Lassa fever outcomes and prognostic factors in Nigeria (LASCOPE): a prospective cohort study

BACKGROUND: Lassa fever is a viral haemorrhagic fever endemic in parts of west Africa. New treatments are needed to decrease mortality, but pretrial reference data on the disease characteristics are scarce. We aimed to document baseline characteristics and outcomes for patients hospitalised with Lassa fever in Nigeria. METHODS: We did a prospective cohort study (LASCOPE) at the Federal Medical Centre in Owo, Nigeria. All patients admitted with confirmed Lassa fever were invited to participate and asked to give informed consent. Patients of all ages, including newborn infants, were eligible for inclusion, as were pregnant women. All participants received standard supportive care and intravenous ribavirin according to Nigeria Centre for Disease Control guidelines and underwent systematic biological monitoring for 30 days. Patients' characteristics, care received, mortality, and associated factors were recorded using standard WHO forms. We used univariable and multivariable logistic regression models to investigate an association between baseline characteristics and mortality at day 30. FINDINGS: Between April 5, 2018, and March 15, 2020, 534 patients with confirmed Lassa fever were admitted to hospital, of whom 510 (96%) gave consent and were included in the analysis. The cohort included 258 (51%) male patients, 252 (49%) female patients, 426 (84%) adults, and 84 (16%) children (younger than 18 years). The median time between first symptoms and hospital admission was 8 days (IQR 7-13). At baseline, 176 (38%) of 466 patients had a Lassa fever RT-PCR cycle threshold (Ct) lower than 30. From admission to end of follow-up, 120 (25%) of 484 reached a National Early Warning Score (second version; NEWS2) of 7 or higher, 67 (14%) of 495 reached a Kidney Disease-Improving Global Outcome (KDIGO) stage of 2 or higher, and 41 (8%) of 510 underwent dialysis. All patients received ribavirin for a median of 10 days (IQR 9-13). 62 (12%) patients died (57 [13%] adults and five [6%] children). The median time to death was 3 days (1-6). The baseline factors independently associated with mortality were the following: age 45 years or older (adjusted odds ratio 16·30, 95% CI 5·31-50·30), NEWS2 of 7 or higher (4·79, 1·75-13·10), KDIGO grade 2 or higher (7·52, 2·66-21·20), plasma alanine aminotransferase 3 or more times the upper limit of normal (4·96, 1·69-14·60), and Lassa fever RT-PCR Ct value lower than 30 (4·65, 1·50-14·50). INTERPRETATION: Our findings comprehensively document clinical and biological characteristics of patients with Lassa fever and their relationship with mortality, providing prospective estimates that could be useful for designing future therapeutic trials. Such trials comparing new Lassa fever treatments to a standard of care should take no more than 15% as the reference mortality rate and consider adopting a combination of mortality and need for dialysis as the primary endpoint. FUNDING: Institut National de la Santé et de la Recherche Médicale, University of Oxford, EU, UK Department for International Development, Wellcome Trust, French Ministry of Foreign Affairs, Agence Nationale de Recherches sur le SIDA et les hépatites virales, French National Research Institute for Sustainable Development

Caractérisations moléculaires de rVSV-ZEBOV, vaccin prototype contre le virus Ebola

The filovirus Ebolavirus (EBOV) is the causative agent of severe viral hemorrhagic fevers in humans that can be lethal in 90% of cases. The current outbreak in the Democratic Republic of Congo and the extraordinary scale of the 2014-2016 outbreak in West Africa, that caused the death of more than 11 000 disease victims, lead the international public health agencies to test several therapeutic approach to limit viral spreading and mortality. Amongst those, the recombinant replication-competent rVSV-ZEBOV virus, that expressed EBOV GP glycoprotein, appears to offer the best protection in animal models and outbreak settings. While its effectiveness and safety have been widely investigated before human trials and despite numerous studies that showed the importance the nature of the glycoproteins which are produced during the infection from the EBOV GP gene that has been inserted in VSV genome are unknown. In this respect, the molecular characterisations of the viral glycoproteins synthesised during rVSV-GP presented in this thesis, offer new insights with which to understand the success of the rVSV-GP vaccine but also the potential viral origins of the severe adverse side effects observed during vaccination and could help in developing a safer vaccine, which currently cannot be used in an immunocompromised populationEbolavirus (EBOV) est un filovirus responsable de fièvres hémorragiques virales sévères chez l’humain, qui peuvent être létales dans 90% des cas. L’actuelle épidémie en République Démocratique du Congo et l’ampleur démesurée de l'épidémie de 2014-2016 en Afrique de l’Ouest, qui a causé la mort de plus de 11 000 personnes, ont poussé les agences sanitaires internationales à tester plusieurs approches thérapeutiques afin d’essayer d’endiguer rapidement la propagation virale et de limiter la mortalité liée au virus lors de futures épidémies. Parmi toutes les stratégies testées, le virus recombinant réplicatif rVSV-ZEBOV qui exprime la glycoprotéine de surface d’EBOV, semble offrir la meilleur protection, aussi bien en modèle animaliers que sur le terrain. Avant d’être testé chez l’humain, de nombreuses études ont permis de mettre en évidence l’efficacité et l’innocuité de ce vaccin prototype. Pourtant et malgré le fait que de nombreuses études ont démontré l’importance et le rôle de la glycoprotéine GP dans l’efficacité des vaccins contre ce virus, aucune étude n’a encore été réalisé sur la nature des glycoprotéines virales synthétisées par le gène GP d’EBOV inséré dans le génome du virus VSV. Ainsi, les caractérisations moléculaires des protéines virales produites lors de l’infection par le virus rVSV-GP décrites dans ces travaux de thèse offrent de nouvelles perspectives pour comprendre le succès de ce vaccin mais aussi l’origine virales dans les effets secondaires sévères observés lors de la vaccination, et pourront aider à développer un vaccin plus sûr, qui n’est actuellement pas utilisable chez les personnes immunodéprimée

Human transmission of Ebola virus

International audienceEver since the first recognised outbreak of Ebolavirus in 1976, retrospective epidemiological analyses and extensive studies with animal models have given us insight into the nature of the pathology and transmission mechanisms of this virus. In this review focusing on Ebolavirus, we present an outline of our current understanding of filovirus human-to-human transmission and of our knowledge concerning the molecular basis of viral transmission and potential for adaptation, with particular focus on what we have learnt from the 2014 outbreak in West Africa. We identify knowledge gaps relating to transmission and pathogenicity mechanisms, molecular adaptation and filovirus ecology

Portugal. Mapas generales. 1716

Escala expresada tambien en 25 Lieües Communes de France.Orientado con rosa de 16 vientos coronada con flor de lis al norte.Toponimia local en castellano y francés.Hidrografía destacada.Poblaciones representadas por conjuntos de edificaciones según su importancia.Relieve por montes de perfil.Costa sombreada por líneas horizontales.Divisiones administrativas de los reinos de la Península Ibérica diferenciados por lindes coloreadas.En la zona inferior izquierda recuadro con "Longitude et Latitude des Principaux Lieux d'Espagne suivant les Nouvelles Observations de Mrs. de l'Academie Royale des Sciencies" y "Avec Privilege du Roy et Aprobation de Mr. de la Hire de l'Academie Royale des Sciencies"Cartela de titulo decorada con cornucopia y acompañada en línea por los escudos de armas de los reinos y regiones de la Península Ibérica

Light-shift mitigation in a microcell-based atomic clock with symmetric auto-balanced Ramsey spectroscopy

International audienceThe mid-term fractional frequency stability of miniaturized atomic clocks can be limited by light-shift effects. In this Letter, we demonstrate the implementation of a symmetric auto-balanced Ramsey (SABR) interrogation sequence in a microcell-based atomic clock based on coherent population trapping. Using this advanced protocol, the sensitivity of the clock frequency to laser power, microwave power, and laser frequency variations is reduced, at least by one order of magnitude, in comparison with continuous-wave or Ramsey interrogation schemes. Light-shift mitigation obtained with the SABR sequence benefits greatly to the clock Allan deviation for integration times between 102 and 105 s. These results demonstrate that such interrogation techniques are of interest to enhance the timekeeping performance of chip-scale atomic clocks