Background During the large 2013-16 Ebola virus outbreak caused by the Zaire Ebola virus, about 20% of cases were reported in children. This study is the first, to our knowledge, to evaluate an Ebola vaccine in children younger than 6 years. We aimed to evaluate the safety, reactogenicity, and immunogenicity of a monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in a paediatric population.Methods This phase 2, randomised, observer-blind, controlled trial was done in a vaccine centre in Mali and a university hospital centre in Senegal. Healthy children were randomly assigned through a web-based system (1:1; stratified by age group, gender, and centre) to receive ChAd3-EBO-Z (day 0) and meningococcal serogroups A,C,W-135,Y tetanus toxoid conjugate vaccine (MenACWY-TT; month 6), or MenACWY-TT (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind from study start until interim day 30 analysis and became single-blind as of interim analysis. Primary outcomes assessed were serious adverse events (up to study end, month 12), solicited local or general adverse events (7 days post-vaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). As secondary endpoints, we evaluated anti-glycoprotein Zaire Ebola virus antibody titres (ELISA) pre-vaccination and 30 days postvaccination. This study is registered with ClinicalTrials.gov, NCT02548078. FindingsFrom Nov 11, 2015, to May 9, 2016, of 776 children screened for eligibility, 600 were randomly assigned (200 [33%] in each age strata: 1-5, 6-12, 13-17 years), 300 (50%) to the ChAd3-EBO-Z/MenACWY-TT group and 300 (50%) to the MenACWY-TT/ChAd3-EBO-Z group; all were included in the total vaccinated cohort. Post-day 0 vaccination, the most common solicited injection site symptom was pain (127 [42%] of 300 in the ChAd3-EBO-Z/ MenACWY-TT group vs 60 [20%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group); the most common solicited general adverse event was fever (95 [32%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 28 [9%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group). Unsolicited adverse events post-day 0 vaccination were reported by 41 (14%) of 300 participants in the ChAd3-EBO-Z/MenACWY-TT group and 24 (8%) of 300 MenACWY-TT/ChAd3-EBO-Z recipients. Serious adverse events were reported for two (1%) of 300 children in each group; none were considered vaccination related. No clinical symptoms of thrombocytopenia were reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentrations (GMC) in the ChAd3-EBO-Z/MenACWY-TT group were 1564 (95% CI 1340-1826) for those aged 13-17 years, 1395 (1175-1655) for 6-12 years, and 2406 (1942-2979) for 1-5 years. Antiglycoprotein Ebola virus IgG antibody responses persisted up to 12 months post-vaccination, with a GMC of 716 (95% CI 619-828) for those aged 13-17 years, 752 (645-876) for 6-12 years, and 1424 (1119-1814) for 1-5 years. Interpretation ChAd3-EBO...

Background: The 2014 Zaire Ebola virus disease epidemic accelerated vaccine development for the virus. We aimed to assess the safety, reactogenicity, and immunogenicity of one dose of monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in adults. Methods This phase 2, randomised, observer-blind, controlled trial was done in study centres in Cameroon, Mali, Nigeria, and Senegal. Healthy adults (≥18 years) were randomly assigned with a web-based system (1:1; minimisation procedure accounting for age, gender, centre) to receive ChAd3-EBO-Z (day 0), or saline placebo (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind until planned interim day 30 analysis, single-blind until month 6, and open-label after month 6 vaccination. Primary outcomes assessed in the total vaccinated cohort, which comprised all participants with at least one study dose administration documented, were serious adverse events (up to study end, month 12); and for a subcohort were solicited local or general adverse events (7 days postvaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). Secondary endpoints (subcohort; per-protocol cohort) evaluated anti-glycoprotein Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02485301.

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Electronic clinical decision support algorithms (CDSAs) have been developed to address high childhood mortality and inappropriate antibiotic prescription by helping clinicians adhere to guidelines. Previously identified challenges of CDSAs include their limited scope, usability, and outdated clinical content. To address these challenges we developed ePOCT+, a CDSA for the care of pediatric outpatients in low- and middle-income settings, and the medical algorithm suite (medAL-suite), a software for the creation and execution of CDSAs. Following the principles of digital development, we aim to describe the process and lessons learnt from the development of ePOCT+ and the medAL-suite. In particular, this work outlines the systematic integrative development process in the design and implementation of these tools required to meet the needs of clinicians to improve uptake and quality of care. We considered the feasibility, acceptability and reliability of clinical signs and symptoms, as well as the diagnostic and prognostic performance of predictors. To assure clinical validity, and appropriateness for the country of implementation the algorithm underwent numerous reviews by clinical experts and health authorities from the implementing countries. The digitalization process involved the creation of medAL-creator, a digital platform which allows clinicians without IT programming skills to easily create the algorithms, and medAL-reader the mobile health (mHealth) application used by clinicians during the consultation. Extensive feasibility tests were done with feedback from end-users of multiple countries to improve the clinical algorithm and medAL-reader software. We hope that the development framework used for developing ePOCT+ will help support the development of other CDSAs, and that the open-source medAL-suite will enable others to easily and independently implement them. Further clinical validation studies are underway in Tanzania, Rwanda, Kenya, Senegal, and India.

Objectif : Apprécier les conditions de transfert médical des nouveau-nés malades dans la région de Dakar. Méthodologie : Il s'agissait d'une étude prospective, transversale et analytique, menée entre août 2013 et janvier 2014, intéressant les cas de transfert néonatal, dans huit centres de santé périphériques (et leurs postes de santé de responsabilité) et trois services de néonatologie de référence de niveau III, dans la région de Dakar (Sénégal). Pour chaque transfert étaient recueillis les aspects sociodémographiques, les données périnatales, la nature des soins prétransfert, les conditions et la durée du transfert ainsi que l'évolution des nouveau-nés. L'analyse des données a été réalisée avec SPSS 21. Résultats : Au total, 130 cas de transfert néonatal ont été documentés. Le transfert était fait des structures périphé-riques vers les hôpitaux de niveau III dans 99 cas (76,1 %) et entre structures de référence dans 31 cas (23,8 %). Il y avait une prédominance masculine (sex-ratio : 1,6). L'âge moyen au moment du transfert était de 72 heures (1 heure à 28 jours de vie), et les transferts précoces avant 48 heures (68 cas) représentaient 52,3 %. Les structures d'accueil n'avaient été avisées que dans 26,9 % des cas. Les principaux motifs de transfert étaient le sepsis (35,4 %), la détresse respiratoire (33,8 %), le faible poids de naissance (FPN) [33,1 %]. En prétransfert, 37,7 % des nouveau-nés n'avaient reçu aucun soin ; 39,2 % avaient été réanimés. L'ambulance n'était utilisée que dans 30 % des cas, le taxi urbain était le moyen de transport le plus utilisé (45,4 %). Il n'y avait pas d'accompagnement par un personnel de santé dans 72,3 % des cas. Le délai moyen avant admission dans une structure de référence était de 3 heures et 30 minutes (maximum de trois jours). Durant le transport, plus de la moitié des nouveau-nés (53,8 %) avaient visité au moins deux structures de référence. À l'arrivée, trois nouveau-nés étaient décé-dés, six étaient en arrêt cardiorespiratoire. Une hypothermie était notée chez 33,8 % des nouveau-nés et une hypoglycé-mie chez 23,8 %. La mortalité parmi les nouveau-nés transférés était de 22,3 % (29 décès).Conclusion : Les transferts néonatals se déroulent dans de mauvaises conditions dans la région de Dakar. L'organisation d'un système de transport néonatal efficace, articulé autour de réseaux régionaux de périnatalité, est une priorité pour tout le Sénégal. Mots clés Nouveau-né · Transfert néonatal · DakarAbstract Objective: To analyze conditions of medical transfer of the sick newborns in the region of Dakar, Senegal. Method: This was a prospective transversal study, between August 2013 and January 2014 (6 months), concerning neonatal transfer in eight health peripheral centers and three Central University neonatal units, all localized in Dakar region. For each transfer, socio-demographic and perinatal data, treatment before transfer, conditions and duration of the transfer, and outcome of newborns were collected. Data was analyzed with SPSS 21. Results: A total of 130 neonatal trans...