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Background: \ud \ud Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants

The advent of pneumococcal conjugate vaccines led to the near disappearance of most of the included serotypes in high-income settings but also the rise of nonvaccine-type colonization and disease. Alternative strategies, using genetically conserved proteins as antigens, have been evaluated preclinically and clinically for years, so far unsuccessfully. One possible explanation for the failure of these efforts is that the choice of antigens may not have been sufficiently guided by an understanding of the gene expression pattern in the context of infection. Here, we present a targeted transcriptomic analysis of 160 pneumococcal genes encoding bacterial surface-exposed proteins in mouse models, human colonization, and human meningitis. We present the overlap of these different transcriptomic profiles. We identify two bacterial genes that are highly expressed in the context of mouse and human infection: SP_0282, an IID component of a mannose phosphotransferase system (PTS), and SP_1739, encoding RNase Y. We show that these two proteins can confer protection against pneumococcal nasopharyngeal colonization and intraperitoneal challenge in a murine model and generate opsonophagocytic antibodies. This study emphasizes and confirms the importance of studies of pneumococcal gene expression of bacterial surface proteins during human infection and colonization and may pave the way for the selection of a protein-based vaccine candidate.

The burden of antimicrobial resistance is a major threat to global health; however, prospective clinical outcome data from Africa are scarce. In Malawi, third-generation cephalosporins are the antibiotics of choice in patients admitted to hospital despite a rapid proliferation of resistance to these drugs. We aimed to quantify the effect of resistance to third-generation cephalosporins on mortality and length of hospital stay among patients with bloodstream infections.We did a prospective cohort study of patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Patients of all ages who had positive blood cultures for Enterobacterales were included, with the exception of those from the genus Salmonella, and were followed up for 180 days. We characterised blood culture isolates using whole-genome sequencing and used Cox regression models to estimate the effect of resistance to third-generation cephalosporins on length of hospital stay, in-hospital mortality, and survival.Between Jan 31, 2018, and Jan 13, 2020, we recruited 326 patients, from whom 220 (68%) of 326 isolates were resistant to third-generation cephalosporins. The case fatality proportion was 45% (99 of 220) in patients with bloodstream infections that were resistant to third-generation cephalosporins, and 34% (36 of 106) in patients with bloodstream infections that were sensitive to third-generation cephalosporins. Resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1·44, 95% CI 1·02-2·04), longer hospital stays (1·5 days, 1·0-2·0) and decreased probability of discharge alive (HR 0·31, 0·22-0·45). Whole-genome sequencing showed a high diversity of sequence types of both Escherichia coli and Klebsiella pneumoniae. Although isolates associated with death were distributed across clades, we identified three E coli clades (ST410, ST617, and ST648) that were isolated from 14 patients who all died.Resistance to third-generation cephalosporins is associated with increased mortality and longer hospital stays in patients with bloodstream infections in Malawi. These data show the urgent need for allocation of resources towards antimicrobial resistance mitigation strategies in Africa.Wellcome Trust and Wellcome Asia and Africa Programme.

BackgroundInvasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants aged MethodsWe conducted laboratory-based prospective IPD surveillance in infants aged Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex PCR and latex agglutination testing.ResultsWe identified 130 cases of culture-confirmed IPD in infants ConclusionVaccine serotypes were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. Further strategies need to be considered to protect this vulnerable population, including maternal or neonatal immunization and implementation of an alternative PCV schedule with a booster dose.SummaryThe incidence of invasive pneumococcal disease in infants in Blantyre, Malawi has declined over the past decade and more significantly after introduction of the pneumococcal conjugate vaccine. Vaccine serotypes have remained the main cause of disease in this population.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Background: The Malawi-Liverpool Wellcome Trust Clinical Research Programme (MLW) has undertaken sentinel surveillance of bloodstream infection and meningitis at Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi for 20 years. Previously, three epidemics of Salmonella bloodstream infection have been identified. Here we provide updated surveillance data on invasive non-typhoidal Salmonella disease from 2011 – 2019. Methods: Surveillance data describing trends in invasive non-typhoidal Salmonella disease and associated antimicrobial susceptibility profiles are presented for the period January 2011 – December 2019. Results: Between January 2011-December 2019, 128,588 blood cultures and 40,769 cerebrospinal fluid cultures were processed at MLW. Overall, 1.00% of these were positive for S. Typhimurium, 0.10% for S. Enteritidis, and 0.05% positive for other Salmonella species. Estimated minimum incidence of invasive non-typhoidal Salmonella (iNTS) disease decreased from 21/100,000 per year in 2011 to 7/100,000 per year in 2019. Over this period, 26 confirmed cases of Salmonella meningitis were recorded (88.5% S. Typhimurium). Between 2011-2019 there was a substantial decrease in proportion of S. Typhimurium (78.5% to 27.7%) and S. Enteritidis (31.8% in 2011 to 0%) that were multidrug-resistant. Resistance to fluoroquinolones and third-generation generation cephalosporins (3GC) remained uncommon, however 3GC increased amongst Salmonella spp. and S. Typhimurium in the latter part of the period. Conclusions: The total number of iNTS bloodstream infections decreased between 2011-2019. Although the number multidrug resistance (MDR) S. Typhimurium and S. Enteritidis isolates has fallen, the number of MDR isolates of other Salmonella spp. has increased, including 3GC isolates.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Outcomes from pneumococcal meningitis (PM) are worse than meningococcal meningitis (MM), particularly in settings with high HIV-1 prevalence, but the reasons are unknown. We compared inflammatory responses between PM and MM in Malawian adults.As compared to MM (n=27, 67% HIV-infected, mortality 11%), patients with PM (n=440, 84% HIV-infected, mortality 54%) were older, had strikingly lower CSF WCC, higher pro-inflammatory cytokine concentrations and higher mortality. PM is characterized by significantly lower CSF WCC, but greater inflammation and higher mortality compared to MM. Mechanistic understanding of blunting of the CSF leukocyte response in PM in-vivo is required.

Typhoid fever, caused by infection with the human-restricted bacterial pathogen Salmonella enterica serovar Typhi, is a major cause of illness and mortality in regions of the world with limited access to improved water and sanitation [1]. Recent estimates have placed the global burden of typhoid fever at 11.9–26.9 million cases and 129 000–270 000 deaths per year [2–5]. Although the endemic burden of typhoid fever in South and Southeast Asia has long been recognized, less is known about the burden of disease in sub-Saharan Africa. In Malawi, as in much of sub-Saharan Africa, nontyphoidal Salmonella (NTS) serovars have been a much more common cause of bloodstream infections over the past 2 decades. Sequential epidemics of Salmonella enterica serovars Typhimurium and Enteritidis have been observed [6]. Salmonella Typhi represented just 2% (105/5061) of Salmonella isolates detected by sentinel surveillance at Queen Elizabeth Central Hospital (QECH) in Blantyre, the largest hospital in Malawi, between 1998 and 2004 [6]. Since 2011, however, there has been a substantial increase in the number of confirmed cases of Salmonella Typhi at QECH. The number of typhoid cases increased from 14 per year during 1998–2010 to 843 cases in 2013. This epidemic of typhoid fever has continued for at least 3 years [7] and coincides with numerous reports of ongoing epidemics of typhoid fever in settings across Africa [7–12]. These epidemics have closely followed the recent global emergence of the H58 haplotype of Salmonella Typhi [13]. The H58 lineage is highly clonal and differentiated from other haplotypes using a simple single nucleotide polymorphism–based typing scheme [14], and is associated with high levels of multidrug resistance [13, 15]. There are a variety of hypotheses that could explain the large increase in typhoid fever cases in Blantyre, including (1) an increase in population density in Blantyre beyond a critical threshold for transmission; (2) waning heterotypic immunity to Salmonella Enteritidis that is cross-protective against Salmonella Typhi; (3) an increase in the prevalence of multidrug resistant (MDR) strains, resulting in prolonged persistence; and (4) the emergence of the MDR H58 haplotype, which has become dominant in many places around the world and may be more transmissible than other strains [13]. The latter 2 hypotheses are tightly coupled, but describe slightly different mechanisms by which the H58 haplotype, and MDR strains more broadly, may have led to the outbreak. Mathematical models provide a platform for assessing the plausibility of these hypotheses to help direct future research efforts. We therefore adapted a mathematical model for the transmission dynamics of typhoid developed previously [16] by fitting to age-specific data on microbiologically confirmed cases of typhoid fever in Blantyre, Malawi. We modified the model to explore the 4 hypotheses outlined above, and examined whether each of them could explain the recent prolonged outbreak of typhoid fever cases in this setting.

Objectives ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates. Methods We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time. Results Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar. Conclusions There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations.

BACKGROUNDBacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance.METHODS In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time.FINDINGSBetween Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (pINTERPRETATIONThe rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting.FUNDINGWellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).

BACKGROUND Acute bacterial meningitis (ABM) causes significant death and disability in children worldwide, with HIV recognized as an established risk factor for infection and negative outcomes. However, additional major risk factors for death and disability in pediatric ABM remain unclear. METHODS We conducted a retrospective analysis of case data from 3 departmental studies of ABM involving 1784 children

Les auteurs presentent l’interet d’articuler des activites presentielles et a distance dans un dispositif de formation d’adultes aux technologies de la formation. Ils decrivent les modalites et principes sous-jacents a sa mise en œuvre a travers une strategie de formation recourant a des scenarios pedagogiques varies. L’efficacite du dispositif est augmentee par la prise en compte du projet personnel des participants, de certains aspects organisationnels ainsi que d’une triple concordance entre competences a developper, activites d’apprentissage et evaluation de ces competences. Deux exemples de scenarios de cours sont detailles : le premier concerne un cours de « Conception du cahier des charges d’un logiciel multimedia de formation », le second celui de « Sciences et technologies de l’information et de la communication ».

Cet article présente les objectifs (motivationnels, métacognitifs, instrumentaux et disciplinaires) d’une formation, une méthode pédagogique, appelée les projets d’animations réciproques multimédias (PARMs) et les procédures d’auto-observation de leur façon d’apprendre vécues par des étudiants universitaires. Le texte rapporte plusieurs activités didacticomathétiques liées aux objectifs de formation, il rappelle les stratégies d’apprentissage préconisées dans les PARMs, puis il présente deux instruments de réflexion métacognitive utilisés à cette fin, soit le « Questionnaire de progrès subjectif » et le « Questionnaire d’autodescription mathétique ». Viennent enfin les résultats consécutifs à l’utilisation de chacun des questionnaires., This article presents the training objectives (motivational, metacognitive, instrumental, and disciplinary) of a pedagogical method known as PARMs (multimedia reciprocal animation project) and procedures for self-observation of learning as experienced by university students. The authors describe a series of didactic-mathetic activities related to training objectives, as well as those learning strategies promoted in the PARMs course. Two instruments to measure metacognitive thinking are presented: « Questionnaire on progress » and « Questionnaire on mathetical self-description ». The results of these questionnaires is then discussed., Este artículo presenta los objetivos (motivacionales, metacognitivos, instrumentales y disciplinarios) de una formación basada en el método pedagógico llamado PARM (Proyecto de animaciones recíprocas multimedia) y los procedimientos de auto-observación respecto de las formas de aprender vivenciadas por estudiantes universitarios. El texto muestra un conjunto de actividades didáctico-matéticas relacionadas con los objetivos de formación, retoma las estrategias de aprendizaje preconizadas en los PARM y presenta dos instrumentos de reflexión metacognitiva utilizados a este fin, o sea el « Cuestionario de progreso subjetivo » y el « Cuestionario de autodescripción matética ». El artículo termina con los resultados obtenidos en cada uno de estos cuestionarios., Dieser Artikel stellt die Zielsetzungen (in Bezug auf Motivation, metakognitive Erkenntnisse, Lerninstrumentarium und fachgebundene Ziele) einer neuen Lernmethode mit Namen PARM (Projet d’animations réciproques multimédias/ Multimediaprojekt für reziproke Animation) vor, weiterhin die Methoden der Selbstbeobachtung beim Lernen an Hand der Erfahrungen von Universitätsstudenten. Die Studie führt eine Reihe von didaktisch-mathetischen [d.h. auf das Lernen hin ausgerichtete, Anm.d.Ü.] Aktivitäten vor, die in enger Beziehung zu den Lernzielen stehen. Darüber hinaus werden die vom Kurs PARM herausgestellten Lernstrategien referiert, außerdem werden zwei für metakognitive Erkenntnisse geeignete Instrumente vorgestellt, die für die Untersuchung verwendet wurden, und zwar der «Fragebogen für subjektive Fortschritte» sowie der «Fragebogen für mathetische Selbstbeschreibung». Den Schluss der Untersuchung bilden die aus den beiden Fragebögen ermittelten Resultate.

This paper relates different strategies developed in order to support the learning process in a blended learning programme involving adults from different backgrounds who are interested in the use of Information and Communication Technologies for Education. Referring to Carre´ and Pearn's model of the seven pillars of self-learning, the author describes some principles, tools and resources that have been developed within the framework of a postgraduate diploma and that could be extended to similar adult training programmes.

Resume Cet article traite de la formation de « tuteurs en ligne », c’est-a-dire intervenant dans un dispositif de formation a distance. Apres avoir situe le tuteur parmi les autres acteurs d’un tel dispositif, l’auteur envisage differentes fonctions tutorales et un profil d’intervention a relativiser selon le type de dispositif de formation envisage. Il presente ensuite une serie de competences necessaires pour devenir tuteur a distance ainsi que diverses experiences de formation de tuteurs. Il propose sept etapes de formation allant du vecu d’une experience d’apprentissage a distance par le futur tuteur jusqu’a la regulation de ses interventions.

Of 176 invasive Streptococcus pneumoniae isolates from children in Malawi, common serotypes were 1 (23%), 6A/B (18%), 14 (6%), and 23F (6%). Coverage with the 7-valent pneumococcal conjugate vaccine (PCV) was 39%; PCV10 and PCV13 increased coverage to 66% and 88%, respectively. We found chloramphenicol resistance in 27% of isolates and penicillin nonsusceptibility in 10% (by using meningitis breakpoints); all were ceftriaxone susceptible.

Currently, it is difficult for a student to pursue higher education without using a digital environment. This leads to the emergence the concept of Personal Learning Environment (PLE). The authors define it and consider his competition or complementarity with the digitals institutional environments. They report exploratory study results on students’ representations about their numeric learning environments and their interests about them. Data comes from questionnaires and interviews. Their analysis shows different profiles related to the PLE. Linking the results to learning theories and aspects of technical and educational design, they propose further investigation and development related to the complementarity of PLE and institutional learning environments (ILE)., À l’heure actuelle, il est difficile pour un étudiant de réaliser des études supérieures sans recourir à un environnement numérique. Cette situation entraine l’émergence du concept d’Environnement Personnel d’Apprentissage (EPA). Les auteures en proposent une définition ainsi qu’une réflexion sur sa concurrence ou complémentarité avec les environnements institutionnels numériques. Elles rapportent les résultats d’une étude exploratoire sur les représentations d’étudiants universitaires à propos de la personnalisation de leurs environnements numériques d’apprentissage et de l’intérêt qu’ils y trouvent. L’analyse de données issues de questionnaires et d’interviews met en évidence différents profils en termes de conception et d’usage d’un EPA. Une mise en relation avec différentes théories de l’apprentissage et divers aspects de l’ingénierie techno-pédagogique permet de dégager des pistes de recherche et de développement en matière de complémentarité des EPA et des environnements d’apprentissage institutionnels (EAI)., Denis Brigitte, Joris Noémie. Environnements Personnels d’Apprentissage : exploration des représentations et usages d’étudiants de l’enseignement supérieur. In: Sciences et Technologies de l'Information et de la Communication pour l'Éducation et la Formation, volume 21, 2014. Évaluation dans les Jeux Sérieux / Les EPA : entre description et conceptualisation. pp. 317-345.

Learning to collaborate is an important educational goal. The concept of collaborative learning is differently defined by several authors. Problem solving and problem-based learning are also important in our educational framework. We shall situate and clarify here the instructional design concepts used in an educational setting based on a “collaborative and problem based learning environment” applied to educational robotics. Educational robotics activities are developed at several school levels (primary, secondary) and in adults' training contexts. The instructional design of such learning activities is based on a constructivist approach of learning. Their educational objectives are varied. In our approach, the goal is not only that the learners acquire specific skills (e.g. knowledge on electricity, electronics, robotics…), but also and mainly demultiplicative, strategic and dynamic skills. The methodology focuses on collaboration to design and develop common projects and on problem solving skills development. The pupils work in small groups (2–4). In the reported research, some learners' interactions have been observed during the activity in a primary school with an observation grid. The analysis of the verbalisations between the learners and their actions on the computers, and the robotics materials coming from those observations offer the opportunity to study the way the learners are collaborating.

Summary The Malawi Adult Meningitis Score prediction tool accurately estimates risk of clinical outcome from bacterial meningitis in sub-Saharan Africa. Clinical trial analysis by risk stratification reveals more severe outcomes in low-risk groups receiving adjunctive glycerol compared to placebo., Background. Acute bacterial meningitis (ABM) in adults residing in resource-poor countries is associated with mortality rates >50%. To improve outcome, interventional trials and standardized clinical algorithms are urgently required. To optimize these processes, we developed and validated an outcome prediction tool to identify ABM patients at greatest risk of death. Methods. We derived a nomogram using mortality predictors derived from a logistic regression model of a discovery database of adult Malawian patients with ABM (n = 523 [65%] cerebrospinal fluid [CSF] culture positive). We validated the nomogram internally using a bootstrap procedure and subsequently used the nomogram scores to further interpret the effects of adjunctive dexamethasone and glycerol using clinical trial data from Malawi. Results. ABM mortality at 6-week follow-up was 54%. Five of 15 variables tested were strongly associated with poor outcome (CSF culture positivity, CSF white blood cell count, hemoglobin, Glasgow Coma Scale, and pulse rate), and were used in the derivation of the Malawi Adult Meningitis Score (MAMS) nomogram. The C-index (area under the curve) was 0.76 (95% confidence interval, .71–.80) and calibration was good (Hosmer-Lemeshow C-statistic = 5.48, df = 8, P = .705). Harmful effects of adjunctive glycerol were observed in groups with relatively low predicted risk of poor outcome (25%–50% risk): Case Fatality Rate of 21% in the placebo group and 52% in the glycerol group (P < .001). This effect was not seen with adjunctive dexamethasone. Conclusions. MAMS provides a novel tool for predicting prognosis and improving interpretation of ABM clinical trials by risk stratification in resource-poor settings. Whether MAMS can be applied to non-HIV-endemic countries requires further evaluation.

This paper describes some research trends in pedagogical robotics that were developed during the past twenty years. Martial Vivet was part of many projects that are provided as examples., Cet article présente quelques-unes des tendances de la recherche en robotique pédagogique au cours des vingt dernières années. Il est illustré par certains développements auxquels Martial Vivet a collaboré., Denis Brigitte. Vingt ans de robotique pédagogique. In: Sciences et techniques éducatives, volume 7 n°1, 2000. Education et informatique. Hommage à Martial Vivet. pp. 195-206.

A case of human melioidosis caused by a novel sequence type of Burkholderia pseudomallei occurred in a child in Malawi, southern Africa. A literature review showed that human cases reported from the continent have been increasing.

Introduction\ud Cryptococcal meningitis is the most common neurological infection in HIV infected patients in Sub Saharan Africa, where gold standard treatment with intravenous amphotericin B and 5 flucytosine is often unavailable or difficult to administer. Fluconazole monotherapy is frequently recommended in national guidelines but is a fungistatic drug compromised by uncertainty over optimal dosing and a paucity of clinical end-point outcome data.\ud \ud Methods\ud From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation.\ud \ud Results\ud Sixty patients were recruited. 26/60 (43%) died by 4 weeks. 35/60 (58.0%) and 43/56 (77%) died or failed treatment by 10 or 52 weeks respectively. Reduced consciousness (Glasgow Coma Score 3 of 5) and confusion (Abbreviated Mental Test Score

Background\ud \ud Malawi commenced the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunisation schedule in November 2011. Here we have tested the utility of high throughput whole genome sequencing to provide a high-resolution view of pre-vaccine pneumococcal epidemiology and population evolutionary trends to predict potential future change in population structure post introduction.\ud \ud Methods\ud \ud One hundred and twenty seven (127) archived pneumococcal isolates from randomly selected adults and children presenting to the Queen Elizabeth Central Hospital, Blantyre, Malawi underwent whole genome sequencing.\ud \ud Results\ud \ud The pneumococcal population was dominated by serotype 1 (20.5% of invasive isolates) prior to vaccine introduction. PCV13 is likely to protect against 62.9% of all circulating invasive pneumococci (78.3% in under-5-year-olds). Several Pneumococcal Molecular Epidemiology Network (PMEN) clones are now in circulation in Malawi which were previously undetected but the pandemic multidrug resistant PMEN1 lineage was not identified. Genome analysis identified a number of novel sequence types and serotype switching.\ud \ud Conclusions\ud \ud High throughput genome sequencing is now feasible and has the capacity to simultaneously elucidate serotype, sequence type and as well as detailed genetic information. It enables population level characterization, providing a detailed picture of population structure and genome evolution relevant to disease control. Post-vaccine introduction surveillance supported by genome sequencing is essential to providing a comprehensive picture of the impact of PCV13 on pneumococcal population structure and informing future public health interventions.

A major aim of the Pragmatic Web is "to support communities to put ontologies in context". As a contribution to this aim, we present the framework we developed to analyze the way we attempted to contextualize the ontologies underlying a set of semantic knowledge services dedicated to communities of practice. The framework was derived from the "Ontology Framework" elaborated by members of the Ontology Engineering community during the Ontology Summit 2007. Both frameworks define a series of "pragmatic dimensions" of ontologies. Because our derived framework does not cover all possible dimensions, we propose to complement it, by relying on existing work from the Ontology Engineering community in general, and from the Pragmatic Web community in particular. In conclusion, we invite the Pragmatic Web community to pursue such a work by jointly elaborating a consensual "Pragmatic Ontology Framework".

Objective\ud To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis.\ud \ud Methods\ud Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection.\ud \ud Results\ud 4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r = −0.91; p

Background Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid. Methods A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid. Results Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection. Conclusions In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa.

This paper reports the characteristics of a post graduate diploma on educational technologies based on a combination of face-to-face and distance activities and assesses its quality. We first define the bases of the training program and present several tools (logbook, portfolio and questionnaires) which have been used to evaluate and regulate both training and the individual learning process. Our observations indicate an increase and better regulation of the quality of the educational and learning processes. On the basis of the results we achieved, we propose that our original design could be extended to similar adult training programs. The way this innovative system is integrated in the universities shows an evolution due to its success that implies a certain kind of return on investment due to the demand of such kinds of device.

Different approaches can be used to evaluate the effects of using microworlds such as control technology. Our approach is based on the regulation process and the use of established tools to observe animator and user behaviour. Some user objectives are established as well as a theoretical animator profile which could promote their attainment. Users’ objectives deal with computing and technological literacy, socialization, problem solving and individual cognitive development. Observation grids have also been developed to evaluate whether there is a gap between intentions or claims and action and whether the animators’ evaluation of their activity is realistic. The observation of users’ and animators’ behaviours in a 5th grade primary classroom provided some practical information to help the animators to take regulation decisions and then to increase their congruence and to reach their objectives.