Inconnu en dehors des jungles asiatiques il y a encore quarante ans, le moustique tigre Aedes albopictus, vecteur de nombreux agents pathogènes humains, s’est désormais établi sur les cinq continents, y compris en ville. En France, il fait l’objet d’un plan national de surveillance de la dengue et du chikungunya et plusieurs cas de transmission autochtones ont été reportés récemment, soulignant ainsi la réalité du risque de transmission dans les zones où ce moustique est implanté. Probablement introduit en région Rhône-Alpes via le transport routier, Ae. albopictus est considéré comme présent et actif dans cinq des huit départements depuis 2013. Il est aujourd’hui question d’identifier les zones favorables à son implantation et comment la colonisation vers ces zones pourrait se faire. Ainsi, l’objectif de notre travail est de construire des cartes de susceptibilité de présence d’Ae. albopictus en Rhône-Alpes par modélisation combinant à la fois les connaissances sur les déterminants climatiques mais aussi environnementaux de son installation.
Biostatistiques et épidémiologieSanté publiqueLicence : https://creativecommons.org/licenses/by/4.0/
Connaître les bases de la modélisation moléculaire : modélisation par homologie, arrimage (docking) de ligands, mutations in silico. Une demi-journée dédiée à la modélisation de vos protéines d'intérêts.
Microbiologie (bactériologie, virologie)Parasitologie et mycologieLicence : https://creativecommons.org/licenses/by-sa/4.0/
Ce travail de thèse a pour objectif d'optimiser la performance sportive au sein d'une discipline complexe qu'est le short-track (patinage de vitesse sur courte piste). Cette recherche de performance est un processus filandreux, car chaque étape qui la compose, nécessite d'être analysée afin d'en extraire les facteurs nécessaires à l'amélioration des résultats. Bien que s'entraîner dur soit nécessaire, les avancées scientifiques des dernières décennies ont démontré qu'il fallait s'entraîner intelligemment. De fait, l'individualisation de l'entraînement trouve alors tout son sens, car chaque individu nécessite une approche qui lui est propre pour atteindre son niveau d'excellence. Le rôle de l'entraîneur est d'identifier les facteurs clés de la performance au sein de sa discipline, et de comprendre l'humain qui existe derrière le sportif afin de le faire progresser. Il lui faut donc mettre en place des méthodes de quantification des charges (internes et externes) éprouvées par les sportifs, afin de pouvoir suivre et comprendre les évolutions (positives et négatives) qu'il en résulte. L'utilisation de ces méthodes permet d'aider l'entraîneur à anticiper les performances à venir grâce à des systèmes de modélisation pouvant prédire des stratégies d'entraînements individualisées. Tout d'abord, dans le présent manuscrit, nous avons abordé la notion de modélisation de l'entraînement en proposant une revue des différents déterminants de la performance, couvrant entre autres des aspects physiques, techniques, tactiques et psychologiques. A partir de ces déterminants, nous nous sommes intéressés aux moyens permettant de les quantifier, avant d'exposer les différentes méthodes de modélisations touchant le domaine sportif. Ensuite, nous nous sommes penchés sur un élément longtemps négligé dans la préparation des sportifs, à savoir la récupération. En effet, l'entraînement épuise l'organisme et lui impose de s'adapter pour évoluer et être en mesure d'absorber les charges à venir,
Les mécanismes associés aux effets indésirables sous immunothérapie et l’identification de profils à risque chez les patients font à ce jour l’objet de nombreuses études. Cependant, les données de toxicités associées à un traitement sont souvent d’une grande complexité et posent de nombreux défis aussi bien en termes de recueil que d’un point de vue méthodologique. L’objectif de cette thèse est d’explorer des approches statistiques permettant de comparer des profils de toxicité associés à un traitement. Du fait de la multi-dimensionnalité de ces données (e.g. temporalité, récurrence, sévérité), évaluer la toxicité d’un traitement peut se faire à travers de nombreux indicateurs donnant soit une mesure absolue du risque de toxicité étudié (e.g. probabilités, taux), soit une mesure relative (e.g. odds ratios, hazard ratios). Une première revue des indicateurs liés aux modèles de régression proposés dans la littérature a mis en lumière des aspects méthodologiques fréquemment négligés dans l’évaluation du risque, en particulier en ce qui concerne la représentation du risque absolu au cours du temps. En réponse à cette observation, deux modèles ont ensuite été explorés au cours de ces travaux. Le premier modèle est un modèle flexible pénalisé du taux de survenue d’un unique évènement de toxicité (e.g. première apparition, grade maximum). L'intérêt de ce modèle réside dans sa capacité à décrire de manière flexible la dynamique du taux au cours du temps en utilisant des splines, tout en intégrant les effets non linéaires et non proportionnels des covariables. L’utilisation de splines s’accompagne toutefois de problématiques de sur-ajustement potentiel. Introduire une pénalisation de la vraisemblance, avec un objectif de lissage, permet de réduire ce phénomène. Le modèle de taux pénalisé a été exploré par simulation en tenant compte des spécificités du contexte des données de toxicité : échantillons de taille modeste, risques compétitifs, non-proportionnalité, dynamique diff
Biostatistiques et épidémiologieImmunologieSanté publiqueLicence : https://creativecommons.org/licenses/by/4.0/
La chromatine, assemblage d’ADN et de protéines, constitue le substrat de l’information génétique dans les cellules eucaryotes. Son organisation tridimensionnelle joue un rôle fondamental dans la régulation génique. Cependant, les mécanismes et les propriétés physiques multi-échelles qui sous-tendent cette organisation, au-delà de la formation des nucléosomes, restent encore mal compris. Dans cette thèse, nous abordons cette problématique à l’aide de concepts issus de la physique des polymères et de la physique statistique. Nos objectifs sont doubles : extraire les propriétés polymériques multi-échelles de la chromatine à partir de données expérimentales récentes (microscopie à super-résolution, m-FISH) et comprendre le couplage entre la dynamique du polymère et le paysage épigénétique. À cette fin, nous avons étudié un modèle de polymère magnétique, permettant d’attribuer à chaque segment un état d’expression ou de répression épigénétique, tout en analysant les transitions de phase et les interactions. Nos travaux, fondés sur l’analyse des fonctions de densité de probabilité des distances entre segments de la chromatine, révèlent la coexistence de deux phases polymériques distinctes : une phase dense et fractale, remplissant l’espace, et une phase plus diluée et confinée, générée par l’extrusion de boucles par des protéines telles que la cohésine ou la formation de gouttelettes via séparation de phase. En nous appuyant sur ces données expérimentales, nous avons démontré l’influence de cette dernière phase sur la fréquence des interactions entre segments, et proposé une méthode pour prédire l’emplacement de ces boucles à l’échelle de la cellule individuelle. Ces résultats ont été modélisés par une marche aléatoire hétérogène, caractérisée par une non-Markovianité due à la phase confinée. En appliquant l’hypothèse de coexistence de ces deux régimes à des données à haute résolution issues du cerveau adulte de la drosophile, nous avons étudié les interactions entre élé
Biologie cellulaire et moléculaireGénétiqueLicence : https://creativecommons.org/licenses/by/4.0/
Ce manuscrit de thèse vise à étudier la transmission de la fièvre typhoïde à Mayotte en utilisant des approches de modélisation mathématique. Nous introduisons tout d'abord le contexte de notre étude, les problématiques associées et les objectifs de la thèse. Un état de l'art sur la modélisation mathématique de la transmission de la fièvre typhoïde est présenté, mettant en évidence la spécificité de notre approche. Nous proposons un modèle initial en deux versions, déterministe et stochastique, pour décrire la dynamique de transmission de la maladie à Mayotte. Nous explorons le comportement du modèle à travers des simulations numériques dans différents scénarios, en mettant en évidence les facteurs clés de la transmission. Cependant, en raison des limitations du jeu de données disponibles, nous proposons un modèle stochastique simplifié et une méthode d'estimation paramétrique. Cette approche nous permet d'ajuster le modèle aux données disponibles et d'estimer les caractéristiques clés de la transmission de la fièvre typhoïde à Mayotte. En enrichissant notre modèle, nous introduisons de nouvelles extensions. Nous incluons un compartiment pour les individus exposés, prenant en compte la durée d'incubation de la maladie. Les propriétés théoriques de ce modèle sont étudiées et illustrées par des simulations numériques. De plus, nous proposons une méthodologie d'estimation des paramètres adaptée à ce nouveau modèle, et des simulations numériques ont été réalisées pour évaluer la performance de notre approche d'estimation. Nous examinons ensuite l'impact de la pluviométrie sur la transmission de la fièvre typhoïde à Mayotte, en utilisant des données publiques de précipitations. Nous identifions une saisonnalité de la pluie et estimons les paramètres du modèle sous différents régimes. Les résultats soulignent l'importance de cette variable météorologique dans la propagation de l'épidémie. Ce manuscrit ouvre des perspectives de recherche, telles que l'extension du modèle à
Biostatistiques et épidémiologieSémiologieMaladies infectieuses et tropicalesLicence : https://creativecommons.org/licenses/by/4.0/
BackgroundDensity dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin.Methodology/Principal findingsDensity dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d’Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model.Conclusions/SignificanceThis is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improving model pred
Biostatistiques et épidémiologieParasitologie et mycologieImmunologieLicence : Creative Commons Attribution License This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The proportion of poorly controlled hypertensives still remains high in the general African population. This is largely due to therapeutic inertia (TI), defined as the failure to intensify or modify treatment in a patient with poorly controlled blood pressure (BP). The objective of this study was to identify the determinants of TI. We conducted a retrospective cohort study from March 2012 to February 2014 of hypertensive patients followed during 4 medical visits. The TI score was the number of visits with TI divided by the number of visits where a therapeutic change was indicated. A random-effects logistic model was used to identify the determinants of TI. A total of 200 subjects were included, with a mean age of 57.98 years and 67% men. The TI score was measured at 85.57% (confidence interval [CI] 95% = [82.41–88.92]). Measured individual heterogeneity was significantly significant (0.78). Three factors were associated with treatment inertia, namely the number of antihypertensive drugs (odd ratios [OR] = 1.27; CI = [1.02–1.58]), the time between consultations (OR = 0.94; CI = [0.91–0.97]), and treatment noncompliance (OR = 15.18; CI = [3.13–73.70]). The random-effects model performed better in predicting high-risk patients with TI than the classical logistic model (P value < .001). Our study showed a high TI score in patients followed in cardiology in Burkina Faso. Reduction of the TI score through targeted interventions is necessary to better control hypertension in our cohort patients.
Biostatistiques et épidémiologiePharmacologieMédecine interne (cardiologie, endocrinologie, néphrologie…)Licence : Creative Commons Attribution License 4.0 (CCBY) This is an open access article distributed under the, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The introduction of MenAfriVac has significantly reduced group A meningococcal meningitis in the African meningitis belt, but epidemics caused by other groups such as C, W, Y and X (MenCWYX) remain a threat. To address this, a new multivalent meningococcal conjugate vaccine (MMCV) has been developed and pre-qualified by WHO. This study extends a previously established transmission dynamic model for MenA to include MenCWYX, enabling evaluation of the potential impact of MMCVs under various vaccination strategies. Using Burkina Faso as a case study, the model simulates mass campaigns targeting different age groups and routine vaccination through the Essential Programme on Immunization (EPI). The results indicate that campaigns targeting 1–29-year-olds are most effective in averting cases and delaying disease resurgence, while 1–19-year-old campaigns offer a resource-efficient alternative. Vaccine efficacy against carriage and the duration of protection significantly influence outcomes; greater efficacy (90% vs. 60%) and longer protection delay resurgence and reduce the number of cases. Routine- only vaccination demonstrates value in lower-risk settings, though it is less effective than combined strategies. Sensitivity analyses confirm the robustness of the ranking of strategies but highlight the importance of accurate estimates of vaccine efficacy and transmission parameters. The findings suggest that countries in the meningitis belt should integrate MMCVs into their immunisation programs, with high-risk countries prioritising catch-up campaigns for children and young adults. Despite data limitations and uncertainties, this model provides valuable insights for optimising vaccine rollout and highlights critical research needs, such as understanding vaccine effectiveness against carriage. These results support informed decision-making to sustain progress against meningitis and protect populations from future epidemics. MMCVs hold great promise in further reducing mening
Microbiologie (bactériologie, virologie)ImmunologieMaladies infectieuses et tropicalesLicence : Creative Commons Attribution License This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Joanna Murray, Roy Head, Sophie Sarrassat, Jennifer Hollowell, Pieter Remes, Matthew Lavoie, Josephine Borghi, Frida Kasteng, Nicolas Meda, Hermann Badolo, Moctar Ouedraogo, Robert Bambara, Simon Cousens
BackgroundA cluster randomised trial (CRT) in Burkina Faso was the first to demonstrate that a radio campaign increased health-seeking behaviours, specifically antenatal care attendance, health facility deliveries and primary care consultations for children under 5 years.MethodsUnder-five consultation data by diagnosis was obtained from primary health facilities in trial clusters, from January 2011 to December 2014. Interrupted time-series analyses were conducted to assess the intervention effect by time period on under-five consultations for separate diagnosis categories that were targeted by the media campaign. The Lives Saved Tool was used to estimate the number of under-five lives saved and the per cent reduction in child mortality that might have resulted from increased health service utilisation. Scenarios were generated to estimate the effect of the intervention in the CRT study areas, as well as a national scale-up in Burkina Faso and future scale-up scenarios for national media campaigns in five African countries from 2018 to 2020.ResultsConsultations for malaria symptoms increased by 56% in the first year (95% CI 30% to 88%; p<0.001) of the campaign, 37% in the second year (95% CI 12% to 69%; p=0.003) and 35% in the third year (95% CI 9% to 67%; p=0.006) relative to the increase in the control arm. Consultations for lower respiratory infections increased by 39% in the first year of the campaign (95% CI 22% to 58%; p<0.001), 25% in the second (95% CI 5% to 49%; p=0.010) and 11% in the third year (95% CI −20% to 54%; p=0.525). Diarrhoea consultations increased by 73% in the first year (95% CI 42% to 110%; p<0.001), 60% in the second (95% CI 12% to 129%; p=0.010) and 107% in the third year (95% CI 43% to 200%; p<0.001). Consultations for other diagnoses that were not targeted by the radio campaign did not differ between intervention and control arms. The estimated reduction in under-five mortality attributable to the radio intervention was 9.7% in the first y
Parasitologie et mycologieMaladies infectieuses et tropicalesPédiatrieLicence : https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original w
Isaac J. Stopard, Antoine Sanou, Eunho Suh, Lauren J. Cator, Matthew B. Thomas, W. Moussa Guelbéogo, N’Falé Sagnon, Ben Lambert, Thomas S. Churcher
Mosquito infection experiments that characterise how sporogony changes with temperature are increasingly being used to parameterise malaria transmission models. In these experiments, mosquitoes are exposed to a range of temperatures, with each group experiencing a single temperature. Diurnal temperature variation can, however, affect the sporogonic cycle of Plasmodium parasites. Mosquito dissection data is not available for all temperature profiles, so we investigate whether mathematical models of mosquito infection parameterised with constant temperature thermal performance curves can predict the effects of diurnal temperature variation. We use this model to predict two key parameters governing disease transmission: the human-to-mosquito transmission probability and extrinsic incubation period – and, embed this model into a malaria transmission model to simulate sporozoite prevalence with and without the effects of diurnal and seasonal temperature variation for a single site in Burkina Faso. Simulations incorporating diurnal temperature variation better predict changes in sporogony in laboratory mosquitoes, indicating that constant temperature experiments can be used to predict the effects of fluctuating temperatures. Including the effects of diurnal temperature variation, however, did not substantially improve the predictive ability of the transmission model to predict changes in sporozoite prevalence in wild mosquitoes, indicating further research is needed in more settings. Mechanistic modelling of the effects of diurnal temperature variation on Plasmodium falciparum sporogony indicates this variation is important in the laboratory, but further validation is required to assess its effect in wild mosquitoes.
Biostatistiques et épidémiologieParasitologie et mycologieMaladies infectieuses et tropicalesLicence : Open Access http://creativecommons.org/licenses/by/4.0/ This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original autho
BackgroundMalaria is a leading cause of mortality worldwide. There is currently conflicting data and interpretation on how variability in climate factors affects the incidence of malaria. This study presents a hierarchical Bayesian modelling framework for the analysis of malaria versus climate factors in West Africa.MethodsThe hierarchical Bayesian framework takes into account spatiotemporal dependencies, and in this paper is applied to annual malaria and climate data from ten West African countries (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Liberia, Mali, Senegal, Sierra Leone, and Togo) during the period 1996-2006.ResultsResults show a statistically significant correspondence between malaria rates and the climate variables considered. The two most important climate factors are found to be average annual temperature and total annual precipitation, and they show negative association with malaria incidence.ConclusionsThis modelling framework provides a useful approach for studying the impact of climate variability on the spread of malaria and may help to resolve some conflicting interpretations in the literature.
Parasitologie et mycologieMaladies infectieuses et tropicalesLicence : http://creativecommons.org/licenses/by/2.0 http://creativecommons.org/publicdomain/zero/1.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (), which permits unrestricted use, distribution, and reproduction in any medium, provided the original
Isobel Routledge, Martin Walker, Robert A. Cheke, Samir Bhatt, Pierre Baleguel Nkot, Graham A. Matthews, Didier Baleguel, Hans M. Dobson, Terry L. Wiles, Maria-Gloria Basañez
BackgroundIn 2012, the World Health Organization set goals for the elimination of onchocerciasis transmission by 2020 in selected African countries. Epidemiological data and mathematical modelling have indicated that elimination may not be achieved with annual ivermectin distribution in all endemic foci. Complementary and alternative treatment strategies (ATS), including vector control, will be necessary. Implementation of vector control will require that the ecology and population dynamics of Simulium damnosum (sensu lato) be carefully considered.MethodsWe adapted our previous SIMuliid POPulation dynamics (SIMPOP) model to explore the impact of larvicidal insecticides on S. damnosum (s.l.) biting rates in different ecological contexts and to identify how frequently and for how long vector control should be continued to sustain substantive reductions in vector biting. SIMPOP was fitted to data from large-scale aerial larviciding trials in savannah sites (Ghana) and small-scale ground larviciding trials in forest areas (Cameroon). The model was validated against independent data from Burkina Faso/Côte d’Ivoire (savannah) and Bioko (forest). Scenario analysis explored the effects of ecological and programmatic factors such as pre-control daily biting rate (DBR) and larviciding scheme design on reductions and resurgences in biting rates.ResultsThe estimated efficacy of large-scale aerial larviciding in the savannah was greater than that of ground-based larviciding in the forest. Small changes in larvicidal efficacy can have large impacts on intervention success. At 93% larvicidal efficacy (a realistic value based on field trials), 10 consecutive weekly larvicidal treatments would reduce DBRs by 96% (e.g. from 400 to 16 bites/person/day). At 70% efficacy, and for 10 weekly applications, the DBR would decrease by 67% (e.g. from 400 to 132 bites/person/day). Larviciding is more likely to succeed in areas with lower water temperatures and where blackfly species have longer
Biostatistiques et épidémiologieParasitologie et mycologieSanté publiqueLicence : Open Access http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/publicdomain/zero/1.0/ This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (), which permits unrestricted use, distribution, and reproduction in any medium, provid
BackgroundPopulations of the Anopheles gambiae complex are found during the rainy season throughout West Africa, even in arid areas with long dry seasons during which mosquitoes appear to be absent. Several hypotheses have been proposed to explain this apparent paradox, including aestivation, dispersal between neighbouring settlements, and long distance migration using high-altitude wind currents.MethodsAn individual-based, spatially explicit model of mosquito populations was developed for a region of West Africa centred on, and including all of, Burkina Faso. Populations associated with human settlements were linked by dispersal and the model incorporated geospatial data on the distribution of settlements, water bodies and rainfall.ResultsLocal dispersal (at rates consistent with experimental data) was necessary to explain observed patterns of rainy season populations across all of the simulation area, but by itself failed to account for the presence of populations in the arid North (the Sahel). The presence of rare dry-season larval sites could explain these northern populations, but seems inconsistent with field surveys. Aestivation by female mosquitoes explained rainy-season populations in all but the very sparsest and driest areas of human habitation, while long-distance migration based on annual wind patterns could account for all observed populations.ConclusionsModelling studies such as this can help assess the potential validity of different hypotheses and suggest priority areas for experimental study. In particular, the results highlight a shortage of empirical research on mosquito dispersal between neighbouring settlements, which may be critically important to the continued presence of many mosquito populations in West Africa. Further research that establishes the extent to which mosquitoes aestivate, and migrate using high altitude winds, is also much needed to understand Sahelian mosquito populations.Electronic supplementary materialThe online version of
Biostatistiques et épidémiologieParasitologie et mycologieMaladies infectieuses et tropicalesLicence : Open Access http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/publicdomain/zero/1.0/ This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (), which permits unrestricted use, distribution, and reproduction in any medium, provid
BackgroundThe persistence of malaria in large parts of sub-Saharan Africa has motivated the development of novel tools to complement existing control programmes, including gene-drive technologies to modify mosquito vector populations. Here, we use a stochastic simulation model to explore the potential of using a driving-Y chromosome to suppress vector populations in a 106 km2 area of West Africa including all of Burkina Faso.ResultsThe consequence of driving-Y introductions is predicted to vary across the landscape, causing elimination of the target species in some regions and suppression in others. We explore how this variation is determined by environmental conditions, mosquito behaviour, and the properties of the gene-drive. Seasonality is particularly important, and we find population elimination is more likely in regions with mild dry seasons whereas suppression is more likely in regions with strong seasonality.ConclusionsDespite the spatial heterogeneity, we suggest that repeated introductions of modified mosquitoes over a few years into a small fraction of human settlements may be sufficient to substantially reduce the overall number of mosquitoes across the entire geographic area.Electronic supplementary materialThe online version of this article (10.1186/s12915-019-0645-5) contains supplementary material, which is available to authorized users.
Biologie cellulaire et moléculaireGénétiqueParasitologie et mycologieLicence : Open Access http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/publicdomain/zero/1.0/ This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (), which permits unrestricted use, distribution, and reproduction in any medium, provid
Nicolas Moiroux, Abdul S Bio-Bangana, Armel Djènontin, Fabrice Chandre, Vincent Corbel, Hélène Guis
BackgroundThe diversity of malaria vector populations, expressing various resistance and/or behavioural patterns could explain the reduced effectiveness of vector control interventions reported in some African countries. A better understanding of the ecology and distribution of malaria vectors is essential to design more effective and sustainable strategies for malaria control and elimination. Here, we analyzed the spatio-temporal risk of the contact between humans and the sympatric An. funestus and both M and S molecular forms of An. gambiae s.s. in an area of Benin with high coverage of vector control measures with an unprecedented level of resolution.MethodsPresence-absence data for the three vectors from 1-year human-landing collections in 19 villages were assessed using binomial mixed-effects models according to vector control measures and environmental covariates derived from field and remote sensing data. After 8-fold cross-validations of the models, predictive maps of the risk of the contact between humans and the sympatric An. funestus and both molecular M and S forms of An. gambiae s.s. were computed.ResultsModel validations showed that the An. funestus, An. gambiae M form, and S form models provided an excellent (Area Under Curve>0.9), a good (AUC>0.8), and an acceptable (AUC>0.7) level of prediction, respectively. The distribution area of the probability of contact between human and An. funestus largely overlaps that of An. gambiae M form but this latter showed important seasonal variation. An. gambiae S form also showed seasonal variation but with different ecological preferences. Landscape data were useful to discriminate between the species’ distributions.ConclusionsThese results showed that available remote sensing data could help in predicting the human-vector contact for several species of malaria vectors at a village level scale. The predictive maps showed seasonal and spatial variations in the risk of human-vector contact for all three vectors. S
Microbiologie (bactériologie, virologie)Parasitologie et mycologiePharmacologieLicence : http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BackgroundGene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. In particular, there is much interest in constructs that target the conserved mosquito doublesex (dsx) gene such that the emergence of functional drive-resistant alleles is unlikely. Proof of principle that these constructs can lead to substantial population suppression has been obtained in population cages, and they are being evaluated for use in sub-Saharan Africa. Here, we use simulation modelling to understand the factors affecting the spread of this type of gene drive over a one million-square kilometre area of West Africa containing substantial environmental and social heterogeneity.ResultsWe found that a driving endonuclease gene targeting female fertility could lead to substantial reductions in malaria vector populations on a regional scale. The exact level of suppression is influenced by additional fitness costs of the transgene such as the somatic expression of Cas9, and its deposition in sperm or eggs leading to damage to the zygote. In the absence of these costs, or of emergent drive-resistant alleles that restore female fertility, population suppression across the study area is predicted to stabilise at ~ 95% 4 years after releases commence. Small additional fitness costs do not greatly affect levels of suppression, though if the fertility of females whose offspring transmit the construct drops by more than ~ 40%, then population suppression is much less efficient. We show the suppression potential of a drive allele with high fitness costs can be enhanced by engineering it also to express male bias in the progeny of transgenic males. Irrespective of the strength of the drive allele, the spatial model predicts somewhat less suppression than equivalent non-spatial models, in p
Parasitologie et mycologieMaladies infectieuses et tropicalesLicence : Open Access http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/publicdomain/zero/1.0/ This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as
Pierre Muhoza, Alain K Koffi, Philip Anglewicz, Peter Gichangi, Georges Guiella, Funmilola OlaOlorun, Elizabeth Omoluabi, P R Sodani, Mary Thiongo, Pierre Akilimali, Amy Tsui, Scott Radloff
AbstractApproximately 214 million women of reproductive age lack adequate access to contraception for their family planning needs, yet patterns of contraceptive availability have seldom been examined. With growing demand for contraceptives in some areas, low contraceptive method availability and stockouts are thought to be major drivers of unmet need among women of reproductive age, though evidence for this is limited. In this research, we examined trends in stockouts, method availability and consumption of specific contraceptive methods in urban areas of four sub-Saharan African countries (Burkina Faso, Democratic Republic of Congo, Kenya and Nigeria) and India. We used representative survey data from the Performance Monitoring for Action Agile Project that were collected in quarterly intervals at service delivery points (SDP) stratified by sector (public vs private), with all countries having five to six quarters of surveys between 2017 and 2019. Among SDPs that offer family planning, we calculated the percentage offering at least one type of modern contraceptive method (MCM) for each country and quarter, and by sector. We examined trends in the percentage of SDPs with stockouts and which currently offer condoms, emergency contraception, oral pills, injectables, intrauterine devices and implants. We also examined trends of client visits for specific methods and the resulting estimated protection from pregnancy by quarter and country. Across all countries, the vast majority of SDPs had at least one type of MCM in-stock during the study period. We find that the frequency of stockouts varies by method and sector and is much more dynamic than previously thought. While the availability and distribution of long-acting reversible contraceptives (LARCs) were limited compared to other methods across countries, LARCs nonetheless consistently accounted for a larger portion of couple years of protection. We discuss findings that show the importance of engaging the private sec
Biostatistiques et épidémiologieGynécologie-obstétriqueSanté publiqueLicence : http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Abou Coulibaly, Adama Baguiya, Jeoffray Diendéré, Franck Garanet, Halima Tougri, Denise Kpebo, Seni Kouanda
BackgroundDespite all the benefits of family planning (FP), African countries still have low contraceptive use and very high fertility rates.AimTo measure modern contraceptive use among young lactating mothers in the context of the free contraceptive policy in the Kaya municipality setting.SettingThis study was conducted in the Kaya municipality, in the Koulsé region, Burkina Faso.MethodsThis study is a secondary data analysis of the Kaya Demographic and Health Surveillance System data collected in the households between May 2022 and October 2022 (cross-sectional study). The dependent variable was the use of a modern contraceptive method (binary). Modified Poisson regression was used to identify associated factors.ResultsThe prevalence of modern contraceptive use among young lactating mothers was 53.9% (n = 536/995), with 41.4% using implants, followed by male condoms (38.2%), injectables (14.6%) and pills (5.4%). Modern contraceptive use was significantly higher among women who discussed FP with their spouses (adjusted prevalence ratios [aPR] = 1.4, 95% confidence interval [CI]: 1.2–1.8, p = 0.001) and among women who had ever used modern contraceptives before the last pregnancy (aPR = 1.9, 95% CI: 1.6–2.4, p < 0.001). Similarly, women in the rich quintile (aPR = 1.5, 95% CI: 1.1–2.0, p = 0.013) and the richest quintile (aPR = 1.5, 95% CI: 1.1–2.1, p = 0.014) were more likely to use modern contraceptives compared to the poorest.ConclusionThe prevalence of modern contraceptive use among young lactating mothers in Kaya is relatively high, with some modifiable factors that still explain contraceptive use.ContributionThis study documented evidence on contraceptive use among young lactating mothers under Burkina Faso’s free FP policy, highlighting equity gaps and actionable levers (communication between couples, prior exposure and men’s involvement).
Biostatistiques et épidémiologieGynécologie-obstétriqueSanté publiqueLicence : Licensee: AOSIS. This work is licensed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
Objectifs : l'objectif principal est de décrire comment les sages-femmes ont adapté leur activité libérale au début de la crise sanitaire de la COVID-19. Les objectifs secondaires sont de décrire la place de la téléconsultation dans l'activité des sages-femmes libérales pendant la crise sanitaire et de savoir si après la fin de la crise sanitaire, poursuivre la téléconsultation serait un atout pour le suivi des femmes. Méthode : dans un premier temps, une enquête préliminaire quantitative par le biais d'un sondage téléphonique a été effectuée auprès de neuf sages-femmes libérales de la Somme. Puis afin de mieux comprendre comment la crise sanitaire a impacté l'activité des sages-femmes libérales, une étude qualitative principale au moyen de six entretiens semi-directifs a été réalisée. Résultats : la réorganisation du système de santé a entrainé l'annulation des soins non-urgents. Les sages-femmes ont annulé la rééducation du périnée, les séances de préparation à la naissance. Elles ont par ailleurs développé la téléconsultation et permis la continuité du suivi lors des sorties précoces. Elles ont donc réorganisé leur activité quotidienne et assuré la continuité des soins. Discussion : plusieurs facteurs ont influencé la réorganisation de l'activité des sages-femmes : le type d'activité avant la crise, le lieu d'exercice et le contexte familial et personnel. La téléconsultation a été massivement utilisée pendant le premier confinement et a connu rapidement un déclin. Comme dans la littérature, les avis sont partagés. Une majorité de sage-femme et leur patientèle n'ont pas demandé à poursuivre la téléconsultation, ce que certains auteurs évoquent. Conclusion : la crise sanitaire a induit le développement des sorties précoces et de la téléconsultation. La téléconsultation a pris une place importante pendant le premier confinement, les sorties précoces ont également permis de garder un contact physique mais surtout de développer des liens avec les maternités. La téléco
Biostatistiques et épidémiologieSémiologieMaladies infectieuses et tropicalesLicence : https://creativecommons.org/licenses/by/4.0/
L’activation de la voie NF-κB contrôle la transcription de nombreux gènes engagés dans des processus physiologiques majeurs tels que l’inflammation et la réponse immune. Néanmoins, son activation chronique est fréquemment associée dans des maladies tels que les cancers. L’organisation tridimensionnelle de la chromatine joue un rôle dans la coordination des régulations transcriptionnelles mise en place lors de l’activation de la voie NF-κB. Mes travaux montrent dans un contexte d’activation de la voie NF-κB par l’oncogène Tax du rétrovirus HTLV-1 que de nombreuses dérégulations d’épissage alternatif sont médiées par le recrutement intragénique du facteur NF-κB p65/RelA à proximité des exons régulés via ses capacité d’interaction avec des facteurs d’épissage, dont l’hélicase à ARN DDX17. Par des approches de Hi-C, 4C et 3C, mes données montrent que les régulations transcriptionnelles et co-transcriptionnelles engendrées par Tax, notamment via l’activation de la voie NF-κB, s’accompagnent d’une réorganisation de l’architecture tridimensionnelle du génome, induisant la formation de complexes multigéniques composés de gènes régulés par Tax dans leur niveau transcriptionnel ou leur épissage alternatif. Les analyses de l’enrichissement à la chromatine de p65/RelA, ainsi que des approches moléculaires permettant de moduler expérimentalement le recrutement de p65/RelA à la chromatine, ont permis d’identifier que la fixation intragénique de p65/RelA participe à la formation de contacts entre gènes et à leurs régulations au niveau de la transcription et de l’épissage alternatif. Ces données apportent de nouvelles connaissances dans les mécanismes de régulation lors de l’infection par HTLV-1 mais également dans les pathologies associées à l’activation de la voie NF-κB.
BiochimieBiologie cellulaire et moléculaireGénétiqueLicence : https://creativecommons.org/licenses/by/4.0/
Pius S. Fasinu, Vamshi K. Manda, Olivia R. Dale, Nosa O. Egiebor, Larry A. Walker, Shabana I. Khan
Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 to assess the effect of the methanolic extracts on the metabolic activity of CYPs. Secondly, the inhibitory effect of the extracts was evaluated on P-glycoproteins (P-gp) using calcein-AM, a fluorescent substrate, in MDCK-II and hMDR1-MDCK-II cells. The inhibition of P-gp activity was determined as a reflection of increase in calcein-AM uptake. Additionally, the enzyme induction potential of the extracts was assessed through the modulation of PXR activity in HepG2 cells transiently transfected with pSG5-PXR and PCR5 plasmid DNA. Significant inhibition of CYP activity (IC50 < 10 µg/mL) was observed with the following herbs: A. muricata [CYP2C9, 3A4 and CYP2D6]; M. indica [CYP2C9]; M. charantia [CYP2C9 and CYP2C19]; P. amarus [CYP2C19, CYP2C9 and CYP3A4]; T. diversifolia [CYP2C19 and CYP3A4]. Extracts of four herbs (P. amarus, M. charantia, T. diversifolia and A. muricata) exhibited significant inhibition of P-gp with IC50 values (µg/mL) of 17 ± 1, 16 ± 0.4, 26 ± 1, and 24 ± 1, respectively. In addition, four herbs (A. mexicana, M. charantia, P. amarus and T. diversifolia) showed a >two-fold increase in induction in PXR activity. These findings suggest that these herbs may be capable of eliciting herb-drug interactions if consumed in high quantities with concomitant use of conventional therapies.
Biologie cellulaire et moléculaireGénétiqueParasitologie et mycologieLicence : http://creativecommons.org/licenses/by/4.0/ Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ().