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8,402 results on '"[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases"'

1. Quantitative Polymerase Chain Reaction from Malaria Rapid Diagnostic Tests to Detect Borrelia crocidurae, the Agent of Tick-Borne Relapsing Fever, in Febrile Patients in Senegal

Author

El Hadji Ibrahima, Ndiaye, Diatta, Georges, Adama Zan, Diarra, Bassene, Hubert, Sokhna, Cheikh, Parola, Philippe, 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), Maladies infectieuses persistantes et émergentes en Afrique de l’Ouest [Dakar, Sénégal] (Equipe 3 - 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 [Brétigny-sur-Orge] (IRBA), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [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, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

In endemic malaria areas, Plasmodium is currently diagnosed mainly through the use of rapid diagnostic tests (RDTs). However, in Senegal, many causes of fever remain unknown. Tick-borne relapsing fever, an often-neglected public health problem, is the main cause of consultation for acute febrile illness after malaria and flu in rural areas. Our objective was to test the feasibility of extracting and amplifying DNA fragments by quantitative polymerase chain reaction (qPCR) from malaria-negative RDTs for Plasmodium falciparum (malaria Neg RDTs P.f) to detect Borrelia spp. and other bacteria. Between January and December 2019, malaria Neg RDTs P.f were collected on a quarterly basis in 12 health facilities in four regions of Senegal. The DNA extracted from the malaria Neg RDTs P.f was tested using qPCR and the results were confirmed by standard PCR and sequencing. Only Borrelia crocidurae DNA was detected in 7.22% (159/2,202) of RDTs. The prevalence of B. crocidurae DNA was higher in July (16.47%, 43/261) and August (11.21%, 50/446). The annual prevalence was 9.2% (47/512) and 5.0% (12/241) in Ngayokhem and Nema-Nding, respectively, health facilities in the Fatick region. Our study confirms that B. crocidurae infection is a frequent cause of fever in Senegal, with a high prevalence of cases in health facilities in the regions of Fatick and Kaffrine. Malaria Neg RDTs P.f are potentially a good source of pathogen sampling for the molecular identification of other causes of fever of unknown origin, even in the most remote areas.

Published
2023

2. The impact of transoesophageal echocardiography in elderly patients with infective endocarditis

Author

N’cho-Mottoh, Marie-Paule B, Erpelding, Marie-Line, Roubaud Baudron, Claire, Delahaye, François, Fraisse, Thibaut, Dijos, Marina, Ennezat, Pierre Vladimir, Fluttaz, Arnaud, Richard, Benjamin, Beaufort, Corinne, Nazeyrollas, Pierre, Brasselet, Camille, Pineau, Olivier, Tattevin, Pierre, Curlier, Elodie, Iung, Bernard, Forestier, Emmanuel, Selton-Suty, Christine, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Bordeaux [Bordeaux], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Alès-Cévennes (CHAC), CHU Grenoble, Centre Hospitalier Métropole Savoie [Chambéry], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Intercommunal Villeneuve-Saint-Georges (CHIV), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pointe-à-Pitre/Abymes [Guadeloupe], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Cardiologie [CHRU Nancy], and The initial research project ELDERL-IE, from which these data were analysed, was supported by a grant of the 'Fondation Coeur et Recherche' (France) in 2013.

Subjects
Elderly, Transoesophageal echocardiography, [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, General Medicine, Infective endocarditis, Cardiology and Cardiovascular Medicine, Geriatric assessment
Abstract

International audience; BACKGROUND: Infective endocarditis (IE) increasingly involves older patients. Geriatric status may influence diagnostic and therapeutic decisions. AIM: To describe transoesophageal echocardiography (TEE) use in elderly IE patients, and its impact on therapeutic management and mortality. METHODS: A multicentre prospective observational study (ELDERL-IE) included 120 patients aged ≥75 years with definite or possible IE: mean age 83.1±5.0; range 75-101 years; 56 females (46.7%). Patients had an initial comprehensive geriatric assessment, and 3-month and 1-year follow-up. Comparisons were made between patients who did or did not undergo TEE. RESULTS: Transthoracic echocardiography revealed IE-related abnormalities in 85 patients (70.8%). Only 77 patients (64.2%) had TEE. Patients without TEE were older (85.4±6.0 vs. 81.9±3.9 years; P=0.0011), had more comorbidities (Cumulative Illness Rating Scale-Geriatric score 17.9±7.8 vs. 12.8±6.7; P=0.0005), more often had no history of valvular disease (60.5% vs. 37.7%; P=0.0363), had a trend toward a higher Staphylococcus aureus infection rate (34.9% vs. 22.1%; P=0.13) and less often an abscess (4.7% vs. 22.1%; P=0.0122). Regarding the comprehensive geriatric assessment, patients without TEE had poorer functional, nutritional and cognitive statuses. Surgery was performed in 19 (15.8%) patients, all with TEE, was theoretically indicated but not performed in 15 (19.5%) patients with and 6 (14.0%) without TEE, and was not indicated in 43 (55.8%) patients with and 37 (86.0%) without TEE (P=0.0006). Mortality was significantly higher in patients without TEE. CONCLUSIONS: Despite similar IE features, surgical indication was less frequently recognized in patients without TEE, who less often had surgery and had a poorer prognosis. Cardiac lesions might have been underdiagnosed in the absence of TEE, hampering optimal therapeutic management. Advice of geriatricians should help cardiologists to better use TEE in elderly patients with suspected IE.

Published
2023

3. Microorganisms associated with hedgehog arthropods

Author

Benkacimi, Linda, Diarra, Adama Zan, Bompar, Jean-Michel, Bérenger, Jean-Michel, Parola, Philippe, 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), and Société Française d'Études et de Protection des Mammifères (SFEPM), Bourges

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Abstract Hedgehogs are small synanthropic mammals that live in rural areas as well as in urban and suburban areas. They can be reservoirs of several microorganisms, including certain pathogenic agents that cause human and animal public health issues. Hedgehogs are often parasitized by blood-sucking arthropods, mainly hard ticks and fleas, which in turn can also carry various vector-born microorganisms of zoonotic importance. Many biotic factors, such as urbanization and agricultural mechanization, have resulted in the destruction of the hedgehog’s natural habitats, leading these animals to take refuge near human dwellings, seeking food and shelter in parks and gardens and exposing humans to zoonotic agents that can be transmitted either directly by them or indirectly by their ectoparasites. In this review, we focus on the microorganisms detected in arthropods sampled from hedgehogs worldwide. Several microorganisms have been reported in ticks collected from these animals, including various Borrelia spp ., Anaplasma spp ., Ehrlichia spp . , and Rickettsia spp. species as well as Coxiella burnetii and Leptospira spp. As for fleas, C. burnetii , Rickettsia spp., Wolbachia spp., Mycobacterium spp. and various Bartonella species have been reported. The detection of these microorganisms in arthropods does not necessarily mean that they can be transmitted to humans and animals. While the vector capacity and competence of fleas and ticks for some of these microorganisms has been proven, in other cases the microorganisms may have simply been ingested with blood taken from an infected host. Further investigations are needed to clarify this issue. As hedgehogs are protected animals, handling them is highly regulated, making it difficult to conduct epidemiological studies on them. Their ectoparasites represent a very interesting source of information on microorganisms circulating in populations of these animals, especially vector-born ones. Graphical abstract

Published
2023

4. Molecular investigation of malaria-infected patients in Djibouti city (2018–2021)

Author

Rahma Abdi Moussa, Nasserdine Papa Mze, Houssein Yonis Arreh, Aicha Abdillahi Hamoud, Kahiya Mohamed Alaleh, Abdoul-Razak Yonis Omar, Warsama Osman Abdi, Samatar Kayad Guelleh, Abdoul-Ilah Ahmed Abdi, Mohamed Houmed Aboubaker, Leonardo K. Basco, Bouh Abdi Khaireh, Hervé Bogreau, Laboratoire de Diagnostic, Caisse Nationale de Sécurité Sociale (CNSS), Djibouti, 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), Laboratoire National de Référence, Hôpital Général Peltier, Ministère de La Santé, Djibouti, Laboratoire de Diagnostic, Caisse Nationale de Sécurité Sociale (CNSS), Djibouti, Republic of Djibouti., Laboratoire de Diagnostic, Centre de Santé Communautaire d'Einguela, Ministère de La Santé, Djibouti, Republic of Djibouti., Caisse Nationale de Sécurité Sociale (CNSS), Djibouti, Programme National de Lutte Contre Le Paludisme, Direction des Programmes de Santé Prioritaires, Ministère de La Santé, Djibouti, Republic of Djibouti., Service de Santé des Forces Armées Djiboutiennes, DSS/RQG, WorldWide Antimalarial Resistance Network Falciparum Haematology Study Group, Unité de Parasitologie, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Parasitology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

Background The Republic of Djibouti is a malaria endemic country that was in pre-elimination phase in 2006–2012. From 2013, however, malaria has re-emerged in the country, and its prevalence has been increasing every year. Given the co-circulation of several infectious agents in the country, the assessment of malaria infection based on microscopy or histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDT) has shown its limitations. This study, therefore, aimed to assess the prevalence of malaria among febrile patients in Djibouti city using more robust molecular tools. Methods All suspected malaria cases reported to be microscopy-positive were randomly sampled (n = 1113) and included in four health structures in Djibouti city over a 4-year period (2018–2021), mainly during the malaria transmission season (January–May). Socio-demographic information was collected, and RDT was performed in most of the included patients. The diagnosis was confirmed by species-specific nested polymerase chain reaction (PCR). Data were analysed using Fisher’s exact test and kappa statistics. Results In total, 1113 patients with suspected malaria and available blood samples were included. PCR confirmed that 788/1113 (70.8%) were positive for malaria. Among PCR-positive samples, 656 (83.2%) were due to Plasmodium falciparum, 88 (11.2%) Plasmodium vivax, and 44 (5.6%) P. falciparum/P. vivax mixed infections. In 2020, P. falciparum infections were confirmed by PCR in 50% (144/288) of negative RDTs. After the change of RDT in 2021, this percentage decreased to 17%. False negative RDT results were found more frequently (P Conclusions The present study confirmed the high prevalence of falciparum malaria and, to a lesser extent, vivax malaria. Nevertheless, 29% of suspected malaria cases were misdiagnosed by microscopy and/or RDT. There is a need to strengthen the capacity for diagnosis by microscopy and to evaluate the possible role of P. falciparum hrp2 gene deletion, which leads to false negative cases of P. falciparum.

Published
2023

5. Absence of Zika virus among pregnant women in Vietnam in 2008

Author

Y.-C. Chiu, D. Baud, A. Fahmi, B. Zumkehr, M. Vouga, L. Pomar, D. Musso, B. C. Thuong, M.P. Alves, M. Stojanov, Materno-Fetal and Obstetrics Research Unit, Department Woman-Mother-Child, Lausanne University Hospital, Lausanne, Switzerland., University of Bern, Centre Hospitalier de l'Ouest Guyanais Franck Joly [Saint-Laurent-du-Maroni, Guyane Française], 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), and Université de Lausanne = University of Lausanne (UNIL)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, 630 Agriculture, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Public Health, Environmental and Occupational Health, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

Background Despite being first identified in 1947, Zika virus-related outbreaks were first described starting from 2007 culminating with the 2015 Latin American outbreak. Hypotheses indicate that the virus has been circulating in Asia for decades, but reports are scarce. Methods We performed serological analysis and screened placental samples isolated in 2008 for the presence of Zika virus from pregnant women in Ho Chi Minh City (Vietnam). Results None of the placental samples was positive for Zika virus. Four serum samples out of 176 (2.3%) specifically inhibited Zika virus, with variable degrees of cross-reactivity with other flaviviruses. While one of the four samples inhibited only Zika virus, cross-reactivity with other flaviviruses not included in the study could not be ruled out. Conclusion Our results support the conclusion that the virus was not present among pregnant women in the Vietnamese largest city during the initial phases of the epidemic wave.

Published
2023

6. Correction: Molecular investigation of malaria-infected patients in Djibouti city (2018–2021)

Author

Moussa, Rahma Abdi, Papa Mze, Nasserdine, Arreh, Houssein Yonis, Hamoud, Aicha Abdillahi, Alaleh, Kahiya Mohamed, Omar, Abdoul-Razak Yonis, Abdi, Warsama Osman, Guelleh, Samatar Kayad, Abdi, Abdoul-Ilah Ahmed, Aboubaker, Mohamed Houmed, Basco, Leonardo, Khaireh, Bouh Abdi, Bogreau, Hervé, Laboratoire de Diagnostic, Caisse Nationale de Sécurité Sociale (CNSS), Djibouti, 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), Laboratoire National de Référence, Hôpital Général Peltier, Ministère de La Santé, Djibouti, Laboratoire de Diagnostic, Caisse Nationale de Sécurité Sociale (CNSS), Djibouti, Republic of Djibouti., Laboratoire de Diagnostic, Centre de Santé Communautaire d'Einguela, Ministère de La Santé, Djibouti, Republic of Djibouti., Caisse Nationale de Sécurité Sociale (CNSS), Djibouti, Programme National de Lutte Contre Le Paludisme, Direction des Programmes de Santé Prioritaires, Ministère de La Santé, Djibouti, Republic of Djibouti., Service de Santé des Forces Armées Djiboutiennes, DSS/RQG, Unité de Parasitologie, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

7. Description of Agathobaculum massiliense sp. nov., a new bacterial species prevalent in the human gut and predicted to produce indole and tryptophan based on genomic analysis

Author

Magdy Wasfy, Reham, Zoaiter, Malak, Bilen, Melhem, Tidjani Alou, Maryam, Lo, Cheikh Ibrahima, Bellali, Sara, Caputo, Aurelia, Alibar, Stéphane, Andrieu, Claudia, Raoult, Didier, Fournier, Pierre Edouard, Million, Matthieu, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Vecteurs - Infections tropicales et méditerranéennes (VITROME), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Molecular Biology, Microbiology
Abstract

International audience

Published
2023

8. Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir/Ritonavir in Patients With COVID-19

Author

Lemaitre, F., Budde, K., Gelder, T. van, Bergan, S., Lawson, R., Noceti, O., Venkataramanan, R., Elens, L., Moes, D.J.A.R., Hesselink, D.A., Pawinski, T., Johnson-Davis, K.L., Winter, B.C.M. de, Pattanaik, S., Brunet, M., Masuda, S., Langman, L.J., Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Leiden University Medical Center (LUMC), University of Oslo (UiO), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), National Center for Liver Transplantation [Montevideo, Uruguay], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Université Catholique de Louvain = Catholic University of Louvain (UCL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Medical University of Warsaw - Poland, University of Utah, Post Graduate Institute of Medical Education and Research [Chandigarh, India] (PGIMER), University of Barcelona, Dokkyo Medical University, Mayo Clinic [Rochester], None, Jonchère, Laurent, Universiteit Leiden, and UCL - SSS/LDRI - Louvain Drug Research Institute

Subjects
Pharmacology, Transplantation, mTOR inhibitors, [SDV]Life Sciences [q-bio], [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Tacrolimus, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Calcineurin inhibitors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug-drug interactions, Pharmacology (medical)
Abstract

International audience; Nirmatrelvir/ritonavir (Paxlovid®) consists of a peptidomimetic inhibitor (Nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (Ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher plasma concentrations and a longer half-life of nirmatrelvir. Co-administration of nirmatrelvir/ritonavir with immunosuppressant drugs (ISDs) is particularly challenging given the major involvement of CYP3A in the metabolism of most of these drugs and their narrow therapeutic ranges. Exposure of ISDs will be drastically increased through the potent ritonavir-mediated inhibition of CYP3A, resulting in an increased risk of adverse drug reactions. While a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejection. Here we provide some general recommendations for therapeutic drug monitoring (TDM) of ISDs and dosing recommendations when co-administered with nirmatrelvir/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day-1, while cyclosporine dosage should be reduced to 20% of the initial dosage during the antiviral treatment. Dosages of mammalian target of rapamycin inhibitors (m-TORis) should also be adjusted while dosages of mycophenolic acid and corticosteroids are expected to be less impacted.

Published
2023

9. Association Between Multidrug-Resistant Bacteria and Mortality in Critically Ill Patients

Author

Gary Duclos, Ines Lakbar, Mohamed Boucekine, Georges Lolo, Nadim Cassir, Marc Leone, Department of Anesthesiology and Intensive Care Unit, Nord Hospital, Assistance Publique Hôpitaux Universitaire de Marseille, CHU Marseille, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Department of Anesthesiology and Intensive Care Unit, Nord Hospital, Assistance Publique Hôpitaux Universitaire de Marseille, Aix Marseille University, Marseille, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service Anesthésie et Réanimation [Hôpital Nord - APHM], and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM]

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Pharmacology (medical), General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

10. In vitro maintenance of the endosymbiont Wolbachia of Dirofilaria immitis

Author

Manoj, Ranju Ravindran Santhakumari, Latrofa, Maria Stefania, Louni, Meriem, Laidoudi, Younes, Fenollar, Florence, Otranto, Domenico, Mediannikov, Oleg, Department of Veterinary Medicine, University of Bari, Valenzano, Bari, Italy, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Medicina Veterinaria, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), 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), Polytechnic University of Bari, and Bu-Ali Sina University

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, General Veterinary, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Insect Science, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Parasitology, General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

11. The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review

Author

Lucas Armange, Adèle Lacroix, Paul Petitgas, Cédric Arvieux, Caroline Piau-Couapel, Patrice Poubeau, Matthieu Revest, Pierre Tattevin, CHU Pontchaillou [Rennes], CHU Saint-Pierre, 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 ), and None

Subjects
Microbiology (medical), TNF-α antagonists, Infectious Diseases, tuberculosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, General Medicine, infliximab, paradoxical reaction, immune reconstitution inflammatory syndrome
Abstract

International audience; Paradoxical reaction (PR) and immune reconstitution inflammatory syndrome (IRIS) are common complications of tuberculosis treatment. Corticosteroids are first-line treatment for severe PR or IRIS, particularly neurological. We report four cases of severe PR or IRIS during tuberculosis treatment who required TNF-α antagonists, and identified 20 additional cases through literature review. They were 14 women and 10 men, with a median age of 36 years (interquartile range, 28-52). Twelve were immunocompromised before tuberculosis: untreated HIV infection (n=6), or immunosuppressive treatment (TNF-α antagonists, n=5; tacrolimus, n=1). Tuberculosis was mostly neuromeningeal (n=15), pulmonary (n=10), lymph node (n=6), and miliary (n=6), multi-susceptible in 23 cases. PR or IRIS started after a median time of 6 weeks (IQR, 4-9) following anti-tuberculosis treatment start, and consisted primarily of tuberculomas (n=11), cerebral vasculitis (n=8), and lymphadenitis (n=6). First-line treatment of PR or IRIS was high-dose corticosteroids in 23 cases. TNF-α antagonists were used as salvage treatment in all cases, with infliximab (n=17), thalidomide (n=6), and adalimumab (n=3). All patients improved, but 6 had neurological sequelae, and 4 had TNF-α antagonist-related severe adverse events. TNF-α antagonists are safe and effective as salvage or corticosteroid-sparing therapeutic for severe PR or IRIS during tuberculosis treatment.

Published
2023

12. Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study

Author

Matthieu Schmidt, David Hajage, Micha Landoll, Benjamin Pequignot, Elise Langouet, Matthieu Amalric, Armand Mekontso-Dessap, Luis Chiscano-Camon, Katy Surman, Dylan Finnerty, Patricia Santa-Teresa, Antonio Arcadipane, Pablo Millán, Roberto Roncon-Albuquerque, Aaron Blandino-Ortiz, Pablo Blanco-Schweizer, Pilar Ricart, Ricardo Gimeno-Costa, Carlos Luis Albacete, Philip Fortuna, Peter Schellongowski, Dieter Dauwe, Hadrien Winiszewski, Antoine Kimmoun, Bruno Levy, Greet Hermans, Giacomo Grasselli, Guillaume Lebreton, Christophe Guervilly, Gennaro Martucci, Christian Karagiannidis, Jordi Riera, Alain Combes, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), 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)-Sorbonne Université (SU), Sorbonne Université (SU), Universität Witten Herdecke, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Marseille, IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Vall d'Hebron University Hospital [Barcelona], Royal Papworth Hospital [Cambridge, UK] (RPH), Hospital General Universitario 'Gregorio Marañón' [Madrid], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Universidad Loyola Andalucía = Loyola University Andalucía, Hospital de São João [Porto], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Rio Hortega University Hospital (Hospital Universitario Río Hortega) [Valladolid, Spain] (RHUH), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia], Centro Hospitalar de Lisboa Central E.P.E, Medizinische Universität Wien = Medical University of Vienna, University Hospitals Leuven [Leuven], Service d'anesthésie et soins intensifs [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Vall d’Hebron Research Institute (VHIR)

Subjects
Pulmonary and Respiratory Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

International audience

Published
2023

13. Performance of a Commercial Multiplex Allele-Specific Polymerase Chain Reaction Kit to Genotype African-Type Glucose-6-Phosphate Dehydrogenase Deficiency

Author

Oum Kelthoum Mamadou, Djigo, Nicolas, Gomez, Mohamed Salem, Ould Ahmedou Salem, Leonardo, Basco, Ali, Ould Mohamed Salem Boukhary, Sébastien, Briolant, Université de Nouakchott Al-Aasriya (UNA), 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), and Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [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, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

8-Aminoquinoline antimalarial drugs (primaquine, tafenoquine) are required for complete cure of Plasmodium vivax malaria, but they are contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In the absence of spectrophotometry, which is a gold standard for measuring G6PD activity, G6PD genotyping is one of the alternatives to establish a database and distribution map of G6PD enzyme deficiency in Mauritania, which has become a new epicenter of P. vivax malaria in West Africa. The aim of our study was to assess the performance of multiplex allele-specific polymerase chain reaction (PCR) (African-type Diaplex C™ G6PD kit) against PCR–restriction fragment length polymorphism and sequencing. Of 146 mutations associated with G6PD A− genotypes in 177 blood samples from Mauritanian patients, all but two samples were identified correctly using multiplex allele-specific PCR (100% sensitivity and 99% specificity; “almost perfect agreement” between allele-specific PCR and PCR-restriction fragment length polymorphism/sequencing, with a kappa coefficient of 0.977). Despite a suboptimal PCR protocol for dried blood spots and the inability of the commercial assay to predict unequivocally the G6PD enzyme level in heterozygous females, the African-type Diaplex C™ G6PD genotyping kit seemed to be a valuable screening tool for male subjects and for research purposes in resource-limited countries where spectrophotometer and DNA sequencing are not available.

Published
2023

14. Which trial do we need? Aminopenicillin-gentamicin versus aminopenicillin-ceftriaxone for Enterococcus faecalis endocarditis

Author

Luque-Paz, David, Cuervo, Guillermo, Miró, José M, Tattevin, Pierre, ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], University of Barcelona, and JMM received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–23. This work was not funded.

Subjects
Microbiology (medical), [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, General Medicine
Abstract

International audience; No abstract available

Published
2023

15. Four uncommon clinical fungi, Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii and Wickerhamomyces anomalus, isolated in superficial samples from Côte d'Ivoire

Author

Ira, Ama Valérie Bonouman, Krasteva, Donika, Kouadjo, Francis, Roger, Fréderic, BELLET, Virginie, Koffi, David, Pottier, Cyrille, Toure, Offianan André, Drakulovski, Pascal, Djaman, Aliko Joseph, Ranque, Stéphane, Bertout, Sébastien, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pasteur de Côte d'Ivoire, Réseau International des Instituts Pasteur (RIIP), 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), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

16. Evaluation of knowledge and experience of fungal infections (mycoses) among clinical doctors in Senegal

Author

Diongue, Khadim, Dembélé, Boubou, Ndiaye, Mouhamadou, Seck, Mame Cheikh, Diallo, Mamadou Alpha, Badiane, Aïda Sadikh, Ndiaye, Daouda, Ranque, Stéphane, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Laboratory of Parasitology and Mycology, Aristide Le Dantec University Hospital, Dakar, CHU Aristide Le Dantec, 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), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

17. Impact of vaccination on the symptoms of hospitalised patients with SARS-CoV-2 Delta variant (B.1.617.1) infection

Author

Olivier E, Sophie A, Maeva L, Jean-François F, Jocelyn M, Emilia F, Sophie B, Cécile J, Gabrielle C, Audrey F, Simon L, Lena S, Pierre C, Aba M, Guillaume Beraud, HAL UVSQ, Équipe, Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), 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, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Limoges, Centre hospitalier d'Ajaccio, Centre hospitalier universitaire de Poitiers (CHU Poitiers), and Groupe Vaccination-Prévention de La Société de Pathologie Infectieuse de Langue Française (SPILF)

Subjects
Male, Microbiology (medical), COVID-19 Vaccines, SARS-CoV-2, Vaccination, COVID-19, Viral Vaccines, General Medicine, Severity, Breakthrough infection, Oxygen, Infectious Diseases, Delta, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Vaccine
Abstract

International audience; Objectives: The diffusion of the SARS-CoV-2 Delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status. Methods: We performed a retrospective observational study on patients hospitalised in 10 centres with a SARS-CoV-2 infection (Delta variant) from July to November 2021 by including all patients who had completed their primary vaccination at least 14 days before hospital admission and the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression. Results: We included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older (75.0 [63.25-84.0] vs. 55.0 [38.0-73.0]; p < 0.001), more frequently males (55.1% (261/474) vs. 46.4% (223/481); p = 0.009), and had more comorbidities (2.0 [1.0-3.0] vs. 1.0 [0.0-2.0]; p < 0.001). Vaccinated patients were less often admitted for Covid-19 (59.3% (281/474) vs. 75.1% (361/481); p < 0.001), had less extended lung lesions (≤25%: 64.3% (117/182) vs. 38.4% (88/229); p < 0.001), required oxygen less frequently (57.5% (229/398) vs. 73.0% (270/370); p < 0.001), at a lower flow (3.0 [0.0-8.7] vs. 6.0 [2.0-50.0] L/min, p < 0.001), and for a shorter duration (3 [0.0-8.0] vs. 6 [2.0-12.0] days, p < 0.001)., and required less frequently intensive care unit admission (16.2% (60/370) vs. 36.0% (133/369); p < 0.001) but had comparable mortality in bivariate analysis (16.7% (74/443) vs. 12.2% (53/433); p = 0.075). Multivariate logistic regression showed that vaccination significantly decreased the risk of death (0.38 [0.20-0.70](p = 0.002), ICU admission (0.31 [0.21-0.47](p < 0.001) and oxygen requirement (0.16 [0.10-0.26](p < 0.001), even among older patients or with comorbidities. Conclusions: Among patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.

Published
2022

18. How Protective are Antibodies to SARS-CoV-2, the Main Weapon of the B-Cell Response?

Author

Stéphanie Pons, Fabrice Uhel, Eric Frapy, Youssouf Sérémé, Lara Zafrani, Hugues Aschard, David Skurnik, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe de Recherche Clinique en Anesthésie Réanimation médecine PEriopératoire (GRC 29 - ARPE), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Hopital Saint-Louis [AP-HP] (AP-HP), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], and Harvard Medical School [Boston] (HMS)

Subjects
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, SARS-CoV-2, mRNA, COVID-19, General Medicine, UN SDG3, Vaccine, Antibodies
Abstract

Since the beginning of the Coronavirus disease (COVID)-19 pandemic in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for more than 600 million infections and 6.5 million deaths worldwide. Given the persistence of SARS-CoV-2 and its ability to develop new variants, the implementation of an effective and long-term herd immunity appears to be crucial to overcome the pandemic. While a vast field of research has focused on the role of humoral immunity against SARS-CoV-2, a growing body of evidence suggest that antibodies alone only confer a partial protection against infection of reinfection which could be of high importance regarding the strategic development goals (SDG) of the United Nations (UN) and in particular UN SDG3 that aims towards the realization of good health and well being on a global scale in the context of the COVID-19 pandemic. In this review, we highlight the role of humoral immunity in the host defense against SARS-CoV-2, with a focus on highly neutralizing antibodies. We summarize the results of the main clinical trials leading to an overall disappointing efficacy of convalescent plasma therapy, variable results of monoclonal neutralizing antibodies in patients with COVID-19 but outstanding results for the mRNA based vaccines against SARS-CoV-2. Finally, we advocate that beyond antibody responses, the development of a robust cellular immunity against SARS-CoV-2 after infection or vaccination is of utmost importance for promoting immune memory and limiting disease severity, especially in case of (re)-infection by variant viruses. Graphical Abstract: [Figure not available: see fulltext.]

Published
2022

19. A large-scale genomic snapshot of Klebsiella spp. isolates in Northern Italy reveals limited transmission between clinical and non-clinical settings

Author

Harry A. Thorpe, Ross Booton, Teemu Kallonen, Marjorie J. Gibbon, Natacha Couto, Virginie Passet, Sebastián López-Fernández, Carla Rodrigues, Louise Matthews, Sonia Mitchell, Richard Reeve, Sophia David, Cristina Merla, Marta Corbella, Carolina Ferrari, Francesco Comandatore, Piero Marone, Sylvain Brisse, Davide Sassera, Jukka Corander, Edward J. Feil, University of Oslo (UiO), University of Bristol [Bristol], Turku University Hospital (TYKS), University of Bath [Bath], Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), University of Glasgow, The Wellcome Trust Sanger Institute [Cambridge], Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione 'Istituto Neurologico Nazionale C. Mondino', Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Pavia = University of Pavia (UNIPV), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, This work was funded by the SpARK project, awarded to E.J.F., ‘The rates and routes of transmission of multidrug-resistant Klebsiella clones and genes into the clinic from environmental sources’, which has received funding under the 2016 Joint Programming Initiative on Antimicrobial Resistance call ‘Transmission dynamics’ (medical research council (MRC) reference no. MR/R00241X/1) and by the French Government’s Investissement d’Avenir program Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (no. ANR-10-LABX-62-IBEID). J.C. and H.A.T. were funded by the European Research Council grant no. 742158. J.C. and T.K. were funded by the Norwegian Research Council grant no. 271162., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Helsinki Institute for Information Technology, Jukka Corander / Principal Investigator, Department of Mathematics and Statistics, and Department of Computer Science

Subjects
11832 Microbiology and virology, Microbiology (medical), Diversity, Carriage, Genotype, Immunology, Genomics, Cell Biology, Antimicrobial resistance, Applied Microbiology and Biotechnology, Microbiology, Pneumoniae, Association, Carbapenems, Italy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Klebsiella, Genetics, Animals, Humans, Antibiotic-resistance
Abstract

Genomic analyses of Klebsiella isolates sampled from multiple human, animal and environmental sources in Northern Italy explore Klebsiella population diversity and show that transmission of multidrug-resistant clones between clinical and environmental settings is scarce.The Klebsiella group, found in humans, livestock, plants, soil, water and wild animals, is genetically and ecologically diverse. Many species are opportunistic pathogens and can harbour diverse classes of antimicrobial resistance genes. Healthcare-associated Klebsiella pneumoniae clones that are non-susceptible to carbapenems can spread rapidly, representing a high public health burden. Here we report an analysis of 3,482 genome sequences representing 15 Klebsiella species sampled over a 17-month period from a wide range of clinical, community, animal and environmental settings in and around the Italian city of Pavia. Northern Italy is a hotspot for hospital-acquired carbapenem non-susceptible Klebsiella and thus a pertinent setting to examine the overlap between isolates in clinical and non-clinical settings. We found no genotypic or phenotypic evidence for non-susceptibility to carbapenems outside the clinical environment. Although we noted occasional transmission between clinical and non-clinical settings, our data point to a limited role of animal and environmental reservoirs in the human acquisition of Klebsiella spp. We also provide a detailed genus-wide view of genomic diversity and population structure, including the identification of new groups.

Published
2022

20. Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation*

Author

Massart, Nicolas, Guervilly, Christophe, Mansour, Alexandre, Porto, Alizée, Flécher, Erwan, Esvan, Maxime, Fougerou, Claire, Fillâtre, Pierre, Duburcq, Thibault, Lebreton, Guillaume, Para, Marylou, Stephan, François, Hraiech, Sami, Ross, James, Schmidt, Matthieu, Vincentelli, André, Nesseler, Nicolas, CHU Pontchaillou [Rennes], Hôpital Yves LE FOLL [Saint-Brieuc], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Nord [CHU - APHM], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Université de Lille, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Marie-Lannelongue, University of California [Davis] (UC Davis), University of California (UC), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome Coronavirus 2 (ECMOSARS) Investigators: Olivier Fouquet, Marc Pierrot, Sidney Chocron, Guillaume Flicoteaux, Philippe Mauriat, Hadrien Roze, Alexandre Ouattara, Olivier Huet, Marc-Olivier Fischer, Claire Alessandri, Raphel Bellaïche, Ophélie Constant, Quentin De Roux, André Ly, Arnaud Meffert, Jean-Claude Merle, Lucile Picard, Elena Skripkina, Thierry Folliguet, Nicolas Mongardon, Antonio Fiore, Nicolas D'ostrevy, Marie-Catherine Morgan, Maxime Nguyen, Pierre-Grégoire Guinot, Lucie Gaide-Chevronnay, Nicolas Terzi, Gwenhaël Colin, Olivier Fabre, Arash Astaneh, Justin Issard, Elie Fadel, Dominique Fabre, Antoine Girault, Iolande Ion, Jean Baptiste Menager, Delphine Mitilian, Julien Guihaire, Olaf Mercier, Jacques Thes, Jerôme Jouan, Thibault Duburcq, Valentin Loobuyck, Sabrina Manganiello, Mouhammed Moussa, Agnes Mugnier, Natacha Rousse, Olivier Desebbe, Roland Henaine, Matteo Pozzi, Jean-Luc Fellahi, Jean-Christophe Richard, Zakaria Riad, Laurent Papazian, Matthias Castanier, Charles Chanavaz, Cyril Cadoz, Sebastien Gette, Guillaume Louis, Erick Portocarrero, Philippe Gaudard, Kais Brini, Nicolas Bischoff, Antoine Kimmoun, Bruno Levy, Mathieu Mattei, Pierre Perez, Alexandre Bourdiol, Yannick Hourmant, Pierre-Joachim Mahé, Bertrand Rozec, Mickaël Vourc'h, Stéphane Aubert, Florian Bazalgette, Claire Roger, Sophie Provenchere, Pierre Jaquet, Brice Lortat-Jacob, Pierre Mordant, Patrick Nataf, Juliette Patrier, Morgan Roué, Romain Sonneville, Alexy Tran-Dinh, Paul-Henri Wicky, Charles Al Zreibi, Bernard Cholley, Yannis Guyonvarch, Sophie Hamada, Claudio Barbanti, Anatole Harrois, Astrid Bertier, Jordi Matiello, Thomas Kerforne, Corentin Lacroix, Nicolas Brechot, Juliette Chommeloux, Alain Combes, Jean Michel Constantin, Cosimo D'alessandro, Pierre Demondion, Alexandre Demoule, Martin Dres, Muriel Fartoukh, Guillaume Hekimian, Charles Juvin, Pascal Leprince, Guillaume Fadel, David Levy, Charles Edouard Luyt, Marc Pineton de Chambrun, Thibaut Schoell, Roxane Nicolas, Maud Jonas, Charles Vidal, Nicolas Allou, Salvatore Muccio, Dario Di Perna, Bruno Mourvillier, Vito-Giovanni Ruggieri, Amedeo Anselmi, Karl Bounader, Yoann Launey, Thomas Lebouvier, Alessandro Parasido, Florian Reizine, Philippe Seguin, Emmanuel Besnier, Dorothée Carpentier, Thomas Clavier, Anne Olland, Pierre-Emmanuel Falcoz, Marion Villard, Fanny Bounes, François Labaste, Vincent Minville, Antoine Guillon, Yannick Fedun, and MORNET, Dominique

Subjects
[SDV] Life Sciences [q-bio], critical care, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV]Life Sciences [q-bio], prone position, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, acute respiratory distress syndrome, extracorporeal membrane oxygenation, mechanical ventilation, Critical Care and Intensive Care Medicine, mortality
Abstract

International audience; Objectives: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS.Design: Retrospective analysis of a multicenter cohort.Patients: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible.Interventions: None.Measurements and main results: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients.Conclusions: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions.

Published
2022

21. Evolution of immune genes is associated with the Black Death

Author

Jennifer Klunk, Tauras P. Vilgalys, Christian E. Demeure, Xiaoheng Cheng, Mari Shiratori, Julien Madej, Rémi Beau, Derek Elli, Maria I. Patino, Rebecca Redfern, Sharon N. DeWitte, Julia A. Gamble, Jesper L. Boldsen, Ann Carmichael, Nükhet Varlik, Katherine Eaton, Jean-Christophe Grenier, G. Brian Golding, Alison Devault, Jean-Marie Rouillard, Vania Yotova, Renata Sindeaux, Chun Jimmie Ye, Matin Bikaran, Anne Dumaine, Jessica F. Brinkworth, Dominique Missiakas, Guy A. Rouleau, Matthias Steinrücken, Javier Pizarro-Cerdá, Hendrik N. Poinar, Luis B. Barreiro, McMaster Ancient DNA Center [Hamilton, Ontario], McMaster University [Hamilton, Ontario], Daicel Arbor Biosciences [Ann Arbor, MI], University of Chicago, Yersinia, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Museum of London, University of South Carolina [Columbia], University of Manitoba [Winnipeg], University of Southern Denmark (SDU), Indiana University [Bloomington], Indiana University System, Rutgers University [Newark], Rutgers University System (Rutgers), Université de Montréal (UdeM), University of Michigan [Ann Arbor], University of Michigan System, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], University of California [San Francisco] (UC San Francisco), University of California (UC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, McGill University = Université McGill [Montréal, Canada], and This work was supported by grant R01-GM134376 to L.B.B., H.P. and J.P.-C., a grant from the Wenner-Gren Foundation to J.F.B. (8702), and the UChicago DDRCC, Center for Interdisciplinary Study of Inflammatory Intestinal Disorders (C-IID) (NIDDK P30 DK042086). The SSHRC Insight Development Grant supported the collection of the Danish samples (430-2017-01193). H.N.P. was supported by an Insight Grant no. 20008499 from the Social Sciences and Humanities Research Council of Canada (SSHRC) and The Canadian Institute for Advanced Research under the Humans and the Microbiome programme. T.P.V. was supported by NIH F32GM140568. X.C. and M. Steinrücken were supported by grant R01GM146051. We also thank the University of Chicago Genomics Facility (RRID:SCR_019196), especially P. Faber, for their assistance with RNA sequencing. H.P. thanks D. Poinar for continued support and manuscript suggestions and editing.

Subjects
Yersinia pestis, General Science & Technology, Denmark, Datasets as Topic, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Aminopeptidases, Ancient, Genetic, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, London, Genetics, Humans, Genetic Predisposition to Disease, DNA, Ancient, Selection, Genetic, Selection, Plague, Multidisciplinary, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Prevention, Immunity, DNA, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Europe, Vector-Borne Diseases, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Infection
Abstract

International audience; Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Published
2022

22. Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study—The ARTHR-IS Study Group

Author

Reinaldo, Espíndola, Venanzio, Vella, Natividad, Benito, Isabel, Mur, Sara, Tedeschi, Eleonora, Zamparini, Johannes G E, Hendriks, Luisa, Sorlí, Oscar, Murillo, Laura, Soldevila, Mathew, Scarborough, Claire, Scarborough, Jan, Kluytmans, Mateo Carlo, Ferrari, Mathias W, Pletz, Iain, Mcnamara, Rosa, Escudero-Sanchez, Cedric, Arvieux, Cecile, Batailler, Frédéric-Antoine, Dauchy, Wai-Yan, Liu, Jaime, Lora-Tamayo, Julia, Praena, Andrew, Ustianowski, Elisa, Cinconze, Michele, Pellegrini, Fabio, Bagnoli, Jesús, Rodríguez-Baño, Maria Dolores, Del Toro, Gabriella, Lindergard, Hospital Universitario Virgen Macarena [Séville], GlaxoSmithKline [Siena, Italy] (GSK), Hospital de la Santa Creu i Sant Pau, University of Bologna/Università di Bologna, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Orthopaedic Surgery and Trauma, Maxima MC, parent, IMIM-Hospital del Mar, Generalitat de Catalunya, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), John Radcliffe Hospital [Oxford University Hospital], Amphia Ziekenhuis = Amphia Hospital [Breda, The Netherlands] (AZ=AH), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Jena University Hospital [Jena], Norfolk and Norwich University Hospital, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406 ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Catharina Hospital, Hospital Universitario HM Sanchinarro [Madrid, Spain], Hospital Universitario Virgen del Rocío [Sevilla], North Manchester General Hospital, This work was supported by the Innovative Medicines Initiative Joint Undertaking (grant agreement No. 115523), COMBACTE-NET consortium (European Union FP7/2007–2013 and GlaxoSmithKline Biologicals SA, as EFPIA partner). European Development Regional Fund ‘‘A way to achieve Europe’’, Operative Program Intelligence Growth 2014-2020. The study sponsor is also funding the journal’s Rapid Service Fee., European Project: 115523,EC:FP7:SP1-JTI,IMI-JU-06-2012,COMBACTE(2013), European Commission, GlaxoSmithKline, European Federation of Pharmaceutical Industries and Associations, Red Española de Investigación en Patología Infecciosa, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Espíndola, Reinaldo, Vella, Venanzio, Benito, Natividad, Mur, Isabel, Tedeschi, Sara, Zamparini, Eleonora, Hendriks, Johannes G E, Sorlí, Luisa, Murillo, Oscar, Soldevila, Laura, Scarborough, Mathew, Scarborough, Claire, Kluytmans, Jan, Ferrari, Mateo Carlo, Pletz, Mathias W, Mcnamara, Iain, Escudero-Sanchez, Rosa, Arvieux, Cedric, Batailler, Cecile, Dauchy, Frédéric-Antoine, Liu, Wai-Yan, Lora-Tamayo, Jaime, Praena, Julia, Ustianowski, Andrew, Cinconze, Elisa, Pellegrini, Michele, Bagnoli, Fabio, Rodríguez-Baño, Jesú, and Del Toro, Maria Dolores

Subjects
STAPHYLOCOCCUSAUREUS, Microbiology (medical), Staphylococcus aureus, Prosthetic joint infection, Infectious Diseases, Functional failure, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical failure, Outcome
Abstract

[Introduction] Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome., [Methods] A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed., [Results] One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin, [Conclusions] TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies., [Trial registration] This study is registered at clinicaltrials.gov, registration no. NCT03826108., This work was supported by the Innovative Medicines Initiative Joint Undertaking (grant agreement No. 115523), COMBACTE-NET consortium (European Union FP7/2007–2013 and GlaxoSmithKline Biologicals SA, as EFPIA partner). R.E, L.S, O. M, R. E-S, J. L–T, J. P, J. R-B and MD. del T are members of the Spanish Network for Research in Infectious Diseases (REIPI), supported by Plan Nacional de I + D + i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001; 0002; 0005; 0009; 0011; 0015), co‐ financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligence Growth 2014‐2020.

Published
2022

23. Luspatercept (RAP-536) modulates oxidative stress without affecting mutation burden in myelodysplastic syndromes

Author

Meunier Mathieu, Chloé Friedrich, Nicolas Ducrot, Johanna Zannoni, Tondeur Sylvie, Nelly Jerraya, Sophie Rousseaux, Florent Chuffart, Olivier Kosmider, Zoubida Karim, Sophie Park, CHU Grenoble, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and karim, zoubida

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Luspatercept, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], PDX mice model, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hematology, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Mice, Oxidative Stress, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Myelodysplastic Syndromes, Mutation, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Animals, RAP-536
Abstract

International audience; In low-risk myelodysplastic syndrome (LR-MDS), erythropoietin (EPO) is widely used for the treatment of chronic anemia. However, initial response to EPO has time-limited effects. Luspatercept reduces red blood cell transfusion dependence in LR-MDS patients. Here, we investigated the molecular action of luspatercept (RAP-536) in an in vitro model of erythroid differentiation of MDS, and also in a in vivo PDX murine model with primary samples of MDS patients carrying or not SF3B1 mutation. In our in vitro model, RAP-536 promotes erythroid proliferation by increasing the number of cycling cells without any impact on apoptosis rates. RAP-536 promoted late erythroid precursor maturation while decreasing intracellular reactive oxygen species level. RNA sequencing of erythroid progenitors obtained under RAP-536 treatment showed an enrichment of genes implicated in positive regulation of response to oxidative stress and erythroid differentiation. In our PDX model, RAP-536 induces a higher hemoglobin level. RAP-536 did not modify variant allele frequencies in vitro and did not have any effect against leukemic burden in our PDX model. These results suggest that RAP-536 promotes in vivo and in vitro erythroid cell differentiation by decreasing ROS level without any remarkable impact on iron homeostasis and on mutated allele burden.

Published
2022

24. Toward more potent imidazopyridine inhibitors of <scp> Candida albicans </scp> Bdf1: Modeling the role of structural waters in selective ligand binding

Author

Yingsheng Zhou, Justin M. Overhulse, Nathan J. Dupper, Yanchun Guo, Boris A. Kashemirov, Kaiyao Wei, Jérôme Govin, Carlo Petosa, Charles E. McKenna, Department of Chemistry, University of Southern California (USC), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)

Subjects
BET inhibition, Binding Sites, receptor-binding model, structural water, General Chemistry, Ligands, molecular dynamics, Computational Mathematics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Candida albicans, Humans, antifungal drugs, bromodomains, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcription Factors
Abstract

International audience; Novel agents to treat invasive fungal infections are urgently needed because the small number of established targets in pathogenic fungi makes the existing drug repertoire particularly vulnerable to the emergence of resistant strains. Recently, we reported that Candida albicans Bdf1, a bromodomain and extra-terminal domain (BET) bromodomain with paired acetyl-lysine (AcK) binding sites (BD1 and BD2) is essential for fungal cell growth and that an imidazopyridine (1) binds to BD2 with selectivity versus both BD1 and human BET bromodomains. Bromodomain binding pockets contain a conserved array of structural waters. Molecular dynamics simulations now reveal that one water molecule is less tightly bound to BD2 than to BD1, explaining the site selectivity of 1. This insight is useful in the performance of ligand docking studies to guide design of more effective Bdf1 inhibitors, as illustrated by the design of 10 new imidazopyridine BD2 ligands 1a–j, for which experimental binding and site selectivity data are presented.

Published
2022

25. Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2

Author

Guillaume Martin-Blondel, Anne-Genevieve Marcelin, Cathia Soulié, Sofia Kaisaridi, Clovis Lusivika-Nzinga, Céline Dorival, Laura Nailler, Anaïs Boston, Cléa Melenotte, André Cabié, Christophe Choquet, François Coustillères, Jean-Philippe Martellosio, Géraldine Gaube, Albert Trinh-Duc, Anne-Marie Ronchetti, Valerie Pourcher, Marie Chauveau, Karine Lacombe, Nathan Peiffer-Smadja, Pierre Housset, Aurore Perrot, Gilles Pialoux, Aurélie Martin, Vincent Dubee, Mathilde Devaux, Jérôme Frey, Charles Cazanave, Roland Liblau, Fabrice Carrat, Youri Yordanov, Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANRS France Recherche Nord & sud Sida-hiv hépatites, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Accueil des Urgences (AGEN - SAU), Centre Hospitalier d'Agen, Centre Hospitalier Sud Francilien, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Hôtel-Dieu de Nantes, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Services de Maladies Infectieuses et Tropicales [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), CHR de Metz-Thionville, CHU Bordeaux [Bordeaux], Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service d'Allergologie et d'Immunologie [CHU Toulouse], Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), 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)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Urgences Adultes [CHU Saint-Antoine], and Gestionnaire, Hal Sorbonne Université

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, COVID-19, Humans, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing
Abstract

International audience; Before the Omicron era, the neutralizing antibody targeting the SARS-CoV2 Spike protein Sotrovimab has been shown to reduce the risk of COVID-19-related hospitalization in patients who are at high risk for progression (1, 2). We recently showed that early administration of Sotrovimab in Omicron-infected patients with very high-risk for progression was associated with a low rate of COVID-19-related hospitalization within one month after treatment administration (3%), and with no death (1). However, the dominance of the Omicron sublineage BA.2 led health agencies to suspend Sotrovimab emergency use authorizations because of its lower neutralizing ability in vitro compared to BA.1 sublineage (3, 4). Clinical efficiency of Sotrovimab to prevent COVID-19 related complications in high-risk patients with mild-to-moderate COVID-19 Omicron BA.2 remains unknown. Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients with mild-to-moderate COVID-19 who received 500 mg of Sotrovimab IV to prevent COVID-19-related complications.

Published
2022

26. Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance

Author

Alexia Chauzy, Nicolas Gregoire, Martine Ferrandière, Sigismond Lasocki, Karim Ashenoune, Philippe Seguin, Matthieu Boisson, William Couet, Sandrine Marchand, Olivier Mimoz, Claire Dahyot-Fizelier, Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], and Chauzy, Alexia

Subjects
Methicillin-Resistant Staphylococcus aureus, Pharmacology, Microbiology (medical), Critical Care, Microbial Sensitivity Tests, Pneumonia, Anti-Bacterial Agents, Cephalosporins, Streptococcus pneumoniae, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Pharmacology (medical), Renal Insufficiency, Monte Carlo Method
Abstract

Objectives Ceftaroline could be suitable to treat early-onset ventilator-associated pneumonia (VAP) because of its antibacterial spectrum. However, augmented renal clearance (ARC) is frequent in ICU patients and may affect ceftaroline pharmacokinetics and efficacy. The objective of the study was to explore the impact of ARC on ceftaroline pharmacokinetics and evaluate whether the currently recommended dosing regimen (600 mg every 12 h) is appropriate to treat VAP in ICU patients. Methods A population pharmacokinetic model was developed using pharmacokinetic data from 18 patients with measured creatinine clearance (CLCR) ranging between 83 and 309 mL/min. Monte Carlo simulations were conducted to determine the PTA and the cumulative fraction of response (CFR) against Streptococcus pneumoniae and MRSA for five dosing regimens. Study registered at ClinicalTrials.gov (NCT03025841). Results Ceftaroline clearance increased non-linearly with CLCR, with lower concentrations and lower probability of reaching pharmacokinetic/pharmacodynamic targets when CLCR increases. For the currently recommended dosing regimen, the probability of having unbound ceftaroline concentrations above the MIC over the entire dose range is greater than 90% for MICs below 0.125 mg/L. Considering the distribution of MICs, this regimen would not be effective against MRSA infections (CFR between 21% and 67% depending on CLCR), but would be effective against S. pneumoniae infections (CFR >86%). Conclusions The recommended dosing regimen of ceftaroline seems sufficient for covering S. pneumoniae in ICU patients with ARC, but not for MRSA. Among the dosing regimens tested it appears that a constant infusion (50 mg/h) after a loading dose of 600 mg could be more appropriate for MRSA infections.

Published
2022

27. Investigating drug resistance of Mycobacterium leprae in the Comoros: an observational deep-sequencing study

Author

Sofie Marijke Braet, Agathe Jouet, Alexandra Aubry, Magalie Van Dyck-Lippens, Esteban Lenoir, Younoussa Assoumani, Abdallah Baco, Aboubacar Mzembaba, Emmanuelle Cambau, Sidra Ezidio Gonçalves Vasconcellos, Leen Rigouts, Philip Noel Suffys, Epco Hasker, Philip Supply, Bouke Catherine de Jong, University of Antwerp (UA), Institute of Tropical Medicine [Antwerp] (ITM), Genoscreen [Lille], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière] (CNR-MyRMA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Damien Foundation, 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, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Supply, Philip, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)

Subjects
Microbiology (medical), [SDV.GEN]Life Sciences [q-bio]/Genetics, Leprostatic Agents, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Microbiology, Comoros, Mycobacterium leprae, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Leprosy, Virology, Drug Resistance, Bacterial, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Drug Therapy, Combination, Human medicine, Rifampin, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Dapsone, Biology
Abstract

Despite strong leprosy control measures, including effective treatment, leprosy persists in the Comoros. As of May, 2022, no resistance to anti-leprosy drugs had been reported, but there are no nationally representative data. Post-exposure prophylaxis (PEP) with rifampicin is offered to contacts of patients with leprosy. We aimed to conduct a countrywide drug resistance survey and investigate whether PEP led to the emergence of drug resistance in patients with leprosy.In this observational, deep-sequencing analysis we assessed Mycobacterium leprae genomes from skin biopsies of patients in Anjouan and Mohéli, Comoros, collected as part of the ComLep (NCT03526718) and PEOPLE (NCT03662022) studies. Skin biopsies that had sufficient M leprae DNA (2000 bacilli in 2 μl of DNA extract) were assessed for the presence of seven drug resistance-associated genes (ie, rpoB, ctpC, ctpI, folP1, gyrA, gyrB, and nth) using Deeplex Myc-Lep (targeted next generation deep sequencing), with a limit of detection of 10% for minority M leprae bacterial populations bearing a polymorphism in these genes. All newly registered patients with leprosy for whom written informed consent was obtained were eligible for inclusion in the survey. Patients younger than 2 years or with a single lesion on the face did not have biopsies taken. The primary outcome of our study was the proportion of patients with leprosy (ie, new cases, patients with relapses or reinfections, patients who received single (double) dose rifampicin-PEP, or patients who lived in villages where PEP was distributed) who were infected with M leprae with a drug-resistant mutation for rifampicin, fluoroquinolone, or dapsone in the Comoros.Between July 1, 2017, and Dec 31, 2020, 1199 patients with leprosy were identified on the basis of clinical criteria, of whom 1030 provided a skin biopsy. Of these 1030 patients, 755 (73·3%) tested positive for the M leprae-specific repetitive element-quantitative PCR (qPCR) assay. Of these 755 patients, 260 (34·4%) were eligible to be analysed using Deeplex Myc-Lep. 251 (96·5%) were newly diagnosed with leprosy, whereas nine (3·4%) patients had previously received multidrug therapy. 45 (17·3%) patients resided in villages where PEP had been administered in 2015 or 2019, two (4·4%) of whom received PEP. All seven drug resistance-associated targets were successfully sequenced in 216 samples, 39 samples had incomplete results, and five had no results. No mutations were detected in any of the seven drug resistance-related genes for any patient with successfully sequenced results.This drug resistance survey provides evidence to show that M leprae is fully susceptible to rifampicin, fluoroquinolones, and dapsone in the Comoros. Our results also show, for the first time, the applicability of targeted sequencing directly on skin biopsies from patients with either paucibacillary or multibacillary leprosy. These data suggest that PEP had not selected rifampicin-resistant strains, although further support for this finding should be confirmed with a larger sample size.Effect:Hope, The Mission To End Leprosy, the Fonds Wetenschappelijk Onderzoek, the EU.

Published
2022

28. Daptomycin Physiology-Based Pharmacokinetic Modeling to Predict Drug Exposure and Pharmacodynamics in Skin and Bone Tissues

Author

Romain Garreau, Damien Montange, Antoine Grillon, François Jehl, Tristan Ferry, Laurent Bourguignon, Sylvain Goutelle, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), CHU Strasbourg, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, 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), Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université de Lyon-Université de Lyon, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE)

Subjects
Pharmacology, MESH: Microbial Sensitivity Tests, MESH: Humans, MESH: Staphylococcal Infections / drug therapy, MESH: Daptomycin / pharmacology, Microbial Sensitivity Tests, Staphylococcal Infections, MESH: Bone and Bones, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bone and Bones, Anti-Bacterial Agents, Daptomycin, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Anti-Bacterial Agents, Humans, Pharmacology (medical), MESH: Staphylococcal Infections / microbiology
Abstract

International audience; Background and objective: Daptomycin has been recommended in the treatment of bone and joint infection. Previous work showed that the approved dosage of daptomycin may be insufficient to achieve optimal exposure in patients with bone and joint infection. However, those studies assumed that bone exposure was similar to steady-state daptomycin-free plasma concentrations. We sought to establish a physiologically based pharmacokinetic (PBPK) model of daptomycin to describe the dynamics of daptomycin disposition in bone and skin tissue.Methods: a PBPK model of daptomycin was built using PK-Sim®. Daptomycin concentrations in plasma and bone were obtained from three previously published studies. Physicochemical drug characteristics, mass balance, anthropometrics, and experimental data were used to build and refine the PBPK model. Internal validation of the PBPK model was performed using the usual diagnostic plots. The final PBPK model was then used to run simulations with doses of 6, 8, 10, and 12 mg/kg/24 h. Pharmacokinetic profiles were simulated in 1.000 subjects and the probabilities of target attainment for the area under the concentration-time curve over the bacterial minimum inhibitory concentration were computed in blood, skin, and bone compartments.Results: the final model showed a good fit of all datasets with an absolute average fold error between 0.5 and 2 for all pharmacokinetic quantities in blood, skin and bone tissues. Results of dosing simulations showed that doses ≥10 mg/kg should be used in the case of bacteremia caused by Staphylococcus aureus with a minimum inhibitory concentration >0.5 mg/L or Enterococcus faecalis with a minimum inhibitory concentration >1 mg/L, while doses ≥12 mg/kg should be used in the case of bone and joint infection or complicated skin infection. When considering a lower minimum inhibitory concentration, doses of 6-8 mg/kg would likely achieve a sufficient success rate. However, in the case of infections caused by E. faecalis with a minimum inhibitory concentration >2 mg/L, a higher dosage and combination therapy would be necessary to maximize efficacy.Conclusions: we developed the first daptomycin PBPK/pharmacodynamic model for bone and joint infection, which confirmed that a higher daptomycin dosage is needed to optimize exposure in bone tissue. However, such higher dosages raise safety concerns. In this setting, therapeutic drug monitoring and model-informed precision dosing appear necessary to ensure the right exposure on an individual basis.

Published
2022

29. Impact of Chemoprophylaxis on Plasmodium vivax and Plasmodium ovale Infection Among Civilian Travelers: A Nested Case-Control Study With a Counterfactual Approach on 862 Patients

Author

Le Goff, Maëlle, Kendjo, Eric, Thellier, Marc, Piarroux, Renaud, Boelle, Pierre Yves, Jauréguiberry, Stéphane, BOELLE, Pierre-Yves, Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière] (CNRpalu), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)

Subjects
Microbiology (medical), Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Plasmodium ovale, travellers, malaria, chemoprophylaxis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Plasmodium vivax
Abstract

Background The impact of chemoprophylaxis targeting Plasmodium falciparum on Plasmodium vivax and Plasmodium ovale, which may remain quiescent as hypnozoites in the liver, is debated. Methods We conducted a nested case-control analysis of the outcomes of P. vivax and P. ovale infections in imported malaria cases in France among civilian travelers from 1 January 2006, to 31 December 2017. Using adjusted logistic regression, we assessed the effect of chemoprophylaxis on the incubation period, time from symptoms to diagnosis, management, blood results, symptoms, and hospitalization duration. We analyzed the effect of blood-stage drugs (doxycycline, mefloquine, chloroquine, chloroquine-proguanil) or atovaquone-proguanil on the incubation period. We used a counterfactual approach to ascertain the causal effect of chemoprophylaxis on postinfection characteristics. Results Among 247 P. vivax– and 615 P. ovale–infected travelers, 30% and 47%, respectively, used chemoprophylaxis, and 7 (3%) and 8 (1%) were severe cases. Chemoprophylaxis users had a greater risk of presenting symptoms >2 months after returning for both species (P. vivax odds ratio [OR], 2.91 [95% confidence interval {CI}, 1.22–6.95], P = .02; P. ovale OR, 2.28 [95% CI, 1.47–3.53], P < .001). Using drugs only acting on the blood stage was associated with delayed symptom onset after 60 days, while using atovaquone-proguanil was not. Conclusions Civilian travelers infected with P. vivax or P. ovale reporting chemoprophylaxis use, especially of blood-stage agents, had a greater risk of delayed onset of illness. The impact of chemoprophylaxis on the outcomes of infection with relapse-causing species calls for new chemoprophylaxis acting against erythrocytic and liver stages.

Published
2022

30. Novel Chronic Anaplasmosis in Splenectomized Patient, Amazon Rainforest

Author

Olivier Duron, Rachid Koual, Lise Musset, Marie Buysse, Yann Lambert, Benoît Jaulhac, Denis Blanchet, Kinan Drak Alsibai, Yassamine Lazrek, Loïc Epelboin, Pierre Deshuillers, Céline Michaud, Maylis Douine, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Laboratoire de Parasitologie [Cayenne, Guyane française], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The research was supported by funding from Investissements d’Avenir grants managed by the Agence Nationale de la Recherche (ANR, France, Laboratoire d’Excellence CEBA, ref. ANR-10-LABX-25-01)., and ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010)

Subjects
Microbiology (medical), Anaplasmosis, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Anaplasma, Rainforest, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemiology, Animals, Humans, Rickettsia Infections, Brazil
Abstract

International audience; We report a case of unusual human anaplasmosis in the Amazon rainforest of French Guiana. Molecular typing demonstrated that the pathogen is a novel Anaplasma species, distinct to all known species, and more genetically related to recently described Anaplasma spp. causing infections in rainforest wild fauna of Brazil.

Published
2022

31. High SARS-CoV-2 seroprevalence in HIV patients originating from sub-Saharan Africa in the Ile-de-France area

Author

Basma ABDI, Aude Laetitia NDOADOUMGUE, Siham DJEBARA, Karen ZAFILAZA, Romain PALICH, Stéphane MAROT, Luminata SCHNEIDER, Marc WIRDEN, Sophie SEANG, Yasmine DUDOIT, Elisa TEYSSOU, Roland TUBIANA, Cathia SOULIE, Marc Antoine VALANTIN, Christine KATLAMA, Vincent CALVEZ, Lambert ASSOUMOU, Anne-Geneviève MARCELIN, Valérie POURCHER, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and ABDI, BASMA

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, seroprevalence, SARS-CoV-2, COVID-19, HIV, humoral immune response, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, risk factors, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; Objectives: We studied the kinetics of SARS-CoV-2 antibodies and identified the associated risk factors with the presence of these antibodies.Methods: In this longitudinal cohort study, we included all PLWHIV. Samples were tested for IgG targeting the nucleocapsid (N) and all positive samples were tested for IgG targeting the spike (S) and IgA targeting S.Results: 1,901 PLWHIV were included: 64.4% male, median age: 53 years (44-60). At inclusion, 254 (13.4%, 95% CI 11.9, 15.0) had positive IgG anti-N. Levels of IgG anti-N, IgG anti-S and IgA anti-S were 3.95 (standard error: 0.16), 199.4 BAU/mL (21.7) and 3.14 (0.21), respectively. Over one year, levels of IgG anti-N and anti-S decreased significantly (-2.83 p

Published
2022

32. Synthesis, Anti-Plasmodial Activities, and Mechanistic Insights of 4-Aminoquinoline-Triazolopyrimidine Hybrids

Author

Shefali Chowdhary, null Shalini, Joel Mosnier, Isabelle Fonta, Bruno Pradines, Nosipho Cele, Pule Seboletswe, Parvesh Singh, Vipan Kumar, Guru Nanak Dev University, Punjab, Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), 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), and University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, Organic Chemistry, Drug Discovery, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Biochemistry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

In the search of new antiplasmodial agents, a multitargeted approach was used in the synthesis of triazolopyrimidine- and 4-aminoquinolines-based hybrids.

Published
2023

33. Identifiability and Observability via decoupled variables: Application to a malaria intra-host model

Author

Bichara, Derdei, Iggidr, Abderrahman, Oumoun, Mohamed, Rapaport, Alain, Sallet, Gauthier, Department of Mathematics [Fullerton], California State University [Fullerton] (CSU), Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria), Université Cadi Ayyad [Marrakech] (UCA), Ecole Nationale des Sciences Appliquées [Marrakech] (ENSA), Mathématiques, Informatique et STatistique pour l'Environnement et l'Agronomie (MISTEA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
observability, parameters identification, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], Parameters estimation, observer, [MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC], identifiability
Abstract

International audience; For a class of systems for which identifiability is difficult to be proved in the original set of coordinates, we show that when there exists a change of variables which decouples some variables i.e., whose dynamics is independent of the parameters, identifiability can then be assessed without having to compute derivatives. Moreover, we show that this allows to consider an observer to reconstruct the state of the system without having to estimate the unknown parameters. The effectiveness of this approach is illustrated on an intra-host model of malaria infection.

Published
2023

34. Monitoring sick leave data for early detection of influenza outbreaks

Author

David R M Smith, Jonathan Bastard, Pearl Anne Ante-Testard, Oumou Salama Daouda, Laura Temime, Tom Duchemin, Helene Neynaud, Kévin Jean, Audrey Duval, Mounia N. Hocine, Rania Assab, Narimane Nekkab, William Dab, Radowan Lounissi, Jérôme-Philippe Garsi, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Malakoff Humanis, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP)-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, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP), Malaria : parasites et hôtes - Malaria : parasites and hosts, TD PhD is funded by Association Nationale de la Recherche et de la Technologie and Malakoff Humanis. JB PhD is funded by the INCEPTION project (PIA/ANR-16-CONV-0005). PAAT PhD is funded by INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), grant number ANRS-12377 B104. DS PhD is funded by a Canadian Institutes of Health Research Doctoral Foreign Study Award (Funding Reference Number 164263) as well as the French government through its National Research Agency project SPHINX-17-CE36–0008-01., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-17-CE36-0008,SPHINx,Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation(2017), TD is supported by Association Nationale de la Recherche et de la Technologie and Malakoff Humanis. JB is supported by the INCEPTION project (PIA/ANR-16-CONV-0005) PAA is supported by INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hepatites), grant number ANRS-12377 B104 DS is supported by a Canadian Institutes of Health Research Doctoral Foreign Study Award (Funding Reference Number 164263) as well as the French government through its National Research Agency project SPHINX-17-CE36-0008-01., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris], Hocine, Mounia N., Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, and Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation - - SPHINx2017 - ANR-17-CE36-0008 - AAPG2017 - VALID

Subjects
Sick-leave, MESH: Influenza, Human / epidemiology, MESH: Public Health Surveillance / methods, 010501 environmental sciences, 01 natural sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Absenteeism, MESH: Sick Leave, Medicine, Public Health Surveillance, MESH: Epidemics, 030212 general & internal medicine, MESH: Incidence, Workplace, MESH: Sentinel Surveillance, MESH: Workplace, MESH: France / epidemiology, [STAT.ME] Statistics [stat]/Methodology [stat.ME], Surveillance, MESH: Middle Aged, Incidence, Middle Aged, Infectious Diseases, Sick leave, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, France, Sick Leave, 0305 other medical science, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Research Article, MESH: Absenteeism, Surveillance Methods, Early detection, Influenza epidemics, Primary care, MESH: Insurance, Health, Sensitivity and Specificity, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Environmental health, Outbreak detection, Influenza, Human, Health insurance, Humans, lcsh:RC109-216, Epidemics, MESH: Influenza, Human / virology, 0105 earth and related environmental sciences, Retrospective Studies, 030505 public health, Insurance, Health, Models, Statistical, MESH: Humans, business.industry, Outbreak, MESH: Retrospective Studies, Influenza, MESH: Sensitivity and Specificity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Sentinel Surveillance, MESH: Models, Statistical
Abstract

Background Workplace absenteeism increases significantly during influenza epidemics. Sick leave records may facilitate more timely detection of influenza outbreaks, as trends in increased sick leave may precede alerts issued by sentinel surveillance systems by days or weeks. Sick leave data have not been comprehensively evaluated in comparison to traditional surveillance methods. The aim of this paper is to study the performance and the feasibility of using a detection system based on sick leave data to detect influenza outbreaks. Methods Sick leave records were extracted from private French health insurance data, covering on average 209,932 companies per year across a wide range of sizes and sectors. We used linear regression to estimate the weekly number of new sick leave spells between 2016 and 2017 in 12 French regions, adjusting for trend, seasonality and worker leaves on historical data from 2010 to 2015. Outbreaks were detected using a 95%-prediction interval. This method was compared to results from the French Sentinelles network, a gold-standard primary care surveillance system currently in place. Results Using sick leave data, we detected 92% of reported influenza outbreaks between 2016 and 2017, on average 5.88 weeks prior to outbreak peaks. Compared to the existing Sentinelles model, our method had high sensitivity (89%) and positive predictive value (86%), and detected outbreaks on average 2.5 weeks earlier. Conclusion Sick leave surveillance could be a sensitive, specific and timely tool for detection of influenza outbreaks.

Published
2023

35. Decline in rabies cases in international travelers during the COVID-19 pandemic

Author

Philippe Gautret, 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), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Public Health, Environmental and Occupational Health, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

36. Pyemotes ventricosus Dermatitis

Author

Berenger, Jean-Michel, Parola, Phillippe, 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), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

37. Non-HACEK gram-negative bacilli endocarditis: a multicentre retrospective case-control study

Author

Sébillotte, M, Boutoille, David, Declerck, Charles, Talarmin, Jean-Philippe, Lemaignen, Adrien, Piau, Caroline, Revest, Matthieu, Tattevin, Pierre, Gousseff, Marie, CHU Pontchaillou [Rennes], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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 hospitalier Bretagne Atlantique (Morbihan) (CHBA), and None

Subjects
Endocarditis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, gram-negative bacilli, Escherichia coli, intravenous drug use, healthcare-associated
Abstract

International audience; BACKGROUND: Infective endocarditis (IE) caused by non-HACEK gram-negative bacilli (GNB) is poorly characterised and may be emerging as a consequence of medical progress. METHODS: We performed an observational retrospective case-control study. Cases were non-HACEK GNB IE, definite or possible (modified Duke criteria), diagnosed in adults between 2007 and 2020 in six French referral hospitals. Two controls were included for each case (IE due to other bacteria, matched by sites and diagnosis date). RESULTS: Non-HACEK GNB were identified in 2.4% (77/3230) of all IE during the study period, with a mean age of 69.2 ± 14.6 years, and a large male predominance (53/77, 69%). Primary pathogens were Escherichia coli (n = 33), Klebsiella sp. (n = 12) and Serratia marcescens (n = 9), including eight (10%) multidrug-resistant GNB. Compared to controls (n = 154: 43% Streptococcus sp., 41% Staphylococcus sp. and 12% Enterococcus sp.), non-HACEK GNB IE were independently associated with intravenous drug use (IVDU, 8% vs. 2%, p = .003), active neoplasia (15% vs. 6%, p = .009), haemodialysis (9% vs. 3%, p = .007) and healthcare-associated IE (36% vs. 18%, p = .002). Urinary tract was the main source of infection (n = 25, 33%) and recent invasive procedures were reported in 29% of cases. Non-HACEK GNB IE were at lower risk of embolism (31% vs. 47%, p = .002). One-year mortality was high (n = 28, 36%). Comorbidities, particularly malignant hemopathy and cirrhosis, were associated with increased risk of death. CONCLUSIONS: Non-HACEK GNB are rarely responsible for IE, mostly as healthcare-associated IE in patients with complex comorbidities (end-stage renal disease, neoplasia), or in IVDUs.

Published
2023

38. Phages against Noncapsulated Klebsiella pneumoniae: Broader Host range, Slower Resistance

Author

Lourenço, Marta, Osbelt, Lisa, Passet, Virginie, Gravey, François, Megrian, Daniela, Strowig, Till, Rodrigues, Carla, Brisse, Sylvain, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Helmholtz Centre for Infection Research (HZI), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was mainly supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) project CRISPR-ATTACK (Advancing CRISPR antimicrobials to combat the bacterial pathogen Klebsiella pneumoniae) under the French Agence Nationale de la Recherche grant ANR-18-JAM2-0004-04, S.B. and 01KI1824 to T.S. C.R. was also supported financially by a Pasteur-Roux fellowship by the Institut Pasteur. The BEBP laboratory is supported by the French Government Investissement d’Avenir Program Laboratoire d’Excellence, Integrative Biology of Emerging Infectious Diseases (ANR10LABX62IBEID). T.S. was also supported by the Federal Ministry of Science under the project DF-AMR2:DECOLONIZE (01KI2131), JPI-AMR Germany (01KI1824) as well as by the German Center for Infection Research (DZIF, TTU 06.826)., We thank Olaya Rendueles Garcia and Eduardo Rocha for sharing the mutant strains that were used for the anti-Kd phage isolation. We thank the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA, especially Marc Monot, Elodie Turc, Laure Lemée and Georges Haustant, for the sequencing project management, the preparation of the genomic libraries, and the sequencing. We thank Melanie Hennart for the bioinformatics methodological input and Anne-Marie Wehenkel for the help with the protein analyses. We are grateful to Jin-Town Wang for sharing the strain NTUH-K2044. We thank Quentin Lamy-Besnier, Chiara Crestani, and Olaya Rendueles Garcia for the critical reading of the manuscript., ANR-18-JAM2-0004,CRISPRattacK(2018), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)

Subjects
Klebsiella pneumoniae, in vivo, bacteriophages, phage therapy, bacteriophage-bacteria interactions, phage resistance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, genomics, host range, bacteriophage therapy, antimicrobial resistance, noncapsulated mutants, phage-bacteria interactions
Abstract

International audience; Klebsiella pneumoniae (Kp), a human gut colonizer and opportunistic pathogen, is a major contributor to the global burden of antimicrobial resistance. Virulent bacteriophages represent promising agents for decolonization and therapy. However, the majority of anti-Kp phages that have been isolated thus far are highly specific to unique capsular types (anti-K phages), which is a major limitation to phage therapy prospects due to the highly polymorphic capsule of Kp. Here, we report on an original anti-Kp phage isolation strategy, using capsule-deficient Kp mutants as hosts (anti-Kd phages). We show that anti-Kd phages have a broad host range, as the majority are able to infect noncapsulated mutants of multiple genetic sublineages and O-types. Additionally, anti-Kd phages induce a lower rate of resistance emergence in vitro and provide increased killing efficiency when in combination with anti-K phages. In vivo, anti-Kd phages are able to replicate in mouse guts colonized with a capsulated Kp strain, suggesting the presence of noncapsulated Kp subpopulations. The original strategy proposed here represents a promising avenue that circumvents the Kp capsule host restriction barrier, offering promise for therapeutic development.IMPORTANCE Klebsiella pneumoniae (Kp) is an ecologically generalist bacterium as well as an opportunistic pathogen that is responsible for hospital-acquired infections and a major contributor to the global burden of antimicrobial resistance. In the last decades, limited advances have been made in the use of virulent phages as alternatives or complements to antibiotics that are used to treat Kp infections. This work demonstrates the potential value of an anti-Klebsiella phage isolation strategy that addresses the issue of the narrow host range of anti-K phages. Anti-Kd phages may be active in infection sites in which capsule expression is intermittent or repressed or in combination with anti-K phages, which often induce the loss of capsule in escape mutants.

Published
2023

39. Pericarditis related to post-acute COVID infection: A case report and review of the literature

Author

Nguyen, Nhu Ngoc, Dudouet, Pierre, Dhiver, Catherine, Gautret, Philippe, 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), Microbes évolution phylogénie et infections (MEPHI), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Abstract Cardiovascular involvement has been described in acute and recovered COVID-19 patients. Here, we present a case of symptomatic pericarditis with persistent symptoms for at least six months after the acute infection and report 66 published cases of pericarditis in discharged COVID patients. Patient mean age ± SD was 49.7 ± 13.3 years, ranging from 15 to 75 years and 57.6% were female. A proportion of 89.4% patients reported at least one comorbidity, with autoimmune and allergic disorders, hypertension and dyslipidaemia, as the most frequent. Only 8.3% of patients experienced severe symptoms of acute COVID-19. The time between acute COVID and pericarditis symptoms varied from 14 to 255 days. Chest pain (90.9%), tachycardia (60.0%) and dyspnoea (38.2%) were the most frequent symptoms in post-acute pericarditis. A proportion of 45.5% and 87% of patients had an abnormal electrocardiogram and abnormal transthoracic ultrasound, respectively. Colchicine combined with non-steroidal anti-inflammatory drug (NSAID) or acetylsalicylic acid (aspirin) were prescribed to 39/54 (72%) patients. Of them, 12 were switched to corticosteroid therapy due to non-response to the first-line treatment. Only 6 patients had persisting symptoms and were considered as non-respondent to therapy. Our report highlights that pericarditis should be suspected in COVID-19 patients with persistent chest pain and dyspnoea when pulmonary function is normal. Treatment with non-steroidal anti-inflammatory and colchicine is usually effective but corticosteroids are sometimes required.

Published
2023

40. Isolation of Carbapenem and Colistin Resistant Gram-Negative Bacteria Colonizing Immunocompromised SARS-CoV-2 Patients Admitted to Some Libyan Hospitals

Author

Khouloud Slimene, Asrra A. Ali, Elhussan A. Mohamed, Allaaeddin El Salabi, Faraj S. Suliman, Agela A. Elbadri, Fadi F. El-fertas, Ahmed El-awjly, Salah A. Shokri, Jean-Marc Rolain, Chedly Chouchani, Université de Tunis El Manar (UTM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Department of Environmental Health, Faculty of Public Health, University of Benghazi, Benghazi, Department of Community Medicine, Omar Al-Mukhtar University, El-Beyda, University of Benghazi, Alhawari Hospital, Benghazi, Benghazi Medical Center, Benghazi, Department of Microbiology, Faculty of Science, Misurata University, Misurata, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), and Université de Carthage - University of Carthage

Subjects
Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, General Immunology and Microbiology, Ecology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Cell Biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

In this work, we describe, for the first time, the occurrence of carbapenem-resistant bacteria colonizing COVID-19 patients who developed hospital-associated infections with carbapenemase-producing, Gram-negative bacteria at some isolation centers of COVID-19 in the eastern part of Libya. Our results confirmed that the overuse of antimicrobials, such as carbapenem antibiotics, during the COVID-19 pandemic has led to the emergence of multidrug-resistant bacteria, mainly K. pneumoniae and A. baumannii , as well as colistin resistance.

Published
2023

41. Updated estimation of cutaneous leishmaniasis incubation period in French Guiana

Author

Blaizot, Romain, Fontaine, Albin, Demar, Magalie, Delon, François, D’oleon, Albane de Bonet, Mayet, Aurélie, de Laval, Franck, de Santi, Vincent Pommier, Briolant, Sébastien, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de Guyane (UG), National Reference Center for Leishmania, Cayenne, 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), Service de Santé des Armées, Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Direction Interarmées du Service de Santé en Guyane, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Background The cutaneous leishmaniasis (CL) incubation period (IP) is defined as the time between parasite inoculation by sandfly bite and the onset of the first CL lesion. IP distribution is difficult to assess for CL because the date of exposure to an infectious bite cannot be accurately determined in endemic areas. IP current estimates for CL range from 14 days to several months with a median around 30–60 days, as established by a few previous studies in both New and Old Worlds. Methodology We estimated CL incubation period distribution using time-to-event models adapted to interval-censored data based on declared date of travels from symptomatic military personnel living in non-endemic areas that were exposed during their short stays in French Guiana (FG) between January 2001 and December 2021. Principal findings A total of 180 patients were included, of which 176 were men (97.8%), with a median age of 26 years. When recorded, the parasite species was always Leishmania guyanensis (31/180, 17.2%). The main periods of CL diagnosis spread from November to January (84/180, 46.7%) and over March-April (54/180, 30.0%). The median IP was estimated at 26.2 days (95% Credible Level, 23.8–28.7 days) using a Bayesian accelerated failure-time regression model. Estimated IP did not exceed 62.1 days (95% CI, 56–69.8 days) in 95% of cases (95 th percentile). Age, gender, lesion number, lesion evolution and infection date did not significantly modify the IP. However, disseminated CL was significantly associated with a 2.8-fold shortening of IP. Conclusions This work suggests that the CL IP distribution in French Guiana is shorter and more restricted than anticipated. As the incidence of CL in FG usually peaks in January and March, these findings suggest that patients are contaminated at the start of the rainy season.

Published
2023

42. Modulation of the E-cadherin in human cells infected in vitro with Coxiella burnetii

Author

Omar Osman, Ikram, Mezouar, Soraya, Brahim-Belhaouari, Djamal, Mege, Jean-Louis, Devaux, Christian Albert, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as an in vitro model to investigate the expression and function of E-cad in response to infection by Coxiella burnetii , the etiological agent of Q fever. Infection of BeWo cells with C . burnetii leads to a decrease in the number of BeWo cells expressing E-cad at their membrane. A shedding of soluble E-cad was associated with the post-infection decrease of membrane-bound E-cad. The modulation of E-cad expression requires bacterial viability and was not found with heat-inactivated C . burnetii . Moreover, the intracytoplasmic cell concentration of β-catenin (β-cat), a ligand of E-cad, was reduced after bacterial infection, suggesting that the bacterium induces modulation of the E-cad/β-cat signaling pathway and CDH1 and CTNNB1 genes transcription. Finally, several genes operating the canonical Wnt-Frizzled/β-cat pathway were overexpressed in cells infected with C . burnetii . This was particularly evident with the highly virulent strain of C . burnetii , Guiana. Our data demonstrate that infection of BeWo cells by live C . burnetii modulates the E-cad/β-cat signaling pathway.

Published
2023

43. Candidate Phyla Radiation, an Underappreciated Division of the Human Microbiome, and Its Impact on Health and Disease

Author

Sabrina Naud, Ahmad Ibrahim, Camille Valles, Mohamad Maatouk, Fadi Bittar, Maryam Tidjani Alou, Didier Raoult, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)

Subjects
Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Mouth, General Immunology and Microbiology, Bacteria, Epidemiology, Microbiota, Public Health, Environmental and Occupational Health, Review, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Infectious Diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Dysbiosis, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract

Candidate phyla radiation (CPR) is an emerging division of the bacterial domain within the human microbiota. Still poorly known, these microorganisms were first described in the environment in 1981 as “ultramicrobacteria” with a cell volume under 0.1 μm(3) and were first associated with the human oral microbiota in 2007. The evolution of technology has been paramount for the study of CPR within the human microbiota. In fact, since these ultramicrobacteria have yet to be axenically cultured despite ongoing efforts, progress in imaging technology has allowed their observation and morphological description. Although their genomic abilities and taxonomy are still being studied, great strides have been made regarding their taxonomic classification, as well as their lifestyle. In addition, advancements in next-generation sequencing and the continued development of bioinformatics tools have allowed their detection as commensals in different human habitats, including the oral cavity and gastrointestinal and genital tracts, thus highlighting CPR as a nonnegligible part of the human microbiota with an impact on physiological settings. Conversely, several pathologies present dysbiosis affecting CPR levels, including inflammatory, mucosal, and infectious diseases. In this exhaustive review of the literature, we provide a historical perspective on the study of CPR, an overview of the methods available to study these organisms and a description of their taxonomy and lifestyle. In addition, their distribution in the human microbiome is presented in both homeostatic and dysbiotic settings. Future efforts should focus on developing cocultures and, if possible, axenic cultures to obtain isolates and therefore genomes that would provide a better understanding of these ultramicrobacteria, the importance of which in the human microbiome is undeniable.

Published
2023

44. Lactonase-mediated inhibition of quorum sensing largely alters phenotypes, proteome, and antimicrobial activities in Burkholderia thailandensis E264

Author

Gonzales, Mélanie, Plener, Laure, Armengaud, Jean, Armstrong, Nicholas, Chabrière, Éric, Daudé, David, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Gene&GreenTK, Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)

Subjects
Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [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, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Introduction Burkholderia thailandensis is a study model for Burkholderia pseudomallei , a highly virulent pathogen, known to be the causative agent of melioidosis and a potential bioterrorism agent. These two bacteria use an (acyl-homoserine lactone) AHL-mediated quorum sensing (QS) system to regulate different behaviors including biofilm formation, secondary metabolite productions, and motility. Methods Using an enzyme-based quorum quenching (QQ) strategy, with the lactonase Sso Pox having the best activity on B. thailandensis AHLs, we evaluated the importance of QS in B. thailandensis by combining proteomic and phenotypic analyses. Results We demonstrated that QS disruption largely affects overall bacterial behavior including motility, proteolytic activity, and antimicrobial molecule production. We further showed that QQ treatment drastically decreases B. thailandensis bactericidal activity against two bacteria ( Chromobacterium violaceum and Staphylococcus aureus ), while a spectacular increase in antifungal activity was observed against fungi and yeast ( Aspergillus niger , Fusarium graminearum and Saccharomyces cerevisiae ). Discussion This study provides evidence that QS is of prime interest when it comes to understanding the virulence of Burkholderia species and developing alternative treatments.

Published
2023

45. Sequencing of monkeypox virus from infected patients reveals viral genomes with APOBEC3‐like editing, gene inactivation, and bacterial agents of skin superinfection

Author

Colson, Philippe, Penant, Gwilherm, Delerce, Jeremy, Boschi, Céline, Wurtz, Nathalie, Bedotto, Marielle, Branger, Stéphanie, Brouqui, Philippe, Parola, Philippe, Lagier, Jean‐christophe, Cassir, Nadim, Tissot-Dupont, Hervé, Million, Matthieu, Aherfi, Sarah, La Scola, Bernard, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre hospitalier d'Avignon, Vecteurs - Infections tropicales et méditerranéennes (VITROME), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

46. Maliibacterium massiliense gen. nov. sp. nov., Isolated from Human Feces and Proposal of Maliibacteriaceae fam. nov

Author

Sory Ibrahima Traore, Cheikh Ibrahima Lo, Maaloum Mossaab, Guillaume Durand, Jean Christophe Lagier, Didier Raoult, Pierre-Edouard Fournier, Florence Fenollar, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Vecteurs - Infections tropicales et méditerranéennes (VITROME), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, General Medicine, Applied Microbiology and Biotechnology, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

47. Multifocal cutaneous phaeohyphomycosis caused by Paraconiothyrium cyclothyrioides in an immunocompromised patient

Author

Malaure, Célie, Hoang, Stella, Bagny, Kelly, Tauziède-Espariat, Arnault, Garcia-Hermoso, Dea, Kamus, Laure, Traversier, Nicolas, Miltgen, Guillaume, Garrigos, Thomas, Laboratoire de microbiologie et virologie [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service des maladies infectieuses [CHU La Réunion], Service de dermatologie [CHU La Réunion], GHU Paris Psychiatrie et Neurosciences, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), and Centre Régional en Antibiothérapie (CRATb)

Subjects
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience

Published
2023

48. An ancient coronavirus from individuals in France, circa 16th century

Author

Hamadou Oumarou Hama, Thomas Chenal, Olivier Pible, Guylaine Miotello, Jean Armengaud, Michel Drancourt, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Archéologie, Terre, Histoire, Sociétés [Dijon] (ARTeHiS), Ministère de la Culture et de la Communication (MCC)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [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, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

49. Tracking Mycoviruses in Public RNAseq Datasets of Malassezia: Three Original Totiviruses Revealed

Author

Boulanouar, Fatima, Ranque, Stéphane, Levasseur, Anthony, 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), Microbes évolution phylogénie et infections (MEPHI), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Malassezia, dsRNA, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, fungal host, skin disorders, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, mycovirus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, transcriptomes, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, fungal evolution, Totivirus
Abstract

International audience; Mycoviruses are viruses that selectively infect and multiply in fungal cells. Malassezia is the most abundant fungus on human skin and is associated with a variety of conditions, including atopic eczema, atopic dermatitis, dandruff, folliculitis, pityriasis versicolor, and seborrheic dermatitis. Here, we conducted mycovirome studies on 194 public transcriptomes of Malassezia (2,568,212,042 paired-end reads) screened against all available viral proteins. Transcriptomic data were assembled de novo resulting in 1,170,715 contigs and 2,995,306 open reading frames (ORFs) that were subsequently tracked for potential viral sequences. Eighty-eight virus-associated ORFs were detected in 68 contigs from 28 Sequence Read Archive (SRA) samples. Seventy-five and thirteen ORFs were retrieved from transcriptomes of Malassezia globosa and Malassezia restricta, respectively. Phylogenetic reconstructions revealed three new mycoviruses belonging to the Totivirus genus and named Malassezia globosa-associated-totivirus 1 (MgaTV1); Malassezia restricta-associated-totivirus 1 (MraTV1) and Malassezia restricta-associated-totivirus 2 (MraTV2). These viral candidates extend our understanding of the diversity and taxonomy of mycoviruses as well as their co-evolution with their fungal hosts. These results reflected the unexpected diversity of mycoviruses hidden in public databases. In conclusion, this study sheds light on the discovery of novel mycoviruses and opens the door to study their impact on disease caused by the host fungus Malassezia and globally, their implication in clinical skin disorders.

Published
2023

50. Effectiveness of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine in Pregnancy: Low Coverage and High Prevalence of Plasmodium falciparum dhfr-dhps Quintuple Mutants as Major Challenges in Douala, an Urban Setting in Cameroon

Author

Eboumbou Moukoko, Carole Else, Kojom Foko, Loick Pradel, Ayina, Angèle, Tornyigah, Bernard, Epote, Annie Rachel, Penda, Ida Calixte, Epee Eboumbou, Patricia, Ebong, Serge Bruno, Texier, Gaetan, Nsango, Sandrine Eveline, Ayong, Lawrence, Tuikue Ndam, Nicaise, Same Ekobo, Albert, Malaria Research Unit, Centre Pasteur Cameroon, Yaoundé, ICMR-National Institute of Malaria Research, Dwarka, New Delhi, Pharmaceutical Sciences Department, Faculty of Medicine and Pharmaceutical Sciences, The University of Douala, University of Ghana, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Haematology Laboratory, Centre Pasteur Cameroon, Yaoundé, Université de Douala, Animal Organisms Biology and Physiology Department, Faculty of Sciences, The University of Douala, 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), Service de Santé des Armées, Centre Pasteur du Cameroun, and Réseau International des Instituts Pasteur (RIIP)

Subjects
[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, effectiveness, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, IPTp-SP, dhps, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, malaria infection, k13 mutations, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, dhfr, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Cameroon, pregnant women
Abstract

International audience; Intermittent preventive treatment in pregnancy with sulfadoxine and pyrimethamine (IPTp-SP) is a key component in the malaria control strategy implemented in Africa. The aim of this study was to determine IPTp-SP adherence and coverage, and the impact on maternal infection and birth outcomes in the context of widespread SP resistance in the city of Douala, Cameroon. Clinical and demographic information were documented among 888 pregnant women attending 3 health facilities, from the antenatal care visit to delivery. Positive samples were genotyped for P. falciparum gene (dhfr, dhps, and k13) mutations. The overall IPTp-SP coverage (≥three doses) was 17.5%, and 5.1% received no dose. P. falciparum prevalence was 16%, with a predominance of submicroscopic infections (89.3%). Malaria infection was significantly associated with locality and history of malaria, and it was reduced among women using indoor residual spraying. Optimal doses of IPTp-SP were significantly associated with reduced infection among newborns and women (secundiparous and multiparous), but there was no impact of IPTp-SP on the newborn bodyweight. Pfdhfr-Pfdhps quintuple mutants were over-represented (IRNI-FGKAA, IRNI-AGKAA), and sextuple mutants (IRNI-AGKAS, IRNI-FGEAA, IRNI-AGKGS) were also reported. The Pfk13 gene mutations associated with artemisinin resistance were not detected. This study highlights the role of ANC in achieving optimal SP coverage in pregnant women, the mitigated impact of IPTp-SP on malaria outcomes, and the high prevalence of multiple SP-resistant P. falciparum parasites in the city of Douala that could compromise the efficacy of IPTp-SP.

Published
2023

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