L'apport des données de contacts détaillées à la modélisation épidémiologique : application au cas des infections nosocomiales à Staphylococcus aureus

Mathematical modeling in epidemiology often assumes that individuals mix at random within a population. Age-structured models allow for more realistic contact rates, depending on the age of individuals, yet such models can’t characterize the heterogeneity at the individual level.In this thesis, we present the results of a prospective, longitudinal study conducted during 6 months in a long-term care facility located in Berck-sur-Mer, France. We show that high-resolution contact structures can be used to design new intervention strategies in order to reduce the spread of nosocomial bacteria and inform models with more realistic contact patterns.After first recalling the usual modeling frameworks used in epidemiology and their underlying hypothesis, we detail the data collected as part of the I-Bird study. This study focuses on understanding how Staphylococcus aureus spreads between individuals in a healthcare setting.In a first study, we provide empirical results that validate the use of electronic records as a good proxy for close-proximity interactions that can lead to the dissemination of S. aureus. We then set out to identify contact-related risk factors for S. aureus colonization, in an effort to detect situation of increased risk. Such situations could help enforce new intervention strategies that rely on the observed contact network, to efficiently reduce the burden of S. aureus, ultimately helping to reduce the spread of multidrug-resistant bacteria.La modélisation mathématique en épidémiologie utilise traditionnellement l’hypothèse de mélange homogène des individus dans la population. Si certains modèles structurés permettent de tenir compte de l’hétérogénéité apparente (spatiale, temporelle), ils permettent rarement de la caractériser à l’échelle d’un individu. Dans cette thèse, nous présentons les résultats de l’analyse conjointe des contacts interindividuels et du portage individuel de Staphylococcus aureus. Ces données, collectées dans l’hôpital de soins de suite de Berck-sur-Mer pendant 6 mois, permettent de mettre en évidence l’intérêt de l’étude des structures de contacts pour établir des nouvelles mesures de contrôle dans la lutte contre les infections nosocomiales, et plus généralement pour apporter un nouveau substrat informatif aux modèles épidémiologiques.Après avoir rappelé dans une première partie les différents modèles usuels utilisés en épidémiologie et les hypothèses qu’ils imposent, nous présentons l’étude I-Bird qui vise à identifier, par l’utilisation des nouvelles technologies de l’information, de nouvelles méthodes pour limiter la dissémination de bactéries nosocomiales.Dans une première étude, nous démontrons que l’utilisation de capteurs électroniques de proximité fournit un proxy valable pour la collecte des interactions interindividuelles pouvant mener à transmission de S. aureus entre patients et personnels soignants dans un établissement de soins de suite et de réadaptation. Nous exploitons ensuite ces données de façon à fournir une évaluation quantitative du risque individuel d’acquisition de S. aureus, dans l’optique de réduire la dissémination de bactéries multirésistantes

Effective inhomogeneous inflation: curvature inhomogeneities of the Einstein vacuum

We consider spatially averaged inhomogeneous universe models and argue that, already in the absence of sources, an effective scalar field arises through foliating and spatially averaging inhomogeneous geometrical curvature invariants of the Einstein vacuum. This scalar field (the `morphon') acts as an inflaton, if we prescribe a potential of some generic form. We show that, for any initially negative average spatial curvature, the morphon is driven through an inflationary phase and leads - on average - to a spatially flat, homogeneous and isotropic universe model, providing initial conditions for pre-heating and, by the same mechanism, a possibly natural self-exit.Comment: 9 pages, 2 figures, to appear in Class. Quant. Grav. as Fast Track Communicatio

Global gravitational instability of FLRW backgrounds - interpreting the dark sectors

The standard model of cosmology is based on homogeneous-isotropic solutions of Einstein's equations. These solutions are known to be gravitationally unstable to local inhomogeneous perturbations, commonly described as evolving on a background given by the same solutions. In this picture, the FLRW backgrounds are taken to describe the average over inhomogeneous perturbations for all times. We study in the present article the (in)stability of FLRW dust backgrounds within a class of averaged inhomogeneous cosmologies. We examine the phase portraits of the latter, discuss their fixed points and orbital structure and provide detailed illustrations. We show that FLRW cosmologies are unstable in some relevant cases: averaged models are driven away from them through structure formation and accelerated expansion. We find support for the proposal that the dark components of the FLRW framework may be associated to these instability sectors. Our conclusion is that FLRW cosmologies have to be considered critically as for their role to serve as reliable models for the physical background.Comment: 15 pages, 13 figures, 1 table. Matches published version in CQ

Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment.

BACKGROUND: Eliminating Plasmodium vivax will require targeting the hidden liver-stage reservoir of hypnozoites. This necessitates new interventions balancing the benefit of reducing vivax transmission against the risk of over-treating some individuals with drugs which may induce haemolysis. By measuring antibodies to a panel of vivax antigens, a strategy of serological-testing-and-treatment (PvSeroTAT) can identify individuals with recent blood-stage infections who are likely to carry hypnozoites and target them for radical cure. This provides a potential solution to selectively treat the vivax reservoir with 8-aminoquinolines. METHODS: PvSeroTAT can identify likely hypnozoite carriers with ~80% sensitivity and specificity. Diagnostic test sensitivities and specificities ranging 50-100% were incorporated into a mathematical model of vivax transmission to explore how they affect the risks and benefits of different PvSeroTAT strategies involving hypnozoiticidal regimens. Risk was measured as the rate of overtreatment and benefit as reduction of community-level vivax transmission. RESULTS: Across a wide range of combinations of diagnostic sensitivity and specificity, PvSeroTAT was substantially more effective than bloodstage mass screen and treat strategies and only marginally less effective than mass drug administration. The key test characteristic determining of the benefit of PvSeroTAT strategies is diagnostic sensitivity, with higher values leading to more hypnozoite carriers effectively treated and greater reductions in vivax transmission. The key determinant of risk is diagnostic specificity: higher specificity ensures that a lower proportion of uninfected individuals are unnecessarily treated with primaquine. These relationships are maintained in both moderate and low transmission settings (qPCR prevalence 10% and 2%). Increased treatment efficacy and adherence can partially compensate for lower test performance. Multiple rounds of PvSeroTAT with a lower performing test may lead to similar or higher reductions in vivax transmission than fewer rounds with a higher performing test, albeit with higher rate of overtreatment. CONCLUSIONS: At current performance, PvSeroTAT is predicted to be a safe and efficacious option for targeting the hypnozoite reservoir towards vivax elimination. P. vivax sero-diagnostic tests should aim for both high performance and ease of use in the field. The target product profiles informing such development should thus reflect the trade-offs between impact, overtreatment, and ease of programmatic implementation

Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika.info:eu-repo/semantics/publishedVersio

Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Far-reaching cellular consequences of tat deletion in Escherichia coli revealed by comprehensive proteome analyses

In Escherichia coli, the Twin-arginine translocation (Tat) pathway secretes a set of folded proteins with important physiological functions to the periplasm and outer membrane. The loss of Tat secretion impairs outer membrane integrity and leads to decreased cell growth. Only recently, the Tat pathway has gained more attention due to its essential role in bacterial virulence and applications in the production of fully folded heterologous proteins. In this study, we investigated the influence of the deletion of all active Tat pathway components on the E. coli cells. The comprehensive proteomic analysis revealed activation of several stress responses and experimentally confirmed the dependence of certain proteins on the Tat system for export. We observed that a tat deletion triggers protein aggregation, membrane vesiculation, synthesis of colanic acid and biofilm formation. Furthermore, the mislocalization of Tat-dependent proteins disturbs iron and molybdenum homeostasis and impairs the cell envelope integrity. The results show that the functional Tat pathway is important for the physiological stability and that its dysfunction leads to a series of severe changes in E. coli cells

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)