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1. Assessment of HIV viral load monitoring in remote settings in Vietnam - comparing people who inject drugs to the other patients.

Author

Louise H Lefrancois, Binh Thanh Nguyen, Tram Thi Phuong Pham, Nhung Thi Hong Le, Huyen Thi Thanh Dao, Tram Hong Tran, Khanh Phuong Ngo, Ha Thi Tong, Huong Thi Thu Phan, Mohand Ait-Ahmed, Thang Hong Pham, Tuan Anh Nguyen, Fabien Taieb, Yoann Madec, and MOVIDA 2 study group

Subjects
Medicine, Science
Abstract

IntroductionIncreasing access to viral load (VL) monitoring is essential to fight HIV epidemics. In remote settings in Vietnam, using dried blood spot (DBS) sampling for specimen collection could improve the situation. Here, people who inject drugs (PWID) represent many newly antiretroviral therapy (ART)-initiated patients. The goals of this evaluation were to evaluate if access to VL monitoring and the rate of virological failure differed between PWID and non-PWID.MethodsProspective cohort study of patients newly initiated on ART in remote settings in Vietnam. DBS coverage at 6, 12 and 24 months of ART was investigated. Factors associated with DBS coverage were identified through logistic regression, as were factors associated with virological failure (VL ≥1,000 copies/mL) at 6, 12 and 24 months of ART.ResultsOverall 578 patients were enrolled in the cohort, of whom 261 (45%) were PWID. DBS coverage improved from 74.7% to 82.9% between 6 and 24 months of ART (p = 0.001). PWID status was not associated with DBS coverage (p = 0.74), but DBS coverage was lower in patients who were late to clinical visits and in those in WHO stage 4 (p = 0.023 and p = 0.001, respectively). The virological failure rate decreased from 15.8% to 6.6% between 6 and 24 months of ART (pConclusionsDespite training and simple procedures, DBS coverage was not perfect. DBS coverage was not associated with PWID status. Close management is required for effective routine HIV VL monitoring. PWID were more at risk of failure, as were patients who were not fully adherent and patients who were late to clinical visits. Specific interventions targeting these patients are needed to improve their outcomes. Overall, efforts in coordination and communication are essential to improve global HIV care.Trial registrationClinical Trial Number: NCT03249493.

Published
2023
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2. Impact of original, B.1.1.7, and B.1.351/P.1 SARS-CoV-2 lineages on vaccine effectiveness of two doses of COVID-19 mRNA vaccines: Results from a nationwide case-control study in France

Author

Tiffany Charmet, Laura Schaeffer, Rebecca Grant, Simon Galmiche, Olivia Chény, Cassandre Von Platen, Alexandra Maurizot, Alexandra Rogoff, Faïza Omar, Christophe David, Alexandra Septfons, Simon Cauchemez, Alexandre Gaymard, Bruno Lina, Louise H Lefrancois, Vincent Enouf, Sylvie van der Werf, Alexandra Mailles, Daniel Levy-Bruhl, Fabrice Carrat, and Arnaud Fontanet

Subjects
COVID-19, Vaccine effectiveness, SARS-CoV-2 variants, epidemiology, case-control study, Public aspects of medicine, RA1-1270
Abstract

Background: We aimed to assess the effectiveness of two doses of mRNA COVID-19 vaccines against COVID-19 with the original virus and other lineages circulating in France. Methods: In this nationwide case-control study, cases were SARS-CoV-2 infected adults with onset of symptoms between 14 February and 3 May 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire on recent activity-related exposures and vaccination history. Information about the infecting virus was based on a screening RT-PCR for either B.1.1.7 or B.1.351/P.1 variants. Findings: Included in our analysis were 7 288 adults infected with the original SARS-CoV-2 virus, 31 313 with the B.1.1.7 lineage, 2 550 with B.1.351/P1 lineages, and 3 644 controls. In multivariable analysis, the vaccine effectiveness (95% confidence interval) seven days after the second dose of mRNA vaccine was estimated at 88% (81-92), 86% (81-90) and 77% (63-86) against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Recent (2 to 6 months) history of virologically confirmed SARS-CoV-2 infection was found to be 83% (76-88), 88% (85-91) and 83% (71-90) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively; and more distant (> 6 months) infections were 76% (54-87), 84% (75-90), and 74% (41-89) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Interpretation: In real-life settings, two doses of mRNA vaccines proved to be effective against COVID-19 with the original virus, B.1.1.7 lineage and B.1.351/P.1 lineages. Funding: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance “Tous unis contre le virus”).

Published
2021
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3. RskA Is a Dual Function Activator-Inhibitor That Controls SigK Activity Across Distinct Bacterial Genera

Author

Frédéric J. Veyrier, Cecilia Nieves, Louise H. Lefrancois, Hana Trigui, Antony T. Vincent, and Marcel A. Behr

Subjects
M. tuberculosis, M. bovis, M. orygis, Yersinia, Sigma factor K, anti-Sigma factor, Microbiology, QR1-502
Abstract

It has been previously shown that RskA, the anti-Sigma factor K of Mycobacterium tuberculosis, inhibits SigK and that mutations in RskA promote high expression of the SigK regulon. The latter observation led us to hypothesize that RskA mutations lead to loss of the anti-Sigma factor function. In this report, we used natural and artificial mutations in RskA to determine the basis of the SigK-RskA partnership. Consistent with predictions, the N-terminal cytoplasmic portion of RskA was sufficient on its own to inhibit SigK. Unexpectedly, RskA also served as an activator of SigK. This activation depended on the same N-terminal region and was enhanced by the membrane-extracellular portion of RskA. Based on this, we engineered similar truncations in a Gram-negative bacterium, namely Yersinia enterocolitica. Again, we observed that, with specific alterations of RskA, we were able to enhance SigK activity. Together these results support an alternative mechanism of anti-Sigma factor function, that we could term modulator (activator-inhibitor) in both Actinobacteria and Gram-negative bacteria, suggesting that Sigma factor activation by anti-Sigma factors could be under-recognized.

Published
2020
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4. Feature of Adhesins Produced by Human Clinical Isolates of Mycobacterium intracellulare, Mycobacterium intracellulare subsp. chimaera and Closely Related Species

Author

Louise H. Lefrancois, Thierry Cochard, Maxime Branger, Olivia Peuchant, Cyril Conde, Adeline Pastuszka, Camille Locht, Philippe Lanotte, and Franck Biet

Subjects
Mycobacterium intracellulare, NTM, adhesins, HBHA, LBP, MAC infection, Biology (General), QH301-705.5
Abstract

The Mycobacterium avium complex includes two closely related species, Mycobacterium avium and Mycobacterium intracellulare. They are opportunistic pathogens in humans and responsible for severe disease in a wide variety of animals. Yet, little is known about factors involved in their pathogenicity. Here, we identified, purified and characterized adhesins belonging to the heparin-binding hemagglutinin (HBHA) and laminin-binding protein (LBP) family from M. intracellulare ATCC13950 and examined clinical isolates from patients with different pathologies associated with M. intracellulare infection for the presence and conservation of HBHA and LBP. Using a recombinant derivative strain of M. intracellulare ATCC13950 producing green fluorescent protein and luciferase, we found that the addition of heparin inhibited mycobacterial adherence to A549 cells, whereas the addition of laminin enhanced adherence. Both HBHA and LBP were purified by heparin-Sepharose chromatography and their methylation profiles were determined by mass spectrometry. Patients with M. intracellulare infection mounted strong antibody responses to both proteins. By using PCR and immunoblot analyses, we found that both proteins were highly conserved among all 17 examined clinical M. intracellulare isolates from patients with diverse disease manifestations, suggesting a conserved role of these adhesins in M. intracellulare virulence in humans and their potential use as a diagnostic tool.

Published
2020
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5. Impact of original, B.1.1.7, and B.1.351/P.1 SARS-CoV-2 lineages on vaccine effectiveness of two doses of COVID-19 mRNA vaccines: Results from a nationwide case-control study in France

Author

Alexandra Septfons, Simon Galmiche, Daniel Lévy-Bruhl, Simon Cauchemez, Sylvie van der Werf, Rebecca Grant, Alexandra Rogoff, Alexandra Maurizot, Cassandre Von Platen, Laura Schaeffer, Faïza Omar, Vincent Enouf, Olivia Chény, Christophe David, Alexandra Mailles, Fabrice Carrat, Bruno Lina, Louise H Lefrancois, Tiffany Charmet, Arnaud Fontanet, Alexandre Gaymard, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Sorbonne Université (SU), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris], Caisse Nationale d'Assurance Maladie des Travailleurs salariés (CNAMTS), Ministère de l'économie et des finances, Ipsos, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), The study was funded by Institut Pasteur and Research & Action Emerging Infectious Diseases (REACTing). AF's laboratory receives support from the Labex IBEID (ANR-10-LABX-62-IBEID) and the INCEPTION project (PIA/ANR-16-CONV-0005) for studies on emerging viruses. TC is funded by the Fondation de France (Alliance 'Tous unis contre le virus'). SW's laboratory receives support from Institut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing (Research & Action Emerging Infectious Diseases), and by the H2020 project 101003589 (RECOVER)., We would like to thank the Action Coordonnée transmission group of the ANRS-MIE for helpful discussions on the study design, and Violette Mouro (Conseil d'Orientation de la Stratégie Vaccinale) for providing us with data on vaccine distribution in France., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Gestionnaire, HAL Sorbonne Université 5, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, Institut Pasteur [Paris] (IP)-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)-Institut Pasteur [Paris] (IP)-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), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), 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)-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), and Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur)

Subjects
medicine.medical_specialty, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Lineage (evolution), case-control study, Biology, Virus, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, Internal Medicine, medicine, 030212 general & internal medicine, 030304 developmental biology, Vaccine effectiveness, 0303 health sciences, Messenger RNA, SARS-CoV-2 variants, Health Policy, Case-control study, COVID-19, Virology, Confidence interval, 3. Good health, Vaccination, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Public aspects of medicine, RA1-1270, Research Paper
Abstract

Background: We aimed to assess the effectiveness of two doses of mRNA COVID-19 vaccines against COVID-19 with the original virus and other lineages circulating in France. Methods: In this nationwide case-control study, cases were SARS-CoV-2 infected adults with onset of symptoms between 14 February and 3 May 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire on recent activity-related exposures and vaccination history. Information about the infecting virus was based on a screening RT-PCR for either B.1.1.7 or B.1.351/P.1 variants. Findings: Included in our analysis were 7 288 adults infected with the original SARS-CoV-2 virus, 31 313 with the B.1.1.7 lineage, 2 550 with B.1.351/P1 lineages, and 3 644 controls. In multivariable analysis, the vaccine effectiveness (95% confidence interval) seven days after the second dose of mRNA vaccine was estimated at 88% (81-92), 86% (81-90) and 77% (63-86) against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Recent (2 to 6 months) history of virologically confirmed SARS-CoV-2 infection was found to be 83% (76-88), 88% (85-91) and 83% (71-90) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively; and more distant (> 6 months) infections were 76% (54-87), 84% (75-90), and 74% (41-89) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Interpretation: In real-life settings, two doses of mRNA vaccines proved to be effective against COVID-19 with the original virus, B.1.1.7 lineage and B.1.351/P.1 lineages. Funding: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance “Tous unis contre le virus”).

Published
2021

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