Genomic sequencing of SARS-CoV-2 in Rwanda reveals the importance of incoming travelers on lineage diversity

COVID-19 transmission rates are often linked to locally circulating strains of SARS-CoV-2. Here we describe 203 SARS-CoV-2 whole genome sequences analyzed from strains circulating in Rwanda from May 2020 to February 2021. In particular, we report a shift in variant distribution towards the emerging sub-lineage A.23.1 that is currently dominating. Furthermore, we report the detection of the first Rwandan cases of the B.1.1.7 and B.1.351 variants of concern among incoming travelers tested at Kigali International Airport. To assess the importance of viral introductions from neighboring countries and local transmission, we exploit available individual travel history metadata to inform spatio-temporal phylogeographic inference, enabling us to take into account infections from unsampled locations. We uncover an important role of neighboring countries in seeding introductions into Rwanda, including those from which no genomic sequences were available. Our results highlight the importance of systematic genomic surveillance and regional collaborations for a durable response towards combating COVID-19.info:eu-repo/semantics/publishe

Ethique de la recherche biomédicale dans les pays émergents : mise en place de comités d'éthique en Afrique

Au fil des années, l'éthique de la recherche médicale a pris une ampleur remarquable. La complexité de l'entreprise de la recherche et les enjeux éthiques que soulève la conduite des essais cliniques dans les pays africains nous ont interpelés. S'interroger sur les formes de protection des populations vulnérables de ces pays du Sud part du constat suivant : la création des comités d'éthique en Afrique a été réalisée pour faciliter l'expansion de la recherche biomédicale au Sud à partir des textes de référence occidentale. L'application des principes éthiques ainsi développés s'intègre difficilement dans la culture africaine et malgré les bienfaits de la recherche médicale, il persiste pour les populations africaines, une impression d'exploitation. Dans ce contexte et pour proposer de nouvelles pistes de réflexion, il nous a semblé important de rassembler certains principes généraux de l'éthique de la recherche et les textes de référence s'y rapportant, dont l'application en Afrique ne s'articule pas harmonieusement avec les valeurs socioculturelles locales. Les notions du consentement éclairé et de l'autonomie de la personne se heurtent à certaines valeurs africaines comme la vie en communauté avec l'appartenance identitaire à son ethnie, dont les intérêts passent avant ceux de l'intéressé. Les particularités liées au contexte africain comme l'analphabétisme, l'inaccessibilité des soins de santé primaires, différentes représentations traditionnelles paraissent inadaptées aux exigences actuelles de l'éthique de la recherche. Ce contraste entre les pays du Nord et ceux du Sud est très perceptible dans ce domaine. Comment solliciter des participants à un projet de recherche pour l'évolution de la médecine moderne quand 80% de ces potentiels participants se soignent par la médecine traditionnelle ? Précisons, cependant, que l'intérêt de poursuivre la recherche médicale dans les pays du Sud ne peut être mis en cause mais la manière de la conduire nécessite une profonde révision. Ainsi pour nous rendre compte concrètement du processus de création des comités d'éthique chargés de protéger les participants à la recherche médicale, une enquête menée dans 20 pays africains a montré l'évolution de l'éthique dans cette région. La consultation des sites ANRS en Afrique et du réseau panafricain des essais cliniques effectuée ultérieurement a confirmé un fonctionnement évolutif du partenariat Nord-Sud. Mais il persiste une nécessité de contextualisation et une indépendance à renforcer. Cette tâche peut être réservée aux scientifiques et chercheurs en sciences humaines et sociales africains. Il convient d'africaniser les principes fondamentaux de l'éthique de la recherche pour que l'africain adhère à la démarche de la recherche médicale conduite dans son milieu en s'appropriant des principes révisés à partir des repères socioculturels qui l'identifient.Over the years, ethics of medical research has grown remarkably. The complexity of the research process and the ethical issues raised by the clinical trials in African countries has drawn our attention. The creation of ethics committees in Africa in order to facilitate the expansion of biomedical research in the Global South based on Western texts has raised questionings on the protection of vulnerable populations in these countries from the South. The implementation of the ethical principles developed in such a way that it integrates with difficulty into the African culture and despite of the benefits of medical research, the impression of exploitation persists among African populations. In this context, and in order to propose new lines of enquiry, it seemed important to gather certain general principles of the ethics of research and the related texts, whose implementation in Africa does not harmoniously integrate with the local socio-cultural values. The notions of informed consent and individual autonomy clash with certain African values like community life with the sense of belonging to its ethnic group, whose interests come before those of the individual. The particularities bound by the African context such as illiteracy, the inaccessibility of primary health care, different traditional representations seem unsuitable for the current requirements of research ethics. This contrast between the countries from the North and from the South is very distinguishable within this field. How to call for participants to a research project for the evolution of modern medicine when 80% of the potential participants treat themselves with traditional medicine? It is important to specify that the interest of pursuing medical research in the countries of the South cannot be questioned, however, the way of conducting research does require a major revision. In order for us to understand the creation process of the ethics committees in charge of protecting the participants in medical research, a survey was conducted in 20 African countries demonstrating the evolution of ethics in this region. The consultation with the ANRS' sites in Africa and the Pan-African clinical trial network that took place subsequently, confirmed an evolving operating North-South partnership. Yet it is still necessary to contextualize and to reinforce independence. This task may be reserved for scientists and researchers in African humanities and social sciences. The fundamental principles of research ethics should be Africanized in order for Africans to adhere to the procedure of medical research conducted in their settings by the appropriation of the revised principles based on the cultural markers that identify them

Predicting Frailty and Geriatric Interventions in Older Cancer Patients: Performance of Two Screening Tools for Seven Frailty Definitions—ELCAPA Cohort

International audienceScreening tools have been developed to identify patients warranting a complete geriatric assessment (GA). However, GA lacks standardization and does not capture important aspects of geriatric oncology practice. We measured and compared the diagnostic performance of screeningtools G8 and modified G8 according to multiple clinically relevant reference standards. We included 1136 cancer patients ≥ 70 years old referred for GA (ELCAPA cohort; median age, 80 years; males, 52%; main locations: digestive (36.3%), breast (16%), and urinary tract (14.8%); metastases,43.5%). Area under the receiver operating characteristic curve (AUROC) estimates were compared between both tools against: (1) the detection of ≥1 or (2) ≥2 GA impairments, (3) the prescription of ≥1 geriatric intervention and the identification of an unfit profile according to (4) a latent classtypology, expert-based classifications from (5) Balducci, (6) the International Society of Geriatric Oncology task force (SIOG), or using (7) a GA frailty index according to the Rockwood accumulation of deficits principle. AUROC values were ≥0.80 for both tools under all tested definitions. They were statistically significantly higher for the modified G8 for six reference standards: ≥1 GA impairment (0.93 vs. 0.89), ≥2 GA impairments (0.90 vs. 0.87), ≥1 geriatric intervention (0.85 vs. 0.81), unfit according to Balducci (0.86 vs. 0.80) and SIOG classifications (0.88 vs. 0.83), and according to the GA frailty index (0.86 vs. 0.84). Our findings demonstrate the robustness of both screening tools against different reference standards, with evidence of better diagnostic performance of the modified G8

Sex Differences in Medicine Acceptability: A New Factor to Be Considered in Medicine Formulation

International audiencePalatability is a recognized driver of medicine acceptability in pediatrics but deemed less relevant in older populations due to sensory decline. Preliminary findings from an observational study implicated palatability problems with one Alzheimer's medicine. Among 1517 observer reports combining multiple measures on medicines uses in patients aged over 64, we focused on two original formulations of memantine (Ebixa (R), tablets (n = 25) and oral solution (n = 60)). Evaluations were scored with an acceptability reference framework (CAST), the rodent Brief Access Taste Aversion (BATA) model tested aversiveness. Focusing on women treated with Ebixa (R) (n = 54), the oral formulation sub-group was classified as negatively accepted, while the coated tablet was associated with the positively accepted cluster. In men, both formulations belonged to the positively accepted profile. Using BATA, the original oral solution was categorized as highly aversive/untolerated while solutions of excipients only were well tolerated. Furthermore, the number of licks was significantly lower in female than in male rats. These results revealed that medicine palatability remains important for acceptability in older populations. Moreover, converging results from humans and animal models highlighted that palatability profiles can significantly vary between the sexes. These drivers should be closely considered during drug development to enhance acceptability in this population

A Decision Support Tool Facilitating Medicine Design for Optimal Acceptability in The Older Population

International audiencePurposeMedicine acceptability, which is of the utmost importance for vulnerable patients’ adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population.MethodsAn observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years). Mapping and clustering explored these multiple observational measures and summarised the main information into an intelligible reference framework. Resampling statistics were used to validate the model’s reliability.ResultsA three-dimensional map and two clusters defining acceptability profiles, as positive or negative, emerged from the 1079 evaluations. Factors of interest (medicines, user features…) were positioned on the map at the barycentre of their evaluations and assigned to an acceptability profile. Focusing on patients’ ability to swallow, we have highlighted the tool’s efficacy in demonstrating the impact of user features on medicine acceptability.ConclusionsThis multivariate approach provides a relevant judgement criterion for this multi-dimensional concept. Facilitating the choice of the most appropriate dosage form to achieve optimal acceptability in a targeted population, this tool is of real potential to improve clinical decisions