26 research outputs found
Études quantitatives de la transmission des maladies infectieuses en population en utilisant des séquences génétiques de pathogènes et des données épidémiologiques individuelles
No full textAmong the methods for the quantitative study of infectious diseases transmission in host populations, molecular epidemiology that reconstructs pathogen phylogenies by using pathogen genetic sequences and mathematical modelling of infectious diseases that fits mechanistic models of disease transmission to epidemiological data such as case counts are of particular interest to epidemiologists. These two approaches rely on different data sources whose availability depends on the setting. They also rely on different concepts and models leading to complementary pictures of disease transmission. The main objective of this thesis is to better understand how viral infectious diseases such as rabies and COVID-19 circulate in host populations using respectively geolocated and timestamped viral genetic sequences and detailed epidemiological data at the individual level. The first part of this thesis focuses on rabies, a neglected tropical zoonosis, that is estimated to cause 59,000 human deaths per year mostly among rural and poor populations in Africa and Asia. Its causing agent, rabies virus (RABV), mainly circulates in domestic dog populations. Despite being a vaccine-preventable disease in both humans and dogs, rabies remains poorly studied and its circulation in dogs poorly understood. First, we reviewed from the literature all mathematical models and molecular epidemiology studies on dog rabies circulation to synthesize the contribution of both approaches to the understanding of rabies dynamics in dogs. Then, we described RABV spread in Cambodia, one of the most affected countries worldwide, using RABV genomes isolated from dogs and Bayesian continuous phylogeography methods. We used Cambodia as a model of endemic circulation of RABV and exemplified how phylogeography can help characterize circulation in such context. We found that introductions from foreign countries are not necessary to sustain transmission in Cambodia. However, these results are conditional on the sampling of the RABV genomes. To further understand how sampling affects Bayesian phylogeography methods, we performed a simulation study where we evaluated the performances of three Bayesian discrete phylogeography algorithms under increasing levels of bias, and tested whether alternative sampling strategies, and integration of incidence data improve the performances of the algorithms under biased sampling conditions. The second part of this thesis concentrates on SARS-CoV-2 transmission at one of the smallest population scale, households. This setting is particularly suitable to detailed follow-up of household members after introduction of a case, and thus, enables to evaluate how susceptibility and infectivity vary between individuals. First, we estimated BNT162b2 vaccine effectiveness against infection and against transmission if infected during the Alpha wave in Israel using a mathematical model of SARS-CoV-2 transmission in partially vaccinated households. We further explored how model misspecification in a context of differing contact patterns between adults and children would impact estimates of relative infectivity and susceptibility of children compared to adults. Overall, this thesis explores how molecular epidemiology and modelling contribute to the understanding of infectious diseases transmission at the population level and highlights the need for data integration.Parmi les méthodes pour l'étude quantitative de la transmission des maladies infectieuses dans les populations, les épidémiologistes ont récemment focalisé leur attention sur l'épidémiologie moléculaire qui vise à reconstruire la phylogénie des pathogènes en utilisant leurs séquences génétiques, et la modélisation mathématique des maladies infectieuses qui ajuste des modèles mécanistes de transmission des maladies à des données épidémiologiques telles que le nombre de cas. Ces deux approches se basent sur des données très différentes dont la disponibilité varie selon le contexte. Les concepts et les modèles qu'elles utilisent permettent d'explorer des facettes différentes de la transmission des maladies. L'objectif principal de cette thèse est de mieux comprendre comment les maladies virales comme la rage et la covid-19 circulent dans les populations hôtes en utilisant pour la première des séquences génétiques virales datées et géolocalisées, et pour la deuxième, des données épidémiologiques à l'échelle individuelle. La première partie de cette thèse s'intéresse à la rage, une zoonose tropicale négligée, responsable d'environ 59,000 morts chaque année principalement dans les populations pauvres et rurales d'Afrique et d'Asie. Son agent étiologique, le virus de la rage (RABV), circule principalement dans les populations canines domestiques dont les modes de transmission restent peu étudiés et mal compris malgré l'existence de vaccins efficaces chez l'homme et l'animal. Nous avons tout d'abord synthétisé dans une revue de la littérature l'apport relatif des modèles mathématiques et de l'épidémiologie moléculaire dans la compréhension des dynamiques de la rage chez le chien. Puis, nous avons décrit la circulation endémique de la rage au Cambodge, un des pays les plus affectés, à partir de génomes de la rage isolés chez le chien et analysés avec des méthodes de phylogéographie Bayésienne continue. Nous avons montré que les introductions depuis d'autres pays ne sont pas nécessaires au maintien de la circulation. Toutefois, ces résultats sont conditionnés par l'échantillonnage des génomes. Pour mieux comprendre leurs impacts sur les méthodes de phylogéographie Bayésienne, nous avons entrepris une étude de simulation dans laquelle nous avons comparé les performances de trois algorithmes de phylogéographie discrète face à un échantillonnage plus ou moins biaisé. Nous avons testé des stratégies d'échantillonnage alternatives et intégré des données épidémiologiques afin d'atténuer l'effet potentiel des biais d'échantillonnage sur la performance des trois algorithmes. La deuxième partie de la thèse se concentre sur la transmission du SARS-CoV-2 dans une des plus petites populations, les ménages. Cette configuration est particulièrement adaptée au suivi détaillé de l'ensemble des membres du foyer après l'introduction d'un cas et permet ainsi d'évaluer comment la susceptibilité et l'infectivité varient au niveau individuel. Dans un premier temps, nous avons estimé l'effectivité vaccinale contre l'infection et la transmission si infecté pendant la vague de variant Alpha en Israël grâce à un modèle de transmission dans des ménages partiellement vaccinés. Nous avons ensuite exploré comment l'hétérogénéité de contact dans les ménages, notamment entre les adultes et les enfants, impacte les estimations de l'infectivité et de la susceptibilité relatives des enfants par rapport aux adultes. En conclusion, cette thèse explore les contributions de l'épidémiologie moléculaire et de la modélisation pour la compréhension de la transmission des maladies infectieuses à différentes échelles de population et souligne la nécessité d'intégrer les données génétiques et épidémiologiques
Responding to disproportionate discipline
No full textLayan Ammouri.Title from PDF cover (viewed on February 20, 2020).This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Includes bibliographical references (pages 47-58).Mode of access: Internet from the Oregon Government Publications Collection.Text in English
Mathematical modelling and phylodynamics for the study of dog rabies dynamics and control: A scoping review
No full textInternational audienceBackground: Rabies is a fatal yet vaccine-preventable disease. In the last two decades, domestic dog populations have been shown to constitute the predominant reservoir of rabies in developing countries, causing 99% of human rabies cases. Despite substantial control efforts, dog rabies is still widely endemic and is spreading across previously rabies-free areas. Developing a detailed understanding of dog rabies dynamics and the impact of vaccination is essential to optimize existing control strategies and developing new ones. In this scoping review, we aimed at disentangling the respective contributions of mathematical models and phylodynamic approaches to advancing the understanding of rabies dynamics and control in domestic dog populations. We also addressed the methodological limitations of both approaches and the remaining issues related to studying rabies spread and how this could be applied to rabies control.Methodology/principal findings: We reviewed how mathematical modelling of disease dynamics and phylodynamics have been developed and used to characterize dog rabies dynamics and control. Through a detailed search of the PubMed, Web of Science, and Scopus databases, we identified a total of n = 59 relevant studies using mathematical models (n = 30), phylodynamic inference (n = 22) and interdisciplinary approaches (n = 7). We found that despite often relying on scarce rabies epidemiological data, mathematical models investigated multiple aspects of rabies dynamics and control. These models confirmed the overwhelming efficacy of massive dog vaccination campaigns in all settings and unraveled the role of dog population structure and frequent introductions in dog rabies maintenance. Phylodynamic approaches successfully disentangled the evolutionary and environmental determinants of rabies dispersal and consistently reported support for the role of reintroduction events and human-mediated transportation over long distances in the maintenance of rabies in endemic areas. Potential biases in data collection still need to be properly accounted for in most of these analyses. Finally, interdisciplinary studies were determined to provide the most comprehensive assessments through hypothesis generation and testing. They also represent new avenues, especially concerning the reconstruction of local transmission chains or clusters through data integration.Conclusions/significance: Despite advances in rabies knowledge, substantial uncertainty remains regarding the mechanisms of local spread, the role of wildlife in dog rabies maintenance, and the impact of community behavior on the efficacy of control strategies including vaccination of dogs. Future integrative approaches that use phylodynamic analyses and mechanistic models within a single framework could take full advantage of not only viral sequences but also additional epidemiological information as well as dog ecology data to refine our understanding of rabies spread and control. This would represent a significant improvement on past studies and a promising opportunity for canine rabies research in the frame of the One Health concept that aims to achieve better public health outcomes through cross-sector collaboration
Kajian Distribusi dan Daya Layan Minimarket di Kecamatan Jekulo Kabupaten Kudus
No full textCommunity needs for information about the minimarket in District Jekulo Kudus Regency indispensable. Through this thesis the author will provide information such as map and Power Distribution Study of Self Minimarket in District Jekulo Kudus, including information contained typology minimarket. This mapping all the information will be more easily understood. The problem in this research is the spread of the location minimarket in District Jekulo Kudus Regency uneven. This study aims to map the location of minimarket and a minimarket include maid power to the community and display information system typology minimarket.
This research area is the District Jekulo Holy District. Variables used consists of a GPS plotingan the data directly in the field, spatial data and attribute data. Spatial data is data that beracuan on location. Attribute data is data obtained from secondary data to support in providing direction laying of new minimarkets.
Processing of the data in this study begins by plotting GPS data into ArcGIS 9.3 and then perform Power Distribution and Self Assessment Minimarket with buffering, after the display forms of information systems at the map and determine recommendations minimarket development time when that will come by considering population density, mean average people or households, road conditions, and the villages of the district transportation route Jekulo Holy District.
From writing thesis can be concluded that the distribution of minimarket in District Jekulo not evenly distributed, there should be additional minimarket in villages unserved and the importance of the type of information system services and merchandise to monitor the development of the minimarket.
Keywords: Mapping, Distribution, Power Layan, Minimarket
Low-Cost Smith-Waterman Acceleration
No full textDue to advancing technology, genetic sequencing has become cheaper over the years. This has caused the demand for computational power to grow even faster than Moore's law. To remedy this problem, we analyzed low-cost hardware solutions to parallelize the computational part of the genetic sequencing. We proposed a novel method for calculating the score matrix of the Smith-Waterman algorithm, which solves the bandwidth bottleneck in earlier solutions. This method calculates the score matrix differentially and a buffer keeps track of the maximum value. Due to the nature of the Smith-Waterman algorithm, the resulting implementation can do the calculations fully in parallel. Since it fits on an Artix 7 XC7A200T chip 908 times, this leads to more than a twelve-fold improvement in performance/price compared to modern supercomputing platforms.Computer EngineeringMicroelectronics & Computer EngineeringElectrical Engineering, Mathematics and Computer Scienc
The Possibility of Addressing Mandatory Rules and Its Adjustments in the Framework of International Commercial Arbitration
No full textMandatory rules are rules that apply to disregard the law chosen by the parties in their agreement. In this article, we will examine and address the role of international commercial arbitration and arbitrators when facing issues related to mandatory rules. It should be stated that mandatory rules pose conflicts for arbitrators because they place the state’s and the parties’ interests in competition. This highlights the main issue of whether the arbitrator should apply the related law when the parties’ agreement does not include this law. In other words, what should the arbitrator do in this case? The answer to this issue varies due to the variety of ways in which the “nature of arbitration” might be legally interpreted. However, a practical solution is needed. In order to reach a practical solution, the author will assess, from a normative approach, the relative benefits of various methodological techniques and their adjustments that are now in use. Then finally, conclusions will be reached regarding the approach and methodological techniques that best balance the parties\u27 interests
Addressing current limitations of household transmission studies by collecting contact data
No full textInternational audienceModeling studies of household transmission data have helped characterize the role of children in influenza and COVID-19 epidemics. However, estimates from these studies may be biased since they do not account for the heterogeneous nature of household contacts. Here, we quantified the impact of contact heterogeneity between household members on the estimation of child relative susceptibility and infectivity. We simulated epidemics of SARS-CoV-2-like and influenza-like infections in a synthetic population of 1,000 households assuming heterogeneous contact levels. Relative contact frequencies were derived from a household contact study according to which contacts are more frequent in the father-mother pair, followed by the child-mother, child-child, and finally child-father pairs. Child susceptibility and infectivity were then estimated while accounting for heterogeneous contacts or not. When ignoring contact heterogeneity, child relative susceptibility was underestimated by approximately 20% in the two disease scenarios. Child relative infectivity was underestimated by 20% when children and adults had different infectivity levels. These results are sensitive to our assumptions of European-style household contact patterns; but they highlight that household studies collecting both disease and contact data are needed to assess the role of complex household contact behavior on disease transmission and improve estimation of key biological parameters
Impact of BNT162b2 Vaccination and Isolation on SARS-CoV-2 Transmission in Israeli Households: An Observational Study
No full textInternational audienceAbstract Several studies have characterized the effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. However, estimates of their impact on transmissibility remain limited. Here, we evaluated the impact of isolation and vaccination (7 days after the second dose) on SARS-CoV-2 transmission within Israeli households. From December 2020 to April 2021, confirmed cases were identified among health-care workers of the Sheba Medical Centre and their family members. Recruited households were followed up with repeated PCR for at least 10 days after case confirmation. Data were analyzed using a data augmentation Bayesian framework. A total of 210 households with 215 index cases were enrolled; 269 out of 667 (40%) susceptible household contacts developed a SARS-CoV-2 infection. Of those, 170 (63%) developed symptoms. Compared with unvaccinated and unisolated adult/teenager (aged >12 years) contacts, vaccination reduced the risk of infection among unisolated adult/teenager contacts (relative risk (RR) = 0.21, 95% credible interval (CrI): 0.08, 0.44), and isolation reduced the risk of infection among unvaccinated adult/teenager (RR = 0.12, 95% CrI: 0.06, 0.21) and child contacts (RR = 0.17, 95% CrI: 0.08, 0.32). Infectivity was reduced in vaccinated cases (RR = 0.25, 95% CrI: 0.06, 0.77). Within households, vaccination reduces both the risk of infection and of transmission if infected. When contacts were unvaccinated, isolation also led to important reductions in the risk of transmission
Addressing current limitations of household transmission studies by collecting contact data
No full textModeling studies of household transmission data have helped characterize the role of children in influenza and coronavirus disease 2019 (COVID-19) epidemics. However, estimates from these studies may be biased since they do not account for the heterogeneous nature of household contacts. Here, we quantified the impact of contact heterogeneity between household members on the estimation of child relative susceptibility and infectivity. We simulated epidemics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like and influenza virus-like infections in a synthetic population of 1000 households, assuming heterogeneous contact levels. Relative contact frequencies were derived from a household contact study according to which contacts are more frequent in the father-mother pair, followed by the child-mother, child-child, and finally child-father pairs. Child susceptibility and infectivity were then estimated while accounting for heterogeneous contacts or not. When ignoring contact heterogeneity, child relative susceptibility was underestimated by approximately 20% in the two disease scenarios. Child relative infectivity was underestimated by 20% when children and adults had different infectivity levels. These results are sensitive to our assumptions of European-style household contact patterns; but they highlight that household studies collecting both disease and contact data are needed to assess the role of complex household contact behavior on disease transmission and improve estimation of key biological parameters
Impact and mitigation of sampling bias to determine viral spread: Evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations
No full textBayesian phylogeographic inference is a powerful tool in molecular epidemiological studies, which enables reconstruction of the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (Bayesian structured coalescent approximation [BASTA] and marginal approximation of the structured coalescent [MASCOT]). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on the simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for the CTMC model. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for the CTMC model, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing the sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.sponsorship: European Union Horizon 2020 project MOOD|874850, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program|ANR-10-LABX-62-IBEID, INCEPTION project|PIA/ANR-16-CONV-0005, FWO, Belgium|G0E1420N, F.R.S.-FNRS, Belgium|F.4515.22, FWO, Belgium|G098321N, International Funds KU Leuven|C14/18/094status: Publishe
