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8,802 results on '"Emerging Infectious Diseases"'

1. Lassa Fever Clinical Course and Prognostic Factors in Nigeria (LASCOPE)

Author

Institut National de la Santé Et de la Recherche Médicale, France, University of Oxford, Irrua Specialist Teaching Hospital, Bernhard Nocht Institute for Tropical Medicine, University Hospital, Bordeaux, University of Bordeaux, PACCI Program, Institut de Recherche pour le Developpement, ANRS, Emerging Infectious Diseases, Federal Medical Centre, Owo, European and Developing Countries Clinical Trials Partnership (EDCTP), and Denis Malvy, Professor of Infectious Diseases and Tropical Medicine

Published
2025

5. European Trial Into Mpox Infection (EPOXI)

Author

European Clinical Research Alliance for Infectious Diseases (ECRAID), Universiteit Antwerpen, Erasmus Medical Center, Hospital Universitario La Paz, ANRS, Emerging Infectious Diseases, and Miquel Ekkelenkamp, Clinical Microbiologist

Published
2024

7. International Study on COVID-19 Vaccine to Assess Immunogenicity, Reactogenicity and Efficacy (InVITE) (InVITE)

Author

Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo, Partnership for Clinical Research in Guinea/Partenariat de Recherche Clinique en Guinée (PREGUI), Partnership for Research on Ebola Virus in Liberia (PREVAIL), University Clinical Research Center, Mali, Onom Foundation and Liver Center, Mexican Emerging Infectious Diseases Clinical Research Network, and Ina-Respond

Published
2024

9. Strategic Timing of Antiretroviral Treatment (START)

Author

National Institute of Allergy and Infectious Diseases (NIAID), Copenhagen HIV Programme (CHIP) -- Copenhagen, Denmark, Medical Research Council, Kirby Institute, Washington D.C. Veterans Affairs Medical Center, ANRS, Emerging Infectious Diseases, German Federal Ministry of Education and Research, NEAT - European AIDS Treatment Network, National Health and Medical Research Council, Australia, National Institutes of Health Clinical Center (CC), National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme LLC, and Tibotec Pharmaceutical Limited

Published
2024

10. ISTH/ANRS 0409s INTEGRATE Lassa Fever Study

Author

Alliance for International Medical Action, University of Bordeaux, Bernhard Nocht Institute for Tropical Medicine, Federal Medical Centre, Owo, Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire, Fondation pour la Recherche Scientifique, Benin, Médecins Sans Frontières, Belgium, Alex Ekwueme Federal University Teaching Hospital, Donka Hospital, Conakry, Centre de Recherche Médicale de Lambaréné, University of Hamburg-Eppendorf, Phebe Hospital, Liberia, University of North Carolina, and ANRS, Emerging Infectious Diseases

Published
2024

15. Different epidemiological profiles in patients with Zika and dengue infection in Tapachula, Chiapas in Mexico (2016–2018): an observational, prospective cohort study

Author

Pablo F. Belaunzarán-Zamudio, Héctor Armando Rincón León, Sandra Caballero Sosa, Emilia Ruiz, José Gabriel Nájera Cancino, Paul Rodriguez de La Rosa, María de Lourdes Guerrero Almeida, John H. Powers, John H. Beigel, Sally Hunsberger, Karina Trujillo, Pilar Ramos, Fernando J. Arteaga-Cabello, Alexander López-Roblero, Raydel Valdés-Salgado, Hugo Arroyo-Figueroa, Eli Becerril, Guillermo Ruiz-Palacios, and for the Mexican Emerging Infectious Diseases Clinical Research Network (La Red)

Subjects
Zika, Dengue, Chikungunya, Emerging diseases, Outbreak, Mexico, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The introduction of Zika and chikungunya to dengue hyperendemic regions increased interest in better understanding characteristics of these infections. We conducted a cohort study in Mexico to evaluate the natural history of Zika infection. We describe here the frequency of Zika, chikungunya and dengue virus infections immediately after Zika introduction in Mexico, and baseline characteristics of participants for each type of infection. Methods Prospective, observational cohort evaluating the natural history of Zika virus infection in the Mexico-Guatemala border area. Patients with fever, rash or both, meeting the modified criteria of PAHO for probable Zika cases were enrolled (June 2016–July 2018) and followed-up for 6 months. We collected data on sociodemographic, environmental exposure, clinical and laboratory characteristics. Diagnosis was established based on viral RNA identification in serum and urine samples using RT-PCR for Zika, chikungunya, and dengue. We describe the baseline sociodemographic and environmental exposure characteristics of participants according to diagnosis, and the frequency of these infections over a two-year period immediately after Zika introduction in Mexico. Results We enrolled 427 participants. Most patients (n = 307, 65.7%) had an acute illness episode with no identified pathogen (UIE), 37 (8%) Zika, 82 (17.6%) dengue, and 1 (0.2%) chikungunya. In 2016 Zika predominated, declined in 2017 and disappeared in 2018; while dengue increased after 2017. Patients with dengue were more likely to be men, younger, and with lower education than those with Zika and UIE. They also reported closer contact with water sources, and with other people diagnosed with dengue. Participants with Zika reported sexual exposure more frequently than people with dengue and UIE. Zika was more likely to be identified in urine while dengue was more likely found in blood in the first seven days of symptoms; but PCR results for both were similar at day 7–14 after symptom onset. Conclusions During the first 2 years of Zika introduction to this dengue hyper-endemic region, frequency of Zika peaked and fell over a two-year period; while dengue progressively increased with a predominance in 2018. Different epidemiologic patterns between Zika, dengue and UIE were observed. Trial registration Clinical.Trials.gov (NCT02831699).

Published
2021
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19. Different therapeutic associations of renin-angiotensin system inhibitors with coronavirus disease 2019 compared with usual pneumonia

Author

Hae-Young Lee, Juhee Ahn, Juhong Park, Chang Kyung Kang, Sung-Ho Won, Dong Wook Kim, Jong-Heon Park, Ki-Hyun Chung, Joon-Sung Joh, JI Hwan Bang, Cheong Hee Kang, Myoung-don Oh, Wook Bum Pyun, The Korean Society of Hypertension, and The National Committee for Clinical Management of Emerging Infectious Diseases

Subjects
covid-19, pneumonia, mortality, angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, Medicine
Abstract

Background/Aims Although it is near concluded that renin-angiotensin system inhibitors do not have a harmful effect on coronavirus disease 2019 (COVID-19), there is no report about whether angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) offer any protective role. This study aimed to compare the association of ARBs and ACEIs with COVID-19-related mortality. Methods All patients with COVID-19 in Korea between January 19 and April 16, 2020 were enrolled. The association of ARBs and ACEIs with mortality within 60 days were evaluated. A comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of pneumonia patients hospitalized in 2019 in Korea. Results Among 10,448 COVID-19 patients, ARBs and ACEIs were prescribed in 1,231 (11.7%) and 57 (0.6%) patients, respectively. After adjusting for age, sex, and history of comorbidities, the ARB group showed neutral association (HR, 1.034; 95% CI, 0.765 to 1.399; p = 0.8270) and the ACEI groups showed no significant associations likely owing to the small population size (HR, 0.736; 95% CI, 0.314 to 1.726; p = 0.4810). When comparing HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia in 2019, the trend of ACEIs showed similar benefits, whereas the protective effect of ARBs observed in the retrospective cohort was absent in COVID-19 patients. Meta-analyses showed significant positive correlation with survival of ACEIs, whereas a neutral association between ARBs and mortality. Conclusions Although ARBs or ACEIs were not associated with fatal outcomes, potential beneficial effects of ARBs observed in pneumonia were attenuated in COVID-19.

Published
2021
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20. Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness

Author

Mexico Emerging Infectious Diseases Clinical Research Network (LaRed), Gamiño-Arroyo, Ana E., Guerrero, M. Lourdes, McCarthy, Sean, Ramírez-Venegas, Alejandra, Llamosas-Gallardo, Beatriz, Galindo-Fraga, Arturo, Moreno-Espinosa, Sarbelio, Roldán-Aragón, Yuri, Araujo-Meléndez, Javier, Hunsberger, Sally, Ibarra-González, Violeta, Martínez-López, Julia, García-Andrade, Luis A., Kapushoc, Heather, Holley, H. Preston, Smolskis, Mary C., Ruiz-Palacios, Guillermo M., and Beigel, John H.

Published
2019

21. A Trial to Confirm a Sustained Virological Suppression Defined as HIV-RNA (FATI-01)

Author

European and Developing Countries Clinical Trials Partnership (EDCTP), German Federal Ministry of Education and Research, National Institute for Medical Research, Tanzania, Treichville Academic hospital center, Division of infectious and tropical diseases (SMIT), ANRS, Emerging Infectious Diseases, Kumasi Centre for Collaborative Research (KCCR), Bernhard Nocht Institute for Tropical Medicine, Pharmaceutical Company (Chiracon GmbH), Pharmaceutical Company (STADA Vietnam Joint Venture Co. Ltd.), and Michael Hoelscher, Chief Investigator

Published
2018

27. Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2 with grinch [version 2; peer review: 3 approved]

Author

Áine O'Toole, Verity Hill, Oliver G. Pybus, Alexander Watts, Issac I. Bogoch, Kamran Khan, Jane P. Messina, The COVID-19 Genomics UK (COG-UK) consortium, Network for Genomic Surveillance in South Africa (NGS-SA), Brazil-UK CADDE Genomic Network, Houriiyah Tegally, Richard R. Lessells, Jennifer Giandhari, Sureshnee Pillay, Kefentse Arnold Tumedi, Gape Nyepetsi, Malebogo Kebabonye, Maitshwarelo Matsheka, Madisa Mine, Sima Tokajian, Hamad Hassan, Tamara Salloum, Georgi Merhi, Jad Koweyes, Jemma L. Geoghegan, Joep de Ligt, Xiaoyun Ren, Matthew Storey, Nikki E. Freed, Chitra Pattabiraman, Pramada Prasad, Anita S. Desai, Ravi Vasanthapuram, Thomas F. Schulz, Lars Steinbrück, Tanja Stadler, Swiss Viollier Sequencing Consortium, Antonio Parisi, Angelica Bianco, Darío García de Viedma, Sergio Buenestado-Serrano, Vítor Borges, Joana Isidro, Sílvia Duarte, João Paulo Gomes, Neta S. Zuckerman, Michal Mandelboim, Orna Mor, Torsten Seemann, Alicia Arnott, Jenny Draper, Mailie Gall, William Rawlinson, Ira Deveson, Sanmarié Schlebusch, Jamie McMahon, Lex Leong, Chuan Kok Lim, Maria Chironna, Daniela Loconsole, Antonin Bal, Laurence Josset, Edward Holmes, Kirsten St. George, Erica Lasek-Nesselquist, Reina S. Sikkema, Bas Oude Munnink, Marion Koopmans, Mia Brytting, V. Sudha rani, S. Pavani, Teemu Smura, Albert Heim, Satu Kurkela, Massab Umair, Muhammad Salman, Barbara Bartolini, Martina Rueca, Christian Drosten, Thorsten Wolff, Olin Silander, Dirk Eggink, Chantal Reusken, Harry Vennema, Aekyung Park, Christine Carrington, Nikita Sahadeo, Michael Carr, Gabo Gonzalez, SEARCH Alliance San Diego, National Virus Reference Laboratory, SeqCOVID-Spain, Danish Covid-19 Genome Consortium (DCGC), Communicable Diseases Genomic Network (CDGN), Dutch National SARS-CoV-2 surveillance program, Division of Emerging Infectious Diseases (KDCA), Tulio de Oliveira, Nuno Faria, Andrew Rambaut, and Moritz U. G. Kraemer

Subjects
Medicine, Science
Abstract

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

Published
2021
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28. Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2 [version 1; peer review: 2 approved]

Author

Áine O'Toole, Verity Hill, Oliver G. Pybus, Alexander Watts, Issac I. Bogoch, Kamran Khan, Jane P. Messina, The COVID-19 Genomics UK (COG-UK) consortium, Network for Genomic Surveillance in South Africa (NGS-SA), Brazil-UK CADDE Genomic Network, Houriiyah Tegally, Richard R. Lessells, Jennifer Giandhari, Sureshnee Pillay, Kefentse Arnold Tumedi, Gape Nyepetsi, Malebogo Kebabonye, Maitshwarelo Matsheka, Madisa Mine, Sima Tokajian, Hamad Hassan, Tamara Salloum, Georgi Merhi, Jad Koweyes, Jemma L. Geoghegan, Joep de Ligt, Xiaoyun Ren, Matthew Storey, Nikki E. Freed, Chitra Pattabiraman, Pramada Prasad, Anita S. Desai, Ravi Vasanthapuram, Thomas F. Schulz, Lars Steinbrück, Tanja Stadler, Swiss Viollier Sequencing Consortium, Antonio Parisi, Angelica Bianco, Darío García de Viedma, Sergio Buenestado-Serrano, Vítor Borges, Joana Isidro, Sílvia Duarte, João Paulo Gomes, Neta S. Zuckerman, Michal Mandelboim, Orna Mor, Torsten Seemann, Alicia Arnott, Jenny Draper, Mailie Gall, William Rawlinson, Ira Deveson, Sanmarié Schlebusch, Jamie McMahon, Lex Leong, Chuan Kok Lim, Maria Chironna, Daniela Loconsole, Antonin Bal, Laurence Josset, Edward Holmes, Kirsten St. George, Erica Lasek-Nesselquist, Reina S. Sikkema, Bas Oude Munnink, Marion Koopmans, Mia Brytting, V. Sudha rani, S. Pavani, Teemu Smura, Albert Heim, Satu Kurkela, Massab Umair, Muhammad Salman, Barbara Bartolini, Martina Rueca, Christian Drosten, Thorsten Wolff, Olin Silander, Dirk Eggink, Chantal Reusken, Harry Vennema, Aekyung Park, Christine Carrington, Nikita Sahadeo, Michael Carr, Gabo Gonzalez, SEARCH Alliance San Diego, National Virus Reference Laboratory, SeqCOVID-Spain, Danish Covid-19 Genome Consortium (DCGC), Communicable Diseases Genomic Network (CDGN), Dutch National SARS-CoV-2 surveillance program, Division of Emerging Infectious Diseases (KDCA), Tulio de Oliveira, Nuno Faria, Andrew Rambaut, and Moritz U. G. Kraemer

Subjects
Medicine, Science
Abstract

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

Published
2021
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29. Comparison of clinical characteristics of Zika and dengue symptomatic infections and other acute illnesses of unidentified origin in Mexico.

Author

Pablo F Belaunzarán-Zamudio, Allyson Mateja, Paola Del Carmen Guerra-de-Blas, Héctor A Rincón-León, Karla Navarro-Fuentes, Emilia Ruiz-Hernández, Sandra Caballero-Sosa, Francisco Camas-Durán, Zoila Priego-Smith, José G Nájera-Cancino, Alexander López-Roblero, Karina Del Carmen Trujillo-Murillo, John H Powers, Sally Hunsberger, Sophia Siddiqui, John H Beigel, Raydel Valdés-Salgado, Guillermo Ruiz-Palacios, and Mexican Emerging Infectious Diseases Clinical Research Network (LaRed)

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

BackgroundOur purpose was to provide a detailed clinical description, of symptoms and laboratory abnormalities, and temporality in patients with confirmed Zika and dengue infections, and other acute illnesses of unidentified origin (AIUO).Methods/ principal findingsThis was a two-year, multicenter, observational, prospective, cohort study. We collected data from patients meeting the Pan American Health Organization's modified case-definition criteria for probable Zika infection. We identified Zika, dengue chikungunya by RT-PCR in serum and urine. We compared characteristics between patients with confirmed Zika and dengue infections, Zika and AIUO, and Dengue and AIUO at baseline, Days 3,7,28 and 180 of follow-up. Most episodes (67%) consistent with the PAHO definition of probable Zika could not be confirmed as due to any flavivirus and classified as Acute Illnesses of Unidentified Origin (AIUO). Infections by Zika and dengue accounted for 8.4% and 16% of episodes. Dengue patients presented with fever, generalized non-macular rash, arthralgia, and petechiae more frequently than patients with Zika during the first 10 days of symptoms. Dengue patients presented with more laboratory abnormalities (lower neutrophils, lymphocytosis, thrombocytopenia and abnormal liver function tests), with thrombocytopenia lasting for 28 days. Zika patients had conjunctivitis, photophobia and localized macular rash more frequently than others. Few differences persisted longer than 10 days after symptoms initiation: conjunctivitis in Zika infections, and self-reported rash and petechia in dengue infections.ConclusionsOur study helps characterize the variety and duration of clinical features in patients with Zika, dengue and AIUO. The lack of diagnosis in most patients points to need for better diagnostics to assist clinicians in making specific etiologic diagnoses.

Published
2021
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36. Different Clinical Presentations of Human Rhinovirus Species Infection in Children and Adults in Mexico.

Author

Galindo-Fraga, Arturo, Guerra-de-Blas, Paola del Carmen, Ortega-Villa, Ana M, Mateja, Allyson, Quiñones, Jesus Arturo Ruiz, Cervantes, Pilar Ramos, Barrientos, Fernando Ledesma, Ortiz-Hernández, Ana A, Llamosas-Gallardo, Beatriz, Ramírez-Venegas, Alejandra, Vázquez, Rafael Valdéz, Chepitel, Daniel Noyola, Moreno-Espinosa, Sarbelio, Powers, John H, Guerrero, M Lourdes, Ruiz-Palacios, Guillermo M, Beigel, John H, and Network, for the Mexican Emerging Infectious Diseases

Subjects
INFLUENZA, SYMPTOMS, CLINICAL trial registries, LEUKOCYTES, LACTATE dehydrogenase, VIRUS identification
Abstract

Background Human rhinoviruses (HRVs) are a common cause of influenza-like illness, with the ability to infect the upper and lower respiratory tracts. In this study we aim to describe the clinical and molecular features of HRV infection in Mexican children and adults. Methods We performed a hospital-based, 4-year multicenter prospective observational cohort study of patients with influenza-like illness. Participants who tested positive for HRV were included. We described demographic, clinical, and laboratory characteristics and the association between HRV types, illness severity, and clinical outcomes. Results Of the 5662 subjects recruited, 1473 (26%) had HRV; of those, 988 (67.1%) were adults (≥18 years) and 485 (32.9%) were children. One hundred sixty-seven (11.33%) samples were sequenced; 101 (60.5%) were rhinovirus species A (HRV-A), 22 (13.2%) were rhinovirus species B (HRV-B), and 44 (26.3%) were rhinovirus species C (HRV-C). Among children and adults, 30.5% and 23.5%, respectively, were hospitalized (non–intensive care unit [ICU]). The odds of HRV-C are higher than HRV-A for participants in the ICU (compared to outpatient) and when platelets, lymphocytes, white blood cells, and lactate dehydrogenase are increased. The odds of HRV-C are higher than HRV-A and HRV-B with shortness of breath. The odds of HRV-A are higher than HRV-B, and the odds of HRV-B are higher than HRV-C, when mild symptoms like muscle ache and headache occur. Conclusions Rhinoviruses are a common cause of influenza-like illness. It is necessary to improve the surveillance, testing, and species identification for these viruses to understand different clinical presentations and risk factors associated with worse outcomes. Clinical Trials Registration. NCT01418287. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Different epidemiological profiles in patients with Zika and dengue infection in Tapachula, Chiapas in Mexico (2016-2018): an observational, prospective cohort study.

Author

Belaunzarán-Zamudio, Pablo F., Rincón León, Héctor Armando, Caballero Sosa, Sandra, Ruiz, Emilia, Nájera Cancino, José Gabriel, de La Rosa, Paul Rodriguez, Guerrero Almeida, María de Lourdes, Powers III, John H., Beigel, John H., Hunsberger, Sally, Trujillo, Karina, Ramos, Pilar, Arteaga-Cabello, Fernando J., López-Roblero, Alexander, Valdés-Salgado, Raydel, Arroyo-Figueroa, Hugo, Becerril, Eli, Ruiz-Palacios, Guillermo, for the Mexican Emerging Infectious Diseases Clinical Research Network (La Red), and Regalado Pineda, Justino

Subjects
DENGUE hemorrhagic fever, ZIKA virus infections, VIRUS diseases, DENGUE viruses, COHORT analysis, CHIKUNGUNYA virus
Abstract

Background: The introduction of Zika and chikungunya to dengue hyperendemic regions increased interest in better understanding characteristics of these infections. We conducted a cohort study in Mexico to evaluate the natural history of Zika infection. We describe here the frequency of Zika, chikungunya and dengue virus infections immediately after Zika introduction in Mexico, and baseline characteristics of participants for each type of infection.Methods: Prospective, observational cohort evaluating the natural history of Zika virus infection in the Mexico-Guatemala border area. Patients with fever, rash or both, meeting the modified criteria of PAHO for probable Zika cases were enrolled (June 2016-July 2018) and followed-up for 6 months. We collected data on sociodemographic, environmental exposure, clinical and laboratory characteristics. Diagnosis was established based on viral RNA identification in serum and urine samples using RT-PCR for Zika, chikungunya, and dengue. We describe the baseline sociodemographic and environmental exposure characteristics of participants according to diagnosis, and the frequency of these infections over a two-year period immediately after Zika introduction in Mexico.Results: We enrolled 427 participants. Most patients (n = 307, 65.7%) had an acute illness episode with no identified pathogen (UIE), 37 (8%) Zika, 82 (17.6%) dengue, and 1 (0.2%) chikungunya. In 2016 Zika predominated, declined in 2017 and disappeared in 2018; while dengue increased after 2017. Patients with dengue were more likely to be men, younger, and with lower education than those with Zika and UIE. They also reported closer contact with water sources, and with other people diagnosed with dengue. Participants with Zika reported sexual exposure more frequently than people with dengue and UIE. Zika was more likely to be identified in urine while dengue was more likely found in blood in the first seven days of symptoms; but PCR results for both were similar at day 7-14 after symptom onset.Conclusions: During the first 2 years of Zika introduction to this dengue hyper-endemic region, frequency of Zika peaked and fell over a two-year period; while dengue progressively increased with a predominance in 2018. Different epidemiologic patterns between Zika, dengue and UIE were observed. Trial registration Clinical.Trials.gov (NCT02831699). [ABSTRACT FROM AUTHOR]

Published
2021
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39. Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness.

Author

Gamiño-Arroyo, Ana E, Guerrero, M Lourdes, McCarthy, Sean, Ramírez-Venegas, Alejandra, Llamosas-Gallardo, Beatriz, Galindo-Fraga, Arturo, Moreno-Espinosa, Sarbelio, Roldán-Aragón, Yuri, Araujo-Meléndez, Javier, Hunsberger, Sally, Ibarra-González, Violeta, Martínez-López, Julia, García-Andrade, Luis A, Kapushoc, Heather, Holley, H Preston, Smolskis, Mary C, Ruiz-Palacios, Guillermo M, Beigel, John H, and (LaRed), Mexico Emerging Infectious Diseases Clinical Research Network

Subjects
INFLUENZA diagnosis, ANTIVIRAL agents, HEALTH facilities, HOSPITAL care, LENGTH of stay in hospitals, INFLUENZA, MEDICAL quality control, POLYMERASE chain reaction, RESPIRATORY infections, INFLUENZA A virus, RANDOMIZED controlled trials, DISCHARGE planning, TREATMENT effectiveness, BLIND experiment, SEVERITY of illness index, ACUTE diseases, INFLUENZA B virus, EVALUATION
Abstract

Background Effective therapeutics for respiratory viruses are needed. Early data suggest that nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness. Methods From March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥1 year old hospitalized with influenza-like illness at 6 hospitals in Mexico. Participants were randomized 1:1 to NTZ (age ≥12 years, 600 mg twice daily; age 4–11 years and 1–3 years, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary endpoint was time from first dose to hospital discharge. Influenza reverse-transcription polymerase chain reaction and Respifinder 22 multiplex test were used for virus detection. Results Of 260 participants enrolled, 257 were randomized and took at least 1 dose of study treatment (intention-to-treat population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization was 6.5 (interquartile range [IQR], 4.0–9.0) days in the NTZ group vs 7.0 (IQR, 4.0–9.0) days in the placebo group (P =.56). Duration of hospitalization between the 2 treatments was similar in children (P =.29) and adults (P =.62), influenza A and B (P =.32), and other respiratory viruses. Seven (5.4%) and 6 (4.7%) participants in the NTZ and placebo groups, respectively, reported serious adverse events. Conclusions Treatment with NTZ did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from NTZ. Clinical Trials Registration NCT02057757. [ABSTRACT FROM AUTHOR]

Published
2019
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40. Clinical characteristics of asthmatic patients with influenza-like illness and risk of severe exacerbations in Mexico.

Author

Paulin-Prado, Paulina, Nishimura, Katherine, Freimanis-Hance, Laura, Hunsberger, Sally, Beigel, John, Fraga, Arturo Galindo, Ortiz Hernandez, Ana A., Llamosas-Gallardo, Beatriz, Moreno-Espinosa, Sarbelio, Magaña-Aquino, Martin, Ruiz Palacios, Guillermo M., Ramirez-Venegas, Alejandra, and Mexico Emerging Infectious Diseases Clinical Research Network

Published
2016
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41. HIV-associated multicentric castelman disease, a report of 5 cases

Author

Jonckheere, Sylvie, Yombi, Jean Cyr, Vincent, Anne, Belkhir, Leïla, Wilmes, Dunja, Vandercam, Bernard, 17th International Symposium on HIV and Emerging Infectious Diseases (ISHEID), UCL - SSS/IREC - Institut de recherche expérimentale et clinique, and UCL - (SLuc) Service de médecine interne générale

Subjects
Generalised lymphadenopathy, Pediatrics, medicine.medical_specialty, business.industry, Constitutional symptoms, Human immunodeficiency virus (HIV), virus diseases, nutritional and metabolic diseases, Disease, medicine.disease_cause, medicine.disease, eye diseases, Infectious Diseases, immune system diseases, hemic and lymphatic diseases, Virology, Poster Presentation, Medicine, business
Abstract

Multicentric Castleman’s disease (MCD) is a rare, non-clonal lymphoproliferative disorder characterized by constitutional symptoms, anaemia and generalised lymphadenopathy.

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42. Nevirapine-associated liver toxicity and hypersensitivity reactions in a cohort of HIV-1-infected patients,clinical analysis

Author

Jonckheere, Sylvie, Yombi, Jean Cyr, Belkhir, Leïla, Vincent, Anne, Vandercam, Bernard, 17th International Symposium on HIV and Emerging Infectious Diseases (ISHEID), UCL - SSS/IREC - Institut de recherche expérimentale et clinique, and UCL - (SLuc) Service de médecine interne générale

Subjects
lcsh:Immunologic diseases. Allergy, Liver injury, Hepatitis B virus, medicine.medical_specialty, Pathology, Nevirapine, business.industry, Hepatitis C, medicine.disease, medicine.disease_cause, Gastroenterology, Discontinuation, Hypersensitivity reaction, Infectious Diseases, Internal medicine, Virology, Poster Presentation, Cohort, medicine, lcsh:RC581-607, Viral hepatitis, business, medicine.drug
Abstract

Antiretroviral drug-related liver injury is a common cause of morbidity and treatment discontinuation in HIV-infected patients. Nevirapine is incriminated as one of the liver toxicity inducer especially in patients with high CD4-cells count. The purpose of our study was to analyze the role of CD4 cell count at treatment initiation and that of several co-factors (Hepatitis C or Hepatitis B virus co-infection, concurrent use of protease inhibitors) on the incidence of liver toxicity and hypersensivity reactions induced by Nevirapine in our HIV1-infected patients.

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43. Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins

Author

Arthur Louche, Amandine Blanco, Thais Lourdes Santos Lacerda, Lison Cancade-Veyre, Claire Lionnet, Célia Bergé, Monica Rolando, Frédérique Lembo, Jean-Paul Borg, Carmen Buchrieser, Masami Nagahama, Francine C. A. Gérard, Jean-Pierre Gorvel, Virginie Gueguen-Chaignon, Laurent Terradot, Suzana P. Salcedo, Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Reproduction et développement des plantes (RDP), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, 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), 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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Meiji Pharmaceutical University, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), SFR Biosciences, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CB lab was funded by the Institut Pasteur and ANR-10-LABX-62-IBEID for the Legionella experiments. These effectors were discovered under the ERA-Net Pathogenomics grant and the remaining work funded by ANR-15-CE15-0011-01 attributed to Suzana Salcedo. The work was completed with the ANR SNAPshot ANR-21-CE15-0024 attributed to Suzana Salcedo., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-15-CE15-0011,NucPath,Caractérisation du rôle cellulaire de nouveaux effecteurs bactériens ciblant les noyaux des cellules hôtes(2015), ANR-21-CE15-0024,SNAPshot,Détournement du stress nucléaire par les bactéries pathogènes(2021), Laurent, Terradot, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Caractérisation du rôle cellulaire de nouveaux effecteurs bactériens ciblant les noyaux des cellules hôtes - - NucPath2015 - ANR-15-CE15-0011 - AAPG2015 - VALID, Détournement du stress nucléaire par les bactéries pathogènes - - SNAPshot2021 - ANR-21-CE15-0024 - AAPG2021 - VALID, and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
[SDV] Life Sciences [q-bio], Multidisciplinary, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract

The cell nucleus is a primary target for intracellular bacterial pathogens to counteract immune responses and hijack host signalling pathways to cause disease. Here we identify two Brucella abortus effectors, NyxA and NyxB, that interfere with host protease SENP3, and this facilitates intracellular replication of the pathogen. The translocated Nyx effectors directly interact with SENP3 via a defined acidic patch (identified from the crystal structure of NyxB), preventing nucleolar localisation of SENP3 at late stages of infection. By sequestering SENP3, the effectors promote cytoplasmic accumulation of nucleolar AAA-ATPase NVL and ribosomal protein L5 (RPL5) in effector-enriched structures in the vicinity of replicating bacteria. The shuttling of ribosomal biogenesis-associated nucleolar proteins is inhibited by SENP3 and requires the autophagy-initiation protein Beclin1 and the SUMO-E3 ligase PIAS3. Our results highlight a nucleomodulatory function of two Brucella effectors and reveal that SENP3 is a crucial regulator of the subcellular localisation of nucleolar proteins during Brucella infection, promoting intracellular replication of the pathogen.

Published
2023
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44. Variants with the N501Y mutation extend SARS-CoV-2 host range to mice, with contact transmission

Author

Sylvie Behillil, Dominique Rousset, Flora Donati, Laurine Levillayer, Grégory Jouvion, Jean Jaubert, Xavier Montagutelli, Vincent Enouf, Mélanie Albert, Sylvie van der Werf, Fabiana Gámbaro, Eduard Baquero Salazar, Etienne Simon-Loriere, Félix A. Rey, Laurine Conquet, Matthieu Prot, Génétique de la souris - Mouse Genetics, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virologie Structurale - Structural Virology, École nationale vétérinaire - Alfort (ENVA), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence des virus respiratoires (dont la grippe et le SARS-CoV2) [Paris] (CNR - laboratoire associé), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur), the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID), the Agence Nationale de la Recherche (Grant No. ANR-20-COVI-0028-01) and the RECOVER project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 101003589. ESL acknowledges funding from the INCEPTION programme (Investissements d’Avenir grant ANR-16-CONV-0005)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0028,HuMoCID,Développement de modèles murins de COVID-19(2020), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), and European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020)

Subjects
Infectivity, Genetics, Mutation rate, variants, reservoir, mice, Rodent, biology, Sars-CoV-2, Host (biology), [SDV]Life Sciences [q-bio], transmission, RNA, host range, Virus, biology.animal, Adaptation, Receptor
Abstract

Receptor recognition is a major determinant of viral host range, as well as infectivity and pathogenesis. Emergences have been associated with serendipitous events of adaptation upon encounters with a novel host, and the high mutation rate of RNA viruses has been proposed to explain their frequent host shifts 1. SARS-CoV-2 extensive circulation in humans has been associated with the emergence of variants, including variants of concern (VOCs) with diverse mutations in the spike and increased transmissibility or immune escape 2. Here we show that unlike the initial virus, VOCs are able to infect common laboratory mice, replicating to high titers in the lungs. This host range expansion is explained in part by the acquisition of changes at key positions of the receptor binding domain that enable binding to the mouse angiotensin-converting enzyme 2 (ACE2) cellular receptor, although differences between viral lineages suggest that other factors are involved in the capacity of SARS-CoV-2 VOCs to infect mice. This abrogation of the species barrier raises the possibility of wild rodent secondary reservoirs and provides new experimental models to study disease pathophysiology and countermeasures.

Published
2023

45. Cytotoxicity of human antibodies targeting the circumsporozoite protein is amplified by 3D substrate and correlates with protection

Author

Aguirre-Botero, Manuela, Wang, Lawrence, Formaglio, Pauline, Aliprandini, Eduardo, Thiberge, Jean-Michel, Schön, Arne, Flores-Garcia, Yevel, Mathis-Torres, Shamika, Flynn, Barbara, da Silva Pereira, Lais, Le Duff, Yann, Hurley, Mathew, Nacer, Adéla, Bowyer, Paul, Zavala, Fidel, Idris, Azza, Francica, Joseph, Seder, Robert, Amino, Rogerio, Infection et Immunité paludéennes - Malaria Infection and Immunity, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), National Institutes of Health [Bethesda] (NIH), Johns Hopkins University (JHU), Johns Hopkins Malaria Research Institute [Baltimore], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare Products Regulatory Agency (MHRA), This work was supported by funds from the Institut Pasteur, the Agence Nationale de la Recherche (ANR, French National Research Agency)/Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – project number SporoSTOP ANR-19-CE15-0027, and the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' – project number ANR-10-LABX-62-IBEID. M.C.A.-B. is funded by the Pasteur - Paris University International PhD Program. A.S. was supported by contract HHSN261200800001E from the National Cancer Institute, NIH. Y.F.-G. and F.Z. thank the Bill and Melinda Gates Foundation and Bloomberg Philanthropies for their continued support. The antibodies provided by the Center for AIDS Reagents repository at the National Institute for Biological Standards and Control, UK (6F8 and 2C4) were produced through the European Commission FP7 European Research Infrastructures for Poverty Related Diseases (EURIPRED) project (INFRA-2012-312661), funded by the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 312661 – EURIPRED. The graphical abstract was created with BioRender.com, We would like to thank the team of the Center for Production and Infection of Anopheles (CEPIA, C2RA, Institut Pasteur) for providing mosquitoes, the staff of Central Animal Facility (C2RA, Institut Pasteur) for animal care, and the team of the Photonic BioImaging platform (UTechS PBI, C2RT, Institut Pasteur) for providing access to the spinning-disk microscope and support., ANR-19-CE15-0027,SporoSTOP,Neutralisation des sporozoïtes de Plasmodium dans la peau de l'hôte(2019), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and European Project: 312661,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2012-1,EURIPRED(2013)

Subjects
[SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract

International audience; Human monoclonal antibodies (hmAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on the sporozoite surface are a promising tool for preventing malaria infection. However, their mechanisms of protection remain unclear. Here, using 13 distinctive PfCSP hmAbs, we provide a comprehensive view of how PfCSP hmAbs neutralize sporozoites in host tissues. Sporozoites are most vulnerable to hmAb-mediated neutralization in the skin. However, rare but potent hmAbs additionally neutralize sporozoites in the blood and liver. Efficient protection in tissues mainly associates with high-affinity and high-cytotoxicity hmAbs inducing rapid parasite loss-of-fitness in the absence of complement and host cells in vitro. A 3D-substrate assay greatly enhances hmAb cytotoxicity and mimics the skin-dependent protection, indicating that the physical stress imposed on motile sporozoites by the skin is crucial for unfolding the protective potential of hmAbs. This functional 3D cytotoxicity assay can thus be useful for downselecting potent anti-PfCSP hmAbs and vaccines.

Published
2023
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46. Estimated protection against COVID-19 based on predicted neutralisation titres from multiple antibody measurements in a longitudinal cohort, France, April 2020 to November 2021

Author

Woudenberg, Tom, Pinaud, Laurie, Garcia, Laura, Tondeur, Laura, Pelleau, Stephane, de Thoisy, Alix, Donnadieu, Françoise, Backovic, Marija, Attia, Mikaël, Hozé, Nathanaël, Duru, Cécile, Koffi, Aymar Davy, Castelain, Sandrine, Ungeheuer, Marie-Noelle, Fernandes Pellerin, Sandrine, Planas, Delphine, Bruel, Timothée, Cauchemez, Simon, Schwartz, Olivier, Fontanet, Arnaud, White, Michael, Epidémiologie et Analyse des Maladies Infectieuses - Infectious Disease Epidemiology and Analytics, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), 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)-Université Paris Cité (UPCité)-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), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Hôpital de Crépy-en-Valois, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Virus et Immunité - Virus and immunity (CNRS-UMR3569), This work was supported by the Fondation pour la Recherche Médicale (CorPopImm to MW), and the French Government's Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (Investissement d'Avenir grant n°ANR-10-LABX-62-IBEID), and INCEPTION programs (Investissement d’Avenir grant ANR-16-CONV-0005), and 'URGENCE COVID-19' fundraising campaign of Institut Pasteur (TooLab project awarded to M.B.). The COVID-Oise cohort is funded by 'Alliance Tous Unis contre le virus' Institut Pasteur, AP-HP and Fondation de France., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)

Subjects
seroprevalence, SARS-CoV-2, humoral immunity, sero-epidemiology, viral immunity, COVID-19, antibodies, protection, neutralising antibodies, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BackgroundThe risk of SARS-CoV-2 (re-)infection remains present given waning of vaccine-induced and infection-acquired immunity, and ongoing circulation of new variants.AimTo develop a method that predicts virus neutralisation and disease protection based on variant-specific antibody measurements to SARS-CoV-2 antigens.MethodsTo correlate antibody and neutralisation titres, we collected 304 serum samples from individuals with either vaccine-induced or infection-acquired SARS-CoV-2 immunity. Using the association between antibody and neutralisation titres, we developed a prediction model for SARS-CoV-2-specific neutralisation titres. From predicted neutralising titres, we inferred protection estimates to symptomatic and severe COVID-19 using previously described relationships between neutralisation titres and protection estimates. We estimated population immunity in a French longitudinal cohort of 905 individuals followed from April 2020 to November 2021.ResultsWe demonstrated a strong correlation between anti-SARS-CoV-2 antibodies measured using a low cost high-throughput assay and antibody response capacity to neutralise live virus. Participants with a single vaccination or immunity caused by infection were especially vulnerable to symptomatic or severe COVID-19. While the median reduced risk of COVID-19 from Delta variant infection in participants with three vaccinations was 96% (IQR: 94–98), median reduced risk among participants with infection-acquired immunity was only 42% (IQR: 22–66).ConclusionOur results are consistent with data from vaccine effectiveness studies, indicating the robustness of our approach. Our multiplex serological assay can be readily adapted to study new variants and provides a framework for development of an assay that would include protection estimates.

Published
2023
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47. 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
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48. Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 omicron sub-lineages

Author

Franck Touret, Emilie Giraud, Jérôme Bourret, Flora Donati, Jaouen Tran-Rajau, Jeanne Chiaravalli, Frédéric Lemoine, Fabrice Agou, Etienne Simon-Lorière, Sylvie van der Werf, Xavier de Lamballerie, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Criblage chémogénomique et biologique (Plateforme) - Chemogenomic and Biological Screening Platform (PF-CCB), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, This work was performed in the framework of the Preclinical Study Group of the French agency for emerging infectious diseases (ANRS-MIE). It was supported by the ANRS-MIE (BIOVAR and PRI projects of the EMERGEN research program) and by the European Commission (European Virus Archive Global project (EVA GLOBAL, grant agreement No 871029) of the Horizon 2020 research and innovation program). The SVDW and ESL laboratories acknowledge funding from the European Commission (RECOVER project, grant agreement No 101003589) of the Horizon 2020 research and innovation program and by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID). The SVDW lab acknowledges funding from Santé publique France (the French national public health agency), the 'Enhancing Whole Genome Sequencing (WGS) and/or Reverse Transcription Polymerase Chain Reaction (RT-PCR) national infrastructures and capacities to respond to the COVID-19 pandemic in the European Union and European Economic Area' Grant Agreement ECDC/HERA/2021/007 ECD. 12221, and the Caisse nationale d’assurance maladie (Cnam), the national health insurance funds. The ESL laboratory acknowledges funding from the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005), the NIH PICREID program (Award Number U01AI151758)., We thank Pr B.Lina for providing the SARS-CoV-2 BA.2, BA.5, and XBB strains. We thank Rayane Amaral and Camille Placidi-Italia for the technical help regarding the molecular biology experiments and the cell culture. We thank Dr Cecile Baronti for her help and expertise regarding BSL3 experiments at UVE. We thank the staff of the National Reference Center for technical help, the team of the Mutualized Platform of Microbiology (P2M) at Institut Pasteur for help with sequencing and bioinformaticians of the Bioinformatics Hub at Institut Pasteur for help with sequence analysis. We are indebted to Dr. H. Mouquet (Institut Pasteur, Paris, France) for providing the Bebtelovimab/LY-Cov1404 antibody. We thank the public and private laboratories for providing specimens and aknowledge the EMERGEN genomic surveillance consortium. We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID and GenBank., 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: 871029,H2020,H2020-INFRAIA-2019-1,EVA-GLOBAL(2020), and European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020)

Subjects
Multidisciplinary, [SDE]Environmental Sciences
Abstract

SummaryThe landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance of multiple sub-variants originating from BA.2, BA.4 and BA.5 Omicron sub-lineages. They harbor a specific set of mutations in the spike that can make them more evasive to therapeutic monoclonal antibodies. In this study, we compared the neutralizing potential of monoclonal antibodies against the Omicron BA.2.75.2, BQ.1, BQ.1.1 and XBB variants, with a pre-Omicron Delta variant as a reference. Sotrovimab retains some activity against BA.2.75.2, BQ.1 and XBB as it did against BA.2/BA.5, but is less active against BQ.1.1. Within the Evusheld/AZD7442 cocktail, Cilgavimab lost all activity against all subvariants studied, resulting in loss of Evusheld activity. Finally, Bebtelovimab, while still active against BA.2.75, also lost all neutralizing activity against BQ.1, BQ.1.1 and XBB variants.

Published
2023
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49. Bacterial capsular polysaccharides with antibiofilm activity share common biophysical and electrokinetic properties

Author

Joaquín Bernal-Bayard, Jérôme Thiebaud, Marina Brossaud, Audrey Beaussart, Céline Caillet, Yves Waldvogel, Laetitia Travier, Sylvie Létoffé, Thierry Fontaine, Bachra Rokbi, Philippe Talaga, Christophe Beloin, Noëlle Mistretta, Jérôme F. L. Duval, Jean-Marc Ghigo, Génétique des Biofilms - Genetics of Biofilms, 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), Universidad de Sevilla / University of Sevilla, Sanofi Pasteur [Marcy-l'Étoile, France], Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Interactions cerveau-immunité - Brain-immune communication, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 842629,Salmofish, Duval, Jerome, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Tracing T3SS effectors in vivo during Salmonella infection in the zebrafish model - Salmofish - 0000-00-00 - 0000-00-00 - 842629 - VALID

Subjects
[SDV] Life Sciences [q-bio], Multidisciplinary, [SDV]Life Sciences [q-bio], [CHIM] Chemical Sciences, General Physics and Astronomy, [CHIM]Chemical Sciences, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract

Bacterial biofilms are surface-attached communities that are difficult to eradicate due to a high tolerance to antimicrobial agents. The use of non-biocidal surface-active compounds to prevent the initial adhesion and aggregation of bacterial pathogens is a promising alternative to antibiotic treatments and several antibiofilm compounds have been identified, including some capsular polysaccharides released by various bacteria. However, the lack of chemical and mechanistic understanding of the activity of these high-molecular-weight polymers limits their use for control of biofilm formation. Here, we screened a collection of 32 purified capsular polysaccharides and identified seven new compounds with non-biocidal activity against biofilms formed by Escherichia coli and/or Staphylococcus aureus. We analyzed the polysaccharide mobility under applied electric field conditions and showed that active and inactive polysaccharide polymers display distinct electrokinetic properties and that all active macromolecules shared high intrinsic viscosity features. Based on these characteristics, we identified two additional antibiofilm capsular polysaccharides with high density of electrostatic charges and their permeability to fluid flow. Our study therefore provides insights into key biophysical properties discriminating active from inactive polysaccharides. This characterization of a specific electrokinetic signature for polysaccharides displaying antibiofilm activity opens new perspectives to identify or engineer non-biocidal surface-active macromolecules to control biofilm formation in medical and industrial settings.Significance statementSome bacteria produce non-biocidal capsular polysaccharides that reduce the adhesion of bacterial pathogens to surfaces. Due to a lack of molecular and structural definition, the basis of their antiadhesion activity is unknown, thus hindering their prophylactic use for biofilm control. Here, we identified nine new active compounds and compared their composition, structure and biophysical properties with other inactive capsular polysaccharides. Despite the absence of specific molecular motif, we demonstrate that all active polysaccharides share common electrokinetic properties that distinguish them from inactive polymers. This characterization of the biophysical properties of antibiofilm bacterial polysaccharide provides key insights to engineer non-biocidal and bio-inspired surface-active compounds to control bacterial adhesion in medical and industrial settings.

Published
2023
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50. The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito

Author

Ferdinand Roesch, Chelsea Cereghino, Lucia Carrau, Alexandra Hardy, Helder Ribeiro-Filho, Annabelle Henrion Lacritick, Cassandra Koh, Jeffrey Marano, Tyler Bates, Pallavi Rai, Christina Chuong, Shamima Akter, Thomas Vallet, Hervé Blanc, Truitt Elliot, Anne M. Brown, Pawel Michalak, Tanya LeRoith, Jesse Bloom, Rafael Elias Marques, Maria-Carla Saleh, Marco Vignuzzi, James Weger-Lucarelli, Virginia Tech [Blacksburg], Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Centro Nacional de Pesquisa em Energia e Materiais = Brazilian Center for Research in Energy and Materials (CNPEM), Virus et Interférence ARN - Viruses and RNA Interference, George Mason University [Fairfax], Program of Genetics, Bioinformatics, and Computational Biology [Blacksburg] (GBCB), University of Haifa [Haifa], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), This work was funded by the DARPA PREEMPT program administered through DARPA Cooperative Agreement HR001118S0017, this funding was awarded to M-C.S., M.V, and J.W-L. This work also received funding from Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID) to M-C.S. and M.V. Further support was provided by startup funds awarded to J.W-L by the Virginia-Maryland College of Veterinary Medicine and a grant from the One Health Research Funding Program awarded to J.W-L and P.M., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)

Subjects
Virology, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, Parasitology, Molecular Biology, Microbiology
Abstract

International audience; Adaptation to mosquito vectors suited for transmission in urban settings is a major driver in the emergence of arboviruses. To better anticipate future emergence events, it is crucial to assess their potential to adapt to new vector hosts. In this work, we used two different experimental evolution approaches to study the adaptation process of an emerging alphavirus, Mayaro virus (MAYV), to Ae. aegypti, an urban mosquito vector of many other arboviruses. We identified E2-T179N as a key mutation increasing MAYV replication in insect cells and enhancing transmission after escaping the midgut of live Ae. aegypti. In contrast, this mutation decreased viral replication and binding in human fibroblasts, a primary cellular target of MAYV in humans. We also showed that MAYV E2-T179N generates reduced viremia and displays less severe tissue pathology in vivo in a mouse model. We found evidence in mouse fibroblasts that MAYV E2-T179N is less dependent on the Mxra8 receptor for replication than WT MAYV. Similarly, exogenous expression of human apolipoprotein receptor 2 and Mxra8 enhanced WT MAYV replication compared to MAYV E2-T179N. When this mutation was introduced in the closely related chikungunya virus, which has caused major outbreaks globally in the past two decades, we observed increased replication in both human and insect cells, suggesting E2 position 179 is an important determinant of alphavirus host-adaptation, although in a virus-specific manner. Collectively, these results indicate that adaptation at the T179 residue in MAYV E2 may result in increased vector competence-but coming at the cost of optimal replication in humans-and may represent a first step towards a future emergence event.Author summary: Mosquito-borne viruses must replicate in both mosquito and vertebrate hosts to be maintained in nature successfully. When viruses that are typically transmitted by forest dwelling mosquitoes enter urban environments due to deforestation or travel, they must adapt to urban mosquito vectors to transmit effectively. For mosquito-borne viruses, the need to also replicate in a vertebrate host like humans constrains this adaptation process. Towards understanding how the emerging alphavirus, Mayaro virus, might adapt to transmission by the urban mosquito vector, Ae. aegypti, we used natural evolution approaches to identify several viral mutations that impacted replication in both mosquito and vertebrate hosts. We show that a single mutation in the receptor binding domain of E2 increased transmission by Ae. aegypti after bypassing the midgut infection barrier but simultaneously reduced replication and pathology in a mouse model. Mechanistic studies suggested that this mutation decreases the dependence of MAYV on human Mxra8 and the putative MAYV receptor human ApoER2 during replication. This suggests MAYV with this mutation alone is unlikely to be maintained in a natural transmission cycle between mosquitoes and humans. Understanding the adaptive potential of emerging viruses is critical to preventing future pandemics.

Published
2023
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