Apports et voies d'amélioration de la représentation des glaciers et de leur évolution au sein d'un modèle hydrologique

Mountainous environments are a privileged place of water and energy exchange. Mountainous rivers feed about 40% of the world population and are subjected to climate change and a growing demography. In this context, the comprehension of meteorological, hydrological and hydrogeological processes is essential for a better overall management of water resource. This PhD study is focused squarely on the mountainous environments where hydrology is influenced by snow cover and glaciers, and introduces a multidisciplinary modeling approach in order to improve our comprehension of the process involved.Today, hydrological models are able to simulate gauged mountainous river streamflows under the influence of snow and glaciers but some uncertainties remain when applying such models out of their calibration phase (for instance in response to a different climate or on a ungauged basin). The main uncertainty source is the lack of knowledge of mountainous precipitations, whose measure is sparse and uncertain. It remains the principal component of the hydrological budget though. In this study, we suggest using the meteorological information provided by snow cover and glaciers as “giant pluviometers” to their reservoir scales, with a conceptual reservoir model associated with the concept of watershed.The information provided by hydrology processes, snow and glaciers is assessed in a multi-objective calibration phase. Results show that, in this configuration, the joint validation of the hydrological model by daily streamflow, annual mass balance and daily local snow depth reduces significantly the uncertainty on the meteorological forcing and improves the model robustness. This preliminary result has motivated, consequently, the local annual mass balance of the glaciers.Also, the representation of glaciers in a hydrological model raises a certain amount of issues, especially in the perspective of simulation long-term hydrological processes. In particular, the consideration of the evolution of the glacier geometry is at an early stage. To this end, we propose, in this study, ways of improvements for the representation of glaciers from a geomorphological perspective. This approach allowed us to build a probabilistic model able to describe the glaciated surfaces within a watershed according to a given topographic contour line.Les environnements montagneux sont un lieu privilégié d'échange d'eau et d'énergie. Les rivières de montagne alimentent en eau 40% de la population mondiale et sont sujettes à une pression démographique et climatique important. Dans ce contexte, la compréhension des processus météorologiques, hydrologiques et hydrogéologiques est fondamentale pour la gestion globale de la ressource en eau. L'étude, présentée dans ce manuscrit de thèse, se positionne au sein des environnements montagneux où l'hydrologie est influencée par le couvert neigeux saisonnier et par les glaciers, et propose une approche de modélisation interdisciplinaire afin d'améliorer la compréhension des processus en jeu.Aujourd'hui, si les modèles sont capables de simuler le débit sur les rivières de montagnes jaugées sous influence nivale et glaciaire, un certain nombre d'incertitudes persistent quant à l'utilisation de tels modèles hors de leur conditions de validation (en réponse à un climat différent ou sur un domaine non-jaugé). La principale source d'incertitude est liée au manque de connaissance des précipitations en montagne, dont la mesure est rare et incertaine. C'est pourtant la principale composante du bilan hydrologique. A cet égard, nous proposons d'exploiter l'information fournie par la géométrie du couvert neigeux et des glaciers, en tant que “pluviomètres géants” à l'échelle de ces réservoirs, dans un modèle hydrologique à réservoirs conceptuels reposant sur la notion de bassin versant.L'information, hydrologique, nivale et glaciaire est évaluée dans un cadre de calibration multi-objectifs. Les résultats montrent que, dans cette configuration, la validation conjointe du modèle hydrologique par le débit journalier, le bilan de masse glaciaire annuel et la hauteur de neige locale journalier permet de réduire fortement l'incertitude sur le forçage météorologique journalier et d'améliorer la robustesse du modèle. Ce résultat préliminaire nous a permis de reconstruire, en conséquence, le bilan de masse local annuel à l'échelle des glaciers.Par ailleurs, la représentation des glaciers au sein d'un modèle hydrologique pose un certain nombre de défis, surtout dans la perspective de simuler les processus hydrologiques à l'échelle pluri-annuelle. En particulier, la prise en compte de l'évolution de la géométrie des glaciers au sein d'un modèle hydrologique est balbutiante. A cet égard, nous proposons, dans cette étude, des axes d'amélioration de la représentation des glaciers au sein d'un modèle hydrologique par un angle d'investigation géomorphologique. Cette approche a permis d'élaborer un modèle probabiliste permettant de décrire les surfaces englacées au sein d'un bassin versant selon une courbe de niveau

Quantifying the value of viral genomics when inferring who infected whom in the 2014–16 Ebola virus outbreak in Guinea

Transmission trees can be established through detailed contact histories, statistical or phylogenetic inference, or a combination of methods. Each approach has its limitations, and the extent to which they succeed in revealing a 'true' transmission history remains unclear. In this study, we compared the transmission trees obtained through contact tracing investigations and various inference methods to identify the contribution and value of each approach. We studied eighty-six sequenced cases reported in Guinea between March and November 2015. Contact tracing investigations classified these cases into eight independent transmission chains. We inferred the transmission history from the genetic sequences of the cases (phylogenetic approach), their onset date (epidemiological approach), and a combination of both (combined approach). The inferred transmission trees were then compared to those from the contact tracing investigations. Inference methods using individual data sources (i.e. the phylogenetic analysis and the epidemiological approach) were insufficiently informative to accurately reconstruct the transmission trees and the direction of transmission. The combined approach was able to identify a reduced pool of infectors for each case and highlight likely connections among chains classified as independent by the contact tracing investigations. Overall, the transmissions identified by the contact tracing investigations agreed with the evolutionary history of the viral genomes, even though some cases appeared to be misclassified. Therefore, collecting genetic sequences during outbreak is key to supplement the information contained in contact tracing investigations. Although none of the methods we used could identify one unique infector per case, the combined approach highlighted the added value of mixing epidemiological and genetic information to reconstruct who infected whom

Ring vaccination with rVSV-ZEBOV under expanded access in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report.

BACKGROUND: In March, 2016, a flare-up of Ebola virus disease was reported in Guinea, and in response ring vaccination with the unlicensed rVSV-ZEBOV vaccine was introduced under expanded access, the first time that an Ebola vaccine has been used in an outbreak setting outside a clinical trial. Here we describe the safety of rVSV-ZEBOV candidate vaccine and operational feasibility of ring vaccination as a reactive strategy in a resource-limited rural setting. METHODS: Approval for expanded access and compassionate use was rapidly sought and obtained from relevant authorities. Vaccination teams and frozen vaccine were flown to the outbreak settings. Rings of contacts and contacts of contacts were defined and eligible individuals, who had given informed consent, were vaccinated and followed up for 21 days under good clinical practice conditions. FINDINGS: Between March 17 and April 21, 2016, 1510 individuals were vaccinated in four rings in Guinea, including 303 individuals aged between 6 years and 17 years and 307 front-line workers. It took 10 days to vaccinate the first participant following the confirmation of the first case of Ebola virus disease. No secondary cases of Ebola virus disease occurred among the vaccinees. Adverse events following vaccination were reported in 47 (17%) 6-17 year olds (all mild) and 412 (36%) adults (individuals older than 18 years; 98% were mild). Children reported fewer arthralgia events than adults (one [<1%] of 303 children vs 81 [7%] of 1207 adults). No severe vaccine-related adverse events were reported. INTERPRETATION: The results show that a ring vaccination strategy can be rapidly and safely implemented at scale in response to Ebola virus disease outbreaks in rural settings. FUNDING: WHO, Gavi, and the World Food Programme

An online decision tree for vaccine efficacy trial design during infectious disease epidemics: The InterVax-Tool.

BACKGROUND: Licensed vaccines are urgently needed for emerging infectious diseases, but the nature of these epidemics causes challenges for the design of phase III trials to evaluate vaccine efficacy. Designing and executing rigorous, fast, and ethical, vaccine efficacy trials is difficult, and the decisions and limitations in the design of these trials encompass epidemiological, logistical, regulatory, statistical, and ethical dimensions. RESULTS: Trial design decisions are complex and interrelated, but current guidance documents do not lend themselves to efficient decision-making. We created InterVax-Tool (http://vaxeval.com), an online, interactive decision-support tool, to help diverse stakeholders navigate the decisions in the design of phase III vaccine trials. InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of the: (1) Primary Endpoint, (2) Target Population, (3) Randomization Scheme, and, (4) Comparator. We provide guidance on how key considerations - grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural - inform each decision in the trial design process. CONCLUSIONS: InterVax-Tool facilitates structured, transparent, and collaborative discussion of trial design, while recording the decision-making process. Users can save and share their decisions, which is useful both for comparing proposed trial designs, and for justifying particular design choices. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!).

BACKGROUND: rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa. METHODS: We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6-17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS: In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9-100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3-100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae. INTERPRETATION: The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters. FUNDING: WHO, UK Wellcome Trust, the UK Government through the Department of International Development, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development)

Electronic Data Management for Vaccine Trials in Low Resource Settings: Upgrades, Scalability, and Impact of ODK

Background: ODK provides software and standards that are popular solutions for off-grid electronic data collection and has substantial code overlap and interoperability with a number of related software products including CommCare, Enketo, Ona, SurveyCTO, and KoBoToolbox. These tools provide open-source options for off-grid use in public health data collection, management, analysis, and reporting. During the 2018–2020 Ebola epidemic in the North Kivu and Ituri regions of Democratic Republic of Congo, we used these tools to support the DRC Ministère de la Santé RDC and World Health Organization in their efforts to administer an experimental vaccine (VSV-Zebov-GP) as part of their strategy to control the transmission of infection. Method: New functions were developed to facilitate the use of ODK, Enketo and R in large scale data collection, aggregation, monitoring, and near-real-time analysis during clinical research in health emergencies. We present enhancements to ODK that include a built-in audit-trail, a framework and companion app for biometric registration of ISO/IEC 19794-2 fingerprint templates, enhanced performance features, better scalability for studies featuring millions of data form submissions, increased options for parallelization of research projects, and pipelines for automated management and analysis of data. We also developed novel encryption protocols for enhanced web-form security in Enketo. Results: Against the backdrop of a complex and challenging epidemic response, our enhanced platform of open tools was used to collect and manage data from more than 280,000 eligible study participants who received VSV-Zebov-GP under informed consent. These data were used to determine whether the VSV-Zebov-GP was safe and effective and to guide daily field operations. Conclusions: We present open-source developments that make electronic data management during clinical research and health emergencies more viable and robust. These developments will also enhance and expand the functionality of a diverse range of data collection platforms that are based on the ODK software and standards

Determinants of Transmission Risk During the Late Stage of the West African Ebola Epidemic.

Understanding risk factors for Ebola transmission is key for effective prediction and design of interventions. We used data on 860 cases in 129 chains of transmission from the latter half of the 2013-2016 Ebola epidemic in Guinea. Using negative binomial regression, we determined characteristics associated with the number of secondary cases resulting from each infected individual. We found that attending an Ebola treatment unit was associated with a 38% decrease in secondary cases (incidence rate ratio (IRR) = 0.62, 95% confidence interval (CI): 0.38, 0.99) among individuals that did not survive. Unsafe burial was associated with a higher number of secondary cases (IRR = 1.82, 95% CI: 1.10, 3.02). The average number of secondary cases was higher for the first generation of a transmission chain (mean = 1.77) compared with subsequent generations (mean = 0.70). Children were least likely to transmit (IRR = 0.35, 95% CI: 0.21, 0.57) compared with adults, whereas older adults were associated with higher numbers of secondary cases. Men were less likely to transmit than women (IRR = 0.71, 95% CI: 0.55, 0.93). This detailed surveillance data set provided an invaluable insight into transmission routes and risks. Our analysis highlights the key role that age, receiving treatment, and safe burial played in the spread of EVD

Contributions and ways of improvement of the representation of glaciers and their evolution in a hydrological model

Les environnements montagneux sont un lieu privilégié d'échange d'eau et d'énergie. Les rivières de montagne alimentent en eau 40% de la population mondiale et sont sujettes à une pression démographique et climatique important. Dans ce contexte, la compréhension des processus météorologiques, hydrologiques et hydrogéologiques est fondamentale pour la gestion globale de la ressource en eau. L'étude, présentée dans ce manuscrit de thèse, se positionne au sein des environnements montagneux où l'hydrologie est influencée par le couvert neigeux saisonnier et par les glaciers, et propose une approche de modélisation interdisciplinaire afin d'améliorer la compréhension des processus en jeu.Aujourd'hui, si les modèles sont capables de simuler le débit sur les rivières de montagnes jaugées sous influence nivale et glaciaire, un certain nombre d'incertitudes persistent quant à l'utilisation de tels modèles hors de leur conditions de validation (en réponse à un climat différent ou sur un domaine non-jaugé). La principale source d'incertitude est liée au manque de connaissance des précipitations en montagne, dont la mesure est rare et incertaine. C'est pourtant la principale composante du bilan hydrologique. A cet égard, nous proposons d'exploiter l'information fournie par la géométrie du couvert neigeux et des glaciers, en tant que “pluviomètres géants” à l'échelle de ces réservoirs, dans un modèle hydrologique à réservoirs conceptuels reposant sur la notion de bassin versant.L'information, hydrologique, nivale et glaciaire est évaluée dans un cadre de calibration multi-objectifs. Les résultats montrent que, dans cette configuration, la validation conjointe du modèle hydrologique par le débit journalier, le bilan de masse glaciaire annuel et la hauteur de neige locale journalier permet de réduire fortement l'incertitude sur le forçage météorologique journalier et d'améliorer la robustesse du modèle. Ce résultat préliminaire nous a permis de reconstruire, en conséquence, le bilan de masse local annuel à l'échelle des glaciers.Par ailleurs, la représentation des glaciers au sein d'un modèle hydrologique pose un certain nombre de défis, surtout dans la perspective de simuler les processus hydrologiques à l'échelle pluri-annuelle. En particulier, la prise en compte de l'évolution de la géométrie des glaciers au sein d'un modèle hydrologique est balbutiante. A cet égard, nous proposons, dans cette étude, des axes d'amélioration de la représentation des glaciers au sein d'un modèle hydrologique par un angle d'investigation géomorphologique. Cette approche a permis d'élaborer un modèle probabiliste permettant de décrire les surfaces englacées au sein d'un bassin versant selon une courbe de niveau.Mountainous environments are a privileged place of water and energy exchange. Mountainous rivers feed about 40% of the world population and are subjected to climate change and a growing demography. In this context, the comprehension of meteorological, hydrological and hydrogeological processes is essential for a better overall management of water resource. This PhD study is focused squarely on the mountainous environments where hydrology is influenced by snow cover and glaciers, and introduces a multidisciplinary modeling approach in order to improve our comprehension of the process involved.Today, hydrological models are able to simulate gauged mountainous river streamflows under the influence of snow and glaciers but some uncertainties remain when applying such models out of their calibration phase (for instance in response to a different climate or on a ungauged basin). The main uncertainty source is the lack of knowledge of mountainous precipitations, whose measure is sparse and uncertain. It remains the principal component of the hydrological budget though. In this study, we suggest using the meteorological information provided by snow cover and glaciers as “giant pluviometers” to their reservoir scales, with a conceptual reservoir model associated with the concept of watershed.The information provided by hydrology processes, snow and glaciers is assessed in a multi-objective calibration phase. Results show that, in this configuration, the joint validation of the hydrological model by daily streamflow, annual mass balance and daily local snow depth reduces significantly the uncertainty on the meteorological forcing and improves the model robustness. This preliminary result has motivated, consequently, the local annual mass balance of the glaciers.Also, the representation of glaciers in a hydrological model raises a certain amount of issues, especially in the perspective of simulation long-term hydrological processes. In particular, the consideration of the evolution of the glacier geometry is at an early stage. To this end, we propose, in this study, ways of improvements for the representation of glaciers from a geomorphological perspective. This approach allowed us to build a probabilistic model able to describe the glaciated surfaces within a watershed according to a given topographic contour line

Developing Global Norms for Sharing Data and Results during Public Health Emergencies.

Vasee Moorthy and colleagues describe the outcomes of a recent, WHO-led meeting on sharing research data and results during public health emergencies