induce αβ T-cell activation. However, the relevance of this activity in pathophysiological contexts in vivo has remained elusive. Since Vγ9Vδ2 T-cells are activated during the early immune response against P.falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites. In P.falciparum-infected patients,Vγ9Vδ2 T-cells presented an increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, Vγ9Vδ2 T-cells readily up-regulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83 and CD86, induced naive αβ T-cell responses, and cross-presented soluble prototypical protein to antigen-specific CD8+ T-cells. Our findings indicate that P. falciparum parasites induce genuine APC properties in Vγ9Vδ2 T-cells and qualify this subset as an alternative professional APC in malaria patients, which could be harnessed for therapeutic interventions and vaccine design.
Published: 2017
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29. International mass gatherings and travel-associated illness: A GeoSentinel cross-sectional, observational study

Author: Wayne Ghesquiere, Andrea K. Boggild, Giles Eperon, Alexandre Duvignaud, Noreen A. Hynes, Kevin C. Kain, Katherine Plewes, Michael Libman, Paul Kelly, Michael Beadsworth, Susan Anderson, Poh Lian Lim, Israel Molina, Lin H. Chen, Jonathan D. Alpern, Sarah Borwein, Carsten Schade Larsen, Emmanuel Bottieau, Emilie Javelle, Kunjana Mavunda, Hilmir Asgeirsson, Nicholas J. Beeching, Elizabeth D. Barnett, François Chappuis, Satoshi Katsuna, Sabine Jordan, Philippe Gautret, Susan Kuhn, Johnnie Yates, Mugen Ujiie, Christian Wejse, Denis Malvy, Mogens Jensenius, Eric Caumes, Joseph Torresi, Karin Leder, Bradley A. Connor, Rainer Weber, Patricia Schlagenhauf, Jesse J. Waggoner, Davidson H. Hamer, Henry M. Wu, Kristina M. Angelo, Thomas Weitzel, Dan Bourque, Perry J.J. van Genderen, Mauro Saio, Brian J. Ward, Marc Mendelson, Hedvig Glans, Cecilia Perret Pérez, Salim Parker, William M. Stauffer, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Division of Global Migration and Quarantine [Atlanta, GA, USA], Centers for Disease Control and Prevention (CDC), Université Paris Descartes - Paris 5 (UPD5), Laboratoire Traitement et Communication de l'Information (LTCI), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Centre for Tropical Diseases [Montréal] (TDC), McGill University = Université McGill [Montréal, Canada], 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), McGill University, and Medical Microbiology & Infectious Diseases
Subjects: medicine.medical_specialty, Oylmpics, Pneumococcal disease, Pneumonia, Viral, 030231 tropical medicine, Article, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, [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, Mass gathering, Humans, Medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, Pandemics, ComputingMilieux_MISCELLANEOUS, Travel, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Surveillance, SARS-CoV-2, business.industry, Public Health, Environmental and Occupational Health, COVID-19, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Religious mass, Vaccination, Pneumonia, Cross-Sectional Studies, Infectious Diseases, Family medicine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Respiratory, Observational study, Hajj, Mass gatherings, Coronavirus Infections, business, Healthcare providers
Abstract: Background Travelers to international mass gatherings may be exposed to conditions which increase their risk of acquiring infectious diseases. Most existing data come from single clinical sites seeing returning travelers, or relate to single events. Methods Investigators evaluated ill travelers returning from a mass gathering, and presenting to a GeoSentinel site between August 2015 and April 2019, and collected data on the nature of the event and the relation between final diagnoses and the mass gathering. Results Of 296 ill travelers, 51% were female and the median age was 54 years (range: 1–88). Over 82% returned from a religious mass gathering, most frequently Umrah or Hajj. Only 3% returned from the Olympics in Brazil or South Korea. Other mass gatherings included other sporting events, cultural or entertainment events, and conferences. Respiratory diseases accounted for almost 80% of all diagnoses, with vaccine preventable illnesses such as influenza and pneumonia accounting for 26% and 20% of all diagnoses respectively. This was followed by gastrointestinal illnesses, accounting for 4.5%. Sixty-three percent of travelers reported having a pre-travel encounter with a healthcare provider. Conclusions Despite this surveillance being limited to patients presenting to GeoSentinel sites, our findings highlight the importance of respiratory diseases at mass gatherings, the need for pre-travel consultations before mass gatherings, and consideration of vaccination against influenza and pneumococcal disease.
Published: 2019
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30. Travel-related health events and their risk factors in HIV-infected sub-Saharan migrants living in France and visiting their native country: The ANRS VIHVO cohort study

Author: Thierry Pistone, Eric Ouattara, Delphine Gabillard, Nathalie Lele, Alexandre Duvignaud, Hugues Cordel, Denis Malvy, Olivier Bouchaud, Sophie Abgrall, Michele Bentata, Bruno Fantin, Cécile Goujard, Sophie Matheron, Odile Launay, Vincent Le Moing, Olivier Lortholary, Paul- Henri Consigny, Matthieu Saada, Christine Katlama, Anne Simon, Cédric Arvieux, Pauline Campa, Pierre-Marie Girard, Marie-Aude Khuong, Jean-Michel Molina, Caroline Lascoux-Combe, David Rey, Murielle Rondeau, Gilles Pialoux, Carine Couzigou, Daniel Vittecoq, Olivier Patey, Philippe Morlat, Michel Duong, Pascal Chavanet, CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Nord, Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), and Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]
Subjects: medicine.medical_specialty, Visiting friends and relatives, Fever, Gastrointestinal Diseases, Respiratory Tract Diseases, 030231 tropical medicine, HIV Infections, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Risk Factors, Medical advice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Health event, Humans, Medicine, Travel medicine, 030212 general & internal medicine, Africa South of the Sahara, Transients and Migrants, Travel, Sub-Saharan Africa, business.industry, Public Health, Environmental and Occupational Health, virus diseases, Migrant, Viral Load, medicine.disease, HIV infection, Malaria, 3. Good health, Infectious Diseases, Anti-Retroviral Agents, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Travel-Related Illness, business, Viral load, Cohort study, Demography
Abstract: International audience; BACKGROUND: Literature on health events in HIV-infected travellers is scarce, particularly in sub-Saharan African (SSA) migrants.METHODS: We investigated health events in HIV-infected SSA migrants living in France during and after travel to their native country. All had a pre-travel plasma viral load (pVL) below 200 copies/mL and were on stable combined antiretroviral therapy (cART). Logistic regression models were used to assess the risk factors for at least one adverse health event or febrile event.RESULTS: Among 264 HIV migrants, pre-travel median CD4 count was 439/mm3 and 27 migrants (6%) experienced a low-level viremia between 50 and 200 copies/mL. One hundred (38%) experienced at least one event (13 experienced two events). The most common events were gastrointestinal, including diarrhoea (n = 29, 26%), respiratory events (n = 20, 18%), and malaria (n = 17, 15%; 1 death). In multivariable analysis, a pre-travel low-level viremia and a lack of pre-travel medical advice significantly increased the risk for any event (OR 4.31, 95% CI, 1.41-13.1; and OR 3.62, 95% CI, 1.38-9.47; respectively). A lack of pre-travel advice significantly increased the risk for febrile event.CONCLUSIONS: Early and tailored counselling on pre-travel medical advice regarding diarrhoea and vector-borne diseases prophylactic measures in HIV-infected SSA migrants should be emphasised before travel to Africa.
Published: 2019
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31. Rheumatism and chronic fatigue, the two facets of post-chikungunya disease: the TELECHIK cohort study on Reunion island

Author: A. Fred, Adrian Fianu, Matthieu Mechain, J. Jaubert, Alexandre Duvignaud, B.-A. Gaüzère, Alain Michault, Patrice Poubeau, Denis Malvy, François Favier, Patrick Gérardin, A. Bertolotti, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Epidemiology, Prevalence, Cohort Studies, 0302 clinical medicine, Medicine, 030212 general & internal medicine, rheumatic disease, Aged, 80 and over, education.field_of_study, Fatigue Syndrome, Chronic, virus diseases, Middle Aged, 3. Good health, Infectious Diseases, Cohort, Female, medicine.symptom, Chikungunya virus, Cohort study, Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Population, Alphavirus, Asymptomatic, IDLIC, Young Adult, 03 medical and health sciences, Rheumatic Diseases, Internal medicine, cohort study, Chronic fatigue syndrome, Humans, education, Original Paper, business.industry, Chronic fatigue, medicine.disease, Chronic Disease, Chikungunya Fever, Chikungunya, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Reunion, chronic fatigue, Rheumatism
Abstract: Prolonged fatigue is increasingly reported among chikungunya virus (CHIKV)-infected populations. We investigated the relationships between CHIKV exposure, long-lasting rheumatic musculoskeletal pain (LRMSP) and chronic fatigue. 1094 participants (512 CHIKV seropositive and 582 seronegative) of the TELECHIK population-based cohort were analysed considering the duration of the manifestations throughout an average 2-year follow-up. Weighted prevalence rates and prevalence ratios for LRMSP, idiopathic chronic fatigue (ICF), and chronic fatigue syndrome (CFS)-like illness, both latter syndromes adapted from Centers for Disease Control (CDC)-1994/Fukuda criteria, were compared. Population attributable fractions (PAF) were estimated to assess the contribution of CHIKV infection to each of the three phenotypes. Among 362 adult subjects who had reported either rheumatic pain or fatigue at the onset of the infection, weighted prevalence rates of LRMSP, ICF and CFS-like illness were respectively of 32.9%, 38.7% and 23.9%, and of 8.7%, 8.5% and 7.4% among initially asymptomatic peers (P < 0.01, respectively). Each of the three outcomes was highly attributable to chikungunya (PAF of 43.2%, 36.2% and 41.0%, respectively). In the sub-cohort of CHIKV-infected subjects, LRMSP, ICF and CFS-like illness, which overlapped in 70%, accounted for 53% of the chronic manifestations. In addition to rheumatic disease, chronic fatigue could be considered in caring for patients with chronic chikungunya disease.
Published: 2018
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32. Furuncular myiasis for the Western dermatologist: treatment in outpatient consultation

Author: Marie-Catherine Receveur, Christophe Vanhecke, Alexandre Duvignaud, Philippe Le Gall, Denis Malvy, and Romain Blaizot
Subjects: Adult, Male, medicine.medical_specialty, Cordylobia, Cordylobia anthropophaga, 030231 tropical medicine, Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, Myiasis, 0302 clinical medicine, medicine, Animals, Humans, biology, Walk-in, business.industry, Diptera, Nodule (medicine), Middle Aged, biology.organism_classification, medicine.disease, Dermatobia hominis, Occlusive dressing, medicine.anatomical_structure, Scalp, Practice Guidelines as Topic, Female, medicine.symptom, business, Travel-Related Illness
Abstract: BACKGROUND Furuncular myiasis is likely to be seen by Western dermatologists because of the increasing number of international travelers but remains unfamiliar to most of them, who tend to refer these patients to hospitals. Different treatments have been proposed, but many of them are not achievable in outpatient consultation. METHODS We reported three typical cases of furuncular myiasis, according to each species involved, and proposed diagnostic and therapeutic guidelines for dermatologists in outpatient consultation. RESULTS One patient, complaining of an inflammatory nodule of the leg with a central punctum, was diagnosed with Dermatobia hominis infection, after a forest walk in French Guiana. One woman returned from Senegal with a nodule of the left buttock. She had been infected by a Cordylobia anthropophaga larva after drying her underwear under a mango tree. One woman living in Cameroon presented with scalp nodules, pain, fatigue, and facial edema. She had been infected by more than 40 larvae of Cordylobia rodhaini after drying her sheets under a mango tree. Manual extraction ensured complete healing in the three patients. We used neither doppler ultrasound nor occlusive dressing. Diagnosis was immediately made thanks to the typical clinical stories. CONCLUSIONS The diagnosis of furuncular myiasis requires only clinical skills and basic knowledge of life cycles. The treatment varies slightly depending on the species involved but is achievable in outpatient consultation and does not require occlusive dressing.
Published: 2017

33. Cervical spondylitis and spinal abscess due to Actinomyces meyeri

Author: Denis Malvy, M. Longy-Boursier, Daniel Moynet, Alexandre Duvignaud, and Emmanuel Ribeiro
Subjects: Microbiology (medical), DNA, Bacterial, Male, medicine.medical_specialty, Pathology, Actinomyces meyeri, Cervical spondylitis, lcsh:QR1-502, Diagnostic tools, Actinomycosis, Polymerase Chain Reaction, MALDI–TOF mass spectrometry, lcsh:Microbiology, lcsh:Infectious and parasitic diseases, RNA, Ribosomal, 16S, Rare case, Medicine, Actinomyces, Humans, lcsh:RC109-216, 16S rRNA, Abscess, Spondylitis, Medicine(all), biology, business.industry, Middle Aged, biology.organism_classification, medicine.disease, Dermatology, Infectious Diseases, Cervical Vertebrae, Spinal Diseases, business, Immunocompetence
Abstract: Human actinomycosis with involvement of the spine is a rare condition although it has been first described a long time ago. It is probably underrecognized since its clinical presentation is often misleading and accurate bacteriological diagnosis is challenging. We herein report a rare case of cervical actinomycosis with paravertebral abscess and spondylitis imputed to an infection by Actinomyces meyeri in a 52-year-old immunocompetent Caucasian man. A. meyeri should be considered as a potential cause for subacute or chronic spondylitis, even in immunocompetent subjects. Modern diagnostic tools such as Matrix-Assisted Laser Desorption–Ionization Time of Flight mass spectrometry and 16S rRNA sequencing are efficient for accurate microbiological identification. Keywords: Actinomyces, Spondylitis, MALDI–TOF mass spectrometry, 16S rRNA
Published: 2014
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34. PO 8473 IMPACT OF EBOLA ON SLEEPING SICKNESS IN COASTAL GUINEA: A RETROSPECTIVE ANALYSIS (2012–2017) FROM THE GUINEAN NATIONAL CONTROL PROGRAMME

Author: Bruno Bucheton, Amadou Leno, Eric Ouattara, Oumou Camara, Hamidou Ilboudo, Alexandre Duvignaud, Philippe Solano, M. Camara, Denis Malvy, and Mamadou Camara
Subjects: medicine.medical_specialty, Ebola virus, business.industry, Transmission (medicine), Health Policy, Public health, Public Health, Environmental and Occupational Health, Psychological intervention, Outbreak, Tropical disease, Disease, medicine.disease_cause, medicine.disease, Environmental health, parasitic diseases, medicine, African trypanosomiasis, business
Abstract: BackgroundCoastal Guinea harbours the most active human African trypanosomiasis (HAT) foci in West Africa. The Guinean government and its partners are conducting HAT control activities to reduce the burden of this neglected tropical disease and, as set-up by WHO, to eliminate it as a public health problem by 2020. Unfortunately, control efforts were deeply impaired during the Ebola outbreak that struck the country in 2014–2015. The aim of the study was to evaluate the impact of this unprecedented outbreak on HAT screening and care activities and more generally on T. brucei gambiense transmission.MethodsA retrospective analysis of the data collected by the HAT-NCP between 2012 and 2013 (pre-Ebola period) and 2014–2015 (Ebola outbreak) has shown an interruption of active HAT screening activities and a rapid decrease of passive HAT screening activities as the Ebola outbreak was spreading. During the Ebola epidemic, HAT patients were also diagnosed in a later stage of the disease and attendance to post-treatment control visits was also severely affected.ResultsOnly 59 HAT patients were diagnosed and treated during the Ebola outbreak (January 2014–October 2015) as compared to 154 before the outbreak (February 2012–December 2013). This potentially large undiagnosed human reservoir of trypanosomes may have contributed to increased transmission levels. After Guinea was declared free of Ebola virus disease, screening activities (both passive and active) were progressively resumed. In 2016 and 2017, Guinea reported 107 and 140 HAT cases, respectively (almost twice as much as during the pre-Ebola period) and became the second most affected country after the Democratic Republic of the Congo.ConclusionA major lesson taken from the Ebola outbreak is that disruption of medical care may lead to a quick HAT burst in areas of high transmission. Current HAT control measures combining screening and tsetse control interventions will help to stay on course for the elimination goal.
Published: 2019
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35. Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin

Author: Lucien Dossou-Gbété, Michel Cot, Félix Atadokpédé, Djimon-Marcel Zannou, Komlan V Agossou, Alexandre Duvignaud, Aldric Afangnihoun, Didier G. Komongui, Jocelyn Akakpo, Lise Denoeud-Ndam, Pierre-Marie Girard, Université Paris Descartes - Paris 5 (UPD5), Service des Maladies Infectieuses et Tropicales A [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, UMR 216, Institut de Recherche pour le Développement (IRD), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), CHU Koutoukou, Cotonou, Hôpital de zone Suru Léré, Cotonou, Centre Hospitalier Universitaire de la Mère et de l'Enfant Lagune (CHU-MEL), Hôpital d'Instruction des Armées Camp Guézo, Service de Santé des Armées, Clinique Louis Pasteur, Cotonou, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 ( UPD5 ), Institut de Recherche pour le Développement ( IRD ), University of Abomey Calavi ( UAC ), Hôpital de la mère et de l'enfant lagune, Cotonou, Hôpital d'instruction des armées, Cotonou, Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), University of Abomey Calavi (UAC), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP]
Subjects: Adult, Pediatrics, medicine.medical_specialty, Fever, HIV Infections, Incidence rate, Cohort Studies, Young Adult, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Medicine, Benin, Humans, Prospective Studies, Malaria, Falciparum, Pregnancy Complications, Infectious, Prospective cohort study, biology, business.industry, Incidence (epidemiology), Incidence, Research, HIV, Plasmodium falciparum, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Attributable fraction, medicine.disease, biology.organism_classification, 3. Good health, Malaria, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Relative risk, Immunology, Attributable risk, Parasitology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Morbidity, business, Cohort study
Abstract: Background Malaria and HIV are two major causes of morbidity and mortality among pregnant women in sub-Saharan Africa. Foetal and neonatal outcomes of this co-infection have been extensively studied. However, little is known about maternal morbidity due to clinical malaria in pregnancy, especially malaria-related fever, in the era of generalized access to antiretroviral therapy and anti-malarial preventive strategies. Methods A cohort study was conducted in order to estimate the incidence rate and to determine the factors associated with malaria-related fever, as well as the maternal morbidity attributable to malaria in a high-transmission setting of South Benin among HIV-infected pregnant women. Four-hundred and thirty-two women who participated in a randomized trial testing strategies to prevent malaria in pregnancy were included and followed until delivery, with at least three scheduled visits during pregnancy. Confirmed malaria-related fever was defined as axillary temperature >37.5°C and a concomitant, positive, thick blood smear or rapid diagnostic test for Plasmodium falciparum. Suspected malaria-related fever was defined as an axillary temperature >37.5°C and the concomitant administration of an anti-malarial treatment in the absence of parasitological investigation. Results Incidence rate for confirmed malaria-related fever was of 127.9 per 1,000 person-year (PY) (95% confidence interval (CI): 77.4-211.2). In multivariate analysis, CD4 lymphocytes (Relative Risk (RR) for a 50 cells/mm3 variation = 0.82; CI: 0.71-0.96), antiretroviral treatment started before inclusion (RR = 0.34; CI: 0.12-0.98) and history of symptomatic malaria in early pregnancy (RR = 7.10; CI: 2.35-22.49) were associated with the incidence of confirmed or suspected malaria-related fever. More than a half of participants with parasitaemia were symptomatic, with fever being the most common symptom. The crude fraction of febrile episodes attributable to malaria was estimated at 91%. Conclusions This work highlights that malaria is responsible for a substantial morbidity in HIV-infected pregnant women, with cellular immunodepression as a major determinant, and establishes the possible advantage offered by the early initiation of antiretroviral treatment. Trial registration PACOME Study has been registered under the number NCT00970879.
Published: 2014
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36. Visceral leishmaniasis due to Leishmania infantum in a kidney transplant recipient living in France

Author: Khaled Ezzedine, Marie-Catherine Receveur, Denis Malvy, Alexandre Duvignaud, and Thierry Pistone
Subjects: Travel, biology, business.industry, Public Health, Environmental and Occupational Health, Antiprotozoal Agents, Middle Aged, biology.organism_classification, medicine.disease, Kidney Transplantation, Transplant Recipients, Kidney transplant recipient, Immunocompromised Host, Morocco, Infectious Diseases, Visceral leishmaniasis, Immunology, medicine, Humans, Leishmaniasis, Visceral, Female, France, Leishmania infantum, business
Published: 2013

37. Disseminated cysticercosis revealed by subcutaneous nodules in a migrant from Cameroon

Author: Alexandre Duvignaud, Denis Malvy, Thierry Pistone, and Marie-Catherine Receveur
Subjects: Male, Radiography, Abdominal, medicine.medical_specialty, Adolescent, Cysticercosis, business.industry, Public Health, Environmental and Occupational Health, Emigrants and Immigrants, Facial Muscles, medicine.disease, Dermatology, Infectious Diseases, Subcutaneous nodule, Abdomen, medicine, Humans, Cameroon, business
Published: 2014
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38. Une lésion du pied

Author: Alexandre Duvignaud, Marie-Catherine Receveur, A Marchesseau, and Denis Malvy
Subjects: Gastroenterology, Internal Medicine, Biology
Published: 2013
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39. Un syndrome des anticorps anti-phospholipides révélé par une hépatite aiguë d’origine ischémique survenant au cours d’une grossesse

Author: Patrick Mercié, Pierre Duffau, E. Ribeiro, Alexandre Duvignaud, and M. Longy-Boursier
Subjects: Gastroenterology, Internal Medicine
Published: 2011
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40. Présentation pseudo tumorale d’une sarcoïdose hépatique

Author: Pierre Duffau, Alexandre Duvignaud, B Le-Bail, C Godard Sebillotte, Patrick Mercié, E. Ribeiro, M. Longy-Boursier, and L Doassans-Cazaban
Subjects: Gastroenterology, Internal Medicine
Published: 2011
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41. Une encéphalite à anticorps anti-NMDAR révélatrice d’un adénocarcinome prostatique

Author: M. Andreu, C. Godard-Sebillotte, O. Descharmes, E. Ribeiro, M. Longy-Boursier, Alexandre Duvignaud, and A. Saint-Lezer
Subjects: Gastroenterology, Internal Medicine
Published: 2011
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42. First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020

Author: Daniel Lévy-Bruhl, Sylvie Behillil, Clément Bassi, Alexandra Mailles, Anne Simondon, Yassoungo Silue, P. Rolland, François Xavier Lescure, Matthieu Mechain, Morgane Stempfelet, Anouk Tabaï, Clément Lazarus, Bruno Coignard, C Campese, Investigation team, Sophie Ismael, Sibylle Bernard Stoecklin, Denis Malvy, Vincent Enouf, Mathieu Nguyen, Laure Meurice, Estelle Yamani, Duc Minh Nguyen, Scarlett Georges, Santé publique France - French National Public Health Agency, Agence Régionale de Santé Ile-de-France [Paris] (ARS IDF), Agence Régionale de la Santé (ARS), Centre National de Référence des virus des infections respiratoires (dont la grippe) [Paris] (CNR), Institut Pasteur [Paris], Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bordeaux GeoSentinel Site [Bordeaux], Service des maladies infectieuses et tropicales [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Direction Générale de la Santé [Paris] (DGS), Ministère des Solidarités et de la Santé [Paris, France], Santé publique France [Saint-Maurice, France] (French National Public Health Agency), parent-French National Public Health Agency, Investigation Team: Laurent Filleul, Stéphanie Vandentorren, Guillaume Spaccaferri, Hélène Prouvost, Mélanie Albert, Marion Barbet, Angela Brisebarre, Flora Donati, Sylvie van der Werf, Alexis Ardoin, Marion Dreyer, Karim Tararbit, Matthieu Amodeo, Elodie Couaillier, Pascal Fabre, Daniel Habold, Didier Che, Gisèle Bendjelloul, Marine Billaudelle Lallemant, Valentine Charachon, Laurène Deconinck, Diane Descamps, Sandrine Gérard, Nadirha Houhou, Quentin Le Hingrat, Isabelle Lolom, Jean-Christophe Lucet, Annabelle Pourbaix, Simon Valayer, Yazdan Yazdanpanah, Alexandre Boyer, Benjamin Clouzeau, Xavier Combes, Arnaud Desclaux, Jean-Michel Dindart, Alexandre Duvignaud, Isabelle Garrigue, Didier Gruson, Marie-Edith Lafon, Pauline Perreau, Thierry Pistone, Maxime Poteau, Eric Tentillier, Pauline Mathieu., Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Direction des régions [Saint-Maurice], Cellule Régionale Ile-de-France [Paris], Santé publique France - French National Public Health Agency [Saint-Maurice, France]-Santé publique France - French National Public Health Agency [Saint-Maurice, France], Agence Régionale de Santé Nouvelle-Aquitaine [Bordeaux] (ARS NA), Cellule Régionale Nouvelle-Aquitaine [Bordeaux], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre opérationnel de réception et de régulation des urgences sanitaires et sociales [Paris], Ministère des Solidarités et de la Santé [Paris, France]-Ministère des Solidarités et de la Santé [Paris, France], Direction alerte et crise [Saint-Maurice], Investigation Team : Laurent Filleul, Stéphanie Vandentorren, Guillaume Spaccaferri, Hélène Prouvost, Mélanie Albert, Marion Barbet, Angela Brisebarre, Flora Donati, Sylvie van der Werf, Alexis Ardoin, Marion Dreyer, Karim Tararbit, Matthieu Amodeo, Elodie Couaillier, Pascal Fabre, Daniel Habold, Didier Che, Gisèle Bendjelloul, Marine Billaudelle Lallemant, Valentine Charachon, Laurène Deconinck, Diane Descamps, Sandrine Gérard, Nadirha Houhou, Quentin Le Hingrat, Isabelle Lolom, Jean-Christophe Lucet, Annabelle Pourbaix, Simon Valayer, Yazdan Yazdanpanah, Alexandre Boyer, Benjamin Clouzeau, Xavier Combes, Arnaud Desclaux, Jean-Michel Dindart, Alexandre Duvignaud, Isabelle Garrigue, Didier Gruson, Marie-Edith Lafon, Pauline Perreau, Thierry Pistone, Maxime Poteau, Eric Tentillier, Pauline Mathieu, Bodescot, Myriam, and Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR)
Subjects: 0301 basic medicine, Male, Epidemiology, MESH: Coronavirus Infections, [SDV]Life Sciences [q-bio], coronavirus, medicine.disease_cause, MESH: Risk Assessment, contact tracing, containment, MESH: Infection Control, 0302 clinical medicine, COVID-19, France, 2019-nCov, Surveillance, SARS-CoV-2, Coronavirus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infection control, MESH: COVID-19, 030212 general & internal medicine, MESH: Travel, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Travel, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, biology, Transmission (medicine), Middle Aged, MESH: China, 3. Good health, Population Surveillance, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Betacoronavirus, Risk assessment, Coronavirus Infections, Adult, medicine.medical_specialty, China, Pneumonia, Viral, Disease cluster, Risk Assessment, MESH: Population Surveillance, MESH: Contact Tracing, 03 medical and health sciences, Betacoronavirus, Virology, medicine, Humans, MESH: SARS-CoV-2, Infection Control, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, MESH: Adult, biology.organism_classification, medicine.disease, MESH: Male, MESH: France, Pneumonia, 030104 developmental biology, MESH: Pneumonia, Viral, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Emergency medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Contact tracing
Abstract: Investigation Team : Santé publique France, Direction des régions, Cellule Régionale Nouvelle Aquitaine, Bordeaux, France: Laurent Filleul, Stéphanie Vandentorren.Santé publique France, Direction des régions, Cellule Régionale Auvergne-Rhône-Alpes, Lyon, France: Guillaume Spaccaferri.Santé publique France, Direction des régions, Cellule Régionale Hauts-de-France, Lille, France: Hélène Prouvost.Centre national de référence Virus des infections respiratoires, dont la grippe, Institut Pasteur, Paris, France: Mélanie Albert, Marion Barbet, Angela Brisebarre, Flora Donati, Sylvie van der Werf.Agence Régionale de Santé Ile-de-France, Paris, France: Alexis Ardoin, Marion Dreyer, Karim Tararbit.Agence Régionale de Santé Nouvelle-Aquitaine, Bordeaux, France: Matthieu Amodeo, Elodie Couaillier, Pascal Fabre, Daniel Habold.Santé publique France, Direction des maladies infectieuses, Saint-Maurice, France: Didier Che.AP-HP, Hôpital Bichat, Service des maladies infectieuses et tropicales, Paris, France: Gisèle Bendjelloul, Marine Billaudelle Lallemant, Valentine Charachon, Laurène Deconinck, Diane Descamps, Sandrine Gérard, Nadirha Houhou, Quentin Le Hingrat, Isabelle Lolom, Jean-Christophe Lucet, Annabelle Pourbaix, Simon Valayer, Yazdan Yazdanpanah.Centre Hospitalier Universitaire de Bordeaux, Bordeaux GeoSentinel Site, Bordeaux, France: Alexandre Boyer, Benjamin Clouzeau, Xavier Combes, Arnaud Desclaux, Jean-Michel Dindart, Alexandre Duvignaud, Isabelle Garrigue, Didier Gruson, Marie-Edith Lafon, Pauline Perreau, Thierry Pistone, Maxime Poteau, Eric Tentillier.Direction Générale de la Santé, Ministère des solidarités et de la santé, Centre opérationnel de réception et de régulation des urgences sanitaires et sociales, Paris, France: Pauline Mathieu; International audience; A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.
Published: 2020
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